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Alzheimer's disease (AD) is a progressive neurodegenerative disorder
characterized by cognitive decline and memory loss. Early detection of AD is
crucial for effective intervention and treatment. In this paper, we propose a
novel approach to AD detection from spontaneous speech, which incorporates
pause information into language models. Our method involves encoding pause
information into embeddings and integrating them into the typical
transformer-based language model, enabling it to capture both semantic and
temporal features of speech data. We conduct experiments on the Alzheimer's
Dementia Recognition through Spontaneous Speech (ADReSS) dataset and its
extension, the ADReSSo dataset, comparing our method with existing approaches.
Our method achieves an accuracy of 83.1% in the ADReSSo test set. The results
demonstrate the effectiveness of our approach in discriminating between AD
patients and healthy individuals, highlighting the potential of pauses as a
valuable indicator for AD detection. By leveraging speech analysis as a
non-invasive and cost-effective tool for AD detection, our research contributes
to early diagnosis and improved management of this debilitating disease.
;Comment: accepted by ICASSP2025. Copyright 2025 IEEE. Personal use of this
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White matter hyperintensities (WMH) are key imaging markers in cognitive aging, Alzheimer's disease (AD), and related dementias. Although automated methods for WMH segmentation have advanced, most provide only global lesion load and overlook their spatial distribution across distinct white matter regions. We propose a deep learning framework for robust WMH segmentation and localization, evaluated across public datasets and an independent Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Our results show that the predicted lesion loads are in line with the reference WMH estimates, confirming the robustness to variations in lesion load, acquisition, and demographics. Beyond accurate segmentation, we quantify WMH load within anatomically defined regions and combine these measures with brain structure volumes to assess diagnostic value. Regional WMH volumes consistently outperform global lesion burden for disease classification, and integration with brain atrophy metrics further improves performance, reaching area under the curve (AUC) values up to 0.97. Several spatially distinct regions, particularly within anterior white matter tracts, are reproducibly associated with diagnostic status, indicating localized vulnerability in AD. These results highlight the added value of regional WMH quantification. Incorporating localized lesion metrics alongside atrophy markers may enhance early diagnosis and stratification in neurodegenerative disorders. ;Accepted at SPIE - Medical Imaging Conference 2026
We present a connectome-informed LLM framework that encodes dynamic fMRI connectivity as temporal sequences, applies robust normalization, and maps these data into a representation suitable for a frozen pre-trained LLM for clinical prediction. Applied to early Alzheimer's detection, our method achieves sensitive prediction with error rates well below clinically recognized margins, with implications for timely Alzheimer's intervention.
An interpretable machine learning (ML) framework is introduced to enhance the
diagnosis of Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) by
ensuring robustness of the ML models' interpretations. The dataset used
comprises volumetric measurements from brain MRI and genetic data from healthy
individuals and patients with MCI/AD, obtained through the Alzheimer's Disease
Neuroimaging Initiative. The existing class imbalance is addressed by an
ensemble learning approach, while various attribution-based and
counterfactual-based interpretability methods are leveraged towards producing
diverse explanations related to the pathophysiology of MCI/AD. A unification
method combining SHAP with counterfactual explanations assesses the
interpretability techniques' robustness. The best performing model yielded
87.5% balanced accuracy and 90.8% F1-score. The attribution-based
interpretability methods highlighted significant volumetric and genetic
features related to MCI/AD risk. The unification method provided useful
insights regarding those features' necessity and sufficiency, further
showcasing their significance in MCI/AD diagnosis.
MEG are non invasive neuroimaging techniques with excellent temporal and
spatial resolution, crucial for studying brain function in dementia and
Alzheimer Disease. They identify changes in brain activity at various Alzheimer
stages, including preclinical and prodromal phases. MEG may detect pathological
changes before clinical symptoms, offering potential biomarkers for
intervention. This study evaluates classification techniques using MEG features
to distinguish between healthy controls and mild cognitive impairment
participants from the BioFIND study. We compare MEG based biomarkers with MRI
based anatomical features, both independently and combined. We used 3 Tesla MRI
and MEG data from 324 BioFIND participants;158 MCI and 166 HC. Analyses were
performed using MATLAB with SPM12 and OSL toolboxes. Machine learning analyses,
including 100 Monte Carlo replications of 10 fold cross validation, were
conducted on sensor and source spaces. Combining MRI with MEG features achieved
the best performance; 0.76 accuracy and AUC of 0.82 for GLMNET using LCMV
source based MEG. MEG only analyses using LCMV and eLORETA also performed well,
suggesting that combining uncorrected MEG with z-score-corrected MRI features
is optimal.
;Comment: 28 pages, 9 figures, 3 tables, 19 supplimetary material
Early detection of Alzheimer's disease from spontaneous speech has emerged as a promising non-invasive screening approach. However, the influence of automatic speech recognition (ASR) quality on downstream clinical language modeling remains insufficiently understood. In this study, we investigate Alzheimer's disease detection using lexical features derived from Whisper ASR transcripts on the ADReSSo 2021 diagnosis dataset. We evaluate interpretable machine-learning models, including Logistic Regression and Linear Support Vector Machines, using TF-IDF text representations under repeated 5x5 stratified cross-validation.
Our results demonstrate that transcript quality has a statistically significant impact on classification performance. Models trained on Whisper-small transcripts consistently outperform those using Whisper-base transcripts, achieving balanced accuracy above 0.7850 with Linear SVM. Paired statistical testing confirms that the observed improvements are significant. Importantly, classifier complexity contributes less to performance variation than ASR transcription quality. Feature analysis reveals that cognitively normal speakers produce more semantically precise object- and scene-descriptive language, whereas Alzheimer's speech is characterized by vagueness, discourse markers, and increased hesitation patterns.
These findings suggest that high-quality ASR can enable simple, interpretable lexical models to achieve competitive Alzheimer's detection performance without explicit acoustic modeling. The study provides a reproducible benchmark pipeline and highlights ASR selection as a critical modeling decision in clinical speech-based artificial intelligence systems. ;22 pages, 7 figures
Alzheimer's disease detection requires expensive neuroimaging or invasive procedures, limiting accessibility. This study explores whether deep learning can enable non-invasive Alzheimer's disease detection through handwriting analysis. Using a dataset of 34 distinct handwriting tasks collected from healthy controls and Alzheimer's disease patients, we evaluate and compare three recurrent neural architectures (LSTM, GRU, RNN) against traditional machine learning models. A crucial distinction of our approach is that the recurrent models process pre-extracted features from discrete strokes, not raw temporal signals. This violates the assumption of a continuous temporal flow that recurrent networks are designed to capture. Results reveal that they exhibit poor specificity and high variance. Traditional ensemble methods significantly outperform all deep architectures, achieving higher accuracy with balanced metrics. This demonstrates that recurrent architectures, designed for continuous temporal sequences, fail when applied to feature vectors extracted from ambiguously segmented strokes. Despite their complexity, deep learning models cannot overcome the fundamental disconnect between their architectural assumptions and the discrete, feature-based nature of stroke-level handwriting data. Although performance is limited, the study highlights several critical issues in data representation and model compatibility, pointing to valuable directions for future research.
Early and accurate diagnosis of Alzheimer's disease (AD), a complex neurodegenerative disorder, requires analysis of heterogeneous biomarkers (e.g., neuroimaging, genetic risk factors, cognitive tests, and cerebrospinal fluid proteins) typically represented in a tabular format. With flexible few-shot reasoning, multimodal integration, and natural-language-based interpretability, large language models (LLMs) offer unprecedented opportunities for prediction with structured biomedical data. We propose a novel framework called TAP-GPT, Tabular Alzheimer's Prediction GPT, that adapts TableGPT2, a multimodal tabular-specialized LLM originally developed for business intelligence tasks, for AD diagnosis using structured biomarker data with small sample sizes. Our approach constructs few-shot tabular prompts using in-context learning examples from structured biomedical data and finetunes TableGPT2 using the parameter-efficient qLoRA adaption for a clinical binary classification task of AD or cognitively normal (CN). The TAP-GPT framework harnesses the powerful tabular understanding ability of TableGPT2 and the encoded prior knowledge of LLMs to outperform more advanced general-purpose LLMs and a tabular foundation model (TFM) developed for prediction tasks. To our knowledge, this is the first application of LLMs to the prediction task using tabular biomarker data, paving the way for future LLM-driven multi-agent frameworks in biomedical informatics. ;accepted by ACM-BCB'25: ACM Conference on Bioinformatics, Computational Biology, and Health Informatics [ACM SIGBio Best Paper Award]
Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions
worldwide, necessitating early and accurate diagnosis for optimal patient
management. In recent years, advancements in deep learning have shown
remarkable potential in medical image analysis. Methods In this study, we
present "ViTranZheimer," an AD diagnosis approach which leverages video vision
transformers to analyze 3D brain MRI data. By treating the 3D MRI volumes as
videos, we exploit the temporal dependencies between slices to capture
intricate structural relationships. The video vision transformer's
self-attention mechanisms enable the model to learn long-range dependencies and
identify subtle patterns that may indicate AD progression. Our proposed deep
learning framework seeks to enhance the accuracy and sensitivity of AD
diagnosis, empowering clinicians with a tool for early detection and
intervention. We validate the performance of the video vision transformer using
the ADNI dataset and conduct comparative analyses with other relevant models.
Results The proposed ViTranZheimer model is compared with two hybrid models,
CNN-BiLSTM and ViT-BiLSTM. CNN-BiLSTM is the combination of a convolutional
neural network (CNN) and a bidirectional long-short-term memory network
(BiLSTM), while ViT-BiLSTM is the combination of a vision transformer (ViT)
with BiLSTM. The accuracy levels achieved in the ViTranZheimer, CNN-BiLSTM, and
ViT-BiLSTM models are 98.6%, 96.479%, and 97.465%, respectively. ViTranZheimer
demonstrated the highest accuracy at 98.6%, outperforming other models in this
evaluation metric, indicating its superior performance in this specific
evaluation metric. Conclusion This research advances the understanding of
applying deep learning techniques in neuroimaging and Alzheimer's disease
research, paving the way for earlier and less invasive clinical diagnosis.
Predicting whether an individual with Alzheimer's disease will experience mild or severe disease progression is essential for personalized treatment. Typically, practitioners seek to predict the distribution of a discrete disease score, conditional on an individual's current MRI volume and their historical disease trajectory. Classical statistical regression models and single-task neural networks are not well-suited for this purpose because fitting separate models is infeasible (since each individual typically has few observations), while ignoring individual-level correlation leads to poor generalization. Meta-learning, in contrast, provides a natural avenue to dynamically predict distributions without retraining and model nonlinear relationships between the outcome and covariates. Motivated by this, we propose a Bayesian meta-learner that is trained on multiple individuals but tailors the predictive disease score distribution to each individual's historical data. Our model predicts on unseen individuals without retraining, scales linearly with the number of historical observations, and is guaranteed to be less overconfident when predicting long-term disease scores compared to its deterministic counterpart. On real-world data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, our model achieves performance competitive with both single-task models and deterministic meta-learners, while substantially improving performance when predicting long-term disease progression.
INTRODUCTION: For many patients and caregivers, a major goal of disease-modifying treatments (DMT) for Alzheimer disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs. METHODS: Participants at the Knight Alzheimer Disease Research Center were selected who were potentially eligible for recent DMT trials: age ≥ 60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating® (CDR®) score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed effects models. RESULTS: 282 participants were followed for an average of 2.9 years (SD 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB>4.5 and in BADLs at CDR-SB>11.5. For individuals with a baseline CDR-SB=2, treatment with lecanemab would extend independence in IADLs for 10 months (95% CI 4-18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6-24 months). DISCUSSION: Independence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that predominantly affects the elderly population and currently has no cure. Magnetic Resonance Imaging (MRI), as a non-invasive imaging technique, is essential for the early diagnosis of AD. MRI inherently contains both spatial and frequency information, as raw signals are acquired in the frequency domain and reconstructed into spatial images via the Fourier transform. However, most existing AD diagnostic models extract features from a single domain, limiting their capacity to fully capture the complex neuroimaging characteristics of the disease. While some studies have combined spatial and frequency information, they are mostly confined to 2D MRI, leaving the potential of dual-domain analysis in 3D MRI unexplored. To overcome this limitation, we propose Spatio-Frequency Network (SFNet), the first end-to-end deep learning framework that simultaneously leverages spatial and frequency domain information to enhance 3D MRI-based AD diagnosis. SFNet integrates an enhanced dense convolutional network to extract local spatial features and a global frequency module to capture global frequency-domain representations. Additionally, a novel multi-scale attention module is proposed to further refine spatial feature extraction. Experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate that SFNet outperforms existing baselines and reduces computational overhead in classifying cognitively normal (CN) and AD, achieving an accuracy of 95.1%.
Accumulation of amyloid beta proteins is a defining feature of Alzheimer's disease, and is usually accompanied by cerebrovascular pathology. Evidence suggests that amyloid beta and cerebrovascular pathology are mutually reinforcing; in particular, amyloid beta suppresses perfusion by constricting capillaries, and hypoperfusion promotes the production of amyloid beta. Here, we propose a whole-brain model coupling amyloid beta and blood vessel through a hybrid model consisting of a reaction-diffusion system for the protein dynamics and porous-medium model of blood flow within and between vascular networks: arterial, capillary and venous. We discretize the resulting parabolic--elliptic system of PDEs by means of a high-order discontinuous Galerkin method in space and an implicit Euler scheme in time. Simulations in realistic brain geometries demonstrate the emergence of multistability, implying that a sufficiently large pathogenic protein seeds is necessary to trigger disease outbreak. Motivated by the "two-hit vascular hypothesis" of Alzheimer's disease that hypoperfusive vascular damage triggers amyloid beta pathology, we also demonstrate that localized hypoperfusion, in response to injury, can destabilize the healthy steady state and trigger brain-wide disease outbreak.
Generative AI framework-based modeling and prediction of longitudinal human brain images offer an efficient mechanism to track neurodegenerative progression, essential for the assessment of diseases like Alzheimer's. Among the existing generative approaches, recent diffusion-based models have emerged as an effective alternative to generate disease progression images. Incorporating multi-modal and non-imaging attributes as conditional information into diffusion frameworks has been shown to improve controllability during such generations. However, existing methods do not explicitly ensure that information from non-imaging conditioning modalities is meaningfully aligned with image features to introduce desirable changes in the generated images, such as modulation of progression-specific regions. Further, more precise control over the generation process can be achieved by introducing progression-relevant structure into the internal representations of the model, lacking in the existing approaches. To address these limitations, we propose a diffusion autoencoder-based framework for disease progression modeling that explicitly enforces alignment between different modalities. The alignment is enforced by introducing an explicit objective function that enables the model to focus on the regions exhibiting progression-related changes. Further, we devise a mechanism to better structure the latent representational space of the diffusion auto-encoding framework. Specifically, we assign separate latent subspaces for integrating progression-related conditions and retaining subject-specific identity information, allowing better-controlled image generation. These results demonstrate that enforcing alignment and better structuring of the latent representational space of diffusion auto-encoding framework leads to more anatomically precise modeling of Alzheimer's disease progression.
Recent advancements in generative AI have fostered the development of highly adept Large Language Models (LLMs) that integrate diverse data types to empower decision-making. Among these, multimodal retrieval-augmented generation (RAG) applications are promising because they combine the strengths of information retrieval and generative models, enhancing their utility across various domains, including clinical use cases. This paper introduces AlzheimerRAG, a Multimodal RAG application for clinical use cases, primarily focusing on Alzheimer's Disease case studies from PubMed articles. This application incorporates cross-modal attention fusion techniques to integrate textual and visual data processing by efficiently indexing and accessing vast amounts of biomedical literature. Our experimental results, compared to benchmarks such as BioASQ and PubMedQA, have yielded improved performance in the retrieval and synthesis of domain-specific information. We also present a case study using our multimodal RAG in various Alzheimer's clinical scenarios. We infer that AlzheimerRAG can generate responses with accuracy non-inferior to humans and with low rates of hallucination.
Individualized Alzheimer's disease (AD) progression prediction requires models that use irregular visits, account for censoring, avoid diagnostic leakage, and provide calibrated horizon risks. We propose PROgression-aware MultI-horizon Survival Estimation for Alzheimer's Disease (PROMISE-AD), a leakage-safe survival framework for predicting conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD dementia using ADNI/TADPOLE tabular histories. PROMISE-AD converts pre-index visits into tokens with standardized measurements, missingness masks, longitudinal changes, time-normalized slopes, visit timing, and non-diagnostic categorical attributes. A temporal Transformer fuses global, attention-pooled, and latest-visit representations to estimate a progression score and latent discrete-time mixture hazards. Training combines survival likelihood, horizon-specific focal risk loss, progression ranking, hazard smoothness, and mixture-balance regularization, followed by validation-set isotonic calibration for 1-, 2-, 3-, and 5-year risks. In held-out testing across three seeds, PROMISE-AD achieved an integrated Brier score (IBS) of 0.085 $\pm$ 0.012, C-index of 0.808 $\pm$ 0.015, and mean time-dependent AUC of 0.840 $\pm$ 0.081 for CN-to-MCI conversion, yielding the lowest IBS among compared methods. For MCI-to-AD conversion, PROMISE-AD achieved the highest C-index (0.894 $\pm$ 0.018) and near-ceiling 5-year discrimination (AUROC 0.997 $\pm$ 0.003; AUPRC 0.999 $\pm$ 0.001), although some baselines had lower IBS. Ablations and interpretability supported longitudinal change features, fused temporal representations, mixture hazards, cognitive and functional measures, APOE4 status, and recent conversion-proximal visits. These findings suggest that progression-aware survival modeling can provide interpretable multi-horizon AD conversion risk estimates.
The development of monoclonal anti-amyloid antibodies, a disease-modifying treatment for Alzheimer’s disease (AD), has raised the necessity to identify the epidemiological profile of the possible target patients who would benefit from such therapy. These are patients in the early stages of AD with biomarker-confirmed brain amyloid positivity. In this study, the epidemiological profile of possible target patients in Austria and Vienna was estimated. The number of patients in the stage of amyloid-beta (Aβ)-positive prodromal AD in Austria and Vienna are 193,500 and 34,700 patients, respectively. The expected patient demand for the upcoming therapy in Austria and Vienna are 61,200 and 11,100 patients, respectively. In the memory clinic of the Vienna General Hospital, the number of treatment-eligible patients for an upcoming anti-amyloid antibody was on average 52.8 patients per year, which is about 10% of the total number of patients visiting the memory clinic every year. Several challenges to provide therapy to the general population include expanding the MCI screening in primary care and increasing the capacity of the healthcare system for biomarker testing, infusion delivery, and ARIA management. The study primarily addresses the status quo of identifying patients on memory clinics through cognitive screening and biomarker testing.
Alzheimer's Disease is a progressive neurological disorder that is one of the
most common forms of dementia. It leads to a decline in memory, reasoning
ability, and behavior, especially in older people. The cause of Alzheimer's
Disease is still under exploration and there is no all-inclusive theory that
can explain the pathologies in each individual patient. Nevertheless, early
intervention has been found to be effective in managing symptoms and slowing
down the disease's progression. Recent research has utilized
electroencephalography (EEG) data to identify biomarkers that distinguish
Alzheimer's Disease patients from healthy individuals. Prior studies have used
various machine learning methods, including deep learning and graph neural
networks, to examine electroencephalography-based signals for identifying
Alzheimer's Disease patients. In our research, we proposed a Flexible and
Explainable Gated Graph Convolutional Network (GGCN) with Multi-Objective
Tree-Structured Parzen Estimator (MOTPE) hyperparameter tuning. This provides a
flexible solution that efficiently identifies the optimal number of GGCN blocks
to achieve the optimized precision, specificity, and recall outcomes, as well
as the optimized area under the Receiver Operating Characteristic (AUC). Our
findings demonstrated a high efficacy with an over 0.9 Receiver Operating
Characteristic score, alongside precision, specificity, and recall scores in
distinguishing health control with Alzheimer's Disease patients in Moderate to
Severe Dementia using the power spectrum density (PSD) of
electroencephalography signals across various frequency bands. Moreover, our
research enhanced the interpretability of the embedded adjacency matrices,
revealing connectivity differences in frontal and parietal brain regions
between Alzheimer's patients and healthy individuals.
Alzheimer's Disease is a neurodegenerative condition characterized by
dementia and impairment in neurological function. The study primarily focuses
on the individuals above age 40, affecting their memory, behavior, and
cognitive processes of the brain. Alzheimer's disease requires diagnosis by a
detailed assessment of MRI scans and neuropsychological tests of the patients.
This project compares existing deep learning models in the pursuit of enhancing
the accuracy and efficiency of AD diagnosis, specifically focusing on the
Convolutional Neural Network, Bayesian Convolutional Neural Network, and the
U-net model with the Open Access Series of Imaging Studies brain MRI dataset.
Besides, to ensure robustness and reliability in the model evaluations, we
address the challenge of imbalance in data. We then perform rigorous evaluation
to determine strengths and weaknesses for each model by considering
sensitivity, specificity, and computational efficiency. This comparative
analysis would shed light on the future role of AI in revolutionizing AD
diagnostics but also paved ways for future innovation in medical imaging and
the management of neurodegenerative diseases.
Brain imaging has allowed neuroscientists to analyze brain morphology in
genetic and neurodevelopmental disorders, such as Down syndrome, pinpointing
regions of interest to unravel the neuroanatomical underpinnings of cognitive
impairment and memory deficits. However, the connections between brain anatomy,
cognitive performance and comorbidities like Alzheimer's disease are still
poorly understood in the Down syndrome population. The latest advances in
artificial intelligence constitute an opportunity for developing automatic
tools to analyze large volumes of brain magnetic resonance imaging scans,
overcoming the bottleneck of manual analysis. In this study, we propose the use
of generative models for detecting brain alterations in people with Down
syndrome affected by various degrees of neurodegeneration caused by Alzheimer's
disease. To that end, we evaluate state-of-the-art brain anomaly detection
models based on Variational Autoencoders and Diffusion Models, leveraging a
proprietary dataset of brain magnetic resonance imaging scans. Following a
comprehensive evaluation process, our study includes several key analyses.
First, we conducted a qualitative evaluation by expert neuroradiologists.
Second, we performed both quantitative and qualitative reconstruction fidelity
studies for the generative models. Third, we carried out an ablation study to
examine how the incorporation of histogram post-processing can enhance model
performance. Finally, we executed a quantitative volumetric analysis of
subcortical structures. Our findings indicate that some models effectively
detect the primary alterations characterizing Down syndrome's brain anatomy,
including a smaller cerebellum, enlarged ventricles, and cerebral cortex
reduction, as well as the parietal lobe alterations caused by Alzheimer's
disease.
Objective
This study introduces the Alzheimer's Disease Common Data Element Ontology for Clinical Trials (AD-CDO), a lightweight, semantically enriched ontology designed to represent and standardize key eligibility criteria concepts in Alzheimer's disease (AD) clinical trials.
Materials and Methods
We extracted high-frequency concepts from more than 1,500 AD clinical trials on ClinicalTrials.gov and organized them into seven semantic categories: Disease, Medication, Diagnostic Test, Procedure, Social Determinants of Health, Rating Criteria, and Fertility. Each concept was annotated with standard biomedical vocabularies, including the UMLS, OMOP Standardized Vocabularies, DrugBank, NDC, and NLM VSAC value sets. To balance coverage and manageability, we applied the Jenks Natural Breaks method to identify an optimal set of representative concepts.
Results
The optimized AD-CDO achieved over 63% coverage of extracted trial concepts while maintaining interpretability and compactness. The ontology effectively captured the most frequent and clinically meaningful entities used in AD eligibility criteria. We demonstrated AD-CDO's practical utility through two use cases: (a) an ontology-driven trial simulation system for formal modeling and virtual execution of clinical trials, and (b) an entity normalization task mapping raw clinical text to ontology-aligned terms, enabling consistency and integration with EHR data.
Discussion
AD-CDO bridges the gap between broad biomedical ontologies and task-specific trial modeling needs. It supports multiple downstream applications, including phenotyping algorithm development, cohort identification, and structured data integration.
Conclusion
By harmonizing essential eligibility entities and aligning them with standardized vocabularies, AD-CDO provides a versatile foundation for ontology-driven AD clinical trial research.
Alzheimer's disease (AD) is the leading cause of dementia, and its early
detection is crucial for effective intervention, yet current diagnostic methods
often fall short in sensitivity and specificity. This study aims to detect
significant indicators of early AD by extracting and integrating various
imaging biomarkers, including radiomics, hippocampal texture descriptors,
cortical thickness measurements, and deep learning features. We analyze
structural magnetic resonance imaging (MRI) scans from the Alzheimer's Disease
Neuroimaging Initiative (ADNI) cohorts, utilizing comprehensive image analysis
and machine learning techniques. Our results show that combining multiple
biomarkers significantly improves detection accuracy. Radiomics and texture
features emerged as the most effective predictors for early AD, achieving AUCs
of 0.88 and 0.72 for AD and MCI detection, respectively. Although deep learning
features proved to be less effective than traditional approaches, incorporating
age with other biomarkers notably enhanced MCI detection performance.
Additionally, our findings emphasize the continued importance of classical
imaging biomarkers in the face of modern deep-learning approaches, providing a
robust framework for early AD diagnosis.
;Comment: SPIE Medical Imaging (MI25)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with
increasing prevalence among the aging population, necessitating early and
accurate diagnosis for effective disease management. In this study, we present
a novel hybrid deep learning framework that integrates both 2D Convolutional
Neural Networks (2D-CNN) and 3D Convolutional Neural Networks (3D-CNN), along
with a custom loss function and volumetric data augmentation, to enhance
feature extraction and improve classification performance in AD diagnosis.
According to extensive experiments, AlzhiNet outperforms standalone 2D and 3D
models, highlighting the importance of combining these complementary
representations of data. The depth and quality of 3D volumes derived from the
augmented 2D slices also significantly influence the model's performance. The
results indicate that carefully selecting weighting factors in hybrid
predictions is imperative for achieving optimal results. Our framework has been
validated on the Magnetic Resonance Imaging (MRI) from Kaggle and MIRIAD
datasets, obtaining accuracies of 98.9% and 99.99%, respectively, with an AUC
of 100%. Furthermore, AlzhiNet was studied under a variety of perturbation
scenarios on the Alzheimer's Kaggle dataset, including Gaussian noise,
brightness, contrast, salt and pepper noise, color jitter, and occlusion. The
results obtained show that AlzhiNet is more robust to perturbations than
ResNet-18, making it an excellent choice for real-world applications. This
approach represents a promising advancement in the early diagnosis and
treatment planning for Alzheimer's disease.
Researchers are constantly trying to develop therapeutic targets in neurodegenerative disorders like Alzheimer's dementia and Parkinson's disease. Despite enormous endeavors, there are several unmet needs. Several contradictory pathophysiological basis of neurodegenerative disorders are considered to be one of the most important cause underpinning. "Gut–brain dysbiosis" has been considered as one of the most crucial link to explore. Contemporary researches have suggested similar pathophysiological mechanisms underpinning Alzheimer's dementia and Parkinson's disease. "Gut–brain dysbiosis" may be the missing thread connecting Alzheimer's dementia and Parkinson's disease prior to the expression of their overt clinical phenotype. Recognition of preclinical phenotype of Alzheimer's dementia and Parkinson's disease have much broader perspective as it will help in building robust therapeutics at the earliest. Authors herein critically analyze the pathophysiological basis of Alzheimer's dementia and Parkinson's disease in relationship with "Gut–brain dysbiosis" and also try to search the preclinical phenotype/s of Alzheimer's dementia and Parkinson's disease pivoting around the Freudian hypothesis.
Retinal optical coherence tomography (OCT) images are the biomarkers for neurodegenerative diseases, which are rising in prevalence. Early detection of Alzheimer's disease using retinal OCT is a primary challenging task. This work utilizes advanced deep learning techniques to classify retinal OCT images of subjects with Alzheimer's disease (AD) and healthy controls (CO). The goal is to enhance diagnostic capabilities through efficient image analysis. In the proposed model, Raw OCT images have been preprocessed with ImageJ and given to various deep-learning models to evaluate the accuracy. The best classification architecture is TransNetOCT, which has an average accuracy of 98.18% for input OCT images and 98.91% for segmented OCT images for five-fold cross-validation compared to other models, and the Swin Transformer model has achieved an accuracy of 93.54%. The evaluation accuracy metric demonstrated TransNetOCT and Swin transformer models capability to classify AD and CO subjects reliably, contributing to the potential for improved diagnostic processes in clinical settings. ;18 pages, 25 figures
25 wetenschappelijke publicaties binnen het domein Amyotrofische Laterale Sclerose
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Amyotrophic lateral sclerosis (ALS) is associated with considerable clinical heterogeneity spanning from diverse disability profiles, differences in UMN/LMN involvement, divergent progression rates, to variability in frontotemporal dysfunction. A multitude of classification frameworks and staging systems have been proposed based on clinical and neuropsychological characteristics, but disease subtypes are seldom defined based on anatomical patterns of disease burden without a prior clinical stratification. A prospective research study was conducted with a uniform imaging protocol to ascertain disease subtypes based on preferential cerebral involvement. Fifteen brain regions were systematically evaluated in each participant based on a comprehensive panel of cortical, subcortical and white matter integrity metrics. Using min–max scaled composite regional integrity scores, a two-step cluster analysis was conducted. Two radiological clusters were identified; 35.5% of patients belonging to ‘Cluster 1’ and 64.5% of patients segregating to ‘Cluster 2’. Subjects in Cluster 1 exhibited marked frontotemporal change. Predictor ranking revealed the following hierarchy of anatomical regions in decreasing importance: superior lateral temporal, inferior frontal, superior frontal, parietal, limbic, mesial inferior temporal, peri-Sylvian, subcortical, long association fibres, commissural, occipital, ‘sensory’, ‘motor’, cerebellum, and brainstem. While the majority of imaging studies first stratify patients based on clinical criteria or genetic profiles to describe phenotype- and genotype-associated imaging signatures, a data-driven approach may identify distinct disease subtypes without a priori patient categorisation. Our study illustrates that large radiology datasets may be potentially utilised to uncover disease subtypes associated with unique genetic, clinical or prognostic profiles.
Background A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS. Methods ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months. Discussion Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group. Trial registration ClinicalTrials.gov NCT04745299 . Registered on Feb 9, 2021. Clinical Research Information Service (CRIS) KCT0005954 . Registered on Mar 4, 2021.
Introduction The absence of nigrosome 1 on brain MRI and the hyperechogenicity of substantia nigra (SNh) by transcranial sonography are two useful biomarkers in the diagnosis of parkinsonisms. We aimed to evaluate the absence of nigrosome 1 in amyotrophic lateral sclerosis (ALS) and to address its meaning. Methods 136 ALS patients were recruited, including 16 progressive muscular atrophy (PMA) and 22 primary lateral sclerosis (PLS) patients. The SNh area was measured planimetrically by standard protocols. The nigrosome 1 status was qualitatively assessed by two blind evaluators in susceptibility weight images of 3T MRI. Demographic and clinical data were collected and the C9ORF72 expansion was tested in all patients. Results Nigrosome 1 was absent in 30% of ALS patients (36% of PLS, 29% of classical ALS and 19% of PMA patients). There was no relationship between radiological and clinical laterality, nor between nigrosome 1 and SNh area. Male sex (OR = 3.63 [1.51, 9.38], p = 0.005) and a higher upper motor neuron (UMN) score (OR = 1.10 [1.02, 1.2], p = 0.022) were independently associated to nigrosome 1 absence, which also was an independent marker of poor survival (HR = 1.79 [1.3, 2.8], p = 0.013). Conclusion In ALS patients, the absence of nigrosome 1 is associated with male sex, UMN impairment and shorter survival. This suggests that constitutional factors and the degree of pyramidal involvement are related to the substantia nigra involvement in ALS. Thus, nigrosome 1 could be a marker of a multisystem degeneration, which in turn associates to poor prognosis.
Introduction Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. Methods This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients’ needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. Perspective It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. Trial registration The study is registered at ClinicalTrails.gov; NCT06418646
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons (MNs). Since the identification of the first ALS mutation in 1993, more than 40 genes have been associated with the disorder. The most frequent genetic causes of ALS are represented by mutated genes whose products challenge proteostasis, becoming unable to properly fold and consequently aggregating into inclusions that impose proteotoxic stress on affected cells. In this context, increasing evidence supports the central role played by autophagy dysfunctions in the pathogenesis of ALS. Indeed, in early stages of disease, high levels of proteins involved in autophagy are present in ALS MNs; but at the same time, with neurodegeneration progression, autophagy-mediated degradation decreases, often as a result of the accumulation of toxic protein aggregates in affected cells. Autophagy is a complex multistep pathway that has a central role in maintaining cellular homeostasis. Several proteins are involved in its tight regulation, and importantly a relevant fraction of ALS-related genes encodes products that directly take part in autophagy, further underlining the relevance of this key protein degradation system in disease onset and progression. In this review, we report the most relevant findings concerning ALS genes whose products are involved in the several steps of the autophagic pathway, from phagophore formation to autophagosome maturation and transport and finally to substrate degradation.
The activation and dysregulation of retrotransposons has been identified in the CNS of individuals with the fatal neurodegenerative disorder Amyotrophic lateral sclerosis (ALS). This includes elements from multiple different families and subfamilies of retrotransposons, however there is limited knowledge of the specific loci from which this expression occurs in ALS. The long interspersed element-1 (L1) is the only autonomous retrotransposon in the human genome and members of this family of elements maintain the ability to mobilise. Despite L1s contributing to 17% of the human genome only 80–100 L1s encode the required proteins for mobilisation and are retrotransposition competent. Identifying the specific loci from which L1 expression occurs will inform on the potential functional consequences of their expression, such as the potential for somatic retrotransposition or DNA damage caused by the endonuclease activity of the ORF2 protein of the L1. Here we characterised L1 loci expression using the L1EM tool ( https://github.com/FenyoLab/L1EM ) in RNA sequencing data from 518 samples across four tissues (motor cortex, frontal cortex, cerebellum and cervical spinal cord) in the Target ALS cohort obtained from the New York Genome Center. There was a significant reduction in total intact L1 expression (those that encode functional proteins) in two brain regions of individuals with ALS compared to controls and clustering of the ALS brain regions occurred based on their intact L1 expression profile. Although overall the levels of L1 expression were reduced in ALS/ALS with other neurological disorder (ND) there were individuals in which L1s were expressed at much higher levels than the rest of the ALS/ALSND cohort. Expressed L1 loci were more frequently located in introns compared to those not expressed and the level of L1 expression positively correlated with the expression of the gene in which it was located. Significant differences were observed in the expression profiles of L1s in ALS and specific features of these elements, such as location in the genome and whether or not they are intact, were significantly associated with those that were expressed in the cohort.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle weakness. Presence of pain in ALS patients is heterogeneously reported in studies, and mostly underrepresented in symptom scales. The aim of this study is to evaluate the efficacy of pharmacological and non-pharmacological therapeutic modalities for pain management in patients with ALS. A systematic review was conducted in four databases; PubMed, Scopus, Clinicaltrials.gov, and Cochrane-Ovid. Five randomized controlled clinical trials were included regarding pharmacological and non-pharmacological pain management interventions in adult patients with confirmed diagnosis of ALS in whom pain was objectively evaluated. Risk of bias assessment was evaluated using the RoB2.0 tool. Eligible studies were reported as a descriptive analysis. This systematic review was registered with PROSPERO ID: CRD42024495009. Five clinical trials regarding pain management strategies in ALS were eligible for analysis. Two out of five were non-pharmacological approaches whilst the remaining three provided pharmacological therapies. Of these, Mexiletine was efficient in terms of pain relief, particularly between 600 and 900 mg per day, whereas Mecasin showed no pain relief at both, high and low doses. Non-pharmacological therapies, such as exercise and osteopathic manual treatment also lacked efficacy in regard to pain management. Clinical trials focusing on pain management strategies for ALS patients are limited. Medical professionals, understandably focused on immediate life-threatening aspects, may inadvertently sideline the nuanced and intricate dimension of pain experienced by patients with ALS.
Background Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. Methods Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. Results The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0–3) in ALS and 0 (0–0) in non-ALS patients ( P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. Discussion The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. Conclusions The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.
Introduction Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG18 is a rare, early-onset, complicated HSP, first reported as linked to biallelic ERLIN2 mutations. Recent cases of late-onset, pure HSP with monoallelic ERLIN2 variants prompt inquiries into the zygosity of such genetic conditions. The observed relationship between phenotype and mode of inheritance suggests a potential dominant negative effect of mutated ERLIN2 protein, potentially resulting in a milder phenotype. This speculation suggests that a wider range of HSP genes could be linked to various inheritance patterns. Purpose and background With documented cases of HSP loci exhibiting both dominant and recessive patterns, this study emphasizes that the concept of zygosity is no longer a limiting factor in the establishment of molecular diagnoses for HSP. Recent cases have demonstrated phenoconversion in SPG18, from HSP to an amyotrophic lateral sclerosis (ALS)-like syndrome. Methods and results This report highlights two cases out of five exhibiting HSP-ALS phenoconversion, discussing an observed prevalence in autosomal dominant SPG18. Additionally, the study emphasizes the relatively high incidence of the c.502G>A variant in monoallelic SPG18 cases. This mutation appears to be particularly common in cases of HSPALS phenoconversion, indicating its potential role as a hotspot for a distinctive SPG18 phenotype with an ALS-like syndrome. Conclusions Clinicians need to be aware that patients with HSP may show ALS signs and symptoms. On the other hand, HSP panels must be included in genetic testing methods for instances of familial ALS.
TDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped human post-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection of Stathmin-2 ( STMN-2 ) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical phenotype is not known. To address these outstanding questions, we used a novel RNA aptamer, TDP-43^APT, to detect TDP-43 pathology and used single molecule in situ hybridization to sensitively reveal TDP-43 loss-of-function and applied these in a deeply phenotyped human post-mortem tissue cohort. We demonstrate that TDP-43^APT identifies pathological TDP-43, detecting aggregation events that cannot be detected by classical antibody stains. We show that nuclear TDP-43 pathology is an early event, occurring prior to cytoplasmic accumulation and is associated with loss-of-function measured by coincident STMN-2 cryptic splicing pathology. Crucially, we show that these pathological features of TDP-43 loss-of-function precede the clinical inflection point and are not required for region specific clinical manifestation. Furthermore, we demonstrate that gain-of-function in the form of extensive cytoplasmic accumulation, but not loss-of-function, is the primary molecular correlate of clinical manifestation. Taken together, our findings demonstrate implications for early diagnostics as the presence of STMN-2 cryptic exons and early TDP-43 aggregation events could be detected prior to symptom onset, holding promise for early intervention in ALS.
Background Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities. Methods The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. Discussion This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS. Trial registration ClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.
Background Loss of motor neurons in amyotrophic lateral sclerosis (ALS) leads to progressive paralysis and death. Dysregulation of thousands of RNA molecules with roles in multiple cellular pathways hinders the identification of ALS-causing alterations over downstream changes secondary to the neurodegenerative process. How many and which of these pathological gene expression changes require therapeutic normalisation remains a fundamental question. Methods Here, we investigated genome-wide RNA changes in C9ORF72-ALS patient-derived neurons and Drosophila , as well as upon neuroprotection taking advantage of our gene therapy approach which specifically inhibits the SRSF1-dependent nuclear export of pathological C9ORF72 -repeat transcripts. This is a critical study to evaluate (i) the overall safety and efficacy of the partial depletion of SRSF1, a member of a protein family involved itself in gene expression, and (ii) a unique opportunity to identify neuroprotective RNA changes. Results Our study shows that manipulation of 362 transcripts out of 2257 pathological changes, in addition to inhibiting the nuclear export of repeat transcripts, is sufficient to confer neuroprotection in C9ORF72-ALS patient-derived neurons. In particular, expression of 90 disease-altered transcripts is fully reverted upon neuroprotection leading to the characterisation of a human C9ORF72-ALS disease-modifying gene expression signature. These findings were further investigated in vivo in diseased and neuroprotected Drosophila transcriptomes, highlighting a list of 21 neuroprotective changes conserved with 16 human orthologues in patient-derived neurons. We also functionally validated the high neuroprotective potential of one of these disease-modifying transcripts, demonstrating that inhibition of ALS-upregulated human KCNN1–3 ( Drosophila SK) voltage-gated potassium channel orthologs mitigates degeneration of human motor neurons and Drosophila motor deficits. Conclusions Strikingly, the partial depletion of SRSF1 leads to expression changes in only a small proportion of disease-altered transcripts, indicating that not all RNA alterations need normalization and that the gene therapeutic approach is safe in the above preclinical models as it does not disrupt globally gene expression. The efficacy of this intervention is also validated at genome-wide level with transcripts modulated in the vast majority of biological processes affected in C9ORF72-ALS. Finally, the identification of a characteristic signature with key RNA changes modified in both the disease state and upon neuroprotection also provides potential new therapeutic targets and biomarkers.
Background Amyotrophic lateral sclerosis (ALS) can present with either bulbar or spinal symptoms, and in some cases, both types of symptoms may be present. In addition, cognitive impairment has been observed in ALS. The study aimed to evaluate the frontal and general cognitive performance in ALS not only cross-sectionally but also longitudinally. Methods and materials The Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were employed to assess cognitive function in 52 adults with ALS and 52 cognitively healthy individuals. The statistical analyses encompassed the Pearson Chi square test, the Skillings-Mack test, the Spearman’s rank correlation coefficient, and the Proportional Odds Logistic Regression Model (POLR). Results Cross-sectionally, lower cognitive performance was associated with ALS diagnosis, older age, and motor functional decline. The cognitive impairment of individuals with bulbar and spinal-bulbar symptoms showed faster deterioration compared to those with spinal symptoms. The spinal subgroup consistently performed worst in delayed recall and attention, while the spinal-bulbar and bulbar subgroups exhibited inferior scores in delayed recall, attention, visuospatial skills, orientation, and verbal fluency. Conclusion The incorporation of cognitive screening in the diagnostic workup of ALS may be beneficial, as early detection can enhance symptom management and improve the quality of life for both individuals with ALS and their care partners.
Mutations in FUS and TBK1 often cause aggressive early-onset amyotrophic lateral sclerosis (ALS) or a late-onset ALS and/or frontotemporal dementia (FTD) phenotype, respectively. Co-occurrence of mutations in two or more Mendelian ALS/FTD genes has been repeatedly reported. However, little is known how two pathogenic ALS/FTD mutations in the same patient interact to shape the final phenotype. We screened 28 ALS patients with a known FUS mutation by whole-exome sequencing and targeted evaluation for mutations in other known ALS genes followed by genotype–phenotype correlation analysis of FUS/TBK1 double-mutant patients. We report on new and summarize previously published FUS and TBK1 double-mutant ALS/FTD patients and their families. We found that, within a family, mutations in FUS cause ALS while TBK1 single mutations are observed in FTD patients. FUS/TBK1 double mutations manifested as ALS and without a manifest difference regarding age at onset and disease duration when compared to FUS single-mutant individuals. In conclusion, TBK1 and FUS variants do not seem to interact in a simple additive way. Rather, the phenotype of FUS/TBK1 double-mutant patients appears to be dominated by the FUS mutation.
Background Uric acid (UA) has emerged as a factor that can modify cognitive function both in the general population and in people with neurodegenerative disorders. Since very few data are available concerning amyotrophic lateral sclerosis (ALS), we explored the correlation of UA levels and cognitive impairment in a large cohort of ALS patients. Methods We enrolled ALS patients consecutively seen at the Turin ALS expert center in the 2007–2018 period who underwent both cognitive/behavioral and UA evaluation at diagnosis. Patients were classified in 5 categories: normal cognition (ALS-CN), isolated cognitive impairment (ALSci), isolated behavioural impairment (ALSbi), cognitive and behavioural impairment (ALScbi), frontotemporal dementia (ALS-FTD). For this study, ALSci, ALSbi and ALScbi were merged as ALS with intermediate cognitive impairment (ALS-INT). Results Out of the 841 ALS patients, 422 had ALS-CN, 271 ALS-INT and 148 ALS-FTD. The mean values of UA were significantly different among the cognitive subgroups of patients, with the lowest values in the ALS-FTD (ALS-CN, 288.5 ± 78.0 (μmol/L; ALS-INT, 289.7 ± 75.5 μmol/L; ALS-FTD, 271.8 ± 74.9 μmol/L; p = 0.046). The frequency of ALS-FTD was significantly higher in the 1st tertile of UA. Lower UA levels were independently associated with FTD (OR 1.32, 95% c.i. 1.01–1.43; p = 0.038) in binary logistic regression. Conclusions We found that in ALS lower UA serum levels are correlated with reduced frequency of co-morbid FTD. Patients with intermediate cognitive impairment showed UA levels similar to ALS-CN but higher than ALS-FTD, implying that higher UA levels can prevent or delay cognitive function deterioration.
There has been a recent shift towards proactive dysphagia intervention in motor neurone disease (MND) to maintain physiological reserve. Pharyngeal high-resolution manometry (PHRM) can quantify swallowing pathophysiology to inform and evaluate proactive dysphagia intervention. This study aims to explore the current use of PHRM as a dysphagia evaluation in adults with MND. A scoping review based on the Joanna Briggs Framework was completed. Four electronic databases (PubMed, EMBASE, CINAHL and Web of Science core) were searched (inception to March 2021) by two independent researchers. Data were analysed according to (i) PHRM protocol and analysis methods and the feasibility of same, (ii) swallow biomechanics data and (iii) dysphagia intervention effects as measured by PHRM. Six studies with 78 people with MND (PwMND) were included. There was considerable variation in PHRM protocol and analysis methods. Five studies reported a 100% completion rate and three studies reported no adverse events. Swallow biomechanics data were reported across all studies. The effects of sensory stimulation, increased bolus consistency, effortful swallow and cricopharyngeal myotomy were evaluated using PHRM with 20 PwMND across four studies with varying effects. Literature on the use of PHRM in PwMND is limited. Variability in PHRM methods restricts comparison of metrics. PHRM appears to be a feasible tool for PwMND. PHRM can provide novel swallow physiology data in PwMND and quantify discrete effects of compensatory and surgical dysphagia interventions not detectable by videofluoroscopy or FEES. Further research on the effects of proactive dysphagia intervention as measured by PHRM is required.
Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array ( n = 15 participants per group (ALS or control)) and proteome profiling ( n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen’s d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.
Introduction To capture the patient’s attitude toward remote monitoring of motor neuron disease (MND) in care and clinical trials, and their concerns and preferences regarding the use of digital technology. Methods We performed an international multi-centre survey study in three MND clinics in The Netherlands, the United Kingdom, and Australia. The survey was co-developed by investigators and patients with MND, and sent to patients by e-mail or postal-mail. The main topics included: patients’ attitude towards remote care, participating in decentralized clinical trials, and preferences for and concerns with digital technology use. Results In total, 332 patients with MND participated. A majority of patients indicated they would be happy to self-monitor their health from home (69%), be remotely monitored by a multidisciplinary care team (75%), and would be willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength most valuable for home-monitoring. The majority of patients considered the use of at least three devices/apps (75%) once a week (61%) to be acceptable for home-monitoring. Fifteen percent of patients indicated they would not wish to perform home-measurements; reporting concerns about the burden and distress of home-monitoring, privacy and data security. Conclusion Most patients with MND exhibited a positive attitude toward the use of digital technology in both care and clinical trial settings. A subgroup of patients reported concerns with home-monitoring, which should be addressed in order to improve widespread adoption of remote digital technology in clinical MND care.
Background Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications. Case presentation A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged. Conclusions Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective, early degeneration of motor neurons in the brain and spinal cord. Motor neurons have long axonal projections, which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability, anterograde and retrograde transport, and signaling between neurons. The formation of protein aggregates which contain cytoskeletal proteins, and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions, including ALS, Alzheimer's disease, Parkinson's disease, Huntington’s disease and Charcot-Marie-Tooth disease. Furthermore, it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately linked. Therefore, dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization, may be common pathways in the initial steps of neurodegeneration. Here we review and discuss known contributors, including variants in genetic loci and aberrant protein activities, which modify cytoskeletal integrity, axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative diseases. Additionally, we explore some emerging pathways that may contribute to this disruption in ALS.
Objectives This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS). Methods Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates. Results Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean ( P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS. Conclusion Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.
Background Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s Methods Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. Results Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. Conclusions Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate.
Background Although percutaneous endoscopic gastrostomy (PEG) offers better access to the gastrointestinal system, in patients with previous abdominal surgery, PEG can be unsuccessful. Laparoscopically assisted percutaneous endoscopic gastrostomy (LAPEG) is indicated for such patients. However, patients with amyotrophic lateral sclerosis (ALS) may be more susceptible to anesthesia-related complications than other patients, requiring the indications for LAPEG, along with perioperative management, to be considered carefully. Case presentation A 70-year-old, male patient with ALS was referred to our hospital for a gastrostomy for progressive dysphagia. He had undergone an open distal gastrectomy for gastric ulcer perforation in his twenties. Upper gastrointestinal endoscopy denied the transillumination sign and focal finger invagination. Because the risk of respiratory complications caused by general anesthesia was not considered serious, the decision was made to perform a LAPEG. Under careful, intraoperative airway management and neuromuscular monitoring, adhesiolysis was performed to increase mobility of the remnant stomach. A gastrostomy tube was inserted through the abdominal wall and into the remnant stomach under laparoscopic and endoscopic guidance. The patient was discharged in stable condition on postoperative day 3 without any respiratory complications. Conclusions LAPEG was able to be performed in a patient with ALS with a previous gastrectomy. A perioperative team comprised of neurologists, endoscopists, surgeons, anesthesiologists, and nurses who are fully conversant with ALS must be assembled to deal with potentially complex medical issues related to the procedure and anesthetic and perioperative management.
Background Previous studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients. Methods We conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research (“starmaze”) that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test). Results Patients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups ( p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups ( p ≥ 0.238). Conclusions This study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.
Background Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. Methods To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. Results [^3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. Conclusions Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.
Each year, the lack of efficient data standardization and interoperability in
cancer care contributes to the severe lack of timely and effective diagnosis,
while constantly adding to the burden of cost, with cancer costs nationally
reaching over $208 billion in 2023 alone. Traditional methods regarding
clinical trial enrollment and clinical care in oncology are often manual,
time-consuming, and lack a data-driven approach. This paper presents a novel
framework to streamline standardization, interoperability, and exchange of
cancer domains and enhance the integration of oncology-based EHRs across
disparate healthcare systems. This paper utilizes advanced LLMs and Computer
Engineering to streamline cancer clinical trials and discovery. By utilizing
FHIR's resource-based approach and LLM-generated mCODE profiles, we ensure
timely, accurate, and efficient sharing of patient information across disparate
healthcare systems. Our methodology involves transforming unstructured patient
treatment data, PDFs, free-text information, and progress notes into enriched
mCODE profiles, facilitating seamless integration with our novel AI and
ML-based clinical trial matching engine. The results of this study show a
significant improvement in data standardization, with accuracy rates of our
trained LLM peaking at over 92% with datasets consisting of thousands of
patient data. Additionally, our LLM demonstrated an accuracy rate of 87% for
SNOMED-CT, 90% for LOINC, and 84% for RxNorm codes. This trumps the current
status quo, with LLMs such as GPT-4 and Claude's 3.5 peaking at an average of
77%. This paper successfully underscores the potential of our standardization
and interoperability framework, paving the way for more efficient and
personalized cancer treatment.
;Comment: 18 pages, 13 figures, accessible and published at: The Young
Researcher Fall 2024 Volume 8, Number 2(Special Edition in Collaboration with
Harvard Undergraduate Openbio Laboratory); Pages 28-45
Exosomes are increasingly recognized as central regulators of organ-specific metastasis, and this review concentrates on their contribution to lung-directed dissemination. Yet, a detailed and integrative synthesis of how exosomes contribute to lung-directed metastatic spread—and what these mechanisms mean for clinical translation—remains largely absent from the current literature. Extracellular vesicles (EVs), particularly exosomes measuring 30–150 nm, are nanoscale, lipid bilayer–enclosed structures secreted by nearly all cell types. In cancer, tumor-derived exosomes act as potent mediators of intercellular signaling, enabling metastatic spread by modulating inflammation, angiogenesis, extracellular matrix dynamics, and immune evasion. Their molecular cargo, especially integrin profiles, plays a decisive role in determining metastatic tropism: integrins α6β4 and α6β1 are strongly associated with pulmonary colonization, while αvβ5 directs metastasis toward the liver. In malignancies such as breast, colorectal, melanoma, and pancreatic cancer, exosomal proteins and RNAs remodel the lung microenvironment, enhancing vascular permeability and attracting stromal and immune components that establish a receptive pre-metastatic niche. Clinically, exosomes are emerging as powerful liquid biopsy biomarkers and as promising platforms for targeted drug delivery. Advances in EV bioengineering now permit tailoring of surface molecules and cargo to improve pulmonary selectivity, for instance, supporting selective delivery of therapeutic payloads to pulmonary tumors or altering immune dynamics within the lung microenvironment, while omics-based and imaging technologies support detailed profiling and tracking. Early clinical trials of exosome-derived vaccines and therapeutic carriers have demonstrated feasibility and safety, although no EV-based therapy has yet achieved regulatory approval. This review integrates mechanistic insights, niche biology, and translational advances to highlight the unique role of exosomes in lung-specific metastasis and their potential as diagnostic and therapeutic tools in precision oncology.
An innovative, case-based continuing medical education course, Health After Cancer: Cancer Survivorship for Primary Care, was developed to engage clinicians in cancer survivorship care. A post-course survey measured the educational impact of the course on learners’ intentions to change practice and changes in attitudes related to interprofessional collaborative practice. Qualitative analysis of free text responses was performed using the immersion-crystallization method. Learners earning continuing education credit ( N = 1202) completed the post-course evaluation survey: 17.4% physicians, 8.0% advanced practice providers, 56.7% nurses, 2.2% pharmacists, 15.7% other health professionals. Learners’ intended practice changes included improving communication ( N = 438), incorporating knowledge into practice ( N = 282), prioritizing survivorship clinical care ( N = 167), and increasing oncology–primary care collaboration for patients ( N = 53). Responses frequently involved more than one theme. Specific actions or knowledge that learners intended to incorporate into practice included improving their assessment of cancer survivor’s risk and concerns ( N = 128), incorporating knowledge of late effects of cancer treatment into practice ( N = 122), educating patients about survivorship topics ( N = 117), increasing empathy and understanding of survivors’ experiences ( N = 94), improving listening skills ( N = 70), and dedicating more time to survivorship care ( N = 63). Learners’ changes in attitudes reflected an increased appreciation for collaboration, especially between oncology and primary care clinicians. A continuing medical education course designed to drive interest in engaging with cancer survivorship topics was effective at shaping learners’ attitudes and intent to change practice, and has the potential to improve communication, care coordination, and healthcare experiences of cancer survivors.
Cancer is a complex and multifaceted global health issue that significantly impacts individuals’ quality of life, daily living, and overall well-being. Recent studies highlight the positive developments in treating psychological symptoms and issues related to cancer through the application of positive psychotherapy (PPT) interventions in individuals diagnosed with cancer. Based on these findings, this study aims to conduct a systematic literature review on the effectiveness of positive psychotherapy-based interventions, which are increasingly applied to individuals diagnosed with cancer. This research is a systematic review. The study employed the PRISMA flow diagram and PRISMA checklist, adhering to evidence-based criteria. Studies conducted from 2019 onward were searched in the Google Scholar, PubMed, ScienceDirect, and Cochrane databases using the keywords “cancer,” “positive psychotherapy”, “PPT,” and “psycho-oncology.” A total of nine studies that met the inclusion criteria were included in the review. Both researchers independently conducted this process, and the studies were evaluated comprehensively from various perspectives. The results of the reviewed studies indicate that PPT interventions could be an effective and alternative method in terms of short-term efficacy in cancer patients. They show improvements in psychological health and variables related to depression, anxiety, post-traumatic stress and growth, happiness, self-awareness, body image, psychological well-being, fear of recurrence, and meaning of life—including life experience, hope, life expectancy, life attitude, and quality of sexual life. Our review supports the short-term efficacy of Positive Psychotherapy (PPT). However, the results should be carefully evaluated, considering the low number of trials. High-quality trials with longer follow-up periods are needed to draw more robust conclusions about the long-term efficacy of PPT.
Cancer is one of the leading causes of death worldwide, making the development of rapid, minimally invasive, label-free and scalable diagnostic strategies a major challenge in modern oncology. In this context, spectroscopic liquid biopsy has emerged as a promising alternative, as it enables the holistic characterization of biochemical alterations in biological fluids. In this work, we propose a multimodal spectroscopic liquid biopsy framework for multicancer detection based on the combination of Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, and Excitation-Emission Matrix (EEM) fluorescence spectroscopy together with Machine Learning (ML) methodologies. Serum samples from breast cancer patients, colorectal cancer patients, and healthy controls were analyzed through the three spectroscopic modalities. After modality-specific preprocessing, low-level data fusion (LLDF) was employed to integrate the complementary biochemical information encoded within the different spectroscopic measurements, and classification was performed using XGBoost models. Seven experimental configurations were evaluated, including the three unimodal approaches, all pairwise bimodal configurations, and the full multimodal approach of FTIR, Raman, and EEM fluorescence. The results show that although several individual modalities achieved high discrimination performance, the multimodal fusion provided the most balanced overall results, reaching a ROC-AUC of 0.997 for breast cancer and 0.994 for colorectal cancer, together with highly balanced sensitivity and specificity values.
Over half a century after the first use of Bacillus Calmette-Guérin (BCG) on bladder cancer treatment by Morales et al., BCG is still the standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) and the most successful example of vaccine against cancer. In this chapter, we describe the origin of BCG, its effect on bladder cancer and the immune system, and the non-specific protective effect of BCG vaccine on viral infections and other forms of cancer.
Cardiotoxicity induced by cancer treatment has become a major clinical
concern, affecting the long-term survival and quality of life of cancer
patients. Effective clinical decision-making, including the detection of cancer
treatment-induced cardiotoxicity and the monitoring of associated symptoms,
remains a challenging task for clinicians. This study investigates the current
practices and needs of clinicians in the clinical decision making of cancer
treatment-induced cardiotoxicity and explores the potential of digital health
technologies to support this process. Through semi-structured interviews with
seven clinical experts, we identify a three-step decision-making paradigm: 1)
symptom identification, 2) diagnostic testing and specialist collaboration, and
3) clinical decision-making and intervention. Our findings highlight the
difficulties of diagnosing cardiotoxicity (absence of unified protocols and
high variability in symptoms) and monitoring patient symptoms (lacking accurate
and timely patient self-reported symptoms). The clinicians also expressed their
need for effective early detection tools that can integrate remote patient
monitoring capabilities. Based on these insights, we discuss the importance of
understanding the dynamic nature of clinical workflows, and the design
considerations for future digital tools to support cancer-treatment-induced
cardiotoxicity decision-making.
;Comment: In Submission
Purpose: A reliable cancer prognosis model for clear cell renal cell
carcinoma (ccRCC) can enhance personalized treatment. We developed a
multi-modal ensemble model (MMEM) that integrates pretreatment clinical data,
multi-omics data, and histopathology whole slide image (WSI) data to predict
overall survival (OS) and disease-free survival (DFS) for ccRCC patients.
Methods: We analyzed 226 patients from The Cancer Genome Atlas Kidney Renal
Clear Cell Carcinoma (TCGA-KIRC) dataset, which includes OS, DFS follow-up
data, and five data modalities: clinical data, WSIs, and three multi-omics
datasets (mRNA, miRNA, and DNA methylation). Separate survival models were
built for OS and DFS. Cox-proportional hazards (CPH) model with forward feature
selection is used for clinical and multi-omics data. Features from WSIs were
extracted using ResNet and three general-purpose foundation models. A deep
learning-based CPH model predicted survival using encoded WSI features. Risk
scores from all models were combined based on training performance. Results:
Performance was assessed using concordance index (C-index) and AUROC. The
clinical feature-based CPH model received the highest weight for both OS and
DFS tasks. Among WSI-based models, the general-purpose foundation model (UNI)
achieved the best performance. The final MMEM model surpassed single-modality
models, achieving C-indices of 0.820 (OS) and 0.833 (DFS), and AUROC values of
0.831 (3-year patient death) and 0.862 (cancer recurrence). Using predicted
risk medians to stratify high- and low-risk groups, log-rank tests showed
improved performance in both OS and DFS compared to single-modality models.
Conclusion: MMEM is the first multi-modal model for ccRCC patients, integrating
five data modalities. It outperformed single-modality models in prognostic
ability and has the potential to assist in ccRCC patient management if
independently validated.
;Comment: 10 pages, 3 figures, 4 tables
Background Recent studies based on hospital and outpatient clinic databases have reported a decline in cancer diagnoses during the COVID-19 pandemic, an observation that has been mainly attributed to halted screenings. Methods We investigated the impact of COVID-19 on cancer incidence in the Campania Region (Italy) among adults followed by their primary care physicians over a 6-year period (2017–2022). Using a single-cohort design, we employed interrupted time series (ITS) analysis to compare cancer incidence rates during the 3 years preceding the pandemic (2017–2019) with those during the three pandemic years (2020–2022). Results We analyzed data from 212,656 individuals and found that the incidence of new cancer diagnoses rose from 14.3 to 23.1 per 1000 person-years when comparing the pre-pandemic to the COVID-19 period. ITS analysis revealed a stable trend in cancer diagnoses before the pandemic, followed by a marked increase of ~8 new cases per month beginning in January 2020, with a peak observed in August 2021. Notably, diagnoses of brain and skin cancers increased by 300% in 2022 compared to 2017. Conclusions Taken together, these findings highlight a concerning increase in cancer diagnoses in the Campania Region during the COVID-19 pandemic, contrasting with earlier reports that pointed to a decline in cases, mostly attributed to interrupted screening services. Several indirect factors might contribute to this trend, including heightened psychosocial stress and shifts in lifestyle behaviors, as well as profound disruptions in access to and continuity of healthcare delivery.
Background Population-based cancer registries remain limited in low- and middle-income countries (LMICs). In Kenya, their coverage is below the 20% threshold recommended by the International Agency for Research on Cancer. Pathology-based registries can provide complementary data in such contexts. This study describes the distribution of cancers diagnosed at a tertiary referral hospital in Nairobi over ten years, and evaluates the completeness of pathology reporting for selected cancers using College of American Pathologists (CAP) protocols. Methods We conducted a retrospective review of all histologically confirmed cancers at the Aga Khan University Hospital, Nairobi, from 2015 to 2024. Data were extracted from the institutional database. The data included region of origin, demographics, cancer site, and histologic diagnosis. Completeness of reporting was assessed in stratified random samples of breast and colorectal cancer reports against the College of American Pathologists (CAP) cancer reporting protocols. Results A total of 32,445 cancer cases were diagnosed over the study period, including 18,899 females and 13,546 males (58.3% and 41.7%, respectively). The median age at diagnosis was 52 years (Interquartile range 41–64) in females and 61 years (Interquartile range 47–71) in males, with an overall median age of 56 years (Interquartile range 43–68). Most cases occurred in the decades between 51 and 60 years (6,816/32,445) and 61–70 years (6,556/32,445). Overall, breast cancer was the most frequent malignancy (7,236/32,445; 22.3%), followed by esophageal (3,839/32,445; 11.8%) and prostate cancer (3,023/32,445; 9.3%). Among women, breast (6,926/18,899; 36.6%), cervical (2,230/18,899; 11.8%), and esophageal cancers (1,610/18,899; 8.5%) predominated, while among men, prostate (3,023/13,546; 22.3%), esophageal (2,229/13,546; 16.5%), and non-Hodgkin lymphoma (957/13,546; 7.1%) were most common. Pediatric cancers (≤ 19 years) accounted for 1,325 cases (4.1%). Completeness of pathology reporting exceeded 95% for most required elements, and it improved from 83.3% in 2015 to over 98% in 2024. Conclusion This large pathology-based dataset highlights the cancer burden in Kenya, with breast and prostate cancers predominating among females and males, respectively. There are regional disparities in sources of referral for certain cancer types. Pediatric malignancies represented a small proportion of cases. Pathology reporting for key data elements was generally of high completeness.
BACKGROUND: Approximately 10% of cases with gastric cancer (GC) exhibit familial clustering, however, only 1–3% of cases can be explained by two known hereditary syndromes: Hereditary Diffuse Gastric Cancer (HDGC) caused by CDH1 and CTNNA1 pathogenic germline variants; and Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS), caused by germline variants in APC 1B promoter. Familial intestinal gastric cancer (FIGC) has been defined clinically, but it remains mostly genetically unexplained. Likewise, the heritability of mixed histology GC remains to be known. We aimed to estimate the frequency of known cancer predisposition gene variants in GC cases with and without a cancer family history, diverse histological subtypes, and varied age of onset. METHODS: We evaluated the contribution of pathogenic or likely pathogenic (P/LP) variants in well-established moderate-to-high penetrance multi-organ cancer predisposition genes for GC risk in a large international multi-centre retrospective cohort study involving 750 patients with GC of early-onset or family history of cancer, either by panel sequencing or whole exome sequencing (WES). Panel sequencing was conducted on 328 cases, while WES was performed on the remaining 422. Tumour sequence analyses were performed on samples from 15 patients with P/LP variants. Mutations identified in five index cases were also tested in their relatives. FINDINGS: We identified 45 patients (6%) with P/LP variants in: ATM (17 cases), BRCA2 (10 cases), MLH1 (five cases), TP53 (three cases), BRCA1, PALB2, RAD51D, and CHEK2 (two patients each), and RAD51C and PMS2 (one case each), all of which were mutually exclusive. The P/LP variant prevalence was higher in intestinal (9.8%) than in diffuse (4.3%) or mixed GC (4.5%) (p-value = 0.023), without difference per mutated gene by histological subtypes. Only 16 of the 45 patients who carried P/LP variants fulfilled the National Comprehensive Cancer Network genetic testing criteria of at least one cancer predisposition syndrome. INTERPRETATION: Our findings indicate that a broader panel of cancer predisposition genes, beyond CDH1 and CTNNA1, should be included in gene panels to investigate germline variants in patients with GC. This would be especially beneficial when there is a family history of cancer, irrespective of histology subtype, as it would increase the chance of identifying patients who could benefit from risk reduction, targeted treatment, and surveillance of other cancer types. FUNDING: 10.13039/100000054National Cancer Institute of the National Institutes of Health, USA; 10.13039/100019348Universidad del Tolima, Colombia; 10.13039/100022965MINCIENCIAS, Colombia; L'OREAL-UNESCO-ICETEX-COLCIENCIAS, Colombia; 10.13039/100019346Instituto Nacional de Cancerología, Colombia; 10.13039/100000043American Association for Cancer Research, USA; 10.13039/100020266ANID Ministerio de Ciencia, Chile; 10.13039/501100002850Fondecyt, Chile; 10.13039/501100002848CONICYT/10.13039/501100018735ANID FONDAP, Chile; 10.13039/501100004881Instituto Mexicano del Seguro Social and 10.13039/501100003141Consejo Nacional de Ciencia y Tecnología, México; IPO Porto, Portugal; 10.13039/501100011733Liga Portuguesa Contra o Cancro, Portugal; Fundacao para a Ciencia e Tecnologia, Portugal; The Auburn Community Cancer Endowed Chair in Basic Research, USA; The Heart, BrEast, and BrAin HeaLth Equity Research (HEAL HER) program, a program made possible by residual class settlement funds in the matter of April Krueger v. Wyeth, Inc., Case No. 03-cv-2496 (US District Court, SD of Calif.), USA.
Purpose A cancer diagnosis during young adulthood can impact identity, relationships, and family building. While young men with cancer face fertility risks, data on fatherhood and partnership outcomes remain limited. This study aimed to examine the hazard ratios (HRs) for fatherhood and partnership formation in young men diagnosed with cancer compared to age-matched comparisons. Methods This nationwide register-based study, based on the DANAC II cohort, included men diagnosed with cancer at 18–39 years (1978–2016) and age-matched male comparisons. Cox regression models estimated HRs of fatherhood and partnership formation, adjusting for time of diagnosis or study entry, immigration status, and pre-diagnosis children. Results Among 16,913 men with cancer and 1,353,040 comparisons, those with cancer had a lower HR of fatherhood (0.88 [95% confidence interval (CI) 0.86–0.91]), the lowest among men with lymphoma, central-nerve system (CNS), and gastrointestinal cancers. Fatherhood probabilities improved over time, with older men showing the greatest gains. Among men who were single at diagnosis or study entry, the HR for partnership formation was similar to the comparison group (1.03 [95% CI 0.99–1.07]), except for those with gastrointestinal or CNS cancers. Conclusions Fatherhood HRs were generally lower than in comparisons, varying by cancer group, age, and diagnosis period. However, single men diagnosed with cancer typically formed partnerships similar to the comparisons. Implications for Cancer Survivors The lower probability of fatherhood highlights the need for and importance of oncofertility counseling, timely fertility preservation referrals, and follow-up care tailored to cancer groups and age at diagnosis.
Deep learning models have shown promise in lung pathology detection from chest X-rays, but widespread clinical adoption remains limited due to opaque model decision-making. In prior work, we introduced ClinicXAI, a human-centric, expert-guided concept bottleneck model (CBM) designed for interpretable lung cancer diagnosis. We now extend that approach and present XpertXAI, a generalizable expert-driven model that preserves human-interpretable clinical concepts while scaling to detect multiple lung pathologies. Using a high-performing InceptionV3-based classifier and a public dataset of chest X-rays with radiology reports, we compare XpertXAI against leading post-hoc explainability methods and an unsupervised CBM, XCBs. We assess explanations through comparison with expert radiologist annotations and medical ground truth. Although XpertXAI is trained for multiple pathologies, our expert validation focuses on lung cancer. We find that existing techniques frequently fail to produce clinically meaningful explanations, omitting key diagnostic features and disagreeing with radiologist judgments. XpertXAI not only outperforms these baselines in predictive accuracy but also delivers concept-level explanations that better align with expert reasoning. While our focus remains on explainability in lung cancer detection, this work illustrates how human-centric model design can be effectively extended to broader diagnostic contexts - offering a scalable path toward clinically meaningful explainable AI in medical diagnostics.
BACKGROUND: Early-onset bowel cancer incidence (age <50 years) has increased worldwide and is highest in Australia, but how this varies across histology and anatomical site remains unclear. We aimed to investigate appendiceal, proximal colon, distal colon, rectal, and anal cancer incidence trends by age and histology in Australia. METHODS: Cancer incidence rate data were obtained from all Australian cancer registries (1990–2020 period). Birth cohort-specific incidence rate ratios (IRRs) and annual percentage change in rates were estimated using age-period-cohort modelling and joinpoint regression. FINDINGS: After excluding neuroendocrine neoplasms, early-onset cancer incidence rose 5–9% annually, yielding 5,341 excess cases (2 per 100,000 person-years; 12% appendix, 45% colon, 36% rectum, 7% anus; 20–214% relative increase). Trends varied by site, period, and age: appendiceal cancer rose from 1990–2020 in 30–49-year-olds; colorectal cancers rose from around 1990–2010 in 20–29-year-olds and from 2010–2020 in 30–39-year-olds; anal cancer rose from 1990–2009 in 40–49-year-olds. Across all sites, IRRs increased with successive birth cohorts since 1960. Notably, adenocarcinoma incidence in the 1990s versus 1950s birth cohort was 2–3-fold for colorectum and 7-fold for appendix. The greatest subtype-specific increases occurred for appendiceal mucinous adenocarcinoma, colorectal non-mucinous adenocarcinoma, and anal squamous cell carcinoma. Only later-onset (age ≥50) colorectal and anal adenocarcinoma rates declined. Appendiceal tumours, neuroendocrine neoplasms (all sites), anorectal squamous cell carcinomas, and colon signet ring cell carcinomas rose across early-onset and later-onset strata. INTERPRETATION: Appendiceal, colorectal, and anal cancer incidence is rising in Australia with variation across age and histology, underscoring the need to identify factors driving these trends. FUNDING: ALM is supported by an Australian Government Research Training Program Scholarship, Rowden White Scholarship, and WP Greene Scholarship. DDB is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator grant (GNT1194896), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to The Colon Cancer Family Registry (CCFR, www.coloncfr.org) from the National Cancer Institute (NCI), National Institutes of Health (NIH) [award U01 CA167551]. MAJ is supported by an NHMRC Investigator grant (GNT1195099), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to the CCFR from NCI, NIH [award U01 CA167551].
Background Cancer treatment refusal is known to lower survival rates and increase cancer symptoms in individuals with cancer. Behavioural motivations of treatment refusal need to be elucidated for better cancer care. Using Q-methodology, a mixed methods research approach, we explored behavioural motivations of treatment refusal in individuals diagnosed with cancer. Method Thirty-nine individuals ( n = 39; age = 49.2 ± 12.2 years) were recruited from Australia, the UK, and the USA, who had refused cancer treatment within the past decade. Participants completed an online demographic questionnaire and a Q-sort activity which required the organisation and ranking of 44 statements on potential treatment refusal motivations. Q-sort data were analysed with an inverted factor analysis. Compositive Q-sorts, distinguishing statements, and demographic data facilitated interpretation of the resulting factors. Results Eight factors, accounting for 66% of total variance, were identified and interpreted. The eight factors were as follows: (1) I was not motivated by my health status, (2) Treatment was too risky for how unwell I was, (3) I was motivated by my age, (4) I did not distrust the medical system and practitioners, (5) Religious and spiritual practices would heal me, (6) I was influenced by my religious and spiritual beliefs, (7) My prognosis was not good enough, and (8) I wanted to heal naturally. Conclusion Diverse motivations for cancer treatment refusal were found, which could help practitioners understand an individual’s considerations regarding treatment decisions. Future research should investigate motivations underpinning cancer treatment refusal and establish person-centred strategies to address concerns when promoting evidence-based cancer treatment.
BACKGROUND: Insular thyroid carcinoma is a rare subtype of thyroid cancer that constitutes an intermediate entity between differentiated (papillary & follicular) and undifferentiated (anaplastic) thyroid cancer. METHODS: This is a retrospective study that included all the patients with insular carcinoma of the thyroid gland who underwent surgical treatment in our department from January 2009 to December 2023. The epidemiological, clinical, and oncological data of the included patients were analyzed. RESULTS: A total of 1690 patients with thyroid cancer were screened. Twenty-four patients were included in the final analysis. The median time to recurrence (95% CI) was 24 months while the Restricted Mean Survival Time (RMST) at time point 24 months (95% CI) was 16.95. The median time to distant metastasis is 60 months while RMST at time point 24 months was 17.1. The median time to death was 55 months. There was a statistically significant difference in the RMST at 24 months for overall survival (OS) as regards older age, presence of comorbidity, multifocality, and lack of adjuvant RAI, but not sex. Male sex and lack of adjuvant RAI therapy were statistically significant independent predictors of the time to locoregional recurrence. There was no statistically significant difference in the time to distant metastasis as regards all the variables. CONCLUSIONS: From our results, we can conclude that male sex, multifocality, and lack of RAI affect survival in patients with insular thyroid carcinoma. Adequate surgical resection of the thyroid gland and draining lymph nodes in addition to radioactive iodine remains the mainstay of treatment.
Background Malnutrition and cachexia are prevalent in advanced cancer patients, contributing to decreased treatment tolerance, impaired quality of life, and reduced survival [ 1 ]. Nutritional interventions, including oral nutritional supplements, enteral nutrition, and parenteral nutrition, have been employed to mitigate these effects [ 2 ]. Objective This systematic review aimed to evaluate the impact of nutritional support interventions on key outcomes in adult patients with advanced cancer, including survival, quality of life, weight stabilization, functional status, treatment tolerance, and biochemical markers [ 3 ]. Methods A comprehensive literature search was performed in accordance with the PRISMA 2020 guidelines [ 4 ] in CENTRAL, PubMed, and Google Scholar for studies published in English within the past 10 years. Eligible studies comprised randomized controlled trials, prospective cohort studies, and observational studies that assessed nutritional interventions in advanced cancer patients. Data extraction and risk of bias assessments were conducted independently by reviewers using the Cochrane Risk of Bias (RoB) and Joanna Briggs Institute (JBI) tools [ 5 ]. Results Nine studies involving 799 patients from eight countries were included. Nutritional interventions were associated with improvements in weight stabilization, lean body mass, and biochemical markers such as albumin and prealbumin [ 6 ]. Functional status was enhanced, particularly when nutritional support was combined with exercise, although the effect on overall survival was inconsistent [ 7 ]. Notably, parenteral nutrition was linked to a higher risk of infections, whereas oral supplementation and multimodal strategies demonstrated higher adherence and fewer adverse events [ 8 ]. Conclusion Individualized multimodal nutritional support may improve treatment tolerance, quality of life, and key nutritional parameters in advanced cancer patients, although its impact on survival remains uncertain [ 9 ]. Future research should focus on standardized protocols and precision nutrition approaches to optimize outcomes in this vulnerable population [ 10 ].
Despite significant medical advancements, cancer remains the second leading cause of death, with over 600,000 deaths per year in the US. One emerging field, pathway analysis, is promising but still relies on manually derived wet lab data, which is time-consuming to acquire. This work proposes an efficient, effective end-to-end framework for Artificial Intelligence (AI) based pathway analysis that predicts both cancer severity and mutation progression, thus recommending possible treatments. The proposed technique involves a novel combination of time-series machine learning models and pathway analysis. First, mutation sequences were isolated from The Cancer Genome Atlas (TCGA) Database. Then, a novel preprocessing algorithm was used to filter key mutations by mutation frequency. This data was fed into a Recurrent Neural Network (RNN) that predicted cancer severity. Then, the model probabilistically used the RNN predictions, information from the preprocessing algorithm, and multiple drug-target databases to predict future mutations and recommend possible treatments. This framework achieved robust results and Receiver Operating Characteristic (ROC) curves (a key statistical metric) with accuracies greater than 60%, similar to existing cancer diagnostics. In addition, preprocessing played an instrumental role in isolating important mutations, demonstrating that each cancer stage studied may contain on the order of a few-hundred key driver mutations, consistent with current research. Heatmaps based on predicted gene frequency were also generated, highlighting key mutations in each cancer. Overall, this work is the first to propose an efficient, cost-effective end-to-end framework for projecting cancer progression and providing possible treatments without relying on expensive, time-consuming wet lab work. ;12 pages, 11 figures, work originally done in 2022/2023 and was awarded as one of the Regeneron Science Talent Search Finalists in 2022
Background The technical challenges and safety concerns of single-incision laparoscopic gastrectomy for overweight and obese gastric cancer patients remain unclear. This study aimed to evaluate the safety and feasibility of single-incision laparoscopic distal gastrectomy (SIDG) compared to multiport laparoscopic distal gastrectomy (MLDG) in overweight and obese gastric cancer patients. Methods This study retrospectively analyzed overweight and obese patients (body mass index ≥ 25 kg/m^2) and pathologic stage T1 primary gastric adenocarcinoma treated with either SIDG or MLDG. The SIDG and MLDG groups were propensity score matched at a 1:2 ratio using age, sex, height, body weight, American Society of Anesthesiologists classification, year of surgery, pathologic N stage, and anastomosis method as covariates. Results After 1:2 matching, the study included patients who underwent SIDG (n = 179) and MLDG (n = 358). No significant difference in the number of retrieved lymph nodes was found between the SIDG and MLDG groups (52.8 ± 19.3 vs. 53.9 ± 21.0, P = 0.56). Operation times were significantly shorter in the SIDG group (170.8 ± 60.0 min vs. 186.1 ± 52.6 min, P = 0.004). The postoperative hospital length of stay was comparable between the 2 groups (SIDG: 5.9 ± 3.4 days vs. MLDG: 6.3 ± 5.1 days, P = 0.23), as was postoperative complication rate (SIDG: 13.4% vs. MLDG: 12.8%, P = 0.89). Conclusions SIDG was shown to be as safe and feasible as MLDG for overweight and obese gastric cancer patients, with comparable early postoperative complication rates without compromising operation time compared to MLDG.
Background Microenvironment-driven drug resistance is a principal barrier to durable response after transarterial chemoembolisation, ablation or radioembolisation for hepatocellular carcinoma, yet the global structure of scholarship linking these domains remains undefined. This bibliometric analysis mapped 25-year publication trends, thematic evolution and collaboration networks at the intersection of interventional oncology, tumour microenvironment and therapeutic resistance. Methods Web of Science Core Collection was searched (1 January 2000–31 December 2024) for records simultaneously referencing liver cancer, interventional therapy, microenvironmental descriptors and resistance terms. After dual-review screening, 939 articles and reviews were retained. Annual output, citation impact and Bradford-zone distributions were generated with bibliometrix 4.2.1. Bradford-zone analysis refers to the distribution of journal productivity, with journals in the first zone representing core literature, and those in subsequent zones reflecting peripheral or niche studies. This method helps assess the concentration of research in key journals and identifies areas of growth in the literature; co-authorship, journal-coupling and keyword-co-occurrence networks were rendered in VOSviewer 1.6.20. Workflow reproducibility was confirmed on a 5% subsample and by comparing fractional with full counting. Results Yearly publications rose from two in 2000 to 130 in 2024, amassing 36 095 citations (mean 38.4 per item). Output spikes in 2013, 2019 and 2021 paralleled seminal reports on hypoxia-driven angiogenesis, CAF activation, and COVID-19-related endothelial dysfunction. The pathophysiological mechanisms of COVID-19-induced endothelial injury, including cytokine-mediated endothelial dysfunction, have been implicated in compromising loco-regional therapies, contributing to resistance mechanisms that affect the efficacy of embolic treatments. China produced 47.3% of documents and sat at the nexus of global collaboration, with prominent links to the United States, Japan and South Korea. Cancer Research, Hepatology and Journal of Hepatology led citation rankings. Keyword overlays revealed a chronological shift from procedure-centric terms to microenvironmental and immunologic nodes—“angiogenesis”, “immune checkpoint”, “nanoparticles”—after 2017. Trend-topic mapping documented a transition from device optimisation toward mechanism-informed combination regimens incorporating anti-VEGF or PD-1 blockade. Conclusion Research on microenvironment-mediated resistance in interventional liver-cancer therapy has expanded rapidly and pivoted toward molecularly targeted, immune-augmented strategies, driven chiefly by high-volume Chinese centres and trans-Pacific partnerships. Priorities now include single-cell analytics, radiomics-guided adaptive embolisation and multinational trials of combination therapy.
PURPOSE: To calculate the incidence of colorectal cancer in Southern Egypt and to describe the epidemiological profiles of people with colorectal cancer in this region. INTRODUCTION: Colorectal cancer (CRC) is one of the common cancers in high income countries but historically CRC has been uncommon in low- and middle-income countries (LMICs). Egypt was among the first countries to report higher incidence of early-onset CRC under age 40. While previous studies on CRC in Egypt over the past 3 decades have focused on Cairo and the northern Nile delta regions, this study focused on CRC in the Southern Egypt, an underserved region with distinct socioeconomic and patient constitutional characteristics. METHODS: We identified 613 CRC patients who received care during 2018-2022 at the Shefa Al-Orman Cancer Hospital (SOH), the main cancer hospital in the Luxor province in Southern Egypt. Data retrieved from the medical records included demographic, clinical, and family history of all patients managed at SOH. We calculated the incidence by two age groups, under age 45 vs. 45 + years, the incidence rate (IR), age- and sex-specific rates, and distribution of clinical characteristics. RESULTS: Twenty-three percent of patients were diagnosed under age 45. The 5-year incidence was 4.5 per 100,000, and the incidence rate (IR) of early-onset was 1.3 vs 18.3 per 100,000 for those 45 + years. Distant metastasis was identified in 28% of patients, and 38% of patients had rectal cancers and 58% of the patients were alive at last follow-up. CONCLUSION: The incidence of early-onset and late-onset CRC is lower in Southern Egypt than the reported incidence from other regions of the country. Future etiologic studies should focus on investigating the socioeconomic and lifestyle factors of Southern Egypt. Clinical studies should also explore factors related to late-stage presentation and low survival in this population. The study may have global implications for the etiology and management of colorectal cancer.
Purpose of Review This study aims to examine the current state of psychosocial oncology (PSO) research concerning Black Canadian communities, focusing on their experiences, psychological states, and non-biological aspects of their cancer journey. Recent Findings Although there has been increased attention to PSO in the past two decades, there remains a lack of studies specifically addressing the experiences of Black Canadians affected by cancer. This is especially concerning considering the disparities identified by PSO researchers among Black individuals in the United States and the acknowledged health inequities affecting Black individuals in Canada. Summary This scoping review identified a total of five studies that highlighted the significance of religion and spirituality in coping with cancer among Black individuals. While faith emerged as a crucial source of strength, there was notable hesitation to discuss religious beliefs in mainstream support settings. Additional barriers, including stigma surrounding cancer, transportation issues, and limited access to care, further complicated their healthcare experiences. This review reveals critical gaps in research regarding the PSO experiences of Black Canadians affected by cancer and underscores the urgent need for additional studies and the development of tailored support programs to address their unique psychosocial needs and barriers to care.
Breast cancer is the most commonly diagnosed cancer in women worldwide, with alcohol consumption recognized as a significant risk factor. While epidemiological studies consistently show a positive correlation between alcohol consumption and increased breast cancer risk, the underlying mechanisms remain unclear. Recent evidence suggests that the gut microbiome—the diverse collection of microorganisms, including bacteria, viruses, and fungi, residing in the gastrointestinal tract—plays a pivotal role in systemic health and disease. This is achieved through its regulation of key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has recently been implicated in the development of breast cancer. We hypothesized that alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that alcohol exposure promotes mammary tumor growth and aggressiveness in MMTV-Wnt1 (Wnt1) transgenic mice, an established model for investigating mechanisms of alcohol-induced tumor promotion. In this study, we sought to determine whether alcohol exposure induces gut dysbiosis in adolescent and adult Wnt1 transgenic mice and their wild-type FVB counterparts. Our findings revealed that alcohol exposure significantly reduced microbiome richness in adult Wnt1 and FVB mice. Alcohol exposure also markedly altered microbiome composition in adolescents and adults in both strains. Additionally, we identified specific microbial taxa that were significantly affected by alcohol exposure. These results demonstrate that alcohol disrupts the gut microbiome in a preclinical breast cancer model, providing insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.
Young adult cancer survivors, defined as persons aged 18–39 who have completed primary curative treatment, constitute a unique group, as they are in a particular life phase forming the foundations of their lives. As a result, they face distinct age-specific challenges in their everyday life related to education, work, and social activities, which negatively impact their quality of life. Rehabilitation may address these challenges, however there is a lack of rehabilitation programmes specifically tailored for young adult cancer survivors. This paper describes the co-production and development of an age-specific and municipality-based cancer rehabilitation programme to improve young adult cancer survivors’ self-efficacy and health-related quality of life. The development included the following steps: (1) reviewing existing literature on cancer rehabilitation programmes for young adults and consulting with relevant stakeholders to gain insights into the target population and the context for implementation; (2) conducting four workshops involving 2–6 young adults, 3–4 professionals, and two researchers and one workshop with 20 young adults and two researchers to co-produce the programmes name, component content, delivery methods, and potential outcomes; and (3) Refine of the programme description. The co-produced programme, Young Adults Taking ACtion, includes one mandatory session for needs identification and goal setting that guides which of the following sessions the young adult cancer survivors will receive: (1) Everyday life, (2) Physical activity, (3) Psychological issues, (4) Education and work, (5) Sexuality and relationships, (6) Funding and grant, and (7) Family and friends. Background Young adult cancer survivors, defined as individuals aged 18–39 who have completed primary curative treatment, face numerous age-specific biopsychosocial late effects that impact health-related quality of life negatively. Rehabilitation can enhance participation in life roles, work, leisure activities and health-related quality of life. However, there is a lack of age-specific cancer rehabilitation for this population, leaving many young adults with diminished self-efficacy in managing their challenges, resulting in unmet needs. This study aimed to co-produce and develop an age-specific, municipality-based cancer rehabilitation intervention programme to improve young adults’ self-efficacy and health-related quality of life. Methods The development process was completed between September 2019 and June 2023 and followed Hawkins et al.’s three-staged framework for co-production: (1) A literature review and stakeholder consultations; (2) four workshops with 2–6 young adult cancer survivors, 3–4 professionals, and two researchers and one workshop with 20 young adult cancer survivors and two researchers to co-produce the name, component content, delivery methods and potential outcomes; and (3) Refinement of the programme and its programme theory. Key findings from each stage informed the subsequent stages. Results The Young Adults Taking ACtion programme was developed. It applies a person-centred approach and is grounded in social cognitive theory and experiential learning theory. It comprises one mandatory component, a needs assessment and goal setting that tailor which of the following seven components the young adults will receive: (1) everyday life, (2) physical activity, (3) psychological issues, (4) education and work, (5) sexuality and relationships, (6) funds and grants, and (7) family and friends. The programme is primarily group-based and will be delivered by an interdisciplinary team over 16 weeks. Conclusions We co-produced a comprehensive, goal-oriented, and peer-based rehabilitation programme for young adult cancer survivors. The engagement of young adults and professionals ensured that the programme aligned with the population’s needs and preferences and was context specific. Thus, it is likely that the programme will be more realistic and feasible to implement in clinical practice.
Purpose of Review Cancer therapies significantly increase cardiovascular disease risk, with cancer patients facing up to 42% higher likelihood of developing cardiovascular complications compared to those without cancer. This review examines current applications of artificial intelligence (AI) in cardio-oncology, focusing on pre-treatment risk prediction, detection of cardiovascular dysfunction during and after therapy, and clinical implementation challenges. Recent Findings AI applications have shown promising results across multiple domains. Machine learning models integrating electronic health records, ECG data, echocardiographic findings, and advanced imaging have demonstrated feasibility in identifying high-risk patients before treatment initiation. For detecting cardiac dysfunction, AI-enhanced tools have shown superior performance in identifying subtle cardiotoxic effects, including AI-ECG and- imaging models detecting reduced ejection fraction with high accuracy, automated strain analysis for early dysfunction detection, and AI-guided handheld ultrasound enabling point-of-care monitoring by non-specialists. Despite these advances, significant barriers prevent clinical implementation, including limited high-quality datasets representing diverse oncology populations, lack of standardized outcome definitions, model interpretability challenges with “black box” systems, and insufficient integration with existing clinical workflows. Summary While AI demonstrates substantial potential for improving outcomes through enhanced risk stratification and early detection, current evidence does not yet support widespread implementation. Success will require rigorous prospective validation, improved interpretability, and comprehensive implementation strategies addressing both technical and human factors.
The TRAIMA project (TRaitement Automatique des Interactions Multimodales en Apprentissage), conducted between March 2019 and June 2020, investigates the potential of automatic processing of multimodal interactions in educational settings. The project addresses a central methodological challenge in educational and interactional research: the analysis of verbal, paraverbal, and non-verbal data is currently carried out manually, making it extremely time-consuming and difficult to scale. TRAIMA explores how machine learning approaches could contribute to the categorisation and classification of such interactions. The project focuses specifically on explanatory and collaborative sequences occurring in classroom interactions, particularly in French as a Foreign Language (FLE) and French as a First Language (FLM) contexts. These sequences are analysed as inherently multimodal phenomena, combining spoken language with prosody, gestures, posture, gaze, and spatial positioning. A key theoretical contribution of the project is the precise linguistic and interactional definition of explanatory discourse as a tripartite sequence (opening, explanatory core, closure), drawing on discourse analysis and interactional linguistics. A substantial part of the research is devoted to the methodological foundations of transcription, which constitute a critical bottleneck for any form of automation. The report provides a detailed state of the art of existing transcription conventions (ICOR, Mondada, GARS, VALIBEL, Ferr{é}), highlighting their respective strengths and limitations when applied to multimodal classroom data. Through comparative analyses of manually transcribed sequences, the project demonstrates the inevitable variability and interpretative dimension of transcription practices, depending on theoretical positioning and analytical goals. Empirical work is based on several corpora, notably the INTER-EXPLIC corpus (approximately 30 hours of classroom interaction) and the EXPLIC-LEXIC corpus, which serve both as testing grounds for manual annotation and as reference datasets for future automation. Particular attention is paid to teacher gestures (kin{é}sic and proxemic resources), prosodic features, and their functional role in meaning construction and learner comprehension. The project also highlights the strategic role of the Techn{é}LAB platform, which provides advanced multimodal data capture (multi-camera video, synchronized audio, eye-tracking, digital interaction traces) and constitutes both a research infrastructure and a test environment for the development of automated tools. In conclusion, TRAIMA does not aim to deliver a fully operational automated system, but rather to establish a rigorous methodological framework for the automatic processing of multimodal pedagogical interactions. The project identifies transcription conventions, annotation categories, and analytical units that are compatible with machine learning approaches, while emphasizing the need for theoretical explicitness and researcher reflexivity. TRAIMA thus lays the groundwork for future interdisciplinary research at the intersection of didactics, discourse analysis, multimodality, and artificial intelligence in education. ;in French language
The rapid advancement of Large Language Models (LLMs) and their integration into autonomous agent systems has created unprecedented opportunities for document analysis, decision support, and knowledge retrieval. However, the complexity of developing, evaluating, and iterating on LLM-based agent workflows presents significant barriers to researchers, particularly those without extensive software engineering expertise. We present FROAV (Framework for RAG Observation and Agent Verification), an open-source research platform that democratizes LLM agent research by providing a plug-and-play architecture combining visual workflow orchestration, a comprehensive evaluation framework, and extensible Python integration. FROAV implements a multi-stage Retrieval-Augmented Generation (RAG) pipeline coupled with a rigorous "LLM-as-a-Judge" evaluation system, all accessible through intuitive graphical interfaces. Our framework integrates n8n for no-code workflow design, PostgreSQL for granular data management, FastAPI for flexible backend logic, and Streamlit for human-in-the-loop interaction. Through this integrated ecosystem, researchers can rapidly prototype RAG strategies, conduct prompt engineering experiments, validate agent performance against human judgments, and collect structured feedback-all without writing infrastructure code. We demonstrate the framework's utility through its application to financial document analysis, while emphasizing its material-agnostic architecture that adapts to any domain requiring semantic analysis. FROAV represents a significant step toward making LLM agent research accessible to a broader scientific community, enabling researchers to focus on hypothesis testing and algorithmic innovation rather than system integration challenges. ;8 pages, 1 figure, 3 tables
Collision avoidance in heterogeneous fleets of uncrewed vessels is challenging because the decision-making processes and controllers often differ between platforms, and it is further complicated by the limitations on sharing trajectories and control values in real-time. This paper presents a pragmatic approach that addresses these issues by adding a control filter on each autonomous vehicle that assumes worst-case behavior from other contacts, including crewed vessels. This distributed safety control filter is developed using control barrier function (CBF) theory and the application is clearly described to ensure explainability of these safety-critical methods. This work compares the worst-case CBF approach with a Collision Regulations (COLREGS) behavior-based approach in simulated encounters. Real-world experiments with three different uncrewed vessels and a human operated vessel were performed to confirm the approach is effective across a range of platforms and is robust to uncooperative behavior from human operators. Results show that combining both CBF methods and COLREGS behaviors achieves the best safety and efficiency. ;8 pages, 10 figures
Electroencephalogram (EEG)-based brain-computer interfaces (BCIs) face significant deployment challenges due to inter-subject variability, signal non-stationarity, and computational constraints. While test-time adaptation (TTA) mitigates distribution shifts under online data streams without per-use calibration sessions, existing TTA approaches heavily rely on explicitly defined loss objectives that require backpropagation for updating model parameters, which incurs computational overhead, privacy risks, and sensitivity to noisy data streams. This paper proposes Backpropagation-Free Transformations (BFT), a TTA approach for EEG decoding that eliminates such issues. BFT applies multiple sample-wise transformations of knowledge-guided augmentations or approximate Bayesian inference to each test trial, generating multiple prediction scores for a single test sample. A learning-to-rank module enhances the weighting of these predictions, enabling robust aggregation for uncertainty suppression during inference under theoretical justifications. Extensive experiments on five EEG datasets of motor imagery classification and driver drowsiness regression tasks demonstrate the effectiveness, versatility, robustness, and efficiency of BFT. This research enables lightweight plug-and-play BCIs on resource-constrained devices, broadening the real-world deployment of decoding algorithms for EEG-based BCI.
This work presents a randomized-tamed Milstein scheme for stochastic differential equations whose drift coefficient exhibits superlinear growth in the state variable and limited temporal regularity, quantified by $β$-Hölder continuity with $β\in (0,1]$. The scheme combines a taming mechanism to control the superlinear state dependence with a drift randomization strategy designed to address the challenges posed by low temporal regularity. Under suitable assumptions on temporal smoothness, the scheme achieves an optimal strong $\mathscr{L}^p$-convergence rate of order one.
Across the world, there is growing interest in new waveforms, Zak-OTFS in particular, and over-the-air implementations are starting to appear. The choice between OFDM and Zak-OTFS is not so much a choice between waveforms as it is an architectural choice between preventing inter-carrier interference (ICI) and embracing ICI. In OFDM, once the Input-Output (I/O) relation is known, equalization is relatively simple, at least when there is no ICI. However, in the presence of ICI the I/O relation is non-predictable and its acquisition is non-trivial. In contrast, equalization is more involved in Zak-OTFS due to inter-symbol-interference (ISI), however the I/O relation is predictable and its acquisition is simple. {Zak-OTFS exhibits superior performance in doubly-spread 6G use cases with high delay/Doppler channel spreads (i.e., high mobility and/or large cells), but architectural choice is governed by the typical use case, today and in the future. What is typical depends to some degree on geography, since large delay spread is a characteristic of large cells which are the rule rather than the exception in many important wireless markets.} This paper provides a comprehensive performance comparison of cyclic prefix OFDM (CP-OFDM) and Zak-OTFS across the full range of 6G propagation environments. The performance results provide insights into the fundamental architectural choice. ;This work has been submitted to the IEEE for possible publication
To address the issues of high operational costs and low energy efficiency (EE) caused by the dense deployment of small base stations (s-BSs) in 5G ultra-dense networks (UDNs), this paper first constructs a multi-objective mathematical optimization model targeting maximizing EE and minimizing the number of active BSs. The model incorporates key constraints including BS operational state, user equipment (UE)-BS connection relationship, and load threshold, laying a theoretical foundation for the coordinated optimization of energy conservation and quality of service. Based on this model, an integrated solution combining UE-BS initial connection optimization and load-sharing based BS sleeping is proposed. In the initial connection phase, with communication quality and BS load as dual constraints, efficient matching between UEs and optimal BSs is achieved through three sequential steps: communication feasibility screening, redundant connection removal, and overload load redistribution. This resolves the problems of load imbalance and difficult identification of redundant BSs in UDNs arising from unordered initial connections. In the BS sleeping phase, a BS sleeping index, comprehensively considering UE transferability and backup BS resources, is innovatively introduced to quantify BS dormancy priority. Through a closed-loop process involving low-load BS screening, adjacent BS load evaluation, and load sharing by two takeover BSs based on their capacity, accurate dormancy of redundant BSs and collaborative load migration are realized. Simulation results in a typical UDNs scenario demonstrate that, compared with the traditional baseline scheme, the proposed solution exhibits significant advantages in convergence speed, optimization of the number of active BSs, and EE improvement. ;11 pages,6 figures
Automated agent workflows can enhance the problem-solving ability of large language models (LLMs), but common search strategies rely on stochastic exploration and often traverse implausible branches. This occurs because current pipelines sample candidate steps from generic prompts or learned policies with weak domain priors, yielding near-random walks over operators, units, and formats. To promote ordered exploration, this paper introduces SCULPT, a constraint-guided approach for Monte Carlo Tree Search (MCTS) that integrates domain-aware scoring into selection, expansion, simulation, and backpropagation. SCULPT scores and prunes actions using a combination of symbolic checks (dimensional consistency, type compatibility, magnitude sanity, depth control, and diversity) and structural pattern guidance, thereby steering the search toward plausible reasoning paths. Under matched LLM configurations, SCULPT yields stable improvements on multiple datasets; additional results with GPT-5.2 assess executor transferability and performance on frontier reasoning models. Overall, domain-aware constraints can improve accuracy while maintaining efficiency and reasoning stability. ;11 pages, 3 figures. Equal contribution: Qitong Fang and Haotian Li. Corresponding authors: Qitong Fang ([email protected]), Haotian Li ([email protected]), Xu Wang ([email protected])
While integrating multiple modalities has the potential to improve environmental monitoring, current approaches struggle to combine data sources with heterogeneous formats or contents. A central difficulty arises when combining continuous gridded data (e.g., remote sensing) with sparse and irregular point observations such as species records. Existing geostatistical and deep-learning-based approaches typically operate on a single modality or focus on spatially aligned inputs, and thus cannot seamlessly overcome this difficulty.
We propose a Geolocation-Aware MultiModal Approach (GAMMA), a transformer-based fusion approach designed to integrate heterogeneous ecological data using explicit spatial context. Instead of interpolating observations into a common grid, GAMMA first represents all inputs as location-aware embeddings that preserve spatial relationships between samples. GAMMA dynamically selects relevant neighbours across modalities and spatial scales, enabling the model to jointly exploit continuous remote sensing imagery and sparse geolocated observations.
We evaluate GAMMA on the task of predicting 103 environmental variables from the SWECO25 data cube across Switzerland. Inputs combine aerial imagery with biodiversity observations from GBIF and textual habitat descriptions from Wikipedia, provided by the EcoWikiRS dataset.
Experiments show that multimodal fusion consistently improves prediction performance over single-modality baselines and that explicit spatial context further enhances model accuracy. The flexible architecture of GAMMA also allows to analyse the contribution of each modality through controlled ablation experiments. These results demonstrate the potential of location-aware multimodal learning for integrating heterogeneous ecological data and for supporting large-scale environmental mapping tasks and biodiversity monitoring. ;under review
Corner detection is widely used in various computer vision tasks, such as image matching and 3D reconstruction. Our research indicates that there are theoretical flaws in Zhang et al.'s use of a simple corner model to obtain a series of corner characteristics, as the grayscale information of two adjacent corners can affect each other. In order to address the above issues, a second-order Gaussian directional derivative (SOGDD) filter is used in this work to smooth two typical high-resolution angle models (i.e. END-type and L-type models). Then, the SOGDD representations of these two corner models were derived separately, and many characteristics of high-resolution corners were discovered, which enabled us to demonstrate how to select Gaussian filtering scales to obtain intensity variation information from images, accurately depicting adjacent corners. In addition, a new high-resolution corner detection method for images has been proposed for the first time, which can accurately detect adjacent corner points. The experimental results have verified that the proposed method outperforms state-of-the-art methods in terms of localization error, robustness to image blur transformation, image matching, and 3D reconstruction. ;11pages, 9 figures
Solving large dense linear systems and eigenvalue problems is a core requirement in many areas of scientific computing, but scaling these operations beyond a single GPU remains challenging within modern programming frameworks. While highly optimized multi-GPU solver libraries exist, they are typically difficult to integrate into composable, just-in-time (JIT) compiled Python workflows. JAXMg provides multi-GPU dense linear algebra for JAX, enabling Cholesky-based linear solves and symmetric eigendecompositions for matrices that exceed single-GPU memory limits. By interfacing JAX with NVIDIA's cuSOLVERMg through an XLA Foreign Function Interface, JAXMg exposes distributed GPU solvers as JIT-compatible JAX primitives. This design allows scalable linear algebra to be embedded directly within JAX programs, preserving composability with JAX transformations and enabling multi-GPU execution in end-to-end scientific workflows.
Studying the optoelectronic structure of materials can require the computation of several thousands of the smallest positive eigenpairs of a pseudo-hermitian Hamiltonian. Iterative eigensolvers may be preferred over direct methods for this task since their complexity is a function of the desired fraction of the spectrum. In addition, they generally rely on highly optimized and scalable kernels such as matrix-vector multiplications that leverage the massive parallelism and the computational power of modern exascale systems. The Chebyshev Accelerated Subspace iteration Eigensolver (ChASE) is able to compute several thousands of the most extreme eigenpairs of dense hermitian matrices with proven scalability over massive parallel accelerated clusters. This work presents an extension of ChASE to solve for a portion of the smallest positive eigenpairs of pseudo-hermitian Hamiltonians as they appear in the treatment of excitonic materials. By exploiting the numerical structure and spectral properties of the Hamiltonian matrix, we preserve the characteristic positive-negative symmetry in the treatment of the eigenvectors and propose an oblique variant of Rayleigh-Ritz projection that features quadratic convergence of the Ritz values with no explicit construction of the dual basis. Additionally, we introduce a parallel implementation of the recursive matrix-product operation appearing in the Chebyshev filter with limited amount of global communications. Our development is supported by a full numerical analysis and experimental tests. ;To be submitted to SISC
Hybrid-Vlasov simulations resolve ion-kinetic effects in the solar wind-magnetosphere interaction, but even 5D (2D + 3V) configurations are computationally expensive. We show that graph-based machine learning emulators can learn the spatiotemporal evolution of electromagnetic fields and lower order moments of ion velocity distribution in the near-Earth space environment from four 5D Vlasiator runs performed with identical steady solar wind conditions. The initial ion number density is systematically varied, while the grid spacing is held constant, to scan the ratio of the characteristic ion skin depth to the numerical grid size. Using a graph neural network (GNN) operating on the 2D spatial simulation grid comprising 670k cells, we demonstrate that both a deterministic forecasting model (Graph-FM) and a probabilistic ensemble forecasting model (Graph-EFM) based on a latent variable formulation are capable of producing accurate predictions of future plasma states. A divergence penalty is incorporated to encourage divergence-freeness in the magnetic fields. For the probabilistic model, a continuous ranked probability score objective is added to improve the calibration of the ensemble forecasts. The trained emulators achieve over two orders of magnitude speedup per time step on a single GPU compared to 100 CPU Vlasiator simulations. Most forecasted fields have Pearson correlations above 0.95 at 50 seconds lead time. However, we find that fields that exhibit near-zero degenerate distributions in the 5D setting are more challenging for the emulator to maintain high correlations for. Overall, these results demonstrate that GNNs provide a viable framework for rapid ensemble generation in hybrid-Vlasov modeling and highlight promising directions for future work.
We investigate whether high-frequency key collisions are a primary bottleneck in Engram-style conditional memory. To isolate the effect of collisions, we introduce Engram-Nine, a collision-free hot-tier extension that maps the most frequent n-grams through a Minimal Perfect Hash Function (MPHF) while retaining the original multi-head hashed lookup as a cold tier. Under a strictly iso-parameter setup, the collision-free design does not consistently improve validation loss.
Through route-stratified evaluation (decomposing per-token loss into hot/cold contributions), we uncover a consistent "hot-to-cold advantage flip" during training: hot (high-frequency) positions initially have lower loss, but cold positions eventually surpass them. Crucially, collision-free configurations flip earlier than collision-prone baselines, suggesting that collisions act as implicit regularization. We also identify a gating mismatch: the gate learns to favor hot positions early in training, but this preference persists even after the flip, assigning higher weights to positions with higher loss.
Our findings suggest that improving lookup precision alone does not guarantee better training outcomes. The dominant limitation may lie in gating credit assignment rather than index accuracy, and collision-induced noise may provide beneficial regularization that should not be naively eliminated.
We present a semi-discrete finite volume scheme for the local NavierStokes-Korteweg and Euler-Korteweg systems. Our scheme is applicable for equidistant Cartesian meshes in one and two space dimensions. In contrast to other works, which employ, for example, hyperbolic approximations of the equations or auxiliary-variable approaches leading to extended systems, our scheme operates directly on the original system. We prove that it conserves mass and momentum and is energy stable. Numerical experiments complement our theoretical findings, showing that the scheme is convergent of order one if employed with explicit or implicit time discretisation.
Speech Emotion Recognition models typically use single categorical labels, overlooking the inherent ambiguity of human emotions. Ambiguous Emotion Recognition addresses this by representing emotions as probability distributions, but progress is limited by unreliable ground-truth distributions inferred from sparse human annotations. This paper explores whether Large Audio-Language Models (ALMs) can mitigate the annotation bottleneck by generating high-quality synthetic annotations. We introduce a framework leveraging ALMs to create Synthetic Perceptual Proxies, augmenting human annotations to improve ground-truth distribution reliability. We validate these proxies through statistical analysis of their alignment with human distributions and evaluate their impact by fine-tuning ALMs with the augmented emotion distributions. Furthermore, to address class imbalance and enable unbiased evaluation, we propose DiME-Aug, a Distribution-aware Multimodal Emotion Augmentation strategy. Experiments on IEMOCAP and MSP-Podcast show that synthetic annotations enhance emotion distribution, especially in low-ambiguity regions where annotation agreement is high. However, benefits diminish for highly ambiguous emotions with greater human disagreement. This work provides the first evidence that ALMs could address annotation scarcity in ambiguous emotion recognition, but highlights the need for more advanced prompting or generation strategies to handle highly ambiguous cases. ;Accepted by ICASSP 2026
The rapid evolution of Multi-modal Large Language Models (MLLMs) has advanced workflow automation; however, existing research mainly targets performance upper bounds in static environments, overlooking robustness for stochastic real-world deployment. We identify three key challenges: dynamic task scheduling, active exploration under uncertainty, and continuous learning from experience. To bridge this gap, we introduce \method{}, a dynamic evaluation environment that simulates a "trainee" agent continuously exploring a novel setting. Unlike traditional benchmarks, \method{} evaluates agents along three dimensions: (1) context-aware scheduling for streaming tasks with varying priorities; (2) prudent information acquisition to reduce hallucination via active exploration; and (3) continuous evolution by distilling generalized strategies from rule-based, dynamically generated tasks. Experiments show that cutting-edge agents have significant deficiencies in dynamic environments, especially in active exploration and continual learning. Our work establishes a framework for assessing agent reliability, shifting evaluation from static tests to realistic, production-oriented scenarios. Our codes are available at https://github.com/KnowledgeXLab/EvoEnv
Tree canopy detection from aerial imagery is an important task for environmental monitoring, urban planning, and ecosystem analysis. Simulating real-life data annotation scarcity, the Solafune Tree Canopy Detection competition provides a small and imbalanced dataset of only 150 annotated images, posing significant challenges for training deep models without severe overfitting. In this work, we evaluate five representative architectures, YOLOv11, Mask R-CNN, DeepLabv3, Swin-UNet, and DINOv2, to assess their suitability for canopy segmentation under extreme data scarcity. Our experiments show that pretrained convolution-based models, particularly YOLOv11 and Mask R-CNN, generalize significantly better than pretrained transformer-based models. DeeplabV3, Swin-UNet and DINOv2 underperform likely due to differences between semantic and instance segmentation tasks, the high data requirements of Vision Transformers, and the lack of strong inductive biases. These findings confirm that transformer-based architectures struggle in low-data regimes without substantial pretraining or augmentation and that differences between semantic and instance segmentation further affect model performance. We provide a detailed analysis of training strategies, augmentation policies, and model behavior under the small-data constraint and demonstrate that lightweight CNN-based methods remain the most reliable for canopy detection on limited imagery. ;Published in the 2026 IEEE International Geoscience and Remote Sensing Symposium (IGARSS 2026) 4 pages, 2 figures
The growing emphasis on 21st-century competencies in postsecondary education, intensified by the transformative impact of generative AI, underscores the need to evaluate how these competencies are embedded in curricula and how effectively academic programs align with evolving workforce and societal demands. Curricular Analytics, particularly recent generative AI-powered approaches, offer a promising data-driven pathway. However, analyzing 21st-century competencies requires pedagogical reasoning beyond surface-level information retrieval, and the capabilities of large language models in this context remain underexplored. In this study, we extend prior curricular analytics research by examining a broader range of curriculum documents, competency frameworks, and models. Using 7,600 manually annotated curriculum-competency alignment scores, we assess the informativeness of different curriculum sources, benchmark general-purpose LLMs for curriculum-to-competency mapping, and analyze error patterns. We further introduce a reasoning-based prompting strategy, Curricular CoT, to strengthen LLMs' pedagogical reasoning. Our results show that detailed instructional activity descriptions are the most informative type of curriculum document for competency analytics. Open-weight LLMs achieve accuracy comparable to proprietary models on coarse-grained tasks, demonstrating their scalability and cost-effectiveness for institutional use. However, no model reaches human-level precision in fine-grained pedagogical reasoning. Our proposed Curricular CoT yields modest improvements by reducing bias in instructional keyword inference and improving the detection of nuanced pedagogical evidence in long text. Together, these findings highlight the untapped potential of institutional curriculum documents and provide an empirical foundation for advancing AI-driven curricular analytics.
Machine unlearning aims to remove specific knowledge (e.g., copyrighted or private data) from a trained model without full retraining. In practice, models are often quantized (e.g., 4-bit) for deployment, but we find that quantization can catastrophically restore forgotten information [1]. In this paper, we (1) analyze why low-bit quantization undermines unlearning, and (2) propose a quantization-aware unlearning method to mitigate this. We first compute weight-change statistics and bucket overlaps in quantization to show that typical unlearning updates are too small to cross quantization thresholds. Building on this insight, we introduce a logits space hinge loss: for each forget example, we force the output logits of the unlearned model to differ from the original model by at least a margin (half the quantization step). This ensures forgotten examples remain distinguishable even after quantization. We evaluate on language and classification tasks (including a Twitter misinformation dataset) and show our method preserves forgetting under 4-bit quantization, whereas existing methods almost entirely recover the forgotten knowledge.
Graph Neural Networks (GNNs) have been widely adopted for Protein Representation Learning (PRL), as residue interaction networks can be naturally represented as graphs. Current GNN-based PRL methods typically rely on single-perspective graph construction strategies, which capture partial properties of residue interactions, resulting in incomplete protein representations. To address this limitation, we propose MMPG, a framework that constructs protein graphs from multiple perspectives and adaptively fuses them via Mixture of Experts (MoE) for PRL. MMPG constructs graphs from physical, chemical, and geometric perspectives to characterize different properties of residue interactions. To capture both perspective-specific features and their synergies, we develop an MoE module, which dynamically routes perspectives to specialized experts, where experts learn intrinsic features and cross-perspective interactions. We quantitatively verify that MoE automatically specializes experts in modeling distinct levels of interaction from individual representations, to pairwise inter-perspective synergies, and ultimately to a global consensus across all perspectives. Through integrating this multi-level information, MMPG produces superior protein representations and achieves advanced performance on four different downstream protein tasks.
We consider (logical) reasoning for regular expressions with lookahead (REwLA). In this paper, we give an axiomatic characterization for both the (match-)language equivalence and the largest substitution-closed equivalence that is sound for the (match-)language equivalence. To achieve this, we introduce a variant of propositional dynamic logic (PDL) on finite linear orders, extended with two operators: the restriction to the identity relation and the restriction to its complement. Our main contribution is a sound and complete Hilbert-style finite axiomatization for the logic, which captures the equivalences of REwLA. Using the extended operators, the completeness is established via a reduction into an identity-free variant of PDL on finite strict linear orders. Moreover, the extended PDL has the same computational complexity as REwLA. ;Long version of a paper accepted at FoSSaCS 2026
The sparse object detection paradigm shift towards dense 3D semantic occupancy prediction is necessary for dealing with long-tail safety challenges for autonomous vehicles. Nonetheless, the current voxelization methods commonly suffer from excessive computation complexity demands, where the fusion process is brittle, static, and breaks down under dynamic environmental settings. To this end, this research work enhances a novel Gaussian-based adaptive camera-LiDAR multimodal 3D occupancy prediction model that seamlessly bridges the semantic strengths of camera modality with the geometric strengths of LiDAR modality through a memory-efficient 3D Gaussian model. The proposed solution has four key components: (1) LiDAR Depth Feature Aggregation (LDFA), where depth-wise deformable sampling is employed for dealing with geometric sparsity, (2) Entropy-Based Feature Smoothing, where cross-entropy is employed for handling domain-specific noise, (3) Adaptive Camera-LiDAR Fusion, where dynamic recalibration of sensor outputs is performed based on model outputs, and (4) Gauss-Mamba Head that uses Selective State Space Models for global context decoding that enjoys linear computation complexity. ;Master Thesis
Accurate forecasts of segment-level sailing durations are fundamental to enhancing maritime schedule reliability and optimizing long-term port operations. However, conventional estimated time of arrival (ETA) models are primarily designed for the immediate next port of call and rely heavily on real-time automatic identification system (AIS) data, which is inherently unavailable for future voyage segments. To address this gap, the study reformulates future-port ETA prediction as a segment-level time-series forecasting problem. We develop a transformer-based architecture that integrates historical sailing durations, destination port congestion proxies, and static vessel descriptors. The proposed framework employs a causally masked attention mechanism to capture long-range temporal dependencies and a multi-task learning head to jointly predict segment sailing durations and port congestion states, leveraging shared latent signals to mitigate high uncertainty. Evaluation on a real-world global dataset from 2021 demonstrates the proposed model consistently outperforms a comprehensive suite of competitive baselines. The result shows a relative reduction of 4.70% in mean absolute error (MAE), 4.95% in mean absolute percentage error (MAPE) and 2.59% in root mean squared error (RMSE) compared with sequential deep learning models. The relative reductions compared with gradient boosting machines are 7.03% in MAE, 39.49% in MAPE and 4.37% in RMSE. The case study conducted on one major destination port further illustrates the model's superior accuracy.
Estimating physically accurate, simulation-ready garments from a single image is challenging due to the absence of image-to-physics datasets and the ill-posed nature of this problem. Prior methods either require multi-view capture and expensive differentiable simulation or predict only garment geometry without the material properties required for realistic simulation. We propose a feed-forward framework that sidesteps these limitations by first fine-tuning a vision-language model to infer material composition and fabric attributes from real images, and then training a lightweight predictor that maps these attributes to the corresponding physical fabric parameters using a small dataset of material-physics measurements. Our approach introduces two new datasets (FTAG and T2P) and delivers simulation-ready garments from a single image without iterative optimization. Experiments show that our estimator achieves superior accuracy in material composition estimation and fabric attribute prediction, and by passing them through our physics parameter estimator, we further achieve higher-fidelity simulations compared to state-of-the-art image-to-garment methods. ;Project Page: https://image2garment.github.io/
Aim Long-haul COVID-19 poses a profound burden to public health. According to the CDC, approximately one in five people who contract COVID-19 have lingering COVID-related symptoms 3 months after testing positive for COVID-19. This paper examines how overall symptom severity in the acute COVID-19 period is related to the risk of developing long COVID and experiencing severe long COVID-related symptoms within the US Veteran population. Subject and methods This study used the Ipsos KnowledgePanel technique to survey 3340 US Veterans and their experiences with COVID-19. Of those surveyed, 658 Veterans had tested positive for COVID-19 and 302 (46%) had symptoms that lasted more than 4 weeks. Veterans reported the types of symptoms they had, the severity of each symptom, and the duration of each symptom. The survey was conducted in October and November of 2021. Results The most common symptoms experienced 4 weeks after testing positive were fatigue, joint pain, headaches, coughing, and fever. Older patients were more likely to experience long COVID, but age was not statistically associated with severity of symptoms experienced during long COVID. The strongest predictors of whether or not a person would develop long COVID and/or severe long COVID symptoms was the severity of their symptoms during the acute phase. Conclusion Understanding the risk factors associated with developing long COVID and severe long COVID will help identify people who would benefit from an intervention that can either mitigate or at least manage the symptoms to prevent further health problems.
As a novel virus, COVID introduced considerable uncertainty into the daily
lives of people all over the globe since late 2019. Relying on twenty-three
semi-structured interviews with parents whose children contracted COVID, we
analyzed how the use of social media moderated parental uncertainty about the
symptoms, prognosis, long-term potential health ramifications of infection,
vaccination, and other issues. We framed our findings using Mishel's
Uncertainty in Illness theory. We propose new components to the theory that
account for technological mediation in uncertainty. We also propose design
recommendations to help parents cope with health uncertainty using social
media.
Since the outbreak in Wuhan (China) at the end of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused instability at various levels of society. While most patients completely recover from their SARS-CoV-2 infection, 10–20% of infected persons and up to 60% of infected patients with cancer develop long COVID. Long COVID is defined as the continuation of symptoms, which cannot be explained by alternative causes, that last longer than four weeks after initial infection. Even though it is generally accepted that patients with cancer are at increased risk of developing severe COVID-19, it is still unclear how long COVID manifests and whether long COVID impacts quality of life in this cohort. Hence, this study observed that patients with cancer reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve. Introduction: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10–20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort. Methods: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection. Results: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes. Conclusion: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve.
We leverage a recently published dataset of Amazon purchase histories,
crowdsourced from thousands of US consumers, to study how online purchasing
behaviors have changed over time, how changes vary across demographic groups,
the impact of the COVID-19 pandemic, and relationships between online and
offline retail. This work provides a case study in how consumer-level purchases
data can reveal purchasing behaviors and trends beyond those available from
aggregate metrics. For example, in addition to analyzing spending behavior, we
develop new metrics to quantify changes in consumers' online purchase frequency
and the diversity of products purchased, to better reflect the growing ubiquity
and dominance of online retail. Between 2018 and 2022 these consumer-level
metrics grew on average by more than 85%, peaking in 2021. We find a steady
upward trend in individuals' online purchasing prior to COVID-19, with a
significant increase in the first year of COVID, but without a lasting effect.
Purchasing behaviors in 2022 were no greater than the result of the
pre-pandemic trend. We also find changes in purchasing significantly differ by
demographics, with different responses to the pandemic. We further use the
consumer-level data to show substitution effects between online and offline
retail in sectors where Amazon heavily invested: books, shoes, and grocery.
Prior to COVID we find year-to-year changes in the number of consumers making
online purchases for books and shoes negatively correlated with changes in
employment at local bookstores and shoe stores. During COVID we find online
grocery purchasing negatively correlated with in-store grocery visits. This
work demonstrates how crowdsourced, open purchases data can enable economic
insights that may otherwise only be available to private firms.
BACKGROUND: The COVID 19 pandemic led to significant disruptions in health services, including immunisation programs, which contributed to a major post-pandemic diphtheria outbreak in Kano State, Nigeria. This region accounted for 85% of the nation's documented diphtheria cases. METHODS: This study examined the epidemiology, clinical characteristics, and mortality outcomes of cases diagnosed between February 2022 and April 2024. Data were collected through the Surveillance Outbreak Response Management and Analysis System (SORMAS), and case definitions followed WHO guidelines. Case fatality rate (CFR) was calculated, and a logistic regression model was used to assess mortality-related risk factors, reporting adjusted odds ratios (AOR). FINDINGS: A total of 18,320 cases were analysed, with the outbreak showing a bimodal distribution. The primary peak occurred in August 2023, followed by a smaller secondary peak in early 2024. The case fatality rate (CFR) was 4.5%. Patients who were not vaccinated had more than double the likelihood of death compared to fully vaccinated individuals (AOR 2.45; 95% CI: 2.05, 2.94, p < 0.0001; logistic regression). Similarly, patients without vaccination documentation also had greater odds, with more than 87% increase likelihood of mortality compared to fully vaccinated individuals (AOR 1.87, 95% CI: 1.27, 2.68, p < 0.0001; logistic regression). INTERPRETATION: Our study reinforces previous reports of the weakening preventive health delivery systems in resource constrained settings, particularly after the disruptions caused by the COVID 19 pandemic leading to the resurgence of vaccine preventable diseases, such as diphtheria. These highlight the need for improved vaccination coverage and surveillance systems. FUNDINGS: This research did not receive any external funding.
OBJECTIVES: Long COVID is a debilitating condition that impacts millions of Americans, but patients and clinicians have little information on how to prevent this disorder. Vaccination is a vital tool in preventing acute COVID-19 and may confer additional protection against Long COVID. There is limited evidence regarding the optimal timing of COVID-19 vaccination (i.e., vaccination schedule) to minimize the risk of Long COVID. METHODS: We applied Longitudinal Targeted Maximum Likelihood Estimation to electronic health record (EHR) data from a retrospective cohort of patients vaccinated against COVID-19 between December 2021 and September 2022. We evaluated the association between binary COVID-19 vaccination status (two or more doses vs. zero doses) and 12-month Long COVID risk among patients diagnosed with acute COVID-19 between December 2021 and September 2022. In addition, we compared the 12-month cumulative risk of Long COVID (ICD-10 code U09.9) among patients diagnosed with acute COVID-19 one to three months after vaccination, three to five months after vaccination, or five to seven months after vaccination while adjusting for relevant high-dimensional baseline and time-dependent covariates. RESULTS: We analyzed EHR data from a retrospective cohort of 1,558,018 patients. In our binary cohort (n = 519,980), we found that vaccinated patients had a lower risk of Long COVID than unvaccinated patients (adjusted marginal risk ratio 0.84 (0.81, 0.88)). In our longitudinal cohort (n = 1,085,291), we did not find a significant difference in Long COVID risk comparing patients who were diagnosed with acute COVID-19 one to three months after vaccination versus patients who were diagnosed with COVID-19 three to five months (adjusted marginal risk ratio 0.93 (95% CI 0.62, 1.41) or 5 to 7 months (adjusted marginal risk ratio 1.06 (95% CI 0.72, 1.56)) after vaccination. CONCLUSIONS: We found that COVID-19 vaccination before SARS-CoV-2 infection was protective against Long COVID, and we did not find that this protection significantly waned within 7 months after vaccination. These findings suggest that COVID-19 vaccination protects against Long COVID.
Background Public transportation plays a major role in the transmission of SARS-CoV2, the virus that causes COVID-19, due to the confined spaces in vehicles. It is therefore very crucial to apply COVID-19 prevention measures in public transportation to reduce risk of COVID-19 transmission. The implementation of these measures depends largely on the public transportation users. We explored the awareness, perceptions and challenges among public transport operators during the implementation of COVID-19 preventive measures in Eastern Uganda. Methods This qualitative study was done in Eastern Uganda in January and February 2021. We conducted four focus group discussions, six in-depth interviews and three key informant interviews to document the awareness, perceptions and challenges faced by public transport operators including 10 boda boda riders, 19 taxi operators and 11 truck (cargo) transporters. All interviews were audio-recorded, transcribed verbatim, and analyzed with the help of NVIVO software version 12 plus using a thematic framework approach. Results We relied on the health belief model to report on four broad themes including: Perceived threat, perceived benefits, perceived barriers and cues to action. Perceived threat Participants were aware of the gravity / seriousness of COVID-19. They were aware that it is an unusual flu whose symptoms are severe and clearly distinguishable from the common flu. They also knew that COVID-19 is easily and quickly transmitted. However they were not aware of the cause of COVID-19. Perceived benefits: the participants perceived a number covid 19 preventive measures as beneficial in preventing COVID-19. These included: COVID 19 vaccination, observing hand hygiene, avoiding touching the ‘soft parts’ (eyes, nose and mouth), quarantining in a hospital setting, wearing a face mask, social distancing,. Perceived barriers: participants reported barriers to implementing COVID 19 preventive measures included Misconceptions about COVID 19, scepticism about COVID-19 vaccination, not breathing well or respiratory problems hinders use of face masks, fear of covid 19 transmission during home isolation, design of the vehicles do not favour social distancing, passengers unwilling to pay the fare, natural reflexes come in the way of not touching soft parts, financial constraints, hostility from passengers due to increased transport fares, law enforcement officials prioritizing the driving permit over implementation of the measures, hostility from law enforcement officials, religious beliefs against the use of alcohol, competing for passengers among public transporters. Cues to action included Mass sensitization by the Ugandan government through the ministry of health with the help of media platforms like television. Conclusions and recommendation Our study brings to light the likely barriers that impede the use of preventive measures in public transportation use during an epidemic / pandemic like COVID-19 which could potentially escalate transmission. During cues to action like sensitization through media, focus should be put to the demystification of myths on COVID-19, highlighting on benefits of using preventive measures and risk of disease. Public transport passengers should be sensitized on risk of COVID-19 transmission during public transportation use and on the importance of complying with COVID-19 preventive measures. We recommend further exploration on the challenges faced by the public transportation passengers in implementing preventive measures in the event of an epidemic like COVID-19. Future research is required to establish a more robust transport model in crisis situations such as a pandemic. In addition, there is need for integration between the public health and public transportation sectors to foster epidemic preparedness for future crises in the context of public transportation.
BACKGROUND: Severe COVID and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokine/chemokine levels. METHODS: We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID patients, MIS-C patients, adult vaccinees, and adult and pediatric healthy controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA. RESULTS: Spike IgG were more afucosylated than bulk IgG during acute adult COVID and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID, with similar trends observed during pediatric COVID/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with pro-inflammatory cytokines in adult COVID and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. CONCLUSIONS: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID and MIS-C immunopathology.
In this chapter provides a comprehensive overview of Long COVID and its most prevalent manifestation, fatigue, tracing the evolution of our understanding from the emergence of COVID-19 in December 2019 through 2024. First, the chapter examines the societal and economic impact of long COVID, affecting an estimated 400 million individuals globally by 2023, with annual economic costs reaching approximately $1 trillion. Through careful analysis of major research milestones and epidemiological studies, the text explores the condition’s prevalence, with fatigue affecting approximately 75% of Long COVID patients. The chapter presents detailed visualizations illustrating the chronological development of COVID-19 and Long COVID research, global cumulative incidence, economic impact across major Western economies, and the distribution of major symptoms. Special attention is given to the complex socioeconomic implications of the condition, including its disproportionate impact on marginalized communities and women and its threat to sustainable development goals. The chapter also examines workforce participation effects, with studies showing affected individuals being 10% less likely to be employed and working 25–50% fewer hours when employed. The text concludes by emphasizing the urgent need for continued research into underlying mechanisms and effective treatment strategies, setting the foundation for the book’s exploration of this significant public health challenge.
Nearly 7.5% U.S. adults have long COVID. Recent epidemiological studies indicated that long COVID, is significantly associated with subsequent brain structure changes. However, it remains unknown if long COVID is causally associated with brain structure change. Here we applied two Mendelian Randomization (MR) methods – Inverse Variance Weighting MR method (IVW) for correlated instrument variables and Component analysis-based Generalized Method of Moments (PC-GMM) – to examine the potential causal relationships from long COVID to brain structure changes. The MR study was based on an instrumental variable analysis of data from a recent long COVID genome-wide association study (GWAS) (3,018 cases and 994,582 controls), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) (Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). We found no significant causal relationship between long COVID and brain structure changes. As we gain more insights into long COVID and its long-term health outcomes, future works are necessary to validate our findings and understand the mechanisms underlying the observed associations, though not causal, of long COVID with subsequent brain structure changes.
Long COVID continues to challenge public health by affecting a significant
segment of individuals who have recovered from acute SARS-CoV-2 infection yet
endure prolonged and often debilitating symptoms. Social media has emerged as a
vital resource for those seeking real-time information, peer support, and
validating their health concerns related to Long COVID. This paper examines
recent works focusing on mining, analyzing, and interpreting user-generated
content on social media platforms such as Twitter, Reddit, Facebook, and
YouTube to capture the broader discourse on persistent post-COVID conditions. A
novel transformer-based zero-shot learning approach serves as the foundation
for classifying research papers in this area into four primary categories:
Clinical or Symptom Characterization, Advanced NLP or Computational Methods,
Policy, Advocacy, or Public Health Communication, and Online Communities and
Social Support. This methodology showcases the adaptability of advanced
language models in categorizing research papers without predefined training
labels, thus enabling a more rapid and scalable assessment of existing
literature. This review highlights the multifaceted nature of Long COVID
research, where computational techniques applied to social media data reveal
insights into narratives of individuals suffering from Long COVID. This review
also demonstrates the capacity of social media analytics to inform clinical
practice and contribute to policy-making related to Long COVID.
Long COVID represents an unprecedented case of patient-led illness definition, emerging through Twitter in May 2020 when patients began collectively naming, documenting, and legitimizing their condition before medical institutions recognized it. This study examines 2.8 million tweets containing #LongCOVID to understand how contested illness communities construct knowledge networks and respond to epistemic injustice. Through topic modeling, reflexive thematic analysis, and exponential random graph modeling (ERGM), we identify seven discourse themes spanning symptom documentation, medical dismissal, cross-illness solidarity, and policy advocacy. Our analysis reveals a differentiated ecosystem of user roles -- including patient advocates, research coordinators, and citizen scientists -- who collectively challenge medical gatekeeping while building connections to established ME/CFS advocacy networks. ERGM results demonstrate that tie formation centers on epistemic practices: users discussing knowledge sharing and community building formed significantly more network connections than those focused on policy debates, supporting characterization of this space as an epistemic community. Long COVID patients experienced medical gaslighting patterns documented across contested illnesses, yet achieved WHO recognition within months -- contrasting sharply with decades-long struggles of similar conditions. These findings illuminate how social media affordances enable marginalized patient populations to rapidly construct alternative knowledge systems, form cross-illness coalitions, and contest traditional medical authority structures.
The public confidence and trust in online healthcare information have been greatly dented following the COVID-19 pandemic, which triggered a significant rise in online health misinformation. Existing literature shows that different datasets have been created to aid with detecting false information associated with this COVID infodemic. However, most of these datasets contain mostly unimodal data, which comprise primarily textual cues, and not visual cues, like images, infographics, and other graphic data components. Prior works point to the fact that there are only a handful of multimodal datasets that support COVID misinformation identification, and they lack an organized, processed and analyzed repository of visual cues. The novel CoVCues dataset, which represents a varied set of image artifacts, addresses this gap and advocates for the use of visual cues towards detecting online health misinformation. As part of validating the contents and utility of our CoVCues dataset, we have conducted a preliminary user assessment study, where different participants have been surveyed through a set of questionnaires to determine how effectively these dataset images contribute to the user perceived information reliability. These survey responses helped provide early insights into how different stakeholder groups interpret visual cues in the context of online health information and communication. The findings from this novel user assessment study offer valuable feedback for refining our CoVCues dataset and for supporting our claim that visual cues are underutilized but useful in combating the COVID infodemic. To our knowledge, this user assessment research study, as described in this paper, is the first of its kind work, involving COVID visual cues, that demonstrates the important role that our CoVCues dataset can potentially play in aiding COVID infodemic related future research work. ;10 pages, To Be Published In Proceedings Of The 1st IEEE Workshop on Healthcare and Medical Device Security, Privacy, Resilience, and Trust (IEEE HMD-SPiRiT), Accepted & Presented At The 7th IEEE International Conference on Trust, Privacy & Security in Intelligent Systems, and Applications (IEEE TPS 2025) on Nov. 11, 2025 in Pittsburgh, PA, USA
The 2020 SARS-CoV-2 coronavirus pandemic highlighted the urgent need for novel small molecule antiviral drugs. (S)- x38 DNDI-6510 is a non-covalent SARS-CoV-2 main protease inhibitor developed by the open science collaboration COVID Moonshot. Here, we report on the metabolic and toxicologic optimization of the lead series previously disclosed by the COVID Moonshot Initiative, leading up to the selection of (S)- x38 DNDI-6510 as the preclinical candidate. We describe the thorough profiling of the series, identifying key risks such as formation of genotoxic metabolites and high clearance, which were successfully addressed during lead optimization. In addition, we disclose the in vitro and in vivo evaluation of (S)- x38 DNDI-6510 in pharmacokinetic and pharmacodynamic models, exploring multiple approaches to ameliorate rodent-specific metabolic clearance, and show that both co-dosing of (S)- x38 DNDI-6510 with an ABT inhibitor and utilizing a metabolically humanized mouse model (8HUM) achieve significant improvements in exposure. Through comparisons of ABT co-dosing and humanized mouse models in efficacy experiments, we demonstrate that continuous exposure over cellular EC (90) is required for SARS-CoV-2 antiviral efficacy in vivo in an antiviral model using a mouse-adapted SARS-CoV-2 strain. Finally, (S)- x38 DNDI-6510 was assessed in maximum tolerated dose experiments in two species, demonstrating significant in vivo PXR-linked auto-induction of metabolism, leading to the discontinuation of this compound. In summary, we report the successful effort to overcome series-specific AMES liabilities in a lead development program. Downstream optimization of existing series will require in-depth optimization of rodent-specific liabilities and metabolic induction profile.
Chronic fatigue syndrome (CFS) remains a subject of scientific research specifically with regards to its association with infections, including the more recently described Long COVID condition. Chronic fatigue and sleep disturbances in Long COVID are intricately linked to disruptions in circadian rhythms, driven by distinct molecular and cellular mechanisms triggered by SARS-CoV-2 infection. This can be driven by various mechanisms including dysregulation of key clock genes (CLOCK, BMAL1, PER2), mitochondrial dysfunction impairing oxidative phosphorylation, and cytokine-induced neuroinflammation (e.g., interleukin-6, tumor necrosis factor-alpha). Epigenetic changes, including DNA methylation at clock-related loci, particularly in peripheral tissues, further contribute to systemic circadian dysregulation. This work underscores the multifaceted molecular and systemic disruptions to circadian regulation in relation to fatigue and sleep disturbances identified as post-infectious sequelae, focusing on the Long COVID condition.
ABSTRACT IMPORTANCE: Over seven million U.S. adults experience "long COVID", or persistent health issues after COVID-19. Multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, but more evidence is needed to guide this recommendation. This study explores the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data. DESIGN: Retrospective cohort study in a multicenter national longitudinal cohort of U.S. adults with history of COVID-19, using health records and survey responses through July 2022 (All of Us CDR 7.0). EXPOSURE(S): Pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional status, indicated by All of Us baseline survey responses and diagnostic/procedure/billing codes. Disease and demographic data covariates were included in the adjusted models. RESULTS: N = 65,464 met inclusion criteria (n=40,655 had post-infection occurrences of at least one symptom (long COVID group), while n=24,809 had none). Adjusted odds ratios within 99% confidence intervals [99% CI] of developing long COVID increased with lower pre-infection self-reported mental health ("Good" compared to "Excellent" AOR=1.14 [1.04,1.25], P>0.000), and more pre-infection symptoms (compared to the median of four, people with zero had much lower odds (AOR=0.15 [0.04,0.61], P=0.008). Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or clinical documentation of functional impairment. CONCLUSIONS. Greater pre-illness symptom burden and lower self-rated mental health increased the odds of long COVID symptoms, after adjusting for demographics, variant, functional status, and individual symptoms. Long COVID represents a change from baseline functioning and health, even in people with pre-infection incident symptoms and functional impairments. This estimation of pre-infection functional status using harmonized electronic health records data demonstrated the feasibility of these data in developing the diagnostic utility of functional status changes in long COVID.
Objective To examine the relationship between physical rehabilitation parameters including an approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting Intensive care units (ICU) at four medical institutions. Patients n = 3780 adults with ICU admission and diagnosis of COVID-19. Interventions We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: (1) mortality; (2) discharge disposition; and (3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) “6-Clicks” (6–24, 24 = greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and main results The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m^2 and 46% (n = 1739) required mechanical ventilation. For 2191 patients who received rehabilitation, the dosage and AM-PAC at discharge were moderately, positively associated (Spearman’s rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R^2 = 0.68, p < 0.001) demonstrates mechanical ventilation (β = − 0.86, p = 0.001), average mobility score in first three sessions (β = 2.6, p < 0.001) and physical rehabilitation dosage (β = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions Greater physical rehabilitation exposure early in the ICU is associated with better physical function at hospital discharge.
Arid regions, the source of most airborne mineral dusts, comprise a third of the Earth’s land surface, where around two billion people are exposed daily to the fine particles raised by wind. Crossing political borders and traveling on air currents around the world, these particles affect the health of their local communities as well as distant populations—putting all at risk for cardiovascular and respiratory illnesses that are overlain with emerging health issues, including potential clinical misdiagnoses of tuberculosis, influenza, and SARS COVID that present similar initial symptoms. Risks of exposure are affected by local and regional weather characteristics and climatic conditions that are in a state of flux. Advances in science and technology promise to reduce the health problems, but windblown dusts and what travels with them can change the fundamental problem and appropriate response. This chapter uses examples of meningitis, asthma, and Valley fever to illustrate how risks may be lowered through an (environmental) dust-health early warning system. A half century of dedicated measurements of particulate air quality and of environmental science enhanced by Earth-orbiting satellites reveal the truth of airborne dust extent, and much of its variability in time and space. These truths have been essential in advancing numerical, dynamic models of the atmosphere which mimic and predict weather systems that loft and transport the airborne dusts that medical sciences and epidemiology prove harmful. The union of many scientific disciplines and services makes possible improved public health around the world.
Background Long COVID involves persistent symptoms after COVID-19 recovery, affecting multiple organ systems for months or years. Risk factors include female sex, prior chronic conditions, severe SARS-CoV-2 infection, reinfections, and lack of vaccination. As a major public health concern, ongoing research continues to investigate its causes, mechanisms, and long-term effects. Methods Proteomic expression analysis of 171 individuals, in two time points, with confirmed SARS-CoV-2 infection, including 133 long COVID patients from the deeply characterized COVICAT cohort, assessed 1395 protein biomarkers using Olink® technology. Statistical analyses with linear mixed models examined protein expression changes, long COVID status, and sex-specific differences. Functional analysis included gene set enrichment analysis and protein–protein interaction networks. Results Findings revealed VEGFA overexpression in long COVID patients (effect size 0.322, SE = 0.098, p = 0.0013), along with sex-specific expression patterns and the influence of sex-hormonal status in females, with significant overexpression of circulating VEGFA levels specifically in postmenopausal women (Mann–Whitney U test p value = 8.55 × 10^−3). Network analysis identified 109 nodes and 274 edges, with VEGFA ranking highest in centrality. Dysregulated chemokine signaling, complement activation, and viral reactivation were also confirmed, consistent with prior studies. Conclusions Using high-throughput proteomic profiling in a population-based cohort, we observed that vascular dysfunction, particularly involving VEGFA, is a key feature of long COVID, especially in milder cases, with significant overexpression of VEGFA in postmenopausal women. Sex-specific proteomic patterns suggest distinct recovery mechanisms, highlighting the need to consider sex, vascular health, and disease severity in the pathogenesis and management of long COVID.
Post-acute sequelae of SARS-CoV-2 infection (Long COVID) frequently persists for months, yet drivers of clinical remission remain incompletely defined.
Here we analyzed 97,564 longitudinal PASC assessments from 13,511 participants with linked vaccination histories to disentangle passive temporal progression from vaccine-associated change.
Using a clinically validated threshold (PASC $\geq 12$), trajectories separated into three phenotypes: Protected (persistently sub-threshold), Refractory (persistently symptomatic), and Responders (transitioning from symptomatic to recovered).
Across the full cohort, symptom severity increased modestly with elapsed time ($r=0.0521$, $P=1.26\times10^{-59}$), whereas cumulative vaccination showed an inverse association with severity ($r=-0.0434$, $P=5.95\times10^{-42}$). In summary, baseline Long COVID severity appears clinically deterministic. In the absence of intervention, symptoms typically persist without spontaneous resolution. Recovery is primarily associated with repeated immunization.
Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients’ clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.
Long COVID, previously known as Post-Acute Sequelae of SARS-CoV-2 (PASC), refers to prolonged symptoms or diagnosable conditions following COVID-19 infection. The neuropsychiatric profile of Long COVID patients remains ambiguous. This study aimed to assess neuropsychiatric symptoms in a retrospective cohort of Long COVID patients (N = 162) at a Rehabilitation Medicine clinic in South Texas. Clinical data from patient records were used to calculate a Symptom Score, and screening tools for stress/PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and quality of life (SWL) were employed to evaluate if Long COVID duration and severity could predict neuropsychiatric outcomes. The majority were female (71%) and Hispanics (53%) who presented for treatment of Long COVID symptoms during the study period, including fatigue (93%), coughing/shortness of breath (81%), fever (67%), anosmia (58%), ageusia (54%), and weight loss (56%). A minority of participants were hospitalized (N = 49) or required ventilator support (N = 5) during acute infection. There was a high burden of neuropsychiatric symptoms, including subjective cognitive impairment (79%), headache (74%), and insomnia (58%). Symptom Score (median = 9, IQR [8,11]) was significantly correlated with increased depression (PHQ-9; p < 0.05), anxiety (GAD-7; p < 0.05) and elevated stress/PTSD (PCL-5; p < 0.05) symptoms. Long COVID patients taking stimulants or mood stabilizers had higher GAD-7 (p < 0.031, p < 0.035) and PHQ-9 (p < 0.034, p < 0.009) scores but not PCL-5 scores. Importantly, duration of Long COVID symptomatology also did not predict PCL-5 scores. No patient factors (e.g., sex, age, BMI, ethnicity) mediated Symptom Score. Nonetheless, historically marginalized groups, such as women and Hispanics, have been disproportionately affected by COVID-19. This study is the first to utilize validated screening tools to determine the presence and severity of neuropsychiatric symptoms in Long COVID patients. These findings may guide clinical management and future research on Long COVID, especially in historically excluded populations. SCOPE STATEMENT: We enthusiastically submit our Original Research article, entitled “ Assessing Neuropsychiatric Symptoms in Long COVID: A Retrospective Cohort Study from a South Texas Long COVID Clinic ” for consideration for publication in the journal Frontiers in Neurology. We believe the scope of our article aligns well with the scope and aim of the journal’s Neurorehabilitation Section. Long COVID is a debilitating neurological disorder with prominent and enduring cognitive and psychological impact. This study sought to characterize Long COVID symptoms from a cohort of patients at a Rehabilitation Medicine/Long COVID clinic in Southwest Texas. We stratified symptoms using validated psychiatric evaluation tools (e.g., PCL-5, GAD-7, PHQ-9, SWL) to determine if and to what extent psychiatric comorbidity exacerbated Long COVID symptoms. Our findings suggest that a Long COVID patient’s depression, anxiety, and stress/post traumatic stress scores are highly correlated with other neurological symptoms. We advance the implementation of a Long COVID “Symptom Score”, as well as the use of validated screening instruments to identify psychiatric features of Long COVID with the goal of maximizing life satisfaction and function over the course of treatment.
IMPORTANCE: Updated knowledge regarding the global prevalence of long COVID (or post-COVID-19 condition), its subtypes, risk factors, and variations across different follow-up durations and geographical regions is necessary for informed public health recommendations and healthcare delivery. OBJECTIVE: The primary objective of this systematic review is to evaluate the global prevalence of long COVID and its subtypes and symptoms in individuals with confirmed COVID-19 diagnosis, while the secondary objective is to assess risk factors for long COVID in the same population. DATA SOURCES: Studies on long COVID published from July 5, 2021, to May 29, 2024, searched from PubMed, Embase, and Web of Science were used for this systematic review. Supplemental updates to the original search period were made. STUDY SELECTION: There were four inclusion criteria: (1) human study population with confirmed COVID-19 diagnosis; (2) appropriate index diagnosis date; (3) outcome must include either prevalence, risk factors, duration, or symptoms of long COVID; and (4) follow-up time of at least two months after the index date. The exclusion criteria were: (1) non-human study population; (1) case studies or reviews; (2) studies with imaging, molecular, and/or cellular testing as primary results; (3) studies with specific populations such as healthcare workers, residents of nursing homes, and/or those living in long-term care facilities; and (4) studies that did not meet the sample size threshold needed to estimate overall prevalence with margin of error of 0.05. DATA EXTRACTION AND SYNTHESIS: Two screeners independently performed screenings and data extraction, and decision conflicts were collectively resolved. The data were pooled using a random-effects meta-analysis framework with a DerSimonian-Laird inverse variance weighted estimator. MAIN OUTCOMES AND MEASURES: The primary estimand (target population parameter of interest) was the prevalence of long COVID and its subtypes among individuals with confirmed COVID-19 diagnoses, and the secondary estimand was effect sizes corresponding to ten common risk factors of long COVID in the same population. RESULTS: A total of 442 studies were included in this mega-systematic review, and 429 were meta-analyzed for various endpoints, avoiding duplicate estimates from the same study. Of the 442 studies, 17.9% of the studies have a high risk of bias. Heterogeneity is evident among meta-analyzed studies, where the I (2) statistic is nearly 100% in studies that estimate overall prevalence. Global estimated pooled prevalence of long COVID was 36% among COVID-19 positive individuals (95% confidence interval [CI] 33%-40%) estimated from 144 studies. Geographical variation was observed in the estimated pooled prevalence of long COVID: Asia at 35% (95% CI 25%-46%), Europe at 39% (95% CI 31%-48%), North America at 30% (95% CI 24%-38%), and South America at 51% (95% CI 35%-66%). Stratifying by follow-up duration, the estimated pooled prevalence for individuals with longer follow-up periods of 1 to 2 years (47% [95% CI 37%-57%]) compared to those with follow-up times of less than 1 year (35% [95% CI 31%-39%]) had overlapping CI and were therefore not statistically distinguishable. Top five most prevalent long COVID subtypes among COVID-19 positive cases were respiratory at 20% (95% CI 14%-28%) estimated from 31 studies, general fatigue at 20% (95% CI 18%-23%) estimated from 121 studies, psychological at 18% (95% CI 11%-28%) estimated from 10 studies, neurological at 16% (95% CI 8%-30%) estimated from 23 studies, and dermatological at 12% (95% CI 8%-17%) estimated from 10 studies. The most common symptom based on estimated prevalence was memory problems estimated at 11% (95% CI 7%-19%) meta-analyzed from 12 studies. The three strongest risk factors for long COVID were being unvaccinated for COVID-19, pre-existing comorbidity, and female sex. Individuals with any of these risk factors had higher odds of having long COVID with pooled estimated odds ratios of 2.34 (95% CI 1.49-3.67) meta-analyzed from 6 studies, 1.59 (95% CI 1.28-1.97) from 13 studies, and 1.55 (95% CI 1.25-1.92) from 22 studies, respectively. CONCLUSIONS AND RELEVANCE: This study shows long COVID is globally prevalent in the COVID-19 positive population with highly varying estimates. The prevalence of long COVID persists over extended follow-up, with a high burden of symptoms 1 to 2 years post-infection. Our findings highlight long COVID and its subtypes as a continuing health challenge worldwide. The heterogeneity of the estimates across populations and geographical regions argues for the need for carefully designed follow-up with representative studies across the world. KEY POINTS: QUESTION: What are the prevalence and patterns of long COVID and its subtypes, and what are the risk factors of long COVID? RESULTS: Meta-analysis of 429 studies published from 2021-2024 estimated a pooled global long COVID prevalence of 36% in COVID-19 positive individuals. Variations in geographical regions showed that South America had the highest pooled prevalence of 51% (95% CI: 35%-66%), and the prevalence does not seem to diminish with extended follow-up (less than 1 year: 35%, 95% CI: 31%-39% vs. 1 to 2 years: 47%, 95% CI: 37%-57%). The estimated pooled prevalence of eight major long COVID subtypes in COVID-19 positive individuals were 20% (respiratory), 20% (general fatigue), 18% (psychological), 16% (neurological), 12% (dermatological), 10% (cardiovascular), 9% (musculoskeletal) and 5% (gastrointestinal). MEANING: Quantitative evidence shows a persistent prevalence of long COVID globally, with a significant burden of symptoms 1 to 2 years post-infection, underscoring the need for having accurate and standardized diagnostic tests and biomarkers for long COVID, a better understanding of the physiology of the condition, its treatment, and its potential effect on healthcare needs and workforce participation. The heterogeneity and wide range of the prevalence estimates call for representative samples in well-designed follow-up studies of long COVID across the world.
Long COVID continues to challenge public health by affecting a considerable
number of individuals who have recovered from acute SARS-CoV-2 infection yet
endure prolonged and often debilitating symptoms. Social media has emerged as a
vital resource for those seeking real-time information, peer support, and
validating their health concerns related to Long COVID. This paper examines
recent works focusing on mining, analyzing, and interpreting user-generated
content on social media platforms to capture the broader discourse on
persistent post-COVID conditions. A novel transformer-based zero-shot learning
approach serves as the foundation for classifying research papers in this area
into four primary categories: Clinical or Symptom Characterization, Advanced
NLP or Computational Methods, Policy Advocacy or Public Health Communication,
and Online Communities and Social Support. This methodology achieved an average
confidence of 0.7788, with the minimum and maximum confidence being 0.1566 and
0.9928, respectively. This model showcases the ability of advanced language
models to categorize research papers without any training data or predefined
classification labels, thus enabling a more rapid and scalable assessment of
existing literature. This paper also highlights the multifaceted nature of Long
COVID research by demonstrating how advanced computational techniques applied
to social media conversations can reveal deeper insights into the experiences,
symptoms, and narratives of individuals affected by Long COVID.
Background The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV. Methods Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms. Discussion The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV. Protocol version Version 4.0 dated 15 March 2024. Trial registration Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27–062022-6058.
OBJECTIVES: People living with HIV (PLWH) face unique psychosocial challenges due to both infection and antiretroviral therapy (ART), one of which is body image disruption. Yet, a comprehensive synthesis of existing research on body image among PLWH is lacking. This study systematically reviewed relevant studies to explore body image issues, identify associated factors, and describe assessment methods and interventions targeting body image in this population. METHODS: Guided by the PRISMA, a thorough search of PsycINFO, PubMed, Embase, and Web of Science was conducted in January 2024, including empirical studies considering Body Image among PLWH published in peer-reviewed English journals, using search terms relevant to HIV and Body image. To include the latest articles, we conducted another round of searches in November 2024. NIH Study Quality Assessment Tools were used to assess the quality of the included studies, and a narrative synthesis was conducted to identify common themes, including definitions of body image, associated factors, measurement instruments, and interventions targeting body image among PLWH. RESULTS: From 2197 publications, 26 studies from 2004 to 2024 met the inclusion criteria, comprising a sample of 4095 PLWH aged 8 to 65 from different countries. Most of the studies were cross-sectional in design and varied in focus. Findings reveal that body image issues are prevalent among PLWH. The majority of studies demonstrated an association between negative body image and psychological comorbidities, including depression, anxiety, social withdrawal, and substance use. Body image dissatisfaction was also associated with physical health factors such as lipodystrophy. BMI measures reported in twelve studies indicated that BMI tends to increase with age in PLWH. Sixteen distinct body image measurement tools were used across studies. CBT-BISC was the only target intervention that showed effectiveness in mitigating body image disturbance and improving ART adherence among PLWH. CONCLUSION: Body image issues represent a critical but often overlooked component of the biopsychosocial challenges faced by PLWH. This is the first comprehensive literature review to exclusively consider body image, associated factors, measurements, and target interventions among PLWH, which highlighted the need for comprehensive, culturally sensitive interventions that address both the physical and psychological dimensions of body image concerns.
Tuberculosis (TB) treatment is highly effective, but response to therapy can vary by geography, race, and ethnicity. We assessed for differences in TB treatment response in a representative and heterogeneous Brazilian population. We estimated genetic ancestry proportion according to major ancestry groups (African, European, and Amerindian ancestry) in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort. RePORT-Brazil is an observational prospective cohort study of individuals with newly-diagnosed, culture-confirmed, pulmonary TB. TB treatment outcomes that were attributed to TB treatment included Grade 2 or higher adverse drug reaction (ADR), Grade 3 or higher ADR, hepatic ADR, and failure/recurrence. Ancestry proportion was the main predictor in logistic regression for each outcome, with adjustments for candidate confounders. There were 941 pulmonary TB patients included in this study. We observed a decreased risk of Grade 2+ ADR when African ancestry proportion increased by 10% (Odds Ratio [OR] 0.41, 95% Confidence Interval [CI] 0.20 -0.85) and an increased risk for Grade 2+ ADR with increasing European ancestry (OR 2.84, 95% CI 1.47 - 5.48). We then performed the same analysis adding HIV status as an interaction term. The decreased risk for Grade 2+ ADR seen for African ancestry proportion did not hold for persons living with HIV; we observed increased risk for Grade 2+ ADR with increasing African ancestry proportion. There were no associations with Amerindian ancestry or for other treatment outcomes. In this Brazilian TB cohort, toxicity risk was associated with African and European ancestry, divergent, and affected by HIV. : Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil. : Clínica de Saúde Rinaldo Delmare, Rio de Janeiro, Brazil. : Secretaria de Saúde de Duque de Caxias, Rio de Janeiro, Brazil. : Instituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, Brazil. : Fundação Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil. : Vanderbilt University Medical Center, Nashville, USA.
During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.
Background Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia. Methods Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life. Discussion This study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy. Trial registration ClinicalTrials.gov NCT05556720. Registered on 23rd August 2022.
Introduction Intracranial fungal infections’ (IcFIs) varying clinical manifestations lead to difficulties in diagnosis and treatment. African populations are disproportionately affected by the high burden of the disease. There is a lack of clarity as to the diagnostic and treatment modalities employed across the continent. In this review, we aim to detail the management, and outcome of IcFIs across Africa. Methods This scoping review was conducted using the Arksey and O'Malley framework. MEDLINE, EMBASE, Cochrane Library, African Index Medicus, and African Journals Online were searched for relevant articles from database inception to August 10th, 2021. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews guidelines were used to report the findings of the review. Results Of the 5,779 records identified, 131 articles were included. The mean age was 35.6 years, and the majority (56.4%) were males. The majority ( n = 8,433/8,693, 97.0%) of IcFIs presented as a meningitis, the most common communicable predisposing factor of IcFIs was HIV/AIDS ( n = 7,815/8,693, 89.9%), and the most common non-communicable risk factor was diabetes mellitus ( n = 32/8,693, 0.4%). Cryptococcus species was the most common ( n = 8,428/8,693, 97.0%) causative organism. The most commonly used diagnostic modality was cerebrospinal (CSF) cultures ( n = 4,390/6,830, 64.3%) for diffuse IcFIs, and MRI imaging (n = 12/30, 40%) for focal IcFIs. The most common treatment modality was medical management with antifungals only ( n = 4,481/8,693, 51.6%). The most commonly used antifungal agent in paediatric, and adult patients was amphotericin B and fluconazole dual therapy (51.5% vs 44.9%). The overall mortality rate was high ( n = 3,475/7,493, 46.3%), and similar for both adult and paediatric patients (47.8% vs 42.1%). Conclusion Most IcFIs occurred in immunosuppressed individuals, and despite the new diagnostic techniques, CSF culture was mostly used in Africa. Antifungals regimens used was similar between children and adults. The outcome of IcFIs in Africa was poor for both paediatric and adult patients.
Timely linkage to HIV care is essential for achieving South Africa’s treatment goals, yet significant gaps persist in the early stages of the HIV care continuum. This study examined multilevel factors influencing linkage to care in a high HIV-prevalence rural district. A prospective convergent mixed-methods cohort study was conducted over 21 months among 1,194 adults newly diagnosed with HIV across 18 facilities in KwaZulu-Natal. Quantitative analyses (Pearson’s chi-square, Mann-Whitney tests, and logistic regression) were used to identify factors associated with linkage to care within three months of diagnosis. Qualitative data from in-depth interviews with 38 purposively selected participants were analysed thematically and triangulated with quantitative findings to provide contextual insights. Overall, 83% of participants linked to care within three months. Linkage was significantly higher among those diagnosed at hospitals (OR = 4.90; 95% CI: 1.87–12.82; p = 0.003), while diagnosis at mobile clinics showed borderline significance. Among women, later sexual debut (≥ 17 years) was associated with increased likelihood of timely linkage. In contrast, condom use at last sex (OR = 0.50; 95% CI: 0.32–0.79; p = 0.03) and substance use (OR = 0.67; 95% CI: 0.47–0.96; p = 0.05) were associated with lower linkage. Qualitative findings highlighted supportive family environments and positive provider interactions as key facilitators of linkage, while stigma, fear of disclosure, confidentiality concerns, preference for traditional or spiritual healing, and health system challenges, including lost clinic files and poor counselling, emerged as significant barriers. These findings underscore the need for patient-centred, stigma-free, and responsive health systems to improve timely linkage to HIV care in high-burden settings.
INTRODUCTION: While voluntary medical male circumcision (VMMC) reduces the individual- level risk of HIV acquisition by approximately 60% in randomised-controlled trials, little is known about the ‘real-world’ long-term effect of medical and traditional male circumcision on the cumulative risk of HIV infection. We estimate the association between these for the first time using a quasi-experimental study design—a household fixed-effects analysis—for sub- Saharan Africa, the global region with the largest HIV burden. METHODS: We pooled individual-level cross-sectional data from the nationally-representative Demographic and Health Surveys and AIDS Indicator Surveys across all sub-Saharan African countries in which the surveys included data on both male circumcision and HIV status. We estimated the association between male circumcision and HIV status using modified Poisson regression models with household fixed-effects—which control for unobserved and observed confounding shared by men living in the same household—and included additional individual- level controls for demographic characteristics, socio-economic factors, and sexual behaviour. RESULTS: We included individual data from 279,351 male participants in 48 nationally- representative surveys conducted in 29 countries between 2003–2018. The mean survey-level prevalence of male circumcision was 65.9% (median 84.5%, IQR 28.8%–68.1%) and HIV was 5.6% (median 2.5%, IQR 1.2%–10.2%). We estimated that male circumcision was significantly associated with a nearly one-fifth reduction in the cumulative risk of HIV infection (adjusted risk ratio 0.81, 95% CI 0.73–0.89). CONCLUSIONS: Male circumcision was associated with a significant reduction in the risk of HIV infection in sub-Saharan Africa over the past two decades. Increased political and financial commitment to VMMC could likely lead to further reductions in HIV prevalence, especially when rolled out as a HIV prevention option in combination with other interventions.
Human immunodeficiency virus (HIV) phylogenetic analysis has been introduced in a select number of jurisdictions globally for the purposes of HIV public health surveillance. Using this epidemiological tool in this way can enhance public health efforts aimed at managing HIV transmission. This application, however, presents many legal and ethical concerns that may counter such efforts, particularly in regulatory environments where HIV transmission can be subject to criminal prosecution. This article uses Victoria, Australia, as a case study and analyses the current regulatory frameworks relevant to HIV transmission and explores how these may influence the future implementation of phylogenetic analysis in this setting. The article concludes by offering a series of regulatory recommendations including considerations relevant to law and policy reform; procedures and practice; education and guidance; and community engagement and research.
BACKGROUND: We previously demonstrated at the Ward 86 human immunodeficiency virus (HIV) clinic in San Francisco that long-acting (LA) cabotegravir (CAB)/rilpivirine (RPV) (LA-CAB/RPV) can rapidly lead to viral suppression in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate the durability of viral suppression in this population. METHODS: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load ≥50 copies/mL) before December 2022. Our primary outcome was viral suppression (viral load <50 copies/mL) with LA-CAB/RPV persistence (not discontinued or late by >14 days) at 48 weeks, using the viral load closest to 48 ± 8 weeks. We also describe viral failure, defined as a <2-log decline in viral load at 4 weeks or a viral load ≥200 copies/mL after initial viral suppression with emergent CAB- or RPV-associated resistance mutations; overall 48-week viral suppression including those switched to alternative antiretroviral therapy (ART). RESULTS: Fifty-nine PWH initiated LA-CAB/RPV with viremia and were included in the analysis; 49% had a CD4 cell count <200/µL, and the median baseline viral load was 42 900 copies/mL (quarter 1–quarter 3, 5272–139 038). At 48 weeks, 47 PWH met the primary outcome of viral suppression with LA-CAB/RPV persistence (80% [95% confidence interval, 67%–89%]). Five had viral failure with resistance (3 with RPV-associated and 2 with CAB- and RPV-associated mutations), and 1 was lost to follow-up. At week 48, 2 of those with viral failure were suppressed on alternative regimens (lenacapavir + bictegravir/tenofovir alafenamide/emtricitabine and CAB + lenacapavir). The overall viral suppression at week 48 with either LA-CAB/RPV or alternative ART was 92% (54 of 59). CONCLUSIONS: In PWH initiating LA-CAB/RPV with initial viremia, 48-week viral suppression (<50 copies/mL) was seen in 92%. LA ART can be an important tool for improving viral suppression among patients who face adherence challenges to oral ART.
To determine whether endorsement patterns of psychosocial symptoms revealed distinct subgroups, or latent classes, of people living with HIV who use substances (PLWH-SU), and to assess whether these classes demonstrated differential health outcomes over time. This study uses data from 801 PLWH-SU initially enrolled across 11 US hospitals during 2012–2014 and followed up in 2017. Latent class analysis included 28 psychosocial items. Regression analysis examined class membership as a predictor of viral suppression. Survival analysis examined class as a predictor of all-cause mortality. The selected model identified five unique classes. Individuals in classes characterized by more severe and more numerous psychosocial symptoms at baseline had lower likelihoods of viral suppression and survival. The study demonstrated the importance of considering patterns of overlapping psychosocial symptoms to identify subgroups of PLWH-SU and reveal their risks for adverse outcomes. Integration of primary, mental health, and substance use care is essential to address the needs of this population.
Option B + provides lifelong ART to pregnant and breastfeeding women with HIV to reduce mother-to-child transmission of HIV (eMTCT) and improve maternal health. The effectiveness of Option B + relies on continuous engagement, but suboptimal monitoring of HIV care hinders our measurements of engagement. Process mapping and quality improvement (PROMAQI) is a quality improvement strategy for healthcare workers (HCWs) to optimize complex processes such as monitoring HIV care. We assessed the acceptability and feasibility of the PROMAQI among HCWs and identified barriers and facilitators for PROMAQI implementation. A cross-sectional study using a mixed method approach was conducted from August 2021 to March 2022 across five urban health facilities participating in PROMAQI implementation n the Lilongwe district, Malawi. We assessed PROMAQI acceptability and feasibility at the end of the study. A 5-point Likert (1 = worst to 5 = best) scale tool was administered to 110 HCWs ( n = 15–33 per facility) involved in PROMAQI implementationThese data were analysed using descriptive statistics Among the 110 HCWs, twenty-two (QI team ( n = 11) and QI implementers ( n = 11)) were purposively selected for in-depth interviews. Thematic analysis was conducted using deducted and inductive approaches. The theoretical framework for acceptability (TFA) was used to identify reasons for acceptability. The Consolidated Framework for Implementation Research (CFIR) was used to characterize the barriers and facilitators of PROMAQI implementation. HCWs recruited had a median age of 37 (32–43) years, 82.0% of whom were female. Most (42%) had completed secondary education, and 84% were nurses and community health workers. The median (IQR) acceptability and feasibility scores for the PROMAQI were 5 (IQR 4–5) and 4 (IQR 4–5), respectively. Reasons for high PROMAQI acceptability included addressing a relevant gap and improving performance. Perceived implementation barriers included poor work attitudes, time constraints, resource limitations, knowledge gaps, and workbook difficulties. The facilitators included communication, mentorship, training, and financial incentives. PROMAQI is a highly acceptable and feasible tool for monitoring engagement of women in Option B + . Addressing these barriers may optimize the implementation of PROMAQI. Scaling up PROMAQI may enhance retention in the Option B + program and facilitate eMTCT.
Cabotegravir intramuscular gluteal injection is approved for HIV treatment (with rilpivirine) and prevention. Thigh muscle is a potential alternative injection site. We aim to characterize cabotegravir pharmacokinetics and its association with demographics following intramuscular thigh injection in comparison with gluteal injection using population pharmacokinetic (PPK) analysis. Fourteen HIV-negative participants received 600 mg single thigh injection in phase 1 study 208832 and 118 participants with HIV received thigh injections 400 mg monthly 4× or 600 mg once-every-2-months 2× after ≥3 years of gluteal injections in phase 3b study ATLAS-2M provided 1,249 cabotegravir concentrations from 366 thigh injections and 1,998 concentrations from 1,618 gluteal injections. The established gluteal PPK model was modified by adding thigh injection compartment and fit to pharmacokinetic data following both gluteal and thigh injections, enabling within-person comparison in ATLAS-2M. Gluteal parameters were fixed. Similar to the gluteal absorption rate constant (KA(gluteal)), the thigh absorption rate constant (KA(thigh)) was slower in females than males and in participants with higher BMI. KA(thigh) was strongly correlated with KA(gluteal) (correlation coefficient 0.766), best described by the additive linear relationship KA(thigh) = KA(gluteal) + 0.0002527 h(−1). Terminal half-life of thigh injection was 26% (male) and 39% (female) shorter than gluteal injection. Relative bioavailability of thigh to gluteal was estimated to be 89.9%. The impact of covariates on cabotegravir exposure following thigh injections was ≤35%. In conclusion, cabotegravir absorption following thigh injection was correlated with, faster than, and 10% less bioavailable than gluteal injection, and correlated with sex and BMI. The cabotegravir thigh PPK model can inform dosing strategies and future study design.
Background Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies. Methods The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes. InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial. Discussion If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region. Trial registration ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1 .
Background Blood transfusions save millions of lives each year, but are also associated with significant health risks, including transfusion-transmitted infections (TTIs). The World Health Organization recommends mandatory screening for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and syphilis prior to transfusion. This study presents the first screening results from a public blood bank in Somaliland. Method Records from blood donors attending the blood bank of Hargeisa Group Hospital, Somaliland from January 2020 throughout December 2022 were reviewed retrospectively. Blood donations were screened using rapid diagnostic tests for HIV, HBsAg, anti-HCV and syphilis. Screening results and baseline demographic data were collected from all unique blood donors. Results Among the 19,021 blood donors, 18,989 (99.8%) were male and the median age was 29 (interquartile range 25–35) years. A total of 310 (1.6%) individuals had one of the four TTIs screened for, of whom 226 (73%) were HBsAg positive. The seroprevalence of HIV was 0.1%; HBsAg 1.2%; anti-HCV 0.1%; and syphilis 0.3%. No co-infections were found. Conclusion The most common TTI was hepatitis B virus infection. The reported seroprevalence of TTIs was low compared to other studies in the region.
BACKGROUND: People with HIV (PWH) are at heightened risk for type 2 diabetes (T2D) and insulin resistance (IR), even with effective antiretroviral therapy (ART). Adipose tissue dysfunction, including subcutaneous adipose tissue (SAT) fibrosis, is a key contributor to metabolic disease. However, the role of SAT fibrosis in IR among PWH remains poorly understood. We therefore investigated the relationship between SAT fibrosis and IR in PWH along with molecular signatures that might distinguish HIV-associated SAT fibrosis from that associated with obesity. METHODS: We studied 112 participants, including 43 PWH and 69 people without HIV (PWoH) and excluding those with established T2D. Body composition was assessed by dual-energy X-ray absorptiometry (DXA), and SAT fibrosis was analyzed by quantifying hydroxyproline levels from biopsies. SAT transcriptional profiles were examined using a targeted fibrosis-related gene panel. Plasma levels of endotrophin, a marker of extracellular matrix remodeling, were also measured. RESULTS: PWH had significantly greater SAT fibrosis compared to PWoH, with the largest differences observed among participants without obesity. In this subgroup, SAT fibrosis was strongly associated with IR, despite the absence of elevated adiposity. Transcriptomic analysis identified a distinct fibrosis-associated gene expression pattern in PWH, marked by upregulation of COL14A1 and key immune-related genes (e.g. CCL4 , NLRP3 ). Pathway analysis further supported upregulated extracellular matrix remodeling and immune activation, along with downregulated thermogenesis, lipid metabolism, and insulin signaling in the SAT of non-obese PWH. Plasma endotrophin levels were significantly elevated in PWH and were independently associated with SAT fibrosis. CONCLUSION: Our findings identify SAT fibrosis as an obesity-independent driver of IR in PWH. Notably, SAT fibrosis predicts IR at normal body fat levels and can be noninvasively monitored through circulating endotrophin, offering a potential biomarker for early intervention. The distinct transcriptional signature of HIV-associated fibrosis reveals unique mechanisms that may underlie heightened metabolic risk in this population and highlight new therapeutic avenues targeting adipose tissue remodeling and metabolic dysfunction. FUNDING: This work was supported by National Institutes of Health grants R01DK141041 (PWH and SKK), R01DK112304 (PWH and SKK), R56DK133997 (PWH and SKK), K08DK124679 (DLA) Robert Wood Johnson Foundation, Harold Amos Medical Faculty Development Program (DLA), NIH T32 Training Grant 5T32DK007418 (MKC), UCSF NORC grant (P30DK098722), National Institutes of Health: UCSF-Bay Area Center for AIDS Research (P30 AI027763). The funding authorities had no role in study design, data collection, analysis, interpretation, the decision to publish, or manuscript preparation.
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among people with HIV (PWH), but the influence of co-infections like tuberculosis (TB) on CVD risk remains underexplored. We aimed to compare cardiometabolic profiles of PWH with and without prior TB to determine if prior TB is associated with distinct cardiometabolic profiles. METHODS: We conducted a comparative, cross-sectional study at a tertiary hospital in Kampala, Uganda. Participants were randomly sampled PWH aged ≥18 years on antiretroviral therapy. Specifically, we enrolled PWH with and without prior active TB (ratio of 1:1). Anthropometric measurements, blood pressure, fasting blood glucose (FBG), lipid profile, and glycated hemoglobin were assessed. RESULTS: A total of 396 participants were enrolled (196 TB survivors and 200 controls). TB survivors had higher median FBG (5.5 vs. 5.1 mmol/l, p<0.001) and a higher prevalence of DM (17.9% vs. 9.5%, p=0.015). However, they had lower body mass index (23.0 vs. 25.1 kg/m², p<0.001) and waist circumference (81.0 vs. 84.0 cm, p=0.026). TB survivors had higher HDL-c levels (1.0 vs. 0.8 mmol/l, p<0.001), lower LDL-c levels (2.7 vs. 3.1 mmol/l, p<0.001) and lower prevalence of dyslipidemia (81.7% vs. 96.5%, p<0.001). Prior TB was independently associated with higher prevalence of elevated FBG (adjusted prevalence ratio (aPR) 1.79, 95% CI 1.10-2.92) and DM (aPR 2.34, 95% CI 1.11-4.94), but decreased risk of obesity (aPR 0.42, 95% CI 0.20-0.88). CONCLUSION: TB survivors with HIV exhibit a higher risk of DM but lower risk of obesity compared to those without a history of TB, indicating a need for blood glucose monitoring among TB survivors.
BACKGROUND: Women comprise 19% of new HIV infections in the U.S. Many women, particularly women of color, are unaware of pre-exposure prophylaxis (PrEP) as an HIV prevention option. We conducted a pilot randomized controlled trial (RCT) to assess feasibility and acceptability of a theory-based, contextually-relevant behavioral intervention, Just4Us, to promote PrEP initiation and adherence among women in New York City and Philadelphia. METHODS: Eligibility criteria included: cisgender women, aged 18-55, not living with HIV, not currently taking PrEP, and meeting PrEP eligibility guidelines. Participants were randomized 3:1 to the Just4Us Education and Activities (E&A) arm or to the Information arm (Info); all were provided with PrEP information and a referral list. E&A arm participants received an individually-delivered session with a counselor-navigator, who provided information, motivation enhancement, skills-building, problem-solving, and referrals. Between baseline and 3-month follow-up, E&A arm participants received phone calls to support linkage to care and text-messages to promote adherence. Feasibility and acceptability were assessed. RESULTS: Eighty-three women were enrolled (61 intervention; 22 Info); 79% were Black, 26% Latina, exceeding diversity and enrollment targets. Attendance rate for the initial E&A and Info intervention session was 100%. Three-month retention rate was high at 90%. E&A arm participants reported feeling “very satisfied/satisfied with the following: overall session, 95%; discussion with counselor-navigator, 97%; tablet activities, 95%; text-messaging set-up, 93%.; and video, 90%. Among Info and E&A arms, 78% felt the session length was just right, and 95% stated that they would recommend/strongly recommend Just4Us to others. CONCLUSIONS: The pilot RCT demonstrated feasibility and acceptability of the Just4Us E&A intervention, a promising intervention to increase uptake of PrEP among cisgender women. The team was able to recruit, implement the interventions with a high degree of fidelity, and retain the target number of PrEP-eligible socially disadvantaged women. Overall, participant feedback indicated they were generally very satisfied with their intervention.
Background Successful HIV treatment programs have turned HIV into a chronic condition, but noncommunicable diseases such as hypertension jeopardize this progress. Hypertension control rates among people with HIV (PWH) are low owing to gaps in patient awareness, diagnosis, effective treatment, and management of both conditions at separate clinic visits. Integrated management, such as in our study, InterCARE, can enhance HIV-hypertension integration and blood pressure (BP) control. Methods Our pilot study was conducted in two Botswana HIV clinics between October 2021 and November 2022. Based on our formative work, we adopted three main strategies; Health worker training on HTN/cardiovascular disease (CVD) management, adaptation of HIV Electronic Health Record (EHR) for HTN/CVD care, and use of treatment partners to support PWH with hypertension for implementation. We employed the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to assess implementation effectiveness and outcomes for BP control at baseline, 6 and 12 months. HIV viral load (VL) suppression was also measured to assess impact of integration on HIV care. Results We enrolled 290 participants; 35 (12.1%) were lost to follow-up, leaving 255 (87.9%) at 12-months. Median age was 54 years (IQR 46–62), and 77.2% were females. Our interventions significantly improved BP control to < 140/90 mmHg (or < 130/80 mmHg if diagnosis of diabetes or chronic kidney disease), from 137/290 participants, 47.2% at baseline to 206/290 participants, 71.0%, at 12 months ( p < 0.001). Among targeted providers, 94.7% received training, with an associated significant increase in counseling on exercise, diet, and medication (all p < 0.001) but EHR use for BP medication prescribing and cardiovascular risk factor evaluation showed no adoption. In the intention-to-treat analysis, HIV VL suppression at 12 months decreased (85.5% vs 93.8%, p = 0.002) due to loss to follow-up but the per protocol analysis showed no difference in VL suppression between baseline and 12 months (97.3% vs 93.3%, p = 0.060). Conclusion The InterCARE pilot study demonstrated that low-cost practical support measures involving the integration of HIV and hypertension/CVD management could lead to improvements in BP control. These results support the need for a large implementation and effectiveness trial. Trial registration ClinicalTrials.gov NCT05414526. Registered 18th May 2022.
Background Human Immunodeficiency Virus (HIV) continues to be the major cause of childhood deaths, particularly in the sub-Saharan African region. In Ethiopia, though several primary studies have been conducted on the incidence of HIV-related child mortality, the pooled incidence density mortality rate among HIV-positive children is unknown. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence density mortality rate among HIV-positive children and identify its associated factors in Ethiopia. Methods We browsed PubMed, HINARI, Science Direct, Google Scholar, African Journals Online, and cross-references using different search terms to identify articles. Quality appraisal was done using the Joanna Briggs Institute checklist. Meta-package was used to estimate the pooled incidence of mortality and hazard ratio (HR) of predictors. Heterogeneity was tested using the I-square statistics. Publication bias was tested using a funnel plot visual inspection and Egger’s test. Data was presented using forest plots and tables. The random effect model was used to compute the pooled estimate. Results The overall pooled incidence density mortality rate among HIV-positive children was 2.52 (95% CI: 1.82, 3.47) per 100 child years. Advanced HIV disease (hazard ratio (HR): 3.45, 95% CI (Confidence Interval): 2.64, 4.51), tuberculosis co-infection (HR: 3.19, 95% CI: 2.08, 4.88), stunting (3.22, 95% CI: 2.46, 4.22), underweight (HR: 2.71, 95% CI: 1.72, 4.26), wasting (HR: 4.14, 95% CI: 2.27, 7.58), didn’t receive Isoniazid preventive therapy (HR: 3.33, 95% CI: 2.22, 4.99), anemia (HR: 3.03, 95% CI: 2.52, 3.64), fair or poor antiretroviral therapy adherence (HR: 4.14, 95% CI: 3.28, 5.28) and didn’t receive cotrimoxazole preventive therapy (HR: 3.82, 95% CI: 2.49, 5.86) were factors associated with a higher hazard of HIV related child mortality. Conclusions The overall pooled incidence density mortality rate among HIV-positive children was high in Ethiopia as compared to the national strategy target. Therefore, counseling on antiretroviral therapy adherence should be strengthened. Regular monitoring of hemoglobin levels and assessment of nutritional status should be done for all children living with HIV. Moreover, healthcare professionals should follow the national HIV treatment guidelines and provide cotrimoxazole preventive therapy and Isoniazid preventive therapy up on the guidelines for children living with HIV. Registration Registered in PROSPERO with ID: CRD42023486902.
The Japanese Society of Internal Medicineaugustus 2024Hiv
OBJECTIVE: This study explored the prognostic factors of in-hospital mortality in patients with Pneumocystis pneumonia (PCP) without human immunodeficiency virus (HIV) infection, using a Japanese nationwide inpatient database. METHODS: We extracted the data of patients with PCP without HIV infection between July 2010 and March 2022 from the Diagnosis Procedure Combination database. We performed multivariable logistic regression analyses to identify the prognostic factors of in-hospital mortality in with PCP without HIV infection. RESULTS: We identified 1,704 patients with PCP without HIV infection and 404 (23.7%) in-hospital deaths. Higher in-hospital mortality was associated with advanced age, male sex [odds ratio (OR), 1.45; 95% confidence interval (CI), 1.06-2.00], a low Barthel index score, non-hematological malignancy (OR, 1.81; 95% CI, 1.22-2.70), receipt of mechanical ventilation (OR, 2.49; 95% CI, 1.47-4.21), and administration of antibiotics (OR, 1.52; 95% CI, 1.12-2.06) and antifungal drugs (OR, 1.83; 95% CI, 1.26-2.67). Lower in-hospital mortality was associated with connective tissue disease and vasculitis (OR, 0.55; 95% CI, 0.37-0.81), hematological malignancy (OR, 0.59; 95% CI, 0.38-0.93), and early trimethoprim-sulfamethoxazole treatment (OR, 0.63; 95% CI, 0.44-0.90). CONCLUSION: These findings will help physicians identify patients who may benefit from early aggressive therapeutic interventions.
Background Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV. Methods In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. We measured CD4 + T cells at baseline and followed the individuals longitudinally via chart review for 12 months. Fecal samples were assessed for parasitic infection, and standard 16S bacterial rRNA sequencing determined microbiome composition. We assessed alpha and beta diversity by clinical factors, e.g., ART duration, CD4 + T cells/µL, parasitic infection, and differential relative abundances via non-parametric tests and adjusted regression. We assessed the relationship between taxa and longitudinal change in CD4 + cells/µL via linear mixed models. Results This analysis of microbiome data among 175 participants found that alpha diversity was lower in participants with < 100 CD4 + T cells/µL versus their peers with higher CD4 + counts. Only the presence of Anaerococcus was inversely associated with CD4 + T cells/µL (Spearman correlation − 0.3207; p-value = 0.0000152). We observed no trends in beta diversity across clinical or demographic groups. Presence of Sutterella and Alcaligenaceae at baseline were associated with increasing CD4 + T cells/µL over time. Conclusions We identified three taxa associated with clinical parameters, and, importantly, that the fecal microbiome is less diverse at lower CD4 + T cells counts, which is concerning for relatively increased dysbiosis and worse outcomes. Given the large prevalence of HIV in Sub-Saharan Africa, key differences in factors that influence microbiome, and the apparent importance of the microbiome in health status, future microbiome research focused on diverse and rural African populations is warranted. Clinical trial Not applicable. This was not a clinical trial as no intervention was applied to the participant.
BACKGROUND: Virus-specific CD8(+) T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8(+) T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8(+) T cells from people on antiretroviral treatment. METHODS: We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8(+) T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8(+) T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons. FINDINGS: Total and HIV-specific CD8(+) T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ(+) TNF-α(+) cells. The superior CD8(+) T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8(+) T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment. INTERPRETATION: CD8(+) T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections. FUNDING: The CESAR trial was sponsored by 10.13039/501100010431IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).
BACKGROUND: Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6(+) Th17-polarised CD4(+) T-cells are not fully restored in people with HIV (PWH). Moreover, long-lived Th17 cells contribute to HIV persistence under ART. However, the molecular mechanisms underlying these observations remain understudied. METHODS: mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6(+)CD4(+) T-cells from successfully ART-treated (ST), elite controllers (EC), and uninfected donors (HD). Gene expression validation was performed by RT-PCR, flow cytometry, and in vitro functional assays. FINDINGS: Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6(+) T-cells of STs and ECs versus HDs. The presence of HIV-DNA in memory CCR6(+) T-cells of ST and EC corresponded with the downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of the HIV-dependency factor MRE11, indicative of higher susceptibility/permissiveness to HIV-1 infection. Furthermore, markers of DNA damage/modification were elevated in memory CCR6(+) T-cells of STs and ECs versus HDs, in line with their increased activation (CD38/HLA-DR), senescence/exhaustion phenotype (CTLA-4/PD-1/CD57) and their decreased expression of proliferation marker Ki-67. INTERPRETATION: These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells. FUNDING: This study was funded by the 10.13039/501100000024Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).
Efficient screening and early diagnosis of HIV are critical for reducing onward transmission. Although large scale laboratory testing is not feasible, the widespread adoption of Electronic Health Records (EHRs) offers new opportunities to address this challenge. Existing research primarily focuses on applying machine learning methods to structured data, such as patient demographics, for improving HIV diagnosis. However, these approaches often overlook unstructured text data such as clinical notes, which potentially contain valuable information relevant to HIV risk. In this study, we propose a novel pipeline that leverages a Large Language Model (LLM) to analyze unstructured EHR text and determine a patient's eligibility for further HIV testing. Experimental results on clinical data from Erasmus University Medical Center Rotterdam demonstrate that our pipeline achieved high accuracy while maintaining a low false negative rate. ;28 pages, 6 figures
Abstract Surface plasmon resonance (SPR)-based biosensors have emerged as a powerful platform for bioprocess monitoring due to their ability to detect biointeractions in real time, without the need for labeling. Paramount for the development of a robust detection platform is the immobilization of a ligand with high specificity and affinity for the in-solution species of interest. Following the 2009 H1N1 pandemic, much effort has been made toward the development of quality control platforms for influenza A vaccine productions, many of which have employed SPR for detection. Due to the rapid antigenic drift of influenza’s principal surface protein, hemagglutinin, antibodies used for immunoassays need to be produced seasonally. The production of these antibodies represents a 6–8-week delay in immunoassay and, thus, vaccine availability. This review focuses on SPR-based assays that do not rely on anti-HA antibodies for the detection, characterization, and quantification of influenza A in bioproductions and biological samples. Key points • The single radial immunodiffusion assay (SRID) has been the gold standard for the quantification of influenza vaccines since 1979. Due to antigenic drift of influenza’s hemagglutinin protein, new antibody reagents for the SRID assay must be produced each year, requiring 6–8 weeks. The resulting delay in immunoassay availability is a major bottleneck in the influenza vaccine pipeline. This review highlights ligand options for the detection and quantification of influenza viruses using surface plasmon resonance biosensors.
Background Several previous studies investigated the associations between temperature and influenza in a single city or region without a national picture. The attributable risk of influenza due to temperature and the corresponding driving factors were unclear. This study aimed to evaluate the spatial distribution characteristics of attributable risk of Influenza-like illness (ILI) caused by adverse temperatures and explore the related driving factors in the United States. Methods ILI, meteorological factors, and PM_2.5 of 48 states in the United States were collected during 2011–2019. The time-stratified case-crossover design with a distributed lag non-linear model was carried out to evaluate the association between temperature and ILI at the state level. The multivariate meta-analysis was performed to obtain the combined effects at the national level. The attributable fraction (AF) was calculated to assess the ILI burden ascribed to adverse temperatures. The ordinary least square model (OLS), spatial lag model (SLM), and spatial error model (SEM) were utilized to identify driving factors. Results A total of 7,716,115 ILI cases were included in this study. Overall, the temperature was negatively associated with ILI risk, and lower temperature gave rise to a higher risk of ILI. AF ascribed to adverse temperatures differed across states, from 49.44% (95% eCI: 36.47% ~ 58.68%) in Montana to 6.51% (95% eCI: -6.49% ~ 16.46%) in Wisconsin. At the national level, 29.08% (95% eCI: 27.60% ~ 30.24%) of ILI was attributable to cold. Per 10,000 dollars increase in per-capita income was associated with the increment in AF (OLS: β = -6.110, P = 0.021; SLM: β = -5.496, P = 0.022; SEM: β = -6.150, P = 0.022). Conclusion The cold could enhance the risk of ILI and result in a considerable proportion of ILI disease burden. The ILI burden attributed to cold varied across states and was higher in those states with lower economic status. Targeted prevention programs should be considered to lower the burden of influenza.
SIMPLE SUMMARY: The basilar artery is a vital cerebral blood vessel common in most vertebrates and constantly supplies blood to the hindbrain where many vital functions are coordinated. Avian basilar arterial responsiveness to vasoactive substances has been characterized only in chickens. In this artery, the endothelium plays an important role in relaxation, and endothelial dependence may explain the lethality of the highly pathogenic avian influenza virus, which reportedly induces apoptosis in the cerebrovascular endothelium. Our present results in ducks suggest a contrast to the previously reported results in chickens with regard to basilar arterial relaxation: The involvement of endothelial nitric oxide as a relaxing factor appears to be reduced in duck basilar arteries. Our research may help scientists to better understand the resistance to the highly pathogenic avian influenza virus that may be conferred by the cerebrovascular endothelium in ducks. ABSTRACT: The basilar arterial endothelium mediates blood vessel relaxation partly through the release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to a high mortality rate in chickens infected with the highly pathogenic avian influenza virus, but interestingly, ducks exhibit a greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated with 5-HT(1) and H(1) receptors, while relaxation is induced with β(3)-adrenergic and M(3) receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated with M(3) and OK receptors but not β(3)-adrenergic receptors in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain the differences in lethality between ducks and chickens when vascular endothelial cells are infected with the virus.
Background Notifiable infectious diseases remain a public health priority in China. Understanding long-term epidemiological patterns and developing low-cost, automated forecasting tools may support timely prevention efforts at the county level. Methods We analyzed 26,756 valid cases of 29 statutory infectious diseases reported in Ziyang County (2013–2023). Diseases with ≥ 500 cumulative cases were selected for primary analysis. Seasonal autoregressive integrated moving average (SARIMA) models were fitted for tuberculosis (TB), influenza, and hand–foot–mouth disease (HFMD), with two training windows (2013–2021 and 2018–2021) used for influenza to account for surveillance updates. Model selection was based on the Akaike information criterion, and forecasts were validated using data from 2022–2023. Results TB, influenza, and HFMD accounted for more than 55% of the cases. The TB incidence steadily decreased, with spring–summer peaks, whereas the incidence of influenza increased after 2019 and peaked in the winter. Short-horizon forecasts were robust across training windows but less accurate in 2022–2023, likely reflecting post-COVID-19 behavioral and policy shifts. HFMD forecasts were unstable because of zero-inflated data. Conclusions The incidence of tuberculosis decreased consistently, whereas the incidence of influenza rebounded sharply after nonpharmaceutical interventions were lifted. The SARIMA models reproduced seasonal patterns but showed limited accuracy for influenza and HFMD, reflecting the influence of surveillance changes, behavioral shifts, and sparse data. These findings highlight the need for complementary approaches—such as models explicitly accounting for structural breaks—to improve the reliability of local infectious disease forecasts.
BACKGROUND: Children under 5 years of age bear the highest burden of severe disease from respiratory illness. Surveillance of respiratory viral infections in hospitalized children informs local burden of disease and may assist in identifying potential sources of epidemics. In resource-limited countries, like Haiti, lack of infrastructure, resources, and oversight are barriers for such surveillance programs. Just before the onset of the pandemic in December 2019, we completed the preparation to implement a respiratory surveillance program at Hôpital Saint Damien (HSD). Furthermore, other major events such as a 7.2 magnitude earthquake and the assassination of the president of Haiti had an impact on the political and economic stability of the country, impacting the hospital and this study. Despite these challenges, we report the preliminary findings of a hospital-based surveillance program of severe acute respiratory illness (SARI) in children at a mother and child hospital in Tabarre, Haiti. METHOD: Participants were included if they were < 18 years of age; met the World Health Organization definition for SARI, which includes presence of 1) cough, 2) history of fever or measured fever ≥ 38 C°, 3) onset within the last 10 days, and 4) requirement of hospitalization; and consented to participate. We collected demographic and clinical data for enrolled patients and obtained a nasopharyngeal swab sample. Samples were rapid tested for influenza A, influenza B, respiratory syncytial virus (RSV), and SARS-CoV-2 and stored and shipped for genomic sequencing. RESULTS: As of January 6th, 2022, we had enrolled and tested 143 patients who presented to the hospital with SARI. Of these cases, 31 were RSV-positive, 7 were positive for influenza B-positive, 1 was positive for influenza A-positive, and 1 was SARS-CoV-2-positive. 97 cases are currently available for descriptive analysis, with 10 RSV-positive cases, 2 influenza B-positive cases, and 1 SARS-CoV-2-positive case. 55% (n= 53) of participants are male, with an average age of 2 years (standard deviation = 2.8 years). Along with fever and cough, 18% (n=17) presented with wheezing, 60% (n=58) presented with shortness of breath, 37% (n=36) presented with tachypnea, 7% (n=7) presented with nasal congestion, 1% (n=1) had a sore throat, 2% (n=2) had nausea, 7% (n=7) were lethargic, and 9% (n=9) had diarrhea. Nearly all enrolled children, 99% (n=96) live in households where coal or biofuel is used for cooking indoors. In regard to type of respiratory tract infection (RTI), 18% (n=17) were upper RTI, 30% (n=29) were lower RTI, and 53% (n=51) were both upper and lower RTI. While sequencing of influenza A and B isolates remains to be conducted, sequencing for the SARS-CoV-2 sample revealed the isolate to be of P.1 lineage. CONCLUSION: In children requiring hospital admission for SARI, our limited testing identified 40 children with respiratory viruses that were circulating during the SARS-CoV-2 pandemic. Identifying these viruses can support healthcare providers to provide better preventions measures, including compliance with vaccination, and administering appropriate therapeutics, such as antibiotics. Further testing with additional primers against other pathogens will be conducted to identify other potential causes of illness.
Influenza viruses cause a common respiratory disease known as influenza. In humans, seasonal influenza viruses can lead to epidemics, with avian influenza viruses of particular concern because they can infect multiple species and lead to unpredictable and severe disease. Therefore, there is an urgent need for a universal influenza vaccine that provides protection against seasonal and pre-pandemic influenza virus strains. The cyclic GMP-AMP (cGAMP) is a promising adjuvant for subunit vaccines that promotes type I interferons production through the stimulator of interferon genes (STING) pathway. The encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles (MPs) enhances its intracellular delivery. In this study, the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology was used to generate H1, H3, and H5 vaccine candidates. Monovalent and multivalent COBRA HA vaccines formulated with cGAMP Ace-DEX MPs were evaluated in a mouse model for antibody responses and protection against viral challenge. Serological analysis showed that cGAMP MPs adjuvanted monovalent and multivalent COBRA vaccines elicited robust antigen-specific antibody responses after a prime-boost vaccination and antibody titers were further enhanced after second boost. Compared to COBRA vaccine groups with no adjuvant or blank MPs, the cGAMP MPs enhanced HAI antibody responses against COBRA vaccination. The HAI antibody titers were not significantly different between cGAMP MPs adjuvanted monovalent and multivalent COBRA vaccine groups for most of the viruses tested in panels. The cGAMP MPs adjuvanted COBRA vaccines groups had higher antigen-specific IgG2a binding titers than the COBRA vaccine groups with no adjuvant or blank MPs. The COBRA vaccines formulated with cGAMP MPs mitigated disease caused by influenza viral challenge and decreased pulmonary viral titers in mice. Therefore, the formulation of COBRA vaccines plus cGAMP MPs is a promising universal influenza vaccine that elicits protective immune responses against human seasonal and pre-pandemic strains.
Background Influenza and flu-like syndromes are difficult to monitor because the symptoms are not specific, laboratory tests are not routinely performed, and diagnosis codes are often lacking or incompletely registered in medical records. This may result in an underestimation of hospital admissions, associated costs, and in-hospital mortality. Therefore, this study aimed to estimate the public health and economic burden of hospitalisations associated with influenza in Italy, at the national and regional levels. Methods This 11-year retrospective study included patients admitted to hospitals for influenza or diagnoses associated with influenza (including respiratory and cardiocirculatory conditions) from 2008/09 to 2018/19. Data on hospitalisations were extracted from the Italian Hospital Discharge Records. Information on weekly influenza-like syndrome incidence and weekly average temperature were used to estimate the burden of influenza in terms of hospital admissions in every Italian region and for different age groups by applying a negative binomial model. The model was also applied to estimate in-hospital mortality and the total costs of influenza and influenza-like hospital admissions. Results Over the study period, in addition to 3,970 average seasonal admissions coded as influenza, we estimated an average of 21,500 excess hospitalization associated with influenza per season, which corresponds to 36.4 cases per 100,000. Most of the excess hospitalisations concerned older individuals (> 65 years) and children (0–4 years) with 86 and 125 cases per 100,000, respectively. Large variations were observed across regions. Overall, the total estimated hospital burden associated with influenza (including respiratory and cardiocirculatory conditions) was approximately €123 m per year. While the in-hospital mortality for admissions with a primary diagnosis of influenza was very low (~ 150 cases per season), cases increased dramatically for primary diagnoses of influenza and pneumonia (about 9,500 cases per season). The average seasonal in-hospital deaths attributable to influenza were equal to 2,775 cases. Conclusions Our findings suggest a remarkable underestimation of the burden of influenza, mostly in the older population but not neglectable in younger individuals. Our results may aid the management of current and future flu seasons and should be used for policy making (e.g., vaccine strategies) and operation management choices (e.g., planning and staffing beds during influenza peaks). Overall, the present study supports the need for increased testing for influenza in Italy to tackle the current underestimation of influenza burden.
BACKGROUND: In the United States, influenza activity during the 2021–2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021–2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2–positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%–49%) overall. CONCLUSIONS: Influenza vaccination in 2021–2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.
Background Influenza is an acutely debilitating respiratory infection, contributing significantly to outpatient visits and hospitalizations. Spain lacks comprehensive and updated data on the burden of influenza, particularly in the outpatient setting. Our study aimed to fill this gap by estimating the clinical and economic burden of physician-diagnosed influenza cases in adults from four Spanish regions, stratified by age groups and presence of comorbidities. Methods A retrospective cost-of-illness study was conducted using data from an electronic medical records database from the National Healthcare Service (NHS) of four Spanish regions for individuals aged ≥ 18 years diagnosed for influenza during the 2017/2018 epidemic season. Health resource utilization and related cost data were collected, including primary care visits, referrals to other specialists, visits to the emergency department, hospitalizations, and prescribed medicines. Results The study reported a total of 28,381 patients aged ≥ 18 years diagnosed with influenza, corresponding to 1,804 cases per 100,000 population. Most patients were aged < 65 years: 60.5% ( n = 17,166) aged 18–49 and 26.3% ( n = 7,451) 50–64 years. A total of 39.2% ( n = 11,132) of patients presented a comorbidity. Cardiovascular diseases were the most common comorbidity reported along with influenza. The mean healthcare cost per case was estimated at €235.1 in population aged 18–49 years, increasing by 1.7 and 4.9 times in those aged 50–64 (€402.0) and ≥ 65 (€1,149.0), respectively. The mean healthcare cost per case was 3.2 times higher in patients with comorbidities. The total healthcare cost of medically attended influenza cases was mainly driven by primary care (45.1%) and hospitalization (42.0%). Patients aged 18–64 years old accounted for 61.9% of the costs of medically attended influenza. Irrespective of age, patients with comorbidities accounted for 67.1% of costs. Conclusions Season 2017/2018 was associated with a considerable burden of influenza in Spain, which increased with age and presence of comorbidities. Individuals with comorbidities accounted for most of the costs of influenza. Results suggest that population aged 18–64 years old is generating the highest share of costs to the NHS when all healthcare costs are considered. Preventive strategies targeting subjects with comorbidities, regardless of age, should be warranted.
BACKGROUND: Influenza is an acute respiratory infectious disease that is highly infectious and seriously damages human health. Reasonable prediction is of great significance to control the epidemic of influenza. METHODS: Our Influenza data were extracted from Shanxi Provincial Center for Disease Control and Prevention. Seasonal-trend decomposition using Loess (STL) was adopted to analyze the season characteristics of the influenza in Shanxi Province, China, from the 1st week in 2010 to the 52nd week in 2019. To handle the insufficient prediction performance of the seasonal autoregressive integrated moving average (SARIMA) model in predicting the nonlinear parts and the poor accuracy of directly predicting the original sequence, this study established the SARIMA model, the combination model of SARIMA and Long-Short Term Memory neural network (SARIMA-LSTM) and the combination model of SARIMA-LSTM based on Singular spectrum analysis (SSA-SARIMA-LSTM) to make predictions and identify the best model. Additionally, the Mean Squared Error (MSE), Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) were used to evaluate the performance of the models. RESULTS: The influenza time series in Shanxi Province from the 1st week in 2010 to the 52nd week in 2019 showed a year-by-year decrease with obvious seasonal characteristics. The peak period of the disease mainly concentrated from the end of the year to the beginning of the next year. The best fitting and prediction performance was the SSA-SARIMA-LSTM model. Compared with the SARIMA model, the MSE, MAE and RMSE of the SSA-SARIMA-LSTM model decreased by 38.12, 17.39 and 21.34%, respectively, in fitting performance; the MSE, MAE and RMSE decreased by 42.41, 18.69 and 24.11%, respectively, in prediction performances. Furthermore, compared with the SARIMA-LSTM model, the MSE, MAE and RMSE of the SSA-SARIMA-LSTM model decreased by 28.26, 14.61 and 15.30%, respectively, in fitting performance; the MSE, MAE and RMSE decreased by 36.99, 7.22 and 20.62%, respectively, in prediction performances. CONCLUSIONS: The fitting and prediction performances of the SSA-SARIMA-LSTM model were better than those of the SARIMA and the SARIMA-LSTM models. Generally speaking, we can apply the SSA-SARIMA-LSTM model to the prediction of influenza, and offer a leg-up for public policy.
Background: Up to 60% of the antibiotics prescribed to patients hospitalized with seasonal influenza are unnecessary. Procalcitonin (PCT) has the potential as an antimicrobial stewardship program (ASP) tool because it can differentiate between viral and bacterial etiology. We aimed to explore the role of PCT as an ASP tool in hospitalized seasonal influenza patients. Methods: We prospectively included 116 adults with seasonal influenza from two influenza seasons, 2018–2020. All data was obtained from a single clinical setting and analyzed by descriptive statistics and regression models. Results: In regression analyses, we found a positive association of PCT with 30 days mortality and the amount of antibiotics used. Influenza diagnosis was associated with less antibiotic use if the PCT value was low. Patients with a low initial PCT (<0.25 µg/L) had fewer hospital and intensive care unit (ICU) days and fewer positive chest X-rays. PCT had a negative predictive value of 94% for ICU care stay, 98% for 30 days mortality, and 88% for bacterial coinfection. Conclusion: PCT can be a safe rule-out test for bacterial coinfection. Routine PCT use in seasonal influenza patients with an uncertain clinical picture, and rapid influenza PCR testing, may be efficient as ASP tools.
Background Dengue fever (DF), influenza, and hand, foot, and mouth disease (HFMD) have had several various degrees of outbreaks in China since the 1900s, posing a serious threat to public health. Previous studies have found that these infectious diseases were often prevalent in the same areas and during the same periods in China. Methods This study combined traditional descriptive statistics and spatial scan statistic methods to analyze the spatiotemporal features of the epidemics of DF, influenza, and HFMD during 2013–2015 in mainland China at the provincial level. Results DF got an intensive outbreak in 2014, while influenza and HFMD were stable from 2013 to 2015. DF mostly occurred during August–November, influenza appeared during November–next March, and HFMD happened during April–November. The peaks of these diseases form a year-round sequence; Spatially, HFMD generally has a much higher incidence than influenza and DF and covers larger high-risk areas. The hotspots of influenza tend to move from North China to the southeast coast. The southeastern coastal regions are the high-incidence areas and the most significant hotspots of all three diseases. Conclusions This study suggested that the three diseases can form a year-round sequence in southern China, and the southeast coast of China is a particularly high-risk area for these diseases. These findings may have important implications for the local public health agency to allocate the prevention and control resources.
The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially post the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days completing daily symptom diaries and collecting nasal swabs, which were tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission before symptomatic onset, infectious period, and latent period. We estimated a mean intrinsic generation time of 3.2 (95% credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95% CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variation in incubation periods. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.
Accurate forecasting of Avian Influenza Virus (AIV) outbreaks within wild bird populations necessitates models that account for complex, multi-scale transmission patterns driven by diverse factors. While conventional spatiotemporal epidemic models are robust for human-centric diseases, they rely on spatial homophily and diffusive transmission between geographic regions. This simplification is incomplete for AIV as it neglects valuable genomic information critical for capturing dynamics like high-frequency reassortment and lineage turnover at the case level (e.g., genetic descent across regions), which are essential for understanding AIV spread. To address these limitations, we systematically formulate the AIV forecasting problem and propose a Bi-Layer genomic-aware heterogeneous graph fusion pipeline. This pipeline integrates genetic, spatial, and ecological data to achieve highly accurate outbreak forecasting. It 1) defines a multi-layered graph structure incorporating information from diverse sources and multiple layers (case and location), 2) applies cross-relation smoothing to smooth information flow across edge types, 3) performs graph fusion that preserves critical structural patterns backed by theoretical spectral guarantees, and 4) forecasts future outbreaks using an autoregressive graph sequence model to capture transmission dynamics. To support research, we release the Avian-US dataset, which provides comprehensive genetic, spatial, and ecological data on US avian influenza outbreaks. BLUE demonstrates superior performance over existing baselines, highlighting the efficacy of integrating multi-layer information for infectious disease forecasting. The code is available at: https://github.com/cruiseresearchgroup/BLUE. ;13 pages, 3 figures, 4 tables. The paper is accepted by The Web Conference 2026
HAL CCSD;American Society for Microbiologyjanuari 2023Griep
International audience;
ABSTRACT The latest outbreaks of high pathogenicity avian influenza viruses (HPAIVs) were the most widespread ever seen in Europe, entailing considerable economic costs and raising public health concerns. Virological surveillance protocols involve reverse transcription quantitative polymerase chain reactions (RT-qPCR) from tracheal and cloacal swabs, which are laborious to perform on a large scale and require special skills. Environmental sampling, and especially dust collection, may represent a rele vant alternative, as it is cheap, non-invasive for animals, simpler, and quicker to carry out. The main drawback of dust samples is that they may contain high amounts of organic substances that can inhibit RT-qPCR reactions. Bovine serum albumin (BSA) is a molecule known to facilitate DNA polymerization in the presence of numerous inhibitors, including those from feces, litter, or food. We tested its use on dust samples collected on 107 farms localized in areas affected by epizootics of clade 2.3.4.4b HPAIV H5N1. We used a latent class modeling approach to compare the performance of three detection protocols: (i) BSA addition to the RT-qPCR reaction mix, (ii) dilution of template RNA, and (iii) a control protocol. Our results indicate that BSA addition to the RT-qPCR reaction mix improved the sensitivity of the method, by neutralizing inhibitors' effect. Indeed, for hemagglutinin (HA) or matrix (M) RNA detection, the sensitivity of the BSA protocol was the highest, followed by that of the control protocol, and that of the dilution protocol. Our results suggest that the use of BSA could be routinely implemented in HPAIV dust monitoring RT-qPCR protocols. IMPORTANCE With the circulation of high pathogenicity avian influenza viruses having intensified considerably in recent years, the European Union is considering the vaccination of farmed birds. A prerequisite for this vaccination is the implementation of drastic surveillance protocols. Environmental sampling is a relevant alternative to animal sampling. However, environmental samples often contain inhibitory compounds in large enough quantities to inhibit RT-qPCR reactions. As bovine serum albumin is a molecule used in many fields to overcome this inhibitory effect, we tested its use on dust samples from poultry farms in areas heavily affected by HPAIV epizootics. Our results show that its use significantly increases the sensitivity of the method.
Centers for Disease Control and Preventionoktober 2022Griep
Zoonotic and pandemic influenza continue to pose threats to global public health. Pandemics arise when novel influenza A viruses, derived in whole or in part from animal or avian influenza viruses, adapt to transmit efficiently in a human population that has little population immunity to contain its onward transmission. Viruses of previous pandemic concern, such as influenza A(H7N9), arose from influenza A(H9N2) viruses established in domestic poultry acquiring a hemagglutinin and neuraminidase from influenza A viruses of aquatic waterfowl. We report a novel influenza A(H3N8) virus in chicken that has emerged in a similar manner and that has been recently reported to cause zoonotic disease. Although they are H3 subtype, these avian viruses are antigenically distant from contemporary human influenza A(H3N2) viruses, and there is little cross-reactive immunity in the human population. It is essential to heighten surveillance for these avian A(H3N8) viruses in poultry and in humans.
BACKGROUND: The European Medicines Agency (EMA) requires enhanced safety surveillance to be conducted for annual seasonal influenza vaccines with the aim of rapidly detecting any potential new safety concerns before the peak immunisation period of the vaccine in any given year. The aim of this study was to detect any clinically significant change in the frequency or severity of expected reactogenicity of the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunisation in Finland for the 2020/21 season. The primary objective was to investigate the frequency of suspected adverse drug reactions (ADRs) occurring within 7 days following vaccination. METHODS: Enhanced passive safety surveillance of individuals vaccinated with IIV4 was conducted from October 9, 2020 to November 30, 2020 across seven sites in Finland. The vaccinee reporting rate and ADR reporting rate were calculated and compared with known or expected safety data in order to identify any clinically significant changes. RESULTS: Data were collected from 1008 individuals with 29 vaccinees reporting 82 suspected ADRs. Of these, 28 people reported 79 suspected ADRs within 7 days following vaccination, corresponding to a vaccinee reporting rate of 2.78% (95% CI: 1.85, 3.99) (ADR reporting rate, 7.84% [95% CI: 6.25, 9.67%]). The most frequently reported ADRs were injection site reactions (vaccination site pain, vaccination site erythema and vaccination site swelling) (n = 46, 2.28%), myalgia (n = 9, 0.89%) and headache (n = 8, 0.79%). No serious suspected adverse events were reported at any point post-vaccination and ADR reporting rates were in general lower compared to those reported for IIV4 in the 2019/20 surveillance study. CONCLUSION: No clinically significant changes in what is known or expected for IIV4 were reported for the 2020/21 season which supports the safety profile of this vaccine and will help maintain public confidence in influenza vaccination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13898-z.
Background Influenza is a contagious respiratory disease posing a huge burden of disease for children around the world. The purpose of this study was to investigate the epidemiologic changes in childhood influenza in Zhengzhou, China, before, during, and after the COVID-19 outbreak. The aim of this study was to determine the impact of the COVID-19 outbreak and related prevention and control policies on the children’s influenza epidemiological trend. Methods All influenza report card data from the Children’s Hospital Affiliated with Zhengzhou University’s Disease Surveillance Reporting Management System were collected and analyzed monthly from January 2018 to December 2023. The period of the study was divided into three phases for comparison: the pre-pandemic period, the pandemic period, and the post-pandemic period. Results Between January 2018 and December 2023, a total of 82,030 children with influenza were diagnosed at our hospital, including 46,453 males and 35,577 females. A total of 11,833 of them had to be hospitalized for influenza, and 321 of them were brought to the ICU. Influenza showed low-level epidemiologic status during the COVID-19 pandemic, and there was a substantial rise in influenza and a surge in the number of cases after the COVID-19 pandemic period. The year 2023 will had the most influenza cases (40,785). The peak incidence of influenza changes in 2022, from July to October, and in 2023, from February to April and from October to December. During the post-pandemic period, the proportion of new-borns and young children among influenza patients decreased, while the proportion of school-age children increased significantly, and the proportion of influenza patients hospitalized and the proportion of ICU admissions decreased. Conclusion Influenza showed low-level epidemiologic status during the COVID-19 pandemic. In the post-pandemic period, there is a large increase in influenza incidence, with a double peak in influenza incidence. The proportion of school-age children with influenza has also increased. As a result, we recommend that influenza vaccination for key populations, particularly school-age children, be completed by October of each year in Henan Province, and that the government and schools increase education about nonpharmacological influenza prevention approaches.
Respiratory infections account for millions of hospital admissions worldwide. The aetiology of respiratory infections can be attributed to a diverse range of pathogens including viruses, bacteria and fungi. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-negative specimens from Wattansoppeng city, South Sulawesi, were analysed to study the spectrum of respiratory viruses. Samples were screened for influenza virus, enterovirus, Paramyxoviridae, Nipah virus, Coronaviridae and Pneumoviridae. Of 210 specimens, 19 were positive for respiratory syncytial virus (RSV)-A, RSV-B, human parainfluenza virus type 1 (HPIV-1), HPIV-2, human rhinovirus (HRV)-A, HRV-B, HRV-C, human metapneumovirus (HMPV), influenza A virus (IAV) and coxsackievirus A6 (CV-A6). Influenza virus was of seasonal H3N2 subtype. The HMPVs were of genotypes B1 and A2a, while one RSV-A was of the ON-1 genotype. The viruses mostly affected children with unknown severity.
Korean Society of Occupational & Environmental Medicinefebruari 2022Griep
BACKGROUND: Influenza illness causes several disruptions to the workforce. The absenteeism that often ensues has economic implications for employers. This study aimed to estimate the cost-benefit of influenza vaccination in a healthcare setting from the employer’s perspective. METHODS: A cross-sectional questionnaire survey was conducted in a private hospital in 2018–2019 comparing voluntary vaccinated with non-vaccinated employees with influenza vaccine. The analyses were made based on self-reporting on absenteeism and presenteeism from Influenza-like illnesses (ILIs). The costs incurred, both direct and indirect costs, were included in the study. A cost-benefit analysis was performed by measuring the cost of the vaccination program. The costs of absenteeism and reduced productivity were calculated using 3 hypothesised levels of effectiveness in the following percentage of productivity of 30%, 50%, and 70%. The costs were also calculated based on four scenarios: with and without operating income and with and without replacement. The benefits of the influenza vaccination from the employer’s perspective were analysed. The benefit to cost ratio was determined. RESULTS: A total of four hundred and twenty-one respondents participated. The influenza vaccination rate was 63.0%. The rate of ILI of 38.1% was significantly lower among vaccinated. The ILI-related absenteeism reported was also significantly lower amongst vaccinated employees at 30% compared to 70% non-vaccinated. Employers could save up to USD 18.95 per vaccinated employee when only labour cost was included or 54.0% of cost savings. The cost-saving rose to USD 155.56 when the operating income per employee was also included. The benefit to cost ratio confirmed that the net cost-benefit gained from the vaccination was more than the net cost of vaccination. CONCLUSIONS: Influenza vaccination for working adults was cost-saving and cost-beneficial when translated into financial investments for the employer. A workplace vaccination demonstrates a significant cost-benefit strategy to be applied in any institutional setting.
Background Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. Results Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. Conclusions Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.
Swine influenza viruses (SIVs) are complex and constantly evolving pathogens that pose serious economic and zoonotic threats. This chapter reviews current understanding of SIVs, including their virology, epidemiology, evolution, diagnosis, and control strategies. SIVs exhibit high genetic diversity, with main subtypes such as H1N1, H1N2, and H3N2 continuing to circulate globally through ongoing antigenic shifts and reassortments. Mechanistic studies have revealed the functions of viral structural and nonstructural proteins, which are crucial for assessing replication, pathogenicity, and host adaptation. Epidemiological surveillance shows specific geographical trends in viral prevalence and evolution, supported by phylogenetic data indicating frequent transmission among humans, pigs, and birds. Advanced molecular techniques improve detection sensitivity and strain differentiation, benefiting outbreak control. The immune response to SIV infection involves complex interactions between the host and the virus, which guide vaccine development. Current prevention strategies include various vaccines, from inactivated forms to nucleic acid-based and universal vaccines. However, significant challenges remain in achieving broad-spectrum immunity due to the virus’s rapid evolution. Future efforts should prioritize developing cross-protective vaccines, improving diagnostic technologies, and implementing One Health approaches to better manage the increasing zoonotic risks of influenza A viruses (IAVs) in swine.
Background The morbidity of influenza in children increased rapidly in decade. Reduning injection (RDN), a small but fine Chinese herbal formula, has antipyretic, antiviral, anti-inflammatory effects. We intend to evaluate the efficacy and safety of RDN for the influenza in children versus Oseltamivir, explore the possible antiviral mechanism of RDN and provide evidence-based medical evidence for rational clinical drug usage. Method We design a randomized, double-blind, double-dummy, parallel control of positive drug, multi-centre clinical study. According to the formula of mean superiority test, a total of 240 patients with influenza in children will be randomized 1:1 into the experimental group and control group. The experimental group will take RDN and Oseltamivir phosphate granule simulants and the control group will take Oseltamivir phosphate granule and RDN simulants. Each group will be treated for 5 days. The primary outcome measure is temperature recovery time, and the secondary outcome measures include time when the fever begins to subside, time and degree of disease to alleviate, disappearance rate of individual symptoms and so on. We will measure before enrollment and each 24 h after treatment for comparison. Discussion The study is launched to evaluate the efficacy and safety of RDN for the treatment of influenza in children and to provide an alternative option for influenza in children. Trial registration This study is registered in ClinicalTrials.gov as NCT04183725, registered on 3 December, 2019.
Co-circulation of SARS-CoV-2 and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in co-infected patients. The initial lack of a readily available COVID-19 vaccine has reinforced the importance of influenza vaccine programmes during the COVID-19 pandemic. Live Attenuated Influenza Vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days pre- or post-SARS-CoV-2 infection. LAIV administration did not exacerbate SARS-CoV-2 disease course or lung pathology with either regimen. Additionally, LAIV administered prior to SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.
Influenza represents one of the biggest health threats facing humanity. Seasonal epidemics can transition to global pandemics, with cross-species infection presenting a continuous challenge. Although vaccines and several anti-viral options are available, constant genetic drifts and shifts vitiate any of the aforementioned prevention and treatment options. Therefore, we describe an approach targeted at the virus’s channel to derive new anti-viral options. Specifically, Influenza A’s M2 protein is a well-characterized channel targeted for a long time by aminoadamantane blockers. However, widespread mutations in the protein render the drugs ineffective. Consequently, we started by screening a repurposed drug library against aminoadamantane-sensitive and resistant M2 channels using bacteria-based genetic assays. Subsequent in cellulo testing and structure-activity relationship studies yielded a combination of Theobromine and Arainosine, which exhibits stark anti-viral activity by inhibiting the virus’s channel. The drug duo was potent against H1N1 pandemic swine flu, H5N1 pandemic avian flu, aminoadamantane-resistant and sensitive strains alike, exhibiting activity that surpassed Oseltamivir, the leading anti-flu drug on the market. When this drug duo was tested in an animal model, it once more outperformed Oseltamivir, considerably reducing disease symptoms and viral RNA progeny. In conclusion, the outcome of this study represents a new potential treatment option for influenza alongside an approach that is sufficiently general and readily applicable to other viral targets.
Background The increase in the resistance of bacterial strains to antibiotics has led to research into the bactericidal potential of non-antibiotic compounds. This study aimed to evaluate in vitro antibacterial/ antibiofilm properties of nisin and selenium encapsulated in thiolated chitosan nanoparticles (N/Se@TCsNPs) against prevalent enteric pathogens including standard isolates of Vibrio (V.) cholerae O1 El Tor ATCC 14,035, Campylobacter (C.) jejuni ATCC 29,428, Salmonella (S.) enterica subsp. enterica ATCC 19,430, Shigella (S.) dysenteriae PTCC 1188, Escherichia (E.) coli O157:H7 ATCC 25,922, Listeria (L.) monocytogenes ATCC 19,115, and Staphylococcus (S.) aureus ATCC 29,733. Methods The synthesis and comprehensive analysis of N/Se@TCsNPs have been completed. Antibacterial and antibiofilm capabilities of N/Se@TCsNPs were evaluated through broth microdilution and crystal violet assays. Furthermore, the study included examining the cytotoxic effects on Caco-2 cells and exploring the immunomodulatory effects of N/Se@TCsNPs. This included assessing the levels of both pro-inflammatory (IL-6 and TNFα) and anti-inflammatory (IL-10 and TGFβ) cytokines and determining the gene expression of TLR2 and TLR4 . Results The N/Se@TCsNPs showed an average diameter of 136.26 ± 43.17 nm and a zeta potential of 0.27 ± 0.07 mV. FTIR spectroscopy validated the structural features of N/Se@TCsNPs. Scanning electron microscopy (SEM) images confirmed their spherical shape and uniform distribution. Thermogravimetric Analysis (TGA)/Differential Scanning Calorimetry (DSC) tests demonstrated the thermal stability of N/Se@TCsNPs, showing minimal weight loss of 0.03%±0.06 up to 80 °C. The prepared N/Se@TCsNPs showed a thiol content of 512.66 ± 7.33 µmol/g ( p < 0.05), an encapsulation efficiency (EE) of 69.83%±0.04 ( p ≤ 0.001), and a drug release rate of 74.32%±3.45 at pH = 7.2 ( p ≤ 0.004). The synthesized nanostructure demonstrated potent antibacterial activity against various isolates, with effective concentrations ranging from 1.5 ± 0.08 to 25 ± 4.04 mg/mL. The ability of N/Se@TCsNPs to reduce bacterial adhesion and internalization in Caco-2 cells underscored their antibiofilm properties ( p ≤ 0.0001). Immunological studies indicated that treatment with N/Se@TCsNPs led to decreased levels of inflammatory cytokines IL-6 (14.33 ± 2.33 pg/mL) and TNFα (25 ± 0.5 pg/mL) ( p ≤ 0.0001), alongside increased levels of anti-inflammatory cytokines IL-10 (46.00 ± 0.57 pg/mL) and TGFβ (42.58 ± 2.10 pg/mL) in infected Caco-2 cells ( p ≤ 0.0001). Moreover, N/Se@TCsNPs significantly reduced the expression of TLR2 (0.22 ± 0.09) and TLR4 (0.16 ± 0.05) ( p < 0.0001). Conclusion In conclusion, N/Se@TCsNPs exhibited significant antibacterial/antibiofilm/anti-attachment/immunomodulatory effectiveness against selected Gram-positive and Gram-negative enteric pathogens. However, additional ex-vivo and in-vivo investigations are needed to fully assess the performance of nanostructured N/Se@TCsNPs.
Background Person with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART. Results We analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3 . Conclusion Our data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.
Background Grapevine fanleaf virus (GFLV) is one of the most detrimental viral pathogens of grapevines worldwide but no information is available on its effect on the root system architecture (RSA) of plant hosts. We used two wildtype GFLV strains and their single amino acid mutants to assess RSA traits in infected Nicotiana benthamiana and evaluate transcriptomic changes in host root gene expression in replicated time course 3’RNA-Seq experiments. Mutations targeted the multi-functional GFLV-encoded protein 1E^Pol*/Sd, a putative RNA-dependent RNA polymerase and determinant of foliar symptoms in N. benthamiana plants. Results Plant infection with wildtype GFLV strain GHu and mutant GFLV strain F13 1E^Pol _G802K, both carrying a lysine in position 802 of protein 1E^Pol*/Sd, resulted in a significantly lower number of root tips (-30%), and a significantly increased average root diameter (+ 20%) at 17 days post inoculation (dpi) in comparison with roots of mock inoculated plants. In contrast, the RSA of plants infected with wildtype GFLV strain F13 and mutant GFLV strain GHu 1E^Pol _K802G, both carrying a glycine in position 802 of protein 1E^Pol*/Sd, resembled that of mock inoculated plants. Modifications of RSA traits were not associated with GFLV titer. Root tissue transcriptome analysis at 17 dpi indicated dysregulation of pattern recognition receptors, plant hormones, RNA silencing, and genes related to the production of reactive oxygen species (ROS). For wildtype GFLV strain GHu, RSA modifications were correlated with an abundant accumulation of ROS in the pericycle of primary roots at 7 dpi and the duration of vein clearing symptom expression in apical leaves. Dysegulation of a hypersensitive response was an overarching gene ontology found through enrichment analyses of 3’RNA-Seq data. Conclusions Our findings revealed the causative role of lysine in position 802 of protein 1E^Pol*/Sd in a novel RSA phenotype during viral infection and documented GFLV- N. benthamiana interactions at the root level based on (i) antiviral response, (ii) receptor mediated production of ROS, and (iii) hormone regulation. A correlation between above and below ground symptoms was reported for the first time in plants infected with wildtype GFLV strain GHu. Further work is warranted to test whether the modified RSA of a plant host might impact GFLV acquisition and transmission by the ectoparasitic dagger nematode Xiphinema index .
Mycological diagnostics play a crucial role in patient management and treatment of invasive fungal infections. Despite the significant global burden of fungal diseases, awareness and diagnostic capabilities in mycology laboratories lag behind other microbiological disciplines. Mycological diagnostics often require microscopic analysis of clinical samples and culture. The interpretation of microscopy requires extensive expertise in clinical mycology. This study aimed to explore the feasibility of remote digital reading for preliminary identification of fungi. In this study, five mycology-trained participants were asked to analyze a total of 474 images divided into three main groups of yeasts (73 images), filamentous fungi (341 images), and direct fluorescent microscopy from clinical samples (60 images). The accuracy of the assessments varied, with an average correct decision rate between 78 and 93% across the three image groups. Individual participant’s performance showed a mean accuracy rate ranging between 76 and 92%. A significant difference was observed in the assessment accuracy across specimen groups and among individual participants (p < 0.05). However, there was no significant interaction effect between participants and image group (p = 0.118). In conclusion, telemycology offers a promising alternative to standard microscopy diagnostics of fungal infections, especially in settings where skilled mycologists are lacking, including low- and middle-income countries.
Fungal infections occur in a wide variety of mammals including cats, dogs, and exotic small mammals. These infections are generally categorized as superficial/cutaneous, subcutaneous, and systemic. While most reported cases involve cats and dogs, fungal infections have also been documented in various exotic small mammal species. Although microbiological diagnostic approaches are similar across patient species, clinical signs and treatment strategies can vary significantly. Managing these infections in veterinary medicine presents unique challenges, particularly in exotic small mammals, due to species-specific differences in pathophysiology, treatment options, and husbandry considerations. In this chapter, we discuss (1) superficial/cutaneous, (2) subcutaneous, (3) systemic fungal infections in cats, dogs, and exotic small mammals, and (4) the challenges with managing these veterinary fungal infections.
Candida auris ( C. auris ) is a yeast that has caused several outbreaks in the last decade. Cell wall chitin plays a primary role in the antifungal resistance of C. auris . Herein, we investigated the potential of chitinase immobilized with UiO-66 to act as a potent antifungal agent against C. auris . Chitinase was produced from Talaromyces varians SSW3 in a yield of 8.97 U/g dry substrate (ds). The yield was statistically enhanced to 120.41 U/g ds by using Plackett–Burman and Box–Behnken design. We synthesized a UiO-66 framework that was characterized by SEM, TEM, XRD, FTIR, a particle size analyzer, and a zeta sizer. The produced framework had a size of 70.42 ± 8.43 nm with a uniform cubic shape and smooth surface. The produced chitinase was immobilized on UiO-66 with an immobilization yield of 65% achieved after a 6 h loading period. The immobilization of UiO-66 increased the enzyme activity and stability, as indicated by the obtained K_d and T_1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the V_max and a decrease in the K_m of 2- and 38-fold, respectively. Interestingly, the antifungal activity of the produced chitinase was boosted against C. auris by loading the enzyme on UiO-66, with an MIC_50 of 0.89 ± 0.056 U/mL, compared to 5.582 ± 0.57 U/mL for the free enzyme. This study offers a novel promising alternative approach to combat the new emerging pathogen C. auris.
Introduction Hormesis describes an inverse dose-response relationship, whereby a high dose of a toxic compound is inhibitory, and a low dose is stimulatory. This study explores the hormetic response of low concentrations of zinc oxide nanoparticles (ZnO NPs) toward Pseudomonas aeruginosa . Method Samples of P. aeruginosa , i.e. the reference strain, ATCC 27,853, together with six strains recovered from patients with cystic fibrosis, were exposed to ten decreasing ZnO NPs doses (0.78–400 µg/mL). The ZnO NPs were manufactured from Peganum harmala using a chemical green synthesis approach, and their properties were verified utilizing X-ray diffraction and scanning electron microscopy. A microtiter plate technique was employed to investigate the impact of ZnO NPs on the growth, biofilm formation and metabolic activity of P. aeruginosa . Real-time polymerase chain reactions were performed to determine the effect of ZnO NPs on the expression of seven biofilm-encoding genes. Result The ZnO NPs demonstrated concentration-dependent bactericidal and antibiofilm efficiency at concentrations of 100–400 µg/mL. However, growth was significantly stimulated at ZnO NPs concentration of 25 µg/mL (ATCC 27853, Pa 3 and Pa 4) and at 12.5 µg/mL and 6.25 µg/mL (ATCC 27853, Pa 2, Pa 4 and Pa 5). No significant positive growth was detected at dilutions < 6.25 µg/mL. similarly, biofilm formation was stimulated at concentration of 12.5 µg/mL (ATCC 27853 and Pa 1) and at 6.25 µg/mL (Pa 4). At concentration of 12.5 µg/mL, ZnO NPs upregulated the expression of LasB ( ATCC 27853, Pa 1 and Pa 4) and LasR and LasI (ATCC 27853 and Pa 1) as well as RhII expression (ATCC 27853, Pa 2 and Pa 4). Conclusion When exposed to low ZnO NPs concentrations, P. aeruginosa behaves in a hormetic manner, undergoing positive growth and biofilm formation. These results highlight the importance of understanding the response of P. aeruginosa following exposure to low ZnO NPs concentrations.
Mangroves are coastal environments that provide resources for adjacent ecosystems due to their high productivity, organic matter decomposition, and carbon cycling by microbial communities in sediments. Since the industrial revolution, the increase of Greenhouse Gases (GHG) released due to fossil fuel burning led to many environmental abnormalities such as an increase in average temperature and ocean acidification. Based on the hypothesis that climate change modifies the microbial diversity associated with decaying organic matter in mangrove sediments, this study aimed to evaluate the microbial diversity under simulated climate change conditions during the litter decomposition process and the emission of GHG. Thus, microcosms containing organic matter from the three main plant species found in mangroves throughout the State of São Paulo, Brazil ( Rhizophora mangle , Laguncularia racemosa , and Avicennia schaueriana ) were incubated simulating climate changes (increase in temperature and pH). The decay rate was higher in the first seven days of incubation, but the differences between the simulated treatments were minor. GHG fluxes were higher in the first ten days and higher in samples under increased temperature. The variation in time resulted in substantial impacts on α-diversity and community composition, initially with a greater abundance of Gammaproteobacteria for all plant species despite the climate conditions variations. The PCoA analysis reveals the chronological sequence in β-diversity, indicating the increase of Deltaproteobacteria at the end of the process. The GHG emission varied in function of the organic matter source with an increase due to the elevated temperature, concurrent with the rise in the Deltaproteobacteria population. Thus, these results indicate that under the expected climate change scenario for the end of the century, the decomposition rate and GHG emissions will be potentially higher, leading to a harmful feedback loop of GHG production. This process can happen independently of an impact on the bacterial community structure due to these changes.
This study used berberine hydrochloride to treat the Asian paddle crab, Charybdis japonica infected with the Gram-negative bacterium Aeromonas hydrophila at concentrations of 0, 100, 200 and 300 mg/L. The effect of berberine hydrochloride on the survival rate and gut microbiota of C. japonica was investigated. Berberine hydrochloride improved the stability of the intestinal flora, with an increase in the abundance of probiotic species and a decrease in the abundance of both pathogenic bacteria after treatment with high concentrations of berberine hydrochloride. Berberine hydrochloride altered peroxidase activity (POD), malondialdehyde (MDA), and lipid peroxidation (LPO) in the intestinal tract compared to the control. Berberine hydrochloride could modulate the energy released from the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the intestinal tract of C. japonica infected with A. hydrophila. Zona occludens 1 (ZO-1), Zinc finger E-box binding homeobox 1 (ZEB1), occludin and signal transducer, and activator of transcription5b (STAT5b) expression were also increased, which improved intestinal barrier function. The results of this study provide new insights into the role of berberine hydrochloride in intestinal immune mechanisms and oxidative stress in crustaceans.
Fungi have been used for medicinal purposes for many centuries. This study, based on 35 historical written sources and 581 in-depth semi-structured interviews from eight countries in the western borderlands of the former Soviet Union, investigates the medicinal use of fungi by local communities. We compared the taxa and uses obtained from fieldwork and historical sources with works that advocated fungi use within Soviet herbals, representing the centralised medical system. During fieldwork, we identified eight locally used fungi and one lichen. The highest numbers of medicinal uses were documented in Russia, Estonia and Ukraine. Studies published before the Soviet era listed 21 fungal taxa and one lichen species used in the study region. However, only six of these taxa were mentioned as used by people in our field studies ( Amanita muscaria , Boletus edulis , Lycoperdon , Morchella , Phallus impudicus and Cetraria islandica ). Notably, these same six taxa were consistently endorsed in Soviet herbals. Of the remaining three taxa recorded in the fieldwork, none were mentioned in historical written sources. However, they were promoted either in Soviet herbals ( Inonotus obliquus , Kombucha ) or later popular publications ( Cantharellus cibarius ). This highlights the significant influence of written sources on the use of fungi for medicinal purposes within the studied local communities.
Background The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. Results Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB , qnrS , oqxA and aac(6’)-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. Conclusions Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA or parC genes, thus the frequency of mutations was very significant and alarming in our region.
Abstract —Myxomycetes are amoeboid fungus-like organisms ( Amoebozoa ) with a unique life cycle characterized by a great morphological diversity of fruiting bodies. Due to the similarity of these structures to the fruiting bodies of some representatives of Ascomycota and Basidiomycota, myxomycetes have been classified as fungi since the first known scientific description in 1654. Only in the 19th century, when their life cycle was studied, did the difference of this group from fungi become clear. During the same period, microscopic structures of fruiting bodies, as well as ornamentation of the spore surface, began to be considered as diagnostic features. Due to this, in the period from the end of the 19th to the middle of the 20th century, a rather stable system was formed. However, as further studies have shown, both macro- and micromorphological characters are often quite variable, depend on environmental conditions, and often result from convergent evolution, which causes difficulties in defining species and taxonomic units of higher ranks. Since the first decade of the 21st century, due to the development of molecular genetic methods and the accumulation of data on nucleotide sequences of marker genes together with the improvement of microscopic studies, it has been possible to obtain data on the evolutionary relationships of different groups of myxomycetes. A milestone in this process was the publication of the first phylogenetic system of myxomycetes in 2019. This work was the starting point for a number of studies on the relationships between different groups of myxomycetes at a lower taxonomic level. Thus, there has been a surge in the number of studies that bring us closer to constructing a natural system.
Opportunistic infections, including mycotic diseases, are increasingly being recognized as a major public health concern in Southeast Asia. The diagnosis of fungal infections from clinical specimens relies mainly on culture and, at select institutions, molecular methods. In certain instances, it is possible to detect fungal elements, such as hyphae and yeast forms, in tissue samples submitted to the histopathology laboratory. Routine examination with hematoxylin and eosin (H and E) staining is sufficient to detect the presence of organisms in most cases. On occasion, special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) may be utilized to highlight fungal structures. Definite species identification of fungi detected on routine histology still relies on correlation with clinical findings and ancillary tests. Among the challenges encountered in the region are the lack of facilities, equipment, and supplies in regular diagnostic laboratories; overreliance on referral laboratories; lack of skilled laboratory personnel; and few opportunities for training and subspecialization in diagnostic mycology. The introduction of newer techniques, such as MALDI-TOF and nucleic acid-based tests, may augment the services related to fungal diagnosis on biopsy specimens. Furthermore, international linkages in the region, especially in tropical medicine, may pave the way toward enhancing mycology services in the region.
The rapid development of the industrial sector has contributed significantly to the global economy and the well-being of individuals, while it has consequences in terms of waste generation, consumption of resources, and energy usage, which require the development of ad hoc strategies and countermeasures to contain their impacts. Covered are microbial bioremediation, bioleaching, bioaugmentation, biostimulation, mycoremediation, and phytoremediation. Among these biological remediation approaches, mycoremediation is beneficial since it can successfully break down a wide variety of contaminants and its efficacy is not restricted to specific concentrations of pollutants. Mycoremediation is a cost-effective and environmentally benign technology that uses fungal biomass to remove hazardous chemicals from polluted water. Mushrooms are fungal fruiting structures that grow from a fibrous mass known as the mycelium. Macro fungi have demonstrated a unique capacity to break down a variety of dangerous and lignin-containing wastes produced by a variety of anthropogenic and natural activities. This chapter establishes approaches that could serve as a prospective framework for addressing the worldwide issue of wastewater.
Chrysomyxa rusts cause significant damage to spruce in both natural forests and plantations. Particularly, Three Chrysomyxa species, Chrysomyxa deformans , Chrysomyxa qilianensis , and Chrysomyxa rhododendri , listed as National Forest Dangerous Pests in China, have severely affected many economically and ecologically important spruce native species in China. Also, Chrysomyxa arctostaphyli , an important plant quarantine fungus, causes a damaging broom rust disease on spruce. Therefore, rapid, and efficient detection tools are urgently needed for proper rust disease detection and management. In this study, a sensitive, genus-specific loop-mediated isothermal amplification (LAMP) assay targeting the ITS-28S rRNA region was developed to detect the presence of Chrysomyxa in spruce needle and bud samples. After optimization and validation, the LAMP assay was found to be sensitive to detect as low as 5.2 fg/µL DNA, making it suitable for rapid on-site testing for rust infection. The assay was also specific to Chrysomyxa species, with no positive signals from other rust genus/species. The application of LAMP in the early detection of rust infections in spruce needles and buds was investigated, and spatial colonization profiles as well as the means of overwintering of Chrysomyxa woroninii in infected buds and branches were verified using the LAMP assay. This LAMP detection method will facilitate further studies on the characteristics of the life cycle and inoculation of other systemic rusts.
Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota ( n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity ( n = 1,086,211), hospitalization ( n = 2,095,324), and susceptibility ( n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.
Background The excessive application of chemical fertilizers in the cultivation of Astragalus mongholicus Bunge results in a reduction in the quality of the medicinal plant and compromises the sustainable productivity of the soil. PGPB inoculant is a hot topic in ecological agriculture research. In the cultivation of Astragalus mongholicus , the screened nitrogen-fixing bacteria can promote plant growth, however, whether it can promote the accumulation of main bioactive components remains unknown. In this study, mixed inoculants containing 5 strains of growth promoting bacteria ( Rhizobium T16 , Sinorhizobium T21 , Bacillus J1 , Bacillus G4 and Arthrobacter J2 ) were used in the field experiment. The metabolic substances in the root tissues of Astragalus mongholicus were identified during the harvest period by non-targeted metabolomics method, and the differential metabolites between groups were identified by statistical analysis. Meanwhile, high-throughput sequencing was performed to analyze the changes of rhizosphere soil and endophytic microbial community structure after mixed microbial treatment. Results The results of non-targeted metabolism indicated a significant increase in the levels of 26 metabolites after treatment including 13 flavonoids, 3 saponins and 10 other components. The contents of three plant hormones (abscisic acid, salicylic acid and spermidine) also increased after treatment, which presumed to play an important role in regulating plant growth and metabolism. Studies on endosphere and rhizosphere bacterial communities showed that Rhzobiaceae, Micromonosporaceae, and Hypomicrobiaceae in endophytic, and Oxalobactereae in rhizosphere were significantly increased after treatment. These findings suggest their potential importance in plant growth promotion and secondary metabolism regulation. Conclusions This finding provides a basis for developing nitrogen-fixing bacteria fertilizer and improving the ecological planting efficiency of Astragalus mongholicus.
Backgorund In recent years, there has been an increasing interest in the field of research into the isolation and characterization of probiotics in the prevention of diseases and the need to maintain the continuity of healthy microbiota. Therefore, the aim of this study is to isolate and identify bacteria found in maternal colostrum, breast milk, adult and infant feces, analyze possible probiotic potential, and reveal the developmental kinetics of selected strains. Results We isolated 40 bacterial species from 4 different sources and identified 19 bacteria in the form of bacilli through molecular biology and carried out studies with 11 of them. Five of the selected strains showed the better results considering bile salt resistance and ability to survive at different pH and antimicrobial effect. When the adhesion capacity in cell culture is examined, the better 2 strains are; Lactobacillus pontis ZZ6780 and Lactobacillus reuteri NBC2680 were selected and the growth kinetics of these strains were demonstrated at the 3 L bioreactor scale. Finally, the growth kinetics of selected strains were determined and the maximum specific growth rate of selected Lactobacillus pontis ZZ6780 and Lactobacillus reuteri NBC2680 was calculated as 0.412 h^− 1 and 0.481 h^− 1, respectively. In addition, the dry cell matter amounts were found to be and 4.45 g/L and 5.23 g/L, respectively. Conclusion This study established the groundwork for the selection of safety probiotics for the development and application of LAB. It is thought that the two strains obtained as a result of this study can be considered as potential probiotic strains in the food, pharmaceutical and cosmetic industries.
Fungal infections have emerged as a significant public health concern, especially with the increasing incidence of severe mycoses caused by pathogens such as Aspergillus fumigatus , Candida auris , Candida albicans , and Cryptococcus neoformans . These fungi, listed as critical priorities by the World Health Organization, pose a heightened risk due to rising antifungal resistance and their severe impact on immunocompromised individuals. This article, coordinated by the Portuguese Association of Medical Mycology, highlights the importance of adopting a One Health perspective to address fungal threats comprehensively. Drawing on interdisciplinary collaboration, the association aims to foster greater awareness, improve diagnostic capabilities, and stimulate research and public health policies in Portugal but also at global level. The paper outlines key strategies for surveillance, prevention, and innovation in fungal diagnostics and therapeutics. Moreover, it emphasizes the urgent need for national coordination and international cooperation in managing fungal infections, advocating for integrative approaches that link human, animal, and environmental health. By presenting a consolidated overview of current challenges and future priorities, this work seeks to enhance preparedness and response mechanisms in the face of escalating fungal threats.
Background Klebsiella pneumoniae is a Gram-negative pathogen that has become a threat to public health worldwide due to the emergence of hypervirulent and multidrug-resistant strains. Cell-surface components, such as polysaccharide capsules, fimbriae, and lipopolysaccharides (LPS), are among the major virulence factors for K. pneumoniae . One of the genes involved in LPS biosynthesis is the uge gene, which encodes the uridine diphosphate galacturonate 4-epimerase enzyme. Although essential for the LPS formation in K. pneumoniae , little is known about the mechanisms that regulate the expression of uge . Ferric uptake regulator (Fur) is an iron-responsive transcription factor that modulates the expression of capsular and fimbrial genes, but its role in LPS expression has not yet been identified. This work aimed to investigate the role of the Fur regulator in the expression of the K. pneumoniae uge gene and to determine whether the production of LPS by K. pneumoniae is modulated by the iron levels available to the bacterium. Results Using bioinformatic analyses, a Fur-binding site was identified on the promoter region of the uge gene; this binding site was validated experimentally through Fur Titration Assay (FURTA) and DNA Electrophoretic Mobility Shift Assay (EMSA) techniques. RT-qPCR analyses were used to evaluate the expression of uge according to the iron levels available to the bacterium. The iron-rich condition led to a down-regulation of uge , while the iron-restricted condition resulted in up-regulation. In addition, LPS was extracted and quantified on K. pneumoniae cells subjected to iron-replete and iron-limited conditions. The iron-limited condition increased the amount of LPS produced by K. pneumoniae . Finally, the expression levels of uge and the amount of the LPS were evaluated on a K. pneumoniae strain mutant for the fur gene. Compared to the wild-type, the strain with the fur gene knocked out presented a lower LPS amount and an unchanged expression of uge , regardless of the iron levels. Conclusions Here, we show that iron deprivation led the K. pneumoniae cells to produce higher amount of LPS and that the Fur regulator modulates the expression of uge , a gene essential for LPS biosynthesis. Thus, our results indicate that iron availability modulates the LPS biosynthesis in K. pneumoniae through a Fur-dependent mechanism.
Background Enterococcus faecium and Staphylococcus aureus are the Gram-positive pathogens of the ESKAPE group, known to represent a great threat to human health due to their high virulence and multiple resistances to antibiotics. Combined, enterococci and S. aureus account for 26% of healthcare-associated infections and are the most common organisms responsible for blood stream infections. We previously showed that the peptidyl-prolyl cis/trans isomerase (PPIase) PpiC of E. faecium elicits the production of specific, opsonic, and protective antibodies that are effective against several strains of E. faecium and E. faecalis . Due to the ubiquitous characteristics of PPIases and their essential function within Gram-positive cells, we hypothesized a potential cross-reactive effect of anti-PpiC antibodies. Results Opsonophagocytic assays combined with bioinformatics led to the identification of the foldase protein PrsA as a new potential vaccine antigen in S. aureus . We show that PrsA is a stable dimeric protein able to elicit opsonic antibodies against the S. aureus strain MW2, as well as cross-binding and cross-opsonic in several S. aureus , E. faecium and E. faecalis strains. Conclusions Given the multiple antibiotic resistances S. aureus and enterococci present, finding preventive strategies is essential to fight those two nosocomial pathogens. The study shows the potential of PrsA as an antigen to use in vaccine formulation against the two dangerous Gram-positive ESKAPE bacteria. Our findings support the idea that PPIases should be further investigated as vaccine targets in the frame of pan-vaccinomics strategy.
Background Coagulase-negative Staphylococcus species are an emerging cause of intramammary infection, posing a significant economic and public health threat. The aim of this study was to assess the occurrence of coagulase-negative Staphylococcus species in bovine milk and dairy farms in Northwestern Ethiopia and to provide information about their antibiotic susceptibility and virulence gene profiles. Methods The cross-sectional study was conducted from February to August 2022. Coagulase-negative Staphylococcus species were isolated from 290 milk samples. Species isolation and identification were performed by plate culturing and biochemical tests and the antimicrobial susceptibility pattern of each isolate was determined by the Kirby-Bauer disc diffusion test. The single-plex PCR was used to detect the presence of virulent genes. The STATA software version 16 was used for data analysis. The prevalence, proportion of antimicrobial resistance and the number of virulent genes detected from coagulase-negative Staphylococcus species were analyzed using descriptive statistics. Results Coagulase-negative Staphylococcus species were isolated in 28.6%, (95% CI: 23.5–34.2) of the samples. Of these, the S. epidermidis , S. sciuri , S. warneri , S. haemolyticus , S. simulans , S. chromogens , S. cohnii , and S. captis species were isolated at the rates of 11, 5.2, 3.4, 3.1, 3.1, 1, 1, and 0.7% respectively. All the isolates showed a high percentage (100%) of resistance to Amoxicillin, Ampicillin, and Cefotetan and 37.5% of resistance to Oxacillin. The majority (54.2%) of coagulase-negative isolates also showed multidrug resistance. Coagulase-negative S taphylococcus species carried the icaD , pvl , mecA , hlb , sec , and hla virulent genes at the rates of 26.5%, 22.1%, 21.7%, 9.6%, 9.6% and 8.4% respectively. Conclusion The present study revealed that the majority of the isolates (54.2%) were found multidrug-resistant and carriage of one or more virulent and enterotoxin genes responsible for intramammary and food poisoning infections. Thus, urgent disease control and prevention measures are warranted to reduce the deleterious impact of coagulase-negative species. To the best of our knowledge, this is the first study in Ethiopia to detect coagulase-negative Staphylococcus species with their associated virulent and food poisoning genes from bovine milk.
Studies on physiological responses to stimuli from physical factors are essential for understanding the dynamics of the microorganisms and higly important for the management of plant diseases. Besides, the development of an epidemiological model for pathogen populations requires studying their physiological responses to physical stimuli. The objective of this study was to evaluate the germination dynamics of spores from six isolates of Bipolaris bicolor under effects of light at 25 °C. Suspensions of 1.6 × 10^5 conidia mL^− 1 from the B. bicolor isolates were inoculated onto Petri dishes containing agar-water culture medium and incubated in a BOD chamber under two physical conditions: (a) constant darkness and (b) constant light for five hours. The study was conducted in a completely randomized design, with a 6 × 2 factorial arrangement (six B. bicolor isolates and two physical conditions) and five replications. The length of the germ tube was measured hourly. The constant darkness resulted in higher mean germ tube growth for the pathogen; however, differences in the final germination percentage were found among the isolates. The isolate F-24-02 exhibited the highest germination adaptability to constant darkness, presenting the longest germ tube length.
Abstract An investigation of freshwater fungi in Thailand resulted in the collection and isolation of a coelomycetous Seriascoma from submerged wood. The combined ITS and LSU sequence data placed the taxon within the sexual morphic Seriascoma acutisporum strains, ZHKUCC 22-0273 and ZHKUCC 22-0274, with high bootstrap support and confirmed the asexual morphic stage of the taxon. Seriascoma acutisporum MFLUCC 24-0091 shares the generic characteristics of having an immersed, eustromatic conidiomata and phialidic, cylindrical to ampulliform, hyaline, aseptate conidiogenous cells bearing hyaline conidia, but with smaller conidiomata and locules compared to other coelomycetous Seriascoma species.
Brain-based learning aligns educational strategies with the brain’s natural processes for absorbing, retaining, and applying knowledge. The purpose of this chapter is to explain the neurophysiology of learning and provide practical strategies that work with, rather than against, the brain’s natural learning mechanisms. When nursing students understand why certain approaches are more effective—like spaced repetition, chunking information, and active reflection—they are able to embrace these methods in their learning. The relationship between brain-based learning and critical thinking is explored through practical examples of how nursing students can apply these concepts in classroom, clinical, and simulation settings. Case studies demonstrate how understanding concepts like neurotransmitter function, memory formation, and the role of sleep in learning helps students optimize their study habits and learning techniques. Interactive learning activities and chapter synthesis exercises help students apply and integrate key concepts.
Recent advancements in neuroimaging and genetic techniques have significantly transformed our understanding of the neurobiological mechanisms underlying substance use disorders (SUDs). Optogenetic and chemogenetic approaches, in conjunction with traditional neuroimaging methods, have offered unprecedented insights into the brain’s response to psychoactive substances. This chapter reviews the current state of knowledge concerning these techniques and their applications in addiction research, highlighting their contributions to elucidating drug-seeking behaviors, neural circuitry, and potential therapeutic strategies.
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The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs—mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs—that play opposing roles in pattern separation and pattern completion, respectively. Although the dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm's sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3 dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared with dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we found that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the dorsoventral difference in hippocampal function.
Society for Neurosciencejuli 2024Neurowetenschappen
We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation-induced (ES; 60 Hz) DA release was recorded in the NAc of single- or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than that in males. Finally, DA release following ES of the medial forebrain bundle at 60 Hz was studied over 4 weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, and sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.
This chapter delves into the foundational aspects of neuroscience, focusing on the neurological correlates of consciousness and their relevance to spiritual wellness. It explores how the quantification of mindfulness and consciousness can contribute to overall well-being through integrative healthcare approaches. The chapter further examines the role of neurotransmitters in influencing cognitive abilities and mental health, highlighting the methods used in the literature to detect and measure low levels of neurotransmitters. This discussion underscores the intersection of neuroscience and spirituality, emphasizing the importance of understanding these biological processes to enhance mental and spiritual health.
This chapter is an introduction to the whole book. It explains why people should care about attention and attention models both in terms of science as it is a first step to our own consciousness but also in terms of technology as artificial intelligence might benefit a lot from the understanding of human or animal attention. Afterwards, the chapters deal with the public of the book which is quite large from students to researchers from different domain like cognitive psychology, engineering, computer science and neuroscience and define the book overview.
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Stress impairs fertility, at least in part, via inhibition of gonadotropin secretion. Luteinizing hormone (LH) is an important gonadotropin that is released in a pulsatile pattern in males and in females throughout the majority of the ovarian cycle. Several models of stress, including acute metabolic stress, suppress LH pulses via inhibition of neurons in the arcuate nucleus of the hypothalamus that coexpress kisspeptin, neurokinin B, and dynorphin (termed KNDy cells) which form the pulse generator. The mechanism for inhibition of KNDy neurons during stress, however, remains a significant outstanding question. Here, we investigated a population of catecholamine neurons in the nucleus of the solitary tract (NTS), marked by expression of the enzyme dopamine beta-hydroxylase (DBH), in female mice. First, we found that a subpopulation of DBH neurons in the NTS is activated (express c-Fos) during metabolic stress. Then, using chemogenetics, we determined that activation of these cells is sufficient to suppress LH pulses, augment corticosterone secretion, and induce sickness-like behavior. In subsequent studies, we identified evidence for suppression of KNDy cells (rather than downstream signaling pathways) and determined that the suppression of LH pulses was not dependent on the acute rise in glucocorticoids. Together these data support the hypothesis that DBH cells in the NTS are important for regulation of neuroendocrine and behavioral responses to stress.
This chapter covers an overview of the relationship between neuropsychology and the legal system, outlining important ideas and how they are used. The chapter explores the field of forensic neuropsychology by synthesizing neuroscience concepts with legal frameworks. It covers subjects including the relationship between the brain and behavior, cognitive evaluation techniques, and the use of neuropsychological evidence in court cases. Case studies demonstrate practical applications, emphasizing the value of comprehending brain function in relation to criminal conduct and guilt. A greater understanding of the complexity of human thought and behavior as well as the possibility of using neuropsychological insights to guide legal decision-making processes are among the main lessons learned. This chapter, which emphasizes the value of interdisciplinary collaboration between neuroscience and law to improve justice outcomes, lays the groundwork for further investigation.
Society for Neurosciencejuli 2024Neurowetenschappen
Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506), are commonly used immunosuppressants for preserving transplanted organs and tissues. However, these drugs can cause severe and persistent pain. GluA2-lacking, calcium-permeable AMPA receptors (CP-AMPARs) are implicated in various neurological disorders, including neuropathic pain. It is unclear whether and how constitutive calcineurin, a Ca(2+)/calmodulin protein phosphatase, controls synaptic CP-AMPARs. In this study, we found that blocking CP-AMPARs with IEM-1460 markedly reduced the amplitude of AMPAR-EPSCs in excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2), but not in inhibitory neurons expressing vesicular GABA transporter, in the spinal cord of FK506-treated male and female mice. FK506 treatment also caused an inward rectification in the current–voltage relationship of AMPAR-EPSCs specifically in VGluT2 neurons. Intrathecal injection of IEM-1460 rapidly alleviated pain hypersensitivity in FK506-treated mice. Furthermore, FK506 treatment substantially increased physical interaction of α2δ-1 with GluA1 and GluA2 in the spinal cord and reduced GluA1/GluA2 heteromers in endoplasmic reticulum-enriched fractions of spinal cords. Correspondingly, inhibiting α2δ-1 with pregabalin, Cacna2d1 genetic knock-out, or disrupting α2δ-1–AMPAR interactions with an α2δ-1 C terminus peptide reversed inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons caused by FK506 treatment. In addition, CK2 inhibition reversed FK506 treatment–induced pain hypersensitivity, α2δ-1 interactions with GluA1 and GluA2, and inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons. Thus, the increased prevalence of synaptic CP-AMPARs in spinal excitatory neurons plays a major role in calcineurin inhibitor-induced pain hypersensitivity. Calcineurin and CK2 antagonistically regulate postsynaptic CP-AMPARs through α2δ-1—mediated GluA1/GluA2 heteromeric assembly in the spinal dorsal horn.
Suppose twentieth-century literary theory had been based on the works of Henri Bergson rather than Ferdinand de Saussure. Would structuralist and poststructuralist theories of language have withstood a Bergsonian critique? Would the institution of literary study be radically different from what it is today? What does this suggest about the future of literary theory?
In this paper, we present a novel robot model of touch, and its representation in an artificial cortex, that aims to capture some of the complexity of human touch. In particular, our approach integrates artificial mechanoception and nociception in an adaptive sensory field (the robot’s “sensory body”), allowing for a more comprehensive simulation of tactile sensations. The robot’s sensory field is then processed by a biologically plausible neural network in a way akin to sensory processing in the somatosensory and anterior cingulate cortex. Findings from our experimental results show our model’s ability to integrate complex data from infrared sensors, leading to the emergence of a spatial sensory body representation in our neural network, with potentially significant implications for robot perception and interaction.
Oxford University Pressseptember 2024Neurowetenschappen
OBJECTIVE: Research demonstrates reduced cognitive flexibility and weak central coherence during acute illness and following recovery from anorexia nervosa (AN). This systematic review investigated if these impairments are present in first-degree relatives of individuals with AN, representing a possible neuropsychological risk profile. METHODS: A systematic review of electronic databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search ended on July 14, 2023. Established search terms and inclusion criteria identified relevant research. Risk of bias was assessed using the Critical Appraisal Skills Program. The review was registered with Prospero international prospective register of systematic reviews (No. CRD42023401268). Study selection, descriptive data, critical appraisal, and risk of bias are presented in tables and figures. RESULTS: The search yielded 10 studies. The included studies conducted neuropsychological assessments of discordant AN relatives and lifetime longitudinal study participants. Most studies found cognitive flexibility and central coherence to be significantly reduced in participants with AN and their relatives compared with controls. One study found decision making to be significantly impaired in AN participants and relatives. Effect sizes were moderate to large. DISCUSSION: Reduced cognitive flexibility and weak central coherence appear to be endophenotypes of AN. Further research is required with relatives concordant for AN to establish whether these biomarkers co-segregate with AN within families. These findings suggest a possibility of developing screeners to identify individuals at risk of AN allowing for early intervention.
Advancements in neuroscience and educational research have provided new opportunities to understand and explore dyscalculia, a specific learning disability that impairs students’ abilities in math and numerical operations. Neuroscientific studies have pinpointed critical brain regions, such as the intraparietal sulcus and left angular gyrus, as central to numerical magnitude processing—a fundamental skill for math competence. Furthermore, the frontal, temporal, and occipital lobes are implicated in math tasks, indicating a comprehensive neural network involved in math cognition. Neuroplasticity underscores the brain’s adaptive responses to new learning experiences, which holds significant implications for educational practices, particularly in the instruction of math. Despite expanding research on dyscalculia, there remains a scarcity of empirical data on the effectiveness of interventions and math support programs specifically for students who are English learners (ELs) in U.S. schools. Educational strategies, such as Dynamic Strategic Math (DSM), integrate culturally relevant materials, multisensory learning, scaffolding, and ample practice to enhance math achievement and retention. By synthesizing empirical studies and meta-analyses, this chapter aims to (a) provide an overview of educational neuroscience research on dyscalculia and (b) establish connections between educational neuroscience research and classroom interventions for ELs with dyscalculia.
The human brain, while incredibly remarkable, is also fragile and susceptible to various issues, including brain tumors and neurological disorders. Fortunately, advanced techniques enable us to detect these anomalies. This research paper focuses on efficiently detecting and analyzing brain tumor types from magnetic resonance imaging (MRI) images. The approach involves creating a deep learning model using EfficientNet convolutional neural network and employing ImageNet for data augmentation. This combination performs exceptionally well on grayscale MRI images from computed tomography scans, achieving a 99.8% accuracy across diverse image data. The model is resilient, working on limited hardware resources, and the web application functions well in low-bandwidth conditions. Besides tumor detection, it provides treatment suggestions, offering a comprehensive solution to various challenges. This project aims to be a sustainable solution, aiding doctors with consistently high accuracy and precision.
Society for Neuroscienceaugustus 2024Neurowetenschappen
MicroRNAs are emerging as crucial regulators within the complex, dynamic environment of the synapse, and they offer a promising new avenue for the treatment of neurological disease. These small noncoding RNAs modify gene expression in several ways, including posttranscriptional modulation via binding to complementary and semicomplementary sites on target mRNAs. This rapid, finely tuned regulation of gene expression is essential to meet the dynamic demands of the synapse. Here, we provide a detailed review of the multifaceted world of synaptic microRNA regulation. We discuss the many mechanisms by which microRNAs regulate gene expression at the synapse, particularly in the context of neuronal plasticity. We also describe the various factors, such as age, sex, and neurological disease, that can influence microRNA expression and activity in neurons. In summary, microRNAs play a crucial role in the intricate and quickly changing functional requirements of the synapse, and context is essential in the study of microRNAs and their potential therapeutic applications.
How can the AI-enabled attention economy be resisted so that our capacities for reflective self-direction are sustained? Grounding itself in Aristotle’s moral philosophy and contemporary neuroscience, this chapter explores how to develop the dispositions, habits, and skills needed to safeguard human agency. These dispositions, habits, and skills, which enable both self-leadership and service, can be cultivated employing the same mechanisms of behavior design that are deployed in the attention economy to hijack attention and erode agency.
Society for Neurosciencejuli 2024Neurowetenschappen
It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography during a saccade task. Human participants (male and female) made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight into when remapped information becomes available. We found that the stimulus could be decoded at the remapped location ∼180 ms post-stimulus onset, but only when the stimulus was presented 100–200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons.
Society for Neuroscienceaugustus 2024Neurowetenschappen
Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of safety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2 h session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals.
Society for Neuroscienceaugustus 2024Neurowetenschappen
Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAG(GABA) neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAG(GABA) neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D(1)-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period.
Oxford University Pressdecember 2024Neurowetenschappen
BACKGROUND: Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord. This cross-sectional study aimed to validate the Arabic version of the Multiple Sclerosis Impact Scale-29 (MSIS-29) using Rasch analysis to assess quality of life in Jordanian MS patients. METHOD: Rasch analysis was conducted to evaluate the suitability of the model for the present study. Model fit was assessed by computing item/person separation reliability, infit and outfit mean square (MSQ) values, Cronbach's alpha, and the Akaike Information Criterion. RESULTS: A total of 301 MS patients were enrolled in the study. Significant likelihood ratios for all three scales (MSIS-29-PHYSICAL, MSIS-29-PSYCHOLOGICAL, and MSIS-29-TOTAL) supported the use of a partial credit Rasch model. An issue with disordered thresholds was resolved by collapsing adjacent response categories. Item reliability scores for MSIS-29-PHYS and MSIS-29-PSYCH were 0.95 and 0.89, respectively, while person reliability scores were 0.92 and 0.84, respectively. Infit and outfit MSQ were within the acceptable range for all items on the MSIS-29-PSYCH scale. However, for the MSIS-29-PHYS scale, item MSIS-29_17 exceeded the acceptable range in both infit (1.93) and outfit (1.82) MSQs, and item MSIS-29_20 exceeded the acceptable range in infit (1.81). The Wright map also indicated that most items were considered relatively easy by the respondents, exhibiting various difficulty levels on the latent scale. CONCLUSION: The Arabic version of the MSIS-29 is a valid and reliable tool for evaluating quality of life in Jordanian MS patients.
Neurorehabilitation builds on the principle that the central nervous system (CNS) is plastic and adapts to the situations the CNS is exposed to. Cases of acquired injury (stroke, traumatic, SCI, concussion), progressive disorders (MS, PD, dementia), or congenital injury (CP) are clinical situations where neuroplasticity becomes relevant. Regardless of how these clinical conditions are treated, the CNS will adapt through physiological processes to the conditions in the different situations. Environmental, clinical, medical, psychological, social, and physical factors all have an influence on how the CNS adapts to neurological injury. This is where clinical personnel become relevant. Because how a person with a lesion to the CNS is treated, has an impact on the plastic changes in the CNS. This chapter will describe some of the possible computational mechanisms that underlie this principle of central nervous plasticity, and how descriptions of both behavior and physiological processes can be formalized with the help of a computational mindset.
Society for Neuroscienceaugustus 2024Neurowetenschappen
Recent studies suggest that time estimation relies on bodily rhythms and interoceptive signals. We provide the first direct electrophysiological evidence suggesting an association between the brain's processing of heartbeat and duration judgment. We examined heartbeat-evoked potential (HEP) and contingent negative variation (CNV) during an auditory duration-reproduction task and a control reaction-time task spanning 4, 8, and 12 s intervals, in both male and female participants. Interoceptive awareness was assessed with the Self-Awareness Questionnaire (SAQ) and interoceptive accuracy through the heartbeat-counting task (HCT). Results revealed that SAQ scores, but not the HCT, correlated with mean reproduced durations with higher SAQ scores associating with longer and more accurate duration reproductions. Notably, the HEP amplitude changes during the encoding phase of the timing task, particularly within 130–270 ms (HEP1) and 470–520 ms (HEP2) after the R-peak, demonstrated interval-specific modulations that did not emerge in the control task. A significant ramp-like increase in HEP2 amplitudes occurred during the duration-encoding phase of the timing but not during the control task. This increase within the reproduction phase of the timing task correlated significantly with the reproduced durations for the 8 s and the 4 s intervals. The larger the increase in HEP2, the greater the under-reproduction of the estimated duration. CNV components during the encoding phase of the timing task were more negative than those in the reaction-time task, suggesting greater executive resources orientation toward time. We conclude that interoceptive awareness (SAQ) and cortical responses to heartbeats (HEP) predict duration reproductions, emphasizing the embodied nature of time.
We’ve long viewed neurological injuries as a black box. Our treatment outcome assessments are often binary, overlooking the many pathogenic mechanisms and their modulators that influence results, such as genetic factors, age, and comorbidities. Even for a given drug, there are numerous variables to consider, including pharmacodynamic specificity, dose, timing, and the effectiveness of the delivery method. This complexity creates a “complex problem mess” that is daunting and intriguing for research. It’s time to develop strategies to track the evolution of neuropathology, ensure drug delivery, and assess the treatment’s impact on the specific injury pathway rather than the net outcome of injury. This chapter describes how we could treat complex neurological diseases by delving into the black box of pathology by using specific injury-guided arterial interventions.
Society for Neuroscienceaugustus 2024Neurowetenschappen
Studies using magnetic brain stimulation indicate the involvement of somatosensory regions in the acquisition and retention of newly learned movements. Recent work found an impairment in motor memory when retention was tested shortly after the application of continuous theta-burst stimulation (cTBS) to the primary somatosensory cortex, compared with stimulation of the primary motor cortex or a control zone. This finding that the somatosensory cortex is involved in motor memory retention whereas the motor cortex is not, if confirmed, could alter our understanding of human motor learning. It would indicate that plasticity in sensory systems underlies newly learned movements, which is different than the commonly held view that adaptation learning involves updates to a motor controller. Here we test this idea. Participants were trained in a visuomotor adaptation task, with visual feedback gradually shifted. Following adaptation, cTBS was applied either to M1, S1, or an occipital cortex control area. Participants were tested for retention 24 h later. It was observed that S1 stimulation led to reduced retention of prior learning, compared with stimulation of M1 or the control area (with no significant difference between M1 and control). In a further control, cTBS was applied to S1 following training with unrotated feedback, in which no learning occurred. This had no effect on movement in the retention test indicating the effects of S1 stimulation on movement are learning specific. The findings are consistent with the S1 participation in the encoding of learning-related changes to movements and in the retention of human motor memory.
Society for Neurosciencejuli 2024Neurowetenschappen
Complex auditory scenes pose a challenge to attentive listening, rendering listeners slower and more uncertain in their perceptual decisions. How can we explain such behaviors from the dynamics of cortical networks that pertain to the control of listening behavior? We here follow up on the hypothesis that human adaptive perception in challenging listening situations is supported by modular reconfiguration of auditory–control networks in a sample of N = 40 participants (13 males) who underwent resting-state and task functional magnetic resonance imaging (fMRI). Individual titration of a spatial selective auditory attention task maintained an average accuracy of ∼70% but yielded considerable interindividual differences in listeners’ response speed and reported confidence in their own perceptual decisions. Whole-brain network modularity increased from rest to task by reconfiguring auditory, cinguloopercular, and dorsal attention networks. Specifically, interconnectivity between the auditory network and cinguloopercular network decreased during the task relative to the resting state. Additionally, interconnectivity between the dorsal attention network and cinguloopercular network increased. These interconnectivity dynamics were predictive of individual differences in response confidence, the degree of which was more pronounced after incorrect judgments. Our findings uncover the behavioral relevance of functional cross talk between auditory and attentional-control networks during metacognitive assessment of one's own perception in challenging listening situations and suggest two functionally dissociable cortical networked systems that shape the considerable metacognitive differences between individuals in adaptive listening behavior.
Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein–lipid interactions and the development of Parkinson pathology. In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. The lipid profile of PD-GBA fibroblasts differed significantly from that of control and idiopathic Parkinson’s disease cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant increase in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter chain length and a decrease in the percentage of longer-chain sphingolipids. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. Lipid extracts from control and PD-GBA fibroblasts were added to recombinant α-synuclein solutions. The kinetics of α-synuclein aggregation were significantly accelerated after addition of PD-GBA extracts as compared to control samples. Amyloid fibrils collected at the end of these incubations contained lipids, indicating α-synuclein–lipid co-assembly. Lipids extracted from α-synuclein fibrils were also analysed by shotgun lipidomics. Data revealed that the lipid content of these fibrils was significantly enriched by shorter-chain sphingolipids. In a final set of experiments, control and PD-GBA fibroblasts were incubated in the presence of the small molecule chaperone ambroxol. This treatment restored glucocerebrosidase activity and sphingolipid levels and composition of PD-GBA cells. It also reversed the pro-aggregation effect that lipid extracts from PD-GBA fibroblasts had on α-synuclein. Taken together, the findings of this study indicate that the L444P GBA mutation and consequent enzymatic loss are associated with a distinctly altered membrane lipid profile that provides a biological fingerprint of this mutation in Parkinson fibroblasts. This altered lipid profile could also be an indicator of increased risk for α-synuclein aggregate pathology.
Parkinson's disease (PD) is a common disorder, linked to α-synuclein aggregates with degeneration of dopaminergic neurons in the substantia nigra. Dysfunction of the noradrenergic system is also associated, with early and intense involvement of the locus coeruleus (LC). A better understanding of the role of noradrenaline is needed to advance our understanding of PD. This thesis begins with the validation of a tracer, 11C-yohimbine, an α2 noradrenergic receptor antagonist. In a second study, 11C-yohimbine PET-MRI scans were performed in parkinsonian patients and controls. Patients showed reduced neuromelanin signal intensity in the LC and decreased tracer binding in extensive cortical regions, the insula, putamen and thalamus. Decreased LC intensity correlated with motor (bradykinesia, motor fluctuations) and non-motor (fatigue, apathy, constipation) symptoms. Decreased tracer binding in the thalamus was associated with tremor, while anxiety was associated with a decrease in the putamen, insula and superior temporal gyrus. We confirm the absence of correlation between LC degeneration and noradrenergic endings. Finally, in a third study, the efficacy of clonidine on impulse control disorders was tested. The results suggest that the treatment is well tolerated, but its efficacy needs to be confirmed by a Phase 3 trial. Our results underline the substantial and multimodal alteration of the noradrenergic system in PD.
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La maladie de Parkinson (MP) est une maladie fréquente, liée à des agrégats d’α-synucleine avec une dégénérescence des neurones dopaminergiques dans la substance noire. Un dysfonctionnement du système noradrénergique est également présent, avec une atteinte précoce et intense du locus coeruleus (LC). Une meilleure connaissance du rôle de la noradrénaline est nécessaire pour progresser sur notre compréhension de la MP. Cette thèse débute par la validation d’un traceur, la 11C-yohimbine, un antagoniste des récepteurs α2 noradrénergique. Dans une deuxième étude, des IRM-TEP à la 11C-yohimbine ont été réalisées chez des patients parkinsoniens et des témoins. Les patients présentaient une réduction de l’intensité du signal de la neuromélanine dans le LC et une diminution de fixation du traceur dans des régions corticales étendues, l’insula, le putamen et le thalamus. La baisse d’intensité du LC était corrélée à des symptômes moteurs (bradykinésie, fluctuations motrices) et non moteurs (fatigue, apathie, constipation). Une diminution de fixation du traceur dans le thalamus était associée aux tremblements tandis que l’anxiété était associée à une diminution dans le putamen, l’insula et le gyrus temporal supérieur. Nous confirmons l’absence de corrélation entre la dégénérescence du LC et des terminaisons noradrénergiques. Enfin, dans une troisième étude, l’efficacité de la clonidine sur les troubles du contrôle des impulsions a été testée. Les résultats sont en faveur d’une bonne tolérance du traitement mais l’efficacité devra être affirmée par un essai de phase 3. Nos résultats soulignent l'altération substantielle et multimodale du système noradrénergique dans la MP.
Mitochondrial impairment is a hallmark feature of neurodegenerative disorders, such as Parkinson disease, and PRKN/parkin-mediated mitophagy serves to remove unhealthy mitochondria from cells. Notably, probiotics are used to alleviate several symptoms of Parkinson disease including impaired locomotion and neurodegeneration in preclinical studies and constipation in clinical trials. There is some evidence to suggest that probiotics can modulate mitochondrial quality control pathways. In this study, we screened 49 probiotic strains and tested distinct stages of mitophagy to determine whether probiotic treatment could upregulate mitophagy in cells undergoing mitochondrial stress. We found two probiotics, Saccharomyces boulardii and Lactococcus lactis, that upregulated mitochondrial PRKN recruitment, phospho-ubiquitination, and MFN degradation in our cellular assays. Administration of these strains to Drosophila that were exposed to paraquat, a mitochondrial toxin, resulted in improved longevity and motor function. Further, we directly observed increased lysosomal degradation of dysfunctional mitochondria in the treated Drosophila brains. These effects were replicated in vitro and in vivo with supra-physiological concentrations of exogenous soluble factors that are released by probiotics in cultures grown under laboratory conditions. We identified methyl-isoquinoline-6-carboxylate as one candidate molecule, which upregulates mitochondrial PRKN recruitment, phospho-ubiquitination, MFN degradation, and lysosomal degradation of damaged mitochondria. Addition of methyl-isoquinoline-6-carboxylate to the fly food restored motor function to paraquat-treated Drosophila. These data suggest a novel mechanism that is facilitated by probiotics to stimulate mitophagy through a PRKN-dependent pathway, which could explain the potential therapeutic benefit of probiotic administration to patients with Parkinson disease.
Humans and other animals appear to frequently base decisions on value attribution that is often not clearly linked to extrinsic outcomes. For example, they prefer opportunities to choose, even when these have no positive impact on future rewards. Thus, access to free choice may be intrinsically rewarding, a form of motivation that invigorates an agent to perform behaviors in and of themselves. This rewarding nature of choice suggests the implication of the basal ganglia system, which is strongly modulated by the dopaminergic system. Dopamine neuron degeneration is responsible for the symptoms of Parkinson's disease (PD). While treatments improve motor function, they can induce behavioral changes. For example, some PD patients treated with dopaminergic treatment show altered sensitivity to extrinsic rewards. Some patients treated with subthalamic nucleus (STN) stimulation, an essential structure in the basal ganglia system, may suffer from impulsive decisions and altered learning from extrinsic rewards. We sought to understand how extrinsic and intrinsic motivations act together during decision making. We developed a new paradigm to identify choice preference as an intrinsic reward in healthy humans as well as patients with PD. First, in healthy subjects, we established that humans prefer choice opportunities for their own sake, independent of the extrinsic rewards associated with these opportunities. We then studied PD patients ON and OFF treatment, which allowed to manipulate the dopaminergic system and basal ganglia that are involved in processing of extrinsic reward. In one patient group, treatment consisted of acute dopamine replacement therapy, and in second patient group treatment consisted of deep brain stimulation (DBS) of the subthalamic nucleus (STN). We found that PD patients ON treatment preferred opportunities to choose even though these did not afford more extrinsic rewards. However, patients lose this preference in conditions that diminish the quantity of dopamine in their brains or by reducing the activation of medial prefrontal cortical areas via deep brain stimulation. In particular, we used probabilistic tractography of cortical fibers from DBS stimulation sites to show that higher connectivity with the right dorsal anterior cingulate cortex was associated with increased choice preference induced by STN-DBS. In the group treated with dopaminergic medication, patients with higher chronic doses of dopaminergic medication showed an increased choice preference. These results advance our understanding of the neurocognitive determinants of intrinsic reward and its interplay with general motivational processes by unmasking motivational mechanisms associated with behavioral impairments observed in PD.
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La préférence pour des situations comportant du choix a été observés chez l’humain et plusieurs espèces animales. Cette préférence pour le choix présente des avantages qui semblent prévaloir sur l’obtention de récompenses plus basiques. Le choix pourrait présenter un caractère intrinsèquement motivant. Ce caractère récompensant du choix suggère l’implication du système des ganglions de la base, impliqué dans les processus de prise de décision et de pérennisation des actions, modulé fortement par le système dopaminergique, responsable de la valuation des stimuli. La dégénérescence des neurones dopaminergiques et l’altération des ganglions de la base qui en résulte, provoque les symptômes de la maladie de Parkinson. Alors que les traitements améliorent la fonction motrice, ils peuvent induire des modifications comportementales. Par exemple, certains patients parkinsoniens sous traitement dopaminergique présentent une sensibilité accrue aux récompenses extrinsèques. Certains patients traités par stimulation du noyau subthalamique (NST), noyau essentiel des ganglions de la base, peuvent souffrir d’une prise de décisions impulsives. Ce travail de recherche utilise un nouveau paradigme permettant de caractériser la préférence pour le choix comme récompense intrinsèque. Dans une première étape, le sujet a la possibilité de choisir librement ou non. Dans une seconde étape, il choisit entre deux images celle qui délivre le plus de récompenses. Pour limiter le biais d’exploration, les sujets ont réalisé un apprentissage préalable des contingences de récompenses. Des sujets sains, des patients parkinsoniens avec traitement dopaminergique et d’autres traités par stimulation cérébrale profonde du NST ont été inclus. Les patients parkinsoniens ont réalisé la tâche sans (OFF) et avec traitement (ON). Afin d’examiner si des patterns de connectivité pourraient expliquer les réponses des patients stimulés, la tractographie probabiliste des fibres corticales incluses dans le volume de tissu activé au sein du NST a été analysée. Premièrement, chez des sujets sains, nous avons établi que les humains préfèrent les possibilités de choix pour elles-mêmes, indépendamment des récompenses extrinsèques associées à ces possibilités. Chez les patients, il existe un effet aigu de la stimulation du NST, les sujets ON préférant le choix à hauteur de celle des sujets sains, indépendamment des récompenses extrinsèques qu’ils ont reçus. Chez les patients OFF, la préférence pour le choix diminue près du seuil d’indifférence (50%). Il existe une connectivité accrue avec le cortex cingulaire antérieur dorsal droit chez les patients ayant le plus d’effet. Les patients avec traitement dopaminergique présentaient une préférence pour le choix accru si leurs doses quotidiennes étaient plus élevées. Ces résultats font progresser notre compréhension des déterminants neurocognitifs de la récompense intrinsèque et de son interaction avec des processus motivationnels généraux en démasquant les mécanismes associés aux troubles comportementaux observées dans la maladie de Parkinson.
Parkinson's disease (PD) is a multifactorial neurodegenerative disease characterized by the degeneration of dopaminergic neurons from the substantia nigra pars compacta (SNc) leading to the development of motor symptoms. Projections of dopaminergic neurons from the SNc to the striatum constitute the nigro-striatal pathway whose activity in the basal ganglia network is essential for the control of voluntary movement. Several clinical and preclinical studies suggest an involvement of vitamin A and it signaling pathway mediated by its active metabolite, retinoic acid (RA), in the development and maintenance of the integrity of the nigro-striatal pathway. However, with aging or deficient dietary intake, a collapse of retinoid signaling is observed, which may contribute to the etiology of PD. Current treatments for PD do not prevent neurodegeneration and are associated to severe long-term side effects, highlighting the need to develop alternative therapeutics.In that context, the general objective of this thesis was to further understand the involvement of retinoid signaling in the functional homeostasis of the nigro-striatal pathway in adulthood, and to determine the potential benefit of vitamin A nutritional supplementation to delay the progression of PD.Results of a first study in an adult rat model of PD with intrastriatal injection of 6-hydroxydopamine (6-OHDA) have revealed a beneficial effect of nutritional vitamin A supplementation on striatal function and an improvement of 6-OHDA-induced motor deficits. However, analyses did not reveal a strong effect of dietary vitamin A intake on the dopaminergic system. Furthermore, the impact of vitamin A bioavailability on striatal neuromodulation in adult rats has been investigated with diets containing different amount of vitamin A (sub-deficient, sufficient or enriched). Here, vitamin A sub-deficiency initiated in adulthood constituted an original approach to model alteration of retinoid signaling excluding developmental effects. Results reveal an involvement of retinoid signaling in the maintenance of the integrity of cholinergic system and the architecture of the striatum in adulthood. Additionally, results suggest a differential sensitivity of the dopaminergic system to vitamin A signaling between adulthood and the developmental period.In conclusion, this thesis work demonstrates the importance of retinoid signaling to maintain physiological activity of the striatum and the nigro-striatal pathway in adulthood. As part of personalized medicine, nutritional supplementation with vitamin A could improve the management of patients and the prevention of PD.
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La maladie de Parkinson (MP) est une maladie neurodégénérative multifactorielle caractérisée par la dégénérescence des neurones dopaminergiques de la substance noire pars compacta (SNc) conduisant à l’apparition de symptômes moteurs. Les projections dopaminergiques de la SNc sur le striatum constituent la voie nigro-striée dont l’activité au sein des ganglions de la base est nécessaire pour le contrôle du mouvement volontaire. Plusieurs études cliniques et pré-cliniques suggèrent une implication de la vitamine A et de sa signalisation médiée par son métabolite actif, l’acide rétinoïque (AR), dans le développement et le maintien de l’intégrité de la voie nigro-striée. Cependant au cours du vieillissement, ou en cas d’apport alimentaire insuffisant, on observe un affaissement de la signalisation des rétinoïdes pouvant contribuer à l’étiologie de la MP. Les traitements actuels de la MP ne préviennent pas la neurodégénérescence et sont associés à de sérieux effets secondaires à long-terme, soulignant la nécessité de développer des stratégies alternatives.C’est dans ce contexte que s’inscrit cette thèse, dont l’objectif principal était de mieux comprendre l’implication de la signalisation des rétinoïdes dans l’homéostasie fonctionnelle de la voie nigro-striée à l’âge adulte et de déterminer le potentiel effet bénéfique d’une supplémentation nutritionnelle en vitamine A pour ralentir la progression de la MP.Les résultats obtenus dans une première étude chez le rat adulte modélisant la MP par une injection intrastriatale de 6-hydroxydopamine (6-OHDA) révèlent un effet bénéfique d’une supplémentation nutritionnelle en vitamine A sur la fonction striatale et une amélioration des déficits moteurs induits par la 6-OHDA. Cependant les analyses ne révèlent pas d’effet majeur de l’apport alimentaire en vitamine A sur le système dopaminergique. Par ailleurs, l’impact de la biodisponibilité en vitamine A sur la neuromodulation du striatum à l’âge adulte a été étudié chez le rat avec des régimes à différentes teneurs en vitamine A (régimes sub-déficient, suffisant et enrichi). Ainsi, la réalisation d’une sub-carence en vitamine A initiée à l’âge adulte a constitué une approche innovante pour modéliser une altération de la signalisation des rétinoïdes en s’affranchissant de l’impact développemental de la carence. Les résultats de cette deuxième étude révèlent l’implication de la signalisation des rétinoïdes dans le maintien de l’intégrité du système cholinergique et de l’architecture du striatum à l’âge adulte. Ils suggèrent également une sensibilité différente du système dopaminergique à la vitamine A entre l’âge adulte et la période développementale.En conclusion, ce travail de thèse démontre l’importance de la signalisation des rétinoïdes pour maintenir l’activité physiologique du striatum et de la voie nigro-striée à l’âge adulte. Dans l’optique d’une médecine personnalisée, une supplémentation nutritionnelle en vitamine A pourrait contribuer à améliorer la prise en charge des patients et la prévention de le MP.
PPINtonus is a system for the early detection of Parkinson's Disease (PD)
utilizing deep-learning tonal analysis, providing a cost-effective and
accessible alternative to traditional neurological examinations. Partnering
with the Parkinson's Voice Project (PVP), PPINtonus employs a semi-supervised
conditional generative adversarial network to generate synthetic data points,
enhancing the training dataset for a multi-layered deep neural network.
Combined with PRAAT phonetics software, this network accurately assesses
biomedical voice measurement values from a simple 120-second vocal test
performed with a standard microphone in typical household noise conditions. The
model's performance was validated using a confusion matrix, achieving an
impressive 92.5 \% accuracy with a low false negative rate. PPINtonus
demonstrated a precision of 92.7 \%, making it a reliable tool for early PD
detection. The non-intrusive and efficient methodology of PPINtonus can
significantly benefit developing countries by enabling early diagnosis and
improving the quality of life for millions of PD patients through timely
intervention and management.
Parkinson's disease is a common neurological disease, entailing a multitude
of motor deficiency symptoms. In this project, we developed a device with an
uploaded edge machine learning algorithm that can detect the onset of freezing
of gait symptoms in a Parkinson's patient. The algorithm achieved an accuracy
of 83.7% in a validation using data from ten patients. The model was deployed
in a microcontroller Arduino Nano 33 BLE Sense Board model and validated in
real-time operation with data streamed to the microcontroller from a computer.
Parkinson's disease (PD) shows heterogeneous, evolving brain-morphometry patterns. Modeling these longitudinal trajectories enables mechanistic insight, treatment development, and individualized 'digital-twin' forecasting. However, existing methods usually adopt recurrent neural networks and transformer architectures, which rely on discrete, regularly sampled data while struggling to handle irregular and sparse magnetic resonance imaging (MRI) in PD cohorts. Moreover, these methods have difficulty capturing individual heterogeneity including variations in disease onset, progression rate, and symptom severity, which is a hallmark of PD. To address these challenges, we propose CNODE (Conditional Neural ODE), a novel framework for continuous, individualized PD progression forecasting. The core of CNODE is to model morphological brain changes as continuous temporal processes using a neural ODE model. In addition, we jointly learn patient-specific initial time and progress speed to align individual trajectories into a shared progression trajectory. We validate CNODE on the Parkinson's Progression Markers Initiative (PPMI) dataset. Experimental results show that our method outperforms state-of-the-art baselines in forecasting longitudinal PD progression. ;Accepted to IEEE International Conference on Bioinformatics and Biomedicine (BIBM) 2025
The prevalence of negative stimuli conventionally observed in young adults decreases during normal aging, oreven evolves into a prevalence of positive stimuli. This age-related effect is called the "positivity effect". Observedin emotional appraisal tasks, this effect disappears in action tendency tasks, suggesting a dissociation betweenemotions and action behaviors. Better understanding the evolution of the link between emotional processes andaction behaviors in normal aging would allow to specify the conditions for the emergence of the positivity effectand to better understand the motor and affective disorders associated with some neurodegenerative pathologiessuch as Parkinson's disease (PD). The first section of my PhD thesis consisted in evaluating the evolution ofemotional processing during normal aging. During a free exploration task of emotional image pairs, a first studyin oculometry show in the elderly a reduced automatic orientation of attention and a more spatially focusedattentional exploration for positive scenes, compared to young and middle-aged adults. At the cerebral level, asecond functional MRI study (fMRI) suggests a cerebral reorganization in normal aging which would reflect anevolution of emotional processing strategies: while young people would rather activate a fronto-limbic networkassociated with the emotional evaluation and regulation and a more complex cognitive processing, the elderly (vsyoung) would activate more regions related to viscero-somatosensory integration, spatial imaging and motorprogramming and regulation in a more embodied strategy of the emotional appraisal. In contrast, the two groups,young and older, differed less in the action tendency task, suggesting similar emotional processing strategies fordeciding motivated action. The second section of my PhD thesis consisted in evaluating the evolution of emotionalprocessing in de novo PD patients using the same protocols of previous studies. The oculometry study (3rd study)reveal in patients, a reduced automatic orientation of attention for emotional scenes (vs neutral) and even more forpositive scenes and an overall more extensive attentional exploration, compared to healthy controls. The fMRIstudy (4th study) reveals, for its part, an hyperactivation of a large temporo-parieto-fronto-limbic networkspecifically in the action tendency task in patients (vs healthy controls), suggesting a mechanism of compensationfor the difficulties encountered by the patients in this task, while their emotional appraisal is relatively preserved.The oculomotor and cerebral patterns specifically observed in de novo PD patients pave the way for theidentification of new early (bio)markers of Parkinson's disease and the action tendency task seems to be a relevanttool in this perspective.
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La prévalence des stimuli négatifs classiquement observée chez de jeunes adultes s’atténue au cours du vieillissement sain, voire évolue vers une prévalence des stimuli positifs. Cet effet lié à l’âge est appelé « effet depositivité ». Présent dans des tâches d’évaluation du ressenti émotionnel, cet effet disparait lors de tâche d’évaluation de la tendance à l’action, suggérant une dissociation entre émotion et comportement d’action. Mieux comprendre l’évolution du lien entre processus émotionnels et comportements d’action au cours du vieillissement sain permettrait de préciser les conditions d’émergence de l’effet de positivité et de mieux comprendre les troubles moteurs et affectifs associés dans certaines pathologies neurodégénératives telles que la maladie de Parkinson. Le premier volet d’études de la thèse a consisté à évaluer l’évolution du traitement émotionnel au cours du vieillissement sain. Lors d’une tâche d’exploration libre de paires d’images émotionnelles, une première étude enoculométrie montre chez les personnes âgées une orientation automatique de l’attention réduite et une exploration attentionnelle plus focalisée spatialement pour les scènes positives, par rapport aux adultes jeunes et d’âge moyen.Au niveau cérébral, une seconde étude en IRM fonctionnelle (IRMf) suggère une réorganisation cérébrale au coursdu vieillissement sain qui traduirait une évolution des stratégies de traitement émotionnel : alors que les jeunes personnes activeraient plutôt un réseau fronto-limbique associé à l’évaluation et la régulation émotionnelles et à un traitement cognitif plus complexe, les personnes âgées (vs jeunes) activeraient davantage des régions liées à l’intégration viscéro-somato sensorielle, à la visualisation spatiale et à la programmation et régulation motrice dans une stratégie plus incarnée de l’évaluation émotionnelle. En revanche, les deux groupes, jeunes et âgés, se distinguent moins dans la tâche de tendance à l’action, suggérant des stratégies cérébrales de traitement émotionnel quasi-analogues pour décider d’une action motivée. Le deuxième volet d’études de la thèse a consisté à évaluer l’évolution du traitement émotionnel chez des patients parkinsoniens de novo en utilisant les mêmes protocoles des études précédentes. L’étude en oculométrie (3ème étude) révèle chez les patients, une orientation automatique de l’attention réduite pour les scènes émotionnelles (vs neutres) et d’autant plus pour les scènes positives et une exploration attentionnelle globalement plus étendue, par rapport aux contrôles sains. L’étude en IRMf (4ème étude)révèle, quant à elle, une suractivation d’un large réseau temporo-parieto-fronto-limbique spécifiquement dans latâche de tendance à l’action chez les patients (vs contrôles sains), suggérant un mécanisme de compensation aux difficultés rencontrées par les patients dans cette tâche, alors que leur évaluation émotionnelle est relativemen tpréservée. Les patterns oculomoteurs et cérébraux observés spécifiquement chez les patients parkinsoniens denovo ouvrent la piste à l’identification de potentiels nouveaux (bio)marqueurs précoces de la maladie de Parkinson et la tâche de tendance à l’action semble être un outil d’intérêt dans cette perspective.
Background Traditionally, functional neurosurgery relied in stereotactic atlases and intraoperative micro-registration in awake patients for electrode placement in Parkinson’s disease. Cumulative experience on target description, refinement of MRI, and advances in intraoperative imaging has enabled accurate preoperative planning and its implementation with the patient under general anaesthesia. Methods Stepwise description, emphasising preoperative planning, and intraoperative imaging verification, for transition to asleep-DBS surgery. Conclusion Direct targeting relies on MRI anatomic landmarks and accounts for interpersonal variability. Indeed, the asleep procedure precludes patient distress. A particular complication to avoid is pneumocephalus; it can lead to brain-shift and potential deviation of electrode trajectory.
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Patients with Parkinson’s disease (PD) notably exhibit impairments in posture and visual attention. The objective of the present study was to determine whether PD patients were able to exhibit adaptive postural control in a goal-directed visual task. We hypothesized that the patients would reduce their centre of pressure (COP) movement and/or postural sway to a lesser extent than age-matched controls in the goal-directed visual (search) task, compared with the control free-viewing task (i.e. a lower degree of relative postural adaptation). We also expected the PD patients to sway more than controls in the goal-directed task (i.e. a lower degree of absolute adaptive postural control). The study included 39 PD patients (mean age: 59; mean Hoehn and Yahr stage: 2.1; mean Movement Disorder Society-Unified Parkinson's Disease Rating Scale score: 22; mean Montreal Cognitive Assessment score: 28 (on-drug) and 40 age-matched adults (mean age: 62 years). The participants gazed domestic ecological images (visual angle: 100°). Movements of the COP, head, upper back and lower-back and variations in pupil dilatation were analysed. As expected, PD patients exhibited greater COP and body sway than controls in both tasks (p<0.05). Unexpectedly, the difference in COP and/or body sway between the two tasks was greater in PD patients than in controls (p<0.05). Our results showed that PD patients are able to exhibit adaptive postural control for goal-directed visual tasks. On a practical level, our findings emphasize the likely benefits of rehabilitation with goal-directed tasks requiring a visual attentional focus (walking on footprints on the ground, etc.).
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Les patients atteints de la maladie de Parkinson (MP) présentent notamment des troubles de la posture et de l'attention visuelle. L'objectif de la présente étude était de déterminer si les patients atteints de MP étaient capables de démontrer un contrôle postural adaptatif dans une tâche visuelle orientée vers un objectif. Nous avons émis l'hypothèse que les patients réduiraient leurs mouvements du centre de pression (COP) et/ou leurs oscillations posturales dans une moindre mesure que des témoins appariés en âge lors de la tâche visuelle orientée vers un objectif (recherche), par rapport à une tâche de vision libre (c’est-à-dire un degré inférieur d'adaptation posturale relative). Nous nous attendions également à ce que les patients atteints de MP oscillent davantage que les témoins dans la tâche orientée (c’est-à-dire un degré inférieur de contrôle postural adaptatif absolu). L'étude a inclus 39 patients atteints de MP (âge moyen : 59 ans ; stade moyen de Hoehn et Yahr : 2,1 ; score moyen à l'échelle MDS-UPDRS : 22 ; score moyen au MoCA : 28, en phase « on » du traitement) et 40 adultes appariés en âge (âge moyen : 62 ans). Les participants ont regardé des images écologiques domestiques (angle visuel : 100°). Les mouvements du COP, de la tête, du haut et du bas du dos ainsi que les variations de dilatation pupillaire ont été analysés. Comme prévu, les patients atteints de MP ont montré des oscillations du COP et du corps plus importantes que les témoins dans les deux tâches (p<0,05). De manière inattendue, la différence dans les oscillations du COP et/ou du corps entre les deux tâches était plus marquée chez les patients atteints de MP que chez les témoins (p<0,05). Nos résultats ont montré que les patients atteints de MP sont capables de démontrer un contrôle postural adaptatif dans des tâches visuelles orientées vers un objectif. Sur un plan pratique, nos résultats soulignent les bénéfices potentiels de la rééducation utilisant des tâches orientées nécessitant une attention visuelle (marcher sur des empreintes au sol, etc.).
Macroautophagy is a catabolic process that coordinates with lysosomes to degrade aggregation-prone proteins and damaged organelles. Loss of macroautophagy preferentially affects neuron viability and is associated with age-related neurodegeneration. We previously found that α-synuclein (α-syn) inhibits lysosomal function by blocking ykt6, a farnesyl-regulated soluble NSF attachment protein receptor (SNARE) protein that is essential for hydrolase trafficking in midbrain neurons. Using Parkinson's disease (PD) patient iPSC-derived midbrain cultures, we find that chronic, endogenous accumulation of α-syn directly inhibits autophagosome-lysosome fusion by impairing ykt6-SNAP-29 complexes. In wild-type (WT) cultures, ykt6 depletion caused a near-complete block of autophagic flux, highlighting its critical role for autophagy in human iPSC-derived neurons. In PD, macroautophagy impairment was associated with increased farnesyltransferase (FTase) activity, and FTase inhibitors restored macroautophagic flux through promoting active forms of ykt6 in human cultures, and male and female mice. Our findings indicate that ykt6 mediates cellular clearance by coordinating autophagic-lysosomal fusion and hydrolase trafficking, and that macroautophagy impairment in PD can be rescued by FTase inhibitors. SIGNIFICANCE STATEMENT The pathogenic mechanisms that lead to the death of neurons in Parkinson's disease (PD) and Dementia with Lewy bodies (LBD) are currently unknown. Furthermore, disease modifying treatments for these diseases do not exist. Our study indicates that a cellular clearance pathway termed autophagy is impaired in patient-derived culture models of PD and in vivo. We identified a novel druggable target, a soluble NSF attachment protein receptor (SNARE) protein called ykt6, that rescues autophagy in vitro and in vivo upon blocking its farnesylation. Our work suggests that farnesyltransferase (FTase) inhibitors may be useful therapies for PD and DLB through enhancing autophagic-lysosomal clearance of aggregated proteins.
BACKGROUND: Parkinson's disease is a progressive neurological disease with limited treatment options. Animal models and a proof-of-concept case series have suggested that photobiomodulation may be an effective adjunct treatment for the symptoms of Parkinson's disease. The aim was to determine the safety and feasibility of transcranial photobiomodulation (tPBM) to reduce the motor signs of Parkinson's disease. METHODS: In this double-blind, randomised, sham-controlled feasibility trial, patients (aged 59–85 years) with idiopathic Parkinson's disease were treated with a tPBM helmet for 12 weeks (72 treatments with either active or sham therapy; stage 1). Treatment was delivered in the participants' homes, monitored by internet video conferencing (Zoom). Stage 1 was followed by 12 weeks of no treatment for those on active therapy (active-to-no-treatment group), and 12 weeks of active treatment for those on sham (sham-to-active group), for participants who chose to continue (stage 2). The active helmet device delivered red and infrared light to the head for 24 min, 6 days per week. The primary endpoints were safety and motor signs, as assessed by a modified Movement Disorders Society revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)-motor scale. This trial is registered with ANZCTR, ACTRN 12621001722886. FINDINGS: Between Dec 6, 2021, and Aug 12, 2022, 20 participants were randomly allocated to each of the two groups (10 females plus 10 males per group). All participants in the active group and 18 in the sham group completed 12 weeks of treatment. 14 participants in the sham group chose to continue to active treatment and 12 completed the full 12 weeks of active treatment. Treatment was well tolerated and feasible to deliver, with only minor, temporary adverse events. Of the nine suspected adverse events that were identified, two minor reactions may have been attributable to the device in the sham-to-active group during the active treatment weeks of the trial. One participant experienced temporary leg weakness. A second participant reported decreased fine motor function in the right hand. Both participants continued the trial. The mean modified MDS-UPDRS-III scores for the sham-to-active group at baseline, after 12 weeks of sham treatment, and after 12 weeks of active treatment were 26.8 (sd 14.6), 20.4 (sd 12.8), and 12.2 (sd 8.9), respectively, and for the active-to-no-treatment group these values were 21.3 (sd 9.4), 16.5 (sd 9.4), and 15.3 (sd 10.8), respectively. There was no significant difference between groups at any assessment point. The mean difference between groups at baseline was 5.5 (95% confidence interval (CI) −2.4 to 13.4), after stage 1 was 3.9 (95% CI −3.5 to 11.3 and after stage 2 was −3.1 (95% CI 2.7 to −10.6). INTERPRETATION: Our findings add to the evidence base to suggest that tPBM is a safe, tolerable, and feasible non-pharmaceutical adjunct therapy for Parkinson's disease. While future work is needed our results lay the foundations for an adequately powered randomised placebo-controlled clinical trial. FUNDING: SYMBYX Pty Ltd.
Background Parkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease. Results The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocardial TH in the PD group was decreased by 65% compared to the control group ( P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group ( P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.
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Neuropeptides are bioactive molecules, made up of small chains of amino acids, with many neuromodulatory properties. Several lines of evidence suggest that neuropeptides, mainly expressed in the central nervous system (CNS), play an important role in the onset of Parkinson's Disease (PD) pathology. The wide spread disruption of neuropeptides has been excessively demonstrated to be related to the pathophysiological symptoms in PD where impairment in motor function per example was correlated with neuropeptides dysregulation in the substantia niagra (SN). Moreover, the levels of different neuropeptides have been found modified in the cerebrospinal fluid and blood of PD patients, indicating their potential role in the manifestation of PD symptoms and dysfunctions. In this review, we outlined the neuroprotective effects of neuropeptides on dopaminergic neuronal loss, oxidative stress and neuroinflammation in several models and tissues of PD. Our main focus was to elaborate the role of orexin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), opioids, angiotensin, carnosine and many others in the protection and/or involvement in the neurodegeneration of striatal dopaminergic cells. Further studies are required to better assess the mode of action and cellular mechanisms of neuropeptides in order to shift the focus from the in vitro and in vivo testing to applicable clinical testing. This review, allows a support for future use of neuropeptides as therapeutic solution for PA pathophysiology.
The Japanese Society of Internal Medicinefebruari 2022Parkinson
OBJECTIVE: To investigate the efficacy of home-based gait training using the wearable Stride Management Assist (SMA) exoskeleton in people with moderately advanced Parkinson's disease. METHODS: This was a single-center, open-label, parallel, randomized controlled trial. We included outpatients with idiopathic Parkinson's disease who were capable of walking independently with or without walk aids and had Hoehn and Yahr stage 2-4 in the ON state. Patients were randomly assigned (1:1 ratio) to receive either SMA gait training (SMA group) or control gait training (control group). All participants underwent gait training for approximately 30 min. These training sessions were conducted 10 times for 3 months. We measured clinical outcomes at baseline and post-intervention. The between-group difference of distance in the three-minute walk test was the primary outcome. RESULTS: Of the 15 randomly assigned participants, 12 (five in the SMA group) completed this study. The between-group difference was a mean of 13.7 meters (standard error of the mean: 7.8) in the 3-minute walk test (p=0.109). The distance traversed increased from 141.4 m to 154.7 m in the SMA group (p=0.023), whereas there was no marked change in the control group. In addition, although there was a decrease in the physiological cost index from 0.29 to 0.13 in the SMA group (p=0.046), it remained unchanged in the control group. CONCLUSION: These findings suggest that home-based SMA gait training may increase the exercise endurance in people with moderately advanced Parkinson's disease.
Background Tremors, psychological difficulties, mental health issues, depression, impulsive acts, and other behavioral abnormalities are all symptoms of Parkinson's disease, a neurodegenerative disorder of the central nervous system. Smilax china ethanolic extract was tested for its anti-Parkinson's activity using a Wistar rat model of rotenone-induced Parkinson's disease. Spectroscopic, acute toxicity and pharmacognostic analyses were performed. Result Brownish, the bark of Smilax china included vascular bundles and fibers upon microscopic inspection and alkaloids, carbohydrates, and phenolic substances upon phytochemical analysis. Acute toxicity testing as per Organization for Economic Corporation and Development 423 (OECD 423) on male Wistar rats revealed no harmful effects. The biochemical analysis of rotenone-induced groups revealed a disproportion. Improved body weight, mobility, coordination, and a lower incidence of catalepsy were seen in animals treated with Smilax china ethanolic extract (100 and 200 mg/kg). Smilax china 200 mg/kg extract substantially lowered motor defects determined by catalepsy score using bar test 17.061.74/s against rotenone-induced group 67.593.27/s. It also prevented the brain from oxidative stress by enhancing superoxide dismutase (SOD) levels to 5.440.01 units/mg protein compared to 2.050.104 units/mg protein in the rotenone-induced group. The vagus nerve, substantia nigra, and basal ganglia of the treated groups indicated a reduction in inflammation and alpha-synuclein destruction. Conclusion Based on our research, an ethanolic extract of Smilax china bark provides an effective antioxidant with promising neuroprotective properties in male Wistar rats induced with Parkinson's disease. Graphical abstract
In this paper, we evaluate the contribution of different handwriting
modalities to the diagnosis of Parkinson's disease. We analyse on-surface
movement, in-air movement and pressure exerted on the tablet surface.
Especially in-air movement and pressure-based features have been rarely taken
into account in previous studies. We show that pressure and in-air movement
also possess information that is relevant for the diagnosis of Parkinson's
Disease (PD) from handwriting. In addition to the conventional kinematic and
spatio-temporal features, we present a group of the novel features based on
entropy and empirical mode decomposition of the handwriting signal. The
presented results indicate that handwriting can be used as biomarker for PD
providing classification performance around 89% area under the ROC curve (AUC)
for PD classification.
;Comment: The work was published by IEEE
We present an artificial intelligence system to remotely assess the motor
performance of individuals with Parkinson's disease (PD). Participants
performed a motor task (i.e., tapping fingers) in front of a webcam, and data
from 250 global participants were rated by three expert neurologists following
the Movement Disorder Society Unified Parkinson's Disease Rating Scale
(MDS-UPDRS). The neurologists' ratings were highly reliable, with an
intra-class correlation coefficient (ICC) of 0.88. We developed computer
algorithms to obtain objective measurements that align with the MDS-UPDRS
guideline and are strongly correlated with the neurologists' ratings. Our
machine learning model trained on these measures outperformed an MDS-UPDRS
certified rater, with a mean absolute error (MAE) of 0.59 compared to the
rater's MAE of 0.79. However, the model performed slightly worse than the
expert neurologists (0.53 MAE). The methodology can be replicated for similar
motor tasks, providing the possibility of evaluating individuals with PD and
other movement disorders remotely, objectively, and in areas with limited
access to neurological care.
Background Following progressive aging of the population worldwide, the prevalence of Parkinson disease is expected to increase in the next decades. Primary prevention of the disease is hampered by limited knowledge of preventable causes. Recent evidence regarding diet and Parkinson disease is inconsistent and suggests that dietary habits such as fat intake may have a role in the etiology. Objective To investigate the association between intake of total and specific types of fat with the incidence of Parkinson disease. Methods Participants from the Swedish National March Cohort were prospectively followed-up from 1997 to 2016. Dietary intake was assessed at baseline using a validated food frequency questionnaire. Food items intake was used to estimate fat intake, i.e. the exposure variable, using the Swedish Food Composition Database. Total, saturated, monounsaturated and polyunsaturated fat intake were categorized into quartiles. Parkinson disease incidence was ascertained through linkages to Swedish population-based registers. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of the association between fat intake from total or specific types of fats and the incidence of Parkinson disease. The lowest intake category was used as reference. Isocaloric substitution models were also fitted to investigate substitution effects by replacing energy from fat intake with other macronutrients or specific types of fat. Results 41,597 participants were followed up for an average of 17.6 years. Among them, 465 developed Parkinson disease. After adjusting for potential confounders, the highest quartile of saturated fat intake was associated with a 41% increased risk of Parkinson disease compared to the lowest quartile (HR Q4 vs. Q1: 1.41; 95% CI: 1.04–1.90; p for trend: 0.03). Total, monounsaturated or polyunsaturated fat intake were not significantly associated with Parkinson disease. The isocaloric substitution models did not show any effect. Conclusions We found that a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson disease. A diet low in saturated fat might be beneficial for disease prevention.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder known for
its impact on motor neurons, causing symptoms like tremors, stiffness, and gait
difficulties. This study explores the potential of vocal feature alterations in
PD patients as a means of early disease prediction. This research aims to
predict the onset of Parkinson's disease. Utilizing a variety of advanced
machine-learning algorithms, including XGBoost, LightGBM, Bagging, AdaBoost,
and Support Vector Machine, among others, the study evaluates the predictive
performance of these models using metrics such as accuracy, area under the
curve (AUC), sensitivity, and specificity. The findings of this comprehensive
analysis highlight LightGBM as the most effective model, achieving an
impressive accuracy rate of 96% alongside a matching AUC of 96%. LightGBM
exhibited a remarkable sensitivity of 100% and specificity of 94.43%,
surpassing other machine learning algorithms in accuracy and AUC scores. Given
the complexities of Parkinson's disease and its challenges in early diagnosis,
this study underscores the significance of leveraging vocal biomarkers coupled
with advanced machine-learning techniques for precise and timely PD detection.
We evaluate the effectiveness of combining brain connectivity metrics with
signal statistics for early stage Parkinson's Disease (PD) classification using
electroencephalogram data (EEG). The data is from 5 arousal states - wakeful
and four sleep stages (N1, N2, N3 and REM). Our pipeline uses an Ada Boost
model for classification on a challenging early stage PD classification task
with with only 30 participants (11 PD , 19 Healthy Control). Evaluating 9 brain
connectivity metrics we find the best connectivity metric to be different for
each arousal state with Phase Lag Index achieving the highest individual
classification accuracy of 86\% on N1 data. Further to this our pipeline using
regional signal statistics achieves an accuracy of 78\%, using brain
connectivity only achieves an accuracy of 86\% whereas combining the two
achieves a best accuracy of 91\%. This best performance is achieved on N1 data
using Phase Lag Index (PLI) combined with statistics derived from the frequency
characteristics of the EEG signal. This model also achieves a recall of 80 \%
and precision of 96\%. Furthermore we find that on data from each arousal
state, combining PLI with regional signal statistics improves classification
accuracy versus using signal statistics or brain connectivity alone. Thus we
conclude that combining brain connectivity statistics with regional EEG
statistics is optimal for classifier performance on early stage Parkinson's.
Additionally, we find outperformance of N1 EEG for classification of
Parkinson's and expect this could be due to disrupted N1 sleep in PD. This
should be explored in future work.
Parkinson's disease (PD) is a progressive disorder in which symptom burden and functional impairment evolve over time, making severity staging essential for clinical monitoring and treatment planning. However, many computational studies emphasize binary PD detection and do not fully use repeated follow-up clinical assessments for stage-aware prediction. This study proposes STEP-PD, a severity-aware machine learning framework to classify PD severity using clinically interpretable boundaries. It leverages all available visits from the Parkinson's Progression Markers Initiative (PPMI) and integrates routinely collected subjective questionnaires and objective clinician-assessed measures. Disease severity is defined using Hoehn and Yahr staging and grouped into three clinically meaningful categories: Healthy, Mild PD (stages 1-2), and Moderate-to-Severe PD (stages 3-5). Three binary classification problems and a three-class severity task were evaluated using stratified cross-validation with imbalance-aware training. To enhance interpretability, SHAP was used to provide global explanations and local patient-level waterfall explanations. Across all tasks, XGBoost achieved the strongest and most stable performance, with accuracies of 95.48% (Healthy vs. Mild), 99.44% (Healthy vs. Moderate-to-Severe), and 96.78% (Mild vs. Moderate-to-Severe), and 94.14% accuracy with 0.8775 Macro-F1 for three-class severity classification. Explainability results highlight a shift from early motor features to progression-related axial and balance impairments. These findings show that multimodal clinical assessments within the PPMI cohort can support accurate and interpretable visit-level PD severity stratification. ;10 pages, 6 figures, 4 tables, accepted at IEEE International Conference on Healthcare Informatics (ICHI 2026)
Relativistic jets in active galactic nuclei (AGNs) are known to accelerate particles to extreme energies, yet the physical origin of very-high-energy (VHE) emission from low-luminosity AGNs (LL AGNs) remains unclear. NGC 4278, a local LLAGN, has recently been identified as a VHE source following detections by LHAASO. In this study, we present a multi-wavelength and multi-messenger analysis to investigate the physical origin of this emission. Swift-XRT monitoring reveals a quasi-quiescent state characterized by a low X-ray flux. Modeling the broadband spectral energy distribution with the leptohadronic code AMES, we find that a standard one-zone synchrotron self-Compton (SSC) model underpredicts the VHE flux by $\sim$70% due to the insufficient target photon density provided by the weak X-ray emission, unless a high Doppler factor ($δ\gtrsim 5$) is invoked. Alternatively, an external inverse-Compton (EIC) scenario-scattering seed photons from a radiatively inefficient accretion flow (RIAF)-successfully reproduces the broadband spectral energy distribution with a modest jet power and Doppler factor. We further explore the neutrino production within a leptohadronic framework. The predicted muon neutrino event rate is highest in the EIC quiescent model, reaching $N_{ν_μ} \sim 0.001$ for a 15-year IceCube observation (assuming 0.1% of the Eddington luminosity is partitioned into high-energy protons). Future multi-messenger observations are essential to unveil the details of the high-energy processes of NGC 4278. ;13 pages, 6 figures, 3 tables, Submitted to ApJ on 09 Jan 2026
Tearing instability, also known as plasmoid instability, is an effective mechanism to speed up magnetic reconnection process, working in a wide range of magnetized plasma systems with different spatial scales, ionization degrees, and collisionality. However, due to observational limitations, observations of {plasma sheet} tearing and the resulting plasmoids are rather scarce. This scarcity significantly hinders our understanding of the role of plasmoids in the reconnection process from an observational perspective. Using high-spatiotemporal multiwavelength observations from the Solar Dynamics Observatory, we traced the entire evolution of a coronal {plasma sheet}. Its formation was driven by the emergence of photospheric magnetic flux, followed by tearing, and eventual decay. The evolution of the {plasma sheet} exhibited two distinct stages. Initially, it rose rapidly, lengthened, and underwent tearing at a low frequency. Subsequently, its ascent slowed, it began to shorten, and the tearing occurred more frequently. Detailed analysis of the reconnecting {plasma sheet} focuses on heating, plasmoid dynamics (formation and ejection), and the resulting reconnection rate change. Two key heating processes are identified: {plasma sheet} tearing and coalescence involving plasmoids and magnetic cusps. More importantly, combining observations with analytical studies suggests that plasmoids are key carriers of magnetic flux fast transferring in the observed torn {plasma sheet}, and their formation and ejection significantly enhance the reconnection rate and facilitate the onset of fast reconnection. ;25 pages, 5 figures
We compare here several modern versions of SPH with a particular focus on the impact of gradient accuracy. We examine specifically an approximation to the "linearly exact" gradients (aLE) with standard SPH kernel gradients and with linearly reproducing kernels (RPKs) that fulfill the lowest order consistency relations exactly by construction. Most of the explored SPH formulations use shock dissipation (i.e. artificial viscosity and conductivity) with slope-limited reconstruction and parameters that trigger on both shocks and noise. We also compare with a recent particle hydrodynamics formulation that uses both RPKs and Roe's approximate Riemann solver instead of shock dissipation. Not too surprisingly, we find that the shock tests are rather insensitive to the gradient accuracy, but whenever instabilities are involved the gradient accuracy plays a crucial role. The reproducing kernel gradients perform best, but they are closely followed by the much simpler aLE gradients. The Riemann solver approach has some (minor) advantages in the shock tests, but shows some resistance against instability growth and at low resolution the corresponding Kelvin-Helmholtz simulations show substantially slower instability growth than the best shock dissipation approaches. Based on the battery of benchmark tests performed here, we consider a shock dissipation approach with reproducing kernels (our versions $V_3$ and $V_5$) as best, but closely followed by a similar version ($V_2$) that uses the simpler and computationally cheaper aLE gradients. ;20 pages, 17 figures
Galaxy clusters serve as a unique and valuable laboratory for probing cosmological models and understanding astrophysics at the high-mass limit of structure formation. Clusters that are dynamically relaxed are especially useful targets of study because of their morphological and dynamical simplicity. However, at redshifts z > 1, very few such clusters have been identified. We present results from new Chandra observations of the cluster SPT-CL J2215-3537 (hereafter SPT J2215), at z = 1.16, the second most distant relaxed, cool-core cluster identified to date. We place constraints on the cluster's total mass profile and investigate its thermodynamic profiles, scaling relations (gas mass, average temperature, and X-ray luminosity), and metal enrichment, resolving the cool core and providing essential context for the massive starburst seen in its central galaxy. We contextualize the thermodynamic and cosmological properties of the cluster within a sample of well-studied, lower-redshift relaxed systems. In this way, SPT J2215 serves as a powerful high-redshift benchmark for understanding the formation of cool cores and the evolution of massive clusters of galaxies. ;13 pages, 8 figures, 2 tables. Accepted in ApJ. Updated acknowledgments in v2
Compact radio sources such as pulsars and FRBs undergo scintillation in the interstellar medium (ISM) when scattered images interfere at the observer. ``Scintillometry'' refers to the range of techniques to extract astrometric information -- such as the angular positions of the images and distances to the scattering screen and source -- from scintillation observations. Pulsar scintillometry has proven to be a powerful technique, revealing rich and unexpected scattering phenomenology in the ISM and also shedding light on the emission physics of pulsars. FRB scintillometry stands to be a similarly powerful probe of FRB emission, as well as structure on tiny scales in ionized media beyond our galaxy, such as the circumgalactic medium (CGM). However, nascent FRB scintillation studies are far from the sophisticated lensing geometry reconstructions that have been performed for scintillating pulsars. In this paper, we introduce a novel theoretical framework for scintillometry, demonstrating that the full astrometric content of scintillation observations is contained within a single underlying observable: the instantaneous spatial wavefield. We relate the instantaneous spatial wavefield to more familiar concepts from the pulsar scintillometry literature, such as the dynamic spectrum. Using this framework, we discuss prospects and limitations for FRB scintillometry, towards the goal of full astrometric reconstructions of FRB lensing geometries. We show how key degeneracies in two-screen scattering measurements can be ameliorated. In addition, we discuss the possibility of inferring dispersion measure gradients across scintillation screens, which may shed light on the highly unconstrained physics of the cool CGM phase on tiny ($\sim 100\,{\rm au}$) scales.
(ABRIDGED BUT NOT TOO FAR) Multiplicity is ubiquitous among massive stars and its understanding is constrained by the sample of well-determined orbits. The immediate goal of M3W is to significantly increase the number of massive multiple systems with well-determined orbits and masses. We will address issues such as multiplicity statistics, the mass function in clusters and the field, the properties of binaries with compact companions and gravitational-wave progenitors, the origin and characteristics of runaways and their 3-D motions, the use of apsidal motion as a probe of stellar interiors, and the mass discrepancy between different methods (evolutionary, spectroscopic, and Keplerian). In this first paper, we present the project; describe the data and tools that will be used, including the disentangling UNWIND tool; analyse the very massive twin binary system GLS 11 448; and briefly introduce some of the following papers of the series. We present a new orbit for GLS 11 448, using UNWIND to obtain for the first time disentangled spectra for the full 3820-11 000 $\mathring{A}$ range for an OB spectroscopic binary. We derive the stellar parameters, making new stellar lines available for the study of O stars. The Aa and Ab components of GLS 11 448, both classified as O3.5 II(f*), are the two most massive O stars ever detected according to the evolutionary masses of 70$\pm$10 M$_\odot$ and 76$\pm$11 M$_\odot$ determined in this paper. We also report the first-ever detection of the interstellar He I 10 830 triplet in absorption in an OB-star sightline. As a by-product of the ISM model derived for UNWIND using GLS 11 448 and five other standard stars, we present the most detailed diffuse-interstellar-band (DIB) library ever built, with a total of 631 DIBs in the 4000-17 100 $\mathring{A}$ range, of which 37 are fitted with multiple-Gaussian profiles and 119 had never been identified before. ;12 pages main content + 8 pages appendix. Submitted to A&A. Version with minor fixes. Comments are welcome
Dark galaxies - systems rich in neutral hydrogen (HI) gas but with no stars - are a common prediction of numerous theoretical models and cosmological simulations. However, the unequivocal identification of such sources in current HI surveys has proven challenging. In this work, we present interferometric follow-up observations with the VLA of a former dark galaxy candidate J0139+4328, originally detected with the single-dish FAST telescope. The improved spatial resolution of the VLA data allow us to identify a faint optical counterpart and characterize the galaxy. Located at a distance of about 31 Mpc, J0139+4328 has a stellar mass of 3 x 10^6 M_Sun and a relatively high gas richness of M_HI/M_star = 18. Despite its high ratio, the galaxy is consistent, within the scatter, with the stellar-to-HI mass relation of HI-selected samples in the literature and with the baryonic Tully-Fisher relation (BTFR), although its kinematic measurement is subject to large uncertainties. This case highlights the potential of modern high-sensitivity HI surveys for detecting low surface brightness, gas-rich galaxies, but underscores the need for careful interpretation of low-resolution HI data, with potentially large centroid errors, and for sufficiently deep optical imaging to ensure robust identification. ;8 pages, 8 figures, accepted for publication in Astronomy & Astrophysics
The production of very-high-energy (VHE, $E_γ \gtrsim 100$ GeV) gamma rays resulting from the scattering of high-energy cosmic-ray protons off axion-like particles (ALPs) populating the dark matter halo of the Milky Way is investigated. By employing the latest instrument response functions for current and future facilities, we demonstrate that ground-based VHE gamma-ray observatories, such as H.E.S.S., CTAO, and SWGO, provide a promising and complementary avenue to probe the yet uncharted ALP-proton coupling $g_{ap}$. Our results show that these experiments can reach sensitivity to couplings above $10^{-2}$ in the $1 - 10^{8}$ eV ALP mass range, a region that remains largely unexplored by supernova and neutron star cooling observations. Interestingly, we demonstrate that this search channel is capable of probing QCD axion dark matter models, assuming two benchmark models for it: the Kim-Shifman-Vainshtein-Zakharov (KSVZ) Dine-Fischler-Srednicki-Zhitnitsky (DFSZ) models, specifically within the MeV mass range. These findings highlight the potential of VHE gamma-ray astronomy to provide unique constraints on the interaction between ALPs and the baryonic sector. ;8 pages, 3 figures
The success of the Large Interferometer For Exoplanets (LIFE) space mission depends on measuring the faint mid-infrared emission spectra of exoplanets while suppressing the glare of a host star. This requires an instrument capable of high-contrast nulling interferometry with exceptional sensitivity. While previous testbeds have proven the principle of deep, stable nulls, they have not combined high contrast with the high throughput and cryogenic operation required for LIFE. Here, we present the architecture of the Nulling Interferometry Cryogenic Experiment (NICE), a mid-infrared nulling testbed, to increase the technological readiness of LIFE. We derive the laboratory requirements necessary to validate the LIFE beam combiner and present the optical design of NICE. Finally, we report results from the ambient \enquote{Warm Bench} precursor, which has successfully demonstrated the required null depth ($< 10^{-5}$) using a polarized narrowband 4.7 um source, and the required throughput (> 17%) using one of the two nulling channels. ;Accepted for publication in JATIS (Journal of Astronomical Telescopes, Instruments, and Systems)
We report the discovery of bimodal structure in the drift rate distribution of upward-drifting burst clusters from the hyperactive repeating fast radio burst FRB 20240114A. Using unsupervised machine learning (UMAP dimensionality reduction combined with HDBSCAN density-based clustering) applied to 233 upward-drifting burst clusters from the FAST telescope dataset, we identify a distinct subpopulation of 45 burst clusters (Cluster C1) with mean drift rates 2.5x higher than typical upward-drifting burst clusters (245.6 vs 98.1 MHz/ms). Gaussian mixture modeling reveals strong evidence for bimodality (delta-BIC = 296.6), with clearly separated modes (Ashman's D = 2.70 > 2) and a statistically significant gap in the distribution (11.3 sigma). Crucially, we demonstrate that this bimodality persists when restricting the analysis to single-component (U1) burst clusters only (delta-BIC = 19.9, Ashman's D = 2.71), confirming that the result is not an artifact of combining single- and multi-component burst clusters with different drift rate definitions. The extreme-drift subpopulation also exhibits systematically lower peak frequencies (-7%), shorter durations (-29%), and distinct clustering in multi-dimensional feature space. These findings are suggestive of two spatially separated emission regions in the magnetosphere, each producing upward-drifting burst clusters with distinct physical characteristics, although confirmation requires observations from additional epochs and sources. ;arXiv admin note: This submission has been withdrawn because it does not meet arXiv's research content quality standards
The successive type-II solar radio bursts observed on 31 July 2012 by the Bruny Island Radio Spectrometer (BIRS) in the frequency range between 62 - 6 MHz is reported and analyzed. The first type-II radio burst shows clear fundamental and harmonic band structures, while only one band is observed for the second type-II radio burst and is considered as the harmonic band. The first type-II radio burst is observed in the frequency range of 57 - 27 MHz between 00:03 - 00:09 UT at the harmonic band. The second type-II burst is observed between 00:18 - 00:27 UT in the frequency range of 43 - 17 MHz. The type-II radio bursts are associated with a C6 class flare located at the south-eastern limb (S24E87) and a CME observed from STEREO and LASCO observations. The EUVI signatures of the CME is observed in the ST-B EUVI FOV between 23:56 (on 30 July 2012) to 00:06 UT (on 31 July 2012), and are observed in the ST-B COR1 FOV between 00:10 - 00:35 UT moving within an average speed of 725 + or - 101 km/s. The CME is observed in the LASCO C2 FOV after 00:12 UT as a partial halo CME moving with an average speed of 486 km/s. The height-time plot shows that the first type-II radio burst was formed by the CME-shock along the shock front and the second type-II radio burst along the shock-dip structure, probably the dip structure results from the shock transiting across the high dense streamer structure. The successive type-II bursts are most likely produced by the single CME shock and their interactions with the streamer structures. The first type-II radio burst by the CME shock and the second type-II radio burst by the CME shock-streamer interactions. ;Accepted for publication in Solar Physics
We study the effects of dark matter on the properties of hybrid neutron stars, in particular the influence on the mass-radius relation, the value of the maximum mass, and the hadron-quark phase transition. To single out the equilibrium configurations of dark-matter-admixed hybrid neutron stars (DHSs), we also study their radial oscillations. Both the stellar structure equations and the radial oscillation equations are solved for the two-fluid system, where the ordinary matter component and dark matter component couple only through gravity. For the ordinary matter components, we adopt the Brueckner-Hartree-Fock method for nuclear matter, and the Dyson-Schwinger or the field-correlator model for quark matter. For the dark matter component, we use a non-self-annihilating self-interacting fermionic model. We find that the presence of dark matter in DHSs leads to a decrease of the critical mass of the hadron-quark phase transition, a related possible onset of quark matter in dark-matter accreting stars, and a significant reduction of radial oscillation frequencies. ;11 pages, 8 figures
We present a strong lensing analysis of the double source plane lens J0946+1006 (colloquially "Jackpot" lens) to measure the inner dark matter density profile, the stellar-to-halo mass ratio, and the stellar initial mass function normalisation using a two component stellar plus dark matter mass model. The stellar mass follows a multi-Gaussian expansion light model with a free global mass-to-light ratio and an allowed radial $M/L$ gradient, while the dark matter is described by an elliptical generalised NFW halo. The double-source-plane geometry provides additional leverage against the mass-sheet transformation and helps constrain the radial mass profile. Despite allowing both a radial stellar $M/L$ gradient and a generalised NFW halo, the data prefer the canonical picture: an approximately constant stellar mass-to-light ratio with a Salpeter-like IMF normalisation, and a dark matter halo consistent with NFW. We infer $M_{\star} = 4.4^{+0.25}_{-0.39}\times 10^{11}\,M_{\odot}$ and an inner halo slope $γ_{\rm in}^{\rm halo} = 1.04^{+0.10}_{-0.14}$. The halo mass is $M_{200}^{\rm halo} = 1.11^{+0.37}_{-0.32}\times 10^{13}\,M_{\odot}$, implying $\log_{10}(M_{200}/M_{\star})=1.41^{+0.13}_{-0.14}$. At fixed halo mass, the inferred stellar mass lies $\sim0.1$ dex above typical literature stellar halo mass relations at similar redshift, which is comparable to the intrinsic scatter of these relations. We expect this approach to provide a practical template for future dark matter studies with the large double-source-plane lens samples from Euclid.
The Radio wave Observations at the Lunar Surface of the photoElectron Sheath (ROLSES) instrument is a radio telescope system designed to characterize the radio and plasma wave environment of the nearside lunar surface at frequencies between 2 kHz and 30 MHz. The ROLSES sensor consists of a set of four 2.5 meter radio monopole antennas onboard the Intuitive Machines (IM 1) lander, Odysseus. The antennas were stowed during launch and deployed after landing on the lunar surface using a frangibolt mechanism. The frequency range is well suited to observing radio waves at frequencies below 15 MHz that cannot be observed from Earth due to the ionospheric cutoff. Radio waves from the Sun, the Milky Way galaxy, Jupiter, Earth's auroral region, and ground-based radio transmitters were expected to be present on the lunar surface. Radio data from each of the 4 antennas, after passing through an isolating pre-amp and signal conditioning analog electronics, were digitized to 14 bits at 120 mega samples per second and then digitally processed by a Field Programmable Gate Array (FPGA) that performs onboard spectral analysis via a Fast Fourier Transform (FFT). Time averaged spectral values are then stored and returned. Also telemetered to Earth are raw waveforms (unprocessed time sequence data) that are useful in studying dust impact on ROLSES antennas. ROLSES data are sent to the lander and subsequently downlinked for further processing. ROLSES is part of NASA's Commercial Lunar Payload Services (CLPS) program. Odysseus landed close to the south pole at Malapert A (80 S). This paper describes the design and operations of the ROLSES instrument and presents initial observations made during transit and surface operations in February 2024. We also describe next version of this instrument (ROLSES 2) currently under development. ;24 paghes, 24 figures, 3 tables, submitted to Journal of Astronomical Instrumentation
Numerous microlensing survey programs have constrained the possibility of dark matter existing in the form of compact objects within the Galactic halo. These constraints on the dark matter fraction were derived under the assumption of isolated, widely separated objects. This work investigates microlensing by primordial black holes (PBHs) organized into clusters. In this scenario, it is necessary to account for both the influence of neighboring PBHs and the collective gravitational potential of the entire cluster, which significantly complicates the microlensing light curve. Events exhibiting such complex light curves elude detection in observational experiments such as MACHO, EROS, OGLE, POINT-AGAPE, and HSC. It is demonstrated that a significant fraction of PBH dark matter (up to 93\% for the models studied) remains undetected in these observational data. However, for all considered cluster models, a substantial population of PBHs still behaves as isolated lenses. Consequently, the clustering of PBHs does not completely eliminate the microlensing constraints on the PBH contribution to dark matter. ;10 pages, 9 figures; Accepted to Astronomy Letters
Quasi-topological theories of gravity are known to resolve black-hole singularities. We investigate whether the same mechanism can remove cosmological singularities. Focusing on non-polynomial curvature quasi-topological gravities in $d=4$ dimensions, we find three generic scenarios with the correct infrared limit but without a Big-Bang singularity, for universes filled with pure radiation or other standard matter. The first scenario yields a universe emerging from a de Sitter phase, a case for which the curvature invariants remain finite but the matter density diverges, albeit only at infinite affine distance. The second one corresponds to a bouncing universe, which requires a multi-valued Lagrangian. The third possibility is an asymptotically Minkowski origin, reminiscent of an eternally loitering universe. The matter energy density for this solution is non-singular even at infinite affine distance and does not enter a super-Planckian regime, but is instead approximately constant for the past eternity. ;17 pages, 4 figures
GECAM is a constellation of all-sky monitors in hard X-ray and gamma-ray band primarily aimed at high energy transients such as gamma-ray bursts, soft gamma-ray repeaters, solar flares and terrestrial gamma-ray flashes. As GECAM has the highest temporal resolution (0.1~$μ$s) among instruments of its kind, it can identify the so-called simultaneous events (STE) that deposit signals in multiple detectors nearly at the same time (with a 0.3~$μ$s window). However, the properties and origin of STE have not yet been explored. In this work, we implemented, for the first time, a comprehensive analysis of the STE detected by GECAM, including their morphology, energy deposition, and the dependence on the geomagnetic coordinates. We find that these STE probably result from direct interactions between high-energy charged cosmic rays and satellite. These results demonstrate that GECAM can detect, identify, and characterize high-energy cosmic rays, making it a Micro Cosmic-Ray Observatory (MICRO) in low Earth orbit. ;15 pages,17 figures
Chaotic trajectories in multi-body dynamical systems play a crucial role in designing low-energy trajectories in astrodynamics. However, predicting these trajectories is inherently difficult, as small errors in initial conditions can grow exponentially, making long-term predictions unreliable. This study introduces a novel methodology using Dynamic Mode Decomposition (DMD) to predict chaotic transitions in the periapsis Poincaré map of the circular restricted three-body problem (CRTBP). Unlike standard DMD approaches that model continuous equations of motion, the proposed method approximates deformations in a low-dimensional Poincaré map, enabling trajectory prediction and revealing transition structures. Two approaches are developed: the Local Deformation Map-based DMD (LDMD) and the Global Deformation Map-based DMD (GDMD). LDMD constructs discrete maps to track local deformations of periapsis sets, while GDMD captures global deformations using widely distributed data. A key advantage of this framework is that it approximates nonlinear chaotic transport using a linear operator, which enables fast prediction of periapsis evolution via matrix powers and direct access to geometric structures. To validate the proposed method, the deformation map is applied to design ballistic transfer trajectories to the Moon using a targeting strategy, demonstrating its practical relevance in astrodynamics. This work highlights the potential of data-driven modeling to bridge chaotic dynamics with systematic trajectory design. ;23 pages, 18 figures
We computed Lyapunov times ($T_L$) for a sample of trans-Neptunian objects (TNOs) and outer main-belt asteroids (MBAs) using three numerical approaches: the variational method and two implementations of the renormalization technique. For each object, $T_L$ was derived both from the nominal orbit and from ensembles of 1001 orbital clones, enabling direct comparison between single-orbit and ensemble-based estimates. Across the sample, the methods generally produced consistent results, though larger discrepancies were observed for some MBAs. TNOs, in contrast, displayed greater consistency across methods, likely due to fewer overlapping resonances. Importantly, clone ensembles provided more robust and reliable stability indicators than nominal-orbit computations. Median values from clone populations reduced method-dependent biases and revealed dynamical behaviors that would remain hidden in single-orbit analyses, especially for objects with poorly constrained orbits or evolving in resonant regions. While our study focused on a limited but diverse set of objects, the methodology can be directly extended to larger populations, offering a systematic framework for exploring the long-term stability and dynamical evolution of main-belt asteroids, trans-Neptunian objects or other classes of objects in the Solar System.
A new pulsar signal-processing pipeline has been developed for observing pulsars with the Diamond Array Radio Telescope at the Gauribidanur radio observatory. The array consists of 32 off-axis dual-polarised LPDAs, with a nominal gain of 22 dBi between 130 and 350 MHz and a 15-degree HPBW at 175 MHz for transit observations on pulsars. Custom-built receivers and real-time data-capture and analysis tools have been developed and used. Receiver output voltages from a transient buffer, as well as full-polar spectral data at both high and low resolutions, suitable for transient searches and pulsar studies. Additionally, full-polar folded profile archives are generated for known pulsars in subintegrations and both coherent and incoherent dedispersion. Custom-developed Python routines, FFT libraries, DSPSR, PSRCHIVE, and Presto modules have been used to build the pipeline. The functionalities of the pipeline were validated with artificially generated pulsar signals and strong celestial sources before it was released for routine observations. Presently, the pipeline is configured to observe pulsars between 170 and 196 MHz, with a daily cadence. Recorded data are reduced in-line immediately following each observation, nearly matching the observation time at a 1:1 ratio. An Intel i9 server captures the data, and an AMD R9 CPU does the primary data reduction. The archives are routinely backed up to a remote system via the internet. The paper presents the architecture of the signal processing pipeline developed, its validation, and initial polarimetric results observing five bright pulsars at 175 MHz. Results also include RM estimates and single-pulse study results for B0953+08, B0531+21, and B1133+16, as well as from monitoring the spin-down of the Crab pulsar over 200 days of observation. Finally, it presents a discussion on the potential improvements for the array.
Multi-Conjugate Adaptive Optics (MCAO) is essential for increasing the corrected Field-of-View (FoV) in astronomical imaging and potentially for free-space optical communications, particularly for small-aperture, transportable systems. We demonstrate the viability and performance of a Refractive-MCAO system utilizing a novel multi-actuator Deformable Lens (DL) as the wavefront correction element. Unlike conventional Deformable Mirrors (DMs), the transmissive nature of the DL simplifies the optical train, making it ideal for compact setups. Using a Shack-Hartmann Wavefront Sensor (SH-WFS) in conjunction with two DLs conjugated to different atmospheric layers, we achieved an extension of the isoplanatic patch up to three times the uncorrected atmospheric isoplanatic angle under moderate turbulence D/r0 = 2. We tested the MCAO system in a setup that emulates a free space optical communication for compact transportable system. In a double-channel, single-mode fiber coupling experiment we demonstrated the efficiency of this method.
Discoveries of ultra-massive magnetic white dwarfs (WDs) and peculiar pulsars have been proposed to originate in double white dwarf (DWD) mergers. There are three possible post-merger central remnants of non-explosive mergers: 1) a stable sub-Chandrasekhar WD; 2) a rapidly rotating super-Chandrasekhar WD; 3) a neutron star (NS). In this work, we explore the thermal transient arising from non-explosive DWD mergers that leave an NS remnant from the prompt collapse of the merged core. The transient is powered by the cooling of the expanding dynamical ejecta, with energy injection from magnetic dipole radiation, which depends on the dipole factor $D = B_d^2/P_0^4$, with $B_d$ and $P_0$ being the surface magnetic field strength and initial rotation period of the newborn NS. We simulate lightcurves in the Legacy Survey of Space and Time (LSST) bands and estimate the horizon and detection rates for these transients across a range of model parameters. We find LSST detection horizons upper limits ranging $30$--$820$ Mpc and corresponding detection rates $10^2$--$10^6$ yr$^{-1}$ for $\log D = 24$--$40$. Accounting for the survey cadence, we find that only configurations with $\log D = 36$--$40$ are detectable within $240$--$760$ Mpc, with detection rates $10^4$--$10^5$ yr$^{-1}$. Combined searches across surveys can compensate for the low cadence and improve the detection rates of fast and less energetic sources. Multi-wavelength campaigns can aid in detecting the spindown radiation at higher energies observable after the optical transient. Observations of these transients will provide direct evidence of the non-explosive DWD mergers, characterise the remnants and progenitor parameters, and the fraction of explosive and non-explosive mergers. ;12 pages, 6 figures, 3 tables, Published in JHEAP. Version 3 includes corrigenda
The formation and early evolution of protoplanetary disks are governed by a wide variety of physical processes during a gravitational collapse. Observations have begun probing disks in their earliest stages, and have favored the magnetically-regulated disk formation scenario. Disks are also expected to exhibit ellipsoidal morphologies in the early phases, an aspect that has been widely overlooked. We aim to describe the birth and evolution of the disk while accounting for the eccentric motions of fluid parcels. Using 3D radiative magnetohydrodynamic (MHD) simulations with ambipolar diffusion, we self-consistently model the collapse of isolated $1~\mathrm{M_\odot}$ and $3~\mathrm{M_\odot}$ cores to form a central protostar surrounded by a disk. We account for dust dynamics, and employ gas tracer particles to follow the thermodynamical history of fluid parcels. We find that magnetic fields and turbulence drive highly anisotropic accretion onto the disk via dense streamers. This streamer-fed accretion, occurring from the vertical and radial directions, drives vigorous internal turbulence that facilitates efficient angular momentum transport and rapid radial spreading. Crucially, the anisotropic inflow delivers material with an angular momentum deficit that continuously generates and sustains significant disk eccentricity ($e\sim 0.1$). Our results reveal ubiquitous eccentric kinematics in Class 0 disks, with direct implications for disk evolution, planetesimal formation, and the interpretation of cosmochemical signatures in Solar System meteorites. ;16 pages, 21 figures. Accepted for publication in A&A on 12/01/2025
The discovery of 2024 YR4 presented the planetary defense community with the most significant impact threat in almost two decades, reaching level 3 on the Torino scale. The community, now mature and well-organized, responded with a global observational effort. Astrometric measurements, forming the basis for orbital refinement and impact prediction, were a central component of this response. In this paper, we present the astrometric data collected by the international community, from the time of discovery until the object became too faint for all existing observational assets, including JWST. We also discuss the coordination role played by the International Asteroid Warning Network, and the importance of publicly available image archives to enable precovery searches.
Timing observation of pulsars orbiting around a supermassive black hole (SMBH) can measure the spacetime around the SMBH to a high precision and thus be a novel probe of the gravity theory. Future high-frequency surveys of the Galactic Centre (GC) region to be performed by the next-generation radio telescopes, such as the SKA, may discover pulsars that orbit around Sagittarius A* (Sgr A*), the SMBH dwelling in our GC. In this paper, we present a realistic pulsar-SMBH timing model based on the post-Newtonian equations of motion of the pulsar. Considering the expected timing precision in the future, we take into account several next-to-leading order light propagation time delays in the timing model. For the first time, we include the effects of proper motion of Sgr A*, which were expected to break the spin measurement degeneracy. We forecast the measurement precision of various parameters of Sgr A*, and discuss the data analysis procedure in the presence of red noise, which can be strong if the pulsar is a normal pulsar. The realistic timing model constructed in this study will serve as a useful tool in future searching and timing of pulsar-SMBH systems in the GC. ;28 pages, 12 figures
Background Eating disorders negatively influence athletes’ health and performance. To achieve a high level of performance and conform to cultural expectations regarding an athletic body type, female athletes often restrict their diets, which can lead to eating disorders. In addition to factors related to the sports environment, adolescent athletes are subject to changes caused by the maturation process. Therefore, the same factors may have different effects on eating disorder risk among adolescent and adult athletes. This study examined the relationship between eating disorder risk, specific aspects of the sports environment (sport type, level of competition [national and international], and training background), and individual aspects (body satisfaction and body mass index) in two groups of athletes: adolescents and adults. Methods The sample included 241 highly trained female athletes aged 12–30 years (M = 20.68, SD = 4.45) recruited from different sports clubs in Poland. The subgroup of adolescents consisted of 82 athletes, while the number of adult athletes was 159. The Eating Attitudes Test questionnaire was used to assess the eating disorder risk among the athletes. Body satisfaction was measured using the Feelings and Attitudes Toward Body Scale incorporated into the Body Investment Scale. Results Eating disorder risk was prevalent among 14.6% of the adolescent and 6.9% of the adult athletes. Significant associations between eating disorder risk and the studied variables were noted only among adolescent athletes. Univariate logistic regression analysis revealed that the occurrence of eating disorder risk was associated with participation in lean non-aesthetic sports (OR = 11.50, 95% CI: 3.58–37.09). Moreover, eating disorder risk was associated with athletes’ lower body satisfaction (OR = 0.80, 95% CI: 0.70–0.92). Body mass index was not included in the final regression model. Conclusions The study indicated that eating disorder risk in adolescent female athletes was related to sport type and body satisfaction. The findings showed that, in adolescent athletes, eating disorder risk was the most associated with practicing lean non-aesthetic sports. Coaches and athletes should be aware that eating disorder risk increases among individuals with a lower body image.
OBJECTIVE: When COVID-19 was declared a global pandemic, collegiate athletic departments faced the difficult decision to postpone or cancel sport activities. Aside from concerns of virus transmission, disruptions in sport impacted student-athletes broadly. This study aimed to investigate athletes’ experiences during the pandemic toward developing a better understanding of athletes’ attitudes about the virus and returning to sport. METHODS: Participants included 245 varsity student-athletes across NCAA sports and divisions who voluntarily completed an online survey between August and October 2020. RESULTS: A positive COVID-19 result during the pandemic was reported by 1 in 4 athletes. Mental health, cancelled seasons, and academic progress were rated the top three COVID-related concerns. Declines in physical fitness were reported by 50% of participants and change in weight was reported by 45%. While agreement that their athletic department was taking COVID-19 seriously was endorsed by 78% of athletes, 26% believed the proposed safety procedures lacked feasibility. Concern about speaking up if the procedures were not followed was endorsed by 79% of athletes. Of the participants, 88% agreed that they have a social responsibility to prevent the spread of COVID-19. Only 44% worried about being exposed to the virus during sport participation. Comfort returning to sport immediately was endorsed by 70% of student-athletes. Just over half said they would get vaccinated if the vaccine became available. CONCLUSIONS: Student-athletes have been affected by the pandemic in several ways. It is evident that athletes are concerned about the pandemic’s impact on mental and physical health and are eager to return to sport.
Background Musculoskeletal pain and its risk factors are rarely assessed in studies on adolescent athletes. The aim was to identify risk factors at baseline that were associated with the persistence or development of musculoskeletal pain at a two-year follow-up in adolescent sport school students, and to study cross-sectional associations at follow-up between musculoskeletal pain and sports performance. Methods Sport school students (79 boys and 52 girls, aged 14 years at baseline) were divided into infrequent (never–monthly) or frequent (weekly–almost daily) pain groups, based on frequency of pain using a pain mannequin. Logistic regression analyses were performed to study longitudinal associations between frequent pain at follow-up and baseline variables: pain group, number of regions with frequent pain, health status by EQ-5D, maturity offset (pre, average, or post peak height velocity), and sports (contact or non-contact). Linear regression analyses were used to study cross-sectional associations between pain groups and 20-m sprint, agility T-test, counter-movement jump, and grip strength at follow-up. Results were stratified by sex. Results A higher percentage of girls than boys reported frequent pain at follow-up (62% vs. 37%; p = 0.005). In boys, frequent pain at follow-up was associated with being pre peak height velocity at baseline (OR 3.884, CI 1.146–13.171; p = 0.029) and participating in non-contact sports (OR 3.429, CI 1.001–11.748; p = 0.050). In girls, frequent pain at follow-up was associated with having frequent pain in two or more body regions at baseline (OR 3.600, CI 1.033–12.542; p = 0.044), having a worse health status at baseline (OR 3.571, CI 1.026–12.434; p = 0.045), and participating in non-contact sports (OR 8.282, CI 2.011–34.116; p = 0.003). In boys, frequent pain was associated with worse performances in 20-m sprint and counter-movement jump, but not in agility T-test and grip strength. Conclusions Baseline risk factors for having frequent pain at follow-up were late maturation in boys, frequent pain and worse health status in girls, and participation in non-contact sports in both sexes. Boys with pain performed worse in sports tests. Coaches and school health-care services should pay attention to the risk factors and work towards preventing pain from becoming persistent.
National Athletic Trainers Associationoktober 2019Sport
Data on the psychosocial implications of sport specialization in pediatric athletes are lacking. Sport specialization often requires increased training hours and may predispose young athletes to social isolation, poor academic performance, increased anxiety, greater stress, inadequate sleep, decreased family time, and burnout. Sport specialization frequently introduces multiple stressors that could be expected to adversely affect mental health and function in young athletes and may increase the risk for burnout. This may be confounded by altered sleep duration and quality, increased drive for elite status, and perfectionistic personality types. The signs and symptoms of burnout in young athletes can be difficult to detect. It is important to be aware of the possible diagnosis of burnout in young athletes who display vague symptoms and a decrease in academic performance. The purpose of this review was to survey the available literature on sport specialization in young athletes and its association with mental health, sleep, the drive for success in sport, and burnout.
OBJECTIVES: To determine the rate of return to sport (RTS) in high-level athletes undergoing bilateral hip arthroscopy and report minimum 1-year patient-reported outcomes (PROs) for this cohort. We hypothesized that RTS rates, as well as sport-specific PROs, will be lower than the rates and scores previously reported in the literature for unilateral hip arthroscopy. METHODS: Data were prospectively collected on all patients undergoing hip arthroscopy at our institution from November 2011 to July 2018. Patients were included if they underwent bilateral hip arthroscopy and were either a high school, collegiate, or professional athlete prior to their first surgery. RTS was defined as a patient’s return to competitive participation in their respective sport. Additional PROs, including modified Harris Hip Score (mHHS), nonarthritic hip score (NAHS), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS), as well as complication rates and future surgeries were documented and compared for all patients. RESULTS: A total of 87 patients met inclusion criteria, for which follow-up was available for 82 (94.3%). At latest follow-up, 44 (53.7%) patients returned to sport. Of patients returning, 56% did so at the same level or higher. The most common reasons for not returning to sport were due to graduation/lifestyle change (47.4%) and hip symptoms (44.7%). Patients returning to sport had significantly higher PROs at latest follow-up relative to those who did not return, including for mHHS (93.7 vs. 87.5), NAHS (94.4 vs. 88.2), HOS-SSS (90.9 vs. 78.2) (P < 0.05). Rates of achieving PASS and MCID for mHHS were not significantly different. However, for HOS-SSS, patients who returned had significantly higher rates of achieving the MCID and PASS. CONCLUSION: Rates of RTS after bilateral hip arthroscopy are lower than those after unilateral hip arthroscopy. When comparing patients that returned to sports and those who did not return, we show that although both groups show a significant improvement in PROs following surgery, those that returned to sport achieved significantly higher scores in all outcome measures. In addition, patients returning to sports showed a significantly higher rate of attaining MCID and PASS scores for the HOS-SSS, possibly attesting to the validity of this score and its thresholds.
Background Exercise, play and sport are essential for the overall development of our children. Through movement, they experience their environment and continue to develop their motor skills and abilities. How different levels of exercise, play and sport affect motor performance will be examined in the present study. Methods Ten preschools with different physical education concepts were compared (sports preschools, recognized physical education preschools, preschool with physical education, preschool without physical education). In all, 855 children (461 male, 394 female, age 58.69 ± 7.75 months) participated in the study. The Karlsruher Motorik Screening für Kindergartenkinder KMS 3–6 was used to assess motor performance. The raw and Z‑scores of the individual test items as well as the total Z‑score were analyzed using analysis of variance (ANOVA). Results The raw scores show significant differences in all variables between the different preschools. The Z‑scores also show significant group differences with the exception of the standing long jump and the total Z‑score. Discussion The significant differences in raw scores, which are in favor of the sports preschool only in stand and reach, are almost entirely due to the significant difference in age and related developmental stage of the children. For the Z‑scores, the significant differences appear to be due to differences in emphasis in the implementation of exercise, play, and sports or lack of consistency in implementation. Furthermore, it is possible that the motor test used is not appropriate to differentiate between these groups. Conclusion The study should be repeated using a different motor test and the results compared. In addition, the programs for exercise, play and sports should be standardized. A longitudinal study could evaluate the effects of exercise, play and sports. Hintergrund Bewegung, Spiel und Sport sind essenziell für die Gesamtentwicklung unserer Kinder. Über Bewegung erfahren sie ihre Umwelt und entwickeln ihre motorischen Fähigkeiten und Fertigkeiten weiter. Aber wie wirkt sich ein unterschiedliches Maß an Bewegung, Spiel und Sport auf die motorische Leistungsfähigkeit aus? Dies soll in der vorliegenden Arbeit überprüft werden. Methodik Es wurden zehn Kindergärten mit unterschiedlichen Bewegungsförderungskonzepten miteinander verglichen (Sportkindergarten, Anerkannter Bewegungskindergarten, Kindergarten mit Bewegungsförderung, Kindergarten ohne Bewegungsförderung). 855 Kinder (461 m, 394 w, Alter 58,69 ± 7,75 Monate) nahmen an der Untersuchung teil. Zur Überprüfung der motorischen Leistungsfähigkeit wurde das Karlsruher Motorik-Screening für Kindergartenkinder KMS 3–6 eingesetzt. Die Roh- und Z‑Werte der einzelnen Testaufgaben sowie der Gesamt-Z-Wert wurden mittels ANOVA analysiert. Ergebnisse Bei den Rohwerten zeigen sich signifikante Unterschiede in allen Variablen zwischen den verschiedenen Kindergärten. Bei den Z‑Werten zeigen sich mit Ausnahme des Standweitsprungs und des Gesamt-Z-Werts ebenfalls signifikante Gruppenunterschiede. Diskussion Die signifikanten Unterschiede bei den Rohwerten, die nur bei der Rumpfbeuge zugunsten des Sportkindergartens ausfallen, sind fast ausschließlich auf den signifikanten Unterschied beim Alter und dem damit zusammenhängenden Entwicklungsstand der Kinder zurückzuführen. Bei den Z‑Werten scheinen die signifikanten Unterschiede auf unterschiedliche Schwerpunktsetzung bei der Umsetzung von Bewegung, Spiel und Sport oder auf mangelnde Konsequenz der Durchführung zurückzuführen sein. Weiterhin ist es möglich, dass das Testverfahren nicht geeignet ist, um zwischen diesen Gruppen zu differenzieren. Ausblick Die Studie sollte mit einem anderen Testverfahren wiederholt und die Ergebnisse miteinander verglichen werden. Zudem sollten die Programme für Bewegung, Spiel und Sport standardisiert werden. Über eine Langzeitstudie können so die Effekte von Bewegung, Spiel und Sport im Kindergarten evaluiert werden.
Air travel has an important role in the spread of viral acute respiratory infections (ARIs). Aircraft offer an ideal setting for the transmission of ARI because of a closed environment, crowded conditions, and close-contact setting. Numerous studies have shown that influenza and COVID-19 spread readily in an aircraft with one virus-positive symptomatic or asymptomatic index case. The numbers of secondary cases differ markedly in different studies most probably because of the wide variation of the infectiousness of the infector as well as the susceptibility of the infectees. The primary risk factor is sitting within two rows of an infectious passenger. Elite athletes travel frequently and are thus prone to contracting an ARI during travel. It is anecdotally known in the sport and exercise medicine community that athletes often contract ARI during air travel. The degree to which athletes are infected in an aircraft by respiratory viruses is unclear. Two recent studies suggest that 8% of Team Finland members traveling to major winter sports events contracted the common cold most probably during air travel. Further prospective clinical studies with viral diagnostics are needed to understand the transmission dynamics and to develop effective and socially acceptable preventive measures during air travel.
The sport of cycling consists of several individual sporting disciplines. Indeed, the world governing body for cycling, Union Cycliste Internationale (UCI), oversees the various cycling disciplines, with each of these disciplines having a number of subcategories. While several sports have undertaken prospective injury surveillance studies to understand the risks of their sport, plan event medical support and develop prevention programmes, limited high-quality studies have been undertaken within cycling. Indeed, this is the first prospective study of cycling injuries, particularly when considering the whole sport of cycling together. This current study will therefore aim to describe the incidence, severity, burden and nature of injuries within elite cycling in those athletes participating across 13 championship events at the inaugural World Championships, Glasgow, August 2023. Injury and exposure definitions will be in line with the IOC Consensus for injury surveillance in cycling. Injury incidence will be reported per 1000 athlete match hours or per number of athletes/cyclists and injury severity will be assessed via estimated median or mean days lost to training/competition. Meanwhile injury burden will be assessed via days of absence/1000 athlete match hours (or per number of athletes exposed) and all these results will be compared between male and female cyclists. This paper will also report the most common specific injuries for male and female cyclists (per 1000 hours of participation or per number of athletes exposed). Statistical differences will be tested for incidence or severity measures between sexes and will be compared to other sports.
Participation in physical and sports activities ‘PSA’ is a health factor. Sport is a form of physical activity ‘PA’ that helps to reach the recommended amount of PA per day. PSA promotions plans are launched by European states. However, sport participation also involves significant risks. Some sports injuries provoke long-term health negative outcomes. Promotion of sport participation faces a paradox. As a mean of healthy state, it implies some risks linked to the modalities of participation. To know the extent of these effects, epidemiological studies are needed. They help to determine adolescents’ subgroups that play sports, and among them, those at greater risk of injury. In France, previous studies are representative of the national population. However, no study estimated sport participation and injury risks factors while focusing on adolescent. Moreover, international findings showed that variation of results exists as function of the life environment of participants. We performed epidemiological retrospectives studies among the adolescent population of a specific French locality: the Bouches-du-Rhône. This one is characterized by a high-level of poverty and inequalities. We made the hypothesis, that results differ compared to those obtained at the national level. In addition of objectives measures of participation and injuries, we asked adolescents about the experiences that they like to live in their favorite sport. This knowledge could be useful to the development of promotion initiatives that are adapted to the tastes of this population. The questioning was inspired by the theory of experience, that suggest the importance of pleasure to understand people’s futures behaviors. We measured retrospective reports of pleasure in three characteristics forms of modern sports: risk-taking, progress and competition. Studies were conducted in schools and followed a sample design that respected the proportion of schools in priority education networks, and outside. Three analysis axes were performed. The first have had the purpose to measure the trends in sport participation between 2001 and 2015. The second have had the purpose to identify adolescents the most at risk of injuries while adding a variable never used in population-studies, the level of competition. The third axe attempted to validate our retrospective reports of pleasure scale and to identify different profiles of participants. Results shows a decline in sport participation, a greater risk of injury from the regional level of competition and an important variation of reported pleasure in experiences of competition and risk-taking. This thesis pointed out the need to develop studies with a narrower geographical scale that the national one. Results differs and could help to the development of local sports policies. In terms of promotion, girls with low socioeconomic status must be a priority. About prevention, an additional effort should be done from the regional level of competition, regardless sports activities.
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La pratique d’activité physique sportive ‘APS’ est un facteur de santé. Le sport est une forme d’activité physique ‘AP’ qui aide à atteindre les taux recommandés journaliers. Des plans de promotion des APS sont adoptés par les Etats Européens. Mais la pratique sportive recèle aussi des risques. Certaines blessures sportives génèrent des troubles de santé à long terme. La promotion de l’activité sportive est face à un paradoxe. Moyen d’être en bonne santé, elle comporte des risques liés aux modalités de pratique. Pour connaître l’ampleur de ces effets, des études épidémiologiques sont nécessaires. Elles aideront à déterminer les sous-groupes d’adolescents sportifs, et parmi eux, ceux qui sont à risque de blessure. En France, les études menées sont représentatives de la population nationale. En revanche, aucune n’a estimé la participation et les facteurs de risque en se focalisant sur la population adolescente. Aussi, la littérature internationale fait ressortir des variations de résultats en fonction de l’environnement de vie des participants. Nous avons donc réalisé des enquêtes épidémiologiques auprès de la population adolescente d’un département français spécifique : les Bouches-du-Rhône. Celui-ci se caractérise par un haut-niveau de pauvreté et d’inégalité. Par hypothèse, les résultats différent de ceux obtenus à l’échelon national. En plus des mesures objectives de participation et de blessures, nous avons questionné les adolescents sur les expériences qu’ils aimaient vivre dans leur sport préféré. Cette connaissance vise le développement d’initiatives de promotion de l’activité sportive adaptées aux goûts de cette population. Le questionnement, inspiré des théories de l’expérience, suggère l’importance du plaisir vécu pour comprendre les actes futurs des individus. Nous avons mesuré les plaisirs rapportés par référence à trois formes d’expériences caractéristiques du sport moderne : le risque, le progrès et la compétition. Les études, réalisées en établissement scolaire, ont suivi un protocole d’échantillonnage respectant les proportions d’établissements en zone d’éducation prioritaire et en dehors. Trois axes d’analyses ont été développés. Le premier avait pour objectif de mesurer l’évolution de la participation sportive de 2001 à 2015. Le deuxième avait pour but d’identifier les adolescents les plus à risque de blessure en utilisant une variable jamais utilisée dans les études de population, le niveau de compétition. Le troisième axe tentait de valider notre échelle de mesure des plaisirs éprouvés dans la pratique et de mettre en évidence des profils de participants. Les résultats obtenus montrent une baisse de la participation sportive, une surexposition au risque de blessure à partir du niveau régional de compétition et une appréciation très variée des expériences du risque et de la compétition. En revanche, l’expérience du progrès est valorisée par tous. Cette thèse met en évidence l’importance de développer des études dont l’échelle géographique est plus restreinte que le niveau national. Les résultats diffèrent et peuvent aider au développement de politiques sportives locales. En terme de promotion, les populations de filles défavorisées doivent être prioritaires. A propos de la prévention, un effort accru doit être concentré sur le niveau régional de compétition et au-delà, et cela quels que soient les sports.
OBJECTIVES: Female sport participation has steadily increased over the past several decades; however, inequalities still exist regarding participation rates, social norms, and available resources. It is possible that inequalities between male and female athletes extend beyond the performance of sport and into medical research. Therefore, the purposes of this systematic review were to 1) compare the number of published studies evaluating male vs. female athletes in various sports, and 2) identify which co-ed sports currently under-represent female athletes in the sports medicine literature. METHODS: All non-review research studies published from 2017-2021 in six top sports medicine journals were considered for inclusion. Only sports medicine studies that isolated athletes, reported study outcomes specific to male and/or female patients, provided study outcomes for specific sport(s), and evaluated three or fewer different sports, were included. The total number of studies reporting on male and/or female athletes were compared for all sports, and odds ratios (OR) were calculated. Comparisons of study design, level of sport participation, outcomes assessed, and study quality were also made based on subject sex. RESULTS: Overall, 669 studies were included the systematic review. Most of the included studies isolated male athletes (70.7%), while 8.8% isolated female athletes and 20.5% included both male and female athletes. Female athletes were more frequently studied in softball and volleyball, while male athletes were more commonly researched in baseball, soccer, American football, basketball, rugby, hockey, and Australian football. Notably, male athletes were largely favored in baseball/softball (91% vs. 5%, OR=18.2), rugby (72% vs. 5%, OR=14.4), soccer (65% vs. 15%, OR=4.3), and basketball (58% vs. 18%, OR=3.2). CONCLUSIONS: Sports medicine research has favored the evaluation of male athletes in most sports, including the majority of co-ed sports. Potential reasons for this inequality of research evaluation include availability of public and database data, financial and promotional incentive, a high percentage of sports medicine clinicians and researchers being male, and sex biases in sport. While the causes of these differences are multi-faceted, researchers should consider both sexes for study inclusion whenever possible and journals should support a more balanced representation of research publications regarding male and female athletes.
International audience;
Athlete Tirunesh Dibaba Sports Training Centre was established in 2009 at Asela (Arsi) under Ethiopian Sports Commission's Sports Academy, establishing programs intending to supply young competitive athletes to the national federations. But trainees with promising performance have been observed leaving from the training centre before they have reached their top performance. From the personal experience of the author, who has been working in this institution as a coach for five years, a high number of trainees are leaving the Centre before they finish their training years and no longer continue their training. What are the main causes leading young Ethiopian promising athletes to drop out from organized sport involvement? In this paper, number of possible factors for dropout has been evaluated, following a comprehensive fieldwork collection of data which include interviews with coaches, with the training centers' medical team and the trainees, but also questionnaires and analysis of secondary data organized by the registrar of the training centre about the trainees.
Background The primary aim of our systematic scoping review was to explore the factors influencing team function and performance across various industries and discuss findings in the context of the high-performance sport support team setting. These outcomes may also be used to inform future research into high-performance teamwork in sport. Methods A systematic scoping review of literature published in English since 2000 reporting team-based performance outcomes and included a performance metric that was ‘team outcome based’ was conducted using search of the Academic Search Ultimate, Medline, Business Source Ultimate, APA PsycInfo, CINAHL, SPORTDiscus, and Military database (ProQuest) using the terms: ‘team’, ‘function’ OR ‘dysfunction’, ‘Perform*’ OR ‘outcome’. Results Application of the search strategy identified a total of 11,735 articles for title and abstract review. Seventy-three articles were selected for full-text assessment with the aim to extract data for either quantitative or qualitative analysis. Forty-six of the 73 articles met our inclusion criteria; 27 articles were excluded as they did not report a performance metric. Eleven studies explored leadership roles and styles on team performance, three studies associated performance feedback to team performance, and 12 studies explored the relationship between supportive behaviour and performance. Team orientation and adaptability as key figures of team performance outcomes were explored in 20 studies. Conclusions Our findings identified 4 key variables that were associated with team function and performance across a variety of industries; (i) leadership styles, (ii) supportive team behaviour, (iii) communication, and (iv) performance feedback. High-performance teams wishing to improve performance should examine these factors within their team and its environment. It is widely acknowledged that the dynamics of team function is important for outcomes in high-performance sport, yet there is little evidence to provide guidance. This inequality between real-world need and the available evidence should be addressed in future research.
International audience;
Although sport activities have beneficial effects on health, excessive practice can lead to exercise addiction (EA). Previous studies have shown comorbidity between EA and alcohol use disorder, but how we could conciliate this observation with the positive effects of sport requests further research. This study aims to investigate the relationship between a proxy of alcohol use disorder and sport practice, more specifically focusing on EA, in a representative sample of the French population. Two thousand and two participants were recruited online and selected to represent the French adult population. Participants were asked to answer questions regarding sport activity, with the EAI questionnaire investigating exercise addiction, and alcohol consumption, with the CAGE questionnaire investigating a proxy of alcohol use disorder (score≥2). Alcohol use and alcohol use disorder were associated with a higher risk of exercise addiction and with more time devoted to collective sports (such as football) and two-person sports (such as tennis). The risk of alcohol use disorder seems to increase with the level of physical activity for collective sport, but to decrease for individual sports (such as running). Results support the hypothesis that the time devoted to different types of sport have different risks for exercise addiction (individual sports being more clearly concerned) and alcohol use disorder (especially for collective sports). Furthermore, the observed association between sport addiction and alcohol use disorder showes that the detrimental effect of sport on the risk of alcohol use disorder could be mediated by high level of sport activities. The social dimension of collective sports should be further investigated to facilitate preventive approaches.
OBJECTIVES: Distal femoral varus osteotomy is an effective treatment for unloading valgus knee malalignment; however, there is limited evidence on the ability for patients to return to athletics following this procedure. The purpose of this study is to report the functional outcomes and return to sport for athletic patients that underwent distal femoral varus osteotomy. METHODS: A consecutive series of athletic patients that had undergone distal femoral varus osteotomy for symptomatic lateral compartment overload and valgus knee malalignment were prospectively reviewed. All patients had a minimum of 2-year follow-up. Radiographs were assessed to determine pre-operative and post-operative alignment. Details regarding sport of interest, ability to return to sport, and timing of return were obtained from the patients. Prospective institutional registries were utilized to collect pre-operative and post-operative Marx Activity Scale and International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) scores; these values were compared using paired t-tests with p < 0.05 as the threshold for significance. RESULTS: A total of 13 patients with a mean age of 24 years (range: 17-35) and a mean follow-up of 43 months (range: 24-74) were included in the study. Six patients underwent medial closing wedge osteotomy, and seven patients underwent lateral opening wedge osteotomy. The mean alignment correction was 8 degrees (range: 5-13). Nine patients underwent one or more concomitant procedures at the time of the osteotomy: 6 lateral femoral condyle osteochondral allografts, 2 partial lateral meniscectomies, 1 lateral meniscus allograft transplantation, and 1 revision anterior cruciate ligament reconstruction. All patients were able to successfully return to their sport of choice (4 soccer, 2 softball, 2 running, 1 football, 1 basketball, 1 ice hockey, 1 volleyball, 1 rowing) at a mean of 11 months (range: 9-13). Furthermore, all 13 patients demonstrated an improvement in both Marx Activity Scale and IKDC scores after surgery. The mean improvement in Marx Activity Scale was 7 (mean pre-op: 4, mean post-op: 11, p < 0.01), and the mean improvement in IKDC score was 36 (mean pre-op: 53, mean post-op: 89, p < 0.01). CONCLUSION: Valgus knee malalignment results in overload of the lateral compartment and can severely limit one’s ability to participate in athletic activities. Correction of valgus knee malalignment through distal femoral varus osteotomy - either medial closing wedge or lateral opening wedge - can reliably result in improvement in function and return to sport, provided that concomitant chondral, meniscal, and ligamentous pathology is addressed. Therefore, distal femoral varus osteotomy should be considered in the athletic population for correction of symptomatic valgus knee malalignment.
OBJECTIVES: Prior studies report lower return to preinjury level of sport in patients who undergo bilateral anterior cruciate ligament (ACL) reconstructions compared to unilateral reconstructions, with the most common cited reason being fear of reinjury. The purpose of our investigation was to compare subsequent return rates and psychological readiness to return to sport (RTS) in patients who underwent bilateral versus unilateral ACL reconstructions. METHODS: A retrospective review of patients who underwent ACL reconstruction at a single academic institution between 2012-2021 with a minimum of 1-year follow-up was conducted. Patients were divided into bilateral and unilateral cohorts. Those who underwent bilateral ACL reconstruction were matched 1:3 to unilateral reconstruction based on age, sex, BMI, and primary sport. Primary outcomes included return to sport, level of RTS and psychological readiness to RTS, assessed by the validated ACL- Return to Sport after Injury (ACL-RSI) scale. Within the ACL-RSI questionnaire, fear and confidence to return to sport were specifically analyzed. Fear to RTS was measured on a scale of 0-100 with 0 equal to extremely fearful and 100 equal to no fear at all. Confidence to RTS was measured on a scale of 0-100 with 0 equal to not at all confidence and 100 equal to fully confident. Statistical analysis was performed in R studio, with chi-square used for categorical values and two-sided t-test for continuous. RESULTS: One hundred eighty-one patients were included, forty-three bilateral ACL reconstructions and one hundred thirty-eight unilateral. The unilateral cohort included 69 (50.0%) males and 69 (50.0%) females and the bilateral cohort included 22 (51.2%) males and 21 (48.8%) females. Mean age was 26.0 (14-56) in the unilateral cohort and 25.2 (14-50) in the bilateral cohort. Mean BMI was 25 (15.3-39.2) in the unilateral cohort and 28 (15.1-39.7[SM1] ) in the bilateral cohorts (p=.08). The percentage of individuals who returned to sport in the bilateral reconstruction cohort was not significantly different from those who returned in the unilateral cohort (79.6% vs 76.7%, p=0.85). There was no significant difference in psychological readiness to RTS (mean score 52.6 for bilateral and 47.4 for unilateral, p=0.31). There was also no significant difference between the level at which bilateral versus unilateral patients returned to sport. 59.6% unilateral returned to the same or higher level and 60.6% bilateral returned to the same or higher level, p=0.92. There was no significant difference in the reported scale of psychological readiness to return to sport (52.6 for bilateral and 47.4 for unilateral, p=0.31). When asked about fear to RTS, the mean scale response was 42.2 in the unilateral cohort and 46.5 in the bilateral (p=0.45). CONCLUSIONS: There is no difference in RTS and level of sport returned to between patients who undergo bilateral ACL reconstructions compared to patients who undergo unilateral ACL reconstructions. Psychological readiness, fear and confidence to return to sport were not different between unilateral and bilateral injuries.
National Athletic Trainers Associationapril 2019Sport
OBJECTIVE: To evaluate sex differences in incidence rates (IRs) of anterior cruciate ligament (ACL) injury by sport type (collision, contact, limited contact, and noncontact). DATA SOURCES: A systematic review was performed using the electronic databases PubMed (1969–January 20, 2017) and EBSCOhost (CINAHL, SPORTDiscus; 1969–January 20, 2017) and the search terms anterior cruciate ligament AND injury AND (incidence OR prevalence OR epidemiology). STUDY SELECTION: Studies were included if they provided the number of ACL injuries and the number of athlete-exposures (AEs) by sex or enough information to allow the number of ACL injuries by sex to be calculated. Studies were excluded if they were analyses of previously reported data or were not written in English. DATA EXTRACTION: Data on sport classification, number of ACL injuries by sex, person-time in AEs for each sex, year of publication, sport, sport type, and level of play were extracted for analysis. DATA SYNTHESIS: We conducted IR and IR ratio (IRR) meta-analyses, weighted for study size and calculated. Female and male athletes had similar ACL injury IRs for the following sport types: collision (2.10/10 000 versus 1.12/10 000 AEs, IRR = 1.14, P = .63), limited contact (0.71/10 000 versus 0.29/10 000 AEs, IRR = 1.21, P = .77), and noncontact (0.36/10 000 versus 0.21/10 000 AEs, IRR = 1.49, P = .22) sports. For contact sports, female athletes had a greater risk of injury than male athletes did (1.88/10 000 versus 0.87/10 000 AEs, IRR = 3.00, P < .001). Gymnastics and obstacle-course races were outliers with respect to IR, so we created a sport category of fixed-object, high-impact rotational landing (HIRL). For this sport type, female athletes had a greater risk of ACL injury than male athletes did (4.80/10 000 versus 1.75/10 000 AEs, IRR = 5.51, P < .001), and the overall IRs of ACL injury were greater than all IRs in all other sport categories. CONCLUSIONS: Fixed-object HIRL sports had the highest IRs of ACL injury for both sexes. Female athletes were at greater risk of ACL injury than male athletes in contact and fixed-object HIRL sports.
Appropriate dietary intake can improve athletes’ health and sport performance and is a direct result of eating behaviours. Therefore, assessing and shaping athletes’ eating behaviours and dietary intake is critical to the provision of sport nutrition services. As such, nutrition practitioners must also consider the determinants of eating behaviours. However, dietary intake, eating behaviours, and its determinants are inconsistently defined in the literature, requiring nutrition practitioners to navigate a complicated landscape of concepts and terminology. This is further complicated by limitations in practically measuring and influencing eating behaviours and dietary intake. The proposed Athlete Nutrition Development Approach was developed to aid practitioners in servicing decisions through the athlete development process, through a three-tiered approach to sport nutrition service delivery. Tier 1 addresses the determinants of eating behaviours, Tier 2 directly addresses eating behaviours and dietary intake, and Tier 3 addresses the consequences of dietary intake in relation to health and sport performance. Each tier includes tools for assessment and development.
BACKGROUND: Many patients live with long-term deficits in knee function after an anterior cruciate ligament reconstruction (ACLR). However, research is inconclusive as to which physical performance measure is most strongly related to long-term patient-reported outcomes after ACLR. HYPOTHESIS: Quadriceps strength would be most strongly associated with patient-reported long-term outcomes after ACLR. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 40 patients (29 female) consented and participated an average of 10.9 years post-ACLR (range, 5-20 years). Patients completed the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) Scale, Knee injury and Osteoarthritis Outcome Score Quality of Life (KOOS QoL) and Sport (KOOS Sport) subscales, and the Tampa Scale of Kinesiophobia (TSK-17). Each patient subsequently performed maximal isometric quadriceps contraction, a 60-second single-leg step-down test, and the single-leg single hop and triple hop for distance tests. Multivariate linear and logistic regression models determined how performance testing was associated with each patient-reported outcome when controlling for time since surgery, age, and TSK-17. RESULTS: When controlling for time since surgery, age at the time of consent, and TSK-17 score, maximal isometric quadriceps strength normalized to body weight was the sole physical performance measure associated with IKDC (P < 0.001), KOOS Sport (P = 0.006), KOOS QoL (P = 0.001), and LEFS scores (P < 0.001). Single-leg step-down, single hop, and triple hop did not enter any of the linear regression models (P > 0.20). Additionally, TSK-17 was associated with all patient-reported outcomes (P ≤ 0.01) while time since surgery was not associated with any outcomes (P > 0.05). CONCLUSION: Isometric quadriceps strength and kinesiophobia are significantly associated with long-term patient-reported outcomes after ACLR. CLINICAL RELEVANCE: These results suggest that training to improve quadriceps strength and addressing kinesiophobia in the late stages of recovery from ACLR may improve long-term self-reported function.
This work questions the articulation between federal and local sport policies, considered as a component of sport’ multi-level governance. It seeks to identify the topics, scales and factors which characterize federal-local relations. To do so, this doctoral thesis strongly draws from inductive methods, insofar as it aims to “dive into the heart” of these relations, in different contexts and levels.A first part takes place in a context of reform of the French governance of sport, instituted in 2018. It justifies to analyze the role played by the groups which represent federal and local sporting interests in this process. A second part questions national sports federations and local authorities’ bilateral relations: notably the determinants of their collaborations and conflicts. It develops a framework which suggests to analyze these relationships as an interactive process operating in a specific local context. It identifies the collaboration’s leveraging factors, e.g. the hosting of major events or the social profile of political leaders. The results have been confronted with a case study of the SaintQuentin-en-Yvelines Agglomeration’ sport policy, because of its partnerships contracted with the French federations of Cycling and Golf. The study treats the partnerships as a “product” of the local sport policy. With the cases of the Olympic Games and the Ryder Cup, this work puts in light the paradoxical role of major sporting event on local sport development. It leverages – opening a policy window – the ability for a national federation and a local authority to collaborate, while it opens new constraints for the structuration of these partnerships in the long run.
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Dans le contexte de réforme de la gouvernance du sport en France, l’analyse de l’articulation entre les politiques sportives fédérales et locales nécessite d’identifier les thématiques, niveaux d’échelles, déterminants et enjeux des relations entre les fédérations sportives et les collectivités territoriales. Il s’agit donc de « plonger au cœur » d’un phénomène social appréhendé comme l’une des composantes de la gouvernance multiscalaire du sport. Cette étude s’appuie, dans cette optique, sur une méthodologie principalement inductive (analyse documentaire, entretiens semi-directifs, observations immergées, etc.) ainsi que sur les apports théoriques de la sociologie de l’action publique.La première partie porte sur le « chantier » de la réforme de gouvernance du sport, engagé en France depuis 2018. Elle analyse le rôle joué par les groupes qui représentent les intérêts sportifs fédéraux et territoriaux dans cette séquence de la politique sportive nationale, envisagée comme un « terrain de jeu » fertile pour l’analyse. Une seconde partie s’intéresse aux ressources, représentations et intérêts de ces organisations en interrogeant les moteurs de leur convergence et/ou de leur confrontation. Ces résultats sont, enfin, affinés par une étude de cas portant sur la politique sportive de la communauté d’agglomération de Saint-Quentin-en-Yvelines. En les replaçant dans leur contexte historique, politique et organisationnel, il s’agit d’analyser les partenariats engagés par cette collectivité avec les fédérations françaises de cyclisme (autour de la programmation du Vélodrome National et de l’accueil des Jeux Olympiques et Paralympiques) et de golf (autour de l’organisation de la Ryder Cup).
BACKGROUND: Previous studies have evaluated functional outcomes and return-to-sport rates after proximal hamstring tendon (HT) repair. PURPOSE: To systematically review the literature in an effort to evaluate return-to-sport rates after proximal HT repair. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify studies that evaluated postoperative lower extremity function and return-to-sport rates in patients after proximal HT repair. Search terms used were “hamstring,” “repair,” “return to sport,” and “return to play.” Patients were assessed based on return to sport, return to preinjury activity level, type of HT tear (complete or partial), and interval from injury to surgery. Patients were also divided into subgroups depending on timing of the surgical intervention: early, <1 month; delayed, 1 to 6 months; and late, >6 months from the time of injury. RESULTS: Sixteen studies (one level 2, five level 3, ten level 4) met the inclusion criteria, including 374 patients with a complete proximal HT tear (CT group) and 93 patients with a partial proximal HT tear (PT group), with a mean follow-up of 2.9 years. Overall, 93.8% of patients (438/467) returned to sport, including 93.0% (348/374) in the CT group and 96.8% (90/93) in the PT group (P = .18). The mean time to return to sport was 5.7 months, and 83.5% of patients (330/395) returned to their preinjury activity level. The early group demonstrated the greatest rate of return to sport at 94.4% (186/197) as well as the quickest time to return at a mean of 4.8 months, although this was not found to be statistically significant. CONCLUSION: Over 90% of patients undergoing repair of a complete or partial proximal HT tear can be expected to return to sport regardless of the tear type. Early surgical interventions of these injuries may be associated with a quicker return to sport, although the rate of return to sport does not differ based on timing of the surgical intervention.
BACKGROUND: Failure rates of up to 20% have been reported after fasciotomy for chronic exertional compartment syndrome (CECS). There is some evidence that postoperative failure and complication rates are higher in the posterior compartments of the lower leg than the anterolateral compartments. Isolated compartment surgery may put patients at risk of requiring revision surgery because of the risk of developing posterior compartment disease. HYPOTHESIS: Isolated anterolateral fasciotomy for CECS, in the absence of posterior compartment symptoms, produces satisfactory functional outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between 2006 and 2012, patients who had positive intracompartment pressure-testing findings and who underwent isolated anterolateral fasciotomy release for CECS were given a self-administered questionnaire. The minimum follow-up was 3 years. The questionnaire addressed time to return to sport and ongoing symptoms. A visual analog scale was used to assess pain during exercise before and after surgery (score: 0, no pain; 10, worst pain imaginable); overall satisfaction with the procedure was assessed as well. Of 31 eligible patients, 20 patients (36 legs operated on) were assessed. RESULTS: Postoperatively, 90% of participants returned to the same or higher level of sport. The mean pain score during exercise before surgery was 8.17, whereas it was 1.74 after surgery. The overall mean patient satisfaction score was 8.64. Only 1 leg (2.8%) went on to develop posterior compartment syndrome. CONCLUSION: Isolated anterolateral fasciotomy for CECS produced excellent functional outcomes. Our rate of recurrence was low compared with those found in the literature, and 90% of participants returned to their same or higher level of sport postoperatively.
Background Patients with axial spondyloarthritis (axSpA) often experience chronic pain and inflammation, resulting in physical impairments, reduced mobility and decreased physical activity. The modified short questionnaire to assess health-enhancing physical activity (mSQUASH) was developed to assess daily physical activity in patients with axSpA. Objective To translate, cross-culturally adapt and linguistically validate the original mSQUASH into German for patients with axSpA. Methods The original mSQUASH was translated from Dutch into German using a multistep process (Beaton method) with forward–backward translations into German by bilingual Dutch-German lay people and experts. Any remaining discrepancies were resolved by a scientific committee, resulting in a prefinal German version. Field testing with cognitive debriefing interviews with patients with axSpA from diverse backgrounds led to a final German version. Results Minor discrepancies, primarily related to formalities, semantic errors and syntax were found during translations. These were addressed, resulting in slight wording modifications. The prefinal German version was validated through cognitive debriefing by 10 patients with axSpA, confirming its linguistic validity and equivalence to the Dutch version. Conclusion Overall, this study confirmed the final German mSQUASH as a comprehensive measurement instrument for daily physical activity. It can now be used as a patient-reported outcome by German patients with axSpA. This can enable cross-linguistic comparisons and expanding its utility across language barriers. Hintergrund Patienten mit axialer Spondyloarthritis (axSpA) leiden oft unter chronischen Schmerzen und entzündlichen Veränderungen, die zu Einschränkungen der körperlichen Funktionsfähigkeit, eingeschränkter Beweglichkeit und verminderter körperlicher Aktivität führen können. Der „Modified-Short QUestionnaire to Assess Health-enhancing physical activity (mSQUASH)“, ein Fragebogen zur Erfassung gesundheitsfördernder körperlicher Aktivität, wurde entwickelt, um die tägliche körperliche Aktivität bei Patienten mit axSpA zu messen. Ziel Es erfolgten eine Übersetzung, interkulturelle Anpassung und linguistische Validierung des originalen mSQUASH ins Deutsche für Patienten mit axSpA. Methoden Der ursprüngliche mSQUASH-Fragebogen wurde in einem mehrstufigen Prozess (Beaton-Methode) der interkulturellen Anpassung mit Vorwärts-Rückwärts-Übersetzungen vom Niederländischen ins Deutsche durch zweisprachige niederländisch-deutsche Laien und Experten übersetzt. Verbleibende Abweichungen wurden in einer Expertengruppe besprochen, was zu einer vorläufigen deutschen Version führte. Kognitive Befragungen von Patienten mit axSpA mit unterschiedlichen soziodemografischen Hintergründen führten dann zur finalen deutschen Version. Ergebnisse Während der Übersetzungen wurden geringfügige Abweichungen hauptsächlich in Bezug auf Formalitäten, semantische Fehler und Syntax festgestellt. Diese wurden angepasst, was zu geringfügigen Änderungen in der Formulierung führte. Die vorläufige deutsche Version wurde durch kognitive Befragungen mit 10 Patienten mit axSpA validiert, wodurch ihre linguistische Validität und Äquivalenz zur niederländischen Version bestätigt wurde. Diskussion Insgesamt bestätigte die Untersuchung, dass der finale deutsche mSQUASH ein geeignetes Instrument zur Erfassung der täglichen körperlichen Aktivität ist. Daher kann der vorliegende Fragebogen als Messinstrument in klinischen Studien und in der klinischen Praxis bei deutschsprachigen Patienten mit axSpA eingesetzt werden. Dies kann länderübergreifende Vergleiche ermöglichen und erweitert den Nutzen des Fragebogens über Sprachbarrieren hinweg.
This thesis investigates the extraction and simulation of fighter interactions, mainly for boxing, by utilizing deep learning techniques: human motion estimation from videos, reinforcement learning-based imitation learning, and physics-based character simulation. In the context of sport analysis from videos, a benchmark protocol is proposed where various contemporary 2D human pose extraction methods are evaluated for their precision in deriving positional information from RGB video recordings of boxers during complex movements and unfavorable filming circumstances. In a second part, the thesis focuses on replicating realistic fighter interactions given motion and interaction data through an innovative methodology for imitating interactions and motions among multiple physically simulated characters derived from unorganized motion capture data. Initially, this technique was demonstrated for simulating light shadow-boxing between two fighters without significant physical contact. Subsequently, it was expanded to accommodate additional interaction data featuring boxing with actual physical contact and other combat activities, along with handling user instructions and interaction restrictions.
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Cette thèse étudie l’extraction et la simulation des interactions entre combattants, principalement pour la boxe, en utilisant des techniques d’apprentissage profond : l’estimation du mouvement humain à partir de vidéos, l’apprentissage par imitation basé sur l’apprentissage par renforcement, et la simulation de personnages basée sur la physique. Dans le contexte de l’analyse sportive à partir de vidéos, un protocole de référence est proposé dans lequel diverses méthodes contemporaines d’extraction de poses humaines en 2D sont évaluées pour leur précision à dériver des informations positionnelles à partir d’enregistrements vidéo RVB de boxeurs lors de mouvements complexes et dans des circonstances de tournage défavorables. Dans une deuxième partie, la thèse se concentre sur la reproduction d’interactions réalistes entre boxeurs à partir de données de mouvement et d’interaction grâce à une méthodologie innovante permettant d’imiter les interactions et les mouvements de plusieurs personnages simulés physiquement à partir de données de capture de mouvement non organisées. Initialement, cette technique a été démontrée pour simuler une boxe légère entre deux combattants sans contact physique significatif. Par la suite, elle a été étendue pour prendre en compte des données d’interaction supplémentaires concernant la boxe avec du contact physique réel et d’autres activités de combat, ainsi que pour gérer les instructions de l’utilisateur et les restrictions d’interaction.
OBJECTIVES
To investigate the mid-term outcomes of exercise therapy in patients with femoroacetabular impingement syndrome (FAIS).
DESIGN
Follow-up study.
SETTING
Clinical setting.
PARTICIPANTS
Twenty-six patients with FAIS who completed a 12-week semi-standardized, progressive exercise therapy program.
MAIN OUTCOME MEASURES
At a mid-term follow-up of 4.6 years, therapy outcome was assessed using (i) the Global Treatment Outcome questionnaire for hip pain, (ii) the Hip Outcome Score (HOS) for hip pain and function in activities of daily living (ADL) and Sport and (iii) the Hip Sports Activity Scale (HSAS) for sport activity level. Mid-term outcomes were compared to pre-symptomatic, pre-therapy, as well as to short-term follow ups (18 weeks).
RESULTS
In patients who completed the exercise program and did not undergo hip surgery (N = 19), mid-term HOS ADL and HOS Sport (P = 0.002) were higher than pre-therapy, and comparable to the 18-week follow-up. Mid-term HSAS was lower than the pre-symptomatic status (P = 0.022), but comparable to the 18-week follow-up.
CONCLUSION
At a mid-term follow-up of 4.6 years, FAIS patients with no subsequent hip surgery maintained the good exercise therapy outcomes and the level of sport activity achieved at short term.
Background Patients with intermediate risk thyroid cancer face the decision of whether or not to undergo radioactive iodine (RAI) treatment after total thyroidectomy. This process is challenging due to the unclear risks and benefits of RAI treatment for intermediate risk disease. The study identified the decisional needs of patients offered RAI treatment for thyroid cancer to inform the development of a web-based patient decision aid (PtDA). Method We used purposive sampling to recruit 23 adult patients with thyroid cancer ( M _age = 39.1; 83% female) from three metropolitan hospitals who were offered RAI treatment. Participants completed an online survey before taking part in one of four 2-h focus groups moderated by a clinical psychologist. Semi-structured interviews explored patients’ experiences, decisional needs, and recommended elements for a PtDA. Two raters independently coded transcripts and used content analysis to analyze qualitative data. Results Content analysis revealed three broad domains: (1) the range of patient involvement in the RAI treatment decision-making process, (2) personal values-based decisional outcomes, and (3) decision aid content recommendations on the basis of patients’ knowledge gaps about RAI treatment. Patients’ recommendations included the need for information on the RAI dose and common side effects, risk stratification, safety precautions for radioactivity, low-iodine diet guidance, and financial costs. Conclusion The study provides patient insights for a targeted web-based PtDA that integrates personal values, risk information, and logistical considerations to support informed decision-making about RAI treatment. Future research to examine the benefits of PtDAs for treatment of intermediate-risk thyroid cancer is needed.
Background This study aimed to investigate the association between central sensitivity to thyroid hormones and all-cause mortality in euthyroid patients with chronic kidney disease (CKD). Methods Data on thyroid function indicators and all-cause mortality for CKD patients were extracted from the NHANES database (2007–2012). Central sensitivities to thyroid hormones were mainly evaluated by Thyroid Feedback Quantile-based Index (TFQI). The Kaplan–Meier method, Cox proportional hazards regression model and subgroup analysis were performed to explore the potential associations between thyroid hormone sensitivity and all-cause mortality. Results A total of 1303 euthyroid CKD patients were enrolled in this study. After a median follow-up of 115 months, 503 participants died. The Kaplan-Meier analysis demonstrated significant variations in survival rates among different levels of TFQI ( P = 0.0015). Cox regression analysis showed that increased levels of TFQI were independent risk factors for all-cause mortality after adjusting for multiple confounding factors (HR = 1.40, 95% CI 1.10–1.79, P = 0.007). Subgroup analysis did not reveal any significant variation in the association between TFQI and all-cause mortality between the subgroups assessed ( P for interaction > 0.05). Conclusion Our study suggests that impaired thyroid hormone sensitivity might be linked to increased mortality in euthyroid CKD patients. Further research is needed to confirm and explore this association.
Thyroid scintigraphy is vital for diagnosing thyroid disorders, yet deep learning (DL) models in this domain often struggle with limited, imbalanced datasets. This study investigates the impact of three data augmentation strategies including Stable Diffusion (SD), Flow Matching (FM), and Conventional Augmentation (CA), on enhancing DL-based classification of disease. Anterior thyroid scintigraphy images from 2,954 patients across nine medical centers were classified into four categories: Diffuse Goiter (DG), Nodular Goiter (NG), Normal (NL), and Thyroiditis (TI). Data augmentation was performed using CA as well as various SD and FM models, creating 18 distinct scenarios. Each augmented dataset was used to train a ResNet18 DL-classifier. Model performance was assessed using class-wise and average precision, recall, F1-score, AUC, and image fidelity metrics (FID and KID). FM-based methods demonstrated top-tier performance, with the Original dataset combined with FM (O+FM) configuration achieving the highest micro, macro, and weighted F1-scores (0.78, 0.77, 0.78) and AUC values (0.95, 0.93, 0.94). While the O+FM+CA model also yielded excellent, balanced results, O+FM was statistically superior, indicating that high-fidelity generative augmentation can supersede conventional heuristics. FM also produced the most realistic images, achieving the lowest overall FID (0.66) and KID (0.83). Among the SD variants, SD1 combining image and prompt inputs was the most effective (macro F1: 0.76; FID: 4.17), showing that physician-generated prompts provide critical clinical context. Integrating FM and clinically-informed SD augmentation substantially improves thyroid scintigraphy classification, highlighting the importance of advanced generative models for robust training on limited datasets. The code is available at: https://github.com/MaziarSabouri/Stable-Diffusion-Scintigraphy-Augmentation
In this study, we develop a new CAD system for accurate thyroid cancer classification with emphasis on feature extraction. Prior studies have shown that thyroid texture is important for segregating the thyroid ultrasound images into different classes. Based upon our experience with breast cancer classification, we first conjuncture that the Discrete Cosine Transform (DCT) is the best descriptor for capturing textural features. Thyroid ultrasound images are particularly challenging as the gland is surrounded by multiple complex anatomical structures leading to variations in tissue density. Hence, we second conjuncture the importance of localization and propose that the Local DCT (LDCT) descriptor captures the textural features best in this context. Another disadvantage of complex anatomy around the thyroid gland is scattering of ultrasound waves resulting in noisy and unclear textures. Hence, we third conjuncture that one image descriptor is not enough to fully capture the textural features and propose the integration of another popular texture capturing descriptor (Improved Local Binary Pattern, ILBP) with LDCT. ILBP is known to be noise resilient as well. We term our novel descriptor as Binary Pattern Driven Local Discrete Cosine Transform (BPD-LDCT). Final classification is carried out using a non-linear SVM. The proposed CAD system is evaluated on the only two publicly available thyroid cancer datasets, namely TDID and AUITD. The evaluation is conducted in two stages. In Stage I, thyroid nodules are categorized as benign or malignant. In Stage II, the malignant cases are further sub-classified into TI-RADS (4) and TI-RADS (5). For Stage I classification, our proposed model demonstrates exceptional performance of nearly 100% on TDID and 97% on AUITD. In Stage II classification, the proposed model again attains excellent classification of close to 100% on TDID and 99% on AUITD. ;15 Pages, 7 Figures, 5 Tables
Precise segmentation of papillary thyroid microcarcinoma (PTMC) during ultrasound-guided radiofrequency ablation (RFA) is critical for effective treatment but remains challenging due to acoustic artifacts, small lesion size, and anatomical variability. In this study, we propose DualSwinUnet++, a dual-decoder transformer-based architecture designed to enhance PTMC segmentation by incorporating thyroid gland context. DualSwinUnet++ employs independent linear projection heads for each decoder and a residual information flow mechanism that passes intermediate features from the first (thyroid) decoder to the second (PTMC) decoder via concatenation and transformation. These design choices allow the model to condition tumor prediction explicitly on gland morphology without shared gradient interference. Trained on a clinical ultrasound dataset with 691 annotated RFA images and evaluated against state-of-the-art models, DualSwinUnet++ achieves superior Dice and Jaccard scores while maintaining sub-200ms inference latency. The results demonstrate the model's suitability for near real-time surgical assistance and its effectiveness in improving segmentation accuracy in challenging PTMC cases.
Medical ultrasound videos are widely used for medical inspections, disease diagnosis and surgical planning. High-fidelity lesion area and target organ segmentation constitutes a key component of the computer-assisted surgery workflow. The low contrast levels and noisy backgrounds of ultrasound videos cause missegmentation of organ boundary, which may lead to small object losses and increase boundary segmentation errors. Object tracking in long videos also remains a significant research challenge. To overcome these challenges, we propose a memory bank-based wavelet filtering and fusion network, which adopts an encoder-decoder structure to effectively extract fine-grained detailed spatial features and integrate high-frequency (HF) information. Specifically, memory-based wavelet convolution is presented to simultaneously capture category, detailed information and utilize adjacent information in the encoder. Cascaded wavelet compression is used to fuse multiscale frequency-domain features and expand the receptive field within each convolutional layer. A long short-term memory bank using cross-attention and memory compression mechanisms is designed to track objects in long video. To fully utilize the boundary-sensitive HF details of feature maps, an HF-aware feature fusion module is designed via adaptive wavelet filters in the decoder. In extensive benchmark tests conducted on four ultrasound video datasets (two thyroid nodule, the thyroid gland, the heart datasets) compared with the state-of-the-art methods, our method demonstrates marked improvements in segmentation metrics. In particular, our method can more accurately segment small thyroid nodules, demonstrating its effectiveness for cases involving small ultrasound objects in long video. The code is available at https://github.com/XiAooZ/MWNet. ;Chenxiao Zhang and Runshi Zhang contributed equally to this work. 14 pages, 11 figures
Purpose: Hashimoto’s thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFβ1) in HT patients with different patterns of thyroid function. Methods: A total of 29 HT patients, with a median age of 52 years (21–68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFβ1 assayed by ELISA. Results: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = −0.60, P < 0.01). Serum TGFβ1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFβ1 (r = −0.75, P < 0.01). Conclusions: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFβ1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFβ1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT.
Background This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. Methods In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. Results According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P < 0.05). Furthermore, AI assistance significantly improved the performance of junior radiologists in the diagnosis of thyroid nodules, and their diagnostic performance was comparable to that of senior radiologists when pathological results were taken as the gold standard (all p > 0.05). Conclusions The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.
Background Thyroid disorders are common endocrine diseases worldwide, with an increasing incidence in recent years. However, the relationship between long-term carbon monoxide (CO) exposure and various types of thyroid disorders remains unclear. This study aimed to explore the association between long-term CO exposure and the odds of thyroid disorders in a Chinese adult population. Methods Data from the Thyroid Disease, Iodine Nutrition, and Diabetes Epidemiology (TIDE) study were used, including 73,900 adult participants from 31 provinces in mainland China. Individual CO exposure levels were assessed using the Space Time Extra Trees model (1 × 1 km high-resolution data). Thyroid disorders were defined according to standard criteria, incorporating serum antibody levels (for thyroid autoimmunity [TA], thyroglobulin antibody [TgAb], and thyroid peroxidase antibody [TPOAb]) and thyroid function tests (for overt and subclinical hyper- and hypothyroidism). Multivariable generalized linear models were used to compute adjusted odds ratios (ORs). Results Higher levels of 5-year average CO exposure were associated with an increased prevalence of TA and TgAb positivity. Participants in the highest CO exposure quartile had 1.19 times the odds of TA and 1.33 times the odds of TgAb positivity compared to those in the lowest quartile. The exposure-response curve revealed a linear positive correlation between CO concentrations and the prevalence of TA and TgAb positivity, independent of iodine status and other confounders. No significant associations were observed for other thyroid disorders. Conclusion In this large cross-sectional study, long-term exposure to higher ambient CO levels was associated with increased odds of TA, particularly TgAb positivity, with evidence of a dose-response relationship. These findings suggest a potential link between ambient CO exposure and TA, though causality cannot be established due to the cross-sectional design. Further longitudinal research is needed to elucidate causal mechanisms and potential interactions with other environmental pollutants.
American Association of Clinical Endocrinologyjanuari 2025Schildklier
BACKGROUND: Thyroglobulin and antithyroglobulin antibodies are used in the surveillance of differentiated thyroid carcinomas. In patients with differentiated thyroid carcinoma who require intravenous immunoglobulin for autoimmune or malignant conditions, surveillance of antithyroglobulin antibodies is challenging. We present a case of a patient with papillary thyroid carcinoma who showed fluctuating antithyroglobulin antibody levels while receiving intravenous immunoglobulin. CASE PRESENTATION: A 41-year-old woman underwent total thyroidectomy, central and left modified neck dissection, and radioactive iodine ablation for multifocal papillary thyroid carcinoma with features of oncocytic and warthin-like variant and metastasis to 1 of 28 left lateral and 1 of 10 central lymph nodes. Ten years later, she contracted COVID-19 and developed COVID-19-associated encephalopathy for which she received intravenous immunoglobulin for 7 months. Five months after intravenous immunoglobulin initiation, surveillance thyroglobulin was <0.8 ng/mL (liquid chromatography with mass spectrometry, <0.4 ng/mL) and antithyroglobulin antibodies increased from undetectable to 97 IU/mL (chemiluminescent immunoassay, ≤1 IU/mL). After the final intravenous immunoglobulin dose, antithyroglobulin antibody levels progressively decreased, reaching 1 IU/mL (chemiluminescent immunoassay, ≤1 IU/mL) 6 months posttreatment. Neck ultrasounds showed no evidence of disease recurrence. DISCUSSION: Intravenous immunoglobulin can affect monitoring of patients with differentiated thyroid carcinomas due to passive transfer of pooled donor antibodies, including antithyroglobulin antibodies. Newly detectable antithyroglobulin antibodies in this patient were likely due to measured donor antithyroglobulin antibodies via intravenous immunoglobulin rather than cancer recurrence. CONCLUSION: In patients with differentiated thyroid carcinomas receiving intravenous immunoglobulin, the presence of donor antithyroglobulin antibodies should be considered when antithyroglobulin antibodies are newly detectable.
Purpose Brain metastasis (BrM) resulting from thyroid cancer remains poorly characterized despite its significant impact on patient outcomes. The current study aims to combine clinical features with genomic sequencing data to identify potential prognostic variables in thyroid cancer BrM. Methods A single-center retrospective cohort study consisting of 1,606 patients who were diagnosed with thyroid cancer and seen at an NCI-designated Comprehensive Cancer Center for a brain magnetic resonance imaging (MRI) between January 1, 2000 and December 31, 2024 was performed, and patients with BrM were identified. Clinical and genomic data were collected, with the latter obtained from the Memorial Sloan Kettering-Integrating Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) clinical sequencing platform. Results 154 patients (median age at BrM diagnosis = 62.4 years [range 18.9–92.5], 69 [45%] male, 85 [55%] female) participated in the study. The median OS from BrM diagnosis was 1.53 years (95%CI = 1.05–1.95 years). 1- and 3-year OS rates were 59.28% (95%CI = 51.02–66.61%) and 33.27% (95%CI = 25.54–41.17%), respectively. In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥ 2, presence of leptomeningeal or dural-based metastasis, whole-brain radiotherapy treatment, pre-BrM diagnosis tyrosine kinase inhibitor treatment, and histological subtypes of poorly-differentiated and anaplastic thyroid cancer were associated with increased risk of mortality. Genomic analysis of matched primary and BrM samples revealed universal conservation of BRAF and NRAS mutations between samples. Conclusion Contemporary thyroid cancer BrM outcomes are dependent on primary malignancy histology and may benefit from further molecular profiling.
Heterogeneous morphological features and data imbalance pose significant challenges in rare thyroid carcinoma classification using ultrasound imaging. To address this issue, we propose a novel multitask learning framework, Channel-Spatial Attention Synergy Network (CSASN), which integrates a dual-branch feature extractor - combining EfficientNet for local spatial encoding and ViT for global semantic modeling, with a cascaded channel-spatial attention refinement module. A residual multiscale classifier and dynamically weighted loss function further enhance classification stability and accuracy. Trained on a multicenter dataset comprising more than 2000 patients from four clinical institutions, our framework leverages a residual multiscale classifier and dynamically weighted loss function to enhance classification stability and accuracy. Extensive ablation studies demonstrate that each module contributes significantly to model performance, particularly in recognizing rare subtypes such as FTC and MTC carcinomas. Experimental results show that CSASN outperforms existing single-stream CNN or Transformer-based models, achieving a superior balance between precision and recall under class-imbalanced conditions. This framework provides a promising strategy for AI-assisted thyroid cancer diagnosis.
Cold Spring Harbor Laboratorynovember 2024Schildklier
BACKGROUND: This study investigates the effects of intranasal dantrolene nanoparticles on inflammation and programmed cell death by pyroptosis in 5XFAD Alzheimer’s Disease (AD) mice. METHODS: 5XFAD and wild type (WT) B6SJLF1/J mice were treated with intranasal dantrolene nanoparticles (5 mg/kg), daily, Monday to Friday, for 12 weeks continuously, starting at 9 months of age. Blood and brain were harvested at 13 months of age, one month after completion of 12 weeks intranasal dantrolene nanoparticle treatment. Blood biomarkers function of liver (Alanine transaminase, ALT), kidney (Creatinine), and thyroid (TSH: Thyroid-stimulating hormone) were measured using ELISA. The changes of whole brain tissue proteins on Ca (2+) release channels on membrane of endoplasmic reticulum (type 2 ryanodine and type 1 InsP3 receptors, RyR-2 and InsP3R-1), lipid peroxidation byproduct malondialdehyde (MDA)-modified proteins, 4-HNE, pyroptosis regulatory proteins (NLR family pyrin domain containing 3 (NLRP3), cleaved caspase-1, full length or N-terminal of Gasdermin D (GSDMD), cytotoxic (IL-1, IL-18, IL-6, TNF-a) and cytoprotective (IL-10) cytokines, astrogliosis (GFAP), microgliosis (IBA-1) and synapse proteins (PSD-95, Synapsin-1) were determined using immunoblotting. Body weights were monitored regularly. RESULTS: Intranasal dantrolene nanoparticles significantly inhibited the increase of RyR-2 and InsP3R-1 proteins, MDA-modified proteins, 4-NHE, pyroptosis regulatory proteins (NLRP3, cleaved caspase-1, N-terminal GSDMD), cytotoxic cytokine (IL-1β, IL-18, IL-6, TNF-α), biomarkers for astrogliosis (GFAP) and microgliosis (IBA-1), and the decrease of cytoprotective cytokine (IL-10) and synaptic proteins (PSD-95, synpasin-1). Intranasal dantrolene nanoparticles for 12 weeks did not affect blood biomarkers for function of liver, kidney, and thyroid, not did it change body weight significantly. CONCLUSION: Intranasal dantrolene nanoparticles significantly inhibit the increase of RyR-2 and InsP (3) R-1 Ca (2+) channel receptor proteins, ameliorate activation of the pyroptosis pathway and pathological inflammation, and the associated loss of synapse proteins. Intranasal dantrolene nanoparticles for three months did not affect liver, kidney and thyroid functions or cause other side effects.
Cold Spring Harbor Laboratorymaart 2025Schildklier
Patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) face a much poorer prognosis than those with differentiated thyroid cancers. Around 25% of PDTCs and 35% of ATCs carry the BRAFV600E mutation, which constitutively activates the MAPK pathway, a key driver of cell growth. Although combining BRAF and MEK inhibitors can shrink tumors, resistance often develops. The exact cause of this resistance remains unclear. We previously found that in PDTC and ATC cells the BRAFV600E mutation is strongly linked to the expression of ETV5, a transcription factor downstream of the MAPK pathway. In the current study, we observed a significant association between ETV5 expression and the activation of p38, a central component of the MAPK14 pathway. Upon reduction of ETV5 levels, p38 expression and activation decreased, along with its upstream regulators MKK3/MKK6. This suggests that the MAPK and p38/MAPK14 pathways are interconnected and that p38 has oncogenic properties in these cancers. Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. We then tested this combination in a genetically engineered mouse model (GEMM) of ATC. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.
Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves’ disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ∼2.9 million genomes and identified 235 known and 501 novel independent variants significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases ( r (2) =0.21-0.97). Telomere maintenance genes contribute to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair, and DNA damage response genes are predominantly associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We evaluated thyroid cancer polygenic risk scores (PRS) for clinical applications in thyroid cancer diagnosis. We found PRS associations with thyroid cancer risk features: multifocality, lymph node metastases, and extranodal extension.
Deep learning (DL) methods dominate thyroid nodule segmentation in ultrasound (US) images, achieving high Dice scores but at the cost of millions of parameters, GPU-dependent training via backpropagation, and limited mathematical tractability. These limitations impede deployment in resource-constrained environments. In this paper, we propose MedSaab-US, a backpropagation-free segmentation framework grounded in the Green Learning paradigm. MedSaab-US extracts multi-scale spatial-frequency features by combining multi-level Discrete Wavelet Transform (DWT) with multi-scale channel-wise Saab (Subspace Approximation with Adjusted Bias) transforms at patch sizes of 5 x 5, 11 x 11, and 21 x 21 pixels. Label-Assisted Greedy (LAG) feature selection retains the most discriminative features, which are fed to an XGBoost classifier for pixel-wise prediction. The Saab transform parameters are determined analytically from data statistics, while XGBoost employs iterative greedy tree construction without requiring backpropagation. Evaluated on the TN3K dataset (2,879 training and 614 test images), MedSaab-US achieves a mean Dice coefficient of 0.4784 +/- 0.2190, precision of 0.5768, and recall of 0.5604, with a model footprint under 500K parameters and CPU-only inference in approximately 0.3 seconds per image. We present this result as an exploratory non-DL baseline for thyroid ultrasound segmentation and analyze the specific challenges posed by isoechoic nodules. An ablation study further quantifies the contribution of each pipeline component, including separate evaluations of LAG feature selection and training-set size. ;Accepted at the IEEE ICIP 2026 LBDL 2 Workshop
Background Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se. Methods We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort ( n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort ( n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity. Results In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1–5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)). Conclusions In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.
American Association of Clinical Endocrinologyseptember 2024Schildklier
BACKGROUND/OBJECTIVE: Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer (TC), rarely found in hyperfunctioning goiter. CASE REPORT: We present a case of a woman treated for breast carcinoma (BCA) found to have a benign hyperfunctioning nodular goiter, its likely transformation to MTC, and its treatment. Family history revealed papillary thyroid cancer in her nephew. DISCUSSION: Most TCs in hyperfunctioning nodules are differentiated carcinomas. Familial MTC or MTC in association with multiple endocrine neoplasia 2 is the expected genetic association in this case. CONCLUSION: The association of BCA and MTC may have been coincidental, given the high prevalence of BCA in females. It could have been the result of a common genetic precursor of both tumors and/or treatment modality such as external beam radiation therapy used to treat BCA. This case highlights the importance of considering MTC as a potential diagnosis even in cases of hyperfunctioning nodular goiter. We call for consideration of calcitonin level measurement in the workup of thyroid nodules in select cases. Close follow-up of thyroid nodules, particularly in patients with another primary malignancy, is important because of possible common genotype triggers.
Timely and accurate diagnosis is crucial in addressing the global rise in thyroid cancer, ensuring effective treatment strategies and improved patient outcomes. We present an intelligent classification method that couples an Adaptive Convolutional Neural Network (CNN) with Cohen-Daubechies-Feauveau (CDF9/7) wavelets whose detail coefficients are modulated by an n-scroll chaotic system to enrich discriminative features. We evaluate on the public DDTI thyroid ultrasound dataset (n = 1,638 images; 819 malignant / 819 benign) using 5-fold cross-validation, where the proposed method attains 98.17% accuracy, 98.76% sensitivity, 97.58% specificity, 97.55% F1-score, and an AUC of 0.9912. A controlled ablation shows that adding chaotic modulation to CDF9/7 improves accuracy by +8.79 percentage points over a CDF9/7-only CNN (from 89.38% to 98.17%). To objectively position our approach, we trained state-of-the-art backbones on the same data and splits: EfficientNetV2-S (96.58% accuracy; AUC 0.987), Swin-T (96.41%; 0.986), ViT-B/16 (95.72%; 0.983), and ConvNeXt-T (96.94%; 0.987). Our method outperforms the best of these by +1.23 points in accuracy and +0.0042 in AUC, while remaining computationally efficient (28.7 ms per image; 1,125 MB peak VRAM). Robustness is further supported by cross-dataset testing on TCIA (accuracy 95.82%) and transfer to an ISIC skin-lesion subset (n = 28 unique images, augmented to 2,048; accuracy 97.31%). Explainability analyses (Grad-CAM, SHAP, LIME) highlight clinically relevant regions. Altogether, the wavelet-chaos-CNN pipeline delivers state-of-the-art thyroid ultrasound classification with strong generalization and practical runtime characteristics suitable for clinical integration. ;Scientific Reports
Introduction Atezolizumab, carboplatin, and etoposide (ACE) therapy is a standard of care for extensive-disease small cell lung cancer (SCLC); however, its safety data are scarce, limiting generalization to the Japanese population. Methods This study aimed to compare the safety of ACE versus carboplatin and etoposide (CE) therapies in Japanese patients using the Diagnosis Procedure Combination (DPC) database by comparing the incidence of adverse events (AEs). Retrospective data on clinical background and AEs were extracted from the DPC database. Incidence rates and restricted mean survival times (RMSTs) up to 6 months were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method. Results A total of 330,774 patients were identified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes, of whom 277 were included in the ACE cohort and 478 in the CE cohort. Among the 19 AEs, the incidence of skin disorder and thyroid dysfunction was significantly higher in the ACE cohort compared with the CE cohort. The adjusted incidence rate ratios were 2.38 (95% confidence interval [CI] 1.04–5.43) for skin disorder and 6.92 (95% CI 2.00–23.89) for thyroid dysfunction. The adjusted RMST differences were − 8.2 days (95% CI − 16.0 to − 0.4 days) for skin disorder and − 8.8 days (95% CI − 15.7 to − 1.9 days) for thyroid dysfunction. Conclusions This study provides evidence regarding the safety of ACE combination therapy in Japanese clinical practice using the DPC database, with results comparable to those reported in pivotal clinical trials. Trial Registration UMIN Clinical Trials Registry ID UMIN000041508.
Thyroid hormones are metabolic indicators to evaluate the physical condition of emergency hospitalized patients, while the relationship between total triiodothyronine and the severity of emergency inpatients is still unclear. To explore the thyroid function levels of inpatients in emergency ward and the status of combined Nonthyroidal illness syndrome (NTIS), and to emphasize the importance of thyroid hormone examination for non-endocrinology inpatients. According to thyroid function of inpatients in emergency ward, they were divided into NTIS group and non-NTIS group, the hematological characteristics and TH levels of each group were analyzed. Based on clinical diagnoses, the hospitalized patients were divided into three major groups, namely infection group, non-infection group and impaired organ function group. Among them, infection group was further divided into sepsis group, lung infection group and local infection group, altogether five groups. The thyroid function levels and low values in each group were evaluated, and the correlation between hormone levels and inflammatory factors, nutritional indicators and the relationship with the risk of death was discussed. The inpatient rate in emergency ward complicated with NTIS was 62.29%, T3 was the most sensitive index of NTIS, followed by FT3. Compared to non-NTIS group, the NTIS group had an increased risk of death. The sepsis group and impaired organ function group had the highest rates of complicated NTIS, reaching 83.33% and 78.12% respectively. Spearman's correlation analysis implied T3/T4/FT3 levels were positively correlated with ALb and PLT (except T4), and negatively correlated with CRP, D-Dimer, IL-6 and Fer. The Receiver Operating Curve (ROC) and Area under the curve (AUC) showed T3 levels alone were strongly associated with the risk of death (AUC 0.750; 95% CI 0.673–0.828; P < 0.001). T3 is the most sensitive indicator for emergency patients, followed by FT3. The decrease of T3 level has a good predictive value for mortality risk. Thyroid function should be monitored in critically ill patients.
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Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with homeostatic processes. They are a major concern for public health, and they can cause adverse long-term effects such as cancer, intellectual impairment, obesity, diabetes, and male infertility. The endocrine system is a complex machinery, with the estrogen (E), androgen (A), and thyroid hormone (T) modes of action being of major importance. In this context, the availability of in silico models for the rapid detection of hazardous chemicals is an effective contribution to toxicological assessments. We developed Qualitative Gene expression Activity Relationship (QGexAR) models to predict the propensities of chemically induced disruption of EAT modalities. We gathered gene expression profiles from the LINCS database tested on two cell lines, i.e., MCF7 (breast cancer) and A549 (adenocarcinomic human alveolar basal epithelial). We optimized our prediction protocol by testing different feature selection methods and classification algorithms, including CATBoost, XGBoost, Random Forest, SVM, Logistic regression, AutoKeras, TPOT, and deep learning models. For each EAT endpoint, the final prediction was made according to a consensus prediction as a function of the best model obtained for each cell line. With the available data, we were able to develop a predictive model for estrogen receptor and androgen receptor binding and thyroid hormone receptor antagonistic effects with a consensus balanced accuracy on a validation set ranging from 0.725 to 0.840. The importance of each predictive feature was further assessed to identify known genes and suggest new genes potentially involved in the mechanisms of action of EAT perturbation.
Objective The aim of this study is to investigate the relationship between the use of high doses of levothyroxine (L-T4) and hearing loss in patients who have undergone surgery for thyroid cancer. Material method After total thyroidectomy for thyroid cancer, patients were divided into two groups according to L-T4 dose below 150 µg and above 150 µg. Demographic characteristics, postoperative duration, radioactive iodine treatment, bone densitometry scans with LDxa and FDxa, and right and left ear hearing levels were statistically compared in both groups. Results The study included 62 patients, 85.5% ( n = 53) of whom were female, with a mean age of 48.8 ± 11.7 years. While 56.45% ( n = 35) of the patients were taking L-T4 below 150 µg 43.55% ( n = 27) were taking L-T4 above 150 µg. The mean postoperative duration of the participants was 4.1 ± 2.7 years, osteopenic 30.7% and osteoporotic 16.13% according to LDxa, osteopenic 29.0% and osteoporotic 1.6% according to FDxa. Hearing loss in both right and left ears was 41.9% and sensorineural hearing loss in both ears was 22.6%. Age, LDxa, FDxa, hearing loss in the right and left ear were found to be significantly different in the two groups above and below 150 µg according to the dose of L-T4 used ( p < 0.05). However, no differences were found according to sex, height, weight, body mass index, postoperative period, or radioactive iodine treatment ( p > 0.05). Both osteopenia and osteoporosis, as well as hearing loss in both the right and left ear, were significantly higher in the group taking L-T4 150 µg or more ( p < 0.05). Conclusion In our study, we found that patients taking 150 µg or more of L-T4 daily were more osteopenic and osteoporotic and had more hearing loss in both ears.
Purpose Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT). Methods AIT patients with pathological thyroid uptake on [^68Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[^18F]FDG PET in terms of SUV_max/SUV_peak/SUV_mean/tissue-to-background ratio (TBR), and with a healthy control group. Results Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [^68Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([^68Ga]Ga-FAPI (SUV_peak): 7.0 vs. 1.7; p = 0.004/(TBR_bloodpool): 6.8 vs. 1.7; p = 0.002; 2-[^18F]FDG (SUV_peak): 3.9 vs. 1.4; p = 0.004/(TBR_bloodpool): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [^68Ga]Ga-FAPI and 2-[18F]FDG PET (SUV_peak: 7.3 vs. 5.6; p = 0.104). Conclusion Patients with AIT show higher thyroid uptake on [^68Ga]Ga-FAPI and 2-[^18F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [^68Ga]Ga-FAPI PET and should prompt a clinical work-up.
Thyroid hormones are crucial regulators of metamorphosis and development in bilaterians, particularly in chordate deuterostomes. Recent evidence suggests a role for thyroid hormone signaling, principally via 3,5,3′,5′-Tetraiodo-L-thyronine (T4), in the regulation of metamorphosis, programmed cell death and skeletogenesis in echinoids (sea urchins and sand dollars) and sea stars. Here, we test whether TH signaling in skeletogenesis is a shared trait of Echinozoa (Echinoida and Holothouroida) and Asterozoa (Ophiourida and Asteroida). We demonstrate dramatic acceleration of skeletogenesis after TH treatment in three classes of echinoderms: sea urchins, sea stars, and brittle stars (echinoids, asteroids, and ophiuroids). Fluorescently labeled thyroid hormone analogues reveal thyroid hormone binding to cells proximal to regions of skeletogenesis in the gut and juvenile rudiment. We also identify, for the first time, a potential source of thyroxine during gastrulation in sea urchin embryos. Thyroxine-positive cells are present in tip of the archenteron. In addition, we detect thyroid hormone binding to the cell membrane and nucleus during metamorphic development in echinoderms. Immunohistochemistry of phosphorylated MAPK in the presence and absence of TH-binding inhibitors suggests that THs may act via phosphorylation of MAPK (ERK1/2) to accelerate initiation of skeletogenesis in the three echinoderm groups. Together, these results indicate that TH regulation of mesenchyme cell activity via integrin-mediated MAPK signaling may be a conserved mechanism for the regulation of skeletogenesis in echinoderm development. In addition, TH action via a nuclear thyroid hormone receptor may regulate metamorphic development. Our findings shed light on potentially ancient pathways of thyroid hormone activity in echinoids, ophiuroids, and asteroids, or on a signaling system that has been repeatedly co-opted to coordinate metamorphic development in bilaterians.
Background Anemia in children on maintenance hemodialysis (HD) leads to poor quality of life. Our study aimed to assess and monitor anemia and iron status management in children on maintenance HD over 18 months using key performance indicators. Methods Key performance indicators, formulated as the percentage of patients achieving the KDIGO (2012) guideline-recommended targets for hemoglobin (Hb) (11–12 g/dl), transferrin saturation (TSAT) (20–40%) and serum ferritin (200–500 ng/ml), were reported quarterly over the 18-month-period of this study. Results This study was carried out over an 18 month-period, from April 1st, 2020, till October 31st, 2021. A total of 78 patients (45 males and 33 females) were included; mean age 12.16 ± 3.3 years and HD duration range 3.0—140.88 months, median 16.51 months. The three most common primary causes of CKD were Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) (29.5%), unknown cause (24.4%), and chronic glomerular diseases (20.5%). The quarterly reported percentages of patients achieving the recommended targets for Hb, TSAT, and serum ferritin ranges were 18.2–35.7%, 38.8–57.1%, and 11.9–26.6%, respectively. Conclusion Although the mean Hb trend was nearing the KDIGO (2012) target, the key performance indicators showed that only a small percentage of our HD patients were achieving the targets for Hb, TSAT, & serum ferritin, thus alerting us to the need to revise our protocol for the management of anemia and iron status. Graphical abstract
Introduction and Hypothesis Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study’s purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women. Methods The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4–8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach’s α co-efficient for internal consistency and Spearman’s correlation coefficients and Wilcoxon rank sum tests for construct validity. Results Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD. Conclusions The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population.
Our aim was to investigate the perception and future expectations of Single-Port (SP) surgery among urology trainees in the United States. A 34-item online survey was distributed to urological residency and fellowship programs across the US, covering demographic profiles, SP training opportunities, perceived educational impact, and future perspectives. Descriptive analysis and multivariable linear regression were used to assess predictors of SP adoption. 201 surveys were completed (28.6% completion rate). Among institutions with an SP platform, about 50% have used it regularly for over 2 years, though often in less than 50% of procedures. While robotic simulators are commonly available, only 17% offer both multi-port and SP simulators, and structured pre-clinical SP training is limited. Approximately 30% of respondents expressed concerns over limited hands-on experience and a steeper learning curve with SP. Around 40% felt that their robotic surgery exposure was negatively impacted by SP's introduction. SP surgery's benefits are seen mostly in the immediate post-operative period and a significant number of respondents foresee a major role for SP in urology. However, proficiency in SP surgery is not seen as crucial for career advancement or job opportunities. Academic job aspirations, SP platform availability, and SP surgery workload are predictors of future SP implementation. Trainees increasingly recognize the clinical benefits of SP procedures but express concerns about the potential negative impact on hands-on experience. Training programs should more systematically integrate SP technology into curricula. There is a correlation between training in high-volume SP centers and future SP adoption.
The use of robots in surgery began in the early 1970s. The actions that could be performed in Laparoscopic practice, which was a common use at the time, were relatively limited compared to the potential of robotic surgery. Robot is minimally invasive technology with wrist capability, tremor filtration and three-dimensional optics advantages compared to laparoscopy. The robotic surgery system has been adopted by urologists in minimally invasive surgery, especially since it facilitates access to depth in the pelvis area. The use of the robotic surgery system has accelerated the transition to minimally invasive surgery and has led to a completely different skill set for the urology surgeon. Because of this advantage, urologists became the first practitioners of robotic surgery technology. Robotic surgery has been used in urological oncology for over 20 years. The use of robotic surgical approaches continues to expand in many surgical fields. In parallel with this expansion, robotics education is becoming more and more important. The development of robotic skills follows the phase of observing, helping, performing under supervision, and finally independent practice. Basic robotic surgery training is divided into two: patient-side training and console training. Patient-side training includes patient positioning, pneumoperitoneum creation, port placement, robot placement, and basic laparoscopic skills. The need for high capacity application without compromising patient care has been met by surgical simulations and especially virtual reality (VR) surgical simulations. VR simulation is increasingly used in medical education and is considered the first and important step in robotic surgery education. Programmed training curricula have been developed for learning the robotic surgery system. While various groups are currently developing the robotics curriculum, there are four prominent groups of curriculums: FRS (Fundamentals of Robotic Surgery), FSRS (Fundamental Skills of Robotic Surgery), BSTC (Basic Skills Training Curriculum) and ERUS (Eau Robotic Urology Section). The Da Vinci Surgical System is considered the gold standard of robot-assisted laparoscopic surgery. Newly produced robotic systems must compete with this current gold standard. Each resulting system should be compared to the da Vinci robotic system to evaluate potential effectiveness and safety. In newly developed robotic surgery systems, it seems that new technologies have been applied by trying to improve the functionality of the old system and have been developed by taking into account the missing features in the installed system. Whether these new features will attract surgeons to adopt and use new robotic systems in clinical practice is a question that needs to be answered in the near future.
Background and Purpose The present study aims to investigate the effects of external neuromuscular electrical stimulation (NMES) on urinary symptoms, pelvic floor muscle strength (PFMS), quality of life (QoL), sexual function, perception of subjective improvement (PSI), and satisfaction in urgency urinary incontinence (UUI). Materials and Methods The randomized sham-controlled study design was employed in this study. Women aged 18–65 years, who were diagnosed with UUI, were randomly allocated into the NMES (external NMES + lifestyle advice, n = 15) and sham groups (sham NMES + lifestyle advice, n = 15). Both groups performed the application for 30 min, three days a week for eight weeks. Urinary symptoms were evaluated by using the International Incontinence Consultation Questionnaire-Short Form (ICIQ-SF) and a 3-day bladder diary. PFMS was assessed using the Modified Oxford Scale (MOS), QoL using the King’s Health Questionnaire (KHQ), and sexual function using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12). The PSI and satisfaction were questioned. Results There was a higher level of decrease in the ICIQ-SF score, the mean number of voids/night and UI, all scores related to the KHQ (excluding interpersonal relationships), and a higher level of increase in maximum voiding volume, MOS scores, PISQ-12-emotional, PISQ-12-physical, and PISQ-12-total scores in the NMES group when compared to the sham group (p < 0.05). PSI and satisfaction were at higher levels in the NMES group than in the sham group (p < 0.05). Conclusions External NMES was an effective and complementary method in reducing urinary symptoms and improving PFMS, QoL, sexual function, PSI, and satisfaction level in women with UUI. Clinical Trial Registration NCT04727983.
Purpose Ileal ureter interposition is a well-established option for complex ureteral strictures. While minimally invasive approaches have evolved, the application of the single-port (SP) robotic platform for ileal ureter reconstruction has not been previously reported. This study presents the first clinical series evaluating the feasibility, technique, and early outcomes of SP robotic ileal ureter reconstruction. Methods We retrospectively reviewed a prospectively maintained database of patients who underwent SP robotic ileal ureter substitution between September 2019 and November 2024 by a single surgeon. Demographic, perioperative, and functional data were analyzed. Surgical success was defined as freedom from reintervention, absence of radiographic obstruction, and stable renal function. Pre- and postoperative renal function was compared using paired statistical analysis. Results Seventeen patients underwent SP robotic ileal ureter reconstruction (29% male), with a mean age of 54 years. Radiation-induced strictures accounted for 70.6% of cases. Unilateral reconstruction was performed in 8 (47.1%), while 8 (47.1) required bilateral reconstruction with V-shaped or reverse-7 configurations, including bladder augmentation in selected cases. One patient (5.9%) underwent unilateral ileal ureter with bladder neck reconstruction. The median ileal segment length was 25 cm. Mean operative time was 308 min, and median blood loss was 70 mL. One intraoperative complication (5.9%) occurred. Postoperative complications were observed in 47%, with 11.8% classified as Clavien–Dindo grade IIIa. Renal function remained stable (preoperative eGFR 56.4 vs. postoperative 57.5 mL/min/1.73 m², p = 0.803). At a median follow-up of 20.5 months, the overall success rate was 94.1%. Conclusions Single-port robotic ileal ureter reconstruction is a feasible and effective technique for complex ureteral strictures, achieving high early success with acceptable morbidity.
Het tumorlysissyndroom (TLS) is een ernstige complicatie bij de behandeling van (hemato-)oncologische patiënten, veroorzaakt door massale afbraak van tumorcellen. Het kan leiden tot acute nierinsufficiëntie, elektrolytstoornissen, hartritmestoornissen en zelfs plotseling overlijden. Bovendien is er een verhoogde kans op vorming van urinezuurstenen. Voor urolithiase worden urologen geregeld betrokken bij de behandeling. Daarbij ligt de focus op drainage en/of steenverwijdering, terwijl een conservatieve aanpak gericht op preventie en behandeling van TLS succesvol kan zijn. Het alkaliseren van urine in de acute fase is risicovol en kan de nierfunctie verder verslechteren. Vroege herkenning van TLS middels samenwerking tussen urologen en (hemato-)oncologen is cruciaal voor een effectieve behandeling van deze patiënten. Tumor lysis syndrome (TLS) is a serious complication in (hemato-)oncology patients caused by the massive breakdown of tumor cells. This may lead to acute renal insufficiency, electrolyte disturbances, cardiac arrhythmias and even sudden death. In addition, there is an increased risk of uric acid stone formation. For urolithiasis, urologists are regularly involved in the treatment that focuses on drainage and/or stone removal. However, a conservative approach preventing and targeting TLS with medication can be effective. Alkalinizing the urine in the acute phase is risky and may further impair kidney function. Early recognition of TLS by means of collaboration between urologists and (hemato-)oncologists is crucial for the effective treatment of these patients.
Robotic-assisted surgery has become increasingly widespread across surgical specialties over the last two decades. However, the high costs associated with robotic systems remain a major limitation to their diffusion. Recently introduced robotic platforms aim to increase market competition and potentially reduce procedural costs. This study evaluated the direct in-hospital costs associated with three robotic platforms in urologic surgery. A retrospective single-center cost analysis was conducted on robotic-assisted procedures performed in 2023. A total of 284 robotic-assisted radical prostatectomies (RALP) were included (200 Da Vinci, 77 Hugo™ RAS, and 7 Versius^®), while 77 robotic-assisted partial nephrectomies were analyzed (57 Da Vinci and 20 Hugo™ RAS). Partial nephrectomy analysis therefore involved only two platforms. Cost estimation was performed using an activity-based costing approach from the hospital/provider perspective, including direct costs related to robotic equipment, maintenance, consumables, operating room occupancy, personnel, and hospitalization. For partial nephrectomy, no statistically significant difference in total direct cost was observed between Da Vinci (€7856.89 ± 1335.76) and Hugo™ (€8226.36 ± 1481.85) platforms ( p = 0.16), although operating room time and related costs were significantly higher with Hugo™ ( p = 0.03 and p = 0.04, respectively). For RALP, mean total costs were €8077.99 (Da Vinci), €7867.92 (Hugo™), and €8430.76 (Versius^®), without statistically significant differences ( p = 0.13). Operative and operating room times were significantly longer with Versius^® ( p < 0.05). Due to the limited number of Versius^® procedures, findings involving this platform should be considered exploratory. In this single-center experience, direct in-hospital costs associated with robotic-assisted urologic procedures appeared broadly comparable across platforms. However, findings should be interpreted cautiously given the retrospective design, unbalanced cohorts, absence of detailed case-mix adjustment, and the limited Versius^® sample size.
Das Zukunftspapier der Arbeitsgruppe „Sektorenübergreifende fachärztliche Versorgung in der Urologie“ greift die tiefgreifenden Herausforderungen auf, vor denen die urologische Versorgung derzeit steht. Demographischer Wandel, Fachkräftemangel, steigender Kostendruck, Digitalisierung und der politische Wandel hin zur Ambulantisierung führen zu einer zunehmenden Belastung sowohl in den Kliniken als auch in den Praxen. Um die flächendeckende und qualitativ hochwertige Versorgung langfristig sichern zu können, sind strukturelle Veränderungen unvermeidlich. Das Papier zeigt Wege auf, wie diese Veränderungen durch gemeinsame, sektorenübergreifende Ansätze gelingen können – etwa durch vernetzte Versorgungsstrukturen, hybride OP-Zentren mit Klinikanbindung, spezialisierte Notfallstrukturen sowie flexible Beschäftigungs- und Weiterbildungskonzepte. Unter dem Leitprinzip „digital vor ambulant vor stationär“ soll eine patientenzentrierte, effiziente und zukunftsfähige Versorgung etabliert werden. Voraussetzung dafür sind verlässliche Rahmenbedingungen, Investitionen, Bürokratieabbau, digitale Interoperabilität und eine kontinuierliche wissenschaftliche Begleitung. Nur durch das gemeinsame Handeln von Klinik und Praxis kann der Wandel erfolgreich gestaltet und die urologische Versorgung auch künftig gesichert werden. Die Urologie ist aufgrund ihres breiten fachlichen Spektrums, ihrer starken Vernetzung und etablierten Strukturen prädestiniert, in der sektorenübergreifenden Versorgung eine Vorreiterrolle einzunehmen. The position paper of the Working Group “Cross-sectoral urological care” addresses the profound challenges currently facing urological healthcare. Demographic change, workforce shortages, increasing financial pressure, digital transformation, and the political shift toward outpatient care are placing growing strain on both hospitals and private practices. To maintain comprehensive, high-quality care, structural changes are essential. This paper outlines how such a transformation can succeed through coordinated, cross-sectoral collaboration—by developing integrated care networks, hybrid surgical centers linked to hospitals, specialized emergency structures, and flexible employment and training models. Guided by the principle “digital before outpatient before inpatient”, the goal is to establish a patient-centered, efficient, and future-oriented care system. Achieving this requires stable conditions, sustainable investment, reduced bureaucracy, digital interoperability, and continuous scientific evaluation. Only through joint efforts between hospitals and outpatient providers can this transformation be successfully achieved and urological care be secured for the future. With its broad clinical spectrum, strong professional networking, and established organizational structures, urology is particularly well positioned to take a leading role in developing cross-sectoral models of care.
Glyphosate is a widely used herbicide that is generally considered safe; however, acute kidney injury (AKI) caused by glyphosate ingestion can be severe and require hemodialysis. We present a unique case of a 68-year-old Japanese man who developed AKI after accidental ingestion of glyphosate and required hemodialysis. Based on the clinical presentation and findings, the patient was diagnosed with renal AKI with severe tubulointerstitial damage. However, the precise pathogenesis of the tubulointerstitial damage remained unclear. An elevated beta-2 microglobulin level discovered by the urinalysis during admission raised the suspicion of tubulointerstitial nephritis caused by glyphosate. Gallium scintigraphy revealed accumulation in both kidneys. A renal biopsy revealed acute tubulointerstitial nephritis rather than acute tubular necrosis, which is commonly observed with glyphosate-induced renal injury. After initiating steroid therapy, his kidney function gradually improved and he was weaned from hemodialysis. This report is the first to describe glyphosate-induced acute tubulointerstitial nephritis that was successfully treated with immunosuppressive therapy. Furthermore, this report highlights the importance of steroid therapy for cases of persistent kidney injury after the discontinuation of agents associated with acute tubulointerstitial nephritis.
Robotic technology has revolutionised minimally invasive urological surgery, enhancing precision and minimising surgical complications. Recent evidence suggests that utilising lower pneumoperitoneum pressures improves clinical outcomes but the comparative impact on post-operative pain remains uncertain. This systematic review analyses the literature on low-pressure pneumoperitoneum to investigate its impact on pain and recovery following robotic-assisted urological surgeries, including prostatectomy, partial ephrectomy, and cystectomy. Post-operative opioid consumption, total operating time, estimated intra-operative bleeding, and total inpatient stay were investigated as secondary outcomes. PubMed, NHS Knowledge and Library Hub, Cochrane Central databases, and EMBASE were searched between January 2010 and May 2024. Any identified studies were reviewed against eligibility criteria by two independent authors prior to inclusion. The review was written in compliance with Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. Nine studies were included: six focused on prostatectomy, two on partial nephrectomy, and one on cystectomy. Low-pressure pneumoperitoneum was found to result in reduced postoperative pain scores, particularly in the immediate recovery period and on postoperative day 1. Despite these improvements, post-operative opioid consumption remained consistent with standard pressures. The surgical workspace was not compromised when pneumoperitoneum pressures were lower. Lowering pneumoperitoneum pressures in robotic-assisted urological surgery appears to reduce immediate postoperative pain scores without increasing overall complications. This has not led to a noticeable reduction in post-operative opioid consumption. The lack of consistent reduction in opioid use and limited high-quality studies highlight the need for further research, particularly for partial nephrectomy and cystectomy.
Medical education is one of the domains that is currently being widely investigated leveraging the capabilities offered by virtual reality (VR) systems. The appeal of such technology is based on the potential cost-effectiveness, portability, safety of training in simulated environments, and the ability to enable training without the need of supervision. One of the approaches that can be utilized during technology-mediated educational activities is gamification, i.e., the use of game design elements in non-game contexts. This approach has the ability to make learning fun, memorable and more effective, as demonstrated by a substantial body of literature. However, whereas a number of studies have investigated the ability of gamification-based VR systems in enhancing learning and training in various domains, the adoption of gamification approaches in VR medical training, and in particular surgical training, is a topic that has been largely overlooked. To bridge this gap, we first co-designed with a pool of urology surgeons a gamification-based VR system for the laser enucleation of the prostate. Subsequently, we conducted a user study with seventeen urology residents to assess the usability and user experience. Our results provide evidence that gamification in VR medical training systems is a valuable strategy to enhance surgical trainees outcomes and motivations. However, our findings also revealed that the lack of realism of the physical aspects involved in real operations, such as force and tactile feedback and visual deformations of the simulated tissues, can drastically hamper the experience that surgeons desire from a VR simulator.
Background We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC). Methods We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan–Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis. Result BMI, T, N, and M are significant in the survival curve with or without tertiary lymphoid structure. BMI, T, N, M and TLS were used to construct a prognostic model for penile squamous cell carcinoma, and the prediction accuracy reached a consensus of 0.884(0.835–0.932), and the decision consensus reached 0.581(0.508–0.655). Conclusion TLS may be a positive prognostic factor for penile squamous cell carcinoma, and the combination of BMI, T, N and M can better evaluate the prognosis of patients.
Die Presse in totalitären Staaten bietet nur einen eingeschränkten Überblick bezüglich der gesellschaftlichen und auch gesundheitlichen Realität. Doch die Auswertung der drei wichtigsten Zeitungen der DDR ( Neues Deutschland, Neue Zeit, Berliner Zeitung ) ermöglicht einen Einblick, wie Propaganda letztlich vergeblich versucht, die Probleme im Gesundheitswesen zu kaschieren und den scheinbaren Erfolg des Sozialismus herauszustellen. The press in totalitarian states offers only a limited overview of social and health realities. However, an analysis of the three most important newspapers in the German Democratic Republic (GDR; Neues Deutschland , Neue Zeit , Berliner Zeitung ) provides insight into how propaganda ultimately attempts in vain to conceal problems in the healthcare system and highlight the apparent triumph of socialism.
This article highlights the evolution, birth and legacy of the world’s first neonatal surgical unit established at Alder Hey Children’s Hospital Liverpool in 1953. Peter Paul Rickham, a creative pioneering and innovative surgeon, is credited here as a major driving force that helped shape and progress the modern day development of neonatal surgery. Rickham’s vision was realised by studying neonatal surgical disorders and the mortality rate of congenital anomalies in Mersey Region while working as a young senior registrar with Isabella Forshall. Rickham defined the extent of the problem(s) and set to work as a newly appointed consultant a vision for improving outcomes with the creation and establishment of a preeminent world leading neonatal surgical unit. Surgeons from all over the world travelled to work, learn and train with Rickham and the paediatric surgical staff team at Alder Hey in the subsequent years to follow. Neonatal anaesthesia greatly advanced by Jackson Rees a colleague working in Liverpool with Rickham allowed huge success to flourish—‘the impossible became possible’. The neonatal surgical unit in Liverpool became the benchmark and prototype for units to develop around the world immediately resulting in improvement in the survival of newborn infants undergoing surgery from 22 to 74%. Rickham’s contributions to neonatal and paediatric surgery are truly remarkable. Alder Hey hosts an international symposium and special dinner with Rickham family members as VIP guests in its calendar of events. A symposium highlight is the Rickham Lecture with the PPR Gold Medal awarded to an international renowned leader in the field of paediatric surgery and the surgical sciences.
Introduction and Hypothesis Urinary tract infections (UTIs) are a common medical problem and prophylaxis of recurrent UTIs is an ongoing clinical challenge. In the present study we examined whether acupuncture is able to prevent recurrent UTIs in women. Methods This multicentre randomised controlled trial, based at a University clinic and private acupuncture clinics, recruited women suffering from recurrent uncomplicated UTIs. Participants were randomised to the acupuncture group or control group. Acupuncture therapy consisted of 12 treatments over a period of 18 weeks, using a set of predefined body and ear acupuncture points. Cranberry products were recommended to all participants as standard of care. Results A total of 137 women were randomised (68 acupuncture, 69 control group) and occurrence of UTIs at 6 and 12 months could be assessed in 123 and 120 women respectively. Acupuncture combined with cranberry slightly increased the proportion of UTI-free women compared with cranberry alone at 6 months (59% vs 46%, p = 0.2). Between 6 and 12 months the proportion of UTI-free women was significantly higher in the acupuncture group (66 vs 45%, p = 0.03). The number of UTIs decreased from baseline to 12 months in both study groups. The number of UTIs at 12 months was significantly lower in the acupuncture group (median difference 1, p = 0.01). Conclusions Segmental acupuncture may be an effective treatment option for women with recurrent UTIs over a longer follow-up period and may limit antibiotics use. Further studies are needed.
Purpose Mirroring global trends, artificial intelligence advances in medicine, notably urolithiasis. It promises accurate diagnoses, effective treatments, and forecasting epidemiological risks and stone passage. This systematic review aims to identify the types of AI models utilised in urolithiasis studies and evaluate their effectiveness. Methods The study was registered with PROSPERO. Pubmed, EMBASE, Google Scholar, and Cochrane Library databases were searched for relevant literature, using keywords such as ‘urology,’ ‘artificial intelligence,’ and ‘machine learning.’ Only original AI studies on urolithiasis were included, excluding reviews, unrelated studies, and non-English articles. PRISMA guidelines followed. Results Out of 4851 studies initially identified, 71 were included for comprehensive analysis in the application of AI in urolithiasis. AI showed notable proficiency in stone composition analysis in 12 studies, achieving an average precision of 88.2% (Range 0.65–1). In the domain of stone detection, the average precision remarkably reached 96.9%. AI’s accuracy rate in predicting spontaneous ureteral stone passage averaged 87%, while its performance in treatment modalities such as PCNL and SWL achieved average accuracy rates of 82% and 83%, respectively. These AI models were generally superior to traditional diagnostic and treatment methods. Conclusion The consolidated data underscores AI’s increasing significance in urolithiasis management. Across various dimensions—diagnosis, monitoring, and treatment—AI outperformed conventional methodologies. High precision and accuracy rates indicate that AI is not only effective but also poised for integration into routine clinical practice. Further research is warranted to establish AI’s long-term utility and to validate its role as a standard tool in urological care.
Purpose Ureterocalicostomy refers to the anastomosis between the lower pole calyces and the ureter. Robotic-assisted laparoscopic ureterocalicostomy (RALUC) is gaining ground, ultimately. The current systematic review summarizes all applications of RALUC in both adults and children. Methods In line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines, three databases (PubMed, Scopus and Cochrane) were screened, from their inception to 16 February 2025. The following search string was used: robotic AND (ureterocalicostomy OR ureterocalicostomies OR ureterocalycostomy OR ureterocalycostomies). Results Eight studies fulfilled all inclusion criteria and were finally considered for qualitative synthesis. The rate of patients who had undergone previous pyeloplasty ranged in included studies from 20% to 100%, while the rate of patients who had undergone a nephrostomy tube placement before the ureterocalicostomy ranged from 38% to 100%. Total operative time ranged from 157.6 (90–240) to 272 min, while estimated blood loss ranged from 27.5 (10–75) to 115 (50–200) mL. Reoperation rates ranged from 0% to 50%, while the success rates ranged from 66.7% to 100%. Finally, taking into consideration the Clavien-Dindo Classification System, the Grade I-II complications ranged from 0% to 40%, while the Grade III-IV ones ranged from 0% to 20%. Conclusion RALUC is a feasible, safe and efficient procedure for patients with complicated ureteropelvic junction obstruction. The implementation of higher-quality studies on larger samples, including comparative ones and randomized controlled trials, is crucial in order to draw safer conclusions.
Background National Health Services (NHS) England mandates that an acute kidney injury (AKI) detection algorithm be embedded in laboratories. We evaluated the implementation of the algorithm and the consistency of alerts submitted to the United Kingdom Renal Registry (UKRR). Methods Code was developed to simulate the syntax of the AKI detection algorithm, executed on data from local laboratories submitted to the UKRR, including alerts and serum creatinine (SCr) results spanning 15 months before and after the alert submission. Acute kidney injury alerts were categorized into stages 0/1/2/3. Inter-rater agreement (Gwet’s AC1) was used to compare local and centrally derived alerts at individual laboratory and commercial laboratory information management system (LIMS) levels, penalizing extreme disagreements. Results The analysis included 9,096,667 SCr results from 29 labs (475,634 patients; median age 72 years, 47% female) between algorithm activation and data extraction (September 30, 2020). Laboratories and the central simulation generated 1,579,633 and 1,646,850 non-zero AKI alerts, respectively. Agreement was high within known laboratory information management system providers (0.97–0.98) but varied across individual laboratories (overall range 0.17–0.98, 0.17–0.23 in three). Agreement tended to be lower (Gwet’s AC1 0.88) with the highest baseline SCr quartile (median 164 μmol/L). Conclusions Overall, alerts submitted to the UKRR are a valid source of AKI surveillance but there are concerns about inconsistent laboratory practices, incomplete adoption of the NHSE algorithm code, alert suppression, and variable interpretation of guidelines. Future efforts should audit and support laboratories with low agreement rates, and explore reasons for lower agreement in individuals with pre-existing CKD. Graphical abstract
Background Inflammatory myofibroblastic tumor (IMT) of urinary bladder is a rare entity of genitourinary tract which has baffled urologists worldwide. Sign and symptoms are site specific. Usually diagnosed on the basis of immunohistochemistry findings. Case presentation 35-year-old female patient presented with gross hematuria since 10 days. Ultrasound revealed a hyperechoic mass from right lateral wall of urinary bladder. Patient was managed with complete transurethral resection of bladder tumor. Histopathology and immunohistochemistry was diagnostic for inflammatory myofibroblastic tumor. 2 months post-surgery patient developed recurrence, following which she was managed with partial cystectomy. Conclusion Inflammatory myofibroblastic tumor diagnosis is very challenging because of rarity of the tumor with non-specific presentation, and confirmation is done only by immunohistochemistry. Patients are usually managed with complete resection of tumor with regular follow-up.
Purpose of Review Near-infrared fluorescence imaging (NIRF) with the use of indocyanine green (ICG) has been recently adopted in pediatric urology after its well-published use in the adult population. As a powerful tool that can help delineate complex anatomy and congenital anomalies, we discuss the various applications of this imaging in minimally invasive and open surgery in pediatric urology. Recent Findings The most reported applications of ICG in pediatric urology are within minimally invasive surgery, particularly varicoceles, renal surgery such as nephrectomies and renal tumor excision, mimicking its use in adult urology. ICG has also been applied to reconstructive urology such as ureteral reconstruction, hypospadias repair and bladder exstrophy. Despite its safety and more widespread use in pediatric surgery, all published studies in pediatric urology to date have been limited to small and single-center experiences, reflecting the novel nature of this technology in this field. Summary ICG has been shown to be safe and effective in children, particularly in those with complex anatomy and in technically challenging surgeries. Future studies should focus on standardized protocols for children and multi-center comparative studies.
Buccal mucosa graft (BMG) ureteroplasty has emerged as a versatile technique for managing long-segment or complex ureteral strictures. However, the optimal surgical approach—Robotic-Assisted (RAS), Laparoscopic, or Open surgery—remains debated. We aimed to systematically evaluate and compare the perioperative outcomes and safety profiles of these three modalities. A systematic literature search was conducted in PubMed, Embase, and Web of Science up to November 2025, following PRISMA 2020 guidelines. Studies reporting outcomes of BMG ureteroplasty via robotic, laparoscopic, or open approaches were included. The primary outcome was surgical success rate. Secondary outcomes included operative time, hospital stay, and complication rates (total and Clavien-Dindo ≥ 3). Statistical analysis was performed using R software with a Generalized Linear Mixed Model (GLMM). Sixteen studies involving 398 patients (Robotic: n = 256; Laparoscopic: n = 98; Open: n = 44) were included. The pooled surgical success rates were uniformly high across all groups: Robotic (90.4%), Laparoscopic (92.5%), and Open (90.9%), with no statistically significant differences ( P > 0.05). However, regarding safety, the robotic approach demonstrated a superior profile. Despite managing complex cases, the robotic cohort exhibited a minimal incidence of major complications (Clavien-Dindo ≥ 3) compared to laparoscopic and open groups. Sensitivity analysis confirmed the robustness of these findings, indicating that the efficacy of RAS is generalizable and not driven by single-center data. Robotic-assisted BMG ureteroplasty achieves excellent functional outcomes comparable to the open gold standard and the laparoscopic approach. In terms of safety, RAS demonstrates a favorable profile with a marked reduction in severe perioperative complications compared to laparoscopic and historical open cohorts. Consequently, RAS represents a safe and effective minimally invasive alternative for complex ureteral reconstruction, offering durability comparable to open repair with minimized morbidity.
Background Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes.
Introduction Complex proximal ureteral strictures can pose significant surgical challenges, including long or obliterated strictures, inability to perform primary anastomotic repairs, fixed renal pelvis, impaired vascular supply from prior surgeries, and poor healing of the proximal ureter. We describe a novel surgical technique for addressing these issues. Methods Our technique involves a combination of ureterolysis, renal pelvis flap creation, and buccal mucosal grafting. The procedure commences with exposure of the renal pelvis, creation of a U-shaped renal pelvis flap as the posterior plate and a buccal mucosa graft as the anterior plate. The omentum is then secured to provide a vascular bed for the graft. Results A total of 4 patients were included, with a mean age of 49 years. The median operating time was 4.08 h. The median post-operative length of stay was 1.5 days. At initial mean radiographic follow-up period of 3.2 months the success rate of the reconstruction was 100% with all patients demonstrating complete resolution of symptoms and radiographic improvement. Long-term follow-up was on average 22.3 months with sustained stability/improvement in radiographic hydronephrosis and symptoms, with no evidence of stricture recurrence. There were no donor site complications. Conclusion This novel surgical technique, involving ureteroplasty with a renal pelvis flap augmentation and buccal mucosal graft (RPFA-BMG), proves effective for complex proximal ureteral reconstruction. It is particularly suitable for long proximal obliterated strictures that require a combination of tissue transfer techniques for successful ureteral reconstruction and achievement of physiologic drainage.
Purpose To compare the safety and efficacy of bilateral same-session retrograde intrarenal surgery (B-RIRS) and unilateral retrograde intrarenal surgery (U-RIRS) for treating renal stones, focusing on stone-free rates (SFR), complications, retreatment rates, operative time, and hospital stay. Materials and methods A systematic review was conducted following PRISMA guidelines. Seven comparative studies met the inclusion criteria. Primary outcomes included SFR and complications (minor: Clavien-Dindo I–II; major: III–V); secondary outcomes comprised retreatment rates, operative time, and hospital stay. Random-effects models were used to generate pooled odds ratios (OR) for categorical outcomes and mean differences (MD) for continuous variables. Subgroup analyses compared adult-only populations with elderly-inclusive cohorts. Results A total of 1,218 patients from seven studies were analyzed. Overall, B-RIRS showed no statistically significant difference in SFR (OR 0.73; 95% CI, 0.43–1.23) compared to U-RIRS, yet subgroup analyses indicated that elderly populations tended to have lower SFR with bilateral procedures. B-RIRS was associated with higher minor (OR 2.55; 95% CI, 1.33–4.90) and major complications (OR 3.16; 95% CI, 1.38–7.24), increased retreatment needs (OR 2.46; 95% CI, 1.48–4.08), and longer operative times (MD 24.99 min; 95% CI, 17.48–32.50). Hospital stay was similar between groups. Conclusions Although B-RIRS facilitates management by reducing multiple anesthesia exposures and maintaining similar SFRs, it appears to be linked with increased complication and retreatment rates, especially in elderly or comorbidity-heavy populations. Carefully selected patients may see more comparable complications. Future randomized trials are needed to confirm these subgroup findings, standardize stone-free definitions, and refine selection criteria for bilateral same-session RIRS.
The successful identification of hazards at an early stage is a cornerstone of public health in the area of food safety. The Swiss Federal Food Safety and Veterinary Office has been running an early detection system since 2018. A group of experts that identifies information concerning hazards and evaluates it periodically carries out the Federal Food Safety and Veterinary Office’s early detection system. The advisory board, a scientific panel of experts from industry, universities, enforcement authorities and reference centres, discusses the topics and makes recommendations to the Swiss Federal Food Safety and Veterinary Office. To date, a total of 37 topics were handled. A monthly newsletter is published on early detection topics. In addition, “Briefing Letters” with an in-depth enquiry are issued on an irregular basis. Die Identifizierung von Gefahren in einem frühen Stadium ist ein zentraler Baustein der öffentlichen Gesundheit im Bereich der Lebensmittelsicherheit. Das Bundesamt für Lebensmittelsicherheit und Veterinärwesen der Schweiz verwendet seit 2018 ein System zur Früherkennung. Dieses stützt sich auf eine Gruppe von Fachpersonen, welche Informationen zu Gefahren identifizieren und periodisch bewerten. Der Beirat, ein wissenschaftliches Gremium von Experten und Expertinnen aus der Wirtschaft, von Hochschulen, Vollzugsbehörden und Referenzzentren erörtert anschließend die Themen und gibt seinerseits Empfehlungen an das Bundesamt für Lebensmittelsicherheit und Veterinärwesen ab. Insgesamt wurden bislang 37 Themen bearbeitet. Monatlich wird ein Newsletter zu Themen der Früherkennung publiziert. Zudem werden unregelmäßig bei Bedarf Briefing Letters mit einer vertieften Recherche zu einem Thema erstellt.
International audience;
Abstract Many cases of wildlife poisoning in Europe have been reported causing population declines, especially in raptors. Toxicovigilance and risk assessment studies are essential to reinforce the knowledge of the number of illegal poisoning cases and the substances involved in these crimes. Many researchers and projects in different institutions have suggested the creation of a network to improve communication and share information between European countries. This article presents the results of the Short-Term Scientific Mission titled “Developing a Network of Analytical Labs and Government Institutions” supported by the COST Action European Raptor Biomonitoring Facility (CA16224), which aims to initiate a network of veterinary forensic toxicology laboratories, in order to improve communication among laboratories to prevent wildlife poisoning, especially in raptors. For this purpose, a questionnaire was designed and sent by email to 119 laboratories in Europe. It contained 39 questions on different topics (e.g. laboratory activities, analytical information). A total of 29 responses were received. Most participant laboratories work on veterinary forensic toxicology research and external cases at the same time, which provides a robust overview of the actual situation in the field. Analytical techniques and data collection methods should be harmonised, and communication between laboratories is encouraged to create a more effective network. The present study established contact between laboratories as an initial step to create a European network and compiled basic data to identify strengths and weaknesses that will help harmonise methodologies across Europe and increase pan-European capacities.
Mary Ann Liebert, Inc., publishersfebruari 2023Dierenarts
High-quality, well-annotated, healthy tissue specimens are crucial to the success of basic and translational research, but often difficult to procure. Postmortem (PM) tissue collections provide the opportunity to collect these healthy biospecimens. PM procurement programs led by biobanks can further contribute by providing researchers with rare biospecimens collected with short postmortem intervals (PMI) in controlled environments. To support biomedical and translational research, the Cornell Veterinary Biobank (CVB), an ISO 20387 accredited core resource at the Cornell University College of Veterinary Medicine, has performed PM tissue collections from research and privately owned animals since 2013. The CVB PM collection team, consisting of a board-certified veterinary pathologist, a licensed veterinary technician collection specialist, and a data capture specialist, performs rapid tissue collections during controlled warm necropsies, with an accepted PMI of ≤2 hours and a target PMI of ≤1 hour. A retrospective analysis of PM collections between 2013 and 2020 was completed, consisting of 4077 aliquots of 1582 biospecimens from 69 donors (48 canine, 16 feline, and 5 equine). An average of 22.93 biospecimens per donor were collected (range: 1–49). The average PMI for standard collections was 43.48 ± 2.30 minutes, starting on average 20.81 ± 1.61 minutes after time of death. Thus far, the CVB has a favorable utilization rate, with 414 aliquots (10.15%) from 350 specimens (20.12%) and 45 animals (65.22%) distributed to researchers. The success of the CVB PM tissue biobanking program, collecting high-quality biospecimens with short PMIs, was due to support from veterinary pathologists, the competence of CVB personnel, and the continuous evolution of methods within a quality management system. Improvement of PM tissue collection programs in biobanks, with standardized practices for all processes and specialized personnel, can enhance the quality and increase utilization of its biospecimens and associated data.
Background The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS. Results English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25–8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12–17.35). The annual proportional birth rate was relatively stable between 2.97–3.51% from 2005–2016. The most common specific diagnoses were periodontal disease ( n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31–22.62), otitis externa ( n = 234, 10.09%, 95% CI: 8.87–11.32), obesity ( n = 229, 9.88%, 95% CI: 8.66–11.09), anal sac impaction ( n = 187, 8.07%, 95% CI: 6.96–9.18), diarrhoea ( n = 113, 4.87%, 95% CI: 4.00–5.75), and aggression ( n = 93, 4.01%, 95% CI: 3.21–4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) ( P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) ( P = 0.010). The median age at death was 11.44 years (IQR 9.46–13.47) and the most common grouped causes of death were neoplasia ( n = 10, 9.26%, 95% CI: 3.79–14.73), mass-associated disorders ( n = 9, 8.33%, 95% CI: 4.45–15.08), and collapse ( n = 8, 7.41%, 95% CI: 3.80–13.94). Conclusions Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS. The English Cocker Spaniel (ECS) is a popular family dog in the UK, but there is limited information regarding common disorders affecting the breed. The goal of this study was to describe demography (age, sex, neuter, and bodyweight), disease occurrence, lifespan, and reasons for death in ECS by using data from the VetCompass™ Programme. The VetCompass™ Programme collects information from anonymised clinical records of dogs attending first-opinion veterinary practices in the UK. This study hypothesised that aggression is more common in males than in females, and in solid-coloured than in bi-coloured ECS dogs. English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. Breed popularity did not vary much from 2005 to 2016, comprising around 3% of all dogs born each year. The average age of dogs in 2016 was 4.57 years and the average adult bodyweight was 15.05 kg. The most common disorders were periodontal disease (infection of the tissues that hold the teeth in place, affecting 20.97% of the dogs), inflammation of the external ear canal (10.09%), obesity (9.88%), anal sac impaction (8.07%), diarrhoea (4.87%), and aggression (4.01%). Aggression was more common in males (4.95%) than in females (2.87%) and in solid-coloured (7.00%) than in bi-coloured (3.66%) dogs. The frequency of aggression also varied across the four most common solid colours (black, liver, golden, red), with golden-coloured dogs showing the most aggression (12.08%). The average lifespan was 11.44 years and the most common cause of death was tumours. This study shows that first-opinion clinical records can help us to understand and enhance breed health. The results can guide veterinarians in giving breed-adapted information to owners of ECS and help breeders to optimise breeding decisions. Further, this information can be used by future ECS owners to make more informed decisions when acquiring a dog if avoidance of aggression is a key priority. Periodontal disease was the most common condition affecting the breed, which highlights the importance of regular veterinary dental checks and as well as tooth brushing in ECS.
Urban sludge contains pharmaceutical residues and various biocides, which are partly treated in wastewater treatment plants. Liquid manure contains also veterinary pharmaceuticals and biocides used to clean livestock installations. Both sludge and manure are spread as agricultural fertilisers. Traces of human and veterinary pharmaceutical residues, as well as biocides, are also present in many rivers and aquifers, and in agricultural soils in France and around the world. The thesis is devoted to the evaluation of transfers of and processes (degradation, infiltration, adsorption, etc.) related to pharmaceutical residues and biocides from both urban sludge and liquid manure spread on fields as fertilizer for agriculture. It is part of the Telesphore project carried out on the SIPIBEL observatory. The main objective is to evaluate the possible contamination of soil and groundwater by pharmaceuticals and biocides due to organic waste products (OWPs) spread for fertilizing. The experimental part is based on three scales experiments: (i) controlled microcosm assays to characterise sorption onto soils and soil/OWP mixtures (ii) lab soil column assays under controlled conditions on soil columns to assess vertical transport and (iii) \textit{in situ} spreading campaigns on lysimeters, under both actual and augmented conditions of OWPs spreading. The sorption parameters obtained from the microcosm assays were used for HYDRUS-1D modelling of reactive transport in the soil columns. The contrasting behaviour of pharmaceutical and biocides residues at the different scales highlights the complexity of the processes involved in the fate of pharmaceutical and biocidal residues after spreading of OWPs. Overall, the results show that manure and sludge spread at agronomic rates do not lead to the accumulation of pharmaceutical and biocidal residues in the soil, and that the flux of compounds retained in the soil or transported to groundwater represent a small fraction of what is spread with the OWPs.
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Les boues urbaines contiennent des résidus pharmaceutiques et des biocides divers, partiellement traités dans les stations d’épuration. Le lisier contient des pharmaceutiques vétérinaires et des biocides utilisés pour le nettoyage des installations d’élevage. Les boues comme les lisiers sont épandus comme fertilisant pour l’agriculture. Des traces de résidus pharmaceutiques humains et vétérinaires, ainsi que des biocides sont ainsi présents dans de nombreuses rivières et aquifères, et dans les sols agricoles en France et dans le monde entier. La thèse est consacrée à l'évaluation des transferts et des processus associés (dégradation, infiltration, adsorption, etc.) liés aux résidus pharmaceutiques et aux biocides provenant à la fois des boues des stations d'épuration urbaines et des lisiers épandus sur les champs comme engrais pour l'agriculture. Elle fait partie du projet Telesphore réalisé sur l'observatoire SIPIBEL. L'objectif principal est d'évaluer la contamination possible par les produits pharmaceutiques et les biocides des sols et des eaux souterraines due à l'épandage de produits résiduaires organiques (PRO) comme fertilisants. La partie expérimentale est bâtie sur trois échelles d’étude (i) des essais en microcosme pour caractériser la sorption à des sols et des mélanges sol/PRO (ii) des essais en conditions contrôlées sur colonnes de sol pour évaluer les transferts verticaux et (iii) des campagnes in situ sur des lysimètres (Fig. 1) soit en condition réelle d’épandage, soit en taux d’application élevé de PRO. Les paramètres de sorption obtenus par les essais en microcosme sont utilisés pour la modélisation sur HYDRUS 1D du transfert réactif des essais sur colonnes de sol.
The Boxer is a medium-large sized, active dog with a short coat and a moderately flat-faced (brachycephalic) skull shape. Despite many decades of popularity in the UK, there is limited published evidence on the overall health profile of Boxers. White-coloured Boxers are thought to be at higher risk of deafness from birth and as a result, white Boxers have traditionally often been culled at birth by breeders. Using anonymised veterinary clinical records collected within the VetCompass Programme at the Royal Veterinary College (RVC), Boxers made up around 1% of all dogs in the UK in 2016, with an average adult bodyweight around 30 kg. The most common colours were brindle (22.82%), dark red (22.62%) and dark red multi-colour (20.92%), with 10.71% white Boxers. Across the 3,219 Boxers in the study, 73.97% had at least one disorder recorded during 2016. The average number of disorders per year did not differ statistically between female and male Boxers, or between white and non-white Boxers. The most common specific disorders in Boxers were ear infection (7.15%), gum mass (5.84%), eye ulcer (5.00%) and dental disease (4.63%). White and non-white dogs did not differ in their risk for any of the 34 most common specific disorders. Only two dogs in the study were recorded with deafness; one white and one non-white. The average lifespan of Boxers overall was 10.46 years. Lifespan did not differ statistically between female and male Boxers, or between white and non-white Boxers. This study identifies ongoing popularity for the Boxer in the UK, with around 10% of these Boxers being white. There was minimal evidence of health differences between male and female Boxers, or between white and non-white Boxers. Among the four most common disorders recorded in Boxers, two are typically common across all types of dogs (ear and dental disease) while two showed strong predisposition in the Boxer breed (gum mass and eye ulcer), suggesting the value of understanding breed-specific health patterns to prioritise health plans for each breed. The overall longevity of Boxer dogs was typical of other breeds of this body size. Background The Boxer is a popular dog breed with a distinctive appearance. However, the breed has been linked with several health conditions, some of which have been associated with its moderately brachycephalic conformation and its white colouration. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Boxers in the UK in 2016. Results The study population of 336,865 dogs included 3,219 (0.96%) Boxers, of which 10.71% were recorded as white. The mean adult bodyweight was 30.43 kg (SD 5.73 kg). Annual disorder counts did not differ statistically between the sexes or between white and non-white Boxers. The most prevalent fine-level precision disorders were otitis externa ( n = 230, 7.15%), epulis (188, 5.84%), corneal ulceration (161, 5.00%) and periodontal disease (149, 4.63%). Of the 34 most common fine-level disorders, none differed in prevalence between white and non-white dogs. The most prevalent disorder groups were skin disorder ( n = 571, 17.74%), neoplasia (457, 14.20%) and ear disorder (335, 10.41%). White Boxers had higher prevalence than non-white Boxers for two disorder groups: dental disorder and brain disorder. The median longevity of 346 Boxers that died during the study was 10.46 years (IQR 9.00–11.98, range 2.76–18.00). Median longevity did not differ statistically between the sexes or between white and non-white Boxers. The most common grouped causes of death were death – unrecorded cause ( n = 73, 21.10%), neoplasia (43, 12.43%) and brain disorder (33, 9.54%). Conclusions There was minimal evidence of substantial health differences between white and non-white Boxers. Among the four most common disorders recorded in Boxers, two were typically common across all types of dogs (otitis externa and periodontal disease) while two suggested strong predispositions for the Boxer breed (epulis and corneal ulceration), showing the value of eliciting breed-specific disorder patterns for insights for potential health reforms. The overall longevity of Boxer dogs was consistent with other breeds of similar body size.
Public Library of Science (PLoS)december 2021Dierenarts
SARS-CoV-2 has clearly shown that efficient management of infectious diseases requires a top-down approach which must be complemented with a bottom-up response to be effective. Here we investigate a novel approach to surveillance for transboundary animal diseases using African Swine (ASF) fever as a model. We collected data both at a population level and at the local level on information-seeking behavior respectively through digital data and targeted questionnaire-based surveys to relevant stakeholders such as pig farmers and veterinary authorities. Our study shows how information-seeking behavior and resulting public attention during an epidemic, can be identified through novel data streams from digital platforms such as Wikipedia. Leveraging attention in a critical moment can be key to providing the correct information at the right moment, especially to an interested cohort of people. We also bring evidence on how field surveys aimed at local workers and veterinary authorities remain a crucial tool to assess more in-depth preparedness and awareness among front-line actors. We conclude that these two tools should be used in combination to maximize the outcome of surveillance and prevention activities for selected transboundary animal diseases such as ASF.
Background Bovine uterine prolapse is a sporadic but life-threatening postpartum condition. The aims of this study were; (i) to determine which clinical findings determined the likelihood of treatment vs. culling, (ii) to identify the treatment methods currently employed by Norwegian veterinary surgeons and evaluate their effect on survival, (iii) to determine if clinical findings at the time of treatment could be used to determine prognosis. Practicing veterinary surgeons in Norway were contacted and asked to fill out a questionnaire on cases of bovine uterine prolapse they attended between February and October 2012. The questionnaires gathered data on signalment, clinical presentation, treatment, and outcome. These data were supplemented with culling data from the Norwegian Dairy and Beef Herd Recording Systems. The chi-squared test and logistic regression modelling was performed to identify likelihood of treatment and cox proportional hazard modelling was performed to identify the hazard of death after treatment. Results Data from 126 cases of bovine uterine prolapse were collected (78 beef and 48 dairy cows). Twenty-six cows (21%) were emergency slaughtered, or underwent euthanasia, without treatment. Of the remaining 100 cases amputation of the uterus was performed once and repositioning was performed in 99 cases. Survival data were missing from 2 of the cases that had undergone treatment leaving a study sample of 97 cases (64 beef and 33 dairy cows). Multivariable logistic regression analysis of the explanatory variables showed that beef cows were more likely to be treated than dairy cows (OR = 0.32, 95% CI 0.13 to 0.81, P = 0.017) and that cows with a significantly oedematous or traumatised uterus were less likely to be treated (OR = 0.26, 95% CI 0.10 to 0.67, P = 0.006). Treatment methods amongst Norwegian practitioners were broadly similar. In a multivariable model cows general clinical state at time of treatment was positively correlated with survival (HR = 0.29, 95% CI 0.29 to 0.73, P = 0.008) and a history of a vaginal prolapse prepartum increased the hazard of death (HR = 2.31, 95% CI 1.08 to 4.95, P = 0.031) in the first 30 days after treatment of a uterine prolapse. In the first 180 days after treatment only veterinary assessment of a cows’ general clinical state was correlated with hazard of death (HR = 0.432, 95% CI 0.20 to 0.91, P = 0.046). Conclusions This study shows that the production system and extent of uterine damage affect the likelihood of treatment, and that practitioners use similar treatment methods. A cows’ general clinical state at time of treatment was positively correlated with survival, and a history of a vaginal prolapse prepartum increased the hazard of death in the first 30 days after treatment of a uterine prolapse.
SIMPLE SUMMARY: The field of veterinary minimally invasive surgery has grown, but there is a lack of easily accessible training tools for practitioners worldwide. While borrowing human medicine simulators helps with basic skills, specific veterinary procedures require specialized training. Some simulators are being developed, validated, and found to be effective for training vets both in basic skills and advanced techniques. Nevertheless, these simulators are of interest mostly for dogs and horses, and their number is small. This study emphasizes the need for more advanced simulators to improve surgical techniques for various animal species. ABSTRACT: Veterinary minimally invasive surgery (MIS) has experienced notable growth in recent years, yet the availability of specialized training tools remains limited and not readily accessible to practitioners worldwide. While borrowing simulators from human medicine practices suffices for acquiring fundamental laparoscopic skills, it proves inadequate when addressing procedure-specific nuances. Veterinary professionals are now taking steps to create simulators tailored to their patients, although the validation process can be time-consuming. Consequently, the availability of advanced laparoscopic simulators for veterinary training remains scarce. The present study aims to highlight custom-made simulators. A comprehensive search across five databases was conducted to uncover the simulators documented from 2010 to 2022. A total of five simulators emerged from this search, with four grounded in a canine model and only one in an equine model. These models underwent validation and were found to be effective in training surgeons for their designated tasks. The findings underscore a limited array of simulators, predominantly catering to two species (horses and dogs). Considering these findings, it is evident that further research is imperative to create laparoscopic simulators capable of facilitating advanced veterinary training. This would enable the continued evolution of surgical techniques across diverse species, including ruminants, small mammals, and non-mammalian animals.
Mesenchymal stem cell (MSC) therapy is a promising approach for treating orthopaedic conditions in veterinary clinical patients. MSCs exhibit remarkable regenerative properties, including multilineage differentiation, immunomodulation, and tissue repair, making them an attractive alternative to conventional therapies. This comprehensive review explores the clinical potential of MSCs in managing a range of canine orthopaedic disorders, including fractures, degenerative joint diseases, and tendon injuries. Evidence from canine clinical studies highlights the ability of MSCs to enhance tissue healing, reduce pain, and restore function, offering valuable insights into their therapeutic utility. Optimizing delivery methods, such as intra-articular injections and scaffold-based approaches, is critical for maximizing therapeutic efficacy. Clinical trials in dogs have shown significant improvements in mobility and recovery, underscoring the relevance of MSC therapy for specific orthopaedic applications. Despite its potential, MSC therapy faces several challenges. One major hurdle is study heterogeneity, which complicates evidence synthesis. Differences in cell sourcing, dosage, and injection frequency make it difficult to establish a consensus on optimal treatment protocols. Future advancements should focus on expanding cell-free approaches utilizing MSC-derived bioactive molecules and extracellular vesicles. Furthermore, collaborative efforts between veterinarians, researchers, and industry partners will be critical in translating preclinical findings into viable commercial veterinary stem cell products. Large-scale, randomized clinical trials with standardized methodologies are necessary to validate the efficacy of MSC therapy across different orthopaedic conditions. Graphical abstract
SIMPLE SUMMARY: The article summarizes the current knowledge on factors related to pregnancy, parturition, and newborns that affect the health status of a puppy and determine its chances for survival and development. The detailed information is provided in terms of breed predispositions, objectives of pregnancy monitoring, potential sources of complications, and veterinary advances in care and treatment of perinatal conditions. Successful pregnancy outcomes still pose challenges in veterinary neonatology; thus, publications presenting the current state of knowledge in this field are in demand. ABSTRACT: The perinatal period has a critical impact on viability of the newborns. The variety of factors that can potentially affect the health of a litter during pregnancy, birth, and the first weeks of life requires proper attention from both the breeder and the veterinarian. The health status of puppies can be influenced by various maternal factors, including breed characteristics, anatomy, quality of nutrition, delivery assistance, neonatal care, and environmental or infectious agents encountered during pregnancy. Regular examinations and pregnancy monitoring are key tools for early detection of signals that can indicate disorders even before clinical signs occur. Early detection significantly increases the chances of puppies’ survival and proper development. The purpose of the review was to summarize and discuss the complex interactions between all elements that, throughout pregnancy and the first days of life, have a tangible impact on the subsequent fate of the offspring. Many of these components continue to pose challenges in veterinary neonatology; thus, publications presenting the current state of knowledge in this field are in demand.
Background Bacterial corneal infections are common and potentially blinding diseases in all species. As antibiotic resistance is a growing concern, alternative treatment methods are an important focus of research. Photoactivated chromophore for keratitis-corneal crosslinking (PACK-CXL) is a promising oxygen radical-mediated alternative to antibiotic treatment. The main goal of this study was to assess the anti-bactericidal efficacy on clinical bacterial isolates of the current standard and an accelerated PACK-CXL treatment protocol delivering the same energy dose (5.4 J/cm^2). Methods Clinical bacterial isolates from 11 dogs, five horses, one cat and one guinea pig were cultured, brought into suspension with 0.1% riboflavin and subsequently irradiated. Irradiation was performed with a 365 nm UVA light source for 30 min at 3mW/cm^2 (standard protocol) or for 5 min at 18mW/cm^2 (accelerated protocol), respectively. After treatment, the samples were cultured and colony forming units (CFU’s) were counted and the weighted average mean of CFU’s per μl was calculated. Results were statistically compared between treated and control samples using a linear mixed effects model. Results Both PACK-CXL protocols demonstrated a significant bactericidal effect on all tested isolates when compared to untreated controls. No efficacy difference between the two PACK-CXL protocols was observed. Conclusion The accelerated PACK-CXL protocol can be recommended for empirical use in the treatment of bacterial corneal infections in veterinary patients while awaiting culture results. This will facilitate immediate treatment, the delivery of higher fluence PACK-CXL treatment within a reasonable time, and minimize the required anesthetic time or even obviate the need for general anesthesia.
SIMPLE SUMMARY: Measuring left atrial size has important prognostic and therapeutic consequences in cardiac diseases. An enlarged left atrium indicates that the cardiac disease is severe. Though cardiac ultrasound examination is the best way to determine left atrial size, this technique is often unavailable in veterinary practices, as it is expensive and requires specific expertise. Therefore, chest X-rays are usually used to decide whether the left atrium is enlarged. With that, practicing veterinarians aim to differentiate cardiac from respiratory diseases, which both can lead to similar clinical signs. However, determining left atrial enlargement on X-rays can be challenging. The authors of this study came up with a simple and reproducible method that might make determining left atrial size on X-rays easier. The study aimed to compare two methods. Dogs with and without cardiac disease were included. The left atrial size of the included dogs had also been determined with ultrasonography to serve as a reference. First, 39 veterinarians and veterinary students interpreted 90 canine chest X-rays subjectively. At least two weeks later, the same observers applied the new method on the same radiographs. The new standardized method did not give a more accurate diagnosis than subjective assessment. ABSTRACT: Background: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. Methods: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. Results: The new method moderately correlated with LA:Ao (r = 0.56–0.66) in all groups. The diagnostic accuracy (72–74%) of the subjective assessment and the new method showed no difference. Conclusions: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation.
Background Quality of life (QoL) provides a comprehensive concept underpinning veterinary decision-making that encompasses factors beyond physical health. It becomes particularly pertinent when seeking responsible choices for chronically ill or old horses that emphasise their well-being and a good QoL over the extension of life. How different stakeholders use the concept of QoL is highly relevant when considering the complexity of these decisions in real-life situations. Methods Seven focus group discussions ( N = 39) were conducted to gain insights into how stakeholders assess and use equine QoL in veterinary care decisions for chronically ill and/or old horses. The discussions included horse owners ( n = 17), equine veterinarians ( n = 7), veterinary officers ( n = 6), farriers ( n = 4), and horse caregivers ( n = 5). The combination of deductive and inductive qualitative content analysis of the group discussions focused on identifying both similarities and differences in the views of these groups regarding QoL for old and/or chronically ill horses. Results Findings show agreement about two issues: the importance of the individuality of the horse for assessing QoL and the relevance of QoL in making decisions about veterinary interventions. We identified differences between the groups with respect to three issues: the time required to assess QoL, stakeholders’ contributions to QoL assessments, and challenges resulting from those contributions. While owners and caregivers of horses emphasised their knowledge of a horse and the relevance of the time they spend with their horse, the veterinarians in the study focused on the differences between their own QoL assessments and those of horse owners. In response to challenges regarding QoL assessments and decision-making, stakeholders described different strategies such as drawing comparisons to human experiences. Conclusions Differences between stakeholders regarding equine QoL assessments contribute to challenges when making decisions about the care of chronically ill or old horses. The results of this study suggest that individual and collaborative reflection about a horse’s QoL should be encouraged, for example by developing practicable QoL assessment tools that support relevant stakeholders in this process.
Background Extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) are important causative agents for infections in humans and animals. At the Equine Veterinary Teaching Hospital of the University of Helsinki, the first infections caused by ESBL-E were observed at the end of 2011 leading to enhanced infection surveillance. Contact patients were screened for ESBL-E by culturing infection sites and rectal screening. This study was focused on describing the epidemiology and microbiological characteristics of ESBL-E from equine patients of the EVTH during 2011–2014, and analysing putative risk factors for being positive for ESBL-E during an outbreak of Klebsiella pneumoniae ST307. Results The number of ESBL-E isolations increased through 2012–2013 culminating in an outbreak of multi-drug resistant K. pneumoniae ST307: bla _CTX-M-1: bla _TEM: bla _SHV during 04–08/2013. During 10/2011–05/2014, altogether 139 ESBL-E isolates were found from 96 horses. Of these, 26 were from infection-site specimens and 113 from rectal-screening swabs. A total of 118 ESBL-E isolates from horses were available for further study, the most numerous being K. pneumoniae (n = 44), Escherichia coli (n = 31) and Enterobacter cloacae (n = 31). Hospital environmental specimens (N = 47) yielded six isolates of ESBL-E. Two identical E. cloacae isolates originating from an operating theatre and a recovery room had identical or highly similar PFGE fingerprint profiles as five horse isolates. In the multivariable analysis, mare–foal pairs (OR 4.71, 95% CI 1.57–14.19, P = 0.006), length of hospitalisation (OR 1.62, 95% CI 1.28–2.06, P < 0.001) and passing of a nasogastric tube (OR 2.86, 95% CI 1.03–7.95, P = 0.044) were associated with being positive for ESBL-E during the K. pneumoniae outbreak. Conclusions The occurrence of an outbreak caused by a pathogenic ESBL-producing K. pneumoniae ST307 strain highlights the importance of epidemiological surveillance of ESBL-E in veterinary hospitals. Limiting the length of hospitalisation for equine patients may reduce the risk of spread of ESBL-E. It is also important to acknowledge the importance of nasogastric tubing as a potential source of acquiring ESBL-E. As ESBL-E were also found in stomach drench pumps used with nasogastric tubes, veterinary practices should pay close attention to appropriate equipment cleaning procedures and disinfection practices.
This doctoral research falls in the area of languages for specific purposes (LSP) and aims to define and characterise a new LSP, veterinary English, from a comparative, intercultural perspective. It aims to cater to the needs of different groups of learners, from undergraduate students to practicing vets who interact with animal owners in English.The first part of the thesis circumscribes the domain of interest, as well as the community and genres concerned. I propose the hypothesis that a veterinary consultation is a cultural social act which requires that a veterinarian working in an intercultural context should have competence in a second culture. In particular, such vets should be aware of the vet's role in society and the place of the animal in the family, in order to respond to clients' expectations. They also need to develop sociopragmatic competence, including for instance the politeness norms which underpin interactional outcomes.I take an ethnographic approach which relies both on the tools of conversation analysis as applied in human medicine and on the contrastive approach favoured by comparative linguistics. My corpus involves filmed consultations in France and the UK, and analysis focuses on parallel sequences in French and British contexts. By closely investigating the language used to co-construct actions in the two communities, it is possible to isolate the cultural influences operating in each. This second section of the dissertation thus focuses on methodology, the concepts employed in analysis, the constitution of the corpus, and data preparation.In the third and final part, I bring together observations from these filmed interactions to analyse the influence of context, models of communication and culturally specific conversational norms. The final chapter re-examines these results in the light of the questions concerning language teaching which provided the initial impetus for this research project. It includes proposals for a veterinary English syllabus and teaching/learning activities to meet the particular needs of learners, particularly with respect to intercultural competences.We trust that this research responds to Van de Yeught's (2016) call for a "collective project" to describe different LSPs both in terms of its methodological approach, inspired by interventionist sociolinguistics, and with respect to the results presented. Future work might confirm the findings of this research using different forms of triangulation.
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Cette thèse s'inscrit dans le domaine des langues de spécialité (LSP) et cherche à définir et caractériser la LSP anglais vétérinaire, en adoptant une perspective comparatiste interculturelle avec pour objectif de mieux répondre aux besoins des différents publics d'apprenants, qu'ils soient étudiants en formation initiale ou praticiens amenés à interagir avec des clients en anglais. La première partie nous permet de circonscrire le domaine, la communauté et les genres concernés, et d'émettre l'hypothèse que la consultation vétérinaire est un acte social culturel, ce qui implique, pour le vétérinaire pratiquant en situation interculturelle, d'être compétent dans la culture de l'Autre : connaître la place du vétérinaire dans la société, de l'animal dans la famille, pour pouvoir répondre aux attentes du client ; avoir développé des compétences sociopragmatiques, telles que les normes de politesse auxquelles se référer dans les interactions finalisées. Notre recherche, d'approche ethnographique, convoque à la fois les outils de l'analyse conversationnelle tels que appliqués au domaine médical, et la démarche contrastive de la linguistique comparée : nous examinons des séquences fonctionnelles issues de deux corpus de consultations filmées en milieu naturel au Royaume-Uni et en France. C'est en étudiant au plus près la langue qui permet la co-construction de l'action par les interactants dans les deux communautés que nous pouvons repérer les influences culturelles dans l'une et dans l'autre. La deuxième partie présente ainsi la méthodologie, les concepts utilisés pour l'analyse, la constitution des corpus et le traitement des données. Dans la troisième partie, nous collectons les observables de nos interactions filmées et les analysons d'un point de vue contextuel, en référence au modèle de communication adopté par les deux communautés et aux normes conversationnelles particulières à chacune. Nous nous appuyons ensuite sur les résultats de notre analyse pour répondre aux questions didactiques qui ont motivé notre projet de recherche et formulons des propositions de programme et d'activités d'enseignement qui répondent aux besoins identifiés chez les apprenants, parmi lesquels nous soulignons le développement de compétences interculturelles. Ce travail constitue une contribution au « projet collectif » de description des LSP, initié par Michel Van der Yeught (2016), tant par l'approche retenue - inspirée d'une autre discipline, celle des sociolinguistes interventionnistes - que par les connaissances produites. Il serait intéressant de confirmer nos résultats par d'autres formes de triangulation.
OBJECTIVES: To estimate the frequency and risk factors for Cushing's syndrome in dogs under UK primary veterinary care. MATERIALS AND METHODS: Dogs with Cushing's syndrome were identified by searching electronic patient records of primary‐care veterinary practices. Pre‐existing and incident cases of Cushing's syndrome during 2016 were included to estimate the 1‐year period prevalence. Incident cases were used to estimate the annual incidence and to identify demographic risk factors for the diagnosis of Cushing's syndrome in dogs, through multivariable logistic regression. RESULTS: Analysis included 970 pre‐existing and 557 incident cases of Cushing's syndrome from a population of 905,544 dogs. The estimated 1‐year period prevalence for Cushing's syndrome in dogs under veterinary care was 0.17% (95% confidence interval 0.16 to 0.18) and incidence was 0.06% (95% confidence interval 0.05 to 0.07). In multivariable logistic regression modelling, the Bichon frise (odds ratio=6.17, 95% confidence interval 4.22 to 9.00), Border terrier (5.40, 95% confidence interval 3.66 to 7.97) and Miniature schnauzer (3.05, 95% confidence interval 1.67 to 5.57) had the highest odds of Cushing's syndrome. The Golden retriever (0.24, 95% confidence interval 0.06 to 0.98) and Labrador retriever (0.30, 95% confidence interval 0.17 to 0.54) were the most protected breeds. Increasing age, bodyweight greater than the breed‐sex mean and being insured also showed increased odds of Cushing's syndrome. CLINICAL SIGNIFICANCE: As Cushing's syndrome is predominately diagnosed and managed in primary‐care practice, this study provides valuable new information of its epidemiology in this setting. Demographics reported are supportive of previous work and additional novel associations identified, such as the Border terrier, could enhance the index of suspicion for veterinarians.
Background Beagles are a popular companion animal dog breed and are generally stated to be a healthy breed. This VetCompass study aimed to report the demography, common disorders and mortality of Beagles under primary veterinary care in the UK. Anonymised clinical records within VetCompass were followed over time to extract disorder and mortality data during 2019 on Beagles under primary veterinary care in the UK. Results Beagles comprised 19,906 (0.88%) of the 2,250,417 dogs in the study population. Annual proportional birth rates showed an increasing breed popularity from 0.41% of all dogs born in 2005 and peaking at 1.06% in 2012, followed by a decrease to 0.90% in 2019. The median adult bodyweight was 18.19 kg (IQR 15.68–21.07). From a random sample of Beagles (3,729/19,906, 18.73%), the most diagnosed disorders were obesity (24.27%, 95% CI: 22.89–25.65), periodontal disease (17.78%, 95% CI: 16.55–19.01), overgrown nail(s) (11.61%, 95% CI: 10.58–12.64), otitis externa (11.18%, 95% CI: 10.17–12.19) and anal sac impaction (10.59%, 95% CI 9.60-11.58). Once disorders were grouped by pathology, the most common group-level disorders were obesity (24.27%, 95% CI: 22.89–25.65), dental disorders (21.48%, 95% CI: 20.16–22.80), ear disorders (13.62%, 95% CI: 12.52–14.72), claw/nail disorders (13.14%, 95% CI: 12.06–14.22) and anal sac disorders (11.10%, 95% CI: 10.09–12.11). The median age at death was 11.28 years (IQR 9.32–13.08) for 322 deaths recorded during the study period. The most common causes of death at group level were neoplasia (19.26%, 95% CI: 14.76–23.75), mass (13.18%, 95% CI: 9.32–17.03), poor quality of life (12.84%, 95% CI: 9.03–16.65), and brain disorders (6.76%, 95% CI: 3.90–9.62). Conclusions Their disorder profile suggests the Beagle breed should not be considered to have an extreme conformation. Owners and veterinary teams should put special emphasis on care related to bodyweight control and dental hygiene in Beagles. Their median age at death of 11.70 years suggests reasonable overall health but neoplasia is a common biomedical cause of death in Beagles. The Beagle is a scenthound originally created to hunt hare but that is now more commonly kept as a companion dog breed. The Beagle is promoted as a generally healthy dog but there is limited published evidence of the health of the subset of the breed that is owned outside of laboratory research. This VetCompass study aimed to report on the demography, common disorders and mortality of Beagles under primary veterinary care in the UK. VetCompass collects anonymised veterinary clinical records for research on canine health. Beagles comprised 0.88% of the 2,250,417 dogs in the current study under veterinary care during 2019 in the UK. The average adult bodyweight of Beagles was 18.19 kg. Male Beagles were on average over 3 kg heavier than female Beagles (19.70 kg vs. 16.59 kg). From a random sample of 3,729 Beagles whose clinical records were examined in more detail, the most common disorders diagnosed were obesity (24.27% of all Beagles affected in 2019), dental disease (17.78%), overgrown nail(s) (11.61%), ear infection (11.18%) and anal sac impaction (10.59%). From 322 dogs that died during the study, the average age at death was 11.28 years. Females outlived males by almost a year (11.70 years vs. 10.75 years). The most common general causes of death were cancer (19.26%,), lumps (13.18%), poor quality of life (12.84%) and brain disorders (6.76%). These results confirm the Beagle as a generally healthy breed, with a lifespan and disorder profile similar to dogs overall. However, owners and veterinary teams should put special emphasis on care related to bodyweight control and dental hygiene in Beagles.
International audience;
The dust level is included in the animal welfare legislation of the European Union, implying assessment of dust levels during veterinary welfare inspections. This study aimed to develop a valid and feasible method for measuring dust levels in poultry barns. Dust levels were assessed in 11 layer barns using six methods: light scattering measurement, the dust sheet test with durations of 1 h and 2–3 h, respectively, visibility assessment, deposition assessment, and a tape test. As a reference, gravimetric measurements were obtained – a method known to be accurate but unsuitable for veterinary inspection. The dust sheet test 2–3 h showed the highest correlation with the reference method with the data points scattered closely around the regression line and the slope being highly significant (p = 0.00003). In addition, the dust sheet test 2–3 h had the highest adjusted R2 (0.9192) and the lowest RMSE (0.3553), indicating a high capability of predicting the true concentration value of dust in layer barns. Thus, the dust sheet test with a test duration of 2–3 h is a valid method for assessing dust levels. A major challenge is the test duration as 2–3 h is longer than most veterinary inspections. Nevertheless, results showed that potentially, with some modifications to the scoring scale, the dust sheet test may be reduced to 1 h without losing validity.
Background Communication skills are a necessary competency in veterinary medicine, and shared decision-making (SDM) between practitioners and patients is becoming increasingly important in veterinary practice as in human medicine. There are few studies that have quantitatively measured SDM in veterinary health care, and the relationship between SDM and consultation satisfaction is unknown. The purpose of this study was to investigate the status of SDM implementation in veterinary hospitals and the relationship between SDM implementation and consultation satisfaction among pet owners. We conducted a cross-sectional study using self-administered questionnaires among pet owners and veterinarians. In total, 77 pet owners who visited a veterinary clinic and 14 veterinarians at the clinics participated in this study. After a veterinary clinic visit, owners were asked to rate their decision-making preferences using the Shared Decision Making Questionnaire for patients (SDM-Q-9) adapted for veterinary medicine, as well as their satisfaction with the consultation. The corresponding veterinarians were asked to complete the veterinary version of the survey (SDM-Q-Doc). Results Most pet owners (64.9%) preferred SDM in veterinary consultations. Cronbach's alpha coefficient of 0.84 for the veterinary SDM-Q-9 and 0.89 for the veterinary SDM-Q-Doc both confirmed high reliability. The Spearman's correlation coefficient between the SDM-Q-9 and consultation satisfaction was 0.526 ( p < 0.001), which was significant. The SDM-Q-Doc was not significantly correlated with either the SDM-Q-9 or pet owner consultation satisfaction. We conducted a sensitivity analysis of correlations among veterinarians; responses on the SDM-Q-Doc to examine the association between the SDM-Q-Doc and SDM-Q-9 and owner satisfaction; the results remained the same and no association was found. Conclusions Our findings suggest that evaluation of SDM among pet owners was associated with their satisfaction with veterinary consultation. Veterinarians may be able to improve the satisfaction level of pet owners by adopting a consultation method that increases SDM. We did not consider the content of veterinary care or the number of visits to the veterinary clinic; future studies should be conducted to confirm the validity of our results.
BACKGROUND: Communication skills are a necessary competency in veterinary medicine, and shared decision-making (SDM) between practitioners and patients is becoming increasingly important in veterinary practice as in human medicine. There are few studies that have quantitatively measured SDM in veterinary health care, and the relationship between SDM and consultation satisfaction is unknown. The purpose of this study was to investigate the status of SDM implementation in veterinary hospitals and the relationship between SDM implementation and consultation satisfaction among pet owners. We conducted a cross-sectional study using self-administered questionnaires among pet owners and veterinarians. In total, 77 pet owners who visited a veterinary clinic and 14 veterinarians at the clinics participated in this study. After a veterinary clinic visit, owners were asked to rate their decision-making preferences using the Shared Decision Making Questionnaire for patients (SDM-Q-9) adapted for veterinary medicine, as well as their satisfaction with the consultation. The corresponding veterinarians were asked to complete the veterinary version of the survey (SDM-Q-Doc). RESULTS: Most pet owners (64.9%) preferred SDM in veterinary consultations. Cronbach's alpha coefficient of 0.84 for the veterinary SDM-Q-9 and 0.89 for the veterinary SDM-Q-Doc both confirmed high reliability. The Spearman's correlation coefficient between the SDM-Q-9 and consultation satisfaction was 0.526 (p < 0.001), which was significant. The SDM-Q-Doc was not significantly correlated with either the SDM-Q-9 or pet owner consultation satisfaction. We conducted a sensitivity analysis of correlations among veterinarians; responses on the SDM-Q-Doc to examine the association between the SDM-Q-Doc and SDM-Q-9 and owner satisfaction; the results remained the same and no association was found. CONCLUSIONS: Our findings suggest that evaluation of SDM among pet owners was associated with their satisfaction with veterinary consultation. Veterinarians may be able to improve the satisfaction level of pet owners by adopting a consultation method that increases SDM. We did not consider the content of veterinary care or the number of visits to the veterinary clinic; future studies should be conducted to confirm the validity of our results.
Background To report the first case of bull’s eye maculopathy associated with veterinary niclosamide. Case presentation A 27-year-old Iranian female presented with a history of reduced vision and photopsia since 3 years, after accidental ingestion of four boluses of veterinary niclosamide. Fundus examination showed atrophy in parafoveal retinal pigmentary epithelium, appearing as bilateral bull’s-eye maculopathy. Optical coherence tomography revealed disruption of the parafoveal ellipsoid zone and outer retinal thinning, appearing as a flying saucer sign. Electroretinography displayed decreased scotopic and photopic amplitudes with normal waveform in both eyes. The causality score was 4, showing “possible” retinopathy due to niclosamide according to Naranjo’s causality assessment algorithm. Based on clinical and ancillary findings, a diagnosis of niclosamide-induced maculopathy was made. Conclusion Veterinary niclosamide is an anthelmintic drug that in higher doses could be detrimental to the human retina. Awareness about its side effects and appropriate drug labeling could prevent accidental toxicity.
SIMPLE SUMMARY: Parasitic infections are a significant problem in veterinary medicine, and their management requires an in-depth understanding of the parasite life cycle, host-parasite interactions, and the appropriate use of antiparasitic drugs. In this study, we aimed to investigate the knowledge, approaches, and practices of veterinarians in Türkiye regarding parasitic infections and antiparasitic drugs usage. Our study surveyed a diverse group of veterinarians working in various fields of veterinary medicine, including small animal, large animal, and mixed animal practices. The results of our study revealed that while veterinarians in Türkiye generally have a good understanding of parasitic infections and antiparasitic drugs, there are still gaps in their practice, particularly regarding testing anthelmintic resistance, using parasitic diagnostic methods, and attending conferences, symposia, and workshops. Overall, our study provides valuable insights into the current state of parasitic infections and anthelmintic resistance management in veterinary medicine in Türkiye. We believe that the findings of our study will help inform the development of more effective strategies for the prevention and treatment of parasitic infections in animals and contribute to the ongoing efforts to improve animal health and welfare in the region. Our results are also expected to raise awareness about anthelminthic resistance and parasite infections among veterinarians in Türkiye. ABSTRACT: Despite a global background of increasing anthelmintic resistance in parasites, little is known about the current parasite control strategies adopted within the livestock industry in Türkiye. The aim of this survey is to identify the parasitic diseases encountered by veterinarians, the methods and drugs used for the diagnosis and treatment of these diseases, parasite control practices, and other related factors. This survey was conducted online between October 2018 and March 2019 with the participation of 607 veterinarians working in different areas from seven different geographical regions of Türkiye. A total of 29 questions were posed to the veterinarians in the online survey. As a result of this survey, it was determined that veterinarians should utilize laboratory methods more frequently for the detection and diagnosis of parasitic diseases and anthelmintic resistance. It was concluded that to effectively implement diagnosis, prevention, and control measures for parasitic diseases, field veterinarians need to establish closer relationships within academia and increase their participation in national and international conferences, symposia, and workshops where knowledge sharing and exchange take place. In conclusion, antiparasitic drug resistance has become increasingly important recently, and therefore measures taken to prevent the development of resistance should be increased.
Drug resistance threatening humans may be linked with antimicrobial and anthelmintic resistance in other species, especially among farm animals and, more in general, in the entire environment. From this perspective, Green Veterinary Pharmacology was proven successful for the control of parasites in small ruminants and for the control of other pests such as varroa in bee farming. As in anthelmintic resistance, antimicrobial resistance (AMR) represents one of the major challenges against the successful treatment of infectious diseases, and antimicrobials use in agriculture contributes to the spread of more AMR bacterial phenotypes, genes, and proteins. With this systematic review, we list Italian plants with documented antimicrobial activity against possible pathogenic microbes. Methods: The literature search included all the manuscripts published since 1990 in PubMed, Web of Science, and Scopus using the keywords (i) “antimicrobial, plants, Italy”; (ii) “antibacterial, plant, Italy”; (iii) “essential oil, antibacterial, Italy”; (iv) “essential oil, antimicrobial, Italy”; (v) “methanol extract, antibacterial, Italy”; (vi) “methanol extract, antimicrobial, Italy”. Results: In total, 105 manuscripts that documented the inhibitory effect of plants growing in Italy against bacteria were included. One hundred thirty-five plants were recorded as effective against Gram+ bacteria, and 88 against Gram−. This will provide a ready-to-use comprehensive tool to be further tested against the indicated list of pathogens and will suggest new alternative strategies against bacterial pathogens to be employed in Green Veterinary Pharmacology applications.
SIMPLE SUMMARY: This is a study related to NDM-5-producing E. coli in companion animals in China. Notably, an E. coli isolate possessing both bla(NDM-5)-bearing plasmid and mcr-1-bearing plasmid was identified in a dog from the same veterinary clinic, where we previously found the mobile IncX3–X4 hybrid plasmid encoding both bla(NDM-5) and mcr-1 in a cat. This observation highlights the diversity of bla(NDM-5)- and mcr-1-harboring plasmids and the transferability of such resistant pathogens from companion animals to humans. Given that colistin is the last-resort antibiotic for treating human infections caused by carbapenem-resistant Enterobacteriaceae, the co-transfer of resistance to both antibiotics may seriously compromise the effectiveness of clinical therapy. ABSTRACT: Carbapenem and colistin are important antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative pathogens. Here, we isolated the bla(NDM-5)-harboring Escherichia coli in companion animals in healthy or diseased companion animals from veterinary clinics in six cities in China from July to November 2016. A total of 129 rectal swabs of healthy or diseased dogs and cats were collected from veterinary clinics in six different cities in China, and the isolates were subjected to carbapenem and colistin susceptibility testing. Resistance genes were confirmed using PCR. Conjugation experiments were conducted to determine the transferability of antibiotic resistance genes (ARGs) in the strains. The isolated rate of bla(NDM-5)-harboring E. coli strains was 3.88% (five strains). These five strains were multidrug resistant to at least three antibiotics and corresponded to four sequence types including ST101. The bla(NDM-5) gene was located on 46 kb IncX3 plasmids in these five strains, and the genetic contexts were shared and were nearly identical to the K. pneumoniae plasmid pNDM5-IncX3 from China. In addition, one strain (CQ6-1) co-harbored bla(NDM-5)-encoding-IncX3 plasmid along with a mcr-1-encoding-IncX4 plasmid, and their corresponding genetic environments were identical to the bla(NDM-5)-IncX3 and mcr-1-IncX4 hybrid plasmid reported previously from the same area and from the same clinic. The results indicated that the similar genetic contexts were shared between these isolates from companion animals, and the IncX3-type plasmids played a key role in the spread of bla(NDM-5) among these bacteria.
Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
25 wetenschappelijke publicaties binnen het domein Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
, voor snelle raadpleging van de bijbehorende wetenschappelijke literatuur.
John Wiley and Sons Inc.december 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Astigmatic mites contain potent allergens that can trigger IgE‐mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, group 1 allergens (Der p 1 and Der f 1), characterized as papain‐like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross‐reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens. METHODS: Based on the high‐quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme‐linked immunosorbent assay. RESULTS: Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE‐binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of D. pteronyssinus. In addition, gene decay events were identified in the skin‐burrowing parasitic mite Sarcoptes scabiei. CONCLUSION: This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component‐resolved diagnosis of mite allergies.
John Wiley and Sons Inc.januari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: Information and communication technologies (ICTs) improve patient‐centered care and are routinely used in Allergic Rhinitis (AR), but patients' preferences and attitudes are unexplored. This study examines AR‐related information preferences and ICT use by AR patients. METHODS: A survey‐based cross‐sectional study was carried out in Ecuador from July to September 2019 in seven centers of reference for allergic disease. Participants were 18 years or older, diagnosed with AR and had access to ICT and the Internet. Descriptive and binomial logistic regressions were performed. A value of less than 0.05 was considered statistically significant. RESULTS: 217 patients were included. 47% (n = 102) used ICTs to learn about AR, of which 38.2% (n = 83) found it useful. Most of participants (75%, n = 164) did not think that ICTs reduce their need to see a doctor. Individuals with poorer quality of life were more likely to utilize ICTs to contact their doctor (OR 1.27, 95% CI 1.04–1.55), and more likely to be interested in AR‐related content (OR 1.23, 95% CI 1.00–1.52). Patients with long‐term AR or other allergies were less likely to use ICTs (OR 0.92 and OR 0.40 respectively). Higher education and lower quality of life may increase AR apps adoption (OR 4.82, 95% CI 1.11–21.00). Academic preparation five‐fold increased ICT use for health provider communication (OR 5.29, 95% CI 1.18–23.72). Mild‐persistent AR enhanced the probabilities of using ICTs to share experiences and communicate with other patients (OR 12.59, 95% CI 1.32–120.35). CONCLUSIONS: Our study emphasizes the importance of tailoring digital resources to patient needs by considering factors such as quality of life, education, and specific subgroups within the AR patient population. Additionally, the findings suggest that while ICTs can play a valuable role in patient education and support, they should complement, rather than replace, traditional medical care for many AR patients.
Lippincott Williams & Wilkinsnovember 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
We previously reported the effectiveness of rush subcutaneous immunotherapy with birch pollen extract (Birch rSCIT) for pollen-food allergy syndrome (PFAS) and the high rate of systemic reactions (SR) during the rapid escalation phase. In this study, we examined whether modifying the dose escalation protocol of Birch rSCIT would reduce SR and maintain therapeutic effects. Birch rSCIT was introduced in 20 patients with PFAS who experienced systemic symptoms upon ingestion of soybeans. Birch rSCIT was implemented using 3 protocols: 2 protocols (nonstep-up group) increased the target dose to more than 1:2 × 10(2) (w/v) in 0.05 mL, while 1 protocol (step-up group) increased the target dose to 1:2 × 10(3) (w/v) in 0.3 mL, and then increased to 1:2 × 10(2) (w/v) in 0.05 mL using the conventional method in the following week. In the nonstep-up group, 4 out of 5 patients (80%), and in the step-up group, 2 out of 15 patients (13.3%) developed SR during rapid escalation. During the rapid escalation phase, the step-up group had significantly fewer SR than the nonstep-up group (P = 0.014). The median ingestible dose of soy milk in the oral food challenge was 3.5 mL before the treatment and increased significantly to 200 mL 1 year after initiating Birch SCIT (P < 0.01). We confirmed that reducing the target antigen dose in Birch rSCIT improved safety and maintained the therapeutic effect for soybean allergy with PFAS.
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Diseaseoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. METHODS: LincR-PPP2R5C from RNA-seq data of CD4(+) T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4(+) T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. RESULTS: LncR-PPP2R5C was significantly higher in CD4(+) T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. CONCLUSIONS: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.
BioMed Centralseptember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Primary Systemic Sclerosis (PSS) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Interstitial lung disease (ILD) is a late demonstration of PSS and cytokines can contribute to the disease pathology. The purpose of the current study was to determine the association between serum interleukin-6 level and pulmonary involvement in progressive systemic sclerosis. METHODS AND MATERIALS: Demographic data and serum interleukin-6 levels were measured for 30 PSS patients with pulmonary involvement (case group) and 30 PSS patients without pulmonary involvement (control group) following informed consent. The disease duration and activity, C-reactive protein (CRP), chest x-ray and highresolution CT scan (HRCT) findings, ejection fraction (EF) and echocardiography findings, and pulmonary artery pressure (PAP) were also determined in both groups. RESULTS: The age of patients in case and control groups was 52.5 ± 9.3 and 43.9 ± 9.7 years, respectively (p = 0.001). No significant difference was found between serum levels of IL-6 in case and control groups (73.1 ± 95.4 vs 46.7 ± 83.6 pg/ml, p = 0.267). However, IL-6 level was significantly higher in male case patients compared to male controls (p = 0.007). The duration of PSS was 11.6 ± 6.4 and 7.4 ± 4.2 years in case and control groups, respectively (p = 0.002). The quantitative CRP and PAP was also significantly higher in case patients (p = 0.01 and p < 0.001, respectively). There was found reticulonodular pattern in 20 (66.7%) of the cases, whereas 28 (93.3%) of the controls had normal Chest X-rays (CXR) (p < 0.001). EF was significantly lower in case patients compared to control patients (p = 0.001). CONCLUSION: The serum level of IL-6 did not appear to have a relationship with pulmonary involvement, hence it could not be regarded as a potential therapeutic target.
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Diseaseoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years. METHODS: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration. RESULTS: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children. CONCLUSIONS: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.
BioMed Centralmaart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: While the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity. OBJECTIVE: To describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes. METHODS: Mothers with infants aged < 19 months old with a diagnosis of AD were recruited from social media and medical clinics in Winnipeg, Canada between October 2021 and May 2022. Infant AD severity was classified using maternal-reported data on the Patient-Oriented Scoring Atopic Dermatitis tool (PO-SCORAD). Quantitative data were collected via a series of questionnaires with a subset of mothers subsequently completing semi-structured interviews. Quantitative and qualitative data were integrated in the discussion. RESULTS: Mothers of infants with moderate/severe AD (6/12) were more likely to report their infant suffering from a higher degree of sleeplessness (i.e., ≥ 5 on a scale of 0–10) over the past 48 h compared to mothers of infants with mild AD (0/18). This was supported by qualitative findings where mothers described how their infant’s sleep quality and quantity worsened with AD severity. Additionally, 7/32 mothers reported that their child’s AD, regardless of severity, disturbed their sleep. Maternal sleep loss was most commonly attributed to infant itching (6/7), followed by worry (4/7). CONCLUSION: Infantile AD severity was associated with worse sleep outcomes for both mothers and infants. We propose that maternal and infantile sleep quality and quantity can be improved by reducing AD severity through adherence to topical treatments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-024-00883-x.
BioMed Centralfebruari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
In this letter to the editor, we present questionnaire-based data assessing the patient journey of adults with moderate–severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the USA and five European countries. These data highlight how long and difficult the patient journey with CRSwNP can be and how improved disease awareness among physicians could lead to more timely diagnosis and treatment, and hence improved management of patients.
Lippincott Williams & Wilkinsoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Food-dependent exercise-induced anaphylaxis is a disorder in which a reaction develops only in association with physical exertion that generally takes place postprandially. The reaction that occurs following food intake after exercise is uncommon. Banana is an infrequent cause of anaphylaxis, which has been previously reported in combination with postprandial exercise in only 1 patient. A probable case of preprandial food-dependent exercise-induced anaphylaxis to banana is described herein together with a brief review of recent related literature.
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Diseaseoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: Suppression of tumorigenicity 2 (ST2) has been proposed as the receptor contributing to neutrophilic inflammation in patients with type 2-low asthma. However, the exact role of ST2 in neutrophil activation remains poorly understood. METHODS: A total of 105 asthmatic patients (classified into 3 groups according to control status: the controlled asthma [CA], partly-controlled asthma [PA], and uncontrolled asthma [UA] groups), and 104 healthy controls were enrolled to compare serum levels of soluble ST2 (sST2) and interleukin (IL)-33. Moreover, the functions of ST2 in neutrophils and macrophages (Mφ) were evaluated ex vivo and in vivo. RESULTS: Serum sST2 levels were significantly higher in the UA group than in the CA or PA groups (P < 0.05 for all) with a negative correlation between serum sST2 and forced expiratory volume in 1 second % (r = −0.203, P = 0.038). Significantly higher expression of ST2 receptors on peripheral neutrophils was noted in the UA group than in the PA or CA groups. IL-33 exerted its effects on the production of reactive oxygen species, the formation of extracellular traps from neutrophils, and Mφ polarization/activation. In neutrophilic asthmatic mice, treatment with anti-ST2 antibody significantly suppressed proinflammatory cytokines (tumor necrosis factor-alpha and IL-17A) as well as the numbers of immune cells (neutrophils, Mφ, and group 3 innate lymphoid cells) in the lungs. CONCLUSIONS: These results suggest that IL-33 induces the activation of neutrophils and Mφ via ST2 receptors, leading to neutrophilic airway inflammation and poor control status of asthma. ST2 could be a therapeutic target for neutrophilic airway inflammation in patients with UA.
BioMed Centralmaart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Circular RNA (circRNA) has the potential to serve as a crucial regulator in the progression of bronchial asthma. The objective of this investigation was to elucidate the functional dynamics of the circ_0070934/miR-199a-5p/Mannoside acetylglucosaminyltransferase 3 (MGAT3) axis in the development of asthma. METHODS: Circ_0070934, miR-199a-5p and MGAT3 in peripheral venous blood of 38 asthmatic patients and 43 healthy controls were detected by qRT-PCR, and the expression of MGAT3 protein was examined by ELISA. The GSE148000 dataset was analyzed for differences in MGAT3. The BEAS-2B cells were transfected with circ_0070934 plasmid and small interfering RNA, miR-199a-5p mimics and inhibitors. The apoptosis level was detected by flow cytometry and MGAT3 was detected by qRT-PCR and Western blot. The expression of E-cadherin, N-cadherin, Vimentin was examined by Western blot. Interleukin-4 (IL-4) and IL-13 were used to co-stimulate BEAS-2B cells as an asthmatic airway epithelial cell model. BEAS-2B cells exposed to type 2 cytokines (IL-4 and IL-13) were treated with circ_0070934 plasmid, and the expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The binding relationships were verified using dual-luciferase reporter assay and miRNA pull-down assay. RESULTS: The expression of circ_0070934 and MGAT3 in peripheral venous blood of asthmatic patients was down-regulated, and the expression of miR-199a-5p was up-regulated. And the expression of MGAT3 was reduced in sputum of asthma patients. Down-regulating the expression of circ_0070934 could promote apoptosis of BEAS-2B cells and increase epithelial-mesenchymal transition (EMT), and this effect can be partially reversed by down-regulating miR-199a-5p. Circ_0070934 could inhibit the process of epithelial mesenchymal transition induced by IL-4 and IL-13 in BEAS-2B cells. In addition, miR-199a-5p could respectively bind to circ_0070934 and MGAT3. CONCLUSION: The findings of this study indicate that circ_0070934 may function as a competitive endogenous RNA (ceRNA) of miR-199a-5p, thereby modulating the expression of MGAT3 and impacting the process of EMT in bronchial epithelial cells. These results contribute to the establishment of a theoretical framework for advancing the prevention and treatment strategies for asthma.
Lippincott Williams & Wilkinsoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by atopic dermatitis, recurrent skin and lung infections, and significantly elevated serum immunoglobulin E levels. Autosomal dominant and loss-of-function pathogenic variants in the STAT3 gene are the most common causes of the disease and studies have shown that the presence of IL-4 receptor (IL-4R) is upregulated in patients with dominant-negative mutations in the STAT3 gene expression. Dupilumab is a monoclonal antibody that targets the IL-4α receptor and improves the symptoms of atopic dermatitis by inhibiting IL-4 and IL-13. We used dupilumab to treat severe dermatitis in a patient with STAT3-HIES and achieved satisfactory results.
BioMed Centraloktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Penicillin allergy is the most commonly reported drug allergy in the US. Despite evidence demonstrating that up to 90% of labels are incorrect, scalable interventions are not well established. As part of a larger mixed methods investigation, we conducted a qualitative study to describe the barriers to implementing a risk-based penicillin de-labeling protocol within a single site Veteran’s hospital. METHODS: We conducted individual and group interviews with multidisciplinary inpatient and outpatient healthcare teams. The interview guides were developed using the Theoretical Domains Framework (TDF) to explore workflows and contextual factors influencing identification and evaluation of patients with penicillin allergy. Three researchers iteratively developed the codebook based on TDF domains and coded the data using thematic analysis. RESULTS: We interviewed 20 clinicians. Participants included three hospitalists, five inpatient pharmacists, one infectious disease physician, two anti-microbial stewardship pharmacists, four primary care providers, two outpatient pharmacists, two resident physicians, and a nurse case manager for the allergy service. The factors that contributed to barriers to penicillin allergy evaluation and de-labeling were classified under six TDF domains; knowledge, skills, beliefs about capabilities, beliefs about consequences, professional role and identity, and environmental context and resources. Participants from all groups acknowledged the importance of penicillin de-labeling. However, they lacked confidence in their skills to perform the necessary evaluations, such as test dose challenges. The fear of inducing an allergic reaction and adding further complexity to patient care exacerbated their reluctance to de-label patients. The lack of ownership of de-labeling initiative was another significant obstacle in establishing consistent clinical workflows. Additionally, heavy workloads, competing priorities, and ease of access to alternative antibiotics prevented the prioritization of tasks related to de-labeling. Space limitations and nursing staff shortages added to challenges in outpatient settings. CONCLUSION: Our findings demonstrated that barriers to penicillin allergy de-labeling fall under multiple behavioral domains. Better role clarification, opportunities to develop necessary skills, and dedicated resources are needed to overcome these barriers. Future interventions will need to employ a systemic approach that addresses each of the behavioral domains influencing penicillin allergy de-labeling with stakeholder engagement of the inpatient and outpatient health care teams. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00842-y.
Lippincott Williams & Wilkinsjanuari 2025Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Coconut (Cocos nucifera) is a fruit belonging to the Arecaceae plant family. It is not a common allergen and literature on it is limited. Currently, there is a lack of data on coconut allergy in Asia, despite it being a fruit commonly used as a food ingredient in tropical Southeast Asia. OBJECTIVE: In this study, we aimed to describe the demographics, clinical features, and natural history of Singaporean children with IgE-mediated coconut allergy. METHODS: A retrospective review was conducted for children diagnosed with coconut allergy in a tertiary pediatric hospital in Singapore between 2017 and 2022. RESULTS: The diagnosis of coconut allergy was made in 41 patients based on convincing history of IgE-mediated allergic reaction and a positive test (prick-to-prick test to coconut water, coconut flesh, and/or specific immunoglobulin E). The median age at first reaction was 20 months (range: 6–96 months) with most reacting on first ingestion (80.5%). Majority presented with cutaneous reactions (90.2%). Anaphylaxis occurred in 9.8%, with all involving cutaneous and respiratory systems. Most reacted to coconut milk (34.1%). Majority (82.9%) had another food allergy and a personal history of atopy (90.2%). Median duration of follow-up was 35 months (range: 3–109). Only 1 of the 41 patients reported natural tolerance at 76 months. CONCLUSIONS: Although a relatively uncommon food allergy, coconut allergy is a significant problem as anaphylaxis occurs in 1 in 10 and appears to be a persistent allergy.
Termedia Publishing Housejanuari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: Skin diseases affect patients at any age, but as each period in life is different, tools used to assess quality of life impairment should be adjusted according to the particular age group. Adolescence is a unique time, when young individuals go through many changes, making them especially vulnerable to stress. AIM: Translation and validation of a Polish language version of the Teenagers Quality of Life questionnaire (T-QoL) questionnaire. MATERIAL AND METHODS: T-QoL was translated following international guidelines. A group of 34 dermatological patients, aged 12–19 years old, with various skin diseases were given the T-QoL as well as the CDLQI or DLQI to complete. They were also asked to complete the T-QoL questionnaire for the second time after 3–5 days. Statistical analysis of the results was performed. RESULTS: The Polish version of T-QoL is internally consistent (Cronbach α 0.893 for the whole questionnaire). Moreover, it presents very good convergent validity (ICC = 0.864). No statistically significant differences between each question were noticed between the first and second time of completing the form. T-QoL scores correlated significantly with DLQI (p = 0.008, r = 0.636) and CDLQI (p < 0.001, r = 0.777) scores. CONCLUSIONS: The Polish version of the T-QoL questionnaire is a reliable instrument with adequate convergent validity, consistency and reproducibility. It can be successfully used to measure quality of life impairment among teenagers.
BioMed Centralseptember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps. METHODS: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023. RESULTS: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment. CONCLUSION: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00841-z.
Doveseptember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: To describe the lung function and clinical control of asthma in patients with N-ERD during three years of medical follow-up using GINA guidelines. METHODS: We evaluated 75 N-ERD and 68 asthma patients (AG). Clinical control, lung function, and asthma treatment were evaluated according to GINA-2014. We compared all variables at baseline and one, two, and three years after treatment. RESULTS: At baseline, the N-ERD group had better basal lung function (LF) than the AG group (p<0.01), and the AG group used higher doses of inhaled corticosteroids than the N-ERD group (52.4% vs 30.5%, p=0.01) and short-term oral corticosteroid (OCS) use (52.4% vs 30.5%, p<0.01). Instead, N-ERD patients needed more use of leukotriene receptor antagonists (LTRA) (29.3% vs 5.9%, p<0.01). This group had better clinical control than the AG group (62.1% vs 34.1%, p<0.01). During the medical follow-up, the LF of the N-ERD group remained at normal values; however, these parameters improved in AG from one year (p<0.01). Likewise, there was a diminished use of high doses of ICS (52.4% vs 33%, p<0.05) and short-term OCS (67.6% vs 20.6%, p<0.01) in asthma patients. However, N-ERD patients still needed more use of LTRAs (p<0.02) during the study. In this context, one-third of N-ERD patients had to use a combination of two drugs to maintain this control. From the second year on, clinical control of asthma was similar in both groups (p>0.05). CONCLUSION: According to GINA guidelines, only one-third of patients with N-ERD can gradually achieve adequate lung function and good asthma control with a high ICS dosage. Only a very small portion of patients will require the continued use of a second medication as an LTRA to keep their asthma under control.
Doveoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Significant morbidity and mortality are associated with poor asthma control. The aim of this study was to determine factors associated with poor control and referral to specialist secondary care services. METHODS: We used primary care data from the Clinical Practice Research Datalink Aurum (CPRD) linked with Hospital Episode Statistics (HES) records from 1st January 2007 to 31st December 2019. We selected patients aged 6–17 years old. Poor control was defined as six or more prescriptions of short-acting beta-agonist (SABA) inhalers, two or more courses of oral corticosteroids (OCS), an Asthma Control test (ACT) or childhood ACT <20, one hospital admission for asthma, or one visit to Accident & Emergency (A&E) department for asthma-related episodes in the 12 months following asthma diagnosis. Asthma severity was defined following GINA guidelines 2021. RESULTS: About 17.6% of children aged between 6 and 17 years with active asthma had poor control. Severe asthma, eczema, food allergies, increased BMI and living in deprived areas were identified as risk factors for poor control. Among those with poor control, referral rates to specialist care were extremely low, only 2% overall. Those with severe asthma were three-times more likely to be referred than those with mild-to-moderate asthma [HR(crude) = 4.04 (95% CI, 3.35–4.87); HR(adj) = 2.72 (95% CI: 2.13–3.49)]. Other factors associated with referral were food allergy and living in a more deprived area. CONCLUSION: Around 1 in 6 children and adolescents with active asthma are not achieving adequate control of their symptoms. Among the subset of 6–17-year olds with poorly controlled asthma, timely referral for specialist advice in secondary care is rare, especially in those with so-called mild asthma who nevertheless are at significant risk for poor asthma outcomes.
Dustri-Verlag Dr. Karl Feistlemei 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Occupational skin and respiratory allergies are among the most common occupational diseases in Germany. The identification of the allergy trigger is essential for the recognition of an occupational allergy as well as for effective individual prevention. However, occupational type I allergens are among the “rare” allergens and the possibilities of guideline-compliant diagnosis using quality-tested skin test solutions is becoming increasingly difficult due to the reduction in commercially available test allergens. In order to guarantee meaningful diagnostic workup for all affected insured persons with suspected occupational type I allergies and to ensure this in the future, a durable optimization, standardization, and availability of allergy tests for occupational allergic diseases is urgently required. The need for action has been recognized by the German Social Accident Insurance (DGUV), and steps to eliminate the diagnostic gaps have been initiated by a joint research project at the Institute for Prevention and Occupational Medicine of the DGUV (IPA) and the Paul Ehrlich Institut (PEI). The evaluation of alternative methods for the production of standardized test allergen solutions can also be used for newly emerging allergens in the workplace. New allergen sources at workplaces and thus also sensitization and allergies among employees can be expected as a result of changes in work processes and the introduction of new technologies and/or working materials, which are also introduced in connection with climate change and the concept of sustainability.
Lippincott Williams & Wilkinsapril 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Peanut allergy is a common food allergy. Accidental peanut exposure can induce anaphylactic symptoms in allergic individuals. In rare cases, pancreatitis can be induced by food allergies. This report describes a 12-year-old girl with recurrent acute pancreatitis (AP) following a peanut allergy induced 8 years after the first episode. The patient experienced the first episode of AP at 4 years old when she accidentally consumed peanut powder ice cream. AP was recurrently induced 8 years later by an oral food challenge test with a small amount of peanuts, despite decreased specific IgE for peanuts and Arah2. This report is the first to demonstrate that AP, as a peanut-induced symptom, is difficult to tolerate over a long period in a patient with peanut allergy. The possibility of AP induction after accidental ingestion, oral food challenge, or oral immunotherapy for peanuts should be considered in patients with peanut allergy.
World Allergy Organizationnovember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: For therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch. OBJECTIVE: To assess current practice on all aspects of biologic therapy by specialists in Germany. METHODS: A questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis. RESULTS: Forty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between “responders”, “partial responders” and “non-responders”. Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP. CONCLUSION: This study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.
Dustri-Verlag Dr. Karl Feistlemaart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Furry pets are beloved companion animals; horse riding is a popular leisure activity. So-called hypoallergenic animals have gained high interest as sensitization to animal dander and allergy to furry animals are widespread. Allergen immunotherapy to furry animals is still limited, and allergen avoidance in addition to symptomatic pharmaceutical treatment is often the only available option. Patients with an existing allergy to furry animals or with an atopic background are seeking for a hypoallergenic alternative. This review summarizes current knowledge and discusses future strategies.
Mary Ann Liebert, Inc., publishersmaart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Poor adherence to inhaled corticosteroids (ICS) is a significant challenge in pediatric asthma, contributing to health inequities. Text-message reminders for ICS therapy are an evidence-based approach that improves pediatric asthma medication adherence, yet has not been widely adopted into practice, partly due to lack of (1) participant input on design and implementation and (2) use of sustainable community linkages. Remote Asthma Link™ (RAL) seeks to fill this gap as a school-linked text-message intervention wherein parents of children with poorly controlled asthma received daily, 2-way text-message reminders for preventive inhaler use. Responses were shared with school nurses who conducted remote check-ins with families. Enrolled children, largely from underserved backgrounds, experienced improvements in medication adherence and asthma health outcomes. While initial results were promising, we have yet to elicit participant input to refine the protocol for more widespread implementation. OBJECTIVE: Examine participant perspectives on barriers and facilitators of RAL implementation. METHODS: Semistructured interviews were conducted May–June 2022 with intervention participants: 10 parents, 7 school nurses, and 4 pediatric providers (n = 21) until thematic saturation was reached. Interview transcripts were coded using thematic analysis. RESULTS: Several facilitators for RAL implementation were identified, including ease of use and accessibility, personal connection to the school nurse, and receipt of a visual notification for habit formation. Barriers included challenges with school nurses reaching parents, poor understanding of program expectations, and lack of reimbursement structure. Participant-proposed solutions to barriers included utilizing alternate communication methods (eg, social media), educational sessions, and meeting with payors to consider reimbursement models. CONCLUSION: RAL is a school-linked text-message intervention demonstrating promise in improving outcomes and equity in asthma care. Key implementation facilitators, barriers, and proposed solutions will inform protocol adaptations to promote successful implementation of this and other text-message interventions into clinical practice.
Lippincott Williams & Wilkinsjuni 2025Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Allergen immunotherapy (AIT) is an evidence-based therapy for allergic rhinitis and allergic asthma. AIT is largely recognized as the only causal treatment of allergic diseases that targets the underlying pathophysiology and may have a disease-modifying effect in addition to the antisymptomatic effect. Carbamylated monomeric allergoids (CMAs) are chemically modified allergens with reduced IgE-binding activity (reduced allergenicity) but full immunogenicity. The carbamylation process allows them to be much smaller than other modified allergens, making them ideal for sublingual immunotherapy (SLIT), and reduced allergenicity makes them safe and well tolerated. CMAs have several advantages over other SLIT products: smaller size for easier absorption through mucosa, greater resistance to proteolytic degradation, greater bioavailability, and reduced allergenicity with full immunogenicity. The tablet form allows for accurate dosing and compliance is easy to monitor. Safety is an especially important consideration when treating conditions in pediatric populations, as is patient compliance. This review focused on the efficacy, safety, and clinical application of monomeric allergoid SLIT for allergic disease in children and its suitability as an alternative to subcutaneous immunotherapy.
Lippincott Williams & Wilkinsfebruari 2025Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Therapies for desensitizing wheat-dependent exercise-induced anaphylaxis (WDEIA), a severe allergic response to wheat ingestion and exercise, remain unestablished. This study aimed to investigate whether continuous ingestion of hypoallergenic 1BS-18 Hokushin bread, which lacks the Gli-B1 locus encoding the ω5-gliadin allergen, could achieve desensitization in adult patients with WDEIA sensitized to ω5-gliadin. METHODS: Sixteen adult patients diagnosed with WDEIA participated in this study. Each patient was administered a safety dose of bread made from 1BS-18 Hokushin wheat, a hypoallergenic wheat that defects the Gli-B1 locus responsible for encoding the ω5-gliadin allergen, over a 12-week period. The safe dose for each individual was determined through a stepwise increase in bread intake and monitored to prevent allergic reactions. Desensitization efficacy was evaluated by measuring basophil activation rates and serum allergen-specific IgE levels specific to wheat proteins using the basophil activation test and ImmunoCAP serum testing. RESULTS: Fourteen of the 16 patients (87.5%) successfully completed the 12-week regimen of 1BS-18 Hokushin bread, with 2 patients (12.5%) discontinuing due to allergic reactions associated with the bread. Evaluation of basophil activation rates and serum allergen-specific IgE levels indicated no significant desensitization effects in any patient. CONCLUSIONS: Approximately 80% of patients with WDEIA were able to safely consume 1BS-18 Hokushin bread at least up to 60 g per day for 12 weeks without severe adverse reactions. However, this regimen did not achieve desensitization, suggesting that further studies may be necessary to explore alternative dosing, duration, or combinations with adjunct therapies for effective desensitization in patients with WDEIA.
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The weathering of basaltic rocks, especially on volcanic islands, plays a crucial role in global carbon cycling. Intense precipitation and warm atmospheric conditions accelerate weathering processes in these environments. While most estimates of weathering rates derive from river chemistry, soils and paleosols remain underexplored. In this study, we investigated the geochemistry of paleosols developed from volcanic rocks in the Azores Archipelago over the past 1 Myr. Precise geochronology of volcanic units bracketing paleosols indicates high soil formation rates (3-180 mm kyr -1 ), similar to modern soil formation rates in tropical volcanic islands. Geochronological evidence suggests a logarithmic decrease of soil formation rates over time, with high initial values reaching near zero in less than 35 kyr. This might be attributed to a combination of cation depletion and precipitation of stable minerals. Paleosols have generally developed faster on pyroclastic deposits than on lava flows. However, those formed on lava flows required less vertical development to sustain high cation exports due to their higher density. Based on the geochemistry of paleosols and their parental materials, we estimated cation exports (0-2600 t km -2 yr -1 ) and associated CO 2 uptake (0-35 × 10 6 Mol km -2 yr -1 ). These estimates generally exceed previous estimates based on the geochemistry of modern rivers in the Eastern Azores, by a factor of up to tenfold. Our data highlight the transient character of weathering processes and the criticality of precise geochronological control to constrain past weathering and soil formation rates. They further imply that atmospheric CO 2 may have experienced short episodes of intense consumption during interglacial stages, possibly contributing to subsequent cooling events over the past 1 Myr.
CCSD;Geological Society of Americajanuari 2022Vulkanologie
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Volcanic tephra fall deposits, which form during explosive eruptions, are commonly characterized in terms of their thickness and grainsize. While significant efforts have been undertaken to relate spatial trends in thickness to plume dispersion processes, comparably few studies have focused on understanding variations in grainsize. Yet, grainsize is a key parameter providing insight into eruption dynamics, from magma fragmentation to plume transport processes, and modulates the impacts of tephra. Here, we present a set of grainsize data extracted from the published record for 56 deposits that represent a range of eruption intensities and magnitudes. We systematically analyze the deposits in terms of modality (bimodal or unimodal grainsize distributions) and provide the median particle diameter with distance from source for component distribution modes. We found that bimodal fall deposits are formed by eruptions with large amounts of fine particles (<100 μm) and that all tephra-fall deposits show characteristic patterns of grainsize decay with distance from source that can be related to eruption plume height and thus intensity. The grainsize decay trends are also related to ash dispersion and deposition processes such as individual particle settling versus collective settling mechanisms. The maximum distance from source reached by particles of different sizes is controlled by a combination of source and transport processes. This data set provides insight into the preservation potential of deposits of different grainsizes at varying distances from their sources. Finally, we emphasize the importance of using grainsize trends in combination with thickness trends to interpret tephra-fall deposit records.
Large volcanic eruptions affect the climate by injecting sulphur dioxide gas into the stratosphere which is converted to sulphate aerosols. These aerosols have the power to warm the stratosphere, cooling the troposphere by reflecting solar radiation. Since the Pinatubo eruption in 1991, which resulted in a global cooling of 0.4◦C, observations have shown that the stratosphere has been regularly impacted by volcanic eruptions of moderate magnitude on a hemispheric scale, but that these events have been less well documented in the tropics. During our research, we carried out simulations by the global model WACCM-CARMA, including chemical and microphysical cycles of Sulphur to study the variability of stratospheric aerosol content in the tropics over the period 2013-2019. The simulations show that the volcanic events of the period (Kelud, Calbuco, Ambae, Raikoke and Ulawun) have significantly influenced the aerosol layer in the tropics, either by direct injection or by transport from distant latitudes.
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Les grandes éruptions volcaniques affectent le climat en injectant du dioxyde de soufre gazeux dans la stratosphère qui se transforme en aérosols sulfatés. Ces aérosols ont le pouvoir de réchauffer la stratosphère entraînant un refroidissement de la troposphère en réfléchissant le rayonnement solaire. Depuis l’éruption du Pinatubo en 1991, qui a entraîné un refroidissement global de 0,4◦C, les observations ont montré que la stratosphère a été régulièrement impactée par des éruptions volcaniques de magnitude modérée à l’échelle de l’hémisphère, mais que ces événements ont été moins bien documentés dans les tropiques. Des simulations par le modèle global WACCM-CARMA incluant les cycles chimiques et microphysiques du soufre, ont été effectuées durant nos travaux de thèse pour étudier la variabilité de la teneur en aérosols stratosphériques dans les tropiques sur la période 2013-2019. Il ressort des simulations que les événements volcaniques de la période (Kelud, Calbuco, Ambae, Raikoke et Ulawun) ont influencé de manière significative la couche d’aérosols dans les tropiques, soit par injection directe, soit par transport depuis des latitudes éloignées.
CCSD;Société géologique de France - EDP Sciencesjanuari 2026Vulkanologie
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The sub-continental lithospheric mantle (SCLM) beneath the Cameroon Volcanic Line (CVL) is vertically and laterally heterogeneous, consisting of a complex mixing of DMM, HIMU, and EM1, affected by modal or cryptic metasomatism, depending on the area. The petrography, whole-rock geochemical data, and minerals’ chemical composition of lavas and mantle xenoliths from the Bini Warack area, combined with Sr isotope compositions, provide constraints on the origin and thermochemical evolution of the SCLM beneath this sector of the CVL. The host lavas are basanite, basalt, and latite with OIB affinity, characterized by moderate to high silica and alkali contents (SiO 2 = 42.35–56.56 wt%, K 2 O+Na 2 O = 2.34–7.07 wt%), a high Ba/Rb ranging from 12.2 to 26.1, a low Rb/Sr from 0.03 to 0.08, strong enrichment in LREE relative to HREE (La N /Yb N : 9.3–30), and moderate enrichment in radiogenic isotopes ( e.g. , 0.702987 < 87 Sr/ 86 Sr initial < 0.703206; 0.512854 < 143 Nd/ 144 Nd initial < 0.512918) with positive εNd initial (+4.84 to +6.09). These features are consistent with an origin of the lavas by a low degree of partial melting (<2%) of a lherzolitic mantle source containing 2% to 6% garnet. These lavas have then evolved by fractional crystallization without any evidence of crustal contamination. The studied mantle xenoliths are spinel-bearing lherzolites, characterized by U/Th ratios typically lower than 1, a slight enrichment in LILE relative to HFSE, and mainly consist of minerals with fertile composition (Fo 84-91 ; spinel Cr#: 0.1–0.22; Al-rich pyroxenes). They are consistent with refractory mantle peridotite that evidences low partial-melting degrees. Trace element concentrations of host lavas (high Ba/Rb: 12.2–26.1 and low Rb/Sr: 0.03–0.08), together with olivine’s crystals chemical features (high Ca/Fe and 100*Mn/Fe ratios; low 100*Ni/Mg ratios) and low Ca/Al ratios (<5) of clinopyroxenes in spinel-bearing lherzolite xenoliths suggest that the SCLM beneath the Bini Warack area is likely a juvenile lithospheric mantle which that undergone a carbonate-rich metasomatism.
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Le manteau lithosphérique sous-continental (MLSC) sous la ligne volcanique du Cameroun (LVC) est verticalement et latéralement hétérogène, constitué d'un mélange complexe de DMM, HIMU et EM1, affecté par un métasomatisme modal ou cryptique selon la zone. La pétrographie, les données géochimiques des roches totales ainsi que la composition chimique des minéraux des laves et des xénolithes mantelliques de la région de Bini Warack, combinées aux compositions isotopiques Sr, fournissent des informations sur l'origine et l'évolution thermochimique du MLSC sous ce secteur de la LVC. Les laves hôtes ont des compositions de basanite, basalte et de latite présentant des affinités avec les OIB, et caractérisées par i) des teneurs modérées à élevées en silice et en alcalins (SiO 2 = 42.35–56.56%, K 2 O+Na 2 O = 2.34–7.07%), ii) de forts rapports Ba/Rb (12.2–26.1), iii) de faibles rapports Rb/Sr (0.03–0.08), iv) un fort enrichissement en terres rares légères par rapport aux terres rares lourdes (La N /Yb N : 9.3–30), et v) un enrichissement modéré en isotopes radiogéniques (0.702987 < 87 Sr/ 86 Sr initial < 0.703206; 0.512854 < 143 Nd/ 144 Nd initial < 0.512918) marqué par des εNd initiaux positifs (+4.84 – +6.09). Ces caractéristiques sont compatibles avec une origine des laves par un faible degré de fusion partielle (moins de 2%) d'un manteau à lherzolite contenant 2 à 6% de grenat. Les laves de Bini Warack ont ensuite évolué par cristallisation fractionnée sans trace de contamination crustale. Les xénolithes quant à eux sont des lherzolites à spinelle, caractérisés par des rapports U/Th généralement inférieurs à 1, un léger enrichissement en LILE par rapport aux HFSE et principalement constitués de minéraux de composition fertile (Fo 84-91; spinelle Cr# : 0.1–0.22; pyroxènes alumineux). Ces xénolithes sont compatibles avec un manteau péridotitique réfractaire ayant subi de faibles degrés de fusion partielle. Les teneurs en éléments traces des laves hôtes (Ba/Rb élevé : 12.2–26.1 et Rb/Sr faible : 0.03–0.08), les caractéristiques chimiques des cristaux d'olivine (rapports Ca/Fe et 100*Mn/Fe élevés; ainsi que les faibles rapports 100*Ni/Mg et Ca/Al <5) des clinopyroxènes des lherzolites étudiées, suggèrent que le MLSC sous la zone de Bini Warack est sans doute un manteau lithosphérique juvenile ayant subi un métasomatisme carbonaté.
International audience;
The extrusion rate of a lava dome is a critical parameter for monitoring silicic eruptions and forecasting their development. Satellite radar backscatter can provide unique information about dome growth during a volcanic eruption when other datasets (e.g., optical, thermal, ground-based measurements, etc.) may be limited. Here, we present an approach for estimating volcanic topography from individual backscatter images. Using data from multiple SAR sensors we apply the method to the dome growth during the 2021 eruption at La Soufrière, St. Vincent. We measure an average extrusion rate of 1.8 m<SUP>3</SUP>s<SUP>-1</SUP> between December 2020 and March 2021 before an acceleration in extrusion rate to 17.5 m<SUP>3</SUP>s<SUP>-1</SUP> in the 2 days prior to the explosive eruption on 9 April 2021. We estimate a final dome volume of 19.4 million m<SUP>3</SUP>, extrapolated from the SAR sensors, with approximately 15% of the total extruded volume emplaced in the last 2 days. A possible explanation for the acceleration in extrusion rate could be the combined emptying of a conduit and reservoir of older material before the ascent of gas-rich magma in April 2021.
International audience;
Chemical mixing of different types of magma, such as basaltic magma and silica-rich, hydrous magma, often triggers volcanic eruptions. However, the kinetics, mechanisms, and rates of sulfide dissolution reactions in hydrous melts are currently unknown, despite the fact that these reactions can influence the sulfur budget in the crust and mantle. I experimentally model dissolution of pyrrhotite minerals in hydrous rhyolite melt at conditions corresponding to the sulfate–sulfide transition field at 1 GPa pressure. The reaction results in the production of FeO, SO42−, H2, H2S and di- and tri-sulfur radical ions, (S2− or S3−) in fluid/melt. The calculated sulfur diffusion coefficient implies extremely fast sulfur diffusion in the hydrous hybrid melt. The production of S-rich magma is controlled by the fastest-ever-recorded chemical diffusion of sulfur in the form of S2− or S3− in hybrid magma under sulfate-sulfide transition conditions. I demonstrate that such dissolution reactions can be responsible for triggering explosive volcanic eruptions (e.g., the 1991 Mount Pinatubo eruption) in volcanic arc settings. The sulfide dissolution reaction can also promote the production of chalcophile metal (sulfur-loving Au, Cu and Pt) ore deposits associated with the formation of volcanic arcs.
International audience;
The oceanic dissolved organic phosphorus (DOP) pool is mainly composed of P-esters and, to a lesser extent, equally abundant phosphonate and P-anhydride molecules. In phosphate-limited ocean regions, diazotrophs are thought to rely on DOP compounds as an alternative source of phosphorus (P). While both P-esters and phosphonates effectively promote dinitrogen (N 2 ) fixation, the role of P-anhydrides for diazotrophs is unknown. Here we explore the effect of P-anhydrides on N 2 fixation at two stations with contrasting biogeochemical conditions: one located in the Tonga trench volcanic arc region (“volcano,” with low phosphate and high iron concentrations), and the other in the South Pacific Gyre (“gyre,” with moderate phosphate and low iron). We incubated surface seawater with AMP (P-ester), ATP (P-ester and P-anhydride), or 3polyP (P-anhydride) and determined cell-specific N 2 fixation rates, nifH gene abundance, and transcription in Crocosphaera and Trichodesmium . Trichodesmium did not respond to any DOP compounds added, suggesting that they were not P-limited at the volcano station and were outcompeted by the low iron conditions at the gyre station. Conversely, Crocosphaera were numerous at both stations and their specific N 2 fixation rates were stimulated by AMP at the volcano station and slightly by 3polyP at both stations. Heterotrophic bacteria responded to ATP and 3polyP additions similarly at both stations, despite the contrasting phosphate and iron availability. The use of 3polyP by Crocosphaera and heterotrophic bacteria at both low and moderate phosphate concentrations suggests that this compound, in addition to being a source of P, can be used to acquire energy for which both groups compete. P-anhydrides may thus leverage energy restrictions to diazotrophs in the future stratified and nutrient-impoverished ocean.
HAL CCSD;Presses Universitaires de Strasbourgjanuari 2023Vulkanologie
International audience;
Which communication channels should be prioritized to make populations aware of local volcanic risks? In the internet age, is it still necessary to privilege the classic channels (radio, television, posters), or are the new communication channels (websites, social media) sufficient? Using an interview-based survey of a population in Peru (n = 76) who have been the object of several volcanic risk communication campaigns using posters, websites, social media and traditional media, we compare the recall (memorization) and perception of these previous campaigns. Two main empirical results emerge from the interviews: 1) Web- sites are proving to be particularly effective communication channels in this context, in stark contrast to the low impact of the printed press; 2) We find that the the same communication campaigns are perceived differently by residents depending on the neighborhood in which they live. This second empirical result advocates for a much more territory-based and localized strategy, where the district by district socio-cultural and geological environment form the foundations for communication strategies.
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Quels sont les canaux de communication à choisir en priorité pour sensibiliser une population à un risque volcanique local. A l'ère d'Internet, faut-il encore privilégier les canaux classiques (radio, télévision, affichage) ou les nouveaux supports de communication (sites web et réseaux sociaux) sont-ils suffisants ? Basée sur une enquête empirique auprès d'une population ciblée par plusieurs campagnes de communication par affichage, sites web, réseaux sociaux et médias classiques, cette recherche étudie de manière comparative la mémorisation et la perception des campagnes précédentes.Finalement, deux grands types de résultats émergent. Les sites web s'avèrent être de nouveaux canaux de communication particulièrement efficaces, notamment par rapport au faible impact de la presse écrite. En même temps, cette étude empirique montre l'importance d'une communication basée sur une logique territoriale, avec des messages différents dans chaque quartier ; ce qui plaide en faveur d'une communication locale beaucoup plus territorialisée.
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Volcanic eruptions eject large amounts of ash and trace gases such as sulfur dioxide (SO 2 ) into the atmosphere. A significant difficulty in mitigating the impact of volcanic SO 2 clouds on air traffic safety is that these gas emissions can be rapidly transported over long distances. The use of space-borne instruments enables the global monitoring of volcanic SO 2 emissions in an economical and risk-free manner. Within the European Space Agency (ESA) Sentinel-5p+ Innovation project, the S5P SO 2 layer height (S5P+I: SO2LH) activities led to the improvements of the retrieval algorithm and generation of the corresponding near real-time S5P SO 2 LH products. These are currently operationally provided, in near real-time, by the German Aerospace Center (DLR) within the framework of the Innovative Products for Analyses of Atmospheric Composition (INPULS) project. The main aim of this paper is to present its extensive verification, accomplished within the S5P+I: SO2LH project, over major recent volcanic eruptions, against collocated space-borne measurements from the IASI/Metop and CALIOP/CALIPSO instruments as well as assess its impact on the forecasts provided by the Copernicus Atmospheric Monitoring Service (CAMS). The mean difference between S5P and IASI observations for the Raikoke 2019, the Nishinoshima 2020 and the La Soufrière-St Vincent 2021 eruptive periods is ∼ 0.5 ± 3 km, while for the Taal 2020 eruption, a larger difference was found, between 3 ± 3 km and 4 ± 3 km. The comparison of the daily mean SO 2 LH further demonstrates the capabilities of this near real-time product, with slopes between 0.8 and 1 and correlation coefficients ranging between 0.6 and 0.8. Comparisons between the S5P SO 2 LH and the CALIOP/CALIPSO ash plumes revealed an expected bias at -2.5 ± 2 km, considering that the injected SO 2 and ash plume locations do not always coincide over an eruption. Furthermore, the CAMS assimilation of the S5P SO 2 LH product led to much improved model output against the non-assimilated IASI LH, with a mean difference of 1.5 ± 2 km, compared to the original CAMS analysis, and improved the geographical spread of the Raikoke volcanic plume following the eruptive days.
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For over 6 months, the 2014-2015 effusive eruption at Holuhraun, Iceland, injected considerable amounts of sulfur dioxide (SO 2 ) into the lower troposphere with a daily rate of up to one-third of the global emission rate, causing extensive air pollution across Europe. The large injection of SO 2 , which oxidises to form sulfate aerosol (SO 2- 4 ), provides a natural experiment offering an ideal opportunity to scrutinise state-of-theart general circulation models' (GCMs) representation of aerosol-cloud interactions (ACIs). Here we present Part 1 of a two-part model inter-comparison using the Holuhraun eruption as a framework to analyse ACIs. We use SO 2 retrievals from the Infrared Atmospheric Sounding Interferometer (IASI) instrument and groundbased measurements of SO 2 and SO 2- 4 mass concentrations across Europe, in conjunction with a trajectory analysis using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model, to assess the spatial and chemical evolution of the volcanic plume as simulated by five GCMs and a chemical transport model (CTM). IASI retrievals of plume altitude and SO 2 column load reveal that the volcanic perturbation is largely contained within the lower troposphere. Compared to the satellite observations, the models capture the spatial evolution and vertical variability of the plume reasonably well, although the models often overestimate the plume altitude. HYSPLIT trajectories are used to attribute to Holuhraun emissions 111 instances of elevated sulfurous surface mass concentrations recorded at European Monitoring and Evaluation Programme (EMEP) stations during September and October 2014. Comparisons with the simulated concentrations show that the modelled ratio of SO 2 to SO 2- 4 during these pollution episodes is often underestimated and overestimated for the young and mature plume, respectively. Models with finer vertical resolutions near the surface are found to better capture these elevated sulfurous ground-level concentrations. Using an exponential function to describe the decay of observed surface mass concentration ratios of SO 2 to SO 2- 4 with plume age, the in-plume oxidation rate constant is estimated as 0.032 ± 0.002 h -1 (1.30 ± 0.08 d e-folding time), with a near-vent ratio of 25 ± 5 (µg m -3 of SO 2 / µg m -3 of SO 2- 4 ). The majority of the corresponding derived modelled oxidation rate constants are lower than the observed estimate. This suggests that the representation of the oxidation pathway/s in the simulated plumes is too slow. Overall, despite their coarse spatial resolutions, the six models show reasonable skill in capturing the spatial and chemical evolution of the Holuhraun plume. This capable representation of the underlying aerosol perturbation is essential to enable the investigation of the eruption’s impact on ACIs in the second part of this study
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Vulcanian eruptions are very common at many volcanoes around the world that erupt intermediate to silicic magmas. This type of eruption generates a wide variability of bombs and blocks preserving information onto the conduit processes that strongly control the dynamics of these events. After 84 years of repose, a new cycle of eruptive activity of Tungurahua volcano (Ecuador) started in October 1999, consisting of recurrent low-to-moderate explosive phases, which included sporadic stronger Strombolian to sub-Plinian pulses, as well as Vulcanian outbursts. The 1 February 2014 eruption was one of the most important Vulcanian events and was characterized by highly energetic explosions resulting from a plug conduit failure that generated a ~ 9 km-high eruptive column and fallback pyroclastic density currents. Four different types of blocks and bombs were found in the deposits of the pyroclastic density currents: dense fragments (DB), breadcrust bombs (BCB), cauliflower bombs (CFB) and foliated, banded bombs (FB). All the different types of bombs have homogenous andesitic bulk-rock compositions but different, highly evolved matrix glass compositions ranging from rhyolitic for BCB to dacitic for CFB and DB, suggesting the occurrence of contrasting shallow crystallization processes within the conduit. The wide variability of the bombs in terms of patterns of surface cracks, external morphologies, internal density and vesicularity gradients records different conditions of formation from a same magma composition.The combination of morphological measurements, compositional data and textural analysis allow us (i) to infer the pre-eruption physical and rheological state of the conduit plug, (ii) to reconstruct the short-scale lateral and vertical gradients characterizing the plug, and (iii) to clarify the specific mechanism controlling the formation conditions of CFB, still poorly defined in the literature.
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The hydration of the martian regolith at decimeter depth scales varies regionally, suggestive of geologically sustained processes, independent of diurnal soil-atmosphere exchange. A combination of factors, including residual hydration from ancient processes in the hydrosphere/cryosphere, seasonal exchange between the crust and atmosphere in the martian critical zone, or structural water in minerals or salts sourced via hydrothermal processes can contribute to such lateral changes in bulk regolith hydration. Here, we consider the theoretical extent of regolith hydration from explosive volcanic eruptions and subsequent hydration. While magmatic degassing has previously been considered as a contributing factor to regolith hydration, the relationship between hydrated regolith and the depositional footprint of volcanic eruption columns and associated atmospheric dispersal remains poorly known. We run simulations of eruptions in an ancient atmosphere over a martian year to account for seasonality and produce theoretical ash deposition maps which are then input into a geographic weighted regression model to predict hydrated regolith. We find that ash deposited via explosive volcanism can help explain certain patterns of hydration enrichment in the martian regolith, including those near Apollinaris Patera Arabia Terra, and Sabea Terra. While the global patterns of regolith hydration cannot be explained by one process alone, we found that hydrated ash likely contributed to hydrated regolith at a commensurable level to other leading hydration mechanisms. <p></p>Plain language summary. The surface of Mars is blanketed by a pervasive layer of regolith, a mixture of unconsolidated sediment of multiple grainsizes that range from very fine dust to larger pebbles. This regolith contains significant amounts of water that are stored in the chemical bonds that make up the individual regolith grains. The amount of water bound in the regolith is spatially inconsistent throughout the planet; some areas contain more water, while others contain less. Several different geologic processes have likely contributed to these inconsistencies, including volcanic processes. While gentle volcanic outgassing has already been considered, here we specifically looked at how explosive volcanism and the associated spreading of volcanic ash in the martian atmosphere may have contributed to hydrated regolith patterns. By using multiple numerical simulations, we found that explosive volcanism likely contributed to certain patterns of hydration in the regolith along with other geologic processes.
Solar flares are often accompanied by filament/prominence eruptions
($\sim10^{4}$ K and $\sim 10^{10-11}$ cm$^{-3}$), sometimes leading to coronal
mass ejections (CMEs) that directly affect the Earth's environment.
`Superflares' are found on some active solar-type (G-type main-sequence) stars,
but the association of filament eruptions/CMEs has not been established. Here
we show that our optical spectroscopic observation of the young solar-type star
EK Draconis reveals the evidence for a stellar filament eruption associated
with a superflare. This superflare emitted a radiated energy of
$2.0\times10^{33}$ erg, and blue-shifted hydrogen absorption component with a
large velocity of $-510$ km s$^{-1}$ was observed shortly after. The temporal
changes in the spectra greatly resemble those of solar filament eruptions.
Comparing this eruption with solar filament eruptions in terms of the length
scale and velocity strongly suggests that a stellar CME occurred. The erupted
filament mass of $1.1\times10^{18}$ g is 10 times larger than those of the
largest solar CMEs. The massive filament eruption and an associated CME provide
the opportunity to evaluate how they affect the environment of young
exoplanets/young Earth and stellar mass/angular-momentum evolution.
;Comment: 40 pages, 4 figures, 4 extended data figures, published in Nature
Astronomy (2021)
V445 Puppis is the only known example of a helium nova, where a layer of
helium-rich gas accretes onto the surface of a white dwarf in a cataclysmic
variable, with runaway helium burning making for the nova event. Speculatively,
helium nova can provide one path to produce a Type Ia supernova (SNIa), within
the larger framework of single-degenerate models. Relatively little has been
known about V445 Pup, with this work reporting the discovery of the orbital
period near 1.87 days. The companion star is 2.65$\pm$0.35 R$_{\odot}$ in
radius as an evolved giant star stripped of its outer hydrogen envelope. The
orbital period immediately before the 2000 eruption was $P_{\rm
pre}$=1.871843$\pm$0.000014 days, with a steady period change of
(-0.17$\pm$0.06)$\times$10$^{-8}$ from 1896--1995. The period immediately after
the nova eruption was $P_{\rm post}$=1.873593$\pm$0.000034 days, with a
$\dot{P}$ of ($-$4.7$\pm$0.5)$\times$10$^{-8}$. The fractional orbital period
change ($\Delta P/P$) is $+$935$\pm$27 ppm. This restricts the mass of the
gases ejected in the nova eruption to be $\gg$0.001M$_{\odot}$, and much
greater than the mass accreted to trigger the nova. So the white dwarf is
losing mass over each eruption cycle, and will not become a SNIa. Further, for
V445 Pup and helium novae in general, I collect observations from 136 normal
SNIa, for which any giant or sub-giant companion star would have been detected,
yet zero companions are found. This is an independent proof that V445 Pup and
helium novae are not SNIa progenitors.
;Comment: ApJ in press
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The southern part of the Mozambique Channel is characterized by a cluster of isolated seamounts, including the Bassas da India atoll and Europa Island, ranging in latitude from 20°S to 22°S and from 38° to 40° in longitude, and located at the Rovuma-Lwandle plate boundary. Only Cenozoic carbonate platforms have previously been studied in this region, with very little work done on the volcanic history. We confirm here the volcanic nature of the basement of the Bassa da India/Europa complex by providing important constraints on the setting of this hitherto poorly understood volcanism.Recent bathymetric surveys and dredging operations allowed us to map and date these seamounts, comprising, from west to east, the Hall Bank, the Jaguar Bank, Bassas da India, Ptolemee, and Europa. In addition, we discovered, to the south of Bassas da India, two large new polygenetic volcanic edifices, Pamela Seamount 1 (PS1) and Pamela Seamount 2 (PS2), showing heights and diameters of up to 900 m and 13 km, respectively. Mapping and statistical analysis carried out revealed that the volcanic structures of the Bassas da India/Europa complex are organized along two main alignments with different stages of development: (i) a NE-SW volcanic alignment characterized by volcanic ridges up to 700 m in height, comprising small individual volcanic cones; and (ii) a NW-SE volcanic alignment in which many large and well-developed individual volcanic cones can be found. From this distribution of the volcanism, we suggest that the large volcanic edifices of the Bassas da India/Europa complex were fed by long-lived magma systems, repeatedly supplied from deep magma reservoirs through a significant network of dykes and faults, with lateral injections of magma guided by a dense network of faults allowing magma to reach the surface along rift-zones. 40Ar/39Ar dating confirms that the volcanism covers a period from the Oligo-Miocene to the Pleistocene, and probably extends to the present day. The two volcanic alignments are also consistent with the tectonic features already recognized for the region and are spatially superimposed by active seismicity. Magma ascent is strongly controlled by large pre-existing crustal structures.
River ecosystem services (RES) are vulnerable to landscape changes mainly by volcanic eruptions. Therefore, this study aims to assess RES in the volcanic area which was affected by the major and minor eruptions of Mount Merapi, Indonesia. The RES referred to the regulating and supporting services of the Krasak River in Jogjakarta. The research involved collecting water and biodiversity samples from two distinct Merapi’s hazard zones (KRB I and KRB II) along the river. Parameters related to regulating services, such as particulate, organic, and nutrient purification, biological control, as well as supporting services like primary productivity, were quantified. We conducted an analysis to understand how landscape conditions interacted with these parameters and employed the t -test to assess differences in RES between the two KRBs. Our findings revealed that the Krasak River exhibited a range of values, including 2.40–5.95 mg/l for Biological Oxygen Demand (BOD), 0.61–3.41 mg/l for nitrate, 0.02–0.11 mg/l for phosphate, 160–60,000 MPN/100 ml for coliform, and 156.3–937 µg/l for chlorophyll-A. These values demonstrated the river’s capacity to perform both regulation and support services. However, certain segments showed variations in ecosystem services, possibly due to the presence of autochthonous matter from aquatic organisms and decomposing organic matters. This showed that volcanic eruption and landscape are closely linked with the water quality and aquatic biodiversity, which affect the ecosystem services.
Improving soft clay soil’s mechanical properties and durability has been the subject of intense research. In this context, traditional stabilizers such as cement and lime have been introduced as the most widely used materials. However, these materials face many challenges due to recent global concerns for reducing greenhouse gas emissions. Therefore, international research is shifting toward using environmentally friendly soil-stabilizing waste materials. This study, for the first time, evaluates the stabilization of kaolin clay soil using lime kiln dust (LKD) as a high CaO content waste pozzolan and volcanic ash (VA) as a natural pozzolan with high SiO 2 and Al 2 O 3 content. In general, it aims to demonstrate the effective performance of these two inexpensive and environmentally friendly additives in improving the mechanical features and durability of kaolin clay soil, thereby providing the necessary groundwork for the practical application of this method in stabilizing soft clay soil. This study included preparing samples with LKD at 3%, 5%, 7%, and 10% of the dry weight of clay and replacing VA with LKD at 0%, 25%, 75%, and 100%. The specimens were cured for 3, 7, and 28 days. After this curing period, the optimal sample was subjected to various freeze-thaw (F-T) cycles at 0, 1, 3, 7, and 10. The samples were examined by conducting compaction, scanning electron microscopy (SEM), unconfined compressive strength (UCS), ultrasonic pulse velocity (UPV), and X-ray diffraction (XRD) at different stages of adding stabilizers, as well as before and after introduction of F-T cycles. Adding LKD and VA further increased the UCS by accelerating pozzolanic and hydration reactions. Also, the mixture of LKD and VA in kaolin soil enhanced F-T durability and indicated less strength deterioration even after 10 cycles compared to the control sample. The optimal mixture of 5% LKD and 25% VA replacement improved 11 times in UCS and showed a slight reduction of only 7% after 10 F-T cycles compared to untreated kaolin clay. Overall, the combination of LKD and VA enhanced the mechanical features of kaolin clay soil and F-T durability, making it a low-cost, sustainable, and eco-friendly option for soil improvement. • Lime Kiln Dust (LKD) and Volcanic Ash (VA) were used for stabilizing kaolin soil • VA enhances the freeze-thaw (F-T) durability of the LKD-stabilized kaolin soil • Enhanced stiffness and toughness observed in kaolin stabilized with LKD and VA • Increased pozzolanic reactions with VA lead to more cementitious products • LKD and VA provide a sustainable solution for kaolin soil stabilization
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Tephrochronology studies the deposits of explosive volcanic eruptions in the stratigraphic record. The Southern (SVZ, 33-46 • S) and Austral (AVZ, 49-55 • S) Volcanic Zones of the Andes are two very active volcanic zones where tephrochronology is of great use. There, it can be used to improve chronologies of paleoenvironmental records in Patagonia, an area providing valuable records at global scale; as well as to identify areas likely to be affected by volcanic eruptions in the future, essential for producing volcanic hazard maps. The close proximity of many volcanic centers with recurrent explosive activity, which have very similar geochemical compositions, and very often poor age constraints, represent a challenge for the study of tephrochronology in the region. In addition to this, the ever-growing amount of tephrochronological information in the area, dispersed in different types of publications which vary greatly in format, makes the integration of the data produced by different actors, and consecutively its interpretation, increasingly difficult. Here we address this issue by compiling the BOOM! dataset, which integrates ~30 years of research on 32 active volcanic centers and 132 different eruptions, which took place during the last 20,000 years. To help users find and reuse data in the large dataset, we developed an online platform which provides user-friendly tools for exploring it, and helps users download subsets of it. To integrate this very heterogeneous information, special attention was given to include information which allows users to evaluate data quality and comparability, as well as to provide tools in the explorer for users to filter data by different criteria. The integration of this dataset opens new perspectives for the development of novel visualizations of tephrochronological data, for example, to better understand the multidimensional uncertainties associated with it. For example, uncertainties associated with analytical precision, with age estimates of both tephra deposits and volcanic eruptions, and of tephra classification. Additionally, it allows for the use of robust statistical tools to correlate tephra deposits, including those based on machine learning algorithms, which are here explored.
HAL CCSD;Académie des sciences (Paris)januari 2022Vulkanologie
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A multichannel seismic reflection profile acquired during the SISMAORE cruise (2021) provides the first in-depth image of the submarine volcanic edifice, named Fani Maore, that formed 50 km east of Mayotte Island (Comoros Archipelago) in 2018–2019. This new edifice sits on a »140 m thick sedimentary layer, which is above a major, volcanic layer up to »1 km thick and extends over 120 km along the profile. This volcanic unit is made of several distinct seismic facies that indicate successive volcanic phases. We interpret this volcanic layer as witnessing the main phase of construction of the Mayotte Island volcanic edifice. A »2.2–2.5 km thick sedimentary unit is present between this volcanic layer and the top of the crust. A complex magmatic feeder system is observed within this unit, composed of saucer-shape sills and seal bypass systems. The deepest tip of this volcanic layer lies below the top-Oligocene seismic horizon, indicating that the volcanism of Mayotte Island likely began around 26.5Ma, earlier than previously assumed.
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Un profil de sismique réflexion multitrace acquis lors de la campagne océanographique SISMAORE (2021) apporte la première image en profondeur du volcan sous-marin Fani Maore, qui s’est formé à 50 km à l’est de l’île de Mayotte (archipel des Comores) en 2018–2019. Ce nouvel édifice repose sur une première couche sédimentaire d’environ 140 m d’épaisseur au-dessus d’une couche volcanique majeure épaisse de 1 km et qui s’étend sur 120 km le long du profil. Cette dernière unité volcanique est constituée de plusieurs faciès sismiques distincts qui indiquent des phases volcaniques successives. Nous interprétons cette couche volcanique comme le témoin de la phase principale de construction de l’édifice volcanique de l’île de Mayotte. Une couverture sédimentaire de »2.2–2.5 km d’épaisseur est présente entre cette couche volcanique et le toit de la croûte. On y observe de nombreux sills en forme de soucoupe ainsi que des zones à faciès de remontées de fluides, dessinant un système d’alimentation magmatique complexe sous la principale couche volcanique. L’extrémité la plus profonde de cette couche volcanique se place en dessous de l’horizon sismique de l’Oligocène supérieur et indique que le volcanisme de l’île de Mayotte a probablement commencé vers 26.5 Ma, plus tôt que ce qui était supposé auparavant.
Springer Science and Business Media LLCoktober 2023Vulkanologie
Abstract Volcanic eruptions can trigger tsunamis, which may cause significant damage to coastal communities and infrastructure. Tsunami generation during volcanic eruptions is complex and often due to a combination of processes. The 1650 eruption of the Kolumbo submarine volcano triggered a tsunami causing major destruction on surrounding islands in the Aegean Sea. However, the source mechanisms behind the tsunami have been disputed due to difficulties in sampling and imaging submarine volcanoes. Here we show, based on three-dimensional seismic data, that ~1.2 km³ of Kolumbo’s northwestern flank moved 500–1000 m downslope along a basal detachment surface. This movement is consistent with depressurization of the magma feeding system, causing a catastrophic explosion. Numerical tsunami simulations indicate that only the combination of flank movement followed by an explosive eruption can explain historical eyewitness accounts. This cascading sequence of natural hazards suggests that assessing submarine flank movements is critical for early warning of volcanogenic tsunamis.
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Volcanic ash provides unique pieces of information that can help to understand the progress of volcanic activity at the early stages of unrest, and possible transitions towards different eruptive styles. Ash contains different types of particles that are indicative of eruptive styles and magma ascent processes. However, classifying ash particles into its main components is not straightforward. Diagnostic observations vary depending on the magma composition and the style of eruption, which leads to ambiguities in assigning a given particle to a given class. Moreover, there is no standardized methodology for particle classification, and thus different observers may infer different interpretations. To improve this situation, we created the web-based platform Volcanic Ash DataBase (VolcAshDB). The database contains > 6,300 multi-focused high-resolution images of ash particles as seen under the binocular microscope from a wide range of magma compositions and types of volcanic activity. For each particle image, we quantitatively extracted 33 features of shape, texture, and color, and petrographically classified each particle into one of the four main categories: free crystal, altered material, lithic, and juvenile. VolcAshDB (https://volcash.wovodat.org) is publicly available and enables users to browse, obtain visual summaries, and download the images with their corresponding labels. The classified images could be used for comparative studies and to train Machine Learning models to automatically classify particles and minimize observer biases.
We examine 3He-rich solar energetic particles (SEPs) detected on 2023 October 24-25 by Solar Orbiter at 0.47 au. The measurements revealed that heavy-ion enhancements increase irregularly with mass, peaking at S. C, and especially N, Si, and S, stand out in the enhancement pattern with large abundances. Except for 3He, heavy ion spectra can only be measured below 0.5 MeV/nucleon. At 0.386 MeV/nucleon, the event showed a huge 3He/4He ratio of 75.2+/-33.9, larger than previously observed. Solar Dynamics Observatory extreme ultraviolet data showed a mini filament eruption at the solar source of 3He-rich SEPs that triggered a straight tiny jet. Located at the boundary of a low-latitude coronal hole, the jet base is a bright, small-scale region with a supergranulation scale size. The emission measure provides relatively cold source temperatures of 1.5 to 1.7 MK between the filament eruption and nonthermal type III radio burst onset. The analysis suggests that the emission measure distribution of temperature in the solar source could be a factor that affects the preferential selection of heavy ions for heating or acceleration, thus shaping the observed enhancement pattern. Including previously reported similar events indicates that the eruption of the mini filament is a common feature of events with heavy-ion enhancement not ordered by mass. Surprisingly, sources with weak magnetic fields showed extreme 3He enrichment in these events. Moreover, the energy attained by heavy ions seems to be influenced by the size and form of jets. ;21 pages, 12 figures, 2 tables. Accepted version of the paper. Publisher typeset PDF and an MP4 animation are provided as ancillary files
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The tectono-volcanic ensemble of the Chaîne des Puys and the Limagne fault, which is part of the West European rift, was inscribed on the UNESCO World Heritage list in 2018 as the Chaîne des Puys-Limagne fault tectonic arena. This site includes (1) the western normal border fault of the graben (the Limagne fault), (2) the shoulder of the graben (the granitic Plateau des Dômes) on which lies a Quaternary volcanic alignment (the Chaîne des Puys), and (3) an inverted relief resulting from erosive action around a Pliocene volcanic lava flow (the Montagne de la Serre). It is shown that, when viewed in a global tectonic context, these structural and volcanic features can be described as a natural scale model, allowing everyone to understand the processes in operation at depth in a continental rift. The property is an inhabited environment that counts 30,000 inhabitants and traditional activities such as pastoral farming and agroforestry. Following its inscription on the World Heritage List, the challenge for the coming years is to coordinate conservation, sustainable development and international stature in the site.
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Hydrothermal or low-temperature volcanic emissions, most commonly occurring in fumarolic environments, dominate the global volcanic landscape. This work presents physicochemical characterization of the aerosols contained in steam- and H2S-rich plumes discharged from La Soufri`ere volcano, in conjunction with the first report on their heavy metal degassing emission rates. Our results indicate that the plume is enriched in certain lithophile (K, Ti, Si, Al, Mn, and Mg) and siderophile (Fe) elements, related to hydrothermal rock leaching, and chalcophile (Sb, As, Zn, Pb, and Tl) elements, which are usually degassed from the magma source. Heavy metal emission rates were found to be below 15 g/d, which are modest compared to available worldwide data. Nevertheless, Cr and Sb emission rates were very similar to those of Lascar volcano (Chile), which instead has produced magmatic eruptions in recent times. We propose that the depth of the magma chamber and the input of meteoric waters play an important role in scavenging heavy metals in the hydrothermal system of magmatic- hydrothermal volcanoes. Notwithstanding low heavy metal emission rates, La Soufri`ere can be regarded as an important pollution source in the Lesser Antilles volcanic arc.
Coronal mass ejections from the Sun are not always initiated along a radial
trajectory; such non-radial eruptions are well known to be caused by the
asymmetry of the pre-eruption magnetic configuration, which is primarily
determined by the uneven distribution of magnetic flux at the photosphere.
Therefore, it is naturally expected that the non-radial eruptions should be
rather common, at least as frequent as radial ones, given the typically
asymmetrical nature of photospheric magnetic flux. However, statistical studies
have shown that only a small fraction of eruptions display non-radial behavior.
Here we aim to shed light on this counterintuitive fact, based on a series of
numerical simulations of eruption initiation in bipolar fields with different
asymmetric flux distributions. As the asymmetry of the flux distribution
increases, the eruption direction tends to deviate further away from the radial
path, accompanied by a decrease in eruption intensity. In case of too strong
asymmetry, no eruption is triggered, indicating that excessively inclined
eruptions cannot occur. Therefore, our simulations suggest that asymmetry plays
a negative role in producing eruption, potentially explaining the lesser
frequency of non-radial solar eruptions compared to radial ones. With
increasing asymmetry, the degree of non-potentiality the field can attain is
reduced. Consequently, the intensity of the pre-eruption current sheet
decreases, and reconnection becomes less efficient, resulting in weaker
eruptions.
;Comment: 7 pages, 5 figures, accept by MNRAS Letters
International audience;
Mangroves are one of the most important but threatened blue carbon ecosystems globally. Rapid urban growth has resulted in nutrient inputs and subsequent coastal eutrophication, associated with an enrichment in organic matter (OM) from algal and sewage sources and substantial changes in greenhouse gas (GHG) emissions. However, the effects of nitrogen (N) and phosphorus (P) enrichment on mangrove soil OM composition and GHG emissions, such as methane (CH4) and carbon dioxide (CO2), are still poorly understood. Here, we aim to evaluate the relationships between CO2 and CH4 efflux with OM composition in exposed soils from three mangrove areas along watersheds with different urbanization levels (Rio de Janeiro State, Brazil). To assess spatial (lower vs. upper intertidal zones) and seasonal (summer vs. winter) variability, we measured soil-air CO2 and CH4 fluxes at low spring tide, analyzing elementary (C, N, and P), isotopic (δ13C and δ15N), and the molecular (n-alkanes and sterols) composition of surface soil OM. A general trend of OM composition was found with increasing urban influence, with higher δ15N (proxy of anthropogenic N enrichment), less negative δ13C, more short-chain n-alkanes, lower C:N ratio (proxies of algal biomass), and higher epicoprostanol content (proxies of sewage-derived OM). The CO2 efflux from exposed soils increased greatly in median (25/75 % interquartile range) from 4.6 (2.9/8.3) to 24.0 (21.5/32.7) mmol m−2 h−1 from more pristine to more urbanized watersheds, independent of intertidal zone and seasonality. The CO2 fluxes at the most eutrophicated site were among the highest reported worldwide for mangrove soils. Conversely, CH4 emissions were relatively low (three orders of magnitude lower than CO2 fluxes), with high peaks in the lower intertidal zone during the rainy summer. Thus, our findings demonstrate the influence of coastal eutrophication on global warming potentials related to enhanced heterotrophic remineralization of blue carbon within mangrove soils.
A range of agroecological practices allow to increase soil organic carbon (SOC) stocks. While it is very positive in terms climate change mitigation and soil health, the permanence of the additional SOC storage can be questioned, in particular in a climate change context. Furthermore, the carbon sink effect will be more effective, even in the short and medium term, if the additional SOC storage is realized in the form of persistent organic carbon (OC) and not in labile OC. The objective of this thesis was to firstly evaluate the biogeochemical stability of the recently stored carbon, and secondly the vulnerability of this carbon to extreme climatic events. To achieve this, we used a multi-method approach (physical fractionation, Rock-Eval thermal analysis, long-term incubation and modelling) to determine carbon fractions and carbon kinetic pools. We assessed carbon vulnerability by determining the sensitivity of SOC mineralization to increasing temperature, decreasing soil moisture and subsequent dry-wet cycles. The different analyses and experiments were performed on topsoil samples (0-30 cm) from temperate Luvisols that were subjected for 20 years to conservation agriculture (CA), organic agriculture (ORG) in the La Cage experiment, and conventional agriculture and organic waste products (OWPs) applications in the QualiAgro experiment. Our study demonstrates that the plots that received the OWPs led more additional C in minerals associated organic matter (MAOM-C) and in particulate organic matter (POM-C), whereas the CA and ORG, led to more additional C in MAOM-C. The PARTYSOCv2.0 model using Rock-Eval thermal analysis parameters revealed that most, if not all of the additional C belonged to the active C pool. These findings suggest that although additional C is mainly associated with MAOM-C, it is probably not stored in a form with a mean residence time exceeding 30 years. The proportion of POM and the incubations experiment revealed a chemical recalcitrance of POM with OWPs. In addition, the carbon-storing soils had similar sensitivity to soil moisture regime and temperature as the baseline ones. Hence, the implementation of these agroecological practices appears to be beneficial to climate change mitigation, even in the context of extreme climatic events. Given the short-term stability of this additional carbon, these agroecological practices must be continued in order to maintain their stock at a high level.
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Différentes pratiques agroécologiques permettent d'augmenter les stocks de carbone organique du sol (COS). Bien que cela soit très positif en termes d'atténuation au changement climatique et de santé des sols, la permanence du stockage additionnel de COS doit être évaluée, en particulier dans un contexte de changement climatique. L'effet puits de carbone sera plus efficace, même à court et moyen terme, si le stockage additionnel de COS est réalisé sous forme de carbone organique (CO) persistant et non de CO labile. L'objectif de cette thèse était d'évaluer d'une part la stabilité biogéochimique du carbone nouvellement stocké, et d'autre part la vulnérabilité de ce carbone face aux événements climatiques extrêmes. Pour cela, nous avons utilisé une approche multiméthodes (fractionnement physique, analyse thermique Rock-Eval, incubation à long terme et modélisation) pour déterminer les fractions de carbone et les compartiments cinétiques de carbone. Nous avons évalué la vulnérabilité du carbone en déterminant la sensibilité de la minéralisation du COS à l'augmentation de la température, à la diminution de l'humidité du sol et à la présence de cycles desiccation/humectation. Les différentes analyses et expériences ont été réalisées sur des échantillons de sol de surface (0-30 cm) provenant de luvisols tempérés soumis pendant 20 ans à l'agriculture de conservation (CA), à l'agriculture biologique (ORG) et à l'agriculture conventionnelle dans l'expérience de La Cage et à des applications de produits résiduaires organiques (PROs) dans l'expérience QualiAgro. Notre étude démontre que les parcelles qui ont reçu les PROs ont conduit à plus de C additionnel dans la matière organique associée aux minéraux (MAOM-C) et dans la matière organique particulaire (POM-C), alors que le CA et l'ORG, ont conduit à plus de C additionnel dans la MAOM-C. Le modèle PARTYSOCv2.0 utilisant les paramètres d'analyse thermique Rock-Eval a révélé que la plupart, sinon la totalité, du C additionnel était dans le compartiment de C actif. Ces résultats suggèrent que, bien que le C additionnel soit principalement associé au MAOM-C, il n'est probablement pas stocké sous une forme dont le temps moyen de résidence dépasse 30 ans. La proportion de POM et les expériences d'incubation ont révélé une récalcitrance chimique des POM avec les PROs. En outre, les sols stockant le carbone avaient une sensibilité similaire au régime d'humidité du sol et à la température que les sols de référence. Ainsi, la mise en œuvre de ces pratiques agroécologiques apparaît bénéfique à l'atténuation au changement climatique, même dans le contexte d'événements climatiques extrêmes. Suite à la stabilité à court terme de ce carbone additionnel, ces pratiques agroécologiques doivent être poursuivies afin de maintenir leur stock à un niveau élevé.
Global warming has become the focus of attention of the international community, and the control of carbon dioxide emissions has become one of the necessary choices for the development strategies of countries around the world. Cities are places where carbon dioxide emissions are concentrated. The key to controlling carbon emissions is to control the carbon emissions of cities. My country is currently in the process of rapid urbanization. Quantitative studies of the carbon cycle at the city level will help to take stock of carbon dioxide emissions in cities. On the other hand, it is helpful to understand the status and role of the urban carbon cycle in the process of the regional carbon cycle. Through the analysis and prediction of the elements influencing the carbon cycle of smart cities, this paper first determines the factors affecting smart cities in the carbon cycle process as industrial carbon emission strength factors, industrial structure effects, economic development factors, and population elements. It is found that the major positive factors affecting the significant add of CO2 emissions in smart cities from 2010 to 2019 are economic development factors and demographic factors, including economic development factors GDP/per capita GDP. The per capita contribution to CO2 emissions is higher than the model established by adjusting the affecting elements of overall CO2 emissions, except that the proportion of economic development factors in total CO2 emissions from 2013 to 2015 was lower than the increase in total CO2 emissions. The comparison can better reflect the relation between CO2 emissions and influencing elements. The main determinants affecting CO2 emissions are the expansion of the financial condition, the increase in the average daily population, and the increase in construction work. The adaptation index is judged to be consistent, indicating that the model adjustment effect is good; finally, the green computing in the smart city predicts the carbon cycle process, and the actual value trend line and the predicted value trend line are not much different from the practical value, the forecast error is small, and the prediction results are credible. Global warming has become the focus of attention of the international community, and carbon emission control has become one of the necessary options in the development strategies of countries around the world. Cities are the places where carbon emissions are concentrated. The key to controlling carbon emissions is to control urban carbon emissions. At present, my country is in the process of rapid urbanization. Quantitative research on the carbon cycle at the city level will help to establish an inventory accounting of urban carbon emissions. On the other hand, it is convenient to deeply understand the status and role of the urban carbon cycle in the process of the regional carbon cycle.
Plants are known to be autotrophic, i.e. photosynthetic, with the ability to synthesise their own organic matter from mineral matter. They act as primary producers, as opposed to secondary consumers such as heterotrophs. However, the frontier between these two forms of nutrition is no longer so marked since the discovery of carnivorous mechanisms in certain plants, as well as the presence of a mixed metabolism in many micro-organisms. Aquatic plants, which are the true pillars of aquatic ecosystems, are subject to multiple pressures, accentuated by pollution and climate change. In addition, aquatic ecosystems are often rich in dissolved organic carbon (DOC), particularly in the case of eutrophication. In these highly productive ecosystems, the water is usually turbid, which limits photosynthesis by submerged plants. These elements have become the basis for a strong hypothesis in favour of parallel carbon nutrition. The objective of this thesis was consequently to explore the previously unknown capacity of mixotrophy (i.e. the possibility of direct use of dissolved organic carbon in addition to photosynthesis) in aquatic plants. This use of DOC would be facilitated by the absence of a cuticle and the contact of the entire surface of the vegetative apparatus with water. Experiments on Lemna minor and Myriophyllum spicatum led to the demonstration of the mixotrophic capacity of these two aquatic plants for which this had never been mentioned before. Among the most striking results was the growth allowed in the dark in the presence of sugar and an increase in growth rate of almost 50% in the light for L. minor in the presence of 10 g.L-1 of glucose. Numerous small labile DOC molecules were tested to give a first overview of the actual usable molecules. Sugars, especially sucrose and its two monomers glucose and fructose, were the molecules with the most significant results. A transcriptomic approach was also carried out in order to better understand the cellular and metabolic mechanisms involved, and to open up new questions on the inheritance or the specific appearance in aquatic environments of such capacities. The sequencing of M. spicatum was carried out in this context, a species that was not yet available in the databases despite its status as a model plant. The hypothesis of a role for the endophytes potentially present was also questioned. A three-method approach (microbial culture, molecular biology technique and genomic analysis) demonstrated the absence of endophytes in our study plants, attributing the mixotrophic capacities directly to the plants and not to their unrevealed internal microbiota. Finally, in a context of chemical contamination, notably by photosynthesis-inhibiting herbicides, the question of the compensatory effect of mixotrophy was the last aspect studied. Very promising results were obtained: in particular, the presence of glucose at a concentration of 10 g.L-1 made it possible to fully compensate for a lethal isoproturon concentration of 480 μg.L-1. The use of organic carbon by aquatic plants could thus constitute a key metabolic alternative, allowing certain species to develop in a polluted environment. In the light of our multiple results, this underestimated phenomenon of mixotrophy could therefore be at the origin of truly unsuspected capacities in many aquatic plants, opening the way to perspectives both on the understanding of their development and on their role in phytoremediation processes and biotechnologies in polluted environments.
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Les plantes sont autotrophes pour le carbone du fait de leurs capacités photosynthétiques, avec par conséquent l'aptitude à produire leur propre matière organique à partir de matière minérale en utilisant l'énergie lumineuse. En tant que producteurs primaires, on les oppose donc classiquement aux consommateurs que sont les hétérotrophes. Or, la frontière entre ces deux formes de nutrition n'est plus si marquée depuis la découverte de la carnivorie chez certaines plantes, ainsi que la présence d'un métabolisme mixte chez de nombreux micro- organismes : la mixotrophie. De même, l'association très commune avec des microorganismes de la rhizosphère (mycorhizes) ou la présence d'endophytes peuvent parfois être à l'origine d'une alimentation carbonée indirecte de la plante par son symbionte, ce que l'on peut alors qualifier de mixotrophie biotrophe. Les plantes aquatiques, éléments structurants des écosystèmes aquatiques, se développent dans des environnements naturellement contraignants et sont également soumises à de multiples pressions d'origine anthropique, comme les pollutions chimiques et les variations climatiques. Les écosystèmes aquatiques sont souvent riches en carbone organique dissous (COD), particulièrement en cas d'eutrophisation. Dans ces écosystèmes très productifs, l'eau est généralement turbide, ce qui limite la photosynthèse des végétaux immergés. La question de l'utilisation du COD pour leur nutrition carbonée peut alors être posée. La présente thèse avait pour objectif d'explorer la capacité de mixotrophie chez les plantes aquatiques, jusqu'alors très peu étudiée. Des expériences menées au laboratoire sur Lemna minor et Myriophyllum spicatum ont conduit à confirmer la capacité mixotrophe chez ces deux plantes aquatiques pour lesquelles cela n'avait jamais encore été évoqué explicitement. Une croissance maintenue à l'obscurité en présence de sucre, ainsi qu'un taux de croissance augmenté de près de 50% à la lumière chez L. minor en présence de 10 g.L-1 de glucose figurent parmi les résultats les plus marquants. Un panel de petites molécules labiles du COD a été testé, de sorte à donner un premier aperçu des molécules utilisables par les plantes. Les sucres, notamment le saccharose et ses deux monomères glucose et fructose sont les molécules présentant les effets les plus marqués. Une approche transcriptomique a également été initiée afin de mieux comprendre les mécanismes cellulaires et métaboliques à l'œuvre, et de soulever de nouvelles questions sur l'héritage ou l'apparition spécifique aux milieux aquatiques de telles capacités. Le séquençage de M. spicatum a été réalisé dans ce cadre. Cette espèce n'était en effet pas encore disponible dans les bases de données malgré son statut de plante modèle et sa position taxonomique clé. L'hypothèse d'un rôle des endophytes potentiellement présents a également été questionnée. Une approche selon trois axes (culture microbienne, recherche de gènes par biologie moléculaire (PCR) ou en analyse de contamination directement dans les génomes séquencés) a permis de démontrer l'absence d'endophyte chez les plantes étudiées, et d'attribuer les capacités mixotrophes directement aux plantes et non à un éventuel microbiote interne. Enfin, dans un contexte de contamination chimique, notamment par des herbicides inhibiteurs de la photosynthèse, la question de l'effet compensateur de la mixotrophie a été étudiée. Des résultats très prometteurs ont été obtenus chez L. minor : la présence de glucose à la concentration de 10 g.L-1 permet notamment de compenser totalement l'effet létal d'une concentration en isoproturon de 480 μg.L-1.[...]
CCSD;American Association for the Advancement of Science (AAAS)juni 2024Klimaatwetenschap
International audience;
La Niña climate anomalies have historically been associated with substantial reductions in the atmospheric CO 2 growth rate. However, the 2021 La Niña exhibited a unique near-neutral impact on the CO 2 growth rate. In this study, we investigate the underlying mechanisms by using an ensemble of net CO 2 fluxes constrained by CO 2 observations from the Orbiting Carbon Observatory-2 in conjunction with estimates of gross primary production and fire carbon emissions. Our analysis reveals that the close-to-normal atmospheric CO 2 growth rate in 2021 was the result of the compensation between increased net carbon uptake over the tropics and reduced net carbon uptake over the Northern Hemisphere mid-latitudes. Specifically, we identify that the extreme drought and warm anomalies in Europe and Asia reduced the net carbon uptake and offset 72% of the increased net carbon uptake over the tropics in 2021. This study contributes to our broader understanding of how regional processes can shape the trajectory of atmospheric CO 2 concentration under climate change.
International audience;
The structure of catalyst containing Ni nanoparticles (NPs) supported over carbon nanofibers/few layer graphene (CNFs/FLG) was tailored via modification of chemical vapor deposition parameters in view of methanation of CO 2 under induction heating mode (IH). High edges-to-graphitic plane ratio in the support achieved due to the specific herringbone morphology of CNFs allowed to get high CO 2 conversion of 85% at relatively low temperature (360°C) at very low Ni loading of only 10%. A design of catalyst included also the use of FLG known for high temperature conductivity and by occasion serving as a support to grow CNFs. The performances of certain catalysts are also tested under "standard" Joule heating in order to check the role of the magnetic and conductive carbon support. The morphology, chemical composition and SAR measurements of the catalysts and carbon supports themselves are addressed and their structure-catalytic performances are discussed.
International audience;
JWST observations of TNOs up to 800 km in diameter show surface ices that include carbon-bearing species such as CO₂, CO, CH₃OH, and complex organic molecules (Pinilla-Alonso et al., 2024). Although surface compositions vary, no systematic trend with object size suggests these variations are dominated by surface processes. The surface compositions of larger TNOs display strong methane bands in addition to H₂O ice and CO₂ (Brown, 2012), and recent hydrogen and carbon isotopic measurements of CH₄ on Eris and Makemake by JWST suggest an internal origin for these species (Grundy et al., 2024). The bulk densities of icy moons and dwarf planets support the idea that their refractory cores contain a mixture of CI chondrite and carbonaceous material, reinforcing the idea that carbon-bearing molecules at their surfaces may originate from internal activity. Oxygen fugacity (fO₂) plays a crucial role in controlling the stability of carbonates, graphite, and associated mineral phases, governing carbon speciation and fluid composition in planetary interiors.We studied the impact of carbon on the mineralogy of trans-Neptunian object (TNO) interiors. We model phase relations in the MgO–SiO₂–Fe–C–H₂ and MgO–SiO₂–CaO–Fe–C–H₂ systems across the P–T range of TNOs (300–1300 K, 1–7000 bar), using thermodynamic modeling with Perple_X (Connolly, 2005) and assuming CI elemental composition. The results reveal that at high fO₂, carbonates (magnesite, dolomite), water, and CO₂ are stable, whereas at lower fO₂, carbon is progressively reduced to graphite, with methane and hydrogen as the dominant volatiles. The stability fields of major species (CO2, H2O, CH4) in COH fluids are bounded by different oxygen fugacity buffers defined by the stability of various carbon-bearing mineral assemblages. Conversely, if fluid composition is fixed, for example by degradation reactions of carbonaceous matter, it will determine the mineral assemblages. Pressure does not significantly influence these transitions, whereas changes in oxygen fugacity and temperature strongly affect the gas species released from the mineral assemblage into metamorphic fluids. Specifically, at high temperatures, reduced phases such as methane are stable, while at lower temperatures, oxidized species and CO₂ are favored. Thus, temperature and oxygen fugacity play a crucial role in controlling the nature of carbon-bearing phases in solids and in fluids that can reach the surface of TNOs.The predicted metamorphic evolution of mineral assemblages shows that the internal composition is directly reflected in fluid composition, which may eventually reach the surface and atmosphere of TNOs. Small TNOs (typically
Carbon sequestration and storage in biomass is one of the most important measures to mitigate climate change. Mediterranean woody crops can sequestrate carbon in the biomass of their permanent structures for decades; however, very few studies have focused on an assessment of biomass and carbon sequestration in these types of crops. This study is the first to estimate above- and belowground biomass carbon stock in Mediterranean woody crops through a bottom-up approach in the NE Iberian Peninsula in 2013. Moreover, this is the first time that an assessment of the annual changes in carbon stock in the study area over a six-year period is presented. For this purpose, eight crop- and site-specific equations relating biomass or biometric variables to crop age were calculated. Most of the data were our own measurements, but unpublished data supplied from other authors as well as data from literature were also considered. Census of Agriculture data was used to scale results from individual data up to the municipality level at the regional scale. Results show that in woody cropland in NE Spain the total biomass carbon stock in 2013 was 5.48 Tg C, with an average value of 16.44 ± 0.18 Mg C ha^−1. Between 2013 and 2019, although there was a 2.8% mean annual decrease in the area covered by woody crops, the carbon stock in the biomass of these crops increased annually by 3.8% due to the growth of the remaining woody cropland. This new estimation of carbon stocks may contribute to better understand carbon balances and serve as a baseline to global inventories. It may also serve to assess and manage carbon storage as an ecosystem service provided by Mediterranean woody cropland for mitigating climate change and, in combination with adaptive strategies, for supporting a productive and resilient agro-food system.
International audience;
Far from being frozen and sterile environments, glaciers are biogeochemical reactors and regulators. In this Review, we discuss the hydrology and biogeochemistry of glacierized environments and their impact on downstream ecosystems. Supraglacial meltwaters export labile organic carbon associated with active supraglacial microbial communities, as well as carbon and nutrients delivered via atmospheric deposition. Meltwaters funnelled to the glacier bed and exiting at the glacier snout transport large quantities of rock flour as well as supraglacial and subglacial-derived organic carbon and nutrients to downstream ecosystems. Subglacial water flow paths influence rock-water contact times and vary greatly, affecting weathering reactions. For instance, the hydrology of mountain glaciers and the Greenland Ice Sheet is typically dominated by seasonal melt with short (hours) to medium (weeks) water residence times, although extended biogeochemical isolation can exist in more isolated parts of the Greenland Ice Sheet. Conversely, the Antarctic Ice Sheet is dominated by basal ice melt and residence times that can exceed years and decades. As a result, the latter supports extended biogeochemical isolation and more advanced chemical weathering. Microbial processes and physical-chemical weathering can both sequester or emit greenhouse gases, but the net effect remains unknown. Meltwaters can potentially fuel biological processes in downstream ecosystems by priming glacierfed streams, fjords, and oceans with rock flour and nutrients. The rapid reduction in glacier area projected for the next century mandates that future research provides a critical assessment of the effects of deglaciation on watershed biogeochemistry, ecology and global biogeochemical cycles.
Observations of the emission of the carbon cycle species (C, C+ CO) are
commonly used to diagnose gas properties in the interstellar medium but are
significantly sensitive to the cosmic-ray ionization rate. The carbon-cycle
chemistry is known to be quite sensitive to the cosmic-ray ionization rate,
$\zeta$, controlled by the flux of low-energy cosmic rays which get attenuated
through molecular clouds. However, astrochemical models commonly assume a
constant cosmic-ray ionization rate in the clouds. We investigate the effect of
cosmic-ray attenuation on the emission of carbon cycle species from molecular
clouds, in particular the [CII] 158 $\mu$m, [CI] 609 $\mu$m and CO (J = 1 - 0)
115.27 GHz lines. We use a post-processed chemical model of diffuse and dense
simulated molecular clouds and quantify the variation in both column densities
and velocity integrated line emission of the carbon cycle with different
cosmic-ray ionization rate models. We find that the abundances and column
densities of carbon cycle species is significantly impacted by the chosen
cosmic-ray ionization rate model: no single constant ionization rate can
reproduce the abundances modelled with an attenuated cosmic-ray model. Further,
we show that constant ionization rate models fail to simultaneously reproduce
the integrated emission of the lines we consider, and their deviations from a
physically derived cosmic-ray attenuation model is too complex to be simply
corrected. We demonstrate that the two clouds we model exhibit a similar
average $A_{\rm V, eff}$ -- $n_{\rm H}$ relationship, resulting in an average
relation between the cosmic-ray ionization rate and density $\zeta(n_{\rm H})$.
We conclude by providing a number of implementation recommendations for CRs in
astrochemical models, but emphasize the necessity for column-dependent
cosmic-ray ionization rate prescriptions.
;Comment: Accepted to A&A. Major results in Figures 4, 6, 10, 13
International audience;
Carbon capture and utilization represents a promising strategy to meet the global energy and climate goals. Under specific conditions, CO2 catalytic hydrogenation with renewable H2 can transform waste CO2 into a chemical feedstock for added-value energy carriers and chemicals. CO2-Fischer–Tropsch synthesis-based-hydrocarbons should contribute to the creation of a circular carbon economy with a significant impact on anthropogenic emission into the atmosphere. This review summarizes the progress achieved toward the single-step hydrogenation of CO2 to long-chain hydrocarbons over oxide-supported Co-based catalysts. Mechanistic aspects are discussed in relation to thermodynamic and kinetic limitations. The main parameters that must be taken into consideration to increase the activity and the selectivity toward compounds of two or more carbon atoms (C2+) are discussed in detail: cobalt active phase, support and metal-support interfaces, and promoters. Finally, particular focus is dedicated to the role of reducible oxide supports and their surface defects on the activation of CO2, as well as on the regulation and evolution of metal-support interactions.
Nanoporous carbons are key materials in many electrochemical applications over a wide variety of competitors (such as noble metals, non-noble metals or metal oxides) due to the diversity of materials with controlled pore architectures combined with adequate bulk and surface properties; particularly, chemical and mechanical stability, biocompatibility, rich surface chemistry and, most importantly, relatively high electronic conductivity.Although some carbons (e.g., graphite, graphene, carbon nanotubes) present electronic properties close to those of metallic electrodes, this feature depends strongly on the spatial arrangement of the carbon atoms. Indeed, most nanoporous carbons are non-polycrystalline materials with a low degree of structural order, as a result of a high density of defects introduced in the twisted graphitic layers upon the development of a nanopore network. As a result, the electron mobility pathway characteristic of the graphenic sheets is greatly reduced, limiting the conductivity of nanoporous carbons (typically 4 5 orders of magnitude lower than graphite). Thus, efforts are yet needed to prepare nanoporous carbons with high and well defined pore architectures combining high electrical conductivity without compromising the porous structure.To increase the conductivity of nanoporous carbon electrodes without compromising the porosity, several strategies have been explored such as: i) doping the carbon material with heteroatoms; ii) coating with a conductive phase such as metallic nanoparticles, metals, other conductive carbon nanostructures; iii) synthesising 3D nanoporous graphene-like architectures, and iv) incorporating a conductive additive in the formulation of carbon electrodes inks. The latter is the common practice for the manufacturing of the electrodes at commercial scale in most electrochemical applications, being carbon black the most popular conductive additive. Based on the previous studies carried out in the group, the objective of this PhD thesis consisted in exploring various synthetic approaches to obtain nanoporous carbons with high porous networks and enhanced conductivity upon incorporating various carbon nanostructures as conductive additives. In a first approach, the additive was incorporated during the synthesis of the nanoporous carbon material itself, rather than as percolator in the ink formulation typically applied for the preparation of electrodes (e.g., carbon material, binder and percolator). In a second approach, 3D nanoporous graphene-like architectures were obtained by hydrothermal approaches. Nanostructured carbon materials were selected to be employed as additives or as starting materials for the synthesis of nanoporous structures. They were chosen upon their composition, morphology and structural features: carbon black (commercial), graphite (commercial), graphene, graphene oxide and reduced graphene oxide (commercial). In this sense, the optimization and analysis of the experimental conditions to synthesise graphene by microwave plasma was carried out. A TIAGO torch microwave discharge at atmospheric pressure was employed allowing the synthesis of graphene by the decomposition of ethanol. The ethanol flow was varied (from 2.00 to 4.00 g/h) showing differences on the gaseous by products generated during the synthesis, under lower gas flow (from 2.00 to 3.4 g/h) the main gases detected were C2H2, CO and C (s), while for higher gas flows (ca. 4.00 g/h) other gases are generated as CH4 and C2H4 reducing the formation of C (s). Consequently, variations in the graphene production rate were observed being the maximum production 1.55 mg/min for ethanol flow of 3.4 g/h. Despite these differences, the features of the graphene material were slightly influenced by the employed ethanol flow. Graphene oxide was also synthesised applying a modified Hummers method to graphite. This method allowed the exfoliation of the graphite and increased its hydrophilic character by the incorporation of O-containing groups (oxygen content ca. 40 %). After the synthesis and characterisation of the nanostructured materials, the first approach of the thesis was developed carrying out the synthesis of the nanoporous carbons by a modification of the polycondensation of resorcinol and formaldehyde mixtures well reported in the literature for the preparation of carbon gels. This approach allows obtaining highly porous materials with tuneable properties compared to conventional activation methods (e.g., physical and chemical activation of a carbon precursor) that usually render materials with broad pore size distributions in both the micropore and the mesopore range. The well controlled pore architectures of carbon gels makes this kind of materials excellent ones for electrochemical purposes. To overcome the drawback of their low electrical conductivity, various carbon nanostructures were incorporated. The protocol for the synthesis of carbon gels was adjusted to allow a homogeneous dispersion of the additive in the carbon/additive composites. Furthermore, the effect of various parameters such as the type, amount; hydrophobic/hydrophilic character and composition of the additive was explored. The study revealed the important role of the nature of the additive not only on the conductivity of the carbon gel/additive composite, but also on the development of the porosity during the synthesis. Carbon additives of hydrophobic nature act as a porogen, favouring the development of multimodal pore architectures, with predominance of large mesopores. Hydrophilic additives hinder the polycondensation reaction, rendering materials with lower porosity. Regarding the conductivity, the composites showed enhanced values, with percolation thresholds of ca. 8 wt.% for carbon black. Comparatively, higher conductivities were obtained for the use of graphene oxide at 12 wt.% (ca. 0.48 S/cm) and carbon black at 24 and 40 wt.% (ca. 0.22 and 0.28 S/cm, respectively). Overall, the results show the preparation of highly porous carbons with controlled mesopore architectures and enhanced conductivity. This facilitates the preparation of conductive carbon electrodes (either in monolithic and powder form), which are materials of interest for multiple processes (e.g., energy storage, supercapacitors, electrochemical sensors).On the second approach, carbon black, graphene oxide and reduced graphene oxide were selected to be used for hydrothermal synthesis (moderate pressure, ca. 200 bar) of 3D structures. Firstly, aqueous suspensions of the three materials were treated ad 150 °C in an autoclave for 12 h. This hydrothermal treatment revealed an increase in the porosity for the graphite oxide and reduced graphite oxide; however, the carbon black was not affected by the hydrothermal treatment. These variations of the material’s behaviour are related with the different nature of the materials. The expansion of the graphene oxide and reduced graphene oxide structures, as well as the partial reduction of the graphene layers allowed the increase of the electrical properties and suggest the possibility of the introduction of linkers between layers to stabilize the porous structure. When the sol-gel synthesis was carried out under hydrothermal conditions, important differences were observed on the porosity of the pristine gels (without additive), mainly in the mesopores range. On the other hand, the synthesis of gel/additive composites under hydrothermal conditions revealed the formation of two phases monoliths due to the sedimentation of the additive. Further research in this topic is carried out in the research group with the aim to improve the synthesis of nanoporous materials with enhanced conductivity by various approaches. These include photo-assisted protocols to accelerate the cross-linking of the sol-gel reactants in ca. 30-60 minutes (thereby preventing sedimentation), and self-assembly of graphene oxide and organic linkers in pillared structures.
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Il existe aujourd'hui un grand nombre de matériaux à base de carbone qui suscitent un énorme intérêt grâce à la combinaison de propriétés physiques et chimique uniques, leur permettant d’être utilisés dans un grand nombre de technologies telles que la catalyse, l'adsorption, le traitement des eaux usées, le stockage de l'énergie, etc. Ces applications sont principalement la conséquence de la chimie de coordination unique des atomes de carbone et leur réactivité chimique, qui permettent l’incorporation à la surface d’une grande variété d’hétéroatomes. Parmi eux, les matériaux carbonés poreux (ou nanoporeux) sont très utilisés dans de nombreuses applications électrochimiques dans les domaines des capteurs et du stockage et conversion d’énergie. Ce choix matériaux à base de carbone se porte sur leur compétitivité par rapport à leurs concurrents -les métaux ou les oxydes métalliques-, grâce à une très grande diversité des matériaux avec des réseaux de pores contrôlées combinées à des propriétés de volume et de surface adéquates ; en particulier, la stabilité chimique et mécanique, la biocompatibilité, la richesse de la chimie de surface. Néanmoins, les propriétés des matériaux carbonés à très haute porosité ne sont pas nécessairement optimales pour des applications électrochimiques, due à une conductivité électronique relativement faible. De manière générale, la cette caractéristique dépend fortement de la disposition spatiale des atomes de carbone (et notamment du procédé de fabrication et du traitement thermique), leur structure, composition, et porosité. L'Union Internationale de Chimie Pure et Appliquée (an anglais IUPAC) définit les matériaux poreux comme des matrices solides composées d'un réseau interconnecté de pores (vides) remplis d'un fluide (liquide ou gaz). Les matériaux carbonés peuvent être considérés comme des atomes de carbone regroupés en cycles aromatiques. De ce fait, ils ont une forte teneur en atomes de carbone hybridés sp2 qui confèrent un ordre bidimensionnel dans les couche carbonées similaire à celles du graphène. Ces couches de carbone sont plus ou moins planes en fonctions de la présence de défauts de bordure dans les feuillets, du dégrée de graphitisation et de la présence des liaisons avec d’autres hétéroatomes (généralement à travers d’atomes de carbone hybridés sp3, avec rupture de la double liaison carbone-carbones de type sp2) pour former des groupes fonctionnels de surface stables. Les couches de graphène sont connectées par des interactions de type Van der Waals soit dans une structure ordonnée (comme dans du graphite ou graphène) ou soit dans un empilement désorganisé des couches (structure turbostratique) comme dans la plupart des matériaux poreux. Cette disposition des couches de graphène est responsable des propriétés physicochimiques des matériaux carbonés. Ainsi, la structure du squelette carboné dans les carbones poreux peut être considérée comme une phase carbonée non organisée composée de formes aromatiques-aliphatiques complexes et de feuilles graphitiques tordues/déformées. Ces feuilles graphitiques (ou cristallites) sont orientées de manière aléatoire et interconnectées, avec des pores, des défauts de bordure et des interstices entre les cristallites, générant finalement des pores de dimensions nanométriques. De manière générale, les propriétés de matériaux carbonés -notamment leur texture poreuse et leur composition- dépendent des celles du matériau d’origine, mais aussi des conditions de synthèse, avec une grande variabilité des propriétés obtenues pour des matériaux carbonés produits à partir du même type de précurseur initiale. Les pores des matériaux à base de carbone sont généralement dispersés sur un large éventail de formes et de tailles. En fonction de leur taille, les pores peuvent se classer en micropores (largeur de pore inférieure à 2 nm), mésopores (largeur entre 2 et 50 nm) et macropores (largeur de pore supérieure à 50 nm). Concernant les propriétés électroniques, certains matériaux carbonés comme le graphite, le graphène, les nanotubes de carbone) présentent des propriétés électroniques proches de celles des électrodes métalliques. Par contre, la plupart des matériaux carbonés nanoporeux présentent une conductivité très limité généralement de 4 à 5 ordres de grandeur inférieurs à ceux du graphite), en raison de son faible degré d'ordre structurel et d'une forte densité de défauts de bordure introduits dans les couches graphitiques tordues lors du développement du réseau de nanopores. En conséquence, la voie de mobilité des électrons caractéristique des feuilles de graphite est fortement réduite. Des efforts sont donc encore nécessaires pour préparer des carbones nanoporeux avec des architectures de pores élevés et bien définis combinant une conductivité électrique élevée sans compromettre la structure poreuse.Pour augmenter la conductivité des électrodes en carbone nanoporeux sans compromettre la porosité, plusieurs stratégies ont été explorées, telles que: i) le dopage du matériau en carbone avec des hétéroatomes (tels que O, N, P ou B); ii) le revêtement avec une phase conductrice telle que des nanoparticules métalliques, des métaux, d'autres nanostructures de carbone conductrices; iii) la synthèse d'architectures 3D de type graphène nanoporeux, et iv) l'incorporation d'un additif conducteur dans la formulation des encres des électrodes en carbone. Ce dernier point est la pratique courante pour la fabrication des électrodes à l'échelle commerciale dans la plupart des applications électrochimiques, le noir de carbone étant l'additif conducteur le plus populaire.Sur la base des études précédentes menées dans le groupe, l'objectif de cette thèse de doctorat consistait à explorer diverses approches synthétiques pour obtenir des carbones nanoporeux à réseau poreux élevé et à conductivité accrue en incorporant diverses nanostructures de carbone comme additifs conducteurs. Une large gamme de nanostructures de carbone a été utilisée comme additifs conducteurs, notamment le noir de carbone, le graphène, le graphite, l'oxyde de graphène et l'oxyde de graphène réduit. Dans une première approche, l'additif a été incorporé lors de la synthèse du matériau de carbone nanoporeux lui même, plutôt que comme percolateur dans la formulation de l'encre généralement appliquée pour la préparation des électrodes (par exemple, matériau en carbone, liant et percolateur). Dans une deuxième approche, des architectures 3D de type graphène nanoporeux ont été obtenues par voie hydrothermale.Des matériaux nanostructurés à base de carbone ont été sélectionnés comme additifs ou comme matériaux de départ pour la synthèse des matériaux de carbone nanoporeux à conductivité amélioré. Ils ont été choisis en fonction de leur composition, de leur morphologie et de leurs caractéristiques structurelles: noir de carbone (commercial), graphite (commercial), graphène, oxyde de graphène et oxyde de graphène réduit (commercial). Dans ce sens, l'optimisation et l'analyse des conditions expérimentales pour la synthèse du graphène par plasma micro-ondes ont été réalisées. Comme on le trouve dans la littérature, les plasmas micro-ondes à pression atmosphérique ont montré leur capacité à synthétiser du graphène de haute qualité à partir de la décomposition de précurseurs organiques en l'absence de substrat. Généralement, un précurseur organique (gaz, phase liquide) est introduit dans un plasma micro-ondes à pression atmosphérique maintenu dans de l'argon en écoulement et contenu dans un réacteur. Un dépôt solide constitué de flocons de graphène se forme alors en aval et est collecté soit par un filtre, soit directement sur les parois du réacteur. Ce processus se déroule en une seule étape, sans nécessiter la séparation du produit d'un substrat ou d'un solvant. En outre, aucun produit chimique dangereux supplémentaire n'est nécessaire, ce qui rend le processus plus respectueux de l'environnement que le LPE et le rGO. L'éthanol était généralement utilisé comme précurseur ; bien que d'autres précurseurs (par exemple, le méthanol, l'éther diméthylique, l'isopropanol) aient été proposés comme alternative à l'éthanol pour alimenter une torche à plasma, seul l'éther diméthylique permet de produire du graphène, tandis que l'isopropanol ne produit que de la suie de carbone et que le méthanol ne produit aucun dépôt solide. L'un des principaux défis de cette technologie -en tant que technique ascendante- est d'augmenter le taux de production de graphène à des valeurs proches de celles des technologies descendantes.Une Torche à Injection Axiale sur Guide d'Ondes (TIAGO) à décharge micro-onde à pression atmosphérique a été utilisée, permettant la synthèse du graphène par décomposition de l'éthanol. Le débit d'éthanol a été varié (de 2.00 à 4.00 g/h), montrant des différences sur les sous-produits gazeux générés pendant la synthèse. Pour un débit de gaz plus faible (de 2.00 à 3.4 g/h), les principaux gaz détectés étaient le C2H2, le CO et le C(s), tandis que pour des débits de gaz plus élevés (environ 4.00 g/h), d'autres gaz sont générés comme le CH4 et le C2H4, réduisant la formation de C (s). En conséquence, des variations dans le taux de production du graphène ont été observées, la production maximale étant de 1.55 mg/min pour un débit d'éthanol de 3.4 g/h. Malgré ces différences, les caractéristiques du graphène ont été légèrement influencées par le flux d'éthanol utilisé.L'oxyde de graphène a également été synthétisé en appliquant une méthode Hummers modifiée. Cette méthode a permis l'exfoliation du graphite et a augmenté son caractère hydrophile par l'incorporation d'une variété de groupes d'oxygène à la surface ave une teneur en oxygène d'environ 40 %. La caractérisation par FTIR et l'analyse thermogravimétrique ont révélé la présence d'anhydrides carbonyles/groupes carboxyliques principalement.Après la synthèse et la caractérisation des additifs de carbone, la première approche de la thèse a été développée en réalisant la synthèse des carbones nanoporeux par une réaction de polycondensation de mélanges de résorcinol et de formaldéhyde bien connus dans la littérature pour la préparation de gels de carbone. Ce protocole de synthèse a présenté quelques défis lorsque la polymérisation a été effectuée en présence des additifs, en raison de la sédimentation des particules pendant la polycondensation. Afin d'obtenir une bonne distribution des additifs de carbone, et des gels polymères et des gels de carbone homogènes, l'approche synthétique a été modifiée en incorporant une agitation mécanique pour améliorer la dispersion de l'additif pendant la réaction de polycondensation.Cette approche permet d'obtenir des matériaux très poreux avec des propriétés accordables par rapport aux méthodes d'activation classiques (par exemple, activation physique et chimique d'un précurseur de carbone) qui rendent généralement des matériaux avec de larges distributions de taille de pores à la fois dans la gamme des micropores et des mésopores. Les architectures de pores bien contrôlées des gels de carbone font de ce type de matériaux d'excellents matériaux pour les applications électrochimiques. En outre, l'effet de divers paramètres tels que le type, la quantité, le caractère hydrophobe/hydrophile et la composition de l'additif ont été étudiés. L'étude a révélé le rôle important de la nature de l'additif non seulement sur la conductivité du composite gel de carbone/additif, mais aussi sur le développement de la porosité pendant la synthèse.Tout d'abord, quatre noirs de carbone ont été sélectionnés comme additifs conducteurs sur la base de leurs différences en termes de morphologie, de taille moyenne des agrégats de nanoparticules et d'ordre graphitique. Ces additifs de carbone ont été utilisés pour préparer un gel et des composites gel de carbone/CB, en incorporant une quantité discrète de chaque noir de carbone (12 % en poids, exprimé en grammes de CB par gramme de résorcine + formaldéhyde) au mélange RF. La caractérisation des composites de gels de carbone a permis de conclure que la nature du noir de carbone utilisé comme additif au gel et au gel de carbone, a une influence importante sur la dispersion de l'additif à travers la matrice polymère ; notamment en termes de taille des particules (30-100 nm), de porosité et de caractéristiques physico-chimiques. La présence d'agrégats de noir de carbone provoque la formation d'un chemin de percolation interconnecté, qui facilite la mobilité de l'électron en augmentant la conductivité électrique. Ainsi, en termes généraux, une taille de particule plus élevée du noir de carbone a produit la formation d'un chemin de percolation continu rendant les composites de gel de carbone avec une conductivité électrique plus élevée. En outre, l'incorporation du noir de carbone a eu un impact important sur le développement du réseau mésoporeux, indépendamment des propriétés morphologiques du noir de carbone incorporé.Pour réaliser l'étude sur l'influence de la quantité d'additif, l'un des noirs de carbone a été sélectionné en raison de son ordre structurel et de sa conductivité élevée. À cette fin, des rapports de masse de noir de carbone compris entre 4 et 40 % en poids (grammes de CB par gramme de réactifs) ont été utilisés. Au-delà de cette quantité, la dispersion du CB dans le mélange des réactifs devenait trop difficile. La variabilité de la quantité de noir de carbone comme additif a montré un impact notable sur les caractéristiques poreuses des composites de gel de carbone, principalement dans la gamme des mésoporeux. Les isothermes d'adsorption/désorption de N2 à -196 °C des échantillons ont montré un point d'inflexion dans les deux branches d'adsorption et de désorption, qui était plus marqué pour des quantités plus importantes de noir de carbone. La caractérisation des matériaux a révélé que l'incorporation du noir de carbone a provoqué le développement d'un réseau mésoporeux interconnecté de cous et de corps rétrécis. En plus, la conductivité électrique a également été influencée, montrant une augmentation de la quantité d'additif incorporée suivant une tendance de percolation.Dans le but d'étudier l'effet du caractère hydrophobe du noir de carbone utilisé comme additif, un des additifs de nature hydrophobe a été oxydé par la méthode Hummers afin d’incorporer des fonctionnalités d'oxygène. Le caractère hydrophobe/hydrophile de l'additif a donné lieu à un paramètre crucial pour les propriétés finales du matériau, tant en ce qui concerne le développement de la porosité que la conductivité électrique. L'incorporation de noir de carbone oxydé au mélange de réactifs a provoqué une brusque diminution du pH du milieu réactionnel ; malgré la bonne dispersion de l'additif du caractère hydrophile (en raison de son affinité avec le solvant de réaction) le composite obtenu ne présente pas un développement de porosité accessible à l’azote à -196 °C. Même si la présence de microporosité étroite (narrow microporosity) doit être confirmé par des mesures d’isothermes d’adsorption d’autres gaz (e.g., CO2 à 0 °C), ce résultant diffère des obtenus en absence de l’a additif et en présence du même additif de caractère hydrophobe. En ce qui concerne les valeurs de conductivité, une légère amélioration a été observée, par rapport à l'additif hydrophobe, principalement associée à la plus grande distribution de l'additif.D'autre part, graphite, oxyde de graphène et oxyde de graphène réduit ont été sélectionnés comme additifs en fonction de leurs différentes caractéristiques structurelles, morphologiques et chimiques. L'étude de ces trois additifs a révélé que le développement de la porosité des composites ne serait pas directement corrélé à la porosité de l'additif. Le réseau poreux du matériau final était principalement lié aux caractéristiques physico-chimiques de l'additif utilisé. Les groupes fonctionnels oxygénés de l'additif et sa capacité à modifier le pH du milieu du réactif sont devenus des paramètres critiques puisqu'ils détermineront le développement de la texture du composite final. De plus, l'ordre et l'agrégation des additifs ont montré un effet de la conductivité électrique des composites de gel de carbone.Enfin, l'un des graphènes synthétisés par plasma a aussi été sélectionné comme additif conducteur. Les composites de gel et de gel de carbone élaborés en incorporant 4 et 12 % en poids de graphène comme additif au mélange RF ont révélé des conductivités similaires des matériaux obtenus avec l'incorporation de noir de carbone, probablement associées à la présence d'agrégats de graphène formés pendant la synthèse du composite.En conclusion, les additifs de carbone de nature hydrophobe agissent comme un porogène, favorisant le développement d'architectures de pores multimodales, avec une prédominance des grands mésopores. Les additifs hydrophiles entravent la réaction de polycondensation, rendant les matériaux moins poreux. En ce qui concerne la conductivité, les composites ont montré des valeurs améliorées, avec des seuils de percolation d'environ 8 % en poids pour le noir de carbone. En comparaison, des conductivités plus élevées ont été obtenues pour l'utilisation de l’oxyde de graphène à 12 % en poids (ca. 0.48 S/cm) et du noir de carbone à 24 et 40 % en poids (ca. 0.22 et 0.28 S/cm, respectivement). Dans l'ensemble, les résultats montrent la préparation de carbones très poreux avec des architectures de mésopores contrôlées et une conductivité accrue. Cela facilite la préparation d'électrodes de carbone conductrices (soit sous forme monolithique, soit sous forme de poudre), qui sont des matériaux intéressants pour de multiples processus (par exemple, le stockage d'énergie, les supercondensateurs, les capteurs électrochimiques).Pour confirmer l'impact bénéfique de l'incorporation des additifs au carbone sur la conductivité électrique des composites de gel de carbone, la caractérisation électrochimique des échantillons a été lancée. Elle n'a pas été incluse dans le noyau du doctorat car les travaux expérimentaux n'ont pas été finalisés pour tous les matériaux préparés. Les électrodes des composites ont été préparées et caractérisées par voltampérométrie cyclique en utilisant une configuration de cellule à 3 électrodes.Dans la seconde approche, le noir de carbone, l'oxyde de graphène et l'oxyde de graphène réduit ont été sélectionnés pour être utilisés pour évaluer l’impact de la synthèse hydrothermale dans leur porosité. Dans un premier temps, les suspensions aqueuses des trois matériaux ont été traitées à 150 °C dans un autoclave pendant 12 heures. Ce traitement hydrothermal a révélé une augmentation de la porosité de l'oxyde de graphite et de l'oxyde de graphite réduit, mais le noir de carbone n'a pas été affecté par le traitement hydrothermal. Ces variations du comportement du matériau sont liées à la nature différente des matériaux. L'expansion de la structure de l'oxyde de graphène et de l'oxyde de graphène réduit, ainsi que la réduction partielle des couches de graphène ont permis l'augmentation des ces propriétés texturales et suggèrent la possibilité d'introduire des agents de liaison entre les couches pour stabiliser la structure poreuse.Lorsque la synthèse sol-gel a été réalisée dans des conditions hydrothermales, des différences importantes ont été observées sur la porosité des gels vierges (sans additif), principalement dans le domaine des mésopores. D'autre part, la synthèse des composites gel/additif dans des conditions hydrothermales a révélé la formation de monolithes à deux phases due à la sédimentation de l'additif. Sur la base des résultats obtenus, il semble que d’autres études doivent être menées pour améliorer la dispersion des additifs de carbone dans les procèdes longs, afin d'éviter la sédimentation et l’obtention de matériaux hétérogènes.
Reducing Carbon dioxide (CO2) emission is vital at both global and national
levels, given their significant role in exacerbating climate change. CO2
emission, stemming from a variety of industrial and economic activities, are
major contributors to the greenhouse effect and global warming, posing
substantial obstacles in addressing climate issues. It's imperative to forecast
CO2 emission trends and classify countries based on their emission patterns to
effectively mitigate worldwide carbon emission. This paper presents an in-depth
comparative study on the determinants of CO2 emission in twenty countries with
high Human Development Index (HDI), exploring factors related to economy,
environment, energy use, and renewable resources over a span of 25 years. The
study unfolds in two distinct phases: initially, statistical techniques such as
Ordinary Least Squares (OLS), fixed effects, and random effects models are
applied to pinpoint significant determinants of CO2 emission. Following this,
the study leverages supervised and unsupervised machine learning (ML) methods
to further scrutinize and understand the factors influencing CO2 emission.
Seasonal AutoRegressive Integrated Moving Average with eXogenous variables
(SARIMAX), a supervised ML model, is first used to predict emission trends from
historical data, offering practical insights for policy formulation.
Subsequently, Dynamic Time Warping (DTW), an unsupervised learning approach, is
used to group countries by similar emission patterns. The dual-phase approach
utilized in this study significantly improves the accuracy of CO2 emission
predictions while also providing a deeper insight into global emission trends.
By adopting this thorough analytical framework, nations can develop more
focused and effective carbon reduction policies, playing a vital role in the
global initiative to combat climate change.
International audience;
Changes in terrestrial carbon storage under environmental and land-use changes remain a critical source of uncertainty in regional and global carbon budgets. We generated global maps of annual live vegetation biomass using L-band microwave vegetation optical depth. Globally, biomass carbon stocks increased from 2010 to 2019 at a rate of 0.50 ± 0.20 PgC yr−1 with a year-to-year variability, closely mirroring the observations of the global atmospheric CO2 growth rate. The main contributors to the global carbon sink are boreal and temperate forests, while wet tropical forests are small carbon sources, from deforestation and agriculture-related disturbances. We found that the tropical deforested and degraded old-growth forests (>140 yr) are nearly carbon neutral whereas temperate and boreal young (< 50 yr) and middle-aged (50–140 yr) forests are the largest sinks. By contrast, dynamic global vegetation models show that all old-growth forests are large sinks and largely ignore the impacts of deforestation and degradation on tropical biomass. Our findings highlight the importance of forest demography when predicting dynamics of future carbon sink under changing climate.
International audience;
The development of new industrial applications in the pharmaceutical, food, and cosmetic f ields uses supercritical carbon dioxide as a solvent or antisolvent in their processes for extracting non-polar molecules. Ethanol (EtOH) is added in small quantities to isolate a polar molecule during a unit operation by solubilization or precipitation. Density measurements in pure carbon dioxide (CO<sub>2</sub>) and in binary CO<sub>2</sub>-EtOH mixtures with mass compositions (ω<sub>CO2</sub> = 0.99 and (ω<sub>CO2</sub> = 0.98) were carried out using a vibrating tube densimeter. The isotherms were determined at temperatures of 303, 308, and 313 K, above the critical temperature, and for a pressure range from 5 to 10 MPa. Fine modeling around the critical point was performed using cubic equations of state with two or three parameters (Peng-Robinson and Coquelet-El Abbadi-Houriez EoS). The Huron-Vidal mixing rule coupled with the NRTL model was employed. To enhance the prediction around the critical point of pure carbon dioxide and binary CO<sub>2</sub>-EtOH mixtures, White’s correction method was used. The results for pure supercritical carbon dioxide show modeling performance with a deviation of 5.8% around the critical point.
Climate change and anthropogenic environmental changes are impacting our planet on a global scale, leading to extreme weather events. However, anthropogenic greenhouse gas emissions are not decreasing. Agricultural surfaces, which make up more than 30% of continental land, play an important role in these emissions, since they are similar to the emissions from global air traffic. These highly anthropized surfaces, directly linked to the environment, are areas of interest for the impact of human activities. Farmland can act as a sink or source of carbon, depending on agricultural practices. The impact of agroecological practices (no-tillage, cover cropping, agroforestry, etc.), which are increasingly used in France, is still poorly understood, particularly with regard to combinations of practices. This thesis focuses on the impact of combined agroecological practices on soil carbon stocks and CO2 emissions to the atmosphere through soil respiration. We modeled soil respiration fluxes and adapted a set of equations to represent the dynamics of soil carbon stocks and fluxes, as well as the priming effect for agroecological (no-till combined with cover cropping) and conventional practices. The first part of the thesis consisted in carrying out a set of spatialized field measurements on maize plots. The two study sites are characterized by very contrasting amounts of carbon: a soil very rich in carbon in 2018 in Lalonquette (64) and another relatively poor in 2019 in Estampes (32). Each study site is composed of two contiguous plots, one under an agroecological itinerary, for 16 years in Lalonquette and 19 years in Estampes (no-till, intermediate cover), the other under a conventional itinerary (tillage, bare soil period). Measurements were carried out on each plot during the season to characterize the soil respiration. In Estampes, the soil of the agroecological plot contains more carbon and show greater soil respiration than the conventional plot. Thus, agroecological practices can increase soil carbon stocks while increasing respiration to the atmosphere. At the Lalonquette site, both plots have higher carbon stocks and lower respiration than at Estampes, but are similar between agroecological and conventional management. The combination of agroecological practices did not have the same effect on the two sites. The positive impact of the combined agroecological practices on soil carbon storage seems to be limited by the soil's capacity to accumulate carbon. Finally, to understand the spatial heterogeneity of respiration fluxes, a principal component analysis completed by a machine learning method in a decision tree forest (or random forest) was performed. The heterogeneity of soil respiration is mainly due to temperature variations for the AE plot and temperature and humidity for the Conv plot, confirming the conclusions of the global data analysis. In a second part, we simulated soil carbon fluxes and stocks for both agroecological and conventional cropping modalities. The SAFYE-CO2 model developed at CESBIO is able to simulate carbon fluxes from the plot scale to the regional scale. A new module, COP for "CO2 flux and Priming effect estimation", has been developed for SAFYE-CO2 model. This module allows to take into account soil carbon stocks, heterotrophic respiration and the estimation of the priming effect from a formalism adapted from the ORCHIDEE-PRIM model. This module allows better quality simulations of soil heterotrophic respiration fluxes by completing the representation of carbon cycle components already taken into account by SAFYE-CO2.
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Le changement climatique et les modifications de l'environnement d'origine anthropique impactent notre planète à l'échelle mondiale, conduisant notamment à des perturbations climatiques extrêmes. Pourtant, les émissions de gaz à effet de serre d'origine anthropiques ne décroissent pas. Les surfaces agricoles, constituants plus de 30% des terres continentales, jouent un rôle important dans ces émissions puisqu'elles sont similaires aux rejets du trafic aérien mondial. Ces surfaces fortement anthropisés et en lien direct avec l'environnement sont des zones d'intérêt de l'impact des activités humaines. Les terres cultivables peuvent se comporter comme des puits ou des sources de carbone, notamment en fonction de la conduite agricole. L'impact des pratiques issues de l'agroécologie (non-labour, couvert intermédiaire, agroforesteries, etc.), de plus en plus utilisées en France, reste cependant mal compris notamment concernant les combinaisons de pratiques. Cette thèse s'intéresse à l'impact de pratiques agroécologiques combinées sur les stocks de carbone du sol et les émissions vers l'atmosphère de CO2 à travers la respiration du sol. Nous avons modélisé les flux de respiration du sol et adapté un ensemble d'équations permettant de représenter la dynamique des stocks et flux de carbone du sol, ainsi que l'effet priming pour des pratiques agroécologiques (non-labour combiné au couvert intermédiaire) et conventionnelles. La première partie de la thèse a consisté à réaliser un ensemble de mesures spatialisées de terrain sur des parcelles de maïs. Les deux sites étudiés sont caractérisés par des quantités de carbone très contrastées : un sol très riche en carbone en 2018 à Lalonquette (64) et un autre relativement pauvre en 2019 à Estampes (32). Chaque site d'étude est composé de deux parcelles contiguës, l'une sous itinéraire agroécologique, depuis 16 ans à Lalonquette et 19 ans à Estampes (non-labour, couvert intermédiaire), l'autre sous itinéraire conventionnel (labour, période de sol nu). Les mesures ont été réalisées sur chaque parcelle au cours de la saison permettant de caractériser la respiration du sol. A Estampes, le sol de la parcelle agroécologique contient plus de carbone et respire plus que la parcelle conventionnelle. Ainsi, les pratiques agroécologiques peuvent augmenter les stocks de carbone du sol tout en augmentant la respiration vers l'atmosphère. Sur le site de Lalonquette, les deux parcelles présentent des stocks de carbone plus important et des respirations plus faibles qu'à Estampes, mais sont similaires entre les conduites agroécologiques et conventionnelles. La combinaison de pratiques agroécologiques n'a donc pas eu le même effet sur les deux sites. L'impact positif des pratiques agroécologiques combinées sur le stockage de carbone du sol semble limité par la capacité du sol à accumuler ce carbone. Enfin, pour comprendre l'hétérogénéité spatiale des flux de respiration, une analyse de composante principale complété par une méthode d'apprentissage automatique (ou machine learning) en forêt d'arbres décisionnels (ou random forest) a été réalisée. L'hétérogénéité de la respiration du sol est principalement due aux variations de température pour la parcelle AE et température et humidité pour la parcelle Conv, confirmant les conclusions de l'analyse globale des données. Dans une deuxième partie, nous avons simulé les flux et stocks de carbone du sol pour les deux modalités de cultures agroécologie et conventionnel. Le modèle SAFYE-CO2 développé au CESBIO est capable de simuler les flux de carbone de l'échelle de la parcelle jusqu'à l'échelle régionale. Un nouveau module, COP pour " CO2 flux and Priming effect estimation ", a été développé pour le modèle SAFYE-CO2. Ce module permet de prendre en compte les stocks de carbone du sol, la respiration hétérotrophe ainsi que l'estimation de l'effet priming à partir d'un formalisme adapté du modèle ORCHIDEE-PRIM.
Subsoils contain more than half of soil organic carbon (SOC) and are expected to experience rapid warming in the coming decades. Yet our understanding of the stability of this vast carbon pool under global warming is uncertain. In particular, the fate of complex molecular structures (polymers) remains debated. Here we show that 4.5 years of whole-soil warming (+4 °C) resulted in less polymeric SOC (sum of specific polymers contributing to SOC) in the warmed subsoil (20–90 cm) relative to control, with no detectable change in topsoil. Warming stimulated the subsoil loss of lignin phenols (−17 ± 0%) derived from woody plant biomass, hydrolysable lipids cutin and suberin, derived from leaf and woody plant biomass (−28 ± 3%), and pyrogenic carbon (−37 ± 8%) produced during incomplete combustion. Given that these compounds have been proposed for long-term carbon sequestration, it is notable that they were rapidly lost in warmed soils. We conclude that complex polymeric carbon in subsoil is vulnerable to decomposition and propose that molecular structure alone may not protect compounds from degradation under future warming.
International audience;
Alkali-rich silicate melts and carbonatitic magmas are key to understanding deep carbon cycling, as they may originate from some of Earth's most carbon-rich mantle reservoirs. Determining whether the high carbon contents of these magmas result from low-degree partial melting of depleted or primitive mantle sources or instead require an enriched mantle source metasomatized by recycled, carbon-rich crustal fluids, is critical to elucidating the geodynamic processes that govern deep carbon transport. Carbon isotopes in magmatic and mantle products provide a valuable tool for this purpose. Oldoinyo Lengai (OL) in Tanzania, the only active carbonatitic volcano, has lacked direct carbon isotopic data from fluid inclusions (FIs), which can reveal deep magmatic processes. Here, we present new δ13C measurements of CO2 in FIs hosted in OL cumulates and mantle xenoliths. Barometry of secondary FIs in lherzolites indicates entrapment at 510–687 MPa (~19–25 km), suggesting deep fluid trapping or reequilibration during magma ascent or storage. Mantle xenoliths show maximum δ13C ≈ −2.7 ‰ (V-PDB), heavier than typical upper mantle values (−4 ‰ to −8 ‰) and comparable to OL fumarole gases. Shallower FIs (22–251 MPa) exhibit lighter δ13C (−5.0 ‰ to −3.7 ‰). Combined with pressure-dependent 4He/40Ar* and CO2/3He ratios, these data support isotopic fractionation during decompression-driven degassing. An open-system degassing model reconstructs the parental melilititic/Mg-nephelinitic magma's δ13C at −0.9 ‰, indicating a mantle source metasomatized by crustal carbon. The model also explains OL carbonatites' lighter δ13C (−6.3 ‰ to −7.8 ‰) as a product of late-stage degassing and shallow crustal liquid immiscibility at 10–12 km depth. Our results shed light on OL's magmatic evolution and deep carbon cycling in sub-continental mantle.
American Chemical Societyoktober 2023Klimaatwetenschap
[Image: see text] Wastewater treatment is notorious for its hefty carbon footprint, accounting for 1–2% of global greenhouse gas (GHG) emissions. Nonetheless, the treatment process itself could also present an innovative carbon dioxide removal (CDR) approach. Here, the calcium (Ca)-rich effluent of a phosphorus (P) recovery system from municipal wastewater (P recovered as calcium phosphate) was used for CDR. The effluent was bubbled with concentrated CO(2), leading to its mineralization, i.e., CO(2) stored as stable carbonate minerals. The chemical and microstructural properties of the newly formed minerals were ascertained by using state-of-the-art analytical techniques. FTIR identified CO(3) bonds and carbonate stretching, XRF and SEM-EDX measured a high Ca concentration, and SEM imaging showed that Ca is well distributed, suggesting homogeneous formation. Furthermore, FIB-SEM revealed rhombohedral and needle-like structures and TEM revealed rod-like structures, indicating that calcium carbonate (CaCO(3)) was formed, while XRD suggested that this material mainly comprises aragonite and calcite. Results imply that high-quality CaCO(3) was synthesized, which could be stored or valorized, while if atmospheric air is used for bubbling, a partial direct air capture (DAC) system could be achieved. The quality of the bubbled effluent was also improved, thus creating water reclamation and circular economy opportunities. Results are indicative of other alkaline Ca-rich wastewaters such as effluents or leachates from legacy iron and steel wastes (steel slags) that can possibly be used for CDR. Overall, it was identified that wastewater can be used for carbon mineralization and can greatly reduce the carbon footprint of the treatment process, thus establishing sustainable paradigms for the introduction of CDR in this sector.
John Wiley and Sons Inc.november 2023Klimaatwetenschap
Microbial metabolism offers a wide variety of opportunities to produce chemicals from renewable resources. Employing such processes of industrial biotechnology provides valuable means to fight climate change by replacing fossil feedstocks by renewable substrate to reduce or even revert carbon emission. Several yeast species are well suited chassis organisms for this purpose, illustrated by the fact that the still largest microbial production of a chemical, namely bioethanol is based on yeast. Although production of ethanol and some other chemicals is highly efficient, this is not the case for many desired bulk chemicals. One reason for low efficiency is carbon loss, which decreases the product yield and increases the share of total production costs that is taken by substrate costs. Here we discuss the causes for carbon loss in metabolic processes, approaches to avoid carbon loss, as well as opportunities to incorporate carbon from CO(2), based on the electron balance of pathways. These aspects of carbon efficiency are illustrated for the production of succinic acid from a diversity of substrates using different pathways.
Anthropogenic greenhouse gases (GHGs) emissions are causing irreversible climate change. To address this issue, the European Union (EU) committed to strong decreases in GHGs emissions. However, to reach carbon (C) neutrality by 2050 it will also be necessary to implement atmospheric C removals by natural sinks, such as soils. To partially compensate for CO2 emissions, the 4 per 1000 initiative of 2015 proposed an annual 4‰ soil organic carbon (SOC) stock increase in the first 30-40 cm depth of the soil. Yet, the feasibility of such an ambitious target is still under debate because it may require substantial and rapid changes in agricultural practices that would be hard to achieve. The most efficient way to increase SOC stocks is to increase the C input to the soil. Pro-cess-based biogeochemical models can simulate the dynamics of SOC and are increasingly used to support decision-makers on SOC mitigation policies. Despite the numerous models available to describe the SOC dynamics, simulations are still somewhat unreliable. This is because uncertainties not only derive from the mechanistic structure of the models and the processes included, but also from the input data and the parameter values used.The objective of this thesis is to estimate the C input required to yearly increase SOC stocks by 4‰ in European croplands. To solve this problem, we build an inverse modeling approach and apply it to a multi-model ensemble to assess the uncertainties of the estimations according to different representations of the SOC dynamics. Then, to improve the simulation of SOC stocks, we test a new, statistically derived, parametrization technique.As a first attempt to provide insights for policymakers, we generate maps of the C input required to reach the 4‰ target in the whole European cropland area, under two scenarios of climate change. Our study demonstrates that there are substantial uncertainties around the C input required to reach a 4‰ target. However, a general pattern emerges at the European cropland scale, where the 4‰ target seems feasible under future scenarios of climate change, only assuming drastic increases of C input to the soil. In particular, higher C input is required in Northern Europe, while higher uncertainties are associated with the European South. The high variability of the simulated C input requirements highlights the advantage of using multi-model ensembles, in order to consider the range of uncertainty linked to their different mechanistic structures. Yet, multi-model ensembles still tend to underestimate the C input required to increase SOC stocks. Major efforts should be made to improve model simulations, especially to capture the effect of additional C input on the accumulation of SOC. At a local scale, the calibration of model parameters was necessary to fit observed SOC stock variations. When long-term SOC stock monitoring is not available, the necessity for improved parametrization techniques emerges. The calibration that we proposed at the European scale improved the simulation of first-year SOC stocks. However, it increased the divergence of predicted SOC stocks across models. Future work should focus on the reduction of model uncertainties in order to provide reliable predictions of future SOC stock variations and their related processes.
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Les émissions anthropiques de gaz à effet de serre (GES) provoquent un changement climatique irréversible. L'Union Européenne (UE) s'est engagée à diminuer fortement ses émissions de GES. Cependant, pour atteindre la neutralité carbone (C) d'ici 2050, elle devra également séquestrer du C atmosphérique dans des puits naturels, tels que les sols. Pour compenser partiellement les émissions de CO2, l'initiative 4 pour 1000 a proposé en 2015 un objectif d'augmentation annuelle de 4‰ des stocks de carbone organique du sol (COS) dans les 30-40 premiers cm de profondeur du sol. Pourtant, la faisabilité d'une telle augmentation fait l'objet de débats car elle pourrait nécessiter des changements substantiels et rapides dans les pratiques agricoles qui seraient difficiles à mettre en œuvre. Le moyen le plus efficace pour accroître les stocks de COS est d'augmenter l'apport de C dans le sol. Les modèles basés sur les processus biogéochimiques peuvent simuler la dynamique du COS et sont de plus en plus utilisés pour aider les décideurs dans leurs politiques d'atténuation du COS. Cependant, malgré les nombreux modèles disponibles pour décrire la dynamique du COS, les simulations sont encore peu fiables. En effet, les incertitudes ne proviennent pas seulement de la structure mécaniste des modèles et des processus qu’ils prennent en compte, mais aussi des données utilisées en entrée et des valeurs des paramètres.L'objectif de cette thèse est d'estimer l'apport de C nécessaire pour augmenter annuellement les stocks de COS de 4‰ dans les terres cultivées européennes. Pour cela, nous avons construit une modélisation inverse et l'avons appliquée à un ensemble multi-modèle. Nous avons ainsi évalué les incertitudes dans les estimations des entrées de C selon différentes représentations de la dynamique du COS. Ensuite, pour améliorer la simulation des stocks de COS, nous avons testé une nouvelle paramétrisation issue de dérivée statistiques.Afin de fournir un premier aperçu aux décideurs politiques, nous avons généré des cartes de l'apport de C nécessaire pour atteindre l'objectif de 4‰ dans l'ensemble des terres cultivées européennes, et ce, pour deux scénarios de changement climatique.Notre étude a démontré qu'il existe des incertitudes substantielles autour de l'apport de C nécessaire. Cependant, un profil général émerge, où atteindre un objectif d'augmentation de 4‰ du stock de COS à l'échelle des terres cultivées européennes semble réalisable pour les scénarios futurs de changement climatique seulement via des augmentations drastiques de d'apport de C. En particulier, un apport de C plus élevé est nécessaire en Europe du Nord, tandis qu’en Europe du Sud les incertitudes sont plus élevées. La grande variabilité dans les simulations d'apport de C nécessaires à l’objectif 4‰ souligne l'avantage d'utiliser des ensembles multi-modèles, afin de prendre en compte la gamme d'incertitudes liées à leurs différentes structures mécanistiques. Cependant, les ensembles multi-modèles ont encore tendance à sous-estimer l'apport de C nécessaire pour augmenter les stocks de COS. Des progrès importants doivent donc encore être faits pour améliorer les simulations des modèles, en particulier pour saisir l'effet d'un apport supplémentaire de C sur l'accumulation de COS. A l'échelle locale, la calibration des paramètres des modèles a été nécessaire pour simuler les variations observées des stocks de COS. Lorsque le suivi à long terme du stock de COS n'est pas disponible, il est nécessaire d'améliorer les techniques de paramétrisation. La calibration que nous avons proposée à l'échelle européenne a amélioré la simulation des stocks de COS de la première année mais a augmenté la divergence des stocks de COS prédits par les modèles. De futurs travaux se concentrant sur la réduction des incertitudes des modèles afin de fournir des prédictions fiables des variations futures des stocks de COS et des processus associés sont donc essentiels.
HAL CCSD;Springer Verlag/EDP Sciences/INRAjanuari 2022Klimaatwetenschap
International audience;
AbstractIn northwestern Ethiopia, a conventional teff (Eragrostis tef (Zucc.) Trotter) monoculture was converted into a rotational agroforestry system (teff-Acacia agroforestry), which consists of the sequence i) teff-Acacia decurrens intercropping (1st year), ii) grass-A. decurrens silvopasture (2nd year), iii) A. decurrens plantation (3rd–4th year), and iv) on-site charcoal production from A. decurrens (end of 4th year). This study is the first one to comprehensively show how the agroforestry system affects soil organic carbon (SOC) and soil nutrients. Soil samples were collected from the teff-Acacia agroforestry and conventional teff fields at two different sites (site I and II) and they were used to determine soil pH, black carbon, SOC, soil total nitrogen (STN), extractable phosphorus (P), potassium (K), magnesium (Mg), sodium (Na), and calcium (Ca) contents. At site I (0–10 cm soil depth), charcoal production spots in teff-Acacia agroforestry had higher soil pH (20%), black carbon (164%), SOC (48%), P (687%), and K (788%) contents compared to outside charcoal production spots. Soil organic carbon and STN contents in the 1st and 2nd teff-Acacia agroforestry rotations were significantly higher (SOC: 112–169%, STN: 100–131%) than teff fields. At site II, SOC stocks (0–100 cm) in the 1st agroforestry rotation were not significantly different from teff fields. However, they were 159% and 244% greater in the 2nd and 3rd agroforestry rotations, respectively, compared to teff fields. Conversion of teff fields to teff-Acacia agroforestry for a 12-year period increased SOC stocks by 21 Mg C ha–1 per year. Our results demonstrated that locally adopted agroforestry practices can increase SOC and nutrients in the long term, thereby contributing to enhanced soil fertility and improved climate change mitigation strategies via carbon sequestration.
International audience;
A methanol island, powered by solar or wind energy, indirectly captures atmospheric CO2 through the ocean and combines it with hydrogen gas to produce a synthetic fuel. The island components include a carbon dioxide extractor, a desalinator, an electrolyzer, and a carbon dioxide-hydrogen reactor to complete this process. In this study, the optimal locations to place such a device in the Mediterranean Sea were determined, based on three main constraints: power availability, environmental risk, and methanol production capability. The island was numerically simulated with a purpose built python package pyseafuel. Data from 20 years of ocean and atmospheric simulation data were used to “force” the simulated methanol island. The optimal locations were found to strongly depend on the power availability constraint, with most optimal locations providing the most solar and/or wind power, due to the limited effect the ocean surface variability had on the power requirements of methanol island. Within this context, optimal locations were found to be the Alboran, Cretan, and Levantine Sea due to the availability of insolation for the Alboran and Levantine Sea and availability of wind power for the Cretan Sea. These locations were also not co-located with areas with larger maximum significant wave heights, thereby avoiding areas with higher environmental risk. When we simulate the production at these locations, a 10 L s−1 seawater inflow rate produced 494.21, 495.84, and 484.70 mL m−2 of methanol over the course of a year, respectively. Island communities in these regions could benefit from the energy resource diversification and independence these systems could provide. However, the environmental impact of such systems is poorly understood and requires further investigation.
Tropical forests are threatened by anthropogenic activities such as conversion into agricultural land, logging and fires. Land-use change and disturbance affect ecosystems not only aboveground, but also belowground including the ecosystems' carbon and nitrogen cycle. We studied the impact of different types of land-use change (intensive and traditional agroforestry, logging) and disturbance by fire on fine root biomass, dynamics, morphology, and related C and N fluxes to the soil via fine root litter across different ecosystems at different elevational zones at Mt. Kilimanjaro (Tanzania). We found a decrease in fine root biomass (80–90%), production (50%), and C and N fluxes to the soil via fine root litter (60–80%) at all elevation zones. The traditional agroforestry 'Chagga homegardens' (lower montane zone) showed enhanced fine root turnover rates, higher values of acquisitive root morphological traits, but similar stand fine root production, C and N fluxes compared to the natural forest. The decrease of C and N fluxes with forest disturbance was particularly strong at the upper montane zone (60 and 80% decrease, respectively), where several patches of Podocarpus forest had been disturbed by fire in the previous years. We conclude that changes on species composition, stand structure and land management practices resulting from land-use change and disturbance have a strong impact on the fine root system, modifying fine root biomass, production and the C and N supply to the soil from fine root litter, which strongly affects the ecosystems' C and N cycle in those East African tropical forest ecosystems.
John Wiley and Sons Inc.december 2021Klimaatwetenschap
The global ocean has absorbed approximately 30% of anthropogenic CO(2) since the beginning of the industrial revolution. However, the spatiotemporal evolution of this important global carbon sink varies substantially on all timescales and has not yet been well evaluated. Here, based on a reconstructed observation‐based product of surface ocean pCO(2) and air–sea CO(2) flux (the MPI‐SOMFFN method), we investigated seasonal to decadal spatiotemporal variations of the ocean CO(2) sink during the past three decades using an adaptive data analysis method. Two predominant variations are modulated annual cycles and decadal fluctuations, which account for approximately 46% and 25% of all extracted components, respectively. Although the whole summer to non‐summer seasonal difference pattern is determined by the Southern Ocean, the non‐summer CO(2) sink at mid‐latitudes in both hemispheres shows an increasing trend (a total increase of approximately 1.0 PgC during the period 1982–2019), while it is relatively stable in summer. On decadal timescales for the global ocean carbon sink, unlike the weakening decade (1990–1999) and the reinvigoration decade (2000–2009) in which the Southern Ocean plays the dominant role, the reinforcement decade (2010–2019) is mainly the result from the weakening source effect in the equatorial Pacific Ocean. Our results suggest that except for the Southern Ocean's role in the global ocean carbon sink, the strengthening non‐summer's sink at mid‐latitudes in both hemispheres and the decadal or longer timescales of equatorial Pacific Ocean dynamics should be fully considered in understanding the oceanic carbon cycle on a global scale.
25 wetenschappelijke publicaties binnen het domein Antimicrobiële resistentie, voor snelle raadpleging van de bijbehorende wetenschappelijke literatuur.
SIMPLE SUMMARY: Women diagnosed with ovarian cancer have 5-year survival rates below 45%. Prediction of patient’s outcome and the onset of drug resistance are still major challenges. The patient’s drug response is influenced by the environment that surrounds the tumor cells. We previously showed that patient-derived tumor tissue can be kept in the lab, alive and retaining aspects of that environment. In this study, we exposed tumor tissue derived from ovarian cancer patients to the chemotherapy patients receive and identified metabolites released by the tumor tissue after treatment (metabolic footprint). Using machine learning, we uncovered metabolic signatures that discriminate tumor tissues with higher vs. lower drug sensitivity. We propose potential biomarkers involved in the production of specific building blocks of cells and energy generation processes. Overall, we established a platform to explore metabolic features of the complex environment of each patient’s tumor that can underpin the discovery of biomarkers of drug response. ABSTRACT: Predicting patient response to treatment and the onset of chemoresistance are still major challenges in oncology. Chemoresistance is deeply influenced by the complex cellular interactions occurring within the tumor microenvironment (TME), including metabolic crosstalk. We have previously shown that ex vivo tumor tissue cultures derived from ovarian carcinoma (OvC) resections retain the TME components for at least four weeks of culture and implemented assays for assessment of drug response. Here, we explored ex vivo patient-derived tumor tissue cultures to uncover metabolic signatures of chemosensitivity and/or resistance. Tissue cultures derived from nine OvC cases were challenged with carboplatin and paclitaxel, the standard-of-care chemotherapeutics, and the metabolic footprints were characterized by LC-MS. Partial least-squares discriminant analysis (PLS-DA) revealed metabolic signatures that discriminated high-responder from low-responder tissue cultures to ex vivo drug exposure. As a proof-of-concept, a set of potential metabolic biomarkers of drug response was identified based on the receiver operating characteristics (ROC) curve, comprising amino acids, fatty acids, pyrimidine, glutathione, and TCA cycle pathways. Overall, this work establishes an analytical and computational platform to explore metabolic features of the TME associated with response to treatment, which can leverage the discovery of biomarkers of drug response and resistance in OvC.
Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M^pro) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and vice versa .
SIMPLE SUMMARY: The prevention and control of mastitis, from a One Health perspective, should balance the risk of intramammary infections, impairing cow health and welfare, and the need of a reduction of antimicrobial usage (e.g., applying selective dry-cow therapy), thus decreasing antimicrobial resistance. This study showed that the application of an early diagnosis (5–16 days after calving) based on PLCC (neutrophils + lymphocyte count/mL) has good accuracy, a sustainable cost, and could potentially reduce the frequency of antimicrobial treatment compared with conventional diagnostic protocols based on SCC at the first milk test after calving. ABSTRACT: Mastitis is a major cause of antimicrobial treatments either during lactation or at drying off. From a One Health perspective, there should be a balance between the risk of IMI that may impair cow health and welfare and the reduction of antimicrobial usage to decrease antimicrobial resistance, as may happen when applying selective dry-cow therapy. This reduction may be achieved by an early and accurate diagnosis followed by prudent and rationale therapeutical protocols. This study aims to assess the accuracy of PLCC (neutrophils + lymphocyte count/mL) in identifying cows at risk of having IMI due to major pathogens (S.aureus, Str.agalactiae, Str.uberis, and Str.dysgalactiae), and to simulate the impact of this early diagnosis on the potential number of treatments using a decision-tree model. The results of this study showed that PLCC had an overall accuracy of 77.6%. The results of the decision-tree model based on data from the 12 participating herds, with an overall prevalence of major pathogens of 1.5%, showed a potential decrease in the number of treatments of about 30% (from 3.4% to 2.5%) when PLCC in early lactation (days 5–16) was used to identify cows at risk for major pathogens compared with using SCC at the first milk test (days 17–43). The study confirmed that it is possible to improve animal health and reduce the risk of antimicrobial use through early IMI detection based on PLCC and applying a rationale and prudent antimicrobial protocol.
Background In Japan, carbapenem-resistant Enterobacterales (CRE) infections were incorporated into the National Epidemiological Surveillance of Infectious Diseases (NESID) in 2014, necessitating mandatory reporting of all CRE infections cases. Subsequently, pathogen surveillance was initiated in 2017, which involved the collection and analysis of CRE isolates from reported cases to assess carbapenemase gene possession. In this surveillance, CRE is defined as (i) minimum inhibitory concentration (MIC) of meropenem ≥2 mg/L (MEPM criteria) or (ii) MIC of imipenem ≥2 mg/L and MIC of cefmetazole ≥64 mg/L (IPM criteria). This study examined whether the current definition of CRE surveillance captures cases with a clinical and public health burden. Methods CRE isolates from reported cases were collected from the public health laboratories of local governments, which are responsible for pathogen surveillance. Antimicrobial susceptibility tests were conducted on these isolates to assess compliance with the NESID CRE definition. The NESID data between April 2017 and March 2018 were obtained and analyzed using antimicrobial susceptibility test results. Results In total, 1681 CRE cases were identified during the study period, and pathogen surveillance data were available for 740 (44.0%) cases. Klebsiella aerogenes and Enterobacter cloacae complex were the dominant species, followed by Klebsiella pneumoniae and Escherichia coli . The rate of carbapenemase gene positivity was 26.5% (196/740), and 93.4% (183/196) of these isolates were of the IMP type. Meanwhile, 315 isolates were subjected to antimicrobial susceptibility testing. Among them, 169 (53.7%) fulfilled only the IPM criteria (IPM criteria-only group) which were susceptible to meropenem, while 146 (46.3%) fulfilled the MEPM criteria (MEPM criteria group). The IPM criteria-only group and MEPM criteria group significantly differed in terms of carbapenemase gene positivity (0% vs. 67.8%), multidrug resistance rates (1.2% vs. 65.8%), and mortality rates (1.8% vs 6.9%). Conclusion The identification of CRE cases based solely on imipenem resistance has had a limited impact on clinical management. Emphasizing resistance to meropenem is crucial in defining CRE, which pose both clinical and public health burden. This emphasis will enable the efficient allocation of limited health and public health resources and preservation of newly developed antimicrobials.
BACKGROUND: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. RESULTS: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. CONCLUSIONS: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-024-04877-0.
Background In this study, we aimed to demonstrate efficacy and laboratory follow-up criteria of nonsurgical antibiotic treatment in uncomplicated acute appendicitis. We established an experimental appendicitis model in rats, and antibiotic treatment was evaluated by biochemical and immunohistochemical changes. Materials and method In the study, 28 rats were divided into 4 groups. Group 1 constituted the group of sham; group 2 was the control group that appendicitis model was created and did not receive any treatment. Group 3 was created as an appendicitis model and was given regular antibiotic treatment. In group 4, appendicitis model was created, and appendectomy was performed on the 2nd day. Blood samples were taken from the rats on the 0, 2nd, and 7th days in all groups. Rats in groups 1, 2, and 3 underwent appendectomy with laparotomy under anesthesia on the 7th day. Serum C-reactive protein (CRP), procalcitonin, and leukocyte levels were measured for biochemical analysis. In immunohistochemical evaluation, inflammation severity of the tissue samples taken from appendices was evaluated. Also, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels of tissue samples were evaluated. Results A statistically significant difference in CRP values was observed between groups 1 and 2 on the 7th day ( p = 0.046), between groups 1 and 4 on 0 and 2nd days ( p = 0.004, p = 0.004), between groups 2 and 3 on 0, 2nd, and 7th days ( p = 0.018, 0.013, 0.025), between groups 2 and 4 on 0, 2nd, and 7th days ( p = 0.002, p = 0.002, p = 0.009), and between groups 3 and 4 on 0 and 2nd days ( p = 0.013, p = 0.025). There was a significant difference in procalcitonin values between groups 1 and 3 on the 7th day ( p = 0.032) and between groups 1 and 4 on day 0 ( p = 0.019). A significant difference was also observed in TNF-α and IL-6 inflammation between groups 2 and 3 ( p = 0.031, p = 0.018) and between groups 2 and 4 ( p = 0.031, p = 0.01). Conclusion Acute uncomplicated and early appendicitis may be treated with antibiotics. According to our results, CRP levels are useful as follow-up criterion in experimental appendicitis model. Clinical studies on the assessment of CRP levels in the course of nonsurgical treatment in the patients with acute appendicitis will reveal out the effectiveness of this marker.
American Chemical Societyaugustus 2022Antimicrobiële resistentie
[Image: see text] Bacterial pathogens especially antibiotic-resistant ones are a public health concern worldwide. To oppose the morbidity and mortality associated with them, it is critical to select an appropriate antibiotic by performing a rapid bacterial diagnosis. Using a combination of Raman spectroscopy and deep learning algorithms to identify bacteria is a rapid and reliable method. Nevertheless, due to the loss of information during training a model, some deep learning algorithms suffer from low accuracy. Herein, we modify the U-Net architecture to fit our purpose of classifying the one-dimensional Raman spectra. The proposed U-Net model provides highly accurate identification of the 30 isolates of bacteria and yeast, empiric treatment groups, and antimicrobial resistance, thanks to its capability to concatenate and copy important features from the encoder layers to the decoder layers, thereby decreasing the data loss. The accuracies of the model for the 30-isolate level, empiric treatment level, and antimicrobial resistance level tasks are 86.3, 97.84, and 95%, respectively. The proposed deep learning model has a high potential for not only bacterial identification but also for other diagnostic purposes in the biomedical field.
BACKGROUND: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). METHODS: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences. FINDINGS: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7–14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages. INTERPRETATION: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. FUNDING: This work was supported in part by awards from the 10.13039/100000030U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the 10.13039/100003085Longer Life Foundation (an RGA/Washington University partnership), the 10.13039/100006108National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the 10.13039/100000060National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the 10.13039/100000002National Institutes of Health (NIH); and to G.D. from 10.13039/100000060NIAID (grant R01AI123394) and the 10.13039/100009633Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of 10.13039/100000002NIH. R.T.’s research was funded by the 10.13039/501100001659Deutsche Forschungsgemeinschaft (DFG; 10.13039/501100001659German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Background The emergence of multidrug-resistant Acinetobacter baumannii strains is increasing worldwide. To overcome these life-threatening infections, the development of new treatment approaches is critical. For this purpose, this study was conducted to determine the antimicrobial photo-sonodynamic therapy (aPSDT) using hypericin nanoparticles (HypNP) in combination with D-Tryptophan (D-Trp) against A. baumannii . Materials and methods HypNP was synthesized and characterized, followed by the determination of the fractional inhibitory concentration (FIC) index of HypNP and D-Trp by checkerboard assay. Next, the antimicrobial and anti-biofilm potential of HypNP@D-Trp-mediated aPSDT against A. baumannii was evaluated. Finally, the anti-virulence activity of aPSDT using HypNP@D-Trp was accessed following the characterization of HypNP@D-Trp interaction with AbaI using in silico virtual screening and molecular docking. Results A synergistic activity in the combination of HypNP and D-Trp against A. baumannii was observed with a FIC index value of 0.5. There was a 5.10 log_10 CFU/mL reduction in the cell viability of A. baumannii when the bacterial cells were treated with 1/2 × MIC of HypNP@D-Trp and subsequently exposed to ultrasound waves and blue light ( P < 0.05). Moreover, a significant biofilm degradation effect on biofilm-associated cells of A. baumannii was observed after treatment with aPSDT using 2 × MIC of HypNP@D-Trp in comparison with the control groups ( P < 0.05). According to the molecular docking analysis of the protein-ligand complex, Hyp with a high affinity for AbaI showed a binding affinity of − 9.41 kcal/mol. Also, the expression level of abaI gene was significantly downregulated by 10.32-fold in A. baumannii treated with aPSDT as comprised with the control group ( P < 0.05). Conclusions It can be concluded that HypNP@D-Trp-mediated aPSDT can be considered a promising strategy to overcome the infections caused by A. baumannii by reducing the growth of bacterial biofilm and decreasing the expression of abaI as a gene involved in A. baumannii biofilm formation.
SIMPLE SUMMARY: P-glycoprotein (P-gp) is an ATP-binding cassette transporter whose overexpression in cancer cells is one of the main causes of multidrug resistance (MDR). Tyrosine kinase inhibitors (TKIs) have been reported to interact with ABC transporters and in some cases, increase the susceptibility of cancer cells to chemotherapy. We investigated the potential of novel TKI pyrazolo[3,4-d] pyrimidines and their prodrugs to inhibit P-gp in two MDR cancer cell lines with P-gp overexpression. The tested compounds were able to suppress P-gp by inhibiting its ATPase activity. Interestingly, prodrugs displayed a stronger potential to modulate P-gp and showed higher interaction energies in the docking simulations compared to their parent drugs. Furthermore, prodrugs showed significant potential to inhibit P-gp activity even in prolonged treatment and therefore to enhance the efficacy of doxorubicin and paclitaxel in MDR cancer cells. All of these characteristics imply that the new TKIs could be considered a valuable strategy for combating resistant cancers, especially in combination with other chemotherapeutics. ABSTRACT: Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P-glycoprotein (P-gp) is the most common alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4-d]pyrimidines on P-gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non-small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P-gp and inhibited its ATPase activity. Their potential P-gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration-dependent manner. The expression studies excluded the indirect effect of TKIs on P-gp through regulation of its expression. A kinetics study showed that TKIs decreased P-gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4-d]pyrimidines with potential for reversing P-gp-mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.
SIMPLE SUMMARY: Estrogen receptor α (ERα) is a key driver and clinical target in breast cancer, with ~75% of women having ERα+ breast tumors at diagnosis. Endocrine therapies (tamoxifen and aromatase inhibitors) targeting ERα are the preferred treatment for ER+/HER2− breast tumors due to their efficacy and tolerance in most patients. However, patients develop resistance to these endocrine therapies and disease progression to metastasis remains a major clinical problem. There are multiple mechanisms involved in the progression to endocrine resistance, including epigenetic changes in non-coding RNAs that regulate cellular pathways leading to cancer progression and metastasis. This paper summarizes the role of long non-coding RNAs regulated by miR-29 in endocrine-resistant breast cancer. ABSTRACT: Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.
Reports analyzing the impact of pediatric antimicrobial stewardship programs (ASP) over long periods of time are lacking. We thus report our ASP experience in a pediatric tertiary referral center over a long-term period from 2011 to 2018. Our ASP was implemented in 2011. The program was based primarily on guideline development with key stakeholders, engaging and educating providers, followed by prospective audit with feedback (PAF). Monitored antibiotics included meropenem, piperacillin–tazobactam, and cefepime, followed by the addition of ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, levofloxacin, linezolid, and vancomycin at various time points. Specifically, the program did not implemented the core strategy of formulary restriction with prior authorization. Process- and outcome-related ASP measures were analyzed. We saw a 32% decrease in overall antibiotic utilization, a 51% decrease in the utilization of antibiotics undergoing PAF, and a 72% reduction in the use of broad-spectrum antibiotics such as meropenem. There was a concomitant increase in organism susceptibility and a reduction in yearly drug purchasing costs of over USD 560,000 from baseline without changes in sepsis-related mortality. Our study highlights that a pediatric ASP based primarily on the principles of guideline development and PAF can improve antibiotic utilization and institutional bacterial susceptibilities without a detrimental impact on patient outcomes by changing the culture of antimicrobial utilization within the institution.
Antimicrobial resistance (AMR) is widely perceived as a threat to human and animal health and a significant One Health issue with extensive and complex factors contributing to its occurrence and spread. Previous studies have surveyed human and animal health professionals to determine their perceptions regarding AMR and antimicrobial use (AMU). There are limited studies exploring the understanding of veterinary students despite their critical role as future antimicrobial prescribers. A cross-sectional survey was administered to an entire cohort of Doctor of Veterinary Medicine Year 2 (DVM2) students (n = 136) to investigate their knowledge and perceptions regarding AMR and AMU prior to formal education on this issue. Ninety students (66.2% of the cohort) completed the survey. There was overwhelming agreement regarding the immediacy of the problem, with 84.4% of students indicating that ‘We must take action on AMR’. Despite more than 94.4% of students correctly defining AMR, specific knowledge regarding AMR impact, contributory causes to AMR and strategies to solve the challenge of AMR was variable. Most students perceived livestock producers to have a significant role in the perpetuation of AMR due to AMU for prophylaxis (71.1% substantial/moderate contribution) and treatment (56.7% substantial/moderate contribution). Over a third of respondents (37.8%) were unsure if AMR could spread from animals to humans. Respondents perceived that various groups (dentists, doctors, veterinarians, professional organisations) are all important in ameliorating the issue of AMR. The implementation of restrictive measures to reduce veterinary prescription of antimicrobials was viewed as less important than strategies involving education, hygiene, surveillance, and guideline development/availability. To encourage the development of good antimicrobial stewardship (AMS) practices, professional veterinary education needs to foster an understanding of the scientific, behavioural and social issues that contribute to AMR and inappropriate AMU, as well as prescribers' personal contribution to AMR perpetuation and amelioration.
SIMPLE SUMMARY: Although rhinitis is a quite common disease in cats, the underlying cause is not easily explored. In addition to responding to the emerging concern regarding antimicrobial resistance and close contact between a pet and its owner, this study investigated bacterial identification and antimicrobial susceptibility in chronic rhinitis in cats. The current study found that rhinitis was more likely in younger and young adult cats, with Pseudomonas spp. being the main bacterial species, as well as multidrug-resistant, followed by Pasteurella spp., Staphylococcus spp., and E. coli. Overall, amikacin, imipenem, and meropenem, which are intravenous antimicrobial agents, exhibited high activity against most bacterial species. However, the use of antimicrobials in categories A and B (EMA) in companion animals are not recommended if other antimicrobial choices are available. Notably, this report reflects on the current antimicrobial resistance situation. Therefore, the appropriate antimicrobial usage and selected drugs should be based on antimicrobial use guidelines, the result of culture, and antimicrobial susceptibility. ABSTRACT: Chronic rhinitis is a quite common upper respiratory tract (URT) disease in cats. As a result of unclear etiology, frequently, multidrug-resistant bacteria are identified. This study investigated bacterial isolations and an antimicrobial susceptibility test (AST) in chronic rhinitis in cats. The medical records of 395 cats with chronic URT signs were reviewed at the Kasetsart University Veterinary Teaching Hospital (KUVTH) between 2016 and 2021 to survey the underlying causes of URT. Then, apart from rhinitis, other causes were excluded to identify the bacterial species and antimicrobial susceptibility. The results indicated that the most frequent finding was neoplasia, followed by rhinitis and anatomical defects. Furthermore, the only significant association was between the age range and disease group, with gender, FIV, or FeLV infection not being significant. Rhinitis was 4.7 times more likely to occur than neoplasia in younger and young adult cats in the age range < 1–3 years compared to the group > 10 years. The main bacterial species was the Pseudomonas species. Antimicrobials with a susceptibility rate of more than 90% were amikacin, gentamicin, ciprofloxacin, norfloxacin, marbofloxacin, imipenem, and meropenem. In conclusion, rhinitis was the second most common chronic URT disease in cats and was more common in younger and young adult cats. The predominant bacteria with AST in this study reflect the antimicrobial resistance situation. Thus, antimicrobial usage should follow antimicrobial use guidelines first.
Antimicrobial Resistance (AMR) is a growing global health challenge that threatens to undo gains in human and animal health. Prevention and control of AMR requires functional antimicrobial stewardship (AMS) program, which is complex and often difficult to implement in low- and middle-income countries. We aimed to describe the processes of establishing and implementing an AMS program at Connaught Hospital in Sierra Leone. The project involved the setting up of an AMS program, capacity building and performing a global point prevalence survey (GPPS) at Sierra Leone’s national referral hospital. Connaught Hospital established a multidisciplinary AMS subcommittee in 2021 to provide AMS services such as awareness campaigns, education and training and review of guidelines. We performed a GPPS on 175 patients, of whom more than half (98, 56.0%) were prescribed an antibiotic: 63 (69.2%) in the surgical wards and 53 (51.2%) in the medical wards. Ceftriaxone (60, 34.3%) and metronidazole (53, 30.3%) were the most common antibiotics prescribed to patients. In conclusion, it is feasible to establish and implement an AMS program in low-income countries, where most hospitalized patients were prescribed an antibiotic.
Background Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. Methods This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. Results Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days. Conclusions In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.
Antibiotic resistance (AR) is a naturally occurring phenomenon with the capacity to render useless all known antibiotics in the fight against bacterial infections. Although bacterial resistance appeared before any human life form, this process has accelerated in the past years. Important causes of AR in modern times could be the over-prescription of antibiotics, the presence of faulty infection-prevention strategies, pollution in overcrowded areas, or the use of antibiotics in agriculture and farming, together with a decreased interest from the pharmaceutical industry in researching and testing new antibiotics. The last cause is primarily due to the high costs of developing antibiotics. The aim of the present review is to highlight the techniques that are being developed for the identification of new antibiotics to assist this lengthy process, using artificial intelligence (AI). AI can shorten the preclinical phase by rapidly generating many substances based on algorithms created by machine learning (ML) through techniques such as neural networks (NN) or deep learning (DL). Recently, a text mining system that incorporates DL algorithms was used to help and speed up the data curation process. Moreover, new and old methods are being used to identify new antibiotics, such as the combination of quantitative structure-activity relationship (QSAR) methods with ML or Raman spectroscopy and MALDI-TOF MS combined with NN, offering faster and easier interpretation of results. Thus, AI techniques are important additional tools for researchers and clinicians in the race for new methods of overcoming bacterial resistance.
A new approach to diabetic foot infections (DFIs) has been investigated, using a nisin-biogel combining the antimicrobial peptide (AMP) nisin with the natural polysaccharide guar-gum. Since in in vivo conditions bacteria may be exposed to decreased antimicrobial concentrations, known as subinhibitory concentrations (sub-MICs), effects of nisin-biogel sub-MIC values corresponding to 1/2, 1/4 and 1/8 of nisin’s minimum inhibitory concentration (MIC) on virulence expression by six Staphylococcus aureus DFI isolates was evaluated by determining bacteria growth rate; expression of genes encoding for staphylococcal protein A (spA), coagulase (coa), clumping factor A (clfA), autolysin (atl), intracellular adhesin A (icaA), intracellular adhesin D (icaD), and the accessory gene regulator I (agrI); biofilm formation; Coa production; and SpA release. Nisin-biogel sub-MICs decreased bacterial growth in a strain- and dose-dependent manner, decreased agrI, atl and clfA expression, and increased spA, coa, icaA and icaD expression. Biofilm formation increased in the presence of nisin-biogel at 1/4 and 1/8 MIC, whereas 1/2 MIC had no effect. Finally, nisin-biogel at sub-MICs did not affect coagulase production, but decreased SpA production in a dose-dependent manner. Results highlight the importance of optimizing nisin-biogel doses before proceeding to in vivo trials, to reduce the risk of virulence factor’s up-regulation due to the presence of inappropriate antimicrobial concentrations.
This study develops an AI-based pose estimation pipeline for quantifying movement kinematics in resistance training. Using videos from Wolf et al. (2025), comprising 303 recordings of 26 participants performing eight upper-body exercises under full (fROM) and lengthened partial (pROM) conditions, we extract joint-angle trajectories using five distinct deep-learning pose estimation models and a unified signal-processing framework. From these trajectories, we derive repetition-level metrics including range of motion (ROM) and repetition duration. We use these outputs as dependent variables in a crossed random-effects model that accounts for participant-, exercise-, and model-level variability to assess systematic differences between ROM conditions. Results indicate that pROM reduces range of motion without significantly affecting repetition duration. Variance decomposition shows that pROM increases both between-participant and between-exercise variability, suggesting reduced consistency in execution. To enable cross-exercise comparison, we model ROM on a logarithmic scale and define %ROM as the proportion of fROM achieved under pROM. While the estimated mean is approximately 56\%, significant heterogeneity across exercises indicates that lengthened partials are not characterized by a fixed proportion of full ROM. The results demonstrate that AI-based motion analysis can provide reliable kinematic insights to inform evidence-based training recommendations.
Immune checkpoint inhibition has emerged as an integral part of the standard-of-care for head and neck squamous cell carcinoma (HNSCC) in recurrent and/or metastatic stages. Clinical responses are impressive but remain limited to a minority of patients. Primary resistance of never-responders is considered to derive from host- and tumor-specific characteristics, the latter comprising tumor immune checkpoint activity, immune contexture, tumor mutational burden, neo-antigen load, and others. Secondary resistance of initially responding patients in addition, appears to be driven predominantly by irreversible T-cell exhaustion and therapy-induced selection of tumor cell clones with mutations in critical genes involved in the response to immune checkpoint inhibition. With particular focus on primary resistance against immune checkpoint inhibition, scientific interest of preclinical and clinical researchers currently aims at the development and evaluation of combined modality treatment approaches. Radiotherapy is a highly promising partner in this regard and represents a crucial treatment modality for patients with locally advanced HNSCC. Historically established as cytotoxic anti-cancer treatment, a growing body of evidence has shown additional locoregional and systemic immunomodulatory effects of radiotherapy. These are largely attributed to reprogramming of the tumor microenvironment driven by dying and senescent irradiated tumor and normal tissue cells and the concomitant cascade of danger signals, chemokines, and cytokines which stimulate immune cell recruitment and activation. Moreover, the irradiated state of tumor cells bears interesting analogy to the anti-viral state, since fragments of nuclear and mitochondrial DNA that are released into the cytosol can stimulate cytosolic nucleic acid sensors to produce intra-tumoral type I interferons which are essential to (re-)activate the cancer immunity cycle and (re-)invigorate systemic anti-tumor T-cell responses. Apart from these tumor adjuvanticity enhancing effects, several reports have also described increased tumor antigenicity upon radiotherapy originating from radiation-induced exposure of neo-antigens. Collectively, radiotherapy thus may serve as a means of personalized in situ vaccination which can synergize with immune checkpoint inhibition and may help to undermine primary resistance. First clinical experiences have shown that scheduling and dosing of such combined modality treatment regimens are challenging. Moreover, recent preclinical evidence suggests that particularly the role of radiation-induced cytokines and interferons appears to be complex in such combined modality settings due to their ambiguous effects on tumor and immune cells in the tumor microenvironment. The signaling cascades that orchestrate immune cell (re-)activation and cell fate decisions in irradiated tumor cells, including tumor cell survival, proliferation, and/or metastasis formation, are intimately interconnected and require further in-depth investigation.
Background CF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches. Methods In this longitudinal study, 30 CF patients (1–18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge. Results The initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved ( P < 0.01). Conclusion Our findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.
Background The therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse. Methods BRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse. Results A total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p= 0.766) and PFS (median: 11.2 vs. 11.0 months, p= 0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p= 0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p= 0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p= 0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p= 0.002) could prolong PRS for patients with secondary platinum-sensitive relapse. Conclusions PARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.
Introduction Probiotic lactobacilli are generally recognized as safe (GRAS) and are being used in several food and pharma formulations. However, growing concern of antibiotic resistance in bacterial strains of food origin and its possible transmission via functional foods is increasingly being emphasized. Objectives This study screened potential probiotic lactic acid bacteria (LAB) strains for their phenotypic and genotypic antibiotic resistance profiles. Methods Susceptibility to different antibiotics was assayed by the Kirby Bauer standard disc diffusion protocol. Both conventional and SYBR-RTq-PCR were used for detection of resistance coding genes. Results A variable susceptibility pattern was documented against different antibiotic classes. LAB strains irrespective of origin displayed marked phenotypic resistance against cephalosporins, aminoglycosides, quinolones, glycopeptides; and methicillin among beta-lactams with few exceptions. In contrast, high sensitivity was recorded against macrolides, sulphonamides and carbapenems sub-group of beta-lactams with some variations. parC, associated with ciprofloxacin resistance was detected in 76.5% of the strains. Other prevalent resistant determinants observed were aac(6?)Ii (42.1%), ermB, ermC (29.4%), and tetM (20.5%). Six (?17.6%) of the isolates were free from genetic resistance determinants screened in this study. Conclusion Study revealed presence of antibiotic resistance determinants among lactobacilli from both fermented foods and human sources.
American Chemical Societyfebruari 2022Antimicrobiële resistentie
[Image: see text] Antibiotic-resistant bacteria are an increasing concern both in everyday life and specialized environments such as healthcare. As the rate of antibiotic-resistant infections rises, so do complications to health and the risk of disability and death. Urgent action is required regarding the discovery of new antibiotics and rapid diagnosis of the resistance profile of an infectious pathogen as well as a better understanding of population and single-cell distribution of the resistance level. High-throughput screening is the major affordance of droplet microfluidics. Droplet screens can be exploited both to look for combinations of drugs that could stop an infection of multidrug-resistant bacteria and to search for the source of resistance via directed-evolution experiments or the analysis of various responses to a drug by genetically identical bacteria. In droplet techniques that have been used in this way for over a decade, aqueous droplets containing antibiotics and bacteria are manipulated both within and outside of the microfluidic devices. The diagnostics problem was approached by producing a series of microfluidic systems with integrated dilution modules for automated preparation of antibiotic concentration gradients, achieving the speed that allowed for high-throughput combinatorial assays. We developed a method for automated emulsification of a series of samples that facilitated measuring the resistance levels of thousands of individual cells encapsulated in droplets and quantifying the inoculum effect, the dependence of resistance level on bacterial cell count. Screening of single cells encapsulated in droplets with varying antibiotic contents has revealed a distribution of resistance levels within populations of clonally identical cells. To be able to screen bacteria from clinical samples, a study of fluorescent dyes in droplets determined that a derivative of a popular viability marker is more suitable for droplet assays. We have developed a detection system that analyzes the growth or death state of bacteria with antibiotics for thousands of droplets per second by measuring the scattering of light hitting the droplets without labeling the cells or droplets. The droplet-based microchemostats enabled long-term evolution of resistance experiments, which will be integrated with high-throughput single-cell assays to better understand the mechanism of resistance acquisition and loss. These techniques underlie automated combinatorial screens of antibiotic resistance in single cells from clinical samples. We hope that this Account will inspire new droplet-based research on the antibiotic susceptibility of bacteria.
International audience;
Carbapenemase-producing Escherichia coli (CP-Ec) represents a major public health threat with a risk of dissemination in the community as has occurred for lineages producing extended-spectrum β-lactamases. To characterize the extent of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Center (F-NRC) laboratory for carbapenemase-producing Enterobacterales were investigated. A total of 691 CP-Ec isolates collected between 2012 and 2015 and 22 isolates collected before 2012 were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug-resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex 23 (CC23) (sequence type 410 [ST410]) and CC10 (ST10 and ST167) and sporadic isolates, including rare ST131 isolates (n = 17). However, the most represented sequence type (ST) was ST38 (n = 92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n = 457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast, blaOXA-181 and blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC.
25 wetenschappelijke publicaties binnen het domein Levensduur en veroudering, voor snelle raadpleging van de bijbehorende wetenschappelijke literatuur.
BioMed Centralnovember 2022Levensduur en veroudering
Background With an increasingly ageing population worldwide, the predominant attitude towards ageing is still negative. Negative stereotypes have detrimental effects on individuals’ physical and mental health. Evidence is required about factors that may predict and change these views. This study aimed to investigate if an older person’s attitude towards dementia, their belief in a just world and sense of coherence is associated with their attitudes to ageing. Methods A 25-min online survey was completed by 2,675 participants aged 50 or over who were current residents of the United Kingdom (UK). Questions included demographics, overall health, dementia carer, dementia relative status and retirement status. Standardised scales used were the Attitudes to Ageing Questionnaire (AAQ), Dementia Attitudes Scale (DAS), Just World Scale (JWS) and Sense of Coherence Scale-13 (SOC). Data was analysed with descriptive, two-tailed bivariate Pearson’s correlations, simple, and hierarchical regression analyses. Results Attitudes to dementia, just world beliefs, and sense of coherence were all significantly positively correlated with AAQ-Total, with SOC sub-scale “Meaningfulness” showing the strongest correlation. In a hierarchical regression model, higher scores on SOC-Meaningfulness, DAS-Total and belief in a just world for oneself all predicted more positive attitudes to ageing. Conclusions The more positive an individual’s attitude to dementia and the stronger they hold the belief that the world is just and coherent, the more likely they are to display positive attitudes to ageing. This initial evidence helps create a greater understanding of the factors that drive attitudes and stigma and may have implications for public health messaging.
BioMed Centraloktober 2023Levensduur en veroudering
Background The therapeutic application of multipotent mesenchymal stem cells (MSCs) encounters significant challenges, primarily stemming from their inadequate growth and limited self-renewal capabilities. Additionally, as MSCs are propagated, their ability to self-renew declines, and the exact cellular and molecular changes responsible for this are poorly understood. This study aims to uncover the complex molecular mechanisms that govern the self-renewal of primitive (p) MSCs. Methods We grew pMSCs using two types of medium, fetal bovine serum (FM) and xeno-free (XM), at both low passage (LP, P3) and high passage (HP, P20). To evaluate LP and HP pMSCs, we examined their physical characteristics, cell surface markers, growth rate, colony-forming ability, BrdU assays for proliferation, telomerase activity, and potential to differentiate into three lineages. Moreover, we conducted RNA-seq to analyze their transcriptome and MNase-seq analysis to investigate nucleosome occupancies. Results When grown in FM, pMSCs underwent changes in their cellular morphology, becoming larger and elongated. This was accompanied by a decrease in the expression of CD90 and CD49f, as well as a reduction in CFE, proliferation rate, and telomerase activity. In addition, these cells showed an increased tendency to differentiate into the adipogenic lineage. However, when grown in XM, pMSCs maintained their self-renewal capacity and ability to differentiate into multiple lineages while preserving their fibroblastoid morphology. Transcriptomic analysis showed an upregulation of genes associated with self-renewal, cell cycle regulation, and DNA replication in XM-cultured pMSCs, while senescence-related genes were upregulated in FM-cultured cells. Further analysis demonstrated differential nucleosomal occupancies in self-renewal and senescence-related genes for pMSCs grown in XM and FM, respectively. These findings were confirmed by qRT-PCR analysis, which revealed alterations in the expression of genes related to self-renewal, cell cycle regulation, DNA replication, differentiation, and senescence. To understand the underlying mechanisms, we investigated the involvement of Wnt and TGFβ signaling pathways by modulating them with agonists and antagonists. This experimental manipulation led to the upregulation and downregulation of self-renewal genes in pMSCs, providing further insights into the signaling pathways governing the self-renewal and senescence of pMSCs. Conclusion Our study shows that the self-renewal potential of pMSCs is associated with the Wnt pathway, while senescence is linked to TGFβ.
BioMed Centraloktober 2023Levensduur en veroudering
Background Living in hilly neighbourhoods can be associated with sedentary behaviour, but no study has compared sedentary behaviour and its associations with frailty, chronic diseases, and poor health between flat and hilly neighbourhoods among older adults. This study, therefore, compared older adults’ sedentary behaviour and its association with frailty, poor health, and chronic disease status between low and hilly neighbourhoods. Methods This study utilised a STROBE-compliant cross-sectional design with sensitivity analyses and a common methods bias assessment. The participants were 1,209 people aged 50^+ years who resided in flat (Ablekuma North, n = 704) and hilly (Kwahu East, n = 505) neighbourhoods in Ghana. The data were analysed with the independent samples t -test and hierarchical linear regression. Results Older adults in the hilly neighbourhood were more sedentary than those in the flat neighbourhood. The association between sedentary behaviour and chronic disease status was significant in both neighbourhoods, but this relationship was stronger in the hilly neighbourhood. Older adults in the flat neighbourhood reported lower sedentary behaviour at higher frailty (β = -0.18; t = -3.2, p < 0.001), but those in the hilly neighbourhood reported higher sedentary behaviour at higher frailty (β = 0.16; t = 3.54, p < 0.001). Conclusions Older adults living in the hilly neighbourhood reported higher sedentary behaviour. In the hilly neighbourhood, sedentary behaviour was more strongly associated with frailty and chronic disease status. Older adults in hilly neighbourhoods may need extra support to avoid sedentary behaviour.
The French overseas départements went through a particularly fast demographic transition and are currently experiencing hastened population ageing within a context of strong economic dependence. Life expectancies in these départements are similar to those of other French départements, also in the oldest age groups. A longer life raises the question of whether the additional years of life are healthy life years. This question is especially crucial in the overseas départements since they are under-equipped in nursing homes and home-care programs. Moreover, the decrease in fertility over the last few decades and the mass emigrations of young adults (18-34 years old) to Metropolitan France are endangering the sustainability of the family-based care model. Using data from three different surveys: Migrations, Family and Ageing (MFV) 2009-2010, Health Barometer 2014 and Daily Life and Health (VQS) 2014, this thesis aims at identifying social, familial, behavioural and environmental factors that increase the risk of experiencing autonomy loss at older ages. This will help anticipate the needs of the older population in order to guide public policies towards the elderly.
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Les départements d’outre-mer ont connu une transition démographique particulièrement rapide et sont aujourd’hui touchés par un vieillissement accéléré de leur population, dans un contexte de dépendance économique très forte. Les espérances de vie dans ces départements sont proches de celle observée dans les autres départements français, y compris aux âges les plus élevés. L’allongement de la vie soulève alors la question de l’état de santé dans lequel sont vécues ces années supplémentaires aux âges élevés. Cette question est particulièrement centrale dans les DOM étant donné le sous-équipement de ces territoires en structures d’accueil pour personnes âgées comme en offre de soins à domicile. De plus, la pérennité du modèle de prise en charge familiale mis en danger par la réduction de la fécondité sur les dernières décennies ainsi que les émigrations massives de 18-34 ans vers la Métropole. Utilisant les données de trois enquêtes différentes : Migrations, Famille et Vieillissement (MFV) 2009-2010, Baromètre Santé DOM 2014 et Vie Quotidienne et Santé (VQS) 2014, cette thèse vise à identifier les facteurs sociaux, familiaux, comportementaux et environnementaux qui augmentent le risque de connaître des situations d’incapacité aux grands âges, et d’anticiper les besoins des plus âgées afin d’orienter au mieux les politiques publiques à destination des personnes âgées.
Cold Spring Harbor Laboratoryoktober 2024Levensduur en veroudering
Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells. We used multiplex, single-cell imaging to build a proteomic map of senescence induction in human epithelial cells induced to senescence over the course of 31 days. We map how the expression of SASP proteins increases alongside other known senescence markers such as p53, p21, and p16 (INK4a) . The aggregated population of cells responded to etoposide with an accumulation of stress response factors over the first 11 days, followed by a plateau in most proteins. At the single-cell level, however, we identified two distinct senescence cell populations, one defined primarily by larger nuclear area and the second by higher protein concentrations. Trajectory inference suggested that cells took one of two discrete molecular paths from unperturbed healthy cells, through a common transitional subpopulation, and ending at the discrete terminal senescence phenotypes. Our results underscore the importance of using single-cell proteomics to identify the mechanistic pathways governing the transition from senescence induction to a mature state of senescence characterized by the SASP.
Corrosion prevention can be achieved in several ways, and the use of epoxy-based coatings is proving to be one of the most effective and economical solutions. It is therefore essential top redict their lifetime by gaining a better understanding of the phenomena occurring in the polymer, particularly when exposed to "physical and/or hygrothermal ageing". In our study, we investigate the role of physical aging of fully cross-linkedDGEBA/Jefamine230 systems on hygrothermal aging, as well as the effect of the coupling of these two aging processes on the physicochemical, mechanical and adhesion properties of coatings deposited on aluminum. The results of our study show that hygrothermal ageing leads to physical ageing, particularly at temperatures close to Tg. This underlines the importance of carefully monitoring the influence of physical ageing on the physicochemical and mechanical properties of epoxy resins when setting up accelerated ageing processes in the laboratory. Moreover, the blister test showed that adhesion is mainly affected by the presence of water at the coating interface, while physical ageing acts to defer this influence by reducing the amount of water at saturation.
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La prévention de la corrosion peut être réalisée de différentes manières, et l'utilisation de revêtements à base d'époxy s'avère être l'une des solutions les plus efficaces et économiques. Il est donc essentiel de prédire leur durée de vie en acquérant une meilleure compréhension des phénomènes qui se produisent dans le polymère, notamment lorsqu'ils sont exposés au "vieillissement physique et/ou hygrothermique". Dans notre étude, nous nous intéressons au rôle du vieillissement physique de système DGEBA/Jefamine230 modèle totalement réticulé sur le vieillissement hygrothermique, ainsi que l’effet du couplage de ces deux vieillissements sur les propriétés physico-chimiques, mécaniques et l’adhésion des revêtements déposé sur aluminium. Les résultats de notre étude mettent en lumière que le vieillissement hygrothermique engendre un vieillissement physique, en particulier à des températures proches de Tg. Cela souligne l'importance de surveiller attentivement l'influence du vieillissement physique sur les propriétés physico-chimiques et mécaniques des résines époxy lors de la mise en place de processus de vieillissement accéléré en laboratoire. Par ailleurs, les essais de cloquage (blister test) ont montré que l'adhésion est principalement impactée par la présence d'eau à l'interface du revêtement, tandis que le vieillissement physique agit en différant cette influence grâce à la réduction de la quantité d'eau à saturation.
Purpose of Review The purpose of this review is to discuss the role of macrophages in the regulation of skeletal health with age, particularly in regard to both established and unexplored mechanisms in driving inflammation and senescence. Recent Findings A multitude of research has uncovered mechanisms of intrinsic aging in macrophages, detrimental factors released by these immune cells, and crosstalk from senescent mesenchymal cell types, which altogether drive age-related bone loss. Furthermore, bone marrow macrophages were recently proposed to be responsible for the megakaryocytic shift during aging and overall maintenance of the hematopoietic niche. Studies on extra-skeletal macrophages have shed light on possible conserved mechanisms within bone and highlight the importance of these cells in systemic aging. Summary Macrophages are a critically important cell type in maintaining skeletal homeostasis with age. New discoveries in this area are of utmost importance in fully understanding the pathogenesis of osteoporosis in aged individuals.
Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass ( P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14–3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.
The age-related loss of skeletal muscle mass and physical function leads to a loss of independence and an increased reliance on health-care. Mitochondria are crucial in the aetiology of sarcopenia and have been identified as key targets for interventions that can attenuate declines in physical capacity. Exercise training is a primary intervention that reduces many of the deleterious effects of ageing in skeletal muscle quality and function. However, habitual levels of physical activity decline with age, making it necessary to implement adjunct treatments to maintain skeletal muscle mitochondrial health and physical function. This review provides an overview of the effects of ageing and exercise training on human skeletal muscle mitochondria and considers several supplements that have plausible mechanistic underpinning to improve physical function in ageing through their interactions with mitochondria. Several supplements, including MitoQ, urolithin A, omega-3 polyunsaturated fatty acids (n3-PUFAs), and a combination of glycine and N-acetylcysteine (GlyNAC) can improve physical function in older individuals through a variety of inter-dependent mechanisms including increases in mitochondrial biogenesis and energetics, decreases in mitochondrial reactive oxygen species emission and oxidative damage, and improvements in mitochondrial quality control. While there is evidence that some nicotinamide adenine dinucleotide precursors can improve physical function in older individuals, such an outcome seems unrelated to and independent of changes in skeletal muscle mitochondrial function. Future research should investigate the safety and efficacy of compounds that can improve skeletal muscle health in preclinical models through mechanisms involving mitochondria, such as mitochondrial-derived peptides and mitochondrial uncouplers, with a view to extending the human health-span.
The probability of detecting technosignatures (i.e. evidence of technological
activity beyond Earth) increases with their longevity, or the time interval
over which they manifest. Therefore, the assumed distribution of longevities
has some bearing on the chances of success of technosignature searches, as well
as on the inferred age of technosignatures following a first contact. Here, we
investigate the possibility that the longevity of technosignatures conforms to
the so-called Lindy's law, whereby, at any time, their remaining life
expectancy is roughly proportional to their age. We show that, if Lindy's law
applies, the general tenet that the first detected technosignature ought to be
very long lived may be overruled. We conclude by discussing the number of
emitters that had to appear, over the history of the Galaxy, in order for one
of them to be detectable today from Earth.
;Comment: 9 pages, 4 figures
Background Cold storage of reared natural enemies is important in terms of planning the release time and quantity, eliminating unpredicted demand increases, and reducing production costs. However, the tolerance of reared natural enemies at low temperatures varies depending on the species and needs to be determined. Eretmocerus mundus Mercet (Hymenoptera: Aphelinidae) is one of the most important natural enemies used in biological control of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) in greenhouses. Results In a laboratory study, longevity, parasitism capacity and functional response of E. mundus adults obtained from 8-days cold-stored red-eyed E . mundus pupae at 10 °C with 45 ± 5% RH conditions were determined. Mean longevity obtained from stored E . mundus pupae of female and male were 23.6 and 16.2 days, respectively. However, parasitism capacity was negatively affected so that the total mean number of immature B . tabaci parasitized by an E . mundus female obtained from cold-stored pupae (13.6) was statistically lower than that obtained from the colony (26.8) reared at room temperature. Adults obtained from both non-stored and stored E . mundus pupae exhibited a type II functional response to increasing host density. Although cold storage did not alter the type of functional response, it negatively affected the maximum attack rate ( α ) and handling time ( Th ) of the parasitoid. The lowest maximum attack rate (1.56) and highest handling time (0.059) were obtained for adults of cold-stored E . mundus pupae. Conclusions The results obtained may contribute to the augmentative biological control of B. tabaci in greenhouses.
As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.
John Wiley and Sons Inc.oktober 2024Levensduur en veroudering
Evidence is accumulating on the connection of early adversities and harsh family environment with epigenetic ageing. We investigated whether early psychosocial resilience is associated with epigenetic ageing in adulthood. We used the population‐based Young Finns data (n = 1593). Early psychosocial resilience was assessed in 1980–1989 across five broad domains: (1) index of psychological strength (self‐esteem at home/in general/at school, perceived possibilities to influence at home, internal life control), (2) index of social satisfaction (perceived support from family/friends and life satisfaction), (3) index of leisure time activities (hobbies and physical fitness), (4) index of responsible health behaviors (infrequent smoking or alcohol consumption), and (5) index of school career (school grades and adaptation). Epigenetic ages were calculated for blood samples from 2011, and the analyses were performed with variables describing age deviation (AgeDev(Hannum), AgeDev(Horvath), AgeDev(Pheno), AgeDev(Grim)) and DunedinPACE. Covariates included early family environment, polygenic risk scores for schizophrenia and major depression, adulthood education, and adulthood health behaviors. All of the early resilience indexes were associated with lower levels of epigenetic ageing in adulthood, most consistently with AgeDev(Grim) and DunedinPACE. The associations of psychological strength and social satisfaction, in particular, seemed to be non‐linear. In a smaller subsample (n = 289), high early resilience was related to lower AgeDev(Grim) over a 25‐year follow‐up in those who had high “baseline” levels of AgeDev(Grim). In conclusion, early resilience seems to associate with lower level of epigenetic ageing in adulthood. Our results tentatively suggest that early resilience may increase “equality in epigenetic ageing” in a general population.
Cold Spring Harbor Laboratoryjuni 2024Levensduur en veroudering
Cellular senescence, a stress-induced stable proliferation arrest associated with an inflammatory Senescence-Associated Secretory Phenotype (SASP), is a cause of aging. In senescent cells, Cytoplasmic Chromatin Fragments (CCFs) activate SASP via the anti-viral cGAS/STING pathway. PML protein organizes PML nuclear bodies (NBs), also involved in senescence and anti-viral immunity. The HIRA histone H3.3 chaperone localizes to PML NBs in senescent cells. Here, we show that HIRA and PML are essential for SASP expression, tightly linked to HIRA’s localization to PML NBs. Inactivation of HIRA does not directly block expression of NF-κB target genes. Instead, an H3.3-independent HIRA function activates SASP through a CCF-cGAS-STING-TBK1-NF-κB pathway. HIRA physically interacts with p62/SQSTM1, an autophagy regulator and negative SASP regulator. HIRA and p62 co-localize in PML NBs, linked to their antagonistic regulation of SASP, with PML NBs controlling their spatial configuration. These results outline a role for HIRA and PML in regulation of SASP.
Background Ovarian ageing causes endocrine disturbances and the degeneration of systemic tissue and organ functions to seriously affect women's physical and mental health, and effective treatment methods are urgently needed. Based on our previous studies using juvenile rhesus monkey bone marrow mesenchymal stem cells (BMMSCs) to treat ovarian ageing in rhesus monkey, we found that BMMSCs improved ovarian structure and function. This study continues to explore the mechanism by which BMMSCs reversed granulosa cell (GC) ageing. Methods A GC ageing model and coculture system of BMMSCs were established, changes in the level of the N6-methyladenosine (m6A) methylation modification were detected, m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) were performed, correlations between m6A peaks and mRNA expression were determined, and the expression of hub genes was identified using Q-PCR, immunofluorescence staining, and western blot. Results Our results showed that H_2O_2 successfully induced GC ageing and that BMMSCs reversed measures of GC ageing. BMMSCs increased the expression of the FTO protein and reduced the overall level of m6A. We identified 797 m6A peaks (348 hypomethylated and 449 hypermethylated peaks) and 817 differentially expressed genes (DEGs) (412 upregulated and 405 downregulated) after aged GCs were cocultured with BMMSCs, which significantly associated with ovarian function and epigenetic modification. The epigenetic repressive mark and important cell cycle regulator lysine demethylase 8 (KDM8) was downregulated at both the mRNA and protein levels, histone H3 was upregulated in aged GCs after BMMSC coculture, and KDM8 was upregulated after FTO was inhibited through FB23. Conclusions Our study revealed an essential role for m6A in BMMSCs in reversing GC ageing, and FTO regulated KDM8 mediates histone H3 changes may as a novel regulatory mechanism in BMMSCs to reverse GC ageing. Graphical Abstract
John Wiley and Sons Inc.april 2022Levensduur en veroudering
Little is known about the biology of grey‐cheeked and black crested mangabeys (Lophocebus albigena and Lophocebus aterrimus, respectively). As these primates face threats in the wild, well‐monitored zoo‐housed populations with up to date registries are becoming increasingly valuable to acquire species knowledge and to support conservation efforts. We used international studbooks to extract demographic and genetic information on 519 mangabeys to investigate how life history and parent‐related variables influence maximum longevity and juvenile mortality. Generalized linear mixed models, as well as survival analyses, were applied. Results showed that females lived significantly longer than males, which is not uncommon in primates. Furthermore, our results indicated that the maximum longevity is lower for individuals living in European zoos versus individuals from North American zoos, which may be due to a combination of environmental differences and potential founder effects. We also show that the maternal maximum longevity is positively related to the maximum longevity of the offspring, which may be explained by the inheritance of “good genes“. However, the age of the mother at the moment of birth was negatively related to the maximum longevity of the offspring, which contradicts literature that states that, in primates, more experienced and thus older mothers will raise their offspring better than less experienced mothers. Instead, it is more likely that an “optimal age range” exists for breeding mothers. Our study provides insights into the population biology of captive mangabeys and may be helpful for identifying future research priorities to optimize primate health and welfare directly ex situ, and indirectly in situ.
Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8^+ T-lymphocytes (CD8^+ T_EMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8^+ T-lymphocytes which were CD8^+ T_EMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8^+ T_EMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/μl (95% CI: 117–452 cells/ μ l, p < 0.004), driven by significant increases from baseline in CD3^+, CD4^+, and CD8^+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8^+ T_EMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.
Ma, Cao et al. uncover dynamic changes of chromatin reorganization in progenitor B cells during ageing, associated with altered H3K27ac levels and expression of genes that are critical for B cell development. The contribution of three-dimensional genome organization to physiological ageing is not well known. Here we show that large-scale chromatin reorganization distinguishes young and old bone marrow progenitor (pro-) B cells. These changes result in increased interactions at the compartment level and reduced interactions within topologically associated domains (TADs). The gene encoding Ebf1, a key B cell regulator, switches from compartment A to B with age. Genetically reducing Ebf1 recapitulates some features of old pro-B cells. TADs that are most reduced with age contain genes important for B cell development, including the immunoglobulin heavy chain ( Igh ) locus. Weaker intra-TAD interactions at Igh correlate with altered variable (V), diversity (D) and joining (J) gene recombination. Our observations implicate three-dimensional chromatin reorganization as a major driver of pro-B cell phenotypes that impair B lymphopoiesis with age.
HAL CCSD;Elsevierjanuari 2023Levensduur en veroudering
International audience;
Having clear insights of the stress factors that the electric vehicle (EV) batteriesencounter during their service lifetime is crucial for more reliable ageing testing andmodelling. Since the first deployment of Li-ion battery based EV, numerous drivingcampaigns with field data were published. The goal of this article is to gather, assessand analyse them in order to quantify the stress factors depending on the EV type. Thetargeted stress factors are the temperature of the cells, the discharging and chargingrates, as well as the SOC ranges. 228 million km of driving and 7.8 million trips worthof data for over 37,000 EV were investigated. Along with this literature enquiry, datafrom an EV in which cells' temperature was monitored for driving, charging andparking conditions, complemented the analysis. For each stress factor, results werecollected, homogenised and compared with each other in order to draw conclusions.Finally, a Risk Probabilistic Number (RPN) was used to evaluate the stress factors withrespect to their impact on the ageing of Li-ion batteries, considering a central Europeanweather. The most critical stress factors for BEV cells are cycling at high mid-SOCregions and high SOC idle times. Concerning HEV cells, high power cycling at mid-SOC regions is the most critical stress, and no stresses were identified during idletimes. PHEV cells' most critical stress factors are large DOD cycling and highcharge/discharge power. Mild and low temperatures are found to be the most commonin such weathers. The RPN analysis serves as a guide for parametrizing and designingreliable accelerated ageing testing on Li-ion batteries depending on their application.
CCSD;Elsevierjanuari 2022Levensduur en veroudering
International audience;
Generally, studies on ageing of power module have very often sought to write phenomenological laws able to give an estimate of their lifespan. These laws, identified experimentally, are empirical functions of the characteristic electrical loads that the component must withstand. As an alternative, this paper presents a first attempt of numerical approach for wire bond ageing in semiconductor power modules that takes account for the different multi-physical coupling mechanisms that occur during the component life. The electro-thermal and thermo-mechanical interactions are physically described and numerically modeled. The calculations show important viscoplastic strains in the connection zones and bonding wires from the first loading cycles. A quasi-cyclic stabilization of the mechanical and thermal states is observed at more than a hundred cycles (viscoplastic shakedown). The creep-fatigue damage mechanisms become then preponderant inducing mechanical-electrical couplings.
BMJ Publishing Groupjuni 2022Levensduur en veroudering
Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Using endothelial colony-forming-cells (ECFC), we have demonstrated accelerated senescence in smokers and patients with COPD compared with non-smokers. Subgroup analysis suggests that ECFC from patients with COPD on inhaled corticosteroids (ICS) (n=14; eight on ICS) exhibited significantly reduced senescence (Senescence-associated-beta galactosidase activity, p21(CIP1)), markers of DNA damage response (DDR) and IFN-γ-inducible-protein-10 compared with patients with COPD not on ICS. In vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS on the DDR, senescence and apoptosis caused by oxidative stress, suggesting a protective molecular mechanism of action of corticosteroids on endothelium.
In France, very small towns have become municipalities with the highest proportion of elderly people, much more than villages and cities. Our study aims to investigate the factors and effects of population ageing on the territorial dynamics of very small towns. It proposes a renewed definition of these municipalities based on a functional approach that takes into account the diversity of French rural areas. Thank to mixed methods (statistical analyses and field studies), the findings show a reinterpretation of the ageing phenomenon in these municipalities. Contrary to popular belief, ageing of very small towns is partly due to their residential attractiveness to a wide variety of retirees. Furthermore, this work highlights the key role of elderly people in maintaining the population, facilities, economic activities, and social life of these rural centers. It also highlights the socio-economic diversity of ageing in these municipalities on a national scale. Finally, this thesis reveals a gap between public policies and socio-economics dynamics observed. It questions the emergence of a new role for very small towns in rural areas and its alignment with public policies.
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En France, les bourgs ruraux sont les communes qui recensent en moyenne la part la plus importante de personnes âgées. Ils se distinguent des villages et des villes. Cette thèse s’attache à interroger les déterminants et les effets du vieillissement de la population sur les dynamiques territoriales des bourgs ruraux. Elle propose pour cela une définition renouvelée de cette catégorie de communes à partir d’une approche fonctionnelle attentive à la diversité des espaces ruraux français. L’articulation de méthodes mixtes (traitements statistiques et enquêtes de terrain) permet d’opérer une relecture profonde du vieillissement de ces communes. À rebours des représentations, cette recherche révèle que ce phénomène d’une ampleur inédite est en partie lié à l’attractivité résidentielle des bourgs ruraux auprès d’une grande diversité de retraités. Ce travail montre, de plus, le rôle clef des personnes âgées dans le maintien de la population, des équipements, des activités économiques et de la vie sociale de ces centres ruraux. Il met, par ailleurs, en lumière la diversité socio-économique du vieillissement des bourgs ruraux à l’échelle nationale. Au regard de ces résultats, notre thèse fait apparaître un décalage entre les stratégies locales menées dans ces communes et les dynamiques socio-économiques observées. Elle questionne, plus largement, l’émergence d’un nouveau rôle des bourgs dans les espaces ruraux et son adéquation avec les politiques menées par l’action publique.
Diabetes mellitus is a major public health problem with a wide range of prevalence among different ethnic groups. Early recognition of pre-diabetes is important to prevent the development of the disease, its complications, co-morbidities, and consequently early death. Insulin resistance (IR) is considered a condition that precedes type 2 diabetes; thus, understanding its underlying causes (genetic and non-genetic factors) will bring us closer to preventing it. The present study aimed to investigate the genetic susceptibility to IR and its impact on estimated longevity in populations with different ethnic origins using randomly selected samples of 372 Hungarian general (HG, as a reference with Caucasian origin) and 334 Roma participants (largest ethnic minority in Europe, with a northern India origin). In the present study, we used the Homeostasis Model Assessment—Insulin Resistance (HOMA—IR) to identify people with IR (>3.63) at the population level. To investigate the genetic predisposition to IR, 29 single nucleotide polymorphisms (SNPs) identified in a systematic literature search were selected and genotyped in sample populations. In the analyses, the adjusted p < 0.0033 was considered significant. Of these 29 SNPs, the commutative effects of 15 SNPs showing the strongest association with HOMA—IR were used to calculate an optimized genetic risk score (oGRS). The oGRS was found nominally significantly (p = 0.019) higher in the Roma population compared to HG one, and it was more strongly correlated with HOMA—IR. Therefore, it can be considered as a stronger predictor of the presence of IR among the Roma (AUCRoma = 0.673 vs. AUCHG = 0.528). Furthermore, oGRS also showed a significant correlation with reduced estimated longevity in the Roma population (β = −0.724, 95% CI: −1.230–−0.218; p = 0.005), but not in the HG one (β = 0.065, 95% CI: −0.388–0.518; p = 0.779). Overall, IR shows a strong correlation with a genetic predisposition among Roma, but not in the HG population. Furthermore, the increased genetic risk of Roma is associated with shorter estimated longevity, whereas this association is not observed in the HG one. Increased genetic susceptibility of Roma to IR should be considered in preventive programs targeting the development of type 2 diabetes, which may also reduce the risk of preventable premature death among them.
Springer Science and Business Media LLCjuni 2023Levensduur en veroudering
Abstract Citrus fruit has long been considered a healthy food, but its role and detailed mechanism in lifespan extension are not clear. Here, by using the nematode C. elegans , we identified that nomilin, a bitter-taste limoloid that is enriched in citrus, significantly extended the animals’ lifespan, healthspan, and toxin resistance. Further analyses indicate that this ageing inhibiting activity depended on the insulin-like pathway DAF-2/DAF-16 and nuclear hormone receptors NHR-8/DAF-12. Moreover, the human pregnane X receptor (hPXR) was identified as the mammalian counterpart of NHR-8/DAF-12 and X-ray crystallography showed that nomilin directly binds with hPXR. The hPXR mutations that prevented nomilin binding blocked the activity of nomilin both in mammalian cells and in C. elegans . Finally, dietary nomilin supplementation improved healthspan and lifespan in D-galactose- and doxorubicin-induced senescent mice as well as in male senescence accelerated mice prone 8 (SAMP8) mice, and induced a longevity gene signature similar to that of most longevity interventions in the liver of bile-duct-ligation male mice. Taken together, we identified that nomilin may extend lifespan and healthspan in animals via the activation of PXR mediated detoxification functions.
BioMed Centraljanuari 2022Levensduur en veroudering
Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.
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