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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.
Understanding the molecular-level mechanisms underpinning Alzheimer's disease (AD) by studying crucial genes associated with the disease remains a challenge. Alzheimer's, being a multifactorial disease, requires understanding the gene-gene interactions underlying it for theranostics and progress. In this article, a novel attempt has been made using a quantum regression to decode how some crucial genes in the AD Amyloid Beta Precursor Protein ($APP$), Sterol regulatory element binding transcription factor 14 ($FGF14$), Yin Yang 1 ($YY1$), and Phospholipase D Family Member 3 ($PLD3$) etc. become influenced by other prominent switching genes during disease progression, which may help in gene expression-based therapy for AD. Our proposed Quantum Regression Network (Alz-QNet) introduces a pioneering approach with insights from the state-of-the-art Quantum Gene Regulatory Networks (QGRN) to unravel the gene interactions involved in AD pathology, particularly within the Entorhinal Cortex (EC), where early pathological changes occur. Using the proposed Alz-QNet framework, we explore the interactions between key genes ($APP$, $FGF14$, $YY1$, $EGR1$, $GAS7$, $AKT3$, $SREBF2$, and $PLD3$) within the CE microenvironment of AD patients, studying genetic samples from the database $GSE138852$, all of which are believed to play a crucial role in the progression of AD. Our investigation uncovers intricate gene-gene interactions, shedding light on the potential regulatory mechanisms that underlie the pathogenesis of AD, which help us to find potential gene inhibitors or regulators for theranostics.
We present and analyze an optimal control problem to model anti-inflammatory treatment strategies for Alzheimer's disease, using a system of differential equations that captures interactions between Aβ-peptides, microglial cells, interleukins, and neurons. These interactions operate through mechanisms such as protein polymerization, inflammation processes, and neural stress responses. In particular, inflammation is highlighted as a key factor in the onset and progression of Alzheimer's disease, driven by a hysteresis effect related to the degradation rate d of monomers and the initial concentration of interleukins. This implies a critical inflammation threshold that determines whether the disease persists over the long term. The optimal control problem we propose seeks to minimize the concentration of toxic oligomers by modulating interleukin production and degradation rates, representing potential anti-inflammatory treatment effects. Under natural constraints on treatment dose efficacy and cumulative exposure, our goal is to assess whether it is possible to shift the system from a persistent disease state to a disease-free equilibrium. We provide a characterization of the optimal solution and supplement our theoretical findings with numerical simulations, which illustrate the system's behavior under different parameter settings and the imposed constraints of the optimal control problem.
Deep learning models in medical imaging typically operate as parametric memory, diagnosing patients by recalling fixed knowledge learned during training. This contrasts sharply with clinical practice, where physicians employ analogical reasoning to diagnose new cases by referencing similar records from past exemplars. While In-Context Learning (ICL) frameworks such as Tabular Prior-Fitted Networks (TabPFN) offer a promising diagnosis-by-reference paradigm, they are designed with tabular-specific inductive priors and rely on non-differentiable preprocessing pipelines, leading to manifold mismatch and gradient fracture when applied to heterogeneous multimodal data. To address these limitations, we propose PromptDx, a novel diagnosis-by-reference framework that leverages a pre-trained TabPFN as an ICL engine while enabling seamless integration with multimodal representations. Our core contribution is a Differentiable Prompt Tuning (DPT) mechanism that aligns a Masked Multimodal Modeling module with the pre-trained ICL engine. By training a lightweight adapter as a differentiable surrogate for the engine's non-differentiable preprocessors, we enable an end-to-end optimization of multimodal prompts within the ICL paradigm. We validate our method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset using 3D MRI and tabular biomarkers. Experiments demonstrate that our approach outperforms traditional parametric baselines. Notably, our method achieves superior performance using only 1% context samples compared to 30% in standard ICL, demonstrating exceptional manifold condensation ability. We further validate the generalizability of our DPT framework across six tabular datasets with diverse scales. Overall, our method offers a more data-efficient and clinically aligned paradigm for Alzheimer's Disease diagnosis.
Alzheimer's disease is a progressive neurodegenerative disorder that remains challenging to predict due to its multifactorial etiology and the complexity of multimodal clinical data. Accurate forecasting of clinically relevant biomarkers, including diagnostic and quantitative measures, is essential for effective monitoring of disease progression. This work introduces L2C-TabPFN, a method that integrates a longitudinal-to-cross-sectional (L2C) transformation with a pre-trained Tabular Foundation Model (TabPFN) to predict Alzheimer's disease outcomes using the TADPOLE dataset. L2C-TabPFN converts sequential patient records into fixed-length feature vectors, enabling robust prediction of diagnosis, cognitive scores, and ventricular volume. Experimental results demonstrate that, while L2C-TabPFN achieves competitive performance on diagnostic and cognitive outcomes, it provides state-of-the-art results in ventricular volume prediction. This key imaging biomarker reflects neurodegeneration and progression in Alzheimer's disease. These findings highlight the potential of tabular foundational models for advancing longitudinal prediction of clinically relevant imaging markers in Alzheimer's disease. ;preprint
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.
Alzheimer's Disease Analysis Model (ADAM) is a multi-agent reasoning large language model (LLM) framework designed to integrate and analyze multimodal data, including microbiome profiles, clinical datasets, and external knowledge bases, to enhance the understanding and classification of Alzheimer's disease (AD). By leveraging the agentic system with LLM, ADAM produces insights from diverse data sources and contextualizes the findings with literature-driven evidence. A comparative evaluation with XGBoost revealed a significantly improved mean F1 score and significantly reduced variance for ADAM, highlighting its robustness and consistency, particularly when utilizing human biological data. Although currently tailored for binary classification tasks with two data modalities, future iterations will aim to incorporate additional data types, such as neuroimaging and peripheral biomarkers, and expand them to predict disease progression, thereby broadening ADAM's scalability and applicability in AD research and diagnostic applications. ;12 pages, 7 figures
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.
Objectives: High classification accuracy of Alzheimer's disease (AD) from structural MRI has been achieved using deep neural networks, yet the specific image features contributing to these decisions remain unclear. In this study, the contributions of T1-weighted (T1w) gray-white matter texture, volumetric information, and preprocessing -- particularly skull-stripping -- were systematically assessed.
Methods: A dataset of 990 matched T1w MRIs from AD patients and cognitively normal controls from the ADNI database were used. Preprocessing was varied through skull-stripping and intensity binarization to isolate texture and shape contributions. A 3D convolutional neural network was trained on each configuration, and classification performance was compared using exact McNemar tests with discrete Bonferroni-Holm correction. Feature relevance was analyzed using Layer-wise Relevance Propagation, image similarity metrics, and spectral clustering of relevance maps.
Results: Despite substantial differences in image content, classification accuracy, sensitivity, and specificity remained stable across preprocessing conditions. Models trained on binarized images preserved performance, indicating minimal reliance on gray-white matter texture. Instead, volumetric features -- particularly brain contours introduced through skull-stripping -- were consistently used by the models.
Conclusions: This behavior reflects a shortcut learning phenomenon, where preprocessing artifacts act as potentially unintended cues. The resulting Clever Hans effect emphasizes the critical importance of interpretability tools to reveal hidden biases and to ensure robust and trustworthy deep learning in medical imaging.
Early and accurate diagnosis of Alzheimer Disease is critical for effective clinical intervention, particularly in distinguishing it from Mild Cognitive Impairment, a prodromal stage marked by subtle structural changes. In this study, we propose a hybrid deep learning ensemble framework for Alzheimer Disease classification using structural magnetic resonance imaging. Gray and white matter slices are used as inputs to three pretrained convolutional neural networks such as ResNet50, NASNet, and MobileNet, each fine tuned through an end to end process. To further enhance performance, we incorporate a stacked ensemble learning strategy with a meta learner and weighted averaging to optimally combine the base models. Evaluated on the Alzheimer Disease Neuroimaging Initiative dataset, the proposed method achieves state of the art accuracy of 99.21% for Alzheimer Disease vs. Mild Cognitive Impairment and 91.0% for Mild Cognitive Impairment vs. Normal Controls, outperforming conventional transfer learning and baseline ensemble methods. To improve interpretability in image based diagnostics, we integrate Explainable AI techniques by Gradient weighted Class Activation, which generates heatmaps and attribution maps that highlight critical regions in gray and white matter slices, revealing structural biomarkers that influence model decisions. These results highlight the frameworks potential for robust and scalable clinical decision support in neurodegenerative disease diagnostics. ;18 pages, 4 figures
The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using UK Biobank CFPs, DL models were trained using 62,876 images from 44,501 unique participants to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability. ;Accepted to the "Journal of Alzheimer's Disease" for publication
Early detection of cognitive disorders such as Alzheimer's disease is critical for enabling timely clinical intervention and improving patient outcomes. In this work, we introduce CogniAlign, a multimodal architecture for Alzheimer's detection that integrates audio and textual modalities, two non-intrusive sources of information that offer complementary insights into cognitive health. Unlike prior approaches that fuse modalities at a coarse level, CogniAlign leverages a word-level temporal alignment strategy that synchronizes audio embeddings with corresponding textual tokens based on transcription timestamps. This alignment supports the development of token-level fusion techniques, enabling more precise cross-modal interactions. To fully exploit this alignment, we propose a Gated Cross-Attention Fusion mechanism, where audio features attend over textual representations, guided by the superior unimodal performance of the text modality. In addition, we incorporate prosodic cues, specifically interword pauses, by inserting pause tokens into the text and generating audio embeddings for silent intervals, further enriching both streams. We evaluate CogniAlign on the ADReSSo dataset, where it achieves an accuracy of 87.35% over a Leave-One-Subject-Out setup and of 90.36% over a 5 fold Cross-Validation, outperforming existing state-of-the-art methods. A detailed ablation study confirms the advantages of our alignment strategy, attention-based fusion, and prosodic modeling. Finally, we perform a corpus analysis to assess the impact of the proposed prosodic features and apply Integrated Gradients to identify the most influential input segments used by the model in predicting cognitive health outcomes.
Imaging and genomic data offer distinct and rich features, and their
integration can unveil new insights into the complex landscape of diseases. In
this study, we present a novel approach utilizing radiogenomic data including
structural MRI images and gene expression data, for Alzheimer's disease
detection. Our framework introduces a novel heterogeneous bipartite graph
representation learning featuring two distinct node types: genes and images.
The network can effectively classify Alzheimer's disease (AD) into three
distinct stages:AD, Mild Cognitive Impairment (MCI), and Cognitive Normal (CN)
classes, utilizing a small dataset. Additionally, it identified which genes
play a significant role in each of these classification groups. We evaluate the
performance of our approach using metrics including classification accuracy,
recall, precision, and F1 score. The proposed technique holds potential for
extending to radiogenomic-based classification to other diseases.
;Comment: 11 pages
This study estimates the association between blood levels of inflammatory markers and cognitive function in adults with Alzheimer’s disease or mild cognitive impairment. A systematic review and meta-analysis were conducted to synthesize data from studies examining the relationship between blood levels of inflammatory markers and cognitive function in adults with Alzheimer’s disease or mild cognitive impairment. The search strategy was applied to the Medline database through MEDLINE (OVID), WEB OF SCIENCE, SCOPUS, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies were selected based on predefined criteria. We included 84 studies in the qualitative synthesis, with 75 incorporated into the meta-analysis. In blood samples, subjects with Alzheimer’s disease showed significantly higher concentrations of IL-1β (mean difference 0.46 [95% CI: 0.35, 0.58]), IL-6 (3.41 [3.05, 3.78]), MCP-1 (26.20 [14.57, 37.82]), and TNF-α (6.68 [5.97, 7.39]), along with lower concentrations of IL-8 (− 1.46 [− 1.85, − 1.08]) and IL-10 (− 3.20 [− 4.21, − 2.20]). This systematic review and meta-analysis demonstrate significant alterations in inflammatory marker concentrations in blood samples of individuals with Alzheimer’s disease and mild cognitive impairment. Elevated levels of IL-1β, IL-6, MCP-1, and TNF-α, alongside reduced IL-8 and IL-10 levels, suggest a robust inflammatory response associated with Alzheimer’s disease.
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
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.
Alzheimer's disease is a progressive neurodegenerative disorder in which mild cognitive impairment (MCI) marks a critical transition between aging and dementia. Neuroimaging modalities, such as structural MRI, provide biomarkers of this transition; however, their high costs and infrastructure needs limit their deployment at a population scale. Speech analysis offers a non-invasive alternative, but speech-only classifiers are developed independently of neuroimaging, leaving decision boundaries biologically ungrounded and limiting reliability on the subtle CN-versus-MCI distinction. We propose MINT (Multimodal Imaging-to-Speech Knowledge Transfer), a three-stage cross-modal framework that transfers biomarker structure from MRI into a speech encoder at training time. An MRI teacher, trained on 1,228 subjects, defines a compact neuroimaging embedding space for CN-versus-MCI classification. A residual projection head aligns speech representations to this frozen imaging manifold via a combined geometric loss, adapting speech to the learned biomarker space while preserving imaging encoder fidelity. The frozen MRI classifier, which is never exposed to speech, is applied to aligned embeddings at inference and requires no scanner. Evaluation on ADNI-4 shows aligned speech achieves performance comparable to speech-only baselines (AUC 0.720 vs 0.711) while requiring no imaging at inference, demonstrating that MRI-derived decision boundaries can ground speech representations. Multimodal fusion improves over MRI alone (0.973 vs 0.958). Ablation studies identify dropout regularization and self-supervised pretraining as critical design decisions. To our knowledge, this is the first demonstration of MRI-to-speech knowledge transfer for early Alzheimer's screening, establishing a biologically grounded pathway for population-level cognitive triage without neuroimaging at inference.
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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Generative modeling frameworks have emerged as an effective approach to capture high-dimensional image distributions from large datasets without requiring domain-specific knowledge, a capability essential for longitudinal disease progression modeling. Recent generative modeling approaches have attempted to capture progression by mapping images into a latent representational space and then controlling and guiding the representations to generate follow-up images from a baseline image. However, existing approaches impose constraints on distribution learning, leading to latent spaces with limited controllability to generate follow-up images without explicit supervision from subject-specific longitudinal images. In order to enable controlled movements in the latent representational space and generate progression images from a baseline image in an unsupervised manner, we introduce a conditionable Diffusion Auto-encoder framework. The explicit encoding mechanism of image-diffusion auto-encoders forms a compact latent space capturing high-level semantics, providing means to disentangle information relevant for progression. Our approach leverages this latent space to condition and apply controlled shifts to baseline representations for generating follow-up. Controllability is induced by restricting these shifts to a subspace, thereby isolating progression-related factors from subject identity-preserving components. The shifts are implicitly guided by correlating with progression attributes, without requiring subject-specific longitudinal supervision. We validate the generations through image quality metrics, volumetric progression analysis, and downstream classification in Alzheimer's disease datasets from two different sources and disease categories. This demonstrates the effectiveness of our approach for Alzheimer's progression modeling and longitudinal image generation. ;Under Review
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.
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.
Understanding the distinction between causation and correlation is critical in Alzheimer's disease (AD) research, as it impacts diagnosis, treatment, and the identification of true disease drivers. This experiment investigates the relationships among clinical, cognitive, genetic, and biomarker features using a combination of correlation analysis, machine learning classification, and model interpretability techniques. Employing the XGBoost algorithm, we identified key features influencing AD classification, including cognitive scores and genetic risk factors. Correlation matrices revealed clusters of interrelated variables, while SHAP (SHapley Additive exPlanations) values provided detailed insights into feature contributions across disease stages. Our results highlight that strong correlations do not necessarily imply causation, emphasizing the need for careful interpretation of associative data. By integrating feature importance and interpretability with classical statistical analysis, this work lays groundwork for future causal inference studies aimed at uncovering true pathological mechanisms. Ultimately, distinguishing causal factors from correlated markers can lead to improved early diagnosis and targeted interventions for Alzheimer's disease.
The FDA approval of disease-modifying Alzheimer's disease therapies marks a major shift in treatment but exposes a critical challenge: identifying patients during the mild cognitive impairment (MCI) stage when intervention is most effective. Despite early biological changes, most diagnoses occur after significant decline. Drawing from over 180 stakeholder interviews conducted through the NSF I-Corps program reveal major detection gaps across primary care, specialty access, and available tools. This commentary highlights the consequences of delayed diagnosis and proposes translational strategies to align early detection with therapeutic opportunity, positioning MCI as the critical window for Alzheimer's disease intervention.
Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.
BACKGROUND: Comprehensive lipidomic studies have demonstrated strong cross-sectional associations between the blood lipidome and late-onset Alzheimer's disease (AD) dementia and its risk factors, yet the longitudinal relationship between lipidome changes and AD progression remains unclear. METHODS: We employed longitudinal lipidomic profiling on 4730 plasma samples from 1517 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to investigate the temporal evolution of lipidomes among diagnostic groups. At baseline (n = 1393), participants were classified as stable diagnosis status including stable AD (n = 243), stable cognitive normal (CN; n = 337), and stable mild cognitive impairment (MCI; n = 413), or converters (AD converters: n = 329; MCI converters: n = 71). We developed a dementia risk classification model to stratify the non-converting MCI group into dementia-like and non-dementia-like MCI based on their baseline lipidomic profiles, aiming to identify early metabolic signatures predictive of dementia progression. FINDINGS: Longitudinal analysis identified significant associations between the change in ether lipid species (including alkylphosphatidylcholine, alkenylphosphatidylcholine, lysoalkylphosphatidylcholine, and lysoalkenylphosphatidylcholine) and AD dementia conversion. Specifically, AD dementia converters show a 3–4.8% reduction in these ether lipid species compared to the non-converting CN and MCI groups, suggesting metabolic dysregulation as a key feature of AD progression. Further, The Dementia Risk Model effectively distinguished MCI from AD dementia converters (AUC = 0.70; 95% CI: 0.66–0.74). Within the MCI group, the model identified a high-risk subgroup with a twofold higher likelihood of conversion to AD dementia compared to the low-risk group. External validation in the ASPREE cohort confirmed its predictive utility, with the Dementia Risk Score discriminating incident dementia from cognitively normal individuals (C-index = 0.75, 95% CI: 0.73–0.78), improving prediction by 2% over the combination of traditional risk factors and APOE genetic risk factor. Additionally, the Dementia Risk Score was significantly associated with reduced temporal lobar fludeoxyglucose uptake (β = −0.286, p = 1.34 × 10(−4)), higher amyloid PET levels (β = 0.308, p = 4.03 × 10(−4)), and elevated p-tau levels (β = 0.167, p = 2.37 × 10(−2)), reinforcing its pathophysiological relevance in tracking neurodegeneration, amyloid burden, and tau pathology. INTERPRETATION: These findings highlight lipidomic profiling as a potential blood-based biomarker for identifying individuals at high risk of AD progression, offering a scalable, non-invasive approach for early detection, risk stratification, and targeted interventions in AD. FUNDING: The 10.13039/501100000925National Health and Medical Research Council of Australia (#1101320 and #1157607); NHMRC Investigator grant (#GNT1197190); Victorian Government’s Operational Infrastructure Support Program; 10.13039/501100001030National Heart Foundation of Australia, Future Leader Fellowship (#102604), and National Health and Medical Research Council Investigator Grant (#2026325); Investigator grant (#2009965) from the 10.13039/501100000925National Health and Medical Research Council of Australia; a National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095); 10.13039/100000002National Institutes of Health grants: P30AG010133, P30AG072976, R01AG019771, R01AG057739, U19AG024904, R01LM013463, R01AG068193, T32AG071444, U01AG068057, U01AG072177, U19AG074879, R01AG069901, R01AG046171, RF1AG051550, RF1AG057452; 10.13039/100000002National Institutes of Health/10.13039/100000049National Institute on Aging grants RF1AG058942, RF1AG059093, U01AG061359, U19AG063744, and R01AG081322, NIH/NLM R01LM012535; FNIH: DAOU16AMPA.
Background To what extent retinal atrophy in neurodegenerative diseases reflects the severity and/or the chronicity of brain pathology or is a local independent phenomenon remains to be clarified. Moreover, whether retinal atrophy has a clinical (diagnostic and prognostic) value in these diseases remains unclear. Objective To add light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis (ALS) and Kennedy’s disease (KD). Methods Thirty-five ALS, thirty-seven KD, and forty-nine age-matched healthy controls (HC) were included in a one-year longitudinal study. Spectrum-domain optical coherence tomography (OCT) was performed at study entry (T0) and after 12 months (T1). Disease duration and functional rating scale (FRS) for ALS and KD patients were correlated to retinal thicknesses. Results Compared to HC, peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly thinner in both ALS (p = 0.034) and KD (p = 0.003). pRNFL was thinner in KD compared to ALS, but the difference was not significant. In KD, pRNFL atrophy significantly correlated with both disease severity (r = 0.296, p = 0.035) and disease duration (r = – 0.308, p = 0.013) while no significant correlation was found in ALS (disease severity: r = 0.147, p = 0.238; disease duration: r = – 0.093, p = 0.459). During the follow-up, pRNFL thickness remained stable in KD while significantly decreased in ALS (p = 0.043). Conclusions Our study provides evidence of retinal atrophy in both ALS and KD and suggests that retinal thinning is a primary local phenomenon in motoneuron diseases. The clinical value of pRNFL atrophy in KD is worthy of further investigation.
Background Drug development for neurodegenerative disorders (NDDs) is a long, complex, and expensive enterprise. Methods to optimize drug development for NDDs are needed. Basket trials have been widely used in oncology and have been promoted by the Food and Drug Administration as a means of enhancing the efficiency of drug development. Discussion We reviewed clinical trials for NDDs registered on clinicaltrials.gov in the past 10 years. We identified 59 basket trials assessing the impact of treatment on more than one NDD in the trial. Forty-one of the trials were for 25 agents addressing symptoms of NDD such as motor impairment, hypotension, or psychosis. Eighteen of the trials assessed 14 disease-modifying therapies; the principal targets were mitochondrial function, tau biology, or alpha-synuclein aggregation. Basket trials are most common in phase 2 but have been conducted in phase 1, phase 3, and phase 4. The duration and size of the basket trials are highly variable depending on their developmental phase and the intent of the trial. Parkinson’s disease was the most common disorder included in basket trials of symptomatic agents, and Alzheimer’s disease was the most common disorder included in basket trials of disease-modifying therapies. Most of the basket trials of symptomatic agents were sponsored by pharmaceutical companies (29 of 41 trials); similarly, most of the basket trials investigating DMTs in basket trials were sponsored by the biopharmaceutical industry (11/17 trials). Conclusions Basket trials may increase drug development efficiency by reducing redundancy in trial implementation, enhancing recruitment, sharing placebo groups, and using biomarkers relevant to the mechanism of action of the treatment across NDDs. There have been relatively few basket trials including multiple NDDs in the same trial conducted over the past 10 years. The use of the basket trial strategy may represent an opportunity to increase the efficiency of development programs for agents to treat NDDs.
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1^G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1^G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1^G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1^G93A mice ( p = 0.003) while not significantly altering microglial reactivity ( p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation ( p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1^G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect ( p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.
Background This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic lateral sclerosis (ALS). Methods We included 265 newly diagnosed ALS patients during 2016–2022 in Stockholm and 207 ALS-free siblings and partners of the patients as controls. Information on body mass index (BMI), smoking, and history of head injuries, diabetes mellitus, hypercholesterolemia, and hypertension was obtained through the Euro-MOTOR questionnaire at recruitment. Patients were followed from diagnosis until death, invasive ventilation, or November 30, 2022. Results Higher BMI at recruitment was associated with lower risk for ALS (OR 0.89, 95%CI 0.83–0.95), especially among those diagnosed after 65 years. One unit increase in the average BMI during the 3 decades before diagnosis was associated with a lower risk for ALS (OR 0.94, 95%CI 0.89–0.99). Diabetes was associated with lower risk of ALS (OR 0.38, 95%CI 0.16–0.90), while hypercholesterolemia was associated with higher risk of ALS (OR 2.10, 95%CI 1.13–3.90). Higher BMI at diagnosis was associated with lower risk of death (HR 0.91, 95%CI 0.84–0.98), while the highest level of smoking exposure (in pack-years) (HR 1.90, 95%CI 1.20–3.00), hypercholesterolemia (HR 1.84, 95%CI 1.06–3.19), and hypertension (HR 1.76, 95%CI 1.03–3.01) were associated with higher risk of death, following ALS diagnosis. Conclusions Higher BMI and diabetes were associated with lower risk of ALS. Higher BMI was associated with lower risk of death, whereas smoking (especially in high pack-years), hypercholesterolemia, and hypertension were associated with higher risk of death after ALS diagnosis.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.
Background and objectives Primary lateral sclerosis (PLS) is a motor neuron disease characterised by loss of the upper motor neurons. Most patients present with slowly progressive spasticity of the legs, which may also spread to the arms or bulbar regions. It is challenging to distinguish between PLS, early-stage amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). The current diagnostic criteria advise against extensive genetic testing. This recommendation is, however, based on limited data. Methods We aim to genetically characterize a PLS cohort using whole exome sequencing (WES) for genes associated with ALS, HSP, ataxia and movement disorders (364 genes) and C9orf72 repeat expansions. Patients fulfilling the definite PLS criteria by Turner et al. and with available DNA samples of sufficient quality were recruited from an on-going, population-based epidemiological study. Genetic variants were classified according to the ACMG criteria and assigned to groups based on disease association. Results WES was performed in 139 patients and the presence of repeat expansions in C9orf72 was analysed separately in 129 patients. This resulted in 31 variants of which 11 were (likely) pathogenic. (Likely) pathogenic variants resulted in 3 groups based on disease association: ALS-FTD ( C9orf72 , TBK1 ), pure HSP ( SPAST , SPG7 ), “ALS-HSP-CMT overlap” ( FIG4 , NEFL , SPG11 ). Discussion In a cohort of 139 PLS patients, genetic analyses resulted in 31 variants (22%) of which 10 (7%) (likely) pathogenic associated with different diseases (predominantly ALS and HSP). Based on these results and the literature, we advise to consider genetic analyses in the diagnostic work-up for PLS.
Background In the sporadic form of amyotrophic lateral sclerosis (ALS), the pathogenicity of rare variants in the causative genes characterizing the familial form remains largely unknown. To predict the pathogenicity of such variants, in silico analysis is commonly used. In some ALS causative genes, the pathogenic variants are concentrated in specific regions, and the resulting alterations in protein structure are thought to significantly affect pathogenicity. However, existing methods have not taken this issue into account. To address this, we have developed a technique termed MOVA (method for evaluating the pathogenicity of missense variants using AlphaFold2), which applies positional information for structural variants predicted by AlphaFold2. Here we examined the utility of MOVA for analysis of several causative genes of ALS. Methods We analyzed variants of 12 ALS-related genes ( TARDBP , FUS , SETX , TBK1 , OPTN , SOD1 , VCP , SQSTM1 , ANG , UBQLN2 , DCTN1 , and CCNF ) and classified them as pathogenic or neutral. For each gene, the features of the variants, consisting of their positions in the 3D structure predicted by AlphaFold2, pLDDT score, and BLOSUM62 were trained into a random forest and evaluated by the stratified fivefold cross validation method. We compared how accurately MOVA predicted mutant pathogenicity with other in silico prediction methods and evaluated the prediction accuracy at TARDBP and FUS hotspots. We also examined which of the MOVA features had the greatest impact on pathogenicity discrimination. Results MOVA yielded useful results (AUC ≥ 0.70) for TARDBP , FUS , SOD1 , VCP , and UBQLN2 of 12 ALS causative genes. In addition, when comparing the prediction accuracy with other in silico prediction methods, MOVA obtained the best results among those compared for TARDBP , VCP , UBQLN2 , and CCNF . MOVA demonstrated superior predictive accuracy for the pathogenicity of mutations at hotspots of TARDBP and FUS . Moreover, higher accuracy was achieved by combining MOVA with REVEL or CADD. Among the features of MOVA, the x, y, and z coordinates performed the best and were highly correlated with MOVA. Conclusions MOVA is useful for predicting the virulence of rare variants in which they are concentrated at specific structural sites, and for use in combination with other prediction methods.
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.
Introduction Even if electromyography (EMG) is routinely used to confirm the diagnosis of amyotrophic lateral sclerosis (ALS), few studies have analysed the correlation between electrophysiological parameters and clinical characteristics of ALS. We assessed if the quantification of active denervation (AD) and chronic denervation (CD) provides clinicians with information about phenotype, disease progression and survival in ALS patients. Methods We studied a cohort of 689 ALS patients recording the following parameters: age and site of onset, survival, MRC scale for muscle strength evaluation, burden of upper and lower motor signs as measured with specific scales (PUMNS and LMNS, respectively), ALSFRS-R, progression rate (ΔFS), MITOS and King’s Staging systems (KSS). We performed EMG on 11 muscles, and calculated semiquantitative AD and CD scores for each limb, as well as for the bulbar and spinal regions. Results We found a positive correlation between AD and CD scores with LMNS (respectively p = 4.4 × 10^–37 and p = 2.8 × 10^–45) and a negative correlation with MRC (respectively p = 4.5 × 10^–35 and p = 3.0 × 10^–35). Furthermore, patients with higher spinal AD and CD scores had significantly lower ALSFRS-R scores, and higher KSS and MITOS stages. Conversely, only AD was associated to higher ΔFS ( p = 1.0 × 10^–6) and shorter survival ( p = 1.1 × 10^–5). Conclusion Our results confirmed that EMG examination represents not only a diagnostic instrument, but also a prognostic tool. In this context, AD seems to be a reliable predictor of disease’s progression and survival while CD better describes functional disability.
Background Amyotrophic lateral sclerosis (ALS) is an irreversible degenerative disease. Placebo-controlled randomized trials are currently the main trial design to assess the clinical efficacy of drugs for ALS treatment. The aim of this study was to establish models to quantitatively describe the course of ALS, explore influencing factors, and provide the necessary information for ALS drug development. Methods We conducted a comprehensive search of PubMed and the Cochrane Library Central Register for placebo-controlled trials that evaluated treatments for ALS. From these trials, we extracted the clinical and demographic characteristics of participants in the placebo group, as well as outcome data, which encompassed overall survival (OS) and Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores, at various time points. Results In total, 47 studies involving 6118 participants were included. Disease duration and the proportion of patients receiving riluzole were identified as significant factors influencing OS in the placebo group. Specifically, the median OS was 35.5 months for a disease duration of 9 months, whereas it was 20.0 months for a disease duration of 36 months. Furthermore, for every 10% increase in the proportion of patients treated with riluzole (100 mg daily), there was an association with a median OS extension of approximately 0.4 months. The estimated time for the ALSFRS-R score in the placebo group to decrease to 50% of its maximum effect from baseline level was approximately 17.5 months, and the time to reach a plateau was about 40 months. Conclusions The established disease course model of the historical placebo group is valuable in the decision-making process for the clinical development of ALS drugs. It serves not only as an external control to evaluate the efficacy of the tested drug in single-arm trials but also as prior information that aids in accurately estimating the posterior distribution of the disease course in the placebo group during small-sample clinical trials.
Background Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. Aim/hypothesis We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. Methods We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. Results 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. Conclusions Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO registration CRD42020223648.
Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale—Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6–584) pwMND, were included. Sensor type included accelerometers ( n = 9), activity monitors ( n = 4), smartphone apps ( n = 4), gait ( n = 3), kinetic sensors ( n = 3), electrical impedance myography ( n = 1) and dynamometers ( n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed.
In the present study, we investigated the associations of cachexia (loss of muscle, weight and fat) and frailty (loss of weight and muscle) status with the risk of developing amyotrophic lateral sclerosis, because these specific terms are rarely used in this research area. In this prospective study, we extracted cachexia and frailty status from the UK Biobank cohort to study the associations of these conditions (as determined via international classification of disease-10 codes) with amyotrophic lateral sclerosis. There was a greater risk of developing amyotrophic lateral sclerosis among individuals with cachexia and frailty status after adjusting for age, sex, income (pounds), body mass index, UK Biobank centers and smoking status. Among individuals with frailty status: a grip strength of < 21 kg, a slow walking speed, and exhaustion (more than half the days or nearly every day) increase the risk of developing amyotrophic lateral sclerosis. We believe that studying cachexia and frailty status can be used to help define and treat amyotrophic lateral sclerosis.
Background We investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication. Methods Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as > 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls. Results 58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4 , hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions. Conclusions Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication.
Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. More than fifty genes carrying causative or disease-modifying variants have been identified since the 1990s, when the first ALS-associated variant in the gene SOD1 was discovered. The most commonly mutated ALS genes in the European populations include the C9orf72 , SOD1 , TARDBP and FUS . Understanding the genetic causes of ALS within a population is becoming more significant, especially in light of the possible development of personalized medicine. Here, we provide clinical and genetic data on familial and sporadic ALS patients in a Greek-Cypriot population-based cohort. Eighty-nine ALS patients, including 21 familial ALS (fALS) (23.6%) and 68 sporadic ALS (sALS) (76.4%), provided the cohort for variant screening of the most common ALS-associated genes. Moreover, next-generation sequencing (NGS) was also performed to identify rare ALS variants, and in silico prediction tools were applied to predict the downstream effect of the variants detected in our study. The pathogenic hexanucleotide G_4C_2 repeat expansion in C9orf72 was the predominant genetic cause (22.47%) of ALS in our population, while variants in six additional ALS-associated genes were identified, including ALS2 , TARDBP , FIG4 , TBK1 , GLT8D1 , and BICD2.
Objective The clinical manifestation of amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration, whereas frontotemporal dementia (FTD) patients show alterations of behavior and cognition. Both share repeat expansions in C9orf72 as the most prevalent genetic cause. Before disease-defining symptoms onset, structural and functional changes at cortical level may emerge in C9orf72 carriers. Here, we characterized oculomotor parameters and their association to neuropsychological domains in apparently asymptomatic individuals with mutations in ALS/FTD genes. Patients and methods Forty-eight carriers of ALS genes, without any clinical symptoms underwent video-oculographic examination, including 22 subjects with C9orf72 mutation, 17 with SOD1 , and 9 with other ALS associated gene mutations ( n = 3 KIF5A ; n = 3 FUS/FUS + TBK1 ; n = 1 NEK1 ; n = 1 SETX ; n = 1 TDP43 ). A total of 17 subjects underwent a follow-up measurement. Data were compared to 54 age- and gender-matched healthy controls. Additionally, mutation carriers performed a neuropsychological assessment. Results In comparison to controls, the presymptomatic subjects performed significantly worse in executive oculomotor tasks such as the ability to perform correct anti-saccades. A gene mutation subgroup analysis showed that dysfunctions in C9orf72 carriers were much more pronounced than in SOD1 carriers. The anti-saccade error rate of ALS mutation carriers was associated with cognitive deficits: this correlation was increased in subjects with C9orf72 mutation, whereas SOD1 carriers showed no associations. Conclusion In C9orf72 carriers, executive eye movement dysfunctions, especially the increased anti-saccade error rate, were associated with cognitive impairment and unrelated to time. These oculomotor impairments are in support of developmental deficits in these mutations, especially in prefrontal areas.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma ( FUS ) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration. Here, we used human induced pluripotent stem cells (hiPSCs) with a R521H or a P525L mutation in FUS and their isogenic controls to generate oligodendrocyte progenitor cells (OPCs) by inducing SOX10 expression from a TET-On SOX10 cassette. Mutant and control iPSCs differentiated efficiently into OPCs. RNA sequencing identified a myelin sheath-related phenotype in mutant OPCs. Lipidomic studies demonstrated defects in myelin-related lipids, with a reduction of glycerophospholipids in mutant OPCs. Interestingly, FUS ^ R521H OPCs displayed a decrease in the phosphatidylcholine/phosphatidylethanolamine ratio, known to be associated with maintaining membrane integrity. A proximity ligation assay further indicated that mitochondria-associated endoplasmic reticulum membranes (MAM) were diminished in both mutant FUS OPCs. Moreover, both mutant FUS OPCs displayed increased susceptibility to ER stress when exposed to thapsigargin, and exhibited impaired mitochondrial respiration and reduced Ca^2+ signaling from ER Ca^2+ stores. Taken together, these results demonstrate a pathological role of mutant FUS in OPCs, causing defects in lipid metabolism associated with MAM disruption manifested by impaired mitochondrial metabolism with increased susceptibility to ER stress and with suppressed physiological Ca^2+ signaling. As such, further exploration of the role of oligodendrocyte dysfunction in the demise of MNs is crucial and will provide new insights into the complex cellular mechanisms underlying ALS.
Background Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease whose spreading and progression mechanisms are still unclear. The ability to predict ALS prognosis would improve the patients’ quality of life and support clinicians in planning treatments. In this paper, we investigate ALS evolution trajectories using Process Mining (PM) techniques enriched to both easily mine processes and automatically reveal how the pathways differentiate according to patients’ characteristics. Methods We consider data collected in two distinct data sources, namely the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) dataset and a real-world clinical register (ALS–BS) including data of patients followed up in two tertiary clinical centers of Brescia (Italy). With a focus on the functional abilities progressively impaired as the disease progresses, we use two Process Discovery methods, namely the Directly-Follows Graph and the CareFlow Miner, to mine the population disease trajectories on the PRO-ACT dataset. We characterize the impairment trajectories in terms of patterns, timing, and probabilities, and investigate the effect of some patients’ characteristics at onset on the followed paths. Finally, we perform a comparative study of the impairment trajectories mined in PRO-ACT versus ALS–BS. Results We delineate the progression pathways on PRO-ACT, identifying the predominant disabilities at different stages of the disease: for instance, 85% of patients enter the trials without disabilities, and 48% of them experience the impairment of Walking/Self-care abilities first. We then test how a spinal onset increases the risk of experiencing the loss of Walking/Self-care ability as first impairment (52% vs. 27% of patients develop it as the first impairment in the spinal vs. the bulbar cohorts, respectively), as well as how an older age at onset corresponds to a more rapid progression to death. When compared, the PRO-ACT and the ALS–BS patient populations present some similarities in terms of natural progression of the disease, as well as some differences in terms of observed trajectories plausibly due to the trial scheduling and recruitment criteria. Conclusions We exploited PM to provide an overview of the evolution scenarios of an ALS trial population and to preliminary compare it to the progression observed in a clinical cohort. Future work will focus on further improving the understanding of the disease progression mechanisms, by including additional real-world subjects as well as by extending the set of events considered in the impairment trajectories.
Background This study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI). Materials N = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0–13) and (2) that of individual symptom clusters (SC; range = 0–6). Diagnostics were explored against an FBI score ≥ than the 95th percentile of the patients’ distribution. Results Both the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS. Discussion The ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: ≥ 3).
Background Amyotrophic lateral sclerosis (ALS) is a degenerative disease that affects the upper and lower motor neurons. The onset of the disease is frequently focal, usually involving the distal segments of the extremities. A dissociated pattern of muscle atrophy is commonly found in the hands and feet. This study aims to investigate the presence (if any) of split indices in ALS patients and to correlate these indices with confounding factors. A total of 48 people were studied. The control group consists of 24 ALS patients and another 24 age- and gender-matched patients. To assess functional status and muscle strength, the ALS functional rating scale (ALSFRS) and the Medical Research Council (MRC) were used, respectively. Sensory and motor nerve conduction, as well as compound muscle action potential (CMAP) amplitude, were recorded from the muscles of the upper and lower limbs. The electromyographic (EMG) activity of 20 motor unit action potentials (MUAPs) from four different areas was also studied. Results Distal CMAP amplitude was reduced in all tested muscles (especially noticed when comparing the reciprocal muscles). In ALS patients, the split foot index (SFI) is significantly higher, while the split elbow index (SEI) is significantly lower. The split foot index (SFI) was found to be negatively related to disease duration, but positively related to ALSFRS scores. The CMAP amplitude was found to be positively related to the MRC score. Conclusion Ankle dorsiflexion muscles are more involved (dissociated) than plantar flexor muscles, and elbow flexors are more involved than extensors. SFI correlates significantly with disease duration and ALSFRS scores.
Background The rationale for this paper is a description of a patient from Southeast Europe with genetically confirmed Huntington’s disease (HD), coexisting with sporadic, bulbar-onset amyotrophic lateral sclerosis (ALS). To the best of our knowledge, the total number of reported cases with confirmed coexistence of HD and ALS is less than 20. Thus, it is an extremely rare condition speculated to be in a range from 2 to 6 per billion, and data from this part of the World are completely missing. Case presentation Here we report a 72-year-old female with a family history of HD who had generalized chorea and hyperreflexia. Using the PCR-based test for the detection of the CAG triplet repeat expansion, the presence of HD was confirmed. After several months, our patient had progressively developed dysarthria and dysphagia, followed by spastic quadriparesis, generalized muscle wasting, spontaneous fasciculations and sialorrhea. The diagnosis of definite ALS was established based on the patient’s neurological status, electromyography findings and current El Escorial criteria. Conclusions Our study emphasizes the need for the recognition of the co-occurrence of clinically distinct and rare genetic disorders, such as HD and ALS. New insights from the studies dealing with these rare topics could significantly contribute to the contest of new gene therapy trials.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 – 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 – 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 – 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 – 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 – 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 – 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.
Background and purpose Muscle ultrasonography has been increasingly recognized as a useful tool for detection of fasciculations. Separately, concordance between dominant hand and onset side has been reported in amyotrophic lateral sclerosis (ALS). The aim of this study was to reveal the distribution of fasciculations in the whole body, focusing on handedness. Methods In 106 consecutive patients with ALS, muscle ultrasonography was systematically performed in 11 muscles (the tongue, and bilateral biceps brachii, 1st dorsal interosseous [FDI], T10-paraspinalis, vastus lateralis and tibialis anterior muscles). The fasciculation intensity was scored from 0 to 3 for each muscle. Results Fasciculations were more frequently found in the limb muscles than the tongue and paraspinalis. Side and handedness analyses revealed that fasciculation intensity in FDI was significantly more prominent on the right (median [inter-quartile range] 2 [0 - 3]) than left (1.5 [0 - 3]; p = 0.016), and in the dominant hand (2 [1 - 3]) than non-dominant side (1.5 [0 - 3]; p = 0.025). The differences were greater in patients with upper limb onset. There were no side differences in the lower limb muscles. Multivariate analyses showed that male patients had more frequent fasciculations in the dominant FDI (β = 0.22, p < 0.05). Conclusion More intensive fasciculations are present in the FDI in the dominant hand and gender might be associated with fasciculation intensities. This distribution pattern of fasciculations might be associated with pathogenesis of ALS.
Background To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case–control study. Methods Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value. Results High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03–2.49, top vs. bottom quartile), but not HDL, LDL, LDL–HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19–2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11–2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48–0.96). Conclusion The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.
Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations in SPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circulation is associated with ALS. Here, we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis. Among the different lipids, accumulation of ceramides, arachidonic acid, and lysophosphatidylcholine is commonly emerging as detrimental to motor neurons. We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
BACKGROUND: TAF1L may play an important role in the occurrence and development of gastric cancer (GC), but the correlation between the expression of TAF1L and the clinicopathological factors and prognosis of GC is still unclear. METHODS: A total of 1053 GC patients in Zhejiang Cancer Hospital between January 1st, 2018 to December 31th, 2019 were screened. Finally, 120 patients met the inclusion criteria. TAF1L expression was detected by immunohistochemistry, and the correlations of TAF1L in clinicopathological characteristics and prognosis were analyzed. TCGA GC dataset was used to perform further bioinformatics analysis. RESULTS: In this study, TAF1L expression was evaluated in 120 clinical samples of GC. TAF1L expression was higher in tumor tissues and was associated with tumor differentiation (p = 0.046), signet-ring cells (p = 0.043), dMMR status (p = 0.011), lympho-vascular invasion (p = 0.038), and neural invasion (p = 0.005) in our cohort. Cases with high expression of TAF1L presented worse mean OS than those with low expression (40.3 months vs. 51.8 months, p = 0.019), and the difference was also significant in HER2-positive cases (20.9 months vs. 51.2 months, p = 0.007) as well as pMMR cases (38.8 months vs. 51.6 months, p = 0.006). Multivariate Cox regression analysis showed that TAF1L (HR = 2.044, 95%CI = 1.007–4.147, p = 0.048) and HER2 status (HR = 2.383, 95%CI = 1.087–5.222, p = 0.030) were independent prognosis factors of these patients. In subgroup analysis, TAF1L was the independent prognostic risk factor in HER2-positive patients (HR = 6.736, 95%CI = 1.373–33.032, p = 0.019). and pMMR patients (HR = 2.291, 95%CI = 1.126–4.660, p = 0.022). Besides, HER2 status was the independent prognostic risk factor in TAF1L-H patients (HR = 4.832, 95%CI = 1.908–12.239, p = 0.001). TCGA dataset also indicated the higher expression of TAF1L in tumors than normal tissues (p < 0.001). High TAF1L expression is linked to worse survival in MSS (11.0 months vs. 35.0 months, p = 0.0046) groups, and is negatively associated with overall survival in HER2-positive cases (24.0 months vs. 57.0 months, p = 0.0039). CONCLUSION: TAF1L is closely related to the occurrence and development of GC. Our results suggested that TAF1L is a significant biomarker for predicting prognosis of GC and may play an important role in immunotherapy and targeted therapy.
Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in
the United States and the second leading cause of cancer-related death among
both genders. Notably, CRC is the leading cause of cancer in younger men less
than 50 years old. Colonoscopy is considered the gold standard for the early
diagnosis of CRC. Skills vary significantly among endoscopists, and a high miss
rate is reported. Automated polyp segmentation can reduce the missed rates, and
timely treatment is possible in the early stage. To address this challenge, we
introduce \textit{\textbf{\ac{FANetv2}}}, an advanced encoder-decoder network
designed to accurately segment polyps from colonoscopy images. Leveraging an
initial input mask generated by Otsu thresholding, FANetv2 iteratively refines
its binary segmentation masks through a novel feedback attention mechanism
informed by the mask predictions of previous epochs. Additionally, it employs a
text-guided approach that integrates essential information about the number
(one or many) and size (small, medium, large) of polyps to further enhance its
feature representation capabilities. This dual-task approach facilitates
accurate polyp segmentation and aids in the auxiliary classification of polyp
attributes, significantly boosting the model's performance. Our comprehensive
evaluations on the publicly available BKAI-IGH and CVC-ClinicDB datasets
demonstrate the superior performance of FANetv2, evidenced by high dice
similarity coefficients (DSC) of 0.9186 and 0.9481, along with low Hausdorff
distances of 2.83 and 3.19, respectively. The source code for FANetv2 is
available at https://github.com/xxxxx/FANetv2.
Background The Association of Breast Surgeons of India (ABSI) periodically publishes national consensus statements to adapt evidence-based breast cancer management to Indian realities. This 2025 update aimed to develop pragmatic, scenario-based guidance and assess concordance between expert recommendations and current clinical practice. Methods An expert panel formulated 40 single-best-answer questions spanning screening, diagnosis, surgery, axillary management, reconstruction, systemic therapy, radiotherapy, genetics, survivorship, and delivery of care. Responses were collected from panel experts ( n = 24) and delegates ( n = 159) at the ABSI Annual Meeting 2025 (Kolkata) using identical Google Forms. Concordance was defined a priori: almost 100% (same top choice, ≥ 90% in both groups), small discordance (same top, ≤ 10% difference), medium discordance (same top, 10–30% difference), significant discordance (> 30% difference or different top choice). Option distributions were compared using chi-square tests. Results Of 40 questions, 10 showed almost complete concordance, 12 small discordance, 17 medium discordance, and 1 significant discordance. Highest agreement included the following: empowering community health officers for early detection, preference for breast-conserving surgery when feasible, SLNB for node-negative early breast cancer, and mandatory fertility/psycho-sexual counselling for young patients. Divergences were noted in HER2 therapy duration in low-risk disease, radiotherapy in DCIS, reconstruction choices, and axillary management in Z0011-eligible macro-metastasis. Conclusion Indian experts and practising surgeons show strong alignment on core surgical principles and supportive care priorities. Targeted guidance is needed for areas of practice variation to ensure uniform, evidence-informed care delivery in India.
The current standard for detecting human epidermal growth factor receptor 2
(HER2) status in breast cancer patients relies on HER2 amplification,
identified through fluorescence in situ hybridization (FISH) or
immunohistochemistry (IHC). However, hematoxylin and eosin (H\&E) tumor stains
are more widely available, and accurately predicting HER2 status using H\&E
could reduce costs and expedite treatment selection. Deep Learning algorithms
for H&E have shown effectiveness in predicting various cancer features and
clinical outcomes, including moderate success in HER2 status prediction. In
this work, we employed a customized weak supervision classification technique
combined with MoCo-v2 contrastive learning to predict HER2 status. We trained
our pipeline on 182 publicly available H&E Whole Slide Images (WSIs) from The
Cancer Genome Atlas (TCGA), for which annotations by the pathology team at Yale
School of Medicine are publicly available. Our pipeline achieved an Area Under
the Curve (AUC) of 0.85 across four different test folds. Additionally, we
tested our model on 44 H&E slides from the TCGA-BRCA dataset, which had an HER2
score of 2+ and included corresponding HER2 status and FISH test results. These
cases are considered equivocal for IHC, requiring an expensive FISH test on
their IHC slides for disambiguation. Our pipeline demonstrated an AUC of 0.81
on these challenging H&E slides. Reducing the need for FISH test can have
significant implications in cancer treatment equity for underserved
populations.
After breast cancer diagnosis, individuals have to cope with various psychological, social, and physical consequences. One such consequence is chronic pain, which can persist even after the completion of active treatments and detrimentally impact quality of life. The published literature highlights the impact of chronic pain on cognitive functions and on decision-making processes. However, little is known about the imbalance in decision-making among cancer survivors suffering from chronic pain. This study aims to explore the cognitive impairment associated with risky decision-making in breast cancer survivors experiencing chronic pain, using the Iowa Gambling Task (IGT). Sixty women voluntarily participated in this prospective, cross-sectional study. Among them, twenty had a history of breast cancer and exhibited a significant level of chronic pain, twenty had previously received a cancer diagnosis but did not experience chronic pain, and twenty had not been diagnosed with cancer. The results revealed that women with chronic pain tend to make significantly more disadvantageous choices in the IGT compared to the other groups. Moreover, participants with chronic pain tend to believe that circumstances will change regardless of their efforts to achieve something. This way of thinking may contribute to reinforcing the observed imbalance in decision-making. Our hypothesis suggests that chronic pain may trigger a “ Cascade Effect ”, exerting multiple influences on decision-making and behaviors. The cognitive overload provoked by chronic pain in breast cancer survivors may not only affect individual cognitive functions, but also have a “ Cascade Effect ” on other psychological dimensions.
Background An increased risk of secondary primary malignancies (SPMs) has been shown in diffuse large B-cell lymphoma (DLBCL) patients after treatment. However, research on SPM outcomes in DLBCL patients is limited. Methods Utilizing the population-based Surveillance, Epidemiology, and End Results Registry (SEER), the authors examined the characteristics, overall survival (OS), and treatments in DLBCL patients who developed secondary cancers of the breast, prostate, lung, colon/rectum, bladder cancers, melanoma, myeloma, and acute leukemia. Each patient was matched by age, sex, race, year of diagnosis, and stage to 50 controls from a general population diagnosed with a non-DLBCL primary the cancer. Results Patients with antecedent DLBCL who developed lung cancer (37.3% vs. 18.3%, P < 0.001) or colon/rectum cancer (45.5% vs. 39.6%, P = 0.032) were more commonly diagnosed at an early stage. Compared with patients in the control group, patients with antecedent DLBCL who developed prostate cancer, melanoma, myeloma, and acute leukemia had significantly worse OS. Conversely, patients who developed lung cancer after their antecedent DLBCL diagnosis showed markedly better OS. Amongst patients with antecedent DLBCL aged over 60, intensive therapy was associated with improved OS compared to supportive care in those being treated for a SPM diagnosis of breast, prostate, lung, colon/rectum, melanoma or bladder cancer, but not myeloma or acute leukemia. The rates of surgical resection were the same between patients with antecedent DLBCL and those in the control group, except for lower prostatectomy rates and higher lobectomy rates among patients with antecedent DLBCL. Conclusions Our findings can assist clinicians in better understanding the survival outcomes of SPMs among patients with antecedent DLBCL while suggesting that long-term follow-up might be useful to detect DLBCL survivors who developed SPMs.
Artificial intelligence (AI) and machine learning (ML) have emerged as transformative tools across the oncology drug development pipeline, spanning from early discovery and compound screening to clinical trial optimization and regulatory oversight. With the growing complexity of cancer biology and the rising demand for precision medicine, AI technologies offer new strategies to accelerate therapeutic innovation, reduce development costs, and improve clinical outcomes. This review synthesizes recent advancements in AI-driven oncology, integrating perspectives from computational modeling, predictive analytics, clinical decision-making, and evolving regulatory frameworks. We highlight how AI-enabled platforms are being employed to identify druggable targets, optimize molecular design, predict drug target interactions, and support preclinical and clinical decision-making. Special attention is given to advanced architectures such as cascade deep forest models, deep learning networks, and the transformative impact of large language models and multimodal AI, including AlphaFold 3, which have demonstrated superior performance in drug target interaction prediction and de novo compound generation. Beyond technical accuracy, we emphasize the importance of “model actionability,” a concept rooted in the ability of AI models to reduce diagnostic and therapeutic uncertainty, thus enhancing their practical value in clinical oncology. Furthermore, we discuss the U.S. Food and Drug Administration’s (FDA) proactive engagement with AI/ML applications, particularly in the context of clinical trials, safety monitoring, and real-world evidence generation. The integration of AI into regulatory science underscores the need for transparency, contextual validation, and risk-based oversight. By bridging scientific innovation with clinical utility and regulatory expectations, this review underscores the pivotal role of AI in advancing oncology drug development and shaping the future of cancer care.
Obesity and cancer are two of the most significant global public health concerns worldwide. Exercise in preventing and managing these diseases has become a prominent area of research, and BSc sport and exercise science (SES) graduates are among the professionals involved in designing exercise programs for these populations. The aims of the present study were (1) to quantify the number of teaching hours focused on exercise in patients with cancer or overweight/obesity and (2) to collect perceptions of SES teachers of whether these hours are enough to prescribe exercise to these populations adequately. An online survey was sent to 97 university teachers from 58 different institutions in Spain offering the sport and exercise sciences degree. The survey included questions designed to ascertain the number of hours lectured on the topics of exercise and cancer or overweight/obesity. Additionally, it aimed to gather teachers’ perceptions of how prepared students were to work with these populations. Seventy-six teachers (representing a 78% response rate) from 52 different centers (representing 88% of the centers) completed the survey. The teachers reported an average of 8.7 class hours dedicated to exercise and cancer and 17.1 class hours dedicated to exercise in patients with overweight/obesity. Teachers expressed low satisfaction with the number of class hours allocated to cancer education (2.2 points out of 5) and a neutral response regarding the allocation of hours to overweight/obesity (3.1 points out of 5). The findings of the current study suggest that Spanish SES students may be receiving a limited amount of instruction in the area of exercise prescription for patients with cancer and overweight/obesity. Although the curriculum is explicitly dedicated to training SES students, teachers believe that additional training in specific exercise prescription for people with cancer would enhance SES qualifications.
HSPA1A, a major heat shock protein, is known to translocate to the plasma membrane (PM) in response to cellular stress and cancer, where it plays protective roles in membrane integrity and stress resistance. Although phosphatidylinositol 4-phosphate [PI(4)P] is essential in this translocation, the signals that trigger and facilitate HSPA1A’s movement remain undefined.Given that membrane lipid composition dynamically shifts during stress, we hypothesized that heat shock-induced PI(4)P changes are crucial for HSPA1A’s PM localization. To test this hypothesis, we investigated the mechanisms driving PI(4)P changes and HSPA1A PM localization under heat shock. Lipidomic analysis, enzyme-linked immunosorbent assay (ELISA), and confocal imaging revealed a rapid PI(4)P increase at the PM post-heat shock, with levels peaking at 0 hours and declining by 8 hours. RNA sequencing and protein quantification indicated no transcriptional increase in PI4KIII alpha, the kinase responsible for PI(4)P synthesis, suggesting an alternative regulatory mechanism. Hypothesizing that heat shock enhances PI4KIII alpha activity, we performed ELISA coupled with immunoprecipitation, confirming a significant rise in PI4KIII alpha activity following heat shock. Functional analyses further demonstrated that RNAi-mediated PI4KIII alpha depletion or pharmacological PI(4)P reduction, using GSK-A1, impairs HSPA1A’s localization to the PM, confirming that HSPA1A translocation is PI(4)P-dependent. Our findings identify PI4KIII alpha activity as a key regulator of PI(4)P accumulation and subsequent HSPA1A recruitment to the PM in stressed and cancer cells. This lipid-mediated response offers new insights into stress adaptation and potentially modifiable pathways for therapeutic interventions to control HSPA1A function in cancer.
High Mobility Group A2 (HMGA2) oncofetal proteins are a distinct category of Transcription Factors (TFs) known as “architectural factors” due to their lack of direct transcriptional activity. Instead, they modulate the three-dimensional structure of chromatin by binding to AT-rich regions in the minor grooves of DNA through their AT-hooks. This binding allows HMGA2 to interact with other proteins and different regions of DNA, thereby regulating the expression of numerous genes involved in carcinogenesis. Consequently, multiple mechanisms exist to finely control HMGA2 protein expression at various transcriptional levels, ensuring precise concentration adjustments to maintain cellular homeostasis. During embryonic development, HMGA2 protein is highly expressed but becomes absent in adult tissues. However, recent studies have revealed its re-elevation in various cancer types. Extensive research has demonstrated the involvement of HMGA2 protein in carcinogenesis at multiple levels. It intervenes in crucial processes such as cell cycle regulation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, cancer cell stemness, and DNA damage repair mechanisms, ultimately promoting cancer cell survival. This comprehensive review provides insights into the HMGA2 protein, spanning from the genetic regulation to functional protein behavior. It highlights the significant mechanisms governing HMGA2 gene expression and elucidates the molecular roles of HMGA2 in the carcinogenesis process. Graphical Abstract
Introduction This article explores the potential role of artificial intelligence (AI) in enhancing the early detection and diagnosis of head and neck squamous cell carcinoma (HNSCC). Discussion The latest data reflecting the growing disparity in HNSCC incidence and mortality across different regions and socioeconomic groups are reviewed, stressing the importance of early detection in improving outcomes. The potential role of AI in improving the accuracy and consistency of endoscopic procedures, particularly in resource-limited settings with limited access to specialized healthcare is discussed. By analyzing current technologies and case studies, the review highlights how AI can democratize access to early cancer detection, improve survival rates, and reduce the financial burden on patients. The integration of AI into healthcare systems can lead to significant cost savings and enhanced accessibility, particularly in underserved populations, where HNSCC is projected to rise dramatically in the coming decades.
OBJECTIVE: To build a nomogram model for predicting the risk of anastomotic leakage (AL) postoperative low rectal cancer based on Lasso-Logistic regression. METHODS: A total of 482 patients with rectal cancer who underwent low rectal cancer surgery in our hospital from June 2017 to May 2023 were selected as the training set, and 127 patients with rectal cancer who underwent low rectal cancer surgery in our hospital from June 2023 to April 2025 were selected as the validation set. According to whether AL occurred postoperative, the patients in the training set were divided into AL group (n = 54) and N-AL group (n = 428). The data of each group were collected, and the influencing factors of AL in patients postoperative with rectal cancer in the training set were analyzed by Lasso-Logistic regression model. H-L goodness-of-fit test, ROC curve and calibration curve were used to analyze the discrimination and consistency of the model. The nomogram model was validated using the validation set. The DCA curve was used to evaluate the clinical utility of the model. RESULTS: In the training set, the AL group had a higher proportion of patients with tumor stage ≥ T3 and longer operation times compared to the N-AL group; additionally, fewer AL patients had a protective stoma, and the tumor was located a shorter distance from the tumor to the anal verge than in the N-AL group. (P < 0.05). Lasso-Logistic regression analysis showed that when the penalty coefficient λ = 0.02735463, the model demonstrated good performance, gender (OR = 3.107), NRS2002 score (OR = 8.619), protective stoma (OR = 0.297), distance from tumor to anal verge (OR = 0.284), operation time (OR = 1.033) were the influencing factors of postoperative AL in low rectal cancer (P < 0.05). The 5 influencing factors were introduced into R software to establish a nomogram model for the risk of postoperative AL in low rectal cancer. The area under the ROC curve was 0.940. H-L goodness of fit test showed that there was no significant difference between the predicted value of the model and the actual observed value (χ(2) = 6.438, P = 0.598). The slope of the calibration curve was close to 1. The validation set showed that the nomogram model had good discrimination and consistency. The DCA curve showed that the model had high clinical utility and net benefit when the risk threshold was between 0.08 and 0.85. CONCLUSION: Gender, NRS2002 rating, diverting ostomy, distance from tumor to anal margin, and operation time are all influencing factors of postoperative AL in low rectal cancer. The nomogram prediction model based on Lasso-Logistic regression has high consistency, discrimination and clinical application value. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04128-y.
Cancer is one of the main causes of morbidity and mortality in Spain and has a significant impact in the workplace, where exposure to carcinogens in the work environment can increase the risk of developing this disease. The lack of communication between oncologists and occupational physicians limits the accurate assessment of cancer as an occupational disease and as a cause of disability. In 2020, the Spanish Society of Medical Oncology (SEOM) and the Spanish Association of Occupational Medicine Specialists (AEEMT) launched a joint initiative to strengthen prevention, reporting, and management of occupational cancer. This consensus provides a structured framework for assessing the occupational origin of cancer, facilitating case notification and classification as occupational contingencies, and supporting informed evaluations of disability and work reintegration in patients with cancer. The collaboration between both societies aims not only to advance occupational cancer prevention but also to promote evidence-based strategies for return-to-work planning.
BACKGROUND: Dupilumab has been added to National Cancer Comprehensive Network (NCCN) guidelines as a therapeutic strategy for managing certain cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy. However, little is known about the implications of dupilumab for cancer outcomes in this population. In this multi-institutional study, we evaluate the impact of dupilumab treatment on survival among ICI recipients. METHODS: We conducted a muti-institutional retrospective cohort study of ICI recipients from the Mass General Brigham Healthcare System and Dana-Farber Cancer Institute. The dupilumab group was compared to two control groups who did not receive dupilumab: with and without cirAEs (control groups 1 and 2, respectively) that were 1:2 matched on sex, race, age at ICI initiation, Charlson Comorbidity Score, year of ICI initiation, and ICI type. Manual chart review was performed to obtain cirAE characteristics, systemic glucocorticoid use, dupilumab treatment, vital status, and last contact date. Time-varying multivariable Cox proportional hazards regressions were used to evaluate the impact of dupilumab on overall survival, adjusted for sex, race, age at ICI initiation, ICI type, Charlson Comorbidity Index score, cancer type, cancer stage at ICI initiation, and systemic glucocorticoid use. RESULTS: A total of 53 cirAE patients treated with dupilumab were compared to two control groups of 106 patients each. Most patients receiving dupilumab demonstrated either complete or partial resolution of their cirAE (88.7%). In multivariable modeling, the overall survival of the dupilumab group was not significantly different from control group 1 (HR=0.74, 95% CI:0.35-1.60, p=0.5) or control group 2 (HR=0.70, 95% CI:0.32-1.51, p=0.4). However, the use of systemic glucocorticoids within two years after ICI initiation was associated with poorer overall survival when comparing the dupilumab group to control group 1 (HR=2.03, 95% CI:1.04-3.96, p=0.039) and control group 2 (HR=2.21, 95% CI:1.25-3.91, p=0.006). CONCLUSIONS: This study suggests that dupilumab is an effective therapeutic option for recalcitrant cirAEs and does not adversely impact mortality. Due to the observed detrimental effects of systemic glucocorticoid therapy, this study supports the need to shift away from systemic glucocorticoid immunosuppression and towards targeted immune modulators for irAE management that are less detrimental to ICI response. • WHAT IS ALREADY KNOWN ON THIS TOPIC: Current guidelines recommend the use of dupilumab in the treatment of certain moderate to severe cutaneous immune related adverse events (cirAE) and systemic glucocorticoids for others. Previous studies have shown dupilumab to be effective for steroid refractory cirAEs; (1) however, the impact dupilumab on survival outcomes among recipients of immune checkpoint inhibitor therapy (ICI) remains under studied. • WHAT THIS STUDY ADDS: This study concludes that dupilumab is an effective modality to treat cirAEs, with 88.7% of patients responding to treatment. Additionally, this study demonstrates a 206-day average delay from cirAE onset to dupilumab treatment suggesting the need for more timely consideration of this therapeutic option. Finally, our results demonstrated that dupilumab does not increase mortality among ICI recipients. • HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: The results of this study suggest that use of dupilumab in the treatment of cirAEs is effective and does not adversely impact mortality in the cancer population. Based on these findings, clinicians should consider dupilumab treatment for cirAEs in the appropriate clinical setting. Moreover, this study provides further evidence for the use of targeted immune modulators as preferred over more commonly utilized broad-based glucocorticoid immunosuppression for the management of immune related adverse events in the setting of ICI therapy.
Objective To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions. Method Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested. Result Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734–0.941) and 0.897 (0.775–1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients. Conclusion The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.
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
Recent advances in machine learning are transforming medical image analysis,
particularly in cancer detection and classification. Techniques such as deep
learning, especially convolutional neural networks (CNNs) and vision
transformers (ViTs), are now enabling the precise analysis of complex
histopathological images, automating detection, and enhancing classification
accuracy across various cancer types. This study focuses on osteosarcoma (OS),
the most common bone cancer in children and adolescents, which affects the long
bones of the arms and legs. Early and accurate detection of OS is essential for
improving patient outcomes and reducing mortality. However, the increasing
prevalence of cancer and the demand for personalized treatments create
challenges in achieving precise diagnoses and customized therapies. We propose
a novel hybrid model that combines convolutional neural networks (CNN) and
vision transformers (ViT) to improve diagnostic accuracy for OS using
hematoxylin and eosin (H&E) stained histopathological images. The CNN model
extracts local features, while the ViT captures global patterns from
histopathological images. These features are combined and classified using a
Multi-Layer Perceptron (MLP) into four categories: non-tumor (NT), non-viable
tumor (NVT), viable tumor (VT), and none-viable ratio (NVR). Using the Cancer
Imaging Archive (TCIA) dataset, the model achieved an accuracy of 99.08%,
precision of 99.10%, recall of 99.28%, and an F1-score of 99.23%. This is the
first successful four-class classification using this dataset, setting a new
benchmark in OS research and offering promising potential for future diagnostic
advancements.
Background Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. Methods We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. Results In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. Conclusions HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.
Data limitation is a significant challenge in applying deep learning to
medical images. Recently, the diffusion probabilistic model (DPM) has shown the
potential to generate high-quality images by converting Gaussian random noise
into realistic images. In this paper, we apply the DPM to augment the deep
ultraviolet fluorescence (DUV) image dataset with an aim to improve breast
cancer classification for intraoperative margin assessment. For classification,
we divide the whole surface DUV image into small patches and extract
convolutional features for each patch by utilizing the pre-trained ResNet.
Then, we feed them into an XGBoost classifier for patch-level decisions and
then fuse them with a regional importance map computed by Grad-CAM++ for whole
surface-level prediction. Our experimental results show that augmenting the
training dataset with the DPM significantly improves breast cancer detection
performance in DUV images, increasing accuracy from 93% to 97%, compared to
using Affine transformations and ProGAN.
;Comment: IEEE International Symposium on Biomedical Imaging 2024
Cancer cachexia is an involuntary weight loss condition characterized by systemic metabolic disorder. A comprehensive flux characterization of this condition however is lacking. Here, we systematically isotope traced eight major circulating nutrients in mice bearing cachectic C26 tumors (cxC26) and food intake-matched mice bearing non-cachectic C26 tumors (ncxC26). We found no difference in whole-body lipolysis and proteolysis, ketogenesis, or fatty acid and ketone oxidation by tissues between the two groups. In contrast, compared to ncxC26 mice ad libitum, glucose turnover flux decreased in food intake-controlled ncxC26 mice but not in cxC26 mice. Similarly, sustained glucose turnover flux was observed in two autochthonous cancer cachexia models despite reduced food intake. We identified glutamine and alanine as responsible for sustained glucose production and tissues with altered use of glucose and lactate in cxC26 mice. We provide a comprehensive view of metabolic alterations in cancer cachexia revealing those distinct from decreased nutrient intake. HIGHLIGHTS: Quantitative fluxomics of cancer cachexia under matched food intake and body weight. Intact lipolysis, proteolysis, ketogenesis, and lipid oxidation in cachectic mice. Sustained glucose consumption in cachectic mice despite reduced food intake. Increased glucose production from glutamine and alanine in cachectic mice.
Treatment selection in breast cancer is guided by molecular subtypes and
clinical characteristics. However, current tools including genomic assays lack
the accuracy required for optimal clinical decision-making. We developed a
novel artificial intelligence (AI)-based approach that integrates digital
pathology images with clinical data, providing a more robust and effective
method for predicting the risk of cancer recurrence in breast cancer patients.
Specifically, we utilized a vision transformer pan-cancer foundation model
trained with self-supervised learning to extract features from digitized
H&E-stained slides. These features were integrated with clinical data to form a
multi-modal AI test predicting cancer recurrence and death. The test was
developed and evaluated using data from a total of 8,161 female breast cancer
patients across 15 cohorts originating from seven countries. Of these, 3,502
patients from five cohorts were used exclusively for evaluation, while the
remaining patients were used for training. Our test accurately predicted our
primary endpoint, disease-free interval, in the five evaluation cohorts
(C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p<0.001]). In a direct
comparison (n=858), the AI test was more accurate than Oncotype DX, the
standard-of-care 21-gene assay, achieving a C-index of 0.67 [0.61-0.74] versus
0.61 [0.49-0.73], respectively. Additionally, the AI test added independent
prognostic information to Oncotype DX in a multivariate analysis (HR: 3.11
[1.91-5.09, p<0.001)]). The test demonstrated robust accuracy across major
molecular breast cancer subtypes, including TNBC (C-index: 0.71 [0.62-0.81],
HR: 3.81 [2.35-6.17, p=0.02]), where no diagnostic tools are currently
recommended by clinical guidelines. These results suggest that our AI test
improves upon the accuracy of existing prognostic tests, while being applicable
to a wider range of patients.
Recently, Computer-Aided Diagnosis (CAD) systems have emerged as
indispensable tools in clinical diagnostic workflows, significantly alleviating
the burden on radiologists. Nevertheless, despite their integration into
clinical settings, CAD systems encounter limitations. Specifically, while CAD
systems can achieve high performance in the detection of lung nodules, they
face challenges in accurately predicting multiple cancer types. This limitation
can be attributed to the scarcity of publicly available datasets annotated with
expert-level cancer type information. This research aims to bridge this gap by
providing publicly accessible datasets and reliable tools for medical
diagnosis, facilitating a finer categorization of different types of lung
diseases so as to offer precise treatment recommendations. To achieve this
objective, we curated a diverse dataset of lung Computed Tomography (CT)
images, comprising 330 annotated nodules (nodules are labeled as bounding
boxes) from 95 distinct patients. The quality of the dataset was evaluated
using a variety of classical classification and detection models, and these
promising results demonstrate that the dataset has a feasible application and
further facilitate intelligent auxiliary diagnosis.
Background The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS. Methods We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460). Results From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04). Conclusions This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
Patients with hereditary breast and ovarian cancer syndrome (HBOC) are associated with an increased risk of developing pancreatic cancer (PC) than the general population. There is no consensus about the clinical value of F-18-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in patients with HBOC. We report a patient with HBOC in whom PC was detected incidentally by PET/CT. A 48-year-old woman complaining of a right breast mass sought evaluation at our hospital. Her older brother died of PC at 49 years of age. Histologic analysis of the breast mass revealed breast cancer (BC). FDG-PET/CT showed unanticipated FDG accumulation in the pancreas. Magnetic resonance cholangiopancreatography (MRCP) revealed a mass in the pancreas approximately 25mm in size. Endoscopic ultrasound guided-fine needle aspiration biopsy (EUS-FNA) demonstrated PC. Genetic testing showed a BRCA2 pathologic variant [NM_000059.4(BRCA2): c.9076C > T (p.Gln3026Ter)]. She was referred to a university hospital and underwent surgery after neoadjuvant chemotherapy for PC. It is difficult to detect operable PC in most patients. The diagnostic utility of PET/CT for PC in high-risk patients, such as those with HBOC, is undetermined. Our case has demonstrated the clinical value of PET/CT in detecting incidental PC in HBOC patients.
Experts weigh in on the risks of moderate drinking — and how people should assess them. Experts weigh in on the risks of moderate drinking — and how people should assess them.
Aspect Extraction (AE) is a key task in Aspect-Based Sentiment Analysis (ABSA), yet it remains difficult to apply in low-resource and code-switched contexts like Taglish, a mix of Tagalog and English commonly used in Filipino e-commerce reviews. This paper introduces a comprehensive AE pipeline designed for Taglish, combining rule-based, large language model (LLM)-based, and fine-tuning techniques to address both aspect identification and extraction. A Hierarchical Aspect Framework (HAF) is developed through multi-method topic modeling, along with a dual-mode tagging scheme for explicit and implicit aspects. For aspect identification, four distinct models are evaluated: a Rule-Based system, a Generative LLM (Gemini 2.0 Flash), and two Fine-Tuned Gemma-3 1B models trained on different datasets (Rule-Based vs. LLM-Annotated). Results indicate that the Generative LLM achieved the highest performance across all tasks (Macro F1 0.91), demonstrating superior capability in handling implicit aspects. In contrast, the fine-tuned models exhibited limited performance due to dataset imbalance and architectural capacity constraints. This work contributes a scalable and linguistically adaptive framework for enhancing ABSA in diverse, code-switched environments.
Composite commits, which entangle multiple unrelated concerns, are prevalent in software development and significantly hinder program comprehension and maintenance. Existing automated untangling methods, particularly state-of-the-art graph clustering-based approaches, are fundamentally limited by two issues. (1) They over-rely on structural information, failing to grasp the crucial semantic intent behind changes, and (2) they operate as ``single-pass'' algorithms, lacking a mechanism for the critical reflection and refinement inherent in human review processes. To overcome these challenges, we introduce Atomizer, a novel collaborative multi-agent framework for composite commit untangling. To address the semantic deficit, Atomizer employs an Intent-Oriented Chain-of-Thought (IO-CoT) strategy, which prompts large language models (LLMs) to infer the intent of each code change according to both the structure and the semantic information of code. To overcome the limitations of ``single-pass'' grouping, we employ two agents to establish a grouper-reviewer collaborative refinement loop, which mirrors human review practices by iteratively refining groupings until all changes in a cluster share the same underlying semantic intent. Extensive experiments on two benchmark C# and Java datasets demonstrate that Atomizer significantly outperforms several representative baselines. On average, it surpasses the state-of-the-art graph-based methods by over 6.0% on the C# dataset and 5.5% on the Java dataset. This superiority is particularly pronounced on complex commits, where Atomizer's performance advantage widens to over 16%. ;Accepted by ICSE 2026
Federated Domain Generalization (FDG) aims to collaboratively train a global model across distributed clients that can generalize well on unseen domains. However, existing FDG methods typically struggle with cross-client data heterogeneity and incur significant communication and computation overhead. To address these challenges, this paper presents a new FDG framework, dubbed FaST-PT, which facilitates local feature augmentation and efficient unseen domain adaptation in a distributed manner. First, we propose a lightweight Multi-Modal Style Transfer (MST) method to transform image embedding under text supervision, which could expand the training data distribution and mitigate domain shift. We then design a dual-prompt module that decomposes the prompt into global and domain prompts. Specifically, global prompts capture general knowledge from augmented embedding across clients, while domain prompts capture domain-specific knowledge from local data. Besides, Domain-aware Prompt Generation (DPG) is introduced to adaptively generate suitable prompts for each sample, which facilitates unseen domain adaptation through knowledge fusion. Extensive experiments on four cross-domain benchmark datasets, e.g., PACS and DomainNet, demonstrate the superior performance of FaST-PT over SOTA FDG methods such as FedDG-GA and DiPrompt. Ablation studies further validate the effectiveness and efficiency of FaST-PT.
We present a new approach for representing and reconstructing multidimensional magnetic resonance imaging (MRI) data. Our method builds on a novel, learned feature-based image representation that disentangles different types of features, such as geometry and contrast, into distinct low-dimensional latent spaces, enabling better exploitation of feature correlations in multidimensional images and incorporation of pre-learned priors specific to different feature types for reconstruction. More specifically, the disentanglement was achieved via an encoderdecoder network and image transfer training using large public data, enhanced by a style-based decoder design. A latent diffusion model was introduced to impose stronger constraints on distinct feature spaces. New reconstruction formulations and algorithms were developed to integrate the learned representation with a zero-shot selfsupervised learning adaptation and subspace modeling. The proposed method has been evaluated on accelerated T1 and T2 parameter mapping, achieving improved performance over state-of-the-art reconstruction methods, without task-specific supervised training or fine-tuning. This work offers a new strategy for learning-based multidimensional image reconstruction where only limited data are available for problem-specific or task-specific training.
Retrieval Augmented Generation (RAG) has made significant strides in overcoming key limitations of large language models, such as hallucination, lack of contextual grounding, and issues with transparency. However, traditional RAG systems consist of three interconnected neural components - the retriever, re-ranker, and generator - whose internal reasoning processes remain opaque. This lack of transparency complicates interpretability, hinders debugging efforts, and erodes trust, especially in high-stakes domains where clear decision-making is essential. To address these challenges, we introduce the concept of Neurosymbolic RAG, which integrates symbolic reasoning using a knowledge graph with neural retrieval techniques. This new framework aims to answer two primary questions: (a) Can retrievers provide a clear and interpretable basis for document selection? (b) Can symbolic knowledge enhance the clarity of the retrieval process? We propose three methods to improve this integration. First is MAR (Knowledge Modulation Aligned Retrieval) that employs modulation networks to refine query embeddings using interpretable symbolic features, thereby making document matching more explicit. Second, KG-Path RAG enhances queries by traversing knowledge graphs to improve overall retrieval quality and interpretability. Lastly, Process Knowledge-infused RAG utilizes domain-specific tools to reorder retrieved content based on validated workflows. Preliminary results from mental health risk assessment tasks indicate that this neurosymbolic approach enhances both transparency and overall performance ;8 pages, 2 Figures, Published in IEEE Intelligent Systems
In safety-critical domains, linguistic ambiguity can have severe consequences; a vague command like "Pass me the vial" in a surgical setting could lead to catastrophic errors. Yet, most embodied AI research overlooks this, assuming instructions are clear and focusing on execution rather than confirmation. To address this critical safety gap, we are the first to define 3D Instruction Ambiguity Detection, a fundamental new task where a model must determine if a command has a single, unambiguous meaning within a given 3D scene. To support this research, we build Ambi3D, the large-scale benchmark for this task, featuring over 700 diverse 3D scenes and around 22k instructions. Our analysis reveals a surprising limitation: state-of-the-art 3D Large Language Models (LLMs) struggle to reliably determine if an instruction is ambiguous. To address this challenge, we propose AmbiVer, a two-stage framework that collects explicit visual evidence from multiple views and uses it to guide an vision-language model (VLM) in judging instruction ambiguity. Extensive experiments demonstrate the challenge of our task and the effectiveness of AmbiVer, paving the way for safer and more trustworthy embodied AI. Code and dataset available at https://jiayuding031020.github.io/ambi3d/.
This paper introduces a diffusion-based framework for universal image segmentation, making agnostic segmentation possible without depending on mask-based frameworks and instead predicting the full segmentation in a holistic manner. We present several key adaptations to diffusion models, which are important in this discrete setting. Notably, we show that a location-aware palette with our 2D gray code ordering improves performance. Adding a final tanh activation function is crucial for discrete data. On optimizing diffusion parameters, the sigmoid loss weighting consistently outperforms alternatives, regardless of the prediction type used, and we settle on x-prediction. While our current model does not yet surpass leading mask-based architectures, it narrows the performance gap and introduces unique capabilities, such as principled ambiguity modeling, that these models lack. All models were trained from scratch, and we believe that combining our proposed improvements with large-scale pretraining or promptable conditioning could lead to competitive models. ;Accepted at NLDL 26
Collaborative perception (CP) is a critical technology in applications like autonomous driving and smart cities. It involves the sharing and fusion of information among sensors to overcome the limitations of individual perception, such as blind spots and range limitations. However, CP faces two primary challenges. First, due to the dynamic nature of the environment, the timeliness of the transmitted information is critical to perception performance. Second, with limited computational power at the sensors and constrained wireless bandwidth, the communication volume must be carefully designed to ensure feature representations are both effective and sufficient. This work studies the dynamic scheduling problem in a multi-region CP scenario, and presents a Timeliness-Aware Multi-region Prioritized (TAMP) scheduling algorithm to trade-off perception accuracy and communication resource usage. Timeliness reflects the utility of information that decays as time elapses, which is manifested by the perception performance in CP tasks. We propose an empirical penalty function that maps the joint impact of Age of Information (AoI) and communication volume to perception performance. Aiming to minimize this timeliness-oriented penalty in the long-term, and recognizing that scheduling decisions have a cumulative effect on subsequent system states, we propose the TAMP scheduling algorithm. TAMP is a Lyapunov-based optimization policy that decomposes the long-term average objective into a per-slot prioritization problem, balancing the scheduling worth against resource cost. We validate our algorithm in both intersection and corridor scenarios with the real-world Roadside Cooperative perception (RCooper) dataset. Extensive simulations demonstrate that TAMP outperforms the best-performing baseline, achieving an Average Precision (AP) improvement of up to 27% across various configurations. ;This work has been submitted to the IEEE for possible publication
The paper introduces a basic logic of knowledge and abduction by extending Levesque logic of only-knowing with an abduction modal operator defined via the combination of basic epistemic concepts. The upshot is an alternative approach to abduction that employs a modal vocabulary and explores the relation between abductive reasoning and epistemic states of only knowing. Furthermore, by incorporating a preferential relation into modal frames, we provide a non-monotonic extension of our basic framework capable of expressing different selection methods for abductive explanations. Core metatheoretic properties of non-monotonic consequence relations are explored within this setting and shown to provide a well-behaved foundation for abductive reasoning. ;In Proceedings ICLP 2025, arXiv:2601.00047
This work investigates the algorithmic complexity of non-classical logics, focusing on superintuitionistic and modal systems. It is shown that propositional logics are usually polynomial-time reducible to their fragments with at most two variables (often to the one-variable or even variable-free fragments). Also, it is proved that predicate logics are usually reducible to their fragments with one or two unary predicate letters and two or three individual variables. The work describes conditions sufficient for such reductions and provides examples where they fail, establishing non-reducibility in those cases. Furthermore, the work provides new complexity bounds for several logics, results on Kripke-incompleteness of predicate calculi, and analogues of the classical theorems of Church and Trakhtenbrot for the logic of quasiary predicates. ;Doctor of Sciences dissertation. In Russian
Continual learning aims to acquire new tasks while preserving performance on previously learned ones, but most methods struggle with catastrophic forgetting. Existing approaches typically treat all layers uniformly, often trading stability for plasticity or vice versa. However, different layers naturally exhibit varying levels of uncertainty (entropy) when classifying tasks. High-entropy layers tend to underfit by failing to capture task-specific patterns, while low-entropy layers risk overfitting by becoming overly confident and specialized. To address this imbalance, we propose an entropy-aware continual learning method that employs a dynamic feedback mechanism to regulate each layer based on its entropy. Specifically, our approach reduces entropy in high-entropy layers to mitigate underfitting and increases entropy in overly confident layers to alleviate overfitting. This adaptive regulation encourages the model to converge to wider local minima, which have been shown to improve generalization. Our method is general and can be seamlessly integrated with both replay- and regularization-based approaches. Experiments on various datasets demonstrate substantial performance gains over state-of-the-art continual learning baselines. ;14 pages
The Time-Slotted Channel Hopping (TSCH) mode of IEEE802.15.4 standard provides ultra high end-to-end reliability and low-power consumption for application in field of Industrial Internet of Things (IIoT). With the evolving of Industrial 4.0, dynamic and bursty tasks with varied Quality of Service (QoS); effective management and utilization of growing number of mobile equipments become two major challenges for network solutions. The existing TSCH-based networks lack of a system framework design to handle these challenges. In this paper, we propose a novel, service-oriented, and hierarchical IoT network architecture named Mobile Node as a Service (Monaas). Monaas aims to systematically manage and schedule mobile nodes as on-demand, elastic resources through a new architectural design and protocol mechanisms. Its core features include a hierarchical architecture to balance global coordination with local autonomy, task-driven scheduling for proactive resource allocation, and an on-demand mobile resource integration mechanism. The feasibility and potential of the Monaas link layer mechanisms are validated through implementation and performance evaluation on an nRF52840 hardware testbed, demonstrating its potential advantages in specific scenarios. On a physical nRF52840 testbed, Monaas consistently achieved a Task Completion Rate (TCR) above 98% for high-priority tasks under bursty traffic and link degradation, whereas all representative baselines (Static TSCH, 6TiSCH Minimal, OST, FTS-SDN) remained below 40%.Moreover, its on-demand mobile resource integration activated services in 1.2 s, at least 65% faster than SDN (3.5 s) and OST/6TiSCH (> 5.8 s).
Visual Question Answering (VQA) requires models to reason over multimodal information, combining visual and textual data. With the development of continual learning, significant progress has been made in retaining knowledge and adapting to new information in the VQA domain. However, current methods often struggle with balancing knowledge retention, adaptation, and robust feature representation. To address these challenges, we propose a novel framework with adaptive memory allocation and global noise filtering called MacVQA for visual question answering. MacVQA fuses visual and question information while filtering noise to ensure robust representations, and employs prototype-based memory allocation to optimize feature quality and memory usage. These designs enable MacVQA to balance knowledge acquisition, retention, and compositional generalization in continual VQA learning. Experiments on ten continual VQA tasks show that MacVQA outperforms existing baselines, achieving 43.38% average accuracy and 2.32% average forgetting on standard tasks, and 42.53% average accuracy and 3.60% average forgetting on novel composition tasks. ;Accepted to AAAI 2026
In this paper, we present the development of 4-DOF robot limbs, which we call Moonbots, designed to connect in various configurations with each other and wheel modules, enabling adaptation to different environments and tasks. These modular components are intended primarily for robotic systems in space exploration and construction on the Moon in our Moonshot project. Such modular robots add flexibility and versatility for space missions where resources are constrained. Each module is driven by a common actuator characterized by a high torque-to-speed ratio, supporting both precise control and dynamic motion when required. This unified actuator design simplifies development and maintenance across the different module types. The paper describes the hardware implementation, the mechanical design of the modules, and the overall software architecture used to control and coordinate them. Additionally, we evaluate the control performance of the actuator under various load conditions to characterize its suitability for modular robot applications. To demonstrate the adaptability of the system, we introduce nine functional configurations assembled from the same set of modules: 4DOF-limb, 8DOF-limb, vehicle, dragon, minimal, quadruped, cargo, cargo-minimal, and bike. These configurations reflect different locomotion strategies and task-specific behaviors, offering a practical foundation for further research in reconfigurable robotic systems. ;Author's version of a manuscript accepted at the International Conference on Space Robotics 2025 (iSpaRo 2025). (c) IEEE
Face verification systems have seen substantial advancements; however, they often lack transparency in their decision-making processes. In this paper, we introduce an innovative Vision-Language Model (VLM) for Face Verification, which not only accurately determines if two face images depict the same individual but also explicitly explains the rationale behind its decisions. Our model is uniquely trained using two complementary explanation styles: (1) concise explanations that summarize the key factors influencing its decision, and (2) comprehensive explanations detailing the specific differences observed between the images. We adapt and enhance a state-of-the-art modeling approach originally designed for audio-based differentiation to suit visual inputs effectively. This cross-modal transfer significantly improves our model's accuracy and interpretability. The proposed VLM integrates sophisticated feature extraction techniques with advanced reasoning capabilities, enabling clear articulation of its verification process. Our approach demonstrates superior performance, surpassing baseline methods and existing models. These findings highlight the immense potential of vision language models in face verification set up, contributing to more transparent, reliable, and explainable face verification systems.
Controllability is a fundamental requirement in video synthesis, where accurate alignment with conditioning signals is essential. Existing classifier-free guidance methods typically achieve conditioning indirectly by modeling the joint distribution of data and conditions, which often results in limited controllability over the specified conditions. Classifier-based guidance enforces conditions through an external classifier, but the model may exploit this mechanism to raise the classifier score without genuinely satisfying the intended condition, resulting in adversarial artifacts and limited effective controllability. In this paper, we propose Attention-Conditional Diffusion (ACD), a novel framework for direct conditional control in video diffusion models via attention supervision. By aligning the model's attention maps with external control signals, ACD achieves better controllability. To support this, we introduce a sparse 3D-aware object layout as an efficient conditioning signal, along with a dedicated Layout ControlNet and an automated annotation pipeline for scalable layout integration. Extensive experiments on benchmark video generation datasets demonstrate that ACD delivers superior alignment with conditioning inputs while preserving temporal coherence and visual fidelity, establishing an effective paradigm for conditional video synthesis.
We consider turn-based stochastic two-player games with a combination of a parity condition that must hold surely, that is in all possible outcomes, and of a parity condition that must hold almost-surely, that is with probability 1. The problem of deciding the existence of a winning strategy in such games is central in the framework of synthesis beyond worst-case where a hard requirement that must hold surely is combined with a softer requirement. Recent works showed that the problem is coNP-complete, and infinite-memory strategies are necessary in general, even in one-player games (i.e., Markov decision processes). However, memoryless strategies are sufficient for the opponent player. Despite these comprehensive results, the known algorithmic solution enumerates all memoryless strategies of the opponent, which is exponential in all cases, and does not construct a winning strategy when one exists.
We present a recursive algorithm, based on a characterisation of the winning region, that gives a deeper insight into the problem. In particular, we show how to construct a winning strategy to achieve the combination of sure and almost-sure parity, and we derive new complexity and memory bounds for special classes of the problem, defined by fixing the index of either of the two parity conditions. ;Extended version of STACS 2026 paper
The proliferation of Large Language Models (LLMs) has been accompanied by a reliance on cloud-based, proprietary systems, raising significant concerns regarding data privacy, operational sovereignty, and escalating costs. This paper investigates the feasibility of deploying a high-performance, private LLM inference server at a cost accessible to Small and Medium Businesses (SMBs). We present a comprehensive benchmarking analysis of a locally hosted, quantized 30-billion parameter Mixture-of-Experts (MoE) model based on Qwen3, running on a consumer-grade server equipped with a next-generation NVIDIA GPU. Unlike cloud-based offerings, which are expensive and complex to integrate, our approach provides an affordable and private solution for SMBs. We evaluate two dimensions: the model's intrinsic capabilities and the server's performance under load. Model performance is benchmarked against academic and industry standards to quantify reasoning and knowledge relative to cloud services. Concurrently, we measure server efficiency through latency, tokens per second, and time to first token, analyzing scalability under increasing concurrent users. Our findings demonstrate that a carefully configured on-premises setup with emerging consumer hardware and a quantized open-source model can achieve performance comparable to cloud-based services, offering SMBs a viable pathway to deploy powerful LLMs without prohibitive costs or privacy compromises.
We study the extent to which standard machine learning algorithms rely on exchangeability and independence of data by introducing a monotone adversarial corruption model. In this model, an adversary, upon looking at a "clean" i.i.d. dataset, inserts additional "corrupted" points of their choice into the dataset. These added points are constrained to be monotone corruptions, in that they get labeled according to the ground-truth target function. Perhaps surprisingly, we demonstrate that in this setting, all known optimal learning algorithms for binary classification can be made to achieve suboptimal expected error on a new independent test point drawn from the same distribution as the clean dataset. On the other hand, we show that uniform convergence-based algorithms do not degrade in their guarantees. Our results showcase how optimal learning algorithms break down in the face of seemingly helpful monotone corruptions, exposing their overreliance on exchangeability.
Public debates about "left-" or "right-wing" news overlook the fact that bias is usually conveyed by concrete linguistic manoeuvres that transcend any single political spectrum. We therefore shift the focus from where an outlet allegedly stands to how partiality is expressed in individual sentences. Drawing on 26,464 sentences collected from newsroom corpora, user submissions and our own browsing, we iteratively combine close-reading, interdisciplinary theory and pilot annotation to derive a fine-grained, sentence-level taxonomy of media bias and propaganda. The result is a two-tier schema comprising 38 elementary bias types, arranged in six functional families and visualised as a "table of media-bias elements". For each type we supply a definition, real-world examples, cognitive and societal drivers, and guidance for recognition. A quantitative survey of a random 155-sentence sample illustrates prevalence differences, while a cross-walk to the best-known NLP and communication-science taxonomies reveals substantial coverage gains and reduced ambiguity.
Background. Reproducibility is essential to the scientific method, but reproduction is often a laborious task. Recent works have attempted to automate this process and relieve researchers of this workload. However, due to varying definitions of reproducibility, a clear problem statement is missing. Objectives. Create a generalisable problem statement, applicable to any empirical study. We hypothesise that we can represent any empirical study using a structure based on the scientific method and that this representation can be automatically extracted from any publication, and captures the essence of the study. Methods. We apply our definition of reproducibility as a problem statement for the automatisation of reproducibility by automatically extracting the hypotheses, experiments and interpretations of 20 studies and assess the quality based on assessments by the original authors of each study. Results. We create a dataset representing the reproducibility problem, consisting of the representation of 20 studies. The majority of author feedback is positive, for all parts of the representation. In a few cases, our method failed to capture all elements of the study. We also find room for improvement at capturing specific details, such as results of experiments. Conclusions. We conclude that our formulation of the problem is able to capture the concept of reproducibility in empirical AI studies across a wide range of subfields. Authors of original publications generally agree that the produced structure is representative of their work; we believe improvements can be achieved by applying our findings to create a more structured and fine-grained output in future work. ;Accepted at RAI Workshop @ AAAI 2026
The rapid advancement of Large Language Models (LLMs) presents a significant challenge to academic integrity within computing education. As educators seek reliable detection methods, this paper evaluates the capacity of three prominent LLMs (GPT-4, Claude, and Gemini) to identify AI-generated text in computing-specific contexts. We test their performance under both standard and 'deceptive' prompt conditions, where the models were instructed to evade detection. Our findings reveal a significant instability: while default AI-generated text was easily identified, all models struggled to correctly classify human-written work (with error rates up to 32%). Furthermore, the models were highly susceptible to deceptive prompts, with Gemini's output completely fooling GPT-4. Given that simple prompt alterations significantly degrade detection efficacy, our results demonstrate that these LLMs are currently too unreliable for making high-stakes academic misconduct judgments. ;10 pages, 5 tables. Accepted for publication at the 59th Hawaii International Conference on System Sciences
Autonomous robotic platforms are playing a growing role across the emergency services sector, supporting missions such as search and rescue operations in disaster zones and reconnaissance. However, traditional red-green-blue (RGB) detection pipelines struggle in low-light environments, and thermal-based systems lack color and texture information. To overcome these limitations, we present an adaptive framework that fuses RGB and long-wave infrared (LWIR) video streams at multiple fusion ratios and dynamically selects the optimal detection model for each illumination condition. We trained 33 You Only Look Once (YOLO) models on over 22,000 annotated images spanning three light levels: no-light (<10 lux), dim-light (10-1000 lux), and full-light (>1000 lux). To integrate both modalities, fusion was performed by blending aligned RGB and LWIR frames at eleven ratios, from full RGB (100/0) to full LWIR (0/100) in 10% increments. Evaluation showed that the best full-light model (80/20 RGB-LWIR) and dim-light model (90/10 fusion) achieved 92.8% and 92.0% mean confidence; both significantly outperformed the YOLOv5 nano (YOLOv5n) and YOLOv11 nano (YOLOv11n) baselines. Under no-light conditions, the top 40/60 fusion reached 71.0%, exceeding baselines though not statistically significant. Adaptive RGB-LWIR fusion improved detection confidence and reliability across all illumination conditions, enhancing autonomous robotic vision performance.
We expose a significant popularity bias in state-of-the-art vision-language models (VLMs), which achieve up to 34% higher accuracy on famous buildings compared to ordinary ones, indicating a reliance on memorization over generalizable understanding. To systematically investigate this, we introduce the largest open benchmark for this task: the YearGuessr dataset, a collection of 55,546 building images with multi-modal attributes from 157 countries, annotated with continuous ordinal labels of their construction year (1001-2024), GPS data, and page-view counts as a proxy for popularity. Using this dataset, we frame the construction year prediction task as ordinal regression and introduce popularity-aware interval accuracy metrics to quantify this bias. Our resulting benchmark of 30+ models, including our YearCLIP model, confirms that VLMs excel on popular, memorized items but struggle significantly with unrecognized subjects, exposing a critical flaw in their reasoning capabilities. Project page: https://sytwu.github.io/BeyondMemo/ ;Project page: https://sytwu.github.io/BeyondMemo/
In this paper, we propose a machine learning model for sparse pairwise comparison matrices (PCMs), combining classical PCM approaches with graph-based learning techniques. Numerical results are provided to demonstrate the effectiveness and scalability of the proposed method.
Long COVID is a heterogeneous condition characterized by a wide range of symptoms that persist for 90 days or more following SARS-CoV-2 infection. Now more than five years out from the onset of the SARS-CoV-2 pandemic, the mechanisms driving Long COVID are just beginning to be elucidated. Adipose tissue has been proposed as a potential reservoir for viral persistence and tissue dysfunction contributing to symptomology seen in Long COVID. To test this hypothesis, we analyzed subcutaneous adipose tissue (SAT) from two cohorts: participants with subacute COVID-19 (28–89 days post-infection) compared to pre-pandemic controls, and participants with Long COVID compared to those with those classified as “indeterminate” based on the RECOVER-Adult Long COVID Research Index (12-47 months post-infection). We found no evidence of persistent SARS-CoV-2 RNA in adipose tissue in any participant. SAT from participants with subacute COVID-19 displayed significant transcriptional remodeling, including depleted immune activation pathways and upregulated Hox genes and integrin interactions, suggesting resident immune cell exhaustion and perturbations in tissue function. However, no consistent changes in gene expression were observed between Long COVID samples and samples from indeterminant participants. Thus, SAT may contribute to inflammatory dysregulation following COVID-19, but does not appear to play a clear role in Long COVID pathophysiology. Further research is needed to clarify the role of adipose tissue in COVID-19 recovery.
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.
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.
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.
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.
The global pandemic due to emergence of COVID 19 has created the unrivaled
public health crisis. It has huge morbidity rate never comprehended in the
recent decades. Researchers have made many efforts to find the optimal solution
of this pandemic. Progressively, drug repurposing is an emergent and powerful
strategy with saving cost, time, and labor. Lacking of identified repurposed
drug candidates against COVID 19 demands more efforts to explore the potential
inhibitors for effective cure. In this study, we used the combination of
molecular docking and machine learning regression approaches to explore the
potential inhibitors for the treatment of COVID 19. We calculated the binding
affinities of these drugs to multitarget proteins using molecular docking
process. We perform the QSAR modeling by employing various machine learning
regression approaches to identify the potential inhibitors against COVID 19.
Our findings with best scores of R2 and RMSE demonstrated that our proposed
Decision Tree Regression (DTR) model is the most appropriate model to explore
the potential inhibitors. We proposed five novel promising inhibitors with
their respective Zinc IDs ZINC (3873365, 85432544, 8214470, 85536956, and
261494640) within the range of -19.7 kcal/mol to -12.6 kcal/mol. We further
analyzed the physiochemical and pharmacokinetic properties of these most potent
inhibitors to examine their behavior. The analysis of these properties is the
key factor to promote an effective cure for public health. Our work constructs
an efficient structure with which to probe the potential inhibitors against
COVID-19, creating the combination of molecular docking with machine learning
regression approaches.
;Comment: 22 pages
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.
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
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.
Many conventional research methods employed in randomized controlled trials were not possible during the height of the COVID-19 pandemic. In particular, behavioral observations are nearly universally gathered in-person. Observational methods are valued for the rich, informative data they produce in comparison to non-observational methods and are a cornerstone of parenting and family research. COVID provided the opportunity to, and indeed necessitated, the transition to fully remote observation. However, little to no studies have investigated whether remotely collected observational data are methodologically sound. This paper assesses the feasibility of remote data collection by describing the transition between in-person and fully remote observational data collection during a Sequential, Multiple Assignment, Randomized Trial (SMART) of a parenting program that took place both before and during the pandemic. Using mixed-methods data from coders, the overall quality of video-recorded data collected both before and during COVID was examined. Coder reliability over time was assessed with intraclass correlation coefficients. Results suggest that the frequency of audio problems, the severity of visual problems, and the level of administration challenges decreased after transitioning to remote data collection. Additionally, coders showed good to excellent reliability coding remotely collected data, and reliability even improved on some measured tasks. Although challenges to remote data collection exist, this study demonstrated that observational data can be collected feasibly and reliably. As observational data collection is a key method to assess parenting practices, these findings should improve researcher confidence in utilizing remote observational methods in prevention science.
Background The emergence of COVID-19 precipitated containment policies (e.g., lockdowns, school closures, etc.). These policies disrupted healthcare, potentially eroding gains for Sustainable Development Goals including for neonatal mortality. Our analysis aimed to evaluate indirect effects of COVID-19 containment policies on neonatal admissions and mortality in 67 neonatal units across Kenya, Malawi, Nigeria, and Tanzania between January 2019 and December 2021. Methods The Oxford Stringency Index was applied to quantify COVID-19 policy stringency over time for Kenya, Malawi, Nigeria, and Tanzania. Stringency increased markedly between March and April 2020 for these four countries (although less so in Tanzania), therefore defining the point of interruption. We used March as the primary interruption month, with April for sensitivity analysis. Additional sensitivity analysis excluded data for March and April 2020, modelled the index as a continuous exposure, and examined models for each country. To evaluate changes in neonatal admissions and mortality based on this interruption period, a mixed effects segmented regression was applied. The unit of analysis was the neonatal unit ( n = 67), with a total of 266,741 neonatal admissions (January 2019 to December 2021). Results Admission to neonatal units decreased by 15% overall from February to March 2020, with half of the 67 neonatal units showing a decline in admissions. Of the 34 neonatal units with a decline in admissions, 19 (28%) had a significant decrease of ≥ 20%. The month-to-month decrease in admissions was approximately 2% on average from March 2020 to December 2021. Despite the decline in admissions, we found no significant changes in overall inpatient neonatal mortality. The three sensitivity analyses provided consistent findings. Conclusion COVID-19 containment measures had an impact on neonatal admissions, but no significant change in overall inpatient neonatal mortality was detected. Additional qualitative research in these facilities has explored possible reasons. Strengthening healthcare systems to endure unexpected events, such as pandemics, is critical in continuing progress towards achieving Sustainable Development Goals, including reducing neonatal deaths to less than 12 per 1000 live births by 2030.
INTRODUCTION: The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown. METHODS: A total of 7361 asymptomatic community-dwelling people enrolled in the Test Us at Home parent study between October 2021 and February 2022. Participants self-collected anterior nasal swabs for SARS-CoV-2 RT-PCR testing every 24-48 hours for 10-14 days, regardless of symptom or infection status. Participants who had no history of COVID-19 at enrollment and who were subsequently found to have ≥1 positive SARS-CoV-2 RT-PCR test during the parent study were recontacted in August 2023 and asked whether they had experienced long COVID, defined as the development of new symptoms lasting 3 months or longer following SARS-CoV-2 infection. Participant’s cycle threshold values were converted into viral loads, and slopes of viral clearance were modeled using post-nadir viral loads. Using a log binomial model with the modeled slopes as the exposure, we calculated the relative risk of subsequently developing long COVID with 1-2 symptoms, 3-4 symptoms, or 5+ symptoms, adjusting for age, number of symptoms, and SARS-CoV-2 variant. Adjusted relative risk (aRR) of individual long COVID symptoms based on viral clearance was also calculated. RESULTS: 172 participants were eligible for analyses, and 59 (34.3%) reported experiencing long COVID. The risk of long COVID with 3-4 symptoms and 5+ symptoms increased by 2.44 times (aRR: 2.44; 95% CI: 0.88-6.82) and 4.97 times (aRR: 4.97; 95% CI: 1.90-13.0) per viral load slope-unit increase, respectively. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance during acute disease than those who never developed long COVID (8.65 [95% CI: 8.28-9.01] vs. 10.0 [95% CI: 9.25-10.8]). The slope of viral clearance was significantly positively associated with long COVID symptoms of fatigue (aRR: 2.86; 95% CI: 1.22-6.69), brain fog (aRR: 4.94; 95% CI: 2.21-11.0), shortness of breath (aRR: 5.05; 95% CI: 1.24-20.6), and gastrointestinal symptoms (aRR: 5.46; 95% CI: 1.54-19.3). DISCUSSION: We observed that longer time from peak viral load to viral RNA clearance during acute COVID-19 was associated with an increased risk of developing long COVID. Further, slower clearance rates were associated with greater number of symptoms of long COVID. These findings suggest that early viral-host dynamics are mechanistically important in the subsequent development of long COVID.
Observational analyses of electronic health record (EHR) data using databases such as the National Clinical Cohort Collaborative include unique challenges for researchers seeking causal inferences, particularly when evaluating subjectively-defined outcomes like Long COVID. We explore several challenges and describe potential solutions. 1. Lack of true negatives: Many diagnoses and conditions either have a positive indicator or a missing status, requiring investigators to carefully consider which patients are likely negative for this condition. 2. Differential monitoring: EHR data include nonrandom missingness driven by patients engaging with the healthcare system at different rates, which is often related to both the exposure and outcome of interest. 3. Bias: EHR data sources face many biases, but are particularly vulnerable to informative missingness, differential monitoring, and model misspecification. 4. Large sample size: High precision (i.e., narrow confidence intervals) paired with potential bias leads to a high risk of incorrectly rejecting the null hypothesis. 5. Defining index time: It is important that investigators deliberately define index time (i.e., t ( 0 ) , baseline) to ensure that they only adjust for baseline confounders and do not adjust for (or condition on) factors that are affected by the exposure of interest (i.e., colliders or mediators). 6. Parameter selection: Investigators should only select parameters that are supported by the data distribution. This manuscript provides an overview of these challenges and solutions, using both simulated data and real-world data, with the outcome of Long COVID as the running example.
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.
Introduction The COVID-19 pandemic period (2020 to 2022) challenged and overstretched the capacity of primary health care services to deliver health care globally. The sector faced a highly uncertain and dynamic period that encompassed anticipation of a new, unknown, lethal and highly transmissible infection, the introduction of various travel restrictions, health workforce shortages, new government funding announcements and various policies to restrict the spread of the COVID-19 virus, then vaccination and treatments. This qualitative study aims to document and explore how the pandemic affected primary health care utilisation and delivery in remote and regional Aboriginal and Torres Strait Islander communities. Methods Semi-structured interviews were conducted with staff working in 11 Aboriginal Community-Controlled Health Services (ACCHSs) in outer regional, remote and very remote Australia. Interviews were transcribed, inductively coded and thematically analysed. Results 248 staff working in outer regional, remote and very remote primary health care clinics were interviewed between February 2020 and June 2021. Participants reported a decline in numbers of primary health care presentations in most communities during the initial COVID-19 lock down period. The reasons for the decline were attributed to community members apprehension to go to the clinics, change in work priorities of primary health care staff (e.g. more emphasis on preventing the virus entering the communities and stopping the spread) and limited outreach programs. Staff forecasted a future spike in acute presentations of various chronic diseases leading to increased medical retrieval requirements from remote communities to hospital. Information dissemination during the pre-vaccine roll-out stage was perceived to be well received by community members, while vaccine roll-out stage information was challenged by misinformation circulated through social media. Conclusions The ability of ACCHSs to be able to adapt service delivery in response to the changing COVID-19 strategies and policies are highlighted in this study. The study signifies the need to adequately fund ACCHSs with staff, resources, space and appropriate information to enable them to connect with their communities and continue their work especially in an era where the additional challenges created by pandemics are likely to become more frequent. While the PHC seeking behaviour of community members during the COVID-19 period were aligned to the trends observed across the world, some of the reasons underlying the trends were unique to outer regional, remote and very remote populations. Policy makers will need to give due consideration to the potential effects of newly developed policies on ACCHSs operating in remote and regional contexts that already battle under resourcing issues and high numbers of chronically ill populations.
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.
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.
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.
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.
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.
Colégio Brasileiro de Cirurgia DigestivaJanuar 2025Covid
BACKGROUND: The COVID-19 pandemic has overloaded healthcare systems worldwide. Other diseases, such as neoplasms, including gastric cancer, remained prevalent and had their treatment compromised. AIMS: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the treatment of gastric cancer and adherence to the recommended preoperative COVID-19 screening protocol. METHODS: A retrospective study evaluated patients diagnosed with gastric adenocarcinoma who underwent surgical treatment between 2015 and 2023. RESULTS: A total of 769 patients with gastric cancer were evaluated and organized into two groups: (i) pre-COVID group and (ii) COVID group. The pre-COVID group consisted of 527 patients operated on between 2015 and 2019, and the COVID group consisted of 242 patients from 2020 to 2023. The average number of surgical procedures per year in the pre-COVID group was 105 and 81 in the COVID group. There was a statistically significant difference between ASA classification (p=0.002) and clinical staging (p=0.015), which were worse in the COVID group. We observed an increase in diagnostic surgeries (p=0.026), with an increase in the minimally invasive route (p<0.001). In patients undergoing curative surgery, there was a greater indication for postoperative ICU (p=0.022) and neoadjuvant chemotherapy (p<0.001). There was no difference in 30- and 90-day mortality. CONCLUSIONS: The surgical and oncological outcomes for patients operated on during the pandemic remained uncompromised, even though many presented with more advanced initial stages and poorer clinical performance. High adherence to protocols and a low rate of complications related to coronavirus indicate that surgeries were performed safely during this period.
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.
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.
Introduction Darunavir and lopinavir solid formulations are recommended protease inhibitors for treating HIV. An evidence review of their effectiveness/efficacy and safety in young populations was needed to inform the 2025 World Health Organization guidelines. Methods We conducted a systematic review of publications reporting efficacy/effectiveness and/or safety of darunavir and/or lopinavir solid formulations in children and/or adolescents with HIV aged 0–19 years, with at least 6 months follow-up. Sources included MEDLINE, Embase, Cochrane Library, recent HIV conferences and trial registries. Data were synthesized narratively. Results We screened 4,196 abstracts and 421 papers. Thirteen studies (including two randomized controlled trials (RCTs)) on darunavir were identified in 1,895 children/adolescents (2% treatment-naïve). Among treatment-experienced participants on ritonavir-boosted darunavir, 86% (198/229) and 95% (143/150) had viral suppression (< 50 or < 400 copies/mL) at 48 weeks in the RCTs and 29% (4/14)-100% (12/12) across seven other studies ( N = 736), respectively. Participants in the four studies ( N = 184) with < 70% suppression were heavily treatment-experienced and unsuppressed at darunavir start. Grade 3/4 adverse events (clinical/laboratory) occurred in 0%-30% of participants on ritonavir-boosted darunavir (seven studies, N = 515; 8–9% in two large RCTs), and adverse events leading to discontinuation or treatment modification in 0%-10% (10 studies, N = 974; 2–3% in two RCTs). Three grade 3/4 adverse events in one study were drug related. Twenty-nine studies (including four randomized trials) on ritonavir-boosted lopinavir solid formulations were identified in 3,605 children/adolescents (17% treatment-naïve). Among treatment-experienced children/adolescents at 48–52 weeks, viral suppression was 80% (179/223) in one RCT and 53% (448/852)-100% (12/12) across five other studies (N = 1305). Across all populations, grade 3/4 adverse events were reported in 8%-60% of participants (four studies, N = 1405; 8–13% in two large RCTs), and events leading to discontinuation or treatment modification in 0%-9% (seven studies, N = 905; 2–3% in two RCTs). Five participants experienced drug-related grade 3/4 adverse events (five studies, N = 1107). Lipid levels were significantly greater with lopinavir versus other regimens (five studies). Conclusions Darunavir was safe in treatment-experienced children and adolescents, and viral suppression was high in RCTs; data were limited in treatment-naïve populations. Viral suppression with lopinavir solid formulations was variable. Lopinavir was generally well-tolerated but compared unfavourably with other drugs in terms of lipid outcomes. PROSPERO number CRD42020204432.
Background HIV infection is a major public health concern among pregnant women globally. Beyond the risk of mother-to-child transmission, it can lead to serious complications and negative pregnancy and neonatal outcomes. In Iran, there is currently no comprehensive meta-analysis evidence measuring the adverse pregnancy and neonatal complications of HIV infection among pregnant women. The review objective is to provide pregnancy outcomes, the prevention of mother-to-child transmission (PMTCT), and antiviral therapy (ART) of pregnant women infected with HIV in Iran. Methods The review systematically searched PubMed, Scopus, ISI, Embase, and also the Iranian national databases up to 25th September 2024. Any records that reported pregnancy and neonatal outcomes among pregnant women in Iran were included in the inclusion criteria. The study outcomes included any pregnancy and neonatal implications related to HIV infection in pregnant women, as well as PMTCT, ART therapy, delivery type, and HIV morbidity in spouse. Meta-analysis was carried out to estimate pooled prevalence with 95% confidence intervals (CIs) for all the study outcomes. Results The study pooled data from 497 pregnant women infected with HIV across seven eligible studies. The majority of participants had no university education, lived in urban areas, and were infected by their spouses. The most frequent adverse pregnancy outcome was abortion. The pooled proportions and 95% CIs for each outcome were: HIV-positive spouses 78% (95% CI: 73–83%), wanted pregnancy 63% (95% CI: 46–80%), ART and/or PMTCT uptake 94% (95% CI: 89–98%), cesarean delivery 88% (95% CI: 77–98%), live birth rate 98% (95% CI: 96–100%), newborns who were HIV positive 1.0% (95% CI: 0.0–1.0%), and newborn prophylaxis 100% (95% CI: 99–100%). Conclusion Although most pregnant women with HIV are enrolled in PMTCT programs and adverse pregnancy and neonatal outcomes are rare, longitudinal, population-based studies are still needed to better understand the situation of pregnant women with HIV in Iran.
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.
Precise and scalable quantification of the genetically intact HIV reservoir is critical for advancing curative strategies. However, current HIV reservoir assays such as the intact proviral DNA assay (IPDA) are limited by quantification failures or misclassification of defective proviral genomes due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR assay that simultaneously targets four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. We benchmarked Q4ddPCR against 3,650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR using the same primer/probe sets. Q4ddPCR enabled intact reservoir quantification in 95% of samples from three independent cohorts and closely matched sequence-confirmed Q4PCR reservoir measurements. In addition, multi-probe readouts revealed clonal intact reservoir dynamics that are not detectable by IPDA. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reported lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays provide greater specificity and more accurately capture the dynamics of the intact HIV reservoir.
Background Human immunodeficiency virus (HIV) is a genus of retroviruses that targets immune cells and may eventually cause immune-deficiency illness. Triple infection of HIV/hepatitis B virus (HBV) /tuberculosis (TB) leads to a worse prognosis than mono-infection. We aimed to unveil the pooled estimation of HIV/HBV/TB co-infection prevalence in Asia, South America, and Africa. Methods A systematic literature search in PubMed, Embase, and the Cochrane Library was performed for studies of the prevalence of HIV/HBV/TB triple infection published from January 1, 1990, to March 31, 2024. The Freeman–Tukey random effects model was used to calculate the pooled prevalence. Results We included 7 studies with in total 6401 participants and 259 triple infection cases. The pooled triple infection rate in the enrolled population was 4.4% (259/6401; 95% CI 2.2%-7.3%). The results of the subgroup analysis showed that the prevalence of triple infection was significantly higher in the South America (82/950, 8.6%; 95% CI 6.8%-10.4%), in men (86/1817, 3.4%; 95% CI 0.7%-7.8%) and patients receiving antiretroviral treatment (125/1611, 7.4%; 95% CI 5.8%–9.2%). However, no significant difference in the triple infection rate was observed among individuals initially diagnosed with HIV or TB. Conclusions This meta-analysis suggests that the prevalence of HIV/HBV/TB triple infection in the regions studied is underestimated, and we should focus more effort on improving novel strategies for identifying triple infection of HIV/HBV/TB. However, additional studies are required to be incorporated in future analyses to provide a pooled estimate of the global pooled prevalence. Clinical trial Not applicable.
Background Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. Methods The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV_1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV_1, forced vital capacity (FVC) and FEV_1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. Results Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV_1 z-score was − 2.0 (0.7) with 44.7% ( n = 155) having an FEV_1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV_1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV_1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. Conclusion There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. Trial registration ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.
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.
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BACKGROUND: Historically, hepatitis C virus (HCV) was difficult to treat among people with HIV. However, treatment with direct-acting antivirals (DAAs) results in 90%-95% of people being cured. There is a need to understand why a proportion of people are not cured. We aimed to examine characteristics that may indicate an increased probability of unsuccessful DAA HCV treatment. METHODS: Data were from the International Collaboration on Hepatitis C Elimination in HIV Cohorts. People who commenced DAA HCV treatment between 2014 and 2019 were included. Unsuccessful treatment was defined as a positive HCV RNA test at a person's first RNA test at least 4 weeks (SVR4+) following the end of treatment. Multivariable mixed-effects logistic regression was used to examine characteristics associated with unsuccessful treatment. RESULTS: Of 4468 people who commenced DAA treatment, 4098 (91.7%) had an SVR test 4+ weeks following the end of treatment, 207 (5%) of whom were unsuccessfully treated. Compared to a CD4+ cell count > 500 cells/mm(3), cell counts < 200 (aOR 1.81, 95%CI 1.00-3.29) and between 200 and 349 (aOR 1.95, 95%CI 1.30-2.93) were associated with increased odds of unsuccessful treatment. Among 1921 people with data on injection drug use in the 12 months prior to treatment, there was some evidence that recent injection drug use was associated with increased odds of unsuccessful treatment; however, this was not statistically significant (aOR 1.67, 95%CI 0.99-2.82). CONCLUSIONS: The overwhelming majority of people were successfully treated for HCV. Overall, 5% of those with an SVR4+ test were unsuccessfully treated; this was more likely among people with evidence of immunodeficiency and those who reported recently injecting drugs.
Background Health inequality in Latin America is particularly severe for individuals living with HIV (PLHIV) and key populations, such as men who have sex with men, transgender women, people who use drugs, and sex workers. Despite regional programs aimed at reducing health inequalities, such as the Sustainable Development Goals and the Sustainable Health Agenda for the Americas 2018–2030, the COVID-19 health crisis has exposed significant shortcomings in national healthcare systems for PLHIV and key populations. The multi-country, community-based research program, EPIC, was developed by Coalition PLUS within an network of community-based organizations engaged in the response to HIV and viral hepatitis. The EPIC program aimed to study the impact of the COVID-19 health crisis on 1) key populations (KP) and/or PLHIV or hepatitis C; 2) community health workers (CHWs) and peer educators; and 3) key innovations and adaptations in HIV/HCV services. The objective of this article is to highlight main issues faced in the region during the COVID-19 health crisis in order to inform national and international policies. Methods A general protocol and study materials were developed and included built-in flexibility to allow participating organizations to adapt the study to local needs in terms of target populations and specific areas of interest. Data were collected through surveys and/or interviews. In total 118 studies were conducted across 31 countries: 66 quantitative ( n = 12,060 among KP or PLHIV or people living with HCV and n = 811 among CHWs) and 52 qualitative ( n = 766 among KP or PLHIV or people living with HCV and n = 136 among CHWs). Discussion Findings in Latin America highlight the difficulties faced by PLHIV and KP in accessing health services, as well as issues of discrimination, violence, and mental health challenges, all of which have been exacerbated by the health crisis. Additionally, the study highlights strategies implemented by community CHWs and peer educators to mitigate the negative impact of the crisis. Moreover, EPIC demonstrates the ability of community agents to generate scientific evidence that raises public awareness of the situation faced by the most vulnerable populations. Conclusion National and international policies must recognize and support the unique capacity of CHWs and peer educators to adapt health interventions to the specific needs of communities. Policymakers are also urged to involve the community in the development of public policies aimed at reducing inequalities and improving the living conditions of vulnerable populations.
Human Immunodeficiency Virus (HIV) stigma constitutes a major barrier to HIV prevention, testing, and treatment, and is associated with harmful consequences for people living with HIV such as discrimination, rejection from family and friends, and treatment nonadherence. This study aimed to understand the drivers, perpetuators, and outcomes of HIV-related stigma among young people living with HIV (YPLWH) in Lima, Peru. From November 2022 to June 2023, we conducted interviews and focus groups with a diverse group of 75 YPWLH, in addition to healthcare providers and HIV advocates, to discuss their experiences of HIV-related stigma. Audio recordings were transcribed verbatim and analyzed for emergent themes using framework analysis. Participants identified the drivers of HIV-related stigma as a lack of information about HIV and misinformation about HIV, and the key power groups who perpetuate this stigma, which included parents and older generations, educators, and healthcare providers. Participants reported outcomes of HIV-related stigma; these included feelings of fear, shame, and loneliness, and enacted behaviors such as treatment nonadherence, nondisclosure of HIV diagnosis, and social avoidance. Participants also reported health outcomes of sickness, death, and HIV transmission, and social outcomes including discrimination from employers, educators, and peers, and loss of social support. These findings are critical to understanding how HIV-related stigma manifests in the cultural context of Lima, Peru, and can be used to inform effective interventions to reduce and mitigate the impacts of HIV-related stigma.
Little is known about serological responses to MVA-BN (JYNNEOS) against mpox in elderly individuals with or without HIV. In this study, MVA-BN induced sustained IgG levels regardless of HIV status even up to one year. Birth before 1973 correlated with higher IgG. MVA-BN unvaccinated individuals with HIV had lower IgG than vaccinated.
Oncogenic retroviruses are known for their pathogenesis via insertional mutagenesis, in which the presence of a provirus and its transcriptional control elements alter the expression of a nearby or surrounding host gene. There are reports of proviral integration driving oncogenesis in people with HIV and the use of HIV-derived vectors for gene therapy has raised concern about oncogenic side effects. To study this issue, we used an ex vivo human CD4+ T cell infection model developed in our laboratory to identify HIV-1 integration sites that might influence cell proliferation or survival. Combining integration site analysis and bulk RNA sequencing, we established that an upregulated STAT3 signature due to proviral insertional mutagenesis was associated with persistent HIV-infected CD4+ T cells. HIV+ persistent cells also expressed a STAT3-related anti-apoptotic and cytotoxic phenotype that resembles that of HIV-associated T cell lymphomas. HIV insertional mutagenesis of STAT3 and expression of its downstream targets provides a model of HIV-associated T cell lymphomas that can be used to further determine the oncogenic drivers of HIV-associated lymphomas, both AIDS- and gene therapy-associated, and, potentially, to evaluate therapeutics against these HIV-associated cancers. AUTHOR SUMMARY: The effects of HIV proviral insertional mutagenesis have been demonstrated in a handful of HIV-associated T cell lymphomas, where integration of an HIV provirus within intron 1 of STAT3 , results in increased expression of the STAT3 protein. To study the effects of HIV insertional mutagenesis, we established an ex vivo culture protocol of primary human CD4+ T cells infected with a replication-incompetent HIV vector with a gfp-reporter. After infection, the HIV/GFP+ cells from all three donors declined, but, over time, 3/6 replicates from one donor populations of infected cells rebounded. The resurgent HIV/GFP+ cells contained a provirus integrated within intron 1 of STAT3 , which led to increases in gene expression, STAT3 activation, and upregulation of a STAT3 -associated anti-apoptotic and cytotoxic phenotype. The STAT3 -associated gene signature shared similarities to the HIV-associated lymphomas with similar integration sites. Additionally, in all 3 replicates, insertional mutagenesis of genes other than STAT3 may have also contributed to clonal expansion of HIV/GFP+ T cells. Overall, we have demonstrated that HIV provirus insertional mutagenesis can influence T cell persistence. Our study provides a primary T cell culture model system that can be used to further study how proviral insertional mutagenesis influences HIV-associated T cell lymphomas and the safety of lentiviral vectors used in gene and cell therapies.
INTRODUCTION: Little is known about how people living with HIV would choose if offered different tuberculosis preventive treatment (TPT) regimens, and under which conditions they would accept treatment. Actionable evidence regarding preference for TPT is needed to inform policy and the development of novel TPT regimens. METHODS: Adults engaged in care at an HIV clinic in Kampala, Uganda, completed a discrete choice experiment survey with nine random choice tasks. In each task, participants first chose between two hypothetical TPT regimens with differing treatment features (number of pills, frequency, duration, adjusted antiretroviral dosage, and side effects). Second, they answered if they would accept the selected treatment, versus taking no treatment. We simulated predicted TPT regimen choice based on hierarchical Bayesian estimation of individual preference weights. RESULTS: Among 400 participants, 394 gave high-quality answers and were included (median age 44, 71.8% female, 91.4% previously received TPT). Across nine tasks, 60.2% (237/394) accepted all selected TPT regimens, 39.3% (155/394) accepted some regimens, and 0.5% (2/394) accepted none. Regimens requiring antiretroviral dosage adjustment were more likely to be unacceptable (adjusted odds ratio, aOR 27.4, 95% confidence interval [CI] 18.5 – 40.7), as were regimens requiring more pills per dose (aOR 24.5 [95% CI 16.6 – 36.3] for 10 pills compared to 1 or 5 pills per dose). Choice simulations showed that if only 6 months of daily isoniazid (6H) was available, 11.9% would prefer no TPT. However, offering a 4-pill, fixed-dose combination 3HP regimen in addition to 6H increased the acceptability from 88.1% to 98.8% (predicted choice of 3HP 94.5%, 6H 4.4%, no TPT 1.2%). CONCLUSIONS: While adults living with HIV in Uganda demonstrate a high willingness to accept different TPT regimens, offering regimens with preferred features, such as 3HP as a fixed-dose combination, could drive TPT acceptance and uptake from high to nearly universal.
Background Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa. Methods We conducted a modelling study to simulate hypertension and CVD across 3000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated two policies compared to current hypertension treatment: 1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy), and 2) CCC plus population-level hypertension screening of adults ≥40 years by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Findings Among adults 45-64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1-7%) to 14% (6-26%); additional CHW screening would improve control to 44% (35-54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3-17%), strokes by 13% (5-23%), and CVD mortality by 9% (3-15%). CCC plus CHW screening would reduce IHD by 28% (19-36%), strokes by 36% (25-47%), and CVD mortality by 25% (17-34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC. Interpretation Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa.
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BACKGROUND: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH). METHODS: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration. We analyzed data on adult PWH with measured alcohol use at any time from 6 months before starting antiretroviral therapy. Five cohorts measured alcohol use with AUDIT-C and others used cohort-specific measures. We harmonized alcohol use as grams/day, calculated using country-level definitions of a standard drink. For Alcohol Use Disorders Identification Test (AUDIT-C), we used Items 1 (frequency) and 2 (number of drinks on a typical day). Where alcohol was measured in categories, we used the mid-point to calculate grams/day. We used multivariable Cox models to estimate associations of alcohol use with mortality. RESULTS: Alcohol use data were available for 83,424 PWH, 22,447 (27%) had AUDIT-C measures and 60,977 (73%) recorded the number of drinks/units per week/day. Of the sample, 19,150 (23%) were female, 54,006 (65%) had White ethnicity, and median age was 42 years. Median alcohol use was 0.3 g/day (interquartile range [IQR] 0-4.8) and 0 g/day (IQR 0-20) for those with and without AUDIT-C. There was a J-shaped relationship between grams/day and mortality, with higher mortality for PWH reporting no alcohol use (adjusted hazard ratio [aHR] 1.46; 95% CI: 1.23-1.72) and heavier (>61.0 g/day) alcohol use (aHR 1.92; 1.41-2.59) compared with 0.1-5.5 g/day among those with AUDIT-C measures. Associations were similar among those with non-AUDIT-C measures. CONCLUSIONS: Grams/day is a useful metric to harmonize diverse measures of alcohol use. Magnitudes of associations of alcohol use with mortality may differ by setting and measurement method. Higher mortality among those with heavier alcohol use strengthens the case for interventions to reduce drinking.
BACKGROUND: Men who have sex with men (MSM) and female sex workers (FSW) are increasingly and disproportionately impacted by HIV in sub-Saharan Africa, yet current PrEP care models in this region are not optimized for these communities. Limited data exist describing experiences and preferences of MSM and FSW with respect to accessing and using PrEP. METHODS: We conducted qualitative, semi-structured interviews with MSM and FSW recruited from three health centers and seven community organizations in Kigali, Rwanda. Data were analyzed using a mixed deductive and inductive approach to describe key themes related to initiating and adhering to PrEP. RESULTS: Participants included 18 MSM and 14 FSW; 12 were using PrEP at the time of interview, 9 had previously used PrEP, and 11 had never used it. Participants highlighted the central role of their social networks as key sources of information about and support for PrEP use, and described a strong motivation to use PrEP as a way to protect both themselves and their communities from HIV. While stigma and discrimination were pervasive, these were experienced differently by MSM and FSW. Participants suggested community access points that allowed more discreet and less frequent contact with health care workers as important and desired strategies to improve engagement. CONCLUSIONS: These findings suggest that leveraging community resources for disseminating information about HIV prevention and delivering PrEP could contribute to successful implementation of PrEP for MSM and FSW in Rwanda and other settings in SSA.
Molecular epidemiology (ME) is a field that integrates molecular biology techniques with traditional epidemiological methods to study the distribution, determinants, and dynamics of disease. In the context of HIV, ME involves analysing genetic sequences of the virus to understand patterns of transmission, evolution, and the relationships between social, behavioural, and biological factors that influence transmission. This holds great promise in the global effort to further reduce HIV transmission, although its use raises significant ethical issues. ME is not currently used in Australia’s public health response to HIV, although experiences from other countries emphasize the importance of community consultation and support to avoid unintended negative consequences, such as deterring individuals from accessing sexual health services. This article explores the perspectives of twenty-three participants, recruited through HIV/sexual health-related organizations in Victoria, Australia, via nineteen semi-structured interviews and one focus group. Participants included people who regularly test for sexually transmissible infections (STIs) and people diagnosed with HIV and/or syphilis/gonorrhoea. Participants often reported vague or no prior understanding of ME (19/23; 82.6 per cent); however, many of those with vague or no understanding were supportive (16/19; 84.2 per cent). A subset of participants raised concerns, including those related to privacy risks, misuse of data, and the disproportionate impact on marginalized groups. These findings reinforce the need for meaningful community engagement and safeguards for potential ethical use of ME in Australia.
Large language models (LLMs) are emerging as valuable tools to support clinicians in routine decision-making. HIV management is a compelling use case due to its complexity, including diverse treatment options, comorbidities, and adherence challenges. However, integrating LLMs into clinical practice raises concerns about accuracy, potential harm, and clinician acceptance. Despite their promise, AI applications in HIV care remain underexplored, and LLM benchmarking studies are scarce. This study evaluates the current capabilities of LLMs in HIV management, highlighting their strengths and limitations. We introduce HIVMedQA, a benchmark designed to assess open-ended medical question answering in HIV care. The dataset consists of curated, clinically relevant questions developed with input from an infectious disease physician. We evaluated seven general-purpose and three medically specialized LLMs, applying prompt engineering to enhance performance. Our evaluation framework incorporates both lexical similarity and an LLM-as-a-judge approach, extended to better reflect clinical relevance. We assessed performance across key dimensions: question comprehension, reasoning, knowledge recall, bias, potential harm, and factual accuracy. Results show that Gemini 2.5 Pro consistently outperformed other models across most dimensions. Notably, two of the top three models were proprietary. Performance declined as question complexity increased. Medically fine-tuned models did not always outperform general-purpose ones, and larger model size was not a reliable predictor of performance. Reasoning and comprehension were more challenging than factual recall, and cognitive biases such as recency and status quo were observed. These findings underscore the need for targeted development and evaluation to ensure safe, effective LLM integration in clinical care.
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.
Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but immunological restauration at mucosal barrier surfaces is not achieved. This fuels microbial translocation, chronic immune activation, and increased comorbidities, including cardiovascular disease (CVD). Here, we sought to identify novel markers of mucosal barrier impairment in the blood to predict the HIV and/or CVD status. Flow cytometry was used to characterize CD326/EpCAM (+) intestinal epithelial cells (IEC); CD4 (+) T-cells; CD8 (+) and CD4 (+) intraepithelial lymphocytes (IELs); and subsets of CD4 (+) T-cells expressing Th17 (CCR6) and gut-homing (Itgβ7) markers. To this aim, we collected peripheral blood mononuclear cells (PBMCs) from 42 ART-treated PWH (HIV (+) ) and 40 uninfected participants (HIV (-) ) from the Canadian HIV and Aging Cohort Study (CHACS). Both groups were categorized based on the presence of coronary atherosclerotic plaques measured by CT scan angiography as total plaque volume (TPV, mm (3) ). Our findings associate the HIV-1 status with increased frequencies of circulating CD326 (+) IEC; CD326 (+) CD4 (+) T-cells with activated (CD69 (+) HLA-DR (+) ) and gut-homing (ItgαE (+) CCR6 (+) CCR9 (+) ) phenotypes, CCR6 (+) Itgβ7 (-) CD4 (+) T-cells; and decreased frequencies of CD8 (+) IELs. Logistic regression analyses confirmed the predictive capacity of the above cellular markers regarding HIV status. Spearman correlation revealed a positive correlation between TPV and CCR6 (+) Itgβ7 (-) and CCR6 (+) Itgβ7 (+) CD4 (+) T-cell frequencies.Together, these results highlighted significant immune dysregulation and persistent mucosal barrier alterations despite effective viral suppression by ART and linked the abundance of CCR6 (+) Itgβ7 (+) and CCR6 (+) Itgβ7 (-) CD4 (+) T-cells to increased atherosclerotic plaque burden. Thus, strategies targeting the gut-immune axis restoration may reduce CVD onset and improve long-term health outcomes in PWH.
Background Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. Methods Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). Results Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. Conclusion CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.
PSGL-1 (P-selectin glycoprotein ligand-1) is a dimeric, mucin-like surface glycoprotein that interacts with selectins on the endothelium, facilitating leukocyte tethering and rolling during transmigration. Previous studies have demonstrated that PSGL-1 acts as an HIV restriction factor, blocking HIV infectivity by hindering particle attachment to target cells. A large part of PSGL-1’s extracellular region consists of a mucin-like domain, characterized by decameric repeats (DR), which comprise 14 to 16 DR tandems. Each DR is composed of 10 consensus amino acids (-A-T/M-E-A-Q-T-T-X-P/L-A/T-) and is notably rich in O-glycosylated threonines (30%) and prolines (10%). A proposed function of the DR is to elongate the protein backbone needed for selectin binding. However, the precise role of DR in PSGL-1’s antiviral mechanisms has yet to be fully elucidated. In this study, we performed DR deletion mutagenesis and molecular modeling, systematically deleting from one DR to all DRs, and quantified their effects on PSGL-1’s antiviral functions. Here, we demonstrate that DR is necessary for PSGL-1’s antiviral activity. Deleting DR did not affect virion incorporation of PSGL-1, but diminished PSGL-1’s ability to hinder virion attachment to target cells. We also discovered that individual single DR mutants retained 3.5 to 18% of the antiviral activity exhibited by full-length PSGL-1, and the basic antiviral activity of DR is cumulative; increasing the number of DRs correlates with heightened antiviral activity. Additionally, the intrinsic anti-HIV capability of DR was found to be transferrable; inserting the DR domain into the extracellular Ig-like domain of CD2 permitted the hybrid CD2-DR molecules to partially acquire the anti-HIV properties of PSGL-1. Further molecular modeling utilizing all-atom replica exchange molecular dynamics simulations highlighted a structure-function relationship between the anti-HIV potency of DR and the elongation of the DR backbone, as measured by DR backbone dihedral angles ([Formula: see text]) and the radial distributions of peptide atom number density ([Formula: see text]). These results collectively suggest that DR serves as an essential antiviral unit within the framework of PSGL-1’s restriction mechanism against HIV.
Since the widespread use of combination antiretroviral therapy, the incidence of opportunistic infections has decreased in HIV infection populations. However, HIV-associated lymphoma become the most common causes of cancer death. Little is known about the epidemiology, survival and treatment of HIV-associated lymphoma patients in China as these are less common than HIV-negative lymphoma. We performed a multi-center retrospectively study to analyze the epidemiology, clinical characteristics and outcomes of HIV-associated lymphoma in China. Totally 407 newly diagnosed HIV-associated lymphoma patients at eleven medical centers from July 2008 to October 2021, were analyzed, as the largest cohort reported in China to date. In the entire cohort, including 373 (91.6%) B-cell lymphoma, 19 (4.7%) HL patients, and 11 (2.7%) T-cell lymphoma. Among B-cell lymphoma, DLBCL was the most common (n = 273, 73.2%), followed by BL (n = 47, 12,6%). The median age was 47 years (range, 18–90) at lymphoma diagnosis, and 332 patients were male (81.6%), 254 patients (62.4%) were diagnosed with advanced stage (III/IV). In the entire cohort, 57 (14.0%) patients did not receive anti-lymphoma treatment, 350 patients (86.0%) underwent chemotherapy as part of their first-line treatment. More than half of them (241/350, 68.9%) had underwent 4 cycles or more of chemotherapy. The median follow-up of our cohort was 65 (36–186) months. The estimated 5-year OS rates in the HL and NHL cohort were 83.6% and 50.9%, respectively. The 5-year OS rates demonstrated an inverse correlation with ART duration prior to lymphoma diagnosis: 65.4% for patients not receiving ART before lymphoma diagnosis, 54.2% for those on ART for less than 12 months, and 42.8% for those on ART for ≥ 12 months ( p = 0.014). This study depicts a broad picture of HIV-associated lymphoma, treatment options and survival information in China. These data suggested that HIV-associated lymphoma patients presented with aggressive clinical characteristics and rituximab, enhanced chemotherapy administration and shorter ART duration before lymphoma diagnosis was significantly associated with improved outcomes.
INTRODUCTION: Tuberculosis (TB) stigma is a critical barrier to timely diagnosis and treatment. Although stigma originates within communities, few studies have quantified community-level TB stigma or its variability across geographic contexts. This study describes methods for capturing community-level TB stigma and examines stigma variability across 93 urban, peri-urban, and rural communities in Buffalo City Metropolitan Health District, South Africa. METHODS: As part of the MISSED TB Outcomes Study, heads of household (HoHs) were surveyed in a geographically clustered random sample of households across demarcated study communities. Validated scales were used to measure perceived community-level TB stigma, HIV stigma, and TB/HIV knowledge. Demographic data, including self-reported household TB and HIV history, were also captured. Community-level data, including TB and HIV stigma, were generated by aggregating individual responses within each study community. Associations between TB stigma and other community-level variables were analyzed using robust linear regression. RESULTS: Surveys were completed by 3,869 households across 93 communities. Median community TB stigma scores varied significantly by community location, with rural communities reporting the lowest stigma and peri-urban communities the highest. TB stigma was positively associated with HIV stigma across all community types, with the strongest associations in urban and rural communities. No associations were observed between TB stigma and TB prevalence, TB knowledge, or household demographics after adjusting for community location. CONCLUSIONS: TB stigma varied meaningfully across communities and was influenced by urbanicity and HIV stigma. These findings suggest that stigma-reduction interventions must be tailored to local contexts and consider community-level determinants beyond individual knowledge or TB burden. The identified variability in TB stigma will inform future multilevel analyses of the TB care cascade in South Africa.
Introduction Men-who-have-sex-with-men (MSM), as well as transgender and non-binary individuals, continue to face a disproportionate burden of stigma, mental health challenges, HIV, and other sexually transmitted infections. To address their needs, public health planners require reliable and comparable data. Monitoring behaviours in these populations also supports the evaluation of health policies. Methods The European-MSM-Internet-Survey (EMIS-2024) builds on our international surveys conducted in 2010 and 2017, expanding its scope to include explicitly transgender women and non-binary people. It provides much-needed data for planning interventions, promoting health, and harmonising behavioural surveillance. A key strength of EMIS-2024 is the use of a shared sampling frame and a core questionnaire across all participating countries. This approach allows meaningful cross-national comparisons, unlike many national surveys with varying methods. The three core consortium partners (Deutsche Aidshilfe, Robert Koch Institute and Maastricht University) led the revision of the EMIS-2017 questionnaire. Results Over 60 partners from 40 countries played a key role in the survey’s success, providing high-quality translations in 35 languages and actively promoting the survey. National partners ensured the survey’s visibility, credibility, and relevance once dating app advertisements or invitations appeared. The survey ran online during the first half of 2024. Overall, 165,380 responses were received, of which 50,330 qualified for the analytic sample. Conclusions and Policy Implications EMIS-2024 demonstrates that large-scale, multi-country sexual health surveys are feasible with public funding. A harmonised questionnaire, shared sampling strategy, and meaningful community involvement were key to generating robust, comparable data across Europe.
Objectives Although a wealth of studies has explored the impact of individual meteorological variables on influenza transmission, investigations of these effects within key subgroups—such as viral type, sex, and age—remain scarce. Moreover, long-term daily time-series influenza surveillance data are exceptionally limited. To address these shortcomings, we herein present a meticulously curated daily time-series dataset spanning approximately 11 years from Kawasaki City, Japan, to facilitate comprehensive analyses of the short-term association between meteorological variables and influenza incidence. This resource also aims to aid researchers, educators, and students by fostering the application of time-series regression modelling in both research and educational contexts. Data description Daily total number of influenza cases and ambient meteorological data—mean, minimum, and maximum temperature (°C); relative humidity (%); wind speed (m s⁻¹); rainfall (mm); sunshine duration (hours); and vapour pressure (hPa)—were collated for Kawasaki City, Japan (March 2014–April 2025). Influenza cases were stratified by virus type (A/B), sex (male/female), and age (0–5, 6–11 months; 1–9 years in single-year bands; 10–14, 15–19, 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, ≥ 80 years).
International audience;
Influenza virus is one of the main causes of respiratory infections worldwide. Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists. In this study, we identified non-steroidal estrogens as potent inhibitors of influenza virus due to their interaction with the hemagglutinin protein, preventing viral entry. This activity is maintained in vitro, ex vivo, and in vivo. Therefore, we found a new domain to target on the hemagglutinin and a class of compounds that could be further optimized for influenza treatment.
BACKGROUND: Streptococcus pneumoniae (Spn) is typically an asymptomatic colonizer of the nasopharynx but it also causes pneumonia and disseminated disease affecting various host anatomical sites. Transition from colonization to invasive disease is not well understood. Studies have shown that such a transition can occur as result of influenza A virus coinfection. METHODS: We investigated the pneumococcal (serotype 19F, strain EF3030) and host transcriptomes with and without influenza A virus (A/California/07 2009 pH1N1) infection at this transition. This was done using primary, differentiated Human Bronchial Epithelial Cells (nHBEC) in a transwell monolayer model at an Air-Liquid Interface (ALI), with multispecies deep RNA-seq. RESULTS: Distinct pneumococcal gene expression profiles were observed in the presence and absence of influenza. Influenza coinfection allowed for significantly greater pneumococcal growth and triggered the differential expression of bacterial genes corresponding to multiple metabolic pathways; in totality suggesting a fundamentally altered bacterial metabolic state and greater nutrient availability when coinfecting with influenza. Surprisingly, nHBEC transcriptomes were only modestly perturbed by infection with EF3030 alone in comparison to that resulting from Influenza A infection or coinfection, which had drastic alterations in thousands of genes. Influenza infected host transcriptomes suggest significant loss of ciliary function in host nHBEC cells. CONCLUSIONS: Influenza A virus infection of nHBEC promotes pneumococcal infection. One reason for this is an altered metabolic state by the bacterium, presumably due to host components made available as result of viral infection. Influenza infection had a far greater impact on the host response than did bacterial infection alone, and this included down regulation of genes involved in expressing cilia. We conclude that influenza infection promotes a pneumococcal metabolic shift allowing for transition from colonization to disseminated disease. AUTHOR SUMMARY: Secondary Streptococcus pneumoniae bacterial infections typically occur after influenza A virus respiratory infection. Such coinfections often lead to invasive pneumococcal disease. The mechanisms involved in this process are not well understood. Here, using an ex vivo human lung bronchial epithelial cell model, we investigated the biological processes of the host and pneumococcus occurring at this niche, during coinfection with multi-species transcriptomics techniques, and in vivo mouse model experimentation. We observed stark differences in global pneumococcal metabolism in different infection states, as well as viral induced epithelial cell changes in ciliary function, potentially aiding pneumococcal dissemination. Overall, this study identified broad and targeted biological processes involved in this host-pathogen interaction.
AIMS: This research assessed healthcare workers' vaccination practices for influenza, hepatitis, and pneumonia, as well as their desire to get COVID-19 vaccine when accessible, and investigated their 7C psychological antecedents (confidence, complacency, collective responsibility, compliance, calculation, constraints and conspiracy). Stress variables and vaccination intention for COVID-19 were also compared to see whether psychological stress had a meditative impact on the relationship. METHODS: An analytical cross-sectional survey was conducted among health care professionals including nurses and doctors of tertiary care hospitals of Rawalpindi. Data were collected from February to April 2021 to get the COVID-19 vaccination when it became available, and looked into their 7C mental forebears (confidence, complacency, collective responsibility, compliance, calculation, constraints and conspiracy). A total of 642 health care professionals voluntarily participated in our research. Demographic Details, questions like pneumonia vaccination, hepatitis vaccination, influenza vaccination and 7C questions were asked. Data were entered and analysed through SPSS 26.0 and Python. Correlation, linear and non linear regression, and mediation analysis were applied. RESULTS: The immunization rates for influenza, hepatitis, and pneumonia vaccines, as well as the percentage of those who received COVID-19 vaccination, were 43.4%, 65.2%, 42.8%, and 39.7%, respectively. Hepatitis vaccination was significantly associated with the 7C model, influenza vaccination with conspiracy, whereas pneumonia was significantly associated with compliance. confidence (r = 0.11), complacency (r = −0.19), constraints (r = −0.20), calculation (r = 0.08), collective responsibility (r = 0.18), and compliance (r = 0.19) were significantly corelated with the COVID-19 Vaccine Intention. Contrary to direct effect, the indirect effect of patient contact frequency (β = −0.01, ρ<0.05) and terrified of contracting virus (β = −0.05, ρ<0.05) via psychological stress on COVID-19 Vaccination intention were significant depicting full mediation. CONCLUSION: For herd immunity, the probability for COVID-19 vaccination uptake among healthcare professionals was less than optimal. The 7C structures may help predict immunization against influenza, hepatitis, and pneumonia, but not vaccination against COVID-19.
Cold Spring Harbor LaboratoryFebruar 2023Influenza
Intracellular pathogens interact with host factors, exploiting those that enhance replication while countering those that suppress it. Genetic screens have begun to define the host:pathogen interface and establish a mechanistic basis for host-directed therapies. Yet, limitations of current approaches leave large regions of this interface unexplored. To uncover host factors with pro-pathogen functions, we developed a novel fitness-based screen that queries factors important during the middle-to-late stages of infection. This was achieved by engineering influenza virus to direct the screen by programing dCas9 to modulate host gene expression. A genome-wide screen identified the cytoplasmic DNA exonuclease TREX1 as a potent pro-viral factor. TREX1 normally degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self DNA. Our mechanistic studies revealed that this same process functions during influenza virus infection to enhance replication. Infection triggered release of mitochondrial DNA into the cytoplasm, activating antiviral signaling via cGAS and STING. TREX1 metabolized the mitochondrial DNA preventing its sensing. Collectively, these data show that self-DNA is deployed to amplify host innate sensing during RNA virus infection, a process tempered by TREX1. Moreover, they demonstrate the power and generality of pathogen driven fitness-based screens to pinpoint key host regulators of intracellular pathogens.
BACKGROUND: Side effects following vaccination intensify vaccine hesitancy, which remains a significant challenge to public health. Research suggests that a proportion of side effects are not caused by the vaccine but are instead associated with psychological factors that influence nocebo responding. PURPOSE: This study investigates the psychological and demographic factors associated with symptom reporting postvaccination, the attribution of these symptoms as side effects, and their influence on future intentions to vaccinate. METHODS: A prospective, longitudinal design was employed with 225 influenza vaccination recipients. Demographic and psychological measures (including anxiety, vaccination attitudes, and side effect expectations) were completed at baseline. Side effects were measured immediately and 1-week following the vaccination. Future intentions to vaccinate were measured 1-week postvaccination. RESULTS: Anxiety (P < .001) and perceived sensitivity to vaccines (P = .044) predicted the number of symptoms reported immediately following vaccination. Anxiety (P < .001) and perceived sensitivity (P = .035) along with baseline symptoms (P < .001) predicted symptoms 1 week following the vaccination. Female gender (P = .003), younger age (P = .018), anxiety (P < .001), and baseline symptoms (P = .009) predicted whether participants attributed symptoms as vaccination side effects. Anti-vaccination attitudes were associated with less intention to vaccinate in the future (P = .033). CONCLUSIONS: Nocebo-associated psychological factors contributed to symptoms experienced after an influenza vaccination. Findings demonstrate that the way symptoms are noticed, and then interpreted as side effects, appear to be separate mechanisms promoted by different factors. This study improves identification of side effect reporters prior to vaccination.
HAL CCSD; American Society for MicrobiologyJuni 2022Influenza
International audience;
Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. Viruses from these two principal sources can be distinguished by their hemagglutinin genes, which segregate into two distinct sublineages (termed B1 and B2) within clade 2.3.4.4b, as well as their different internal gene compositions. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe.
Klinische Qualitätssteuerung (KQS) meint ein Qualitätsmanagement im klinischen Bereich. Vermutlich aufgrund der Coronapandemie meldeten sich im Jahr 2020 deutlich mehr influenzaimpfwillige Patient*innen als in den Vorjahren, sodass sich abzeichnete, dass für Hochrisikopatient*innen nicht ausreichend Impfdosen zur Verfügung stehen würden. Um dem Problem zu begegnen, setzten wir einen KQS-Zyklus in Gang. Bei diesem Artikel handelt es sich explizit nicht um eine wissenschaftliche Arbeit, sondern um die exemplarische Beschreibung einer Priorisierung und einer KQS als Beispiel, zur Anregung und zur Diskussion. Wir erstellten folgenden Prozess: 1. Evaluation des Ist-Zustands; 2. Priorisierung der Patient*innen, die sich als impfwillig gemeldet hatten, und Impfung der Hochrisikogruppe zuerst; 3. Identifikation, telefonische Kontaktierung und Impfung der Hochrisikopatient*innen, die sich nicht selbstständig als impfwillig gemeldet hatten. Patient*innen über 60-Jahre mit chronisch obstruktiver Lungenerkrankung (COPD) wurden als Indikatorgruppe gewählt. Zunächst waren nur 3 (8 %) unserer 38 COPD-Patient*innen gegen Influenza geimpft. Nach Priorisierung und Impfung der Hochrisikogruppe in der Liste der Impfwilligen waren 25 (66 %) der insgesamt 38 COPD-Patient*innen geimpft. Nach telefonischer Einladung und Aufforderung waren zuletzt 28 (74 %) der 38 Patient*innen geimpft. Dies entspricht einer Steigerung der Impfquote der über 60-jährigen COPD-Patient*innen von 8 % auf 74 % und damit nahezu dem Zielwert der Weltgesundheitsorganisation (WHO). Hausärzt*innen müssen sich gelegentlich mit Ressourcenknappheit auseinandersetzen und sich mit Strategien beschäftigen, ihr zu begegnen. Unter anderem in diesem Zusammenhang bietet sich eine KQS in der Hausarztpraxis an. Die Praxisverwaltungssysteme (PVS) sollten für diesen Zweck von Seiten der Hersteller benutzerfreundlicher gestaltet werden. We understand clinical quality governance (CQG) as quality management in the clinical domain. In 2020, presumably due to the coronavirus pandemic, more patients requested to be vaccinated against influenza as compared to previous years so that it became apparent that there would be a shortage for high-risk patients. To meet the problem, we started a CQG process. This article is explicitly not a research article but an exemplary description of a CQG process intended as a stimulus and for discussion. We initiated the following process: (1) evaluation of the present state, (2) patients who already had requested a vaccination were prioritized and vaccinated first, and (3) contacting via telephone and vaccination of high-risk patients not on the list. We chose patients with chronic obstructive pulmonary disease (COPD) older than 60 years as an indicator for the group of highest priority. In the beginning only 3 (8%) of our 38 patients with COPD were vaccinated against influenza. After prioritization and vaccination of the high-risk collective in the list of those who had requested to be vaccinated, 25 (66%) of our 38 patients with COPD were vaccinated. After a phone call of high-risk patients not on the list, 28 (74%) patients were vaccinated. This represents an increase of vaccination coverage from 8% to 74% which is close to the rate recommended by the World Health Organization (WHO). In times of a pandemic, family physicians occasionally have to deal with a scarcity of resources and have to develop strategies for fair resource allocation. Not only in this context is CQG worth the effort. The generation of list queries could be improved by the providers of electronic patient records.
BACKGROUND: The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma). METHODS: This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017–2019). The RiiQ™ Symptom Scale and EuroQol 5‐Dimensions 5‐Levels (EQ‐5D‐5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post‐discharge. RESULTS: Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post‐discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post‐discharge. Participants with CRF reported more moderate‐to‐severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(−) participants post‐discharge. EQ‐5D‐5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains. CONCLUSIONS: Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ‐5D‐5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies.
Tabriz University of Medical SciencesSeptember 2021Influenza
Purpose: The aminoadamantane derivative of L-histidyl-1-adamantayl ethylamine hydrochloride (HCl*H-His-Rim) has showed a high inhibition level against influenza A virus strains in vitro. The aim of this work is to search and establish evidence of the direct effect of the drug on influenza A virus proton channel M2. Methods: The compound HCl*H-His-Rim was obtained by classical peptide synthesis methods. Influenza A virus mutants of A/PuertoRico/8/34(H1N1) strain were obtained by reverse genetics methods. The mutant samples of the virus were cultured on chicken embryos with a virus titer in the hemagglutination test. ELISA was carried out on Madin-Darby canine kidney (MDCK) monolayer cells when multiplying the virus 10(-4)-10(-6). The binding stability of HCl*H-His-Rim was compared to those of M2 (S31N) and M2 (S31N_A30T) channels by molecular dynamic (MD) modeling. The calculation was performed taking into account the interaction with the model lipid bilayer (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) in the presence of water molecules in accordance with the three-center model. Results: It was found that HCl*H-His-Rim is a direct action drug against influenza A. The most likely conformation of drug binding to target protein has been shown. It has been found that the A30T mutation reduces the binding energy of the drug, and the results obtained in vitro have confirmed the data calculated in silico. Conclusion: The mechanism of action of HCl*H-His-Rim is directly related to the suppression of the function of the proton channel M2 of influenza A virus.
[Image: see text] Reverse genetics (RG) systems have been instrumental for determining the molecular aspects of viral replication, pathogenesis, and for the development of therapeutics. Here, we demonstrate that genes encoding the influenza surface antigens hemagglutinin and neuraminidase have varying stability when cloned into a common RG plasmid and transformed into Escherichia coli. Using GFP as a reporter, we demonstrate that E. coli expresses the target genes in the RG plasmid at low levels. Incorporating lac operators or a transcriptional terminator into the plasmid reduced expression and stabilized the viral genes to varying degrees. Sandwiching the viral gene between two lac operators provided the largest contribution to stability and we confirmed the stabilization is Lac repressor-dependent and crucial for subsequent plasmid propagations in E. coli. Viruses rescued from the lac operator-stabilized plasmid displayed similar kinetics and titers to the original plasmid in two different viral backbones. Together, these results indicate that silencing transcription from the plasmid in E. coli helps to maintain the correct influenza gene sequence and that the lac operator addition does not impair virus production. It is envisaged that sandwiching DNA segments between lac operators can be used for reducing DNA segment instability in any plasmid that is propagated in E. coli which express the Lac repressor.
This retrospective study included COPD patients who attended our medical center between January and October 2018, and analyzed the outcomes of their influenza vaccination, including medical visits, hospitalization, medical expenses, and the incidence of respiratory failure. Airflow limitation was stratified according to GOLD guidelines. Overall, 543 COPD patients were enrolled, including 197, 113, 126, and 107 mild, moderate, severe, and very severe patients, respectively. Of all the participants, 238 received an influenza vaccination (43.8%), which significantly reduced hospital utilization for moderate (odds ratio [OR] 0.22, 95%CI 0.09–0.51), severe (OR 0.19, 95%CI 0.08–0.44), and very severe patients (OR 0.15, 95%CI 0.05–0.5) compared to mild patients (OR 0.51, 95%CI 0.2–1.26); reduced emergency department utilization for moderate (OR 0.33, 95%CI 0.14–0.77), severe (OR 0.22, 95%CI 0.10–0.52), and very severe patients (OR 0.30, 95%CI 0.10–0.88) compared to mild patients (OR 0.64, 95%CI 0.30–1.37); and reduced the occurrence of respiratory failure for moderate (OR 0.20, 95%CI 0.06–0.68), severe (OR 0.40, 95%CI 0.16–0.98), and very severe patients (OR 0.36, 95%CI 0.15–0.82) compared to mild patients (OR 0% CI 0.14–3.20). Influenza vaccination is more effective in COPD patients with moderate, severe, and very severe airflow obstruction than in those with mild obstruction with respect to hospital utilization, emergency department utilization, and respiratory failure.
Live bird markets (LBMs) are considered hotspots for Avian Influenza Viruses (AIVs). In such markets, AIVs pose threats to both poultry and public health. Within LBMs, AIVs spread through various routes, including direct contact, environmental contamination, and aerosol transmission. Unique factors in Egyptian LBMs, such as the coexistence of wild and domestic birds, increase transmission risks between birds as well as spill-overs into exposed humans. Understanding the transmission dynamics of AIVs is vital for implementing effective control measures. We conducted a study in four Egyptian LBMs located in Mediterranean coast cities from November 2021 to March 2023. In this study we tested 3,971 samples from poultry, wild birds, and the environment, out of which 692 (17.4%) were positive for AIV. Poultry exhibited a higher prevalence (42.2%) than wild birds (34.4%). Environmental samples, including water (30.8%), surfaces (17.2%), and air (18.2%), also tested positive for AIV. Diverse AIV subtypes, including H5N1, H9N2, H5/H9 co-infection, and H5N8, were detected among avian species and the environment. Temporal analysis revealed fluctuating IAV positivity rates from November 2021 to March 2023. These results emphasize the importance of continuous surveillance, resource allocation, and multisectoral collaboration to protect poultry and human health, and prevent novel influenza strains’ emergence in Egyptian LBMs.
Background Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. Methods Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students’ t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. Results PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body’s metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. Conclusions This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.
BACKGROUND: Common air pollutants such as ozone (O(3)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and particulate matter play significant roles as influential factors in influenza-like illness (ILI). However, evidence regarding the impact of O(3) on influenza transmissibility in multi-subtropical regions is limited, and our understanding of the effects of O(3) on influenza transmissibility in temperate regions remain unknown. METHODS: We studied the transmissibility of influenza in eight provinces across both temperate and subtropical regions in China based on 2013 to 2018 provincial-level surveillance data on influenza-like illness (ILI) incidence and viral activity. We estimated influenza transmissibility by using the instantaneous reproduction number ([Formula: see text] ) and examined the relationships between transmissibility and daily O(3) concentrations, air temperature, humidity, and school holidays. We developed a multivariable regression model for [Formula: see text] to quantify the contribution of O(3) to variations in transmissibility. RESULTS: Our findings revealed a significant association between O(3) and influenza transmissibility. In Beijing, Tianjin, Shanghai and Jiangsu, the association exhibited a U-shaped trend. In Liaoning, Gansu, Hunan, and Guangdong, the association was L-shaped. When aggregating data across all eight provinces, a U-shaped association was emerged. O(3) was able to accounted for up to 13% of the variance in [Formula: see text] . O(3) plus other environmental drivers including mean daily temperature, relative humidity, absolute humidity, and school holidays explained up to 20% of the variance in [Formula: see text] . CONCLUSIONS: O(3) was a significant driver of influenza transmissibility, and the association between O(3) and influenza transmissibility tended to display a U-shaped pattern. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08769-w.
Cold Spring Harbor LaboratoryOktober 2024Influenza
BACKGROUND: Sleep is increasingly recognized as essential to human health, yet the adverse health consequences of acute sleep deprivation are unknown. Using actigraphic, genomic, and health data from the All of Us ( AoU ) Research Program, we characterized the detrimental health consequences of acute sleep deprivation in the American public. METHODS: LOESS smoothing was performed on sleep estimates from Fitbit users (N = 14,681) between June 1, 2016 and July 1, 2022. Dates when population minutes slept were less than the 90% confidence interval of the LOESS regression were named acute sleep deprivation events (ASDEs). Phenome-wide disease incidence among the AoU population (N = 287,012) in the 10 days post-ASDE was compared to a preceding reference period by McNemar test. Circadian rhythm and sleep duration-associated SNPs were screened to identify genotypes associated with shorter ASDE sleep duration. Influences of sleep and circadian genotype on post-ASDE influenza risk were modeled using binomial family generalized estimating equations. FINDINGS: We identified 32 ASDEs spanning political and non-political events. A phenome-wide screen found increased risk of influenza (OR = 1.54 [1.40, 1.70], P -value = 1.00 x 10 (-18) ) following ASDEs. 56 SNPs were associated with decreased sleep duration on ASDEs. Higher quantiles of ASDE-related SNP genotype burden were associated with less ASDE sleep duration and a greater risk of influenza-associated healthcare visits. INTERPRETATION: National political and non-political events are associated with acute sleep deprivation and greater influenza risk which is amplified by sleep genotypes. These findings should inform public health vigilance surrounding major national events.
Background Seasonal influenza and other respiratory tract infections are serious public health problems that need to be further addressed and investigated. Internet search data are recognized as a valuable source for forecasting influenza or other respiratory tract infection epidemics. However, the selection of internet search data and the application of forecasting methods are important for improving forecasting accuracy. The aim of the present study was to forecast influenza epidemics based on the long short-term memory neural network (LSTM) method, Baidu search index data, and the influenza-like-illness (ILI) rate. Methods The official weekly ILI% data for northern and southern mainland China were obtained from the Chinese Influenza Center from 2018 to 2021. Based on the Baidu Index, search indices related to influenza infection over the corresponding time period were obtained. Pearson correlation analysis was performed to explore the association between influenza-related search queries and the ILI% of southern and northern mainland China. The LSTM model was used to forecast the influenza epidemic within the same week and at lags of 1–4 weeks. The model performance was assessed by evaluation metrics, including the mean square error (MSE), root mean square error (RMSE) and mean absolute error (MAE). Results In total, 24 search queries in northern mainland China and 7 search queries in southern mainland China were found to be correlated and were used to construct the LSTM model, which included the same week and a lag of 1–4 weeks. The LSTM model showed that ILI% + mask with one lag week and ILI% + influenza name were good prediction modules, with reduced RMSE predictions of 16.75% and 4.20%, respectively, compared with the estimated ILI% for northern and southern mainland China. Conclusions The results illuminate the feasibility of using an internet search index as a complementary data source for influenza forecasting and the efficiency of using the LSTM model to forecast influenza epidemics.
Background Despite thousands of influenza cases annually recorded by surveillance systems around the globe, estimating the transmission patterns of seasonal influenza is challenging. Methods We develop an age-structured mathematical model to influenza transmission to analyze ten consecutive seasons (from 2010 to 2011 to 2019–2020) of influenza epidemiological and virological data reported to the Italian surveillance system. Results We estimate that 18.4–29.3% of influenza infections are detected by the surveillance system. Influenza infection attack rate varied between 12.7 and 30.5% and is generally larger for seasons characterized by the circulation of A/H3N2 and/or B types/subtypes. Individuals aged 14 years or less are the most affected age-segment of the population, with A viruses especially affecting children aged 0–4 years. For all influenza types/subtypes, the mean effective reproduction number is estimated to be generally in the range 1.09–1.33 (9 out of 10 seasons) and never exceeding 1.41. The age-specific susceptibility to infection appears to be a type/subtype-specific feature. Conclusions The results presented in this study provide insights on type/subtype-specific transmission patterns of seasonal influenza that could be instrumental to fine-tune immunization strategies and non-pharmaceutical interventions aimed at limiting seasonal influenza spread and burden.
Cold Spring Harbor LaboratoryOktober 2021Influenza
INTRODUCTION: Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort. METHODS: We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression. RESULTS: There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38–1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95–1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98–1.25) and MI (HR 0.93, 95% CI 0.85–1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19–1.56) and PE (HR 1.82, 95% CI 1.57–2.10) in patients with COVID-19. CONCLUSION: In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.
Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen‐specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections.
Huangqin Su (HQS) tablet is mainly composed of baicalein which has been evaluated for its ability to inhibit influenza. The present study aimed to investigate the effect of HQS and oseltamivir phosphate (OS) (single or combination therapy) on influenza-induced acute pneumonia in male and female ICR mice. The regulatory effect of HQS on gut microbiota was also studied by using 16 s rDNA sequencing, and the targets and mechanisms of HQS against influenza were comprehensively analyzed by network pharmacology. Pharmacodynamic results, including lung index and pathological changes, showed that HQS exhibited significant anti-influenza efficacy and could improve the efficacy of low-dose OS ( P < 0.05 and P < 0.01, respectively). The results of 16 s rDNA sequencing revealed that HQS modulated the gut microbiota and remarkably enriched the abundance of Lactobacillus . The findings of network pharmacology research suggested that the anti-influenza mechanism of HQS was related to TLRs, MAPK, and other signal transduction pathways. Taken together, this study identified the possibility of the combined use of HQS and OS and demonstrated the role of HQS in modulating the gut microbiota of mice against influenza. Network pharmacology studies also suggested that the anti-influenza effect of HQS was related to TLRs, MAPK, TNF, and other signaling pathways.
BACKGROUND. Influenza predisposes individuals to bacterial co-infections, which can result in disseminated infection and bacteremia. We describe the epidemiology and outcomes of blood culture co-detections among those hospitalized with influenza over 2 influenza seasons. METHODS. We sampled individuals of all ages from FluSurv-NET, a US population–based surveillance network of persons hospitalized with laboratory-confirmed influenza, during the 2022–2023 and 2023–2024 seasons. Surveillance staff collected information on bacterial blood cultures within 3 days before or 3 days following admission. We described patient characteristics and in-hospital outcomes, stratified by culture positivity, number of positive cultures, and type of co-detection, using unweighted counts and weighted percentages to account for the complex survey design. RESULTS. Overall, 14 316 patients were included, with a median (interquartile range) age of 57 (14–74) years, 53.6% female, 52.0% non-Hispanic White, and 25.6% with ≥4 categories of underlying medical conditions. Of these, 50.8% had ≥1 blood cultures obtained and 5.2% overall had ≥1 bacterial co-detections. Intensive care unit admission occurred for 9.6%, 19.2%, 31.2%, and 47.9% among patients with no blood cultures, negative cultures, 1 co-detection, and >1 co-detection documented, respectively; in-hospital mortality occurred in 1.5%, 3.3%, 9.4%, and 14.5%, respectively. Among patients with positive cultures, 22.1% had Staphylococcus aureus and 7.5% had Streptococcus pneumoniae co-detections; both were associated with severe illness (with 22.4% in-hospital mortality each). DISCUSSION. Bacterial co-detections in persons hospitalized with influenza were associated with poor in-hospital outcomes. Efforts to prevent severe influenza and bacterial co-infections, including through vaccination, may reduce substantial morbidity and mortality from influenza.
Background Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019 (COVID-19) and influenza. Nonetheless, with COVID-19 restrictions lifted, an unanticipated outbreak of the influenza B/Victoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong, southern China. The mechanism underlying this phenomenon remains unknown. To better prepare for potential influenza outbreaks during COVID-19 pandemic, we studied the molecular epidemiology and phylogenetics of influenza A(H3N2) and B/Victoria that circulated during the COVID-19 pandemic in this region. Methods From January 1, 2018 to December 31, 2022, we collected throat swabs from 173,401 patients in Guangdong who had acute respiratory tract infections. Influenza viruses in the samples were tested using reverse transcription-polymerase chain reaction, followed by subtype identification and sequencing of hemagglutinin (HA) and neuraminidase (NA) genes. Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples. A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation. Results During the early period of COVID-19 control, various influenza viruses were nearly undetectable in respiratory specimens. When control measures were relaxed in January 2020, the influenza infection rate peaked at 4.94% (39/789) in December 2021, with the influenza B/Victoria accounting for 87.18% (34/39) of the total influenza cases. Six months later, the influenza infection rate again increased and peaked at 11.34% (255/2248) in June 2022; influenza A/H3N2 accounted for 94.51% (241/255) of the total influenza cases in autumn 2022. The diverse geographic distribution of HA genes of B/Victoria and A/H3N2 had drastically reduced, and most strains originated from China. The rate of B/Victoria HA evolution (3.11 × 10^−3, P < 0.05) was 1.7 times faster than before the COVID-19 outbreak (1.80 × 10^−3, P < 0.05). Likewise, the H3N2 HA gene’s evolution rate was 7.96 × 10^−3 ( P < 0.05), which is 2.1 times faster than the strains’ pre-COVID-19 evolution rate (3.81 × 10^−3, P < 0.05). Conclusions Despite the extraordinarily low detection rate of influenza infection, concealed influenza transmission may occur between individuals during strict COVID-19 control. This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and B/Victoria viruses. Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.
CCSD;Oxford University PressDezember 2024Influenza
International audience;
Influenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication. In this study, we present an advanced biological tool, the antiparallel helical RNP-like complex, assembled from recombinant N-terminally truncated NP and short synthetic RNA. The 3.0 Å cryo-electron microscopy structure details for the first time the whole RNA pathway across NP as well as NP-NP interactions that drive the antiparallel helical assembly accommodating major and minor grooves. Our findings show that the surface of the protein can harbour several conformations of the RNA, confirming that the number of nucleobases that binds to NP is not fixed, but ranges probably between 20 and 24. Taking all together, our data provide details to further understand the genome encapsidation and explain the inherent flexibility of influenza A virus vRNPs.
Background The safety of milk production in terms of foodborne infections is a worldwide issue, particularly in developing countries where production is often unhygienic. A cross-sectional study was conducted from December 2018 to August 2019 in the Meta District of Eastern Hararghe Zone, Oromia Regional State, Ethiopia. We aim to assess milk hygiene practices among smallholder dairy farmers, estimate the prevalence of Staphylococcus aureus in raw cow milk and swabs, assess associated risk factors, and the antimicrobial susceptibility test of S. aureus isolates. Face-to-face interviews with 30 respondents randomly selected from smallholder dairy farmers were used to assess the potential risk factors for S. aureus contaminations in milk. A total of 177 samples were examined using standard microbiological testing. The disc diffusion technique was also employed to assess the antibiotic susceptibility of the isolates. The data was analyzed using STATA^® version 14.0 statistical software. Results According to the milk hygiene assessment, 80% of respondents did not wash cow udder before milking, did not use detergent to clean milk containers, and did not keep milk refrigerated before consumption or sale, while 63.3% of milk consumers ingested raw milk. They had never heard of staphylococci foodborne disease. Likewise, the overall prevalence of S. aureus was 12.42% (95%CI: 8.32–18.98). The prevalence of S. aureus in udder milk, equipment swabs, and milkers’ hands was 18.8%, 26.7%, and 30%, respectively. The prevalence of S. aureus in milk is significantly associated with age, and mastitis history ( p < 0.05). Moreover, old and mastitis positive animals were eight (OR: 8.40; 95%CI: 1.68–41.89) and four (OR: 4.33; 95%CI: 1.37–13.66) times more likely to be infected by S. aureus than adult, and mastitis negative animal. The isolates were resistant to penicillin G (97.4%) and tetracycline (69.2%) whereas susceptible to kanamycin, streptomycin, vancomycin, and cefotaxime, at 84.6%, 71.8%, 64%, and 58.8%, respectively. Conclusion This study revealed the presence of antimicrobial-resistant patterns of S. aureus on commonly used antibiotics, as well as inadequate milk handling practices in the study area. Thus, awareness should be created on proper milk handling and hygiene as well as appropriate uses of antibiotics should be encouraged.
Background Hemodialysis patients are at risk of acquiring healthcare-related infections due to using non-sterile water to prepare hemodialysis fluid. Therefore, microbiological control and monitoring of used water are of crucial importance. Materials and methods In this work, we identified bacterial populations occupying a hemodialysis water distribution system for almost a 6-month period in Ahvaz city, southwest of Iran. A total of 18 samples from three points were collected. We found high colony counts of bacteria on R2A agar. 31 bacteria with different morphological and biochemical characteristics were identified by molecular-genetic methods based on 16 S rRNA gene sequencing. Endotoxin concentrations were measured, using Endosafe^® Rapid LAL Single-Test Vials. Results A diverse bacterial community was identified, containing predominantly Gram-negative bacilli. The most frequently isolated genus was Sphingomonas . Five species including M. fortuitum , M. lentiflavum , M.szulgai , M. barrassiae , and M. gordonae was identified .Despite the presence of Gram-negative bacteria the endotoxin analysis of all samples revealed that their endotoxin values were below the detection limit. Conclusion The members of Sphingomonas genus along with Bosea and mycobacteria could be regarded as pioneers in surface colonization and biofilm creation. These bacteria with others like Pelomonas, Bradyrhizobium , staphylococcus , and Microbacterium may represent a potential health risk to patients under hemodialysis treatment.
Objective We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks. Methods 932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and bla _KPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems. Results We found a significant inverse correlation between the presence of CRISPR and R-M systems and bla _KPC plasmids in K. pneumoniae , especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in bla _KPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder bla _KPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of bla _KPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity. Conclusions Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP.
Background Taxol, derived from Taxus trees, is a valuable natural resource for the development of anticancer drugs. Endophytic fungi from Taxus trees are a promising alternative source of Taxol. However, the impact of plant-endophytic microbial interaction on the host’s Taxol biosynthesis is largely unknown. Results In the current study, the diversity of endophytic fungi in three different Taxus species was analyzed using Internal Transcribed Spacer sequencing. A total of 271 Operational Taxonomic Units (OTUs) were identified, grouping into 2 phyla, 8 classes, 16 orders, 19 families, and 19 genera. Alpha and beta diversity analysis indicated significant differences in endophytic fungal communities among the various Taxus trees. At the genus level, Alternaria and Davidiella were predominantly found in T. mairei and T. media , respectively. By utilizing a previously published dataset, a Pearson correlation analysis was conducted to predict the taxol biosynthesis-related fungal genera. Following screening, two isolates of Alternaria (L7 and M14) were obtained. Effect of inoculation with Alternaria isolates on the gene expression and metabolite accumulation of T. mairei was determined by transcriptomic and untargeted metabolomic studies. The co-inoculation assay suggests that the two Alternaria isolates may have a negative regulatory effect on taxol biosynthesis by influencing hormone signaling pathways. Conclusion Our findings will serve as a foundation for advancing the production and utilization of Taxus and will also aid in screening endophytic fungi related to taxol production.
Background Antimicrobial resistance is a global concern, linking bacterial genotype and phenotype. However, variability in antibiotic susceptibility within bacterial populations can lead to misclassification. Heteroresistance exemplifies this, where isolates have subpopulations less susceptible than the main population. This study explores heteroresistance in Gram-negative bacteria, distinguishing between carbapenem-sensitive isolates and stable heteroresistant isolates (SHIs). Methods A total of 151 Gram-negative clinical isolates including Klebsiella pneumoniae , Pseudomonas aeruginosa , Escherichia coli , Acinetobacter baumannii and Proteus mirabilis from various sources were included. Heteroresistant isolates and their stability were detected by disc-diffusion technique while genotypic analysis was carried out by PCR and efflux activity was assessed by ethidium bromide (EtBr)-agar cartwheel method. Results A total of 51 heteroresistant subpopulations were detected, producing 16 SHIs upon stability-detection. Amplified resistance genes and EtBr-agar cartwheel method showed a significant difference between resistant subpopulations and their corresponding-sensitive main populations. Conclusion Genotypic analysis confirmed that genetic mutation can lead to resistance development although the main populations were sensitive, thereby leading to treatment failure. This is a neglected issue which should be highly considered for better treatment outcomes.
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.
Background The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported. Results We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria . Extending antibiotic exposure to 2–3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1β (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001). Conclusions Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses,
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.
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.
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.
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.
Background Enterocytozoon bieneusi is the most common species found in humans. Although E. bieneusi has been investigated in humans, genotype profile of E. bieneusi is not known in Türkiye. Methods In this study, we screened E. bieneusi in patients ( n = 94) with different types of malignant solid tumors by Real Time PCR and then sequenced E. bieneusi positive samples. All cancer patients were undergoing chemotherapy and had diarrhea. Moreover, as control groups, we also screened E. bieneusi in patients with diarrhea ( n = 50) and without diarrhea ( n = 50). Results Among all patients analyzed, 33 (17%) were found to be E. bieneusi -positive. As the patients were categorized, the molecular prevalence of E. bieneusi increased to 25.5% among cancer patients with diarrhea. However, the molecular prevalence of E. bieneusi was found to be lower in patients with presenting only diarrhea (8%) and patients without diarrhea (10%). The high molecular prevalence value detected among cancer patients with diarrhea was also statistically significant compared to other patient groups (P = 0.00112 and P = 0.0269). Among the 33 Real Time PCR positive samples, 10 of them were amplified by nested PCR and among these 10 samples, 6 of them were successfully genotyped. The phylogenetic tree showed the presence of D and Type IV which were also identified in stray cats living in İzmir in our previous study. Conclusions High molecular prevalence value indicates the importance of screening stool samples of cancer patients with diarrhea for E. bieneusi and genotyping results indicate that D and Type IV are circulating between humans and cats.
Background Legionella pneumophila is a Gram-negative intracellular bacillus and is the causative agent of a severe form of pneumonia called Legionnaires’ disease which accounts for 2-9% of cases of community acquired pneumonia. It produces an extremely large protein belonging to the RTX ( R epeats in T o X in) family, called RtxA, and we previously reported that RtxA is transported by a dedicated type 1 secretion system (T1SS) to the cell surface. RTX proteins have been shown to participate in the virulence or biofilm formation of various bacteria, the most studied models being the pore forming hemolysin A (HlyA) of Escherichia coli and the biofilm associated protein LapA of P. fluorescens. LapA localization depends on the enzymatic release by LapD/LapG complex activity. This study aimed to elucidate the dual localization (cell surface associated or released state) of L. pneumophila RTX protein (RtxA) and whether this released versus sequestered state of RtxA plays a role in L. pneumophila virulence. Results The hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (position 108–109). Consistently, a strain lacking LapG protease maintains RtxA on the cell surface, whereas a strain lacking the c-di-GMP receptor LapD does not exhibit cell surface RtxA because of its continuous cleavage and release, as in the LapA-D-G model of Pseudomonas fluorescens . Interestingly, our data point out a key role of RtxA in enhancing the infection process of amoeba cells, regardless of its location (embedded or released); therefore, this may be the result of a secondary role of this surface protein. Conclusions This is the first experimental identification of the cleavage site within the RTX protein family. The primary role of RtxA in Legionella is still questionable as in many other bacterial species, hence it sounds reasonable to propose a major function in biofilm formation, promoting cell aggregation when RtxA is embedded in the outer membrane and facilitating biofilm dispersion in case of RtxA release. The role of RtxA in enhancing the infection process may be a result of its action on host cells (i.e., PDI interaction or pore-formation), and independently of its status (embedded or released).
Medicinal mushrooms, such as Taiwanofungus camphoratus , Inonotus obliquus , and Tropicoporus linteus , have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus , I. obliquus and T. linteus are explored.
Chytrids, often overshadowed by their other fungal counterparts, take center stage as we unravel the mysteries surrounding new species within Rhizophydiales and explore their unique characteristics. In the broader spectrum of chytrids, their significance lies not only in their roles as decomposers but also as key players in nutrient cycling within aquatic ecosystems as parasites and saprobes. Baited soil and aquatic samples collected from various provinces of Thailand, yielded new species of the Rhizophydiales ( Chytridiomycota ), some of which expanded previously single species genera. Our investigation incorporated a combination of morphological and phylogenetic approaches, enabling us to identify these isolates as distinct taxa. The novel isolates possess distinguishing features, such as variations in size and shape of the sporangium and zoospores, that somewhat differentiate them from described taxa. To confirm the novelty of the species, we employed robust phylogenetic analyses using maximum likelihood and bayesian methods. The results provided strong support for the presence of eight distinct lineages within the Rhizophydiales , representing our newly discovered species. Furthermore, we employed Poisson Tree Processes to infer putative species boundaries and supplement evidence for the establishment of our new Rhizophydiales species. By meticulously exploring their morphological characteristics and genetic makeup, we expand the known catalogue of fungal diversity by describing Alphamyces thailandicus , Angulomyces ubonensis, Gorgonomyces aquaticus, G. chiangraiensis , G. limnicus , Pateramyces pingflumenensis , Terramyces aquatica, and T. flumenensis and also provide valuable insights into the intricacies of this order. This newfound knowledge not only enriches our understanding of Rhizophydiales but also contributes significantly to the broader field of mycology, addressing a critical gap in the documentation of fungal species. The identification and characterization of these eight novel species mark a noteworthy stride towards a more comprehensive comprehension of fungal ecosystems and their vital role.
Background Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages. Results A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360 kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor. Conclusions fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.
Background The global over-reliance on non-renewable fossil fuels has led to the emission of greenhouse gases, creating a critical global environmental challenge. There is an urgent need for alternative solutions like biofuels. Advanced biofuel is a renewable sustainable energy generated from lignocellulosic plant materials, which can significantly contribute to mitigating CO_2 emissions. Microbial Carbohydrate Active Enzymes (CAZymes) are the most crucial enzymes for the generation of sustainable biofuel energy. The present study designed shotgun metagenomics approaches to assemble, predict, and annotate, aiming to gain an insight into the taxonomic diversity, annotate CAZymes, and identify carbohydrate hydrolyzing CAZymes from microbiomes in Menagesha suba forest soil for the first time. Results The microbial diversity based on small subunit (SSU) rRNA analysis revealed the dominance of the bacterial domain representing 81.82% and 92.31% in the studied samples. Furthermore, the phylum composition result indicated the dominance of the phyla Proteobacteria (23.08%, 27.27%), Actinobacteria (11.36%, 20.51%), and Acidobacteria (10.26%, 15.91%). The study also identified unassigned bacteria which might have a unique potential for biopolymer hydrolysis. The metagenomic study revealed that 100,244 and 65,356 genes were predicted from the two distinct samples. A total number of 1806 CAZyme genes were identified, among annotated CAZymes, 758 had a known enzyme assigned to CAZymes. Glycoside hydrolases (GHs) CAZyme family contained most of the CAZyme genes with known enzymes such as β-glucosidase, endo-β-1,4-mannanase, exo-β-1,4-glucanase, α-L-arabinofuranosidase and oligoxyloglucan reducing end-specific cellobiohydrolase. On the other hand, 1048 of the identified CAZyme genes were putative CAZyme genes with unknown enzymatical activity and the majority of which belong to the GHs family. Conclusions In general, the identified putative CAZymes genes open up an opportunity for the discovery of new enzymes responsible for hydrolyzing biopolymers utilized for biofuel energy generation. This finding is used as a first-hand piece of evidence to serve as a benchmark for further and comprehensive studies to unveil novel classes of bio-economically valuable genes and their encoded products.
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.
Background Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris . Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis. Results The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects. Conclusions This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.
(1) The EXS2600 platform demonstrated superior capability in distinguishing between Fusarium species. (2) The data demonstrated that EXS2600 platform provided comparable results and was suitable for filamentous identification. (3) The EXS2600 platform significantly reduced the TAT for the processing of positive cultures in tissue specimens. Objectives Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is extensively employed for the identification of filamentous fungi on MALDI Biotyper (Bruker Daltonics) and Vitek MS (biomerieux), but the performance of fungi identification on new EXS2600 (Zybio) is still unknow. Our study aims to evaluate the new EXS2600 system's (Zybio) ability to rapidly identify filamentous fungi and determine its effect on turnaround time (TAT) in our laboratory. Methods We tested 117 filamentous fungi using two pretreatment methods: the formic acid sandwich (FA-sandwich) and a commercial mold extraction kit (MEK, Zybio). All isolates were confirmed via sequence analysis. Laboratory data were extracted from our laboratory information system over two 9-month periods: pre-EXS (April to December 2022) and post-EXS (April to December 2023), respectively. Results The total correct identification (at the species, genus, or complex/group level) rate of fungi was high, FA-sandwich (95.73%, 112/117), followed by MEK (94.02%, 110/117). Excluding 6 isolates not in the database, species-level identification accuracy was 92.79% (103/111) for FA-sandwich and 91.89% (102/111) for MEK; genus-level accuracy was 97.29% (108/111) and 96.39% (107/111), respectively. Both methods attained a 100% correct identification rate for Aspergillus , Lichtheimia , Rhizopus Mucor and Talaromyces species , and were able to differentiate between Fusarium verticillioides and Fusarium proliferatum within the Fusarium fujikuroi species complex. Notably, high confidence was observed in the species-level identification of uncommon fungi such as Trichothecium roseum and Geotrichum candidum . The TAT for all positive cultures decreased from pre EXS2600 to post (108.379 VS 102.438, P < 0.05), and the TAT for tissue decreased most (451.538 VS 222.304, P < 0.001). Conclusions The FA-sandwich method is more efficient and accurate for identifying filamentous fungi with EXS2600 than the MEK. Our study firstly evaluated the performance of fungi identification on EXS2600 and showed it is suitable for clinical microbiology laboratories use.
The phenotypic and genotypic plasticity of Candida species has been extensively characterized in Western literature, while countries in the Eastern Hemisphere are increasingly incorporating these findings into both research and clinical strategies. In Southeast Asia, however, the landscape is more complex. Some nations have taken a more limited role, focusing primarily on clinical identification, with research and surveillance receiving less emphasis. Conversely, other countries in the region actively contribute to global efforts to monitor Candida, including the surveillance of multidrug-resistant strains such as Candidozyma auris. The historical context, distribution patterns, and regional insights into Candida across Southeast Asian countries have been explored in various individual publications; however, a more comprehensive and comparative analysis remains limited. This chapter addresses the gap by presenting an up-to-date, region-wide synthesis of Candida -related data throughout Southeast Asia.
Background Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes ( Grus nigricollis ). Results In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis ( P < 0.05, LDA > 2) found that Pyxidiophora , Pseudopeziza , Sporormiella , Geotrichum , and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. Conclusions This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host’s food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.
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.
Rhodococcus equi ( R. equi ) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi . The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi . The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.
Background Mangroves are complex and dynamic coastal ecosystems under frequent fluctuations in physicochemical conditions related to the tidal regime. The frequent variation in organic matter concentration, nutrients, and oxygen availability, among other factors, drives the microbial community composition, favoring syntrophic populations harboring a rich and diverse, stress-driven metabolism. Mangroves are known for their carbon sequestration capability, and their complex and integrated metabolic activity is essential to global biogeochemical cycling. Here, we present a metabolic reconstruction based on the genomic functional capability and flux profile between sympatric MAGs co-assembled from a tropical restored mangrove. Results Eleven MAGs were assigned to six Bacteria phyla, all distantly related to the available reference genomes. The metabolic reconstruction showed several potential coupling points and shortcuts between complementary routes and predicted syntrophic interactions. Two metabolic scenarios were drawn: a heterotrophic scenario with plenty of carbon sources and an autotrophic scenario with limited carbon sources or under inhibitory conditions. The sulfur cycle was dominant over methane and the major pathways identified were acetate oxidation coupled to sulfate reduction, heterotrophic acetogenesis coupled to carbohydrate catabolism, ethanol production and carbon fixation. Interestingly, several gene sets and metabolic routes similar to those described for wastewater and organic effluent treatment processes were identified. Conclusion The mangrove microbial community metabolic reconstruction reflected the flexibility required to survive in fluctuating environments as the microhabitats created by the tidal regime in mangrove sediments. The metabolic components related to wastewater and organic effluent treatment processes identified strongly suggest that mangrove microbial communities could represent a resourceful microbial model for biotechnological applications that occur naturally in the environment.
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.
Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis−stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-024-01334-8.
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.
This chapter explores the intricate relationship between love and artificial intelligence (AI) from an interdisciplinary and theoretical perspective. It analyzes the significance of love amid current technological developments, focusing on AI’s potential and limits in simulating this human experience. From a neuroscientific standpoint, it examines how love’s neurochemistry can be modeled using AI. The technological perspective sheds light on the development of emotionally intelligent systems and their role in interpersonal relationships, including the limitations of machine empathy. Psychological and cultural perspectives are integrated to investigate both individual and societal perceptions of love. This includes an exploration of how AI challenges and transforms our notions of intimacy, attachment, and closeness, as well as how narratives in art and media reflect these changes. The chapter concludes with an interdisciplinary synthesis, demonstrating that while AI can serve as a tool for analyzing and simulating love, it cannot capture the essence of this profoundly human phenomenon. Rather than offering definitive answers, the chapter contributes to ongoing discussions about the role of AI in emotional and social contexts.
Human’s robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes made to the cerebral cortex. This paper reviews the biology and evolution of mammalian cortical radial glial cells (primary neural stem cells) and introduces the concept that a genetically step wise process, based on a core molecular pathway already in use, is the evolutionary process that has molded cortical neurogenesis. The core mechanism, which has been identified in our recent studies, is the extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor, is an increase in SHH signaling in radial glia, that antagonizes ERK-BMP7 signaling. Finally, I propose that: (1) SHH signaling is not a key regulator of primate cortical expansion and folding; (2) human cortical radial glial cells do not generate neocortical interneurons; (3) human-specific genes may not be essential for most cortical expansion. I hope this review assists colleagues in the field, guiding research to address gaps in our understanding of cortical development and evolution.
This chapter offers a detailed examination of the neurophysiological mechanisms underlying neural activity, emphasizing the roles of neurotransmitters, neuroplasticity, and the effects of psychoactive substances. It starts with a discussion of fundamental neuronal functions, including action potentials and synaptic transmission. The chapter then explores long-term potentiation (LTP) and long-term depression (LTD) as critical mechanisms of synaptic plasticity. It further investigates the involvement of neurotransmission systems in various brain circuits related to inhibitory control, decision-making, and reward processing. The impact of psychoactive substances on these systems is analyzed, highlighting changes in neurotransmitter balance and subsequent neuroplastic adaptations. Particular attention is given to the mesocorticolimbic pathway and its modulation by drugs of abuse, as well as the roles of glutamate and GABAergic systems. The chapter concludes by examining the effects of substance use on brain function and behavior, particularly how these alterations persist during withdrawal and influence overall neuroadaptation.
Borderline personality disorder is characterized by challenges in interpersonal relationships and self-image, impulsivity, and affective instability. Putative neurobiological mechanisms have deepened understanding of the pathophysiology of the disorder, yet challenges remain in the provision of effective treatment. Psychotherapy is the first-line treatment for BPD and though a range of evidence-based modalities are supported, rates of nonresponse are approximately 50%. One approach to improving treatment outcomes concerns research at the cross-disciplinary intersection of neurobiology and psychotherapy. A comprehensive overview of psychotherapy studies that have incorporated biological markers will be provided in this chapter, including neuroimaging, genetics, and neuroendocrine studies. Most studies have investigated task-related brain activation, mainly using affective paradigms that have implicated primarily frontotemporal and limbic regions. High between-study heterogeneity and an overall small number of studies, particularly genetics and neuroendocrine studies, preclude firm conclusions. Recent developments in the field and recommendations for future progress will be discussed.
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.
Mesoscale imaging of calcium dynamics has emerged as a powerful technique to study the coordination of activity of multiple cortical regions simultaneously during awake behavior. While much of the work in the field has focused on studying cortical dynamics during head-fixed preparations, we have recently developed the mini-mScope—a head mounted widefield imaging microscope capable of imaging large swathes of the dorsal cortex of freely behaving mice. In this chapter, we guide the reader with methodological details to build and use the mini-mScope for widefield Ca^2+ imaging in freely behaving mice performing complex behaviors such as spatial navigation.
Neuropsychology had its semi-structured foundations in the eighteenth century with phrenology, a pseudoscience that proposed a relationship between facial characteristics and cognitive abilities. In the nineteenth century, neuropsychology established itself as a scientific discipline, with the work of Franz Joseph Gall and others. The localizationist perspective sought, during this period, to address brain areas responsible for specific functions, such as language and memory, through postmortem identification and correlation of individuals who clinically exhibited motor and language deficits associated with acquired brain lesions. In the twentieth century, advances in neuroimaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), allowed for the visualization of the living brain and the study of real-time brain activity. Standardized neuropsychological tests were developed to assess specific cognitive functions, and new theoretical approaches, such as cognitive neuropsychology and social neuropsychology, emerged. In the twenty-first century, neuropsychology integrated with other disciplines, such as neuroscience, cognitive psychology, and neurology. The understanding of brain plasticity and the role of neuropsychological rehabilitation advanced significantly. Advanced neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), are used to study brain activity during cognitive tasks. Ongoing developments include integration with artificial intelligence (AI) and machine learning, the development of new evidence-based therapeutic interventions for neuropsychological disorders, and the use of neuropsychology to enhance understanding and treatment of mental health conditions, such as depression and anxiety. This chapter aims to outline the historical development of neuropsychology, explore the main theoretical and methodological contributions that have shaped the discipline, and discuss contemporary and future advances in the field, highlighting the importance of neuroimaging techniques and integrated approaches for the study of the brain and cognition.
Society for NeuroscienceJuli 2024Neurowissenschaften
Many neurons including vasopressin (VP) magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON) generate afterhyperpolarizations (AHPs) during spiking to slow firing, a phenomenon known as spike frequency adaptation. The AHP is underlain by Ca(2+)-activated K(+) currents, and while slow component (sAHP) features are well described, its mechanism remains poorly understood. Previous work demonstrated that Ca(2+) influx through N-type Ca(2+) channels is a primary source of sAHP activation in SON oxytocin neurons, but no obvious channel coupling was described for VP neurons. Given this, we tested the possibility of an intracellular source of sAHP activation, namely, the Ca(2+)-handling organelles endoplasmic reticulum (ER) and mitochondria in male and female Wistar rats. We demonstrate that ER Ca(2+) depletion greatly inhibits sAHPs without a corresponding decrease in Ca(2+) signal. Caffeine sensitized AHP activation by Ca(2+). In contrast to ER, disabling mitochondria with CCCP or blocking mitochondria Ca(2+) uniporters (MCUs) enhanced sAHP amplitude and duration, implicating mitochondria as a vital buffer for sAHP-activating Ca(2+). Block of mitochondria Na(+)-dependent Ca(2+) release via triphenylphosphonium (TPP(+)) failed to affect sAHPs, indicating that mitochondria Ca(2+) does not contribute to sAHP activation. Together, our results suggests that ER Ca(2+)-induced Ca(2+) release activates sAHPs and mitochondria shape the spatiotemporal trajectory of the sAHP via Ca(2+) buffering in VP neurons. Overall, this implicates organelle Ca(2+), and specifically ER–mitochondria-associated membrane contacts, as an important site of Ca(2+) microdomain activity that regulates sAHP signaling pathways. Thus, this site plays a major role in influencing VP firing activity and systemic hormonal release.
This research analyzed the influence of innovation in marketing through the tools derived from the studies of cognitive neuroscience and its relationship with marketing; these two areas have generated a new trend called neuromarketing, which is a new way of applying knowledge about the functioning of the brain and its effect on purchasing decisions; this type of study allows organizations to learn new innovative strategies on how to attract customers and influence the purchasing decisions of consumers, neuroscientific studies applied to marketing use technological tools to identify tastes or preferences when making purchases. In this article, an analysis was conducted on the relationship between the brain’s sensory responses to marketing stimuli and the purchase decision. A sample of 123 university students was taken for the study; the metrics were performed in three phases: In the first phase, images of distinguished brand graphics were used; in the second phase, pictures of the brands with all the elements that compose it were presented, and in the third phase, a video was shown of a commercial with A.I. about a recognized brand. The scientific method is quantitative, experimental level, and cross-sectional in scope. The evaluation was carried out through a Likert-type survey to measure the consumers’ purchase decision-making. For the analysis, advanced statistical techniques of SSPS were used; the conclusion of the study allowed us to know the relationship between brain stimuli generated by marketing and consumer purchase decisions; the results show a greater inclination towards stimuli with movement used with A.I.; these provide information that could help in the development of business strategies, this research can also be used by the scientific community, to continue developing similar studies to understand what mechanisms are most effective in influencing consumer purchasing decisions and ultimately increase their success in the market.
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.
This chapter offers an overview of the neurobiology of human movement. The functions of specific areas and sites within the nervous system and how their integrative action ensures various aspects of movement will be described. A sequential approach will be adopted, commencing with the muscle and spinal cord, progressing through the brain stem and descending motor tracts, the motor cortex, and finally the basal ganglia and the cerebellum. While this may suggest serial processing, it is essential to recognize that the processing underlying human movements relies on parallel and integrated activities within and between the networks. The chapter concludes with a synthesis of the different elements and a description of how three critical movement behaviors are generated: reaching and grasping, balance and posture, and locomotion. Throughout the text, the implications of basic neurobiology in the context of neurorehabilitation will be emphasized.
Society for NeuroscienceJuli 2024Neurowissenschaften
The resurgent sodium current (I(NaR)) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I(NaR) is thought to drive high rates of repetitive neuronal firing. However, I(NaR) is often studied in combination with the persistent or noninactivating portion of sodium currents (I(NaP)). We used dynamic clamp to test how I(NaR) and I(NaP) individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned I(NaR) does not scale repetitive firing rates due to its rapid decay at subthreshold voltages and that subthreshold I(NaP) is critical in regulating neuronal firing rate. Adjustments to the voltage-gated sodium conductance model used in these studies revealed I(NaP) and I(NaR) can be inversely scaled by adjusting occupancy in the slow-inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune I(NaP) and Purkinje neuron repetitive firing rates.
Society for NeuroscienceJuli 2024Neurowissenschaften
Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown. We hypothesized that dysregulated acetylcholine (ACh) release upon demyelination contributes to ligand-mediated activation hindering myelin repair. Following chronic cuprizone (CPZ)-induced demyelination (male and female mice), we observed a 2.5-fold increase in ACh concentration. This increase in ACh concentration could be attributed to increased ACh synthesis or decreased acetylcholinesterase-/butyrylcholinesterase (BChE)-mediated degradation. Using choline acetyltransferase (ChAT) reporter mice, we identified increased ChAT-GFP expression following both lysolecithin and CPZ demyelination. ChAT-GFP expression was upregulated in a subset of injured and uninjured axons following intraspinal lysolecithin-induced demyelination. In CPZ-demyelinated corpus callosum, ChAT-GFP was observed in Gfap(+) astrocytes and axons indicating the potential for neuronal and astrocytic ACh release. BChE expression was significantly decreased in the corpus callosum following CPZ demyelination. This decrease was due to the loss of myelinating oligodendrocytes which were the primary source of BChE. To determine the role of ligand-mediated muscarinic signaling following lysolecithin injection, we administered neostigmine, a cholinesterase inhibitor, to artificially raise ACh. We identified a dose-dependent decrease in mature oligodendrocyte density with no effect on OPC recruitment. Together, these results support a functional role of ligand-mediated activation of muscarinic receptors following demyelination and suggest that dysregulation of ACh homeostasis directly contributes to failure of remyelination in MS.
Society for NeuroscienceJuli 2024Neurowissenschaften
It was proposed that a reorganization of the relationships between cognitive functions occurs in dementia, a vision that surpasses the idea of a mere decline of specific domains. The complexity of cognitive structure, as assessed by neuropsychological tests, can be captured by exploratory graph analysis (EGA). EGA was applied to the neuropsychological assessment of people (humans) with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD; total N = 638). Both sexes were included. In AD, memory scores detach from the other cognitive functions, and memory subdomains reduce their reciprocal relation. SCD showed a pattern of segregated neuropsychological domains, and MCI showed a noisy and less stable pattern. Results suggest that AD drives a reorganization of cognitive functions toward a less-fractionated architecture compared with preclinical conditions. Cognitive functions show a reorganization that goes beyond the performance decline. Results also have clinical implications in test interpretations and usage.
Society for NeuroscienceJuni 2024Neurowissenschaften
The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain–body communication, and is often studied for its role in “fight-or-flight” and “freezing” responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals—yet, the present task posed only the most minimal (if any) “threat,” with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.
Society for NeuroscienceJuli 2024Neurowissenschaften
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.
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.
Society for NeuroscienceJuli 2024Neurowissenschaften
Phospholipids (PLs) are asymmetrically distributed at the plasma membrane. This asymmetric lipid distribution is transiently altered during calcium-regulated exocytosis, but the impact of this transient remodeling on presynaptic function is currently unknown. As phospholipid scramblase 1 (PLSCR1) randomizes PL distribution between the two leaflets of the plasma membrane in response to calcium activation, we set out to determine its role in neurotransmission. We report here that PLSCR1 is expressed in cerebellar granule cells (GrCs) and that PLSCR1-dependent phosphatidylserine egress occurred at synapses in response to neuron stimulation. Synaptic transmission is impaired at GrC Plscr1(−/−) synapses, and both PS egress and synaptic vesicle (SV) endocytosis are inhibited in Plscr1(−/−) cultured neurons from male and female mice, demonstrating that PLSCR1 controls PL asymmetry remodeling and SV retrieval following neurotransmitter release. Altogether, our data reveal a novel key role for PLSCR1 in SV recycling and provide the first evidence that PL scrambling at the plasma membrane is a prerequisite for optimal presynaptic performance.
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.
Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-024-01330-y.
Society for NeuroscienceJuli 2024Neurowissenschaften
While ipsilesional cortical electroencephalography has been associated with poststroke recovery mechanisms and outcomes, the role of the cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that poststroke motor control relies on increased corticocerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting poststroke motor rehabilitation. We investigated the excitability of the ipsilesional cortex, the dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, 10 human participants (two women) at the end of 4–8 months of DN deep brain stimulation (DBS) showed (1) significantly improved motor control indexed by computerized motor tasks; (2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and (3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the poststroke state and its connectivity with the ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of corticocerebellar-cortical network after stroke and its modulation by DN-DBS.
Migraine is a prevalent neurological disorder which encompasses severe headaches accompanied by various sensory sensitivities. When it becomes chronic, characterized by frequent attacks, it can be a very disabling disease with significant social and economic burdens. The typical treatment options for chronic migraine are pharmacological and non-pharmacological, with mixed and unsatisfying outcomes. Indeed, the effective management involves identifying triggers, modifying risk factors, and balancing pharmacological and non-pharmacological treatments to minimize medication overuse and address other possible associated factors, included mental health issues. In this chapter, we will analyze the topic of catastrophizing in migraine. Catastrophizing is a psychological characteristic of migraineurs. It consists of a disadaptive mindset made of irrational beliefs where negative events are exaggerated leading to heightened emotional distress and a belief in worst-case scenarios, while doubting one’s ability to cope. Catastrophic thinking can result in feelings of helplessness, depression, and anxiety, representing an extreme form of worrying that extends into pathological symptoms. Many literature studies documented catastrophizing in migraine, in both clinical and experimental settings, and some studies also revealed that some social variables, such as stigma for chronic illness, can mediate the relationship between migraine symptoms and catastrophizing. This negative mindset impacts not only adults but also children with migraines, with consequences on their overall quality of life, and parental catastrophizing can worsen their tendency toward catastrophic thoughts. Recently, also neuroscience investigated the relation between migraine and catastrophizing, finding changes in brain connectivity and central sensitization mechanisms as possible contributors. Nevertheless, the exact underlying mechanisms remain incompletely understood. To date, pharmacological treatments such as erenumab and OnabotulinumtoxinA and non-pharmacological treatments such as neurostimulation or behavioral approaches showed efficacy in relieving both migraine symptoms and catastrophizing, sometimes revealing some placebo effects. In this case as well, further studies delving into techniques such as mindfulness, psychoeducational interventions, and cognitive-behavioral therapy will be useful in determining the effectiveness of these treatments. To conclude, migraine is not the only chronic pain disease characterized by the catastrophic thinking. Indeed, many studies documented the presence of this cognitive feature in rheumatic diseases such as fibromyalgia, or in painful neuropathies. Also in this case, neuroimaging helped in revealing some cortical abnormalities which may contribute to the relation between catastrophizing and chronic pain symptoms. Further studies are needed to explore this relation while psychological intervention aimed at this cognitive schema would be helpful for patients in getting out from the negative loop of catastrophizing and awfulizing, possibly developing a more optimistic outlook, or at least acceptance, toward debilitating conditions such as those characterized by chronic pain.
AIMS: Neuropsychiatric symptoms including depression, apathy and psychosis are experienced by the majority of patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. Acetylcholine deficit is thought to contribute to neuropsychiatric symptoms in Parkinson's disease. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia (PDD), but the consensus for the use of rivastigmine earlier in the disease course is unclear. This systematic review aims to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia. METHODS: EMBASE, MEDLINE, PsychINFO, Cochrane CENTRAL, NGLC, NICE Evidence and medRxiv.org were searched for studies with terms relating to Population (Parkinson's disease) and intervention (rivastigmine). 1922 references were identified, of which 358 were duplications. Inclusion criteria were: diagnosis of Parkinson's disease, rivastigmine intervention and the presence of neuropsychiatric symptoms or falls. Articles were excluded if they only related to patients with dementia. Following title and abstract review, 1331 articles were excluded. After full text review, 9 articles remained, which underwent a risk of bias analysis. RESULTS: Outcomes were heterogenous, so were not suitable for meta-analysis. Therefore, the results are presented in narrative form. The articles included 6 Randomised Controlled Trials (RCTs), 2 open-label trials and 1 case-series. Three of the studies focused on psychosis. Two of these studies indicated a benefit of rivastigmine on psychotic symptoms in Parkinson's disease. However, these studies were an open label trial and a case series, and the results were not reproduced during RCT. One RCT indicated benefit of rivastigmine in rapid eye movement behaviour disorder (RBD). One RCT showed improvements in apathy after treatment with rivastigmine. Two RCTs demonstrated a reduction in falls with rivastigmine treatment compared to placebo. One RCT showed a significant improvement on a performance-based measure of cognitive ability. One study identified brain areas that were hypoactive in hallucinating Parkinson's patients, and the reduced activity could be restored with rivastigmine. This restoration of activity was associated with improved attention compared to baseline. CONCLUSION: There is evidence that rivastigmine is beneficial for RBD and apathy in Parkinson's disease, independently from the presence of dementia. There is high level evidence that rivastigmine reduces falls, which may be due to improved attention. The impact of rivastigmine on psychotic symptoms is less clear, but is supported by current theoretical models which involve acetylcholine dysfunction in the generation of visual hallucinations in Parkinson's disease.
Gait-based Parkinson's disease assessment increasingly relies on heterogeneous sensors, but clinical systems rarely collect all modalities simultaneously. New sensors may arrive through device upgrades, protocol changes, or multi-center deployment, while historical patient data are often unavailable because of privacy and storage constraints. This modality-incremental setting faces three challenges: unreliable cross-modal distillation, modality-specific statistical shifts, and reduced plasticity after preservation. We propose MOSAIC, a compact continual learning framework. First, we identify the Toxic Teacher phenomenon and introduce Modality-Specific Warm-Up to stabilize newly learned modality representations before distillation. Second, we propose a statistics-decoupled MSBN architecture that isolates sensor statistics while maintaining a shared semantic backbone. Third, we design a curriculum-guided repulsive objective for Plasticity Recovery, preserving legacy knowledge while recovering modality-specific capacity. Experiments on three multimodal Parkinson's gait datasets show that MOSAIC improves final performance and mitigates forgetting. Project code is available at: https://github.com/minlinzeng/MOSAIC_Modality-Specific-Adaptation-for-Incremental-Continual-Learning-in-PD-Gait-Assessment.git
International audience;
The objective of the Interreg ParkinsonCom project is the co-construction of a communication assistive technology for people with Parkinson’s disease. For this purpose, a user-centered design approach has been implemented, involving direct users as well as caregivers and various specialists in the health field, in the analysis, design, prototyping and preliminary and final evaluation stages. A prototype is the subject of the demonstration.
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Le projet Interreg ParkinsonCom a pour objectif la co-construction d’un outil d’aide à la communication pour des personnes atteintes de la maladie de Parkinson. Pour cela, une démarche de conception centrée utilisateur a été mise en place, impliquant des utilisateurs directs ainsi que des aidants et différents spécialistes du domaine de la santé, dans les étapes d’analyse, conception, prototypage et évaluation préliminaires et finales de l’outil. Un prototype fait l’objet de la démonstration.
Parkinson's Disease (PD) significantly impacts driving abilities, often
leading to early driving cessation or accidents due to reduced motor control
and increasing reaction times. To diminish the impact of these symptoms, we
developed PANDA (Parkinson's Assistance and Notification Driving Aid), a
multi-modality real-time alert system designed to monitor driving patterns
continuously and provide immediate alerts for irregular driving behaviors,
enhancing driver safety of individuals with PD. The system was developed
through a participatory design process with 9 people with PD and 13 non-PD
individuals using a driving simulator, which allowed us to identify critical
design characteristics and collect detailed data on driving behavior. A user
study involving individuals with PD evaluated the effectiveness of PANDA,
exploring optimal strategies for delivering alerts and ensuring they are timely
and helpful. Our findings demonstrate that PANDA has the potential to enhance
the driving safety of individuals with PD, offering a valuable tool for
maintaining independence and confidence behind the wheel.
Background Physical activity and exercise play a key role in managing Parkinson disease. This study aimed to: 1) determine if physiotherapy supported by telehealth helped people with Parkinson disease (PwP) to adhere to a home-based exercise program and maintain their physical activity; and 2) understand their experiences of using telehealth during the COVID-19 pandemic. Methods A mixed methods program evaluation involving a retrospective file audit from a student-run physiotherapy clinic and semi-structured interviews exploring participants’ experiences of telehealth. Ninety-six people with mild to moderate disease received home-based telehealth physiotherapy for 21 weeks. The primary outcome was adherence to the prescribed exercise program. Secondary outcomes were measures of physical activity. Interviews were conducted with 13 clients and seven students and analysed thematically. Results Adherence to the prescribed exercise program was high. The mean (SD) proportion of prescribed sessions completed was 108% (46%). On average clients spent 29 (12) minutes per session, and 101 (55) minutes per week exercising. Physical activity levels were maintained, with clients taking 11,226 (4,832) steps per day on entry to telehealth, and 11,305 (4,390) steps per day on exit from telehealth. The semi-structured interviews identified important features of a telehealth service required to support exercise; a flexible approach of clients and therapists, empowerment, feedback, a therapeutic relationship, and mode of delivery. Conclusions PwP were able to continue exercising at home and maintain their physical activity when physiotherapy was provided via telehealth. The flexible approach of both the client and the service was imperative.
Dementia in Parkinson's disease (PD) has become a major factor affecting the quality of life of patients with Parkinson's disease. Early detection and timely prevention can delay the progression of dementia, improve the quality of life of patients, and reduce the burden on society. This article is aimed at studying how to analyze the efficacy of moxibustion in the treatment of Parkinson's disease through meta-analysis on the basis of smart medicine. This article puts forward the related conceptual knowledge of smart medicine and meta-analysis and moxibustion treatment and proposes a deep learning method based on smart medicine to analyze the effects of moxibustion treatment on patients. The experiment in this article can be seen from the data in one of the figures that the highest curative effect of using a single moxibustion to treat Parkinson's disease is about 46%, while the curative effect of using a combination of moxibustion and Western medicine has reached 90%. It can be seen that a single moxibustion is not as effective as a combination of the two for Parkinson's disease. From the data in one of the tables, it can be seen that the proportion of Parkinson's disease in 2016 was 15%, showing an increase of 5%. By 2020, the proportion of Parkinson's disease was as high as 38%, and the growth rate reached 9%. It can be seen that the prevalence of this disease is getting higher and higher. Parkinson's disease has caused many undesirable effects on patients, such as slow movement, mental disorders, and a decline in mental state. Therefore, it is urgent to study the treatment of Parkinson's disease. Moxibustion can improve the patient's blood circulation and help the patient's local limbs to recover more easily and can help improve the patient's motor function.
Parkinson's disease, which affects more than 7 million people worldwide, is caused by the progressive loss of dopamine neurons in the midbrain. In addition to the characteristic motor symptoms of the disease, Parkinson's patients also have difficulty performing complex movements requiring motor learning. The primary motor cortex (M1) is crucial for this learning, and its activity is altered in parkinsonian patients. The objective of this project was to study the targets and the mechanism of action of dopamine in M1 during motor learning. We first demonstrated that parvalbumin (PV) neurons are the major neuronal population expressing D2-like dopamine receptors in layer 5 of M1 in mice. Activation of these receptors was able to increase the excitability and synaptic transmission of PVneurons on its target cells. We then showed that learning a new fine motor taskin duced a decrease in excitability and synaptic transmission of PV neurons.Moreover, specific dopaminergic depletion in M1 prevented fine motor learning and also altered the excitability of PV neurons. These dopamine-depleted mice also showed impaired short-term plasticity of their synaptic transmission to pyramidal cells. These data show that PV neurons in M1 layer 5 undergo dopamine-dependentplasticity when learning a new fine motor task. We next focused on a feature of cortical PV neurons, the perineuronal nets (PNN). These PNN are part of the extracellular matrix and form a mesh-like structure that wraps the soma andproximal dendrites of neurons, mainly PV neurons in M1. These PNN are known to 9 act as an inhibitor of cortical plasticity and that their depletion creates a newplasticity window. Our results showed that PNN are reduced in M1 during motorlearning, opening a new plasticity window. We also showed that the decrease inexcitability of PV neurons in M1 was sufficient to induce a decrease in PNN. Finally, using in vivo calcium imaging we observed the impact of the dopaminergic lesion at a larger scale, showing that the activity of M1 pyramidal cells during motor learningis decreased. This project allowed us to better understand the role of dopamine modulation of M1 circuitry, highlighting PV as a target for cortical dopamine and thus a potential source of dysfunction in M1 pathophysiology
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La maladie de Parkinson, qui affecte plus de 7 millions de personnes dans le monde, est due à la perte progressive des neurones dopaminergiques du mésencéphale. En plus des symptômes moteurs caractéristiques de la maladie, les patients parkinsoniens rencontrent des difficultés à exécuter des mouvements complexes nécessitant un apprentissage moteur. Le cortex moteur primaire (M1) est crucial pour cet apprentissage, et son activité est altérée chez les patients parkinsoniens. L’objectif de ce projet était d’étudier les cibles et le mécanisme d’action de la dopamine dans M1 pendant l’apprentissage moteur. Nous avons mis en évidence que les neurones à par valbumine (PV) sont les neurones majoritaires exprimant les récepteurs D2 à la dopamine dans la couche 5 du M1 chez la souris.L’activation de ces récepteurs augmente l’excitabilité et la transmission synaptique des neurones PV sur ses cellules cibles. Nous avons ensuite montré que l’apprentissage d’une nouvelle tâche motrice fine induit une diminution de l’excitabilité et de la transmission synaptique des neurones PV. De plus, la déplétion dopaminergique spécifiquement au niveau de M1 chez des souris empêche l’apprentissage moteur fin et altère également l’excitabilité des neurones PV. Ces souris déplétées en dopamine présentent également une altération de la plasticité à court terme de leur transmission synaptique vers les cellules pyramidales. Ces effets tendent à montrer que les neurones PV de la couche 5 du M1 subissent des plasticités dopamine-dépendantes lors de l’apprentissage d’une nouvelle tâche motrice fine.11Nous nous sommes ensuite intéressés à une caractéristique des neurones PV corticaux, les réseaux périneuronaux (PNN, pour perineuronal nets en anglais). Ces PNN font partie de la matrice extracellulaire et forme une structure en filet qui enveloppe le soma et les dendrites proximales des neurones, principalement les neurones PV dans M1. Ces PNN sont connus pour agir comme inhibiteur de la plasticité corticale et leur diminution ouvre une fenêtre de plasticité. Nos résultats ont montré en effet que les PNN sont réduits dans M1 au cours de l’apprentissage moteur. Nous avons également mis en évidence que la diminution de l’excitabilité des neurones PV du M1 était suffisante pour induire une diminution des PNN. Enfin,l’utilisation de l’imagerie calcique in vivo nous a permis d’enregistrer de façon longitudinale l’activité des cellules pyramidales dans M1 chez des animaux réalisant la tâche motrice. En suivant l’activité du réseau chez des souris contrôles et chez des souris déplétées en dopamine au niveau de M1, nous avons pu étudier aussi l’impact de la lésion dopaminergique à plus grande échelle. Ainsi, les analyses préliminaires montrent que l’activité des cellules pyramidales du M1 pendant l’apprentissage moteur est diminuée. Ce projet a permis de mieux comprendre le rôle de la modulation dopaminergique du M1, mettant en évidence les neurones PV comme cible de la dopamine corticale et donc comme source potentielle de dysfonctionnement dans la pathologie de M1.
Parkinson's disease (PD) is a neurodegenerative illness that progresses and is long-lasting. It becomes more difficult to talk, write, walk, and do other basic functions when the brain's dopamine-generating neurons are injured or killed. There is a gradual rise in the intensity of these symptoms over time. Using Parkinson's Telemonitoring Voice Data Set from UCI and deep neural networks, we provide a strategy for predicting the severity of Parkinson's disease in this research. An unprocessed speech recording contains a slew of unintelligible data that makes correct diagnosis difficult. Therefore, the raw signal data must be preprocessed using the signal error drop standardization while the features can be grouped by using the wavelet cleft fuzzy algorithm. Then the abnormal features can be selected by using the firming bacteria foraging algorithm for feature size decomposition process. Then classification was made using the deep brooke inception net classifier. The performances of the classifier are compared where the simulation results show that the proposed strategy accuracy in detecting severity of the Parkinson's disease is better than other conventional methods. The proposed DBIN model achieved better accuracy compared to other existing techniques. It is also found that the classification based on extracted voice abnormality data achieves better accuracy (99.8%) over PD prediction; hence it can be concluded as a better metric for severity prediction.
The Japanese Society of Internal MedicineFebruar 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.
International audience;
Objective: Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease. In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations.Methods: Data from the French Parkinson Disease Genetics national multicenter cohort study were used. Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021. Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes. Vital status was collected from the National death register for participants born in France. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression.Results: Of the 2,037 patients with Parkinson's disease, 889 had died after a follow-up of up to 30 years. Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival.Interpretation: Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations. Differences in severity and disease progression among monogenic forms of Parkinson's disease likely explain these findings, which has important consequences for genetic counselling and choice of end points for future clinical trials for targeted therapies. ANN NEUROL 2023.
Medication for neurological diseases such as the Parkinson's disease usually
happens remotely away from hospitals. Such out-of-lab environments pose
challenges in collecting timely and accurate health status data. Individual
differences in behavioral signals collected from wearable sensors also lead to
difficulties in adopting current general machine learning analysis pipelines.
To address these challenges, we present a method for predicting the medication
status of Parkinson's disease patients using the public mPower dataset, which
contains 62,182 remote multi-modal test records collected on smartphones from
487 patients. The proposed method shows promising results in predicting three
medication statuses objectively: Before Medication (AUC=0.95), After Medication
(AUC=0.958), and Another Time (AUC=0.976) by examining patient-wise historical
records with the attention weights learned through a Transformer model. Our
method provides an innovative way for personalized remote health sensing in a
timely and objective fashion which could benefit a broad range of similar
applications.
;Comment: Accepted to ICDH-2023. Camera ready with supplementary material
The aim of this prospective study was to investigate autonomic function in Parkinson’s disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson’s Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.
Background Sex hormones affect the pathogenesis of Parkinson patients and it has been suggested that gender is the most important factor in the development and progression of Parkinson’s disease. Studies have shown that the second to fourth digit ratio (2D:4D) is affected by the prenatal testosterone and estrogen levels and can predict predisposition to disease. In addition, decreased muscle strength in people with Parkinson’s has been repeatedly reported. Hand grip strength (HGS) is a suitable measure to evaluate the musculoskeletal system among the elderly and it is considered as an indicator of the overall strength of the body. This study aimed at investigating the relationship between Parkinson’s disease and HGS and 2D:4D ratio. Methods In this study 117 elderly men with Parkinson disease (mean age of 61.66 ± 11.28 years) and 156 healthy control subjects (mean age of 61.86 ± 6.29 years) participated. After determining the level of disability of Parkinson patients by a neurologist (level of disability in the range of 1–4), anthropometric indices (height, weight, length of the second and fourth fingers) and maximum HGS were measured. Results Although 2D:4D ratios (right and left hand) of male patients with Parkinson’s disease were higher than those of healthy males, this difference was not statistically significant (P = 0.12, P = 0.40; respectively). Conversely, HGS for the right and left hands of Parkinson patients were significantly lower than those of healthy males (P = 0.02, P = 0.03; respectively). The results showed a significant negative relationship between Parkinson disease and the right and left HGS (R = -0.16, P = 0.005; R = -0.17, P = 0.003; respectively). Parkinson disease had no significant relationship with 2D:4D of the right hand, left hand, mean finger ratio and D_R−L 2D:4D (P > 0.05). The regression results showed that the right and left HGS were not able to predict Parkinson disease (P = 0.25, P = 0.16; respectively). Conclusion We concluded that HGS was negatively associated with the Parkinson disease, but conversely, 2D:4D may not be a valuable biomarker of elevated risk of Parkinson in elderly males.
Background The loss of dopamine neurons in the substantia nigra, as well as other mostly catecholaminergic neurons, causes many of the motor symptoms that define Parkinson's disease. Parkinson's disease is commonly thought of as a movement disorder, the significant prevalence of psychiatric complications such as cognitive impairment, and psychosis suggests it should be considered a neuropsychiatric illness, and all behavioral complications are linked to growing disability and the medication. Main body Apart from the disease-induced abnormalities, there are several other side effects of the disease and also from the medication used to prevent the disease. This article focuses on the pathogenesis of Parkinson’s disease and also the behavioral abnormalities caused by the disease and its medication. The study's data were gathered by searching several review articles and research papers from a variety of sources, including Elsevier, PubMed, Research Gate, Journal of Pharmaceutical Science, etc., from the year 1985 to 2021. Parkinson's disease is a neurodegenerative disease caused by a variety of complex processes. It is responsible not just for motor symptoms, but also for a variety of behavioral symptoms that can arise as a result of the disease and/or medication. Conclusion Only symptomatic drugs are available; thus, finding treatments that directly address the disease mechanisms causing Parkinson’s disease is essential. To alleviate the disease's burden on patients and their families, better treatments for the neuropsychiatric repercussions of Parkinson's disease are required. Graphical Abstract
Flexible Endoscopic Evaluation of Swallowing (FEES) is one of two diagnostic gold standards for pharyngeal dysphagia in Parkinson's disease (PD), however, validated global outcome measures at the patient level are widely lacking. The Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES) represents such an outcome measure but has been validated primarily for head and neck cancer collectives. The objective of this study was, therefore, to investigate the validity of the DIGEST-FEES in patients with PD. Content validity was evaluated with a modified Delphi expert survey. Subsequently, 66 FEES videos in PD patients were scored with the DIGEST-FEES. Criterion validity was determined using Spearman's correlation coefficient between the DIGEST-FEES and the Penetration-Aspiration Scale (PAS), the Yale-Residue-Rating-Scale, the Functional-Oral-Intake-Scale (FOIS), and the swallowing-related Unified-Parkinson-Disease-Rating-Scale (UPDRS) items. Inter-rater reliability was determined using 10 randomly selected FEES-videos examined by a second rater. As a result, the overall DIGEST-FEES-rating exhibited significant correlations with the Yale-Valleculae-Residue-Scale ( r = 0.84; p < 0.001), the Yale-Pyriform-Sinus-Residue-Scale ( r = 0.70; p < 0.001), the FOIS ( r = − 0.55, p < 0.001), and the UPDRS-Swallowing-Item-Score ( r = 0.42, p < 0.001). Further, the DIGEST-FEES-safety subscore correlated with the PAS ( r = 0.63, p < 0.001). Inter-rater reliability was high for the overall DIGEST-FEES rating (quadratic weighted kappa of 0.82). Therefore, DIGEST-FEES is a valid and reliable score to evaluate overall pharyngeal dysphagia severity in PD. Nevertheless, the modified Delphi survey identified domains where DIGEST-FEES may need to be specifically adapted to PD or neurological collectives in the future.
BACKGROUND: Sex hormones affect the pathogenesis of Parkinson patients and it has been suggested that gender is the most important factor in the development and progression of Parkinson’s disease. Studies have shown that the second to fourth digit ratio (2D:4D) is affected by the prenatal testosterone and estrogen levels and can predict predisposition to disease. In addition, decreased muscle strength in people with Parkinson’s has been repeatedly reported. Hand grip strength (HGS) is a suitable measure to evaluate the musculoskeletal system among the elderly and it is considered as an indicator of the overall strength of the body. This study aimed at investigating the relationship between Parkinson’s disease and HGS and 2D:4D ratio. METHODS: In this study 117 elderly men with Parkinson disease (mean age of 61.66 ± 11.28 years) and 156 healthy control subjects (mean age of 61.86 ± 6.29 years) participated. After determining the level of disability of Parkinson patients by a neurologist (level of disability in the range of 1–4), anthropometric indices (height, weight, length of the second and fourth fingers) and maximum HGS were measured. RESULTS: Although 2D:4D ratios (right and left hand) of male patients with Parkinson’s disease were higher than those of healthy males, this difference was not statistically significant (P = 0.12, P = 0.40; respectively). Conversely, HGS for the right and left hands of Parkinson patients were significantly lower than those of healthy males (P = 0.02, P = 0.03; respectively). The results showed a significant negative relationship between Parkinson disease and the right and left HGS (R = -0.16, P = 0.005; R = -0.17, P = 0.003; respectively). Parkinson disease had no significant relationship with 2D:4D of the right hand, left hand, mean finger ratio and D(R−L) 2D:4D (P > 0.05). The regression results showed that the right and left HGS were not able to predict Parkinson disease (P = 0.25, P = 0.16; respectively). CONCLUSION: We concluded that HGS was negatively associated with the Parkinson disease, but conversely, 2D:4D may not be a valuable biomarker of elevated risk of Parkinson in elderly males.
Parkinson's Disease (PD) is the second most common neurodegenerative
disorder. The existing assessment method for PD is usually the Movement
Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to
assess the severity of various types of motor symptoms and disease progression.
However, manual assessment suffers from high subjectivity, lack of consistency,
and high cost and low efficiency of manual communication. We want to use a
computer vision based solution to capture human pose images based on a camera,
reconstruct and perform motion analysis using algorithms, and extract the
features of the amount of motion through feature engineering. The proposed
approach can be deployed on different smartphones, and the video recording and
artificial intelligence analysis can be done quickly and easily through our
APP.
;Comment: Technical report for AI WALKUP, an APP winning 3rd Prize of 2022 HUST
GS AI Innovation and Design Competition
International audience;
Background<p>Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later.</p></div> <div>Methods<p>We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these prodromal factors and the risk of receiving a diagnosis of AD, PD, or ALS.</p></div> <div>Findings<p>We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later.</p></div> <div>Interpretation<p>Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics are specific to ALS.</p></div> <div>Funding<p>EU Joint Programme -Neurodegenerative Disease Research.
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.
Objective: We present the PaHaW Parkinson's disease handwriting database,
consisting of handwriting samples from Parkinson's disease (PD) patients and
healthy controls. Our goal is to show that kinematic features and pressure
features in handwriting can be used for the differential diagnosis of PD.
Methods and Material: The database contains records from 37 PD patients and 38
healthy controls performing eight different handwriting tasks. The tasks
include drawing an Archimedean spiral, repetitively writing orthographically
simple syllables and words, and writing of a sentence. In addition to the
conventional kinematic features related to the dynamics of handwriting, we
investigated new pressure features based on the pressure exerted on the writing
surface. To discriminate between PD patients and healthy subjects, three
different classifiers were compared: K-nearest neighbors (K-NN), ensemble
AdaBoost classifier, and support vector machines (SVM). Results: For predicting
PD based on kinematic and pressure features of handwriting, the best performing
model was SVM with classification accuracy of Pacc = 81.3% (sensitivity Psen =
87.4% and specificity of Pspe = 80.9%). When evaluated separately, pressure
features proved to be relevant for PD diagnosis, yielding Pacc = 82.5% compared
to Pacc = 75.4% using kinematic features. Conclusion: Experimental results
showed that an analysis of kinematic and pressure features during handwriting
can help assess subtle characteristics of handwriting and discriminate between
PD patients and healthy controls.
;Comment: 23 pages
Background Mobile gait sensors represent a compelling tool to objectify the severity of symptoms in patients with idiopathic Parkinson’s disease (iPD), but also to determine the therapeutic benefit of interventions. In particular, parameters of Deep Brain stimulation (DBS) with its short latency could be accurately assessed using sensor data. This study aimed at gaining insight into gait changes due to different DBS parameters in patients with subthalamic nucleus (STN) DBS. Methods An analysis of various gait examinations was performed on 23 of the initially enrolled 27 iPD patients with chronic STN DBS. Stimulation settings were previously adjusted for either amplitude, frequency, or pulse width in a randomised order. A linear mixed effects model was used to analyse changes in gait speed, stride length, and maximum sensor lift. Results The findings of our study indicate significant improvements in gait speed, stride length, and leg lift measurable with mobile gait sensors under different DBS parameter variations. Notably, we observed positive results at 85 Hz, which proved to be more effective than often applied higher frequencies and that these improvements were traceable across almost all conditions. While pulse widths did produce some improvements in leg lift, they were less well tolerated and had inconsistent effects on some of the gait parameters. Our research suggests that using lower frequencies of DBS may offer a more tolerable and effective approach to enhancing gait in individuals with iPD. Conclusions Our results advocate for lower stimulation frequencies for patients who report gait difficulties, especially those who can adapt their DBS settings remotely. They also show that mobile gait sensors could be incorporated into clinical practice in the near future.
It makes no difference whether a person is male or female when it comes to neurodegenerative disorders; both sexes are equally susceptible to their devastating effects. Sometimes, it is unclear why a person in their life got a condition that is well-known in the world, such as Parkinson's disease. Other times, it is evident why the individual obtained the ailment (PD). In modern times, a variety of cutting-edge algorithms that are based on treatment protocols have been developed for the purpose of diagnosing Parkinson's disease. The approach that is presented in this article is the most current one; it was created using deep learning, and it can predict how severely Parkinson's disease would affect a patient. In order to diagnose this condition, it is necessary to conduct a comprehensive medical history, a history of any past treatments, physical exams, and certain blood tests and brain films. Because they are less time-consuming and costly, diagnoses are becoming an increasingly important part of medical practice. The diagnosis of Parkinson's disease by the physician is supported by the findings of the present research, which analyzed the voices of 253 participants. Preprocessing is done in order to get the most accurate results possible from the data. In order to carry out the technique of balancing, a methodical sampling approach was used to choose the data that would afterwards be evaluated. Using a feature selection approach that was determined by the magnitude of the label's influence, many data groups were created and organized. DT, SVM, and kNN are three methods that are used in classification algorithms and performance assessment criteria. The model was developed as a result of selecting the classification method and data group that had the greatest performance value. This decision led to the creation of the model. During the process of building the model, the SVM technique was used, and data comprising 45% of the original data set were utilized. The information was arranged in descending order of significance, beginning with the most pertinent. In addition to achieving exceptional outcomes in every other aspect of the project, the performance accuracy target was successfully met at 86 percent. As a consequence of this, it has been decided that the physician will be provided with medical decision support with the assistance of the data set obtained from the speech recordings of the individual who may have Parkinson's disease and the model that has been developed. This has led to the conclusion that medical decision support will be offered to the physician.
We have incorporated a hadron interaction tuning based on accelerator data into our atmospheric neutrino flux calculation, which has been used to analyze atmospheric neutrino oscillations at Super-Kamiokande. This new approach enables a more direct evaluation of the flux uncertainty than a conventional tuning using atmospheric muons.
The neutrino flux calculated with this new tuning is 5\%--10\% smaller but still consistent with our previously published prediction within its uncertainty. The flavor ratio $(ν_μ+\barν_μ)/(ν_e+\barν_e)$ and $\barν/ν$ ratios were consistent with the previous prediction. Based on the measurement errors of the accelerator data, we evaluated the flux uncertainty associated with the new tuning to be 7\%--9\% in the $E_ν <$ 1 GeV region, which was difficult to assess with the conventional tuning. The flux uncertainty in the $1<E_ν<10$ GeV region was evaluated to be 5\%--7\%, which is an improvement over the conventional tuning. ;29 pages, 17 figures
The Vera C. Rubin observatory is expected to produce 10 million transient alerts per night in ugrizy filters, whilst Euclid is a visible to near-infrared space telescope engaged in a wide field survey. We present a prototype system to automatically match the transient alerts from Rubin to Euclid observations. The system produces joint light-curves containing both visible and near-infrared photometry, and joint image cutouts. Using Zwicky Transient Facility alerts as a proxy for Rubin, we demonstrate the system in use in cases where Euclid did and did not detect the transient and highlight the value that can be added in each case. For transients detected by Euclid these benefits include identifying the supernovae (SNe) in observations taken prior to ground-based detection, thereby better constraining the explosion time, such as SN 2024pvw detected ~3 d prior to ground based detections. In cases where Euclid did not detect the transient, we demonstrate the benefit of adding Euclid observations to improve host morphology measurements and associations. ;16 Pages, 8 Figures, Accepted in RASTI
Theoretical models of the evolution of supermassive black hole (SMBH) pairs in post-merger remnant galaxies are necessary to motivate observational searches for dual active galactic nuclei (AGN) and gravitational wave sources. Studies have explored the dynamical evolution of SMBH pairs under the influence of dynamical friction to calculate pairing times and predict the expected population of dual-AGNs at various redshifts. We formulate a three-dimensional dynamical model of SMBH pairs in the innermost kiloparsec of a post-merger galaxy to investigate the impact of orbital inclination with respect to the galactic disk on pairing times. The SMBH pairs are evolved in 81 different galaxy configurations initialized using a Gauss-Seidel Poisson solver. The dynamics are calculated for 12 distinct initial inclinations ranging from 0 to 75 degrees in each of the galaxies to gauge the impact of inclination on pairing time. Orbits characterized by initial inclinations greater than 20 degrees frequently require longer pairing times when compared to uninclined orbits. Pairing times for orbits with inclinations $\gtrsim 45$ degrees often exceed 14 Gyr. Galaxies with higher mass SMBH pairs and faster rotating disks generally shorten pairing times relative to galaxies with less massive or slower rotating disks when the inclination is $\lesssim 45$ degrees. The model suggests that SMBH pairs that form from mergers at inclinations $\lesssim 20$ degrees are likely progenitors of dual-AGN and gravitational wave sources. ;17 pages, 12 figures, 2 tables, accepted for publication in ApJ
We present a detailed analysis of the structural parameters of the globular cluster M 15 using g- and i-band photometric data from Pan-STARRS1 DR2. The central coordinates ($X_{\rm{C}}, Y_{\rm{C}}$), ellipticity ($ε$), and position angle (PA) are derived via two independent methods: ellipse fitting of the two-dimensional stellar number isodensity distribution and Markov Chain Monte Carlo (MCMC) sampling. Our analysis of 38 stellar density intervals reveals a cluster center offset by only $4\,.\!\!^{\prime\prime}1\pm9\,.\!\!^{\prime\prime}6$ from the commonly accepted in the literature value, a good agreement on the order of our map resolution. We find a radial variation in the ellipticity, with a mean value of $ε=0.09\pm0.02$ for the inner region ($R\leq4\,.\!\!^{\prime}5$) and $ε=0.04\pm0.02$ for the outer region ($R>4\,.\!\!^{\prime}5$), where the errors correspond to $1σ$. The MCMC analysis of 75 datasets yields a mean $ε=0.022\pm0.005$ for the entire cluster. The PA remains constant with increasing distance from the cluster center, $\rm{PA}=44\,.\!\!{\rm{^\circ}}4\pm16\,.\!\!{\rm{^\circ}}2$, and the MCMC method providing a consistent value of $\rm{PA}=46\,.\!\!{\rm{^\circ}}6\pm7\,.\!\!{\rm{^\circ}}1$. Our results are in agreement with some recent studies but challenge others, suggesting that a single $ε$ value may be insufficient to fully characterize the overall oblateness of M 15 due to incompleteness and crowding effects in its core.
One objective of Artemis science is to determine the impact human activities have on the lunar environment, which might compromise science objectives and measurements. We perform a preliminary analysis of the contamination associated with airlock venting and outgassing from a prototype lunar-module geometry intended to host astronauts on the lunar surface. The air flow generated by the depressurization of the airlock, expanding in the lunar exosphere, is studied using the Direct Simulation Monte Carlo (DSMC) method for two different venting configurations and the particle flux on the surface is computed as a function of the distance from the the module. Outgassing from the main body of the module -- assumed to be covered with a Multi-Layer Insulation (MLI) blanketing -- and from the solar panels is then analyzed using a view-factor method, employing outgassing rates from the literature.Our results give preliminary indications of the distance at which contamination levels fall below the values characteristic of native species in the lunar atmosphere. Scientific measurements targeting 40Ar should be carried farther than 30--100 meters from the module, while the detection of lower-abundance species such as polar-crater water might require to travel up to and beyond 3 km from the module.
The spatial and kinematic structure of the circumgalactic medium (CGM) remains poorly constrained observationally. In this article we compute the clustering of CIV absorption systems at cosmic noon using quasar pairs. We analyze VLT/UVES and Keck/HIRES high-resolution spectra (R = 45000) of a sample of 8 projected and 4 lensed quasar pairs that probe transverse separations, $Δr$, from sub-kpc to a few Mpc, over the redshift range 1.6 < z < 3.3. We detect and fit Voigt profiles to a total of 141 CIV systems, corresponding to 620 velocity components across all quasar lines-of-sight. We compute the two-point correlation function of CIV, $ξ(Δv, Δr)$, where $Δv$ is the velocity difference between components across all available scales. We find a strong dependence of $ξ(Δr)$ with $Δr$ at all velocities. $ξ(Δr)$ reaches a sharp peak at the smallest scales analyzed here, $Δr\approx 0.1$ kpc, decreases steadily up to $Δr\approx 5$ kpc and remains flat up to $Δr\approx 500$ kpc, where it begins to decrease again. By fitting power-laws to the projected transverse correlation function $Ξ(Δr)$, we infer two coherence lengths: $r_1 = 654^{+100}_{-87}$ kpc, which we interpret as a representative size for the CIV enriched regions at $z\approx 2$, and $r_2 = 4.70^{+1.60}_{-1.19}$ kpc for the individual CIV-bearing "clouds". Projecting instead in $Δr$, we find consistent amplitudes of $ξ(Δv)$ with previous work using quasars and extended background sources. Our results suggest that CIV may be a good tracer of not only the small, internal structure of the circumgalactic medium, but also of the way in which galaxies cluster at cosmic noon. ;Accepted for publication in A&A
We study quintessential inflation in the framework of metric-affine gravity. It is well known that non-minimal couplings with the Holst invariant can generate a quasi-pole inflationary behaviour resulting in a Starobinsky-like phenomenology. The same quasi-pole behaviour can also be used in order to "flatten" the scalar potential in the Dark Energy era providing a successful framework for quintessential inflation. Agreement with all the observational constraints, reduces the predicted scalar spectral index to a narrow window: $0.966 \lesssim n_s \lesssim 0.967$, making the model highly testable and falsifiable. ;20 pages, 7 figures, 1 table
The next great leap in Martian exploration will be the return of samples to Earth. To ensure the maximum scientific return from studying these samples, the development and utilisation of nondestructive analytical techniques are essential to enable early three-dimensional characterisation of their interiors. Neutron computed tomography is a powerful method in this context: it is highly sensitive to hydrogen and complements the more conventional X-ray computed tomography. Because the distribution and nature of hydrous phases are central to understanding the habitability, the climatic and geological evolution, and potential biosignatures of Mars, identifying hydrogenbearing phases in Martian crustal rocks is of particular importance. Using the only Martian crustal material available on Earth, the NWA 7034 meteorite and its pairs, we show that combined neutron and X-ray computed tomography enables non-destructive sample-wide mapping of hydrogen and reveals the distribution and petrographic contexts of hydrous phases. We identify hydrogen-rich iron oxyhydroxides within ancient igneous clasts, forming a macroscopic mineralogical water reservoir within the meteorite. These alteration assemblages closely resemble those observed in samples collected by the Perseverance rover in Jezero crater, where hydrated iron oxyhydroxides are also present. This similarity suggests that such phases may represent a widespread near-surface water reservoir on early Mars. ;E.B. Naver and K. W. Nikolajsen have contributed equally
Mixing by hydrodynamical instabilities plays a key role in cloud-wind interactions, causing cloud destruction in the adiabatic limit and facilitating cloud survival with efficient radiative cooling. However, the rate of mixing in numerical simulations is sensitive to the smallest resolved scale, and the relationship between resolution and cloud evolution is under-explored. Using a set of cloud-crushing simulations, we investigate the effects of numerical resolution on cloud survival and acceleration. Modeling both adiabatic and radiative cases, in a subsonic and supersonic wind, we find that cloud survival and velocity does depend on the numerical resolution, however, no single resolution requirement can be applied to all scenarios. In the radiative subsonic case, we find that mass growth and acceleration appear converged at only 4 cells per cloud radius. Conversely, in the supersonic regime, we see a clear dependence of cloud destruction and velocity on resolution that is not converged even at 48 cells per cloud radius, implying that accurately capturing cloud destruction may require higher resolution than capturing growth. We also present a simple model illustrating how ram pressure accelerates cool clouds at early times before mixing kicks in as an acceleration mechanism. ;14 pages, 7 figures, accepted for publication in ApJ
The fate of massive stars during the latest stages of their evolution is highly dependent on their mass-loss rate and geometry. These processes have a significant influence on stars with masses between 25 and 40 Msun, i.e., type II SN progenitors. We aim to investigate the mass-loss history, geometry, and physical conditions of the yellow hypergiant in a post-RSG stage, IRAS 17163-3907. We place it in context with another famous yellow hypergiant, IRC+10420. We combine M-band high-resolution CRIRES+ spectroscopy with VLTI/MATISSE mid-infrared L-band interferometry, and FORS2 optical spectropolarimetry to probe both the small-scale circumstellar structure and the large-scale dusty environment of IRAS 17163. The CRIRES+ spectrum provides the first M-band coverage of IRAS 17163, revealing prominent low-excitation metal lines and hydrogen recombination features, but lacking the pronounced CO absorption seen in IRC+10420. The MATISSE observations reveal the first high angular scales of the source in the L-band and spatially resolve the Brα line-emitting region, which hints at a marginally asymmetric and variable ionised wind. FORS2 spectropolarimetry points to deviations from perfect spherical symmetry also on larger scales. The data show no evidence for a binary companion within the explored parameter space, indicating that the observed clumpy and time-variable mass loss is likely intrinsic to the star rather than companion-driven. Our results demonstrate that IRAS 17163 hosts a dense, structured, and time-variable wind, coexisting with extended dusty shells. The comparison with IRC+10420 highlights diversity among post-RSG YHGs. These findings emphasise the role of clumpy and near-symmetric mass-loss in shaping the circumstellar medium of evolved massive stars, with implications for their subsequent evolution and core-collapse supernova progenitor properties. ;Accepted for publication in A&A (27 pages including 8 pages appendix, 17 figures, 5 tables)
We review the algebraic definition of the efficiency of a polarization modulation scheme, which is commonly adopted for solar and stellar spectro-polarimetry applications, and generalize it to allow distinct states of the modulation cycle to have arbitrary throughput and different photon-noise statistics for each state. Such a generalization becomes necessary to model and optimize the polarimetric efficiency of instruments implementing spatial polarization modulation schemes, where different optical paths are assigned to different polarization analysis states, which may be characterized by different throughput values. The proposed algebraic extension also proves essential for introducing a workable concept of the efficiency of a polarization calibration scheme, which can then be used to create a merit function for the optimization of calibration sequences, which take into account the specific characteristics of the polarimetric instrument and of its calibration optics.
Nanophase iron (npFe) plays a crucial role in controlling the optical, chemical, and physical evolution of lunar regolith grains. While in-situ formation of npFe via reduction of native Fe-bearing minerals has long been considered a dominant pathway, recent mineralogical evidence from X.Zeng et al. (2025) reveals that the source of a significant fraction of npFe may be delivered directly by exotic micrometeoroid impacts (exotic npFe). Yet the atomic-scale processes governing how exotic np-Fe forms and survives during hypervelocity impacts remain largely unknown. To quantitatively compare in-situ and exotic delivery and formation of npFe, we perform a series of innovative atomistic modeling of micrometeoroid impacts with distinct projectile target compositions: (1) SiO$_2$ projectiles on Fe$_2$SiO$_4$ targets (in-situ formation), (2) Fe$_2$SiO$_4$ projectiles on SiO$_2$ targets (exotic delivery). Our results reveal distinct mechanistic fingerprints: in-situ np-Fe forms diffusely and radially around the impact site, whereas exotic np-Fe is efficiently retained and concentrated in asymmetric, momentum-aligned clusters. These contrasting spatial signatures provide a potential diagnostic criterion for distinguishing exotic versus in-situ np-Fe in returned lunar soils. In agreement with Chang'e-5 observations, our simulations demonstrate that exotic np-Fe production can be substantial, particularly in Fe-poor terrains such as highland regions. These findings highlight the need to account for exotic np-Fe when interpreting space weathering processes and remote-sensing data for the Moon and other airless bodies. ;9 pages, 4 figures, in press at PSJ
We present cosmological parameters measurements from the full combination of DESI DR1 galaxy clustering data described with large-scale structure effective field theory. By incorporating additional datasets (photometric galaxies and CMB lensing cross-correlations) and extending the bispectrum likelihood to smaller scales using a consistent one-loop theory computation, we achieve substantial gains in constraining power relative to previous analyses. Combining with the latest DESI baryon acoustic oscillation data and using cosmic microwave background (CMB) priors on the power spectrum tilt and baryon density, we obtain tight constraints on the $Λ$CDM model, finding the Hubble constant $H_0=69.08\pm 0.37~\mathrm{km}\,\mathrm{s}^{-1}\mathrm{Mpc}^{-1}$, the matter density fraction $Ω_m=0.2973\pm 0.0050$, and the mass fluctuation amplitude $σ_8 = 0.815\pm 0.016$ (or the lensing parameter $S_8\equivσ_8\sqrt{Ω_m/0.3}=0.811\pm 0.016$), corresponding to $0.6\%$, $1.7\%$, and $2\%$ precision respectively. Adding the Pantheon+ supernova sample (SNe), we find a preference of $2.6σ$ for the $w_0w_a$ dynamical dark energy model from low-redshift data alone, which increases to $2.8σ$ when exchanging the SNe with Planck CMB data. Combining full-shape data with BAO, CMB, and SNe likelihoods, we improve the dark energy figure-of-merit by $18\%$ and bound the sum of the neutrino masses to $M_ν<0.057$ eV in $Λ$CDM and $M_ν<0.095$ eV in the $w_0w_a$ dynamical dark energy model (both at 95\% CL). This represents an improvement of $25\%$ over the background expansion constraints and the strongest bound on neutrino masses in $w_0w_a$CDM to date. Our results suggest that the preference for the normal ordering of neutrino mass states holds regardless of the cosmological background model, and is robust in light of tensions between cosmological datasets. ;39 pages, 5 tables, 6 figures
Interstellar dust plays a crucial role in gas cooling and molecule formation, influencing galaxy evolution. However, the composition and structure of dust in distant galaxies are still poorly understood. We have started a JWST MIRI MRS program investigating the dust features in gas-rich and dusty galaxies at redshifts $z<$1.2, with strong 2175~Å bumps detected in absorption along the lines of sight to distant background quasars. Here we describe our program strategy, and present MIRI MRS observations of IR dust features at $z=0.5-1.2$ in five quasar spectra that form the first part of our full sample. We identify artifacts in MIRI MRS data that affect the background in IFU cubes, and propose methods to reduce their effects. We pay special attention to modeling the quasar mid-IR continuum, which shows significant variation depending on AGN morphology, redshift, and black hole mass. Dust in foreground galaxies produces significant absorption from the 10~$μ$m silicate feature in all five quasar spectra. Compared with the average 10~$μ$m silicate feature in the diffuse ISM of the Milky Way, we find differences in the absorption peak position, width of the features, and asymmetry of the profiles. A detailed study of these silicate features is presented in our next paper (Klimenko et al. 2026b). In two quasar spectra, we tentatively detect weak IR features near 3.0 and 3.4~$μ$m. Their strengths are comparable to those seen in the Milky Way ISM, but follow-up observations are required to confirm these detections. ;23 pages, 8 figures
Type Ia Supernovae (SNe Ia) are well known for their role as standardizable cosmological candles. Their uniformity is credited to their single origin as thermonuclear explosions of White dwarf (WD) stars. Nevertheless, some SNe Ia break this regularity. Prominently, the Iax subclass are less energetic and remarkably diverse, raising questions about their progenitor systems. While no progenitor system of a normal SN Ia has ever been detected, a luminous blue star was identified in pre-explosion images of the site of the bright SN Iax SN 2012Z, suggested to be a helium giant companion star acting as a mass donor to a WD SN progenitor. This is in line with models of weak mass accretion of a WD from a binary companion, producing an explosion that does not fully disrupt the star. However, these models fail to explain the properties of the faintest Type Iax explosions, suggesting either they originate from other WD binary systems, or even from massive progenitor stars. Here, we present the faint SN Iax SN 2024vjm - possibly the faintest supernova observed to date. Using a deep pre-explosion image taken by the recently launched Euclid space mission, we show that its progenitor system must be fainter than the helium giant SN Iax progenitor candidate of SN 2012Z, as well as that of the luminous red companion or remnant of the faint SN 2008ha, and may require a subdwarf helium star as a mass donor. The deep image also provides strong arguments against a massive star origin for this faint supernova. Our observations argue that SN 2024vjm is a WD explosion, but we find that remarkably faint SNe Iax fade more slowly than bright ones, i.e., they evolve in an opposite manner from the famous Phillips relation that makes regular SNe Ia cosmological candles.
I consider recent observations of ultramassive black holes. These appear to confirm theoretical predictions that the relation between central black hole mass $M$ and spheroid velocity dispersion $σ$ has the same form $M \propto σ^4$ in spiral galaxies, elliptical galaxies, and cluster ellipticals, but has differing normalizations. These arise from the need for longer black hole accretion episodes to expel the gas otherwise potentially able to feed the holes in the latter two types of host. In a sample drawn from a mixture of galaxy host types the fitted power of $σ$ will slightly exceed the theoretically-derived value of 4 because of the differing normalizations. The observed hole masses do not currently reach the theoretical maximum values possible for disc accretion, set by the equality of the ISCO and self-gravity radii, probably because the host galaxies have insufficient gas. ;Accepted for MNRAS
The physical conditions of the intergalactic medium (IGM) during the final stages of cosmic reionization ($z\sim5.0-6.0$) are not yet fully understood. Recent reports of unexpectedly large-scale ($\ge 150 h^{-1}\mathrm{cMpc}$) correlation in Ly-$α$ transmission flux using extended XQR-30 quasar spectra pose interesting challenges on the reionization end stages. In this work, we investigate the Ly-$α$ forest dark-gap distribution (defined as regions with transmitted flux below 0.05) as another sensitive tracer of the IGM, using an efficient, large-volume ($\sim 1 ~\mathrm{Gpc}$) simulation framework. By constructing a suite of physically motivated model variants (i.e, varying the reionization redshift, IGM temperature, and ionizing-photon mean free path), we generate synthetic sightlines and compare their predicted cumulative distribution of dark gaps with that of observed spectra (at redshift intervals of $Δz=0.2$). We find that most of the models achieve qualitatively consistent agreement with the data. The scenario involving a slightly later reionization completion ($z\sim 5.4$) provides the closest match, while a short constant mean free path model is disfavored by the data at lower redshifts. These findings give qualitative support for the emerging scenario of reionization end extending to $z\le5.7$, although they can not rule out a slightly early reionization with enhanced post-ionization ultraviolet (UV) background fluctuations. A similar conclusion arises from the redshift distribution of long dark gap ($L\ge 30 ~h^{-1}\mathrm{cMpc}$) fraction. However, the model variants are still not able to reproduce the observed strong flux correlations at unusually large scales, which remains open for further investigations. ;Accepted in A&A, 9 pages, 6 figures (+ Appendices)
Various existing models of the Gum Nebula differ significantly in their parameters and suggested origins, which can be independently tested for consistency with data on some key observables of pulsars in the direction of the nebula. Our analysis of such data on the Vela pulsar, assuming a dominant scattering region in its foreground, suggests that the fractional distance of the scatterer is $0.89 \pm 0.01$, and for the given distance of the Vela pulsar, it translates to $254 \pm 16$ pc. Using independent distances of ten pulsars, we suggest a refined description of the Gum Nebula electron density model with its basic morphology similar to that used in the YMW16 model, which now provides better estimates of pulsar distances in these directions. In our new Gum Nebula model, as expected, the Vela pulsar would be behind the frontal edge of the Gum shell, which was intriguingly located in front of the nebula in the YMW16 model. We also present a new technique to better constrain the pulsar distances using their dispersion measure and temporal broadening simultaneously, and find that it is less affected by the uncertainties in the Galactic electron density distribution models. Notably, the new approach shows that the expected temporal broadening as a function of trial distance does not follow a monotonic increasing trend, but instead exhibits oscillations at regions of enhanced electron density. This behaviour is expected, as the method employs the integral form of temporal broadening with the appropriate weighting kernel, leading to more reliable estimates. ;Accepted for publication in MNRAS, 10 pages, 6 figures
Many small satellites in the Solar System have sub-synchronous orbits, meaning their orbits are decaying due to tidal dissipation. Unless they have substantial material strength, they will eventually tidally disrupt before reaching their planet's surface. We studied the fate of rubble-pile satellites as they migrate inward, with a particular focus on the case of Phobos. We used a combination of analytic estimates and numerical simulations to determine the failure mode and tidal disruption distance of a Phobos-like satellite, as a function of its shape and cohesive strength. Both analytically and numerically, we identify a regime for satellites with low cohesive strengths whereby their surface can be tidally stripped without undergoing internal failure. Our numerical simulations demonstrate that Phobos will be destroyed beyond 2 Mars radii if it has a bulk strength similar to those estimated for small bodies recently visited by spacecraft. Based on our results and some additional arguments, we suggest that previous studies on the fate of Phobos have overestimated its strength, and therefore underestimated its tidal disruption distance. We also speculate that if Phobos undergoes some tidal stripping, its ultimate fate may be determined by runaway collisional erosion rather than a pure tidal disruption. However, the ultimate tidal disruption distance for Phobos will depend on its unknown internal structure and bulk material properties, which will be constrained by JAXA's Martian Moons eXploration (MMX) mission and its IDEFIX rover. These results have implications for theories about the origin and evolution of the Martian moons and for tidal disruptions of other small, irregularly shaped satellites. ;Published in A&A. For published version and associated movie, see https://doi.org/10.1051/0004-6361/202557988
Mini-EUSO is the first space-borne detector of the JEM-EUSO (Joint Exploratory Missions for Extreme Universe Space Observatory) program, operating on the International Space Station (ISS) since October 2019. Designed to search for Ultra-High Energy Cosmic Rays (UHECRs) above 10$^{21}~$eV and capable of placing a stringent upper limit on their flux at these extreme energies, paving the way to future space-based UHECR observatories, Mini-EUSO has completed more than 150 observation sessions over five years, accumulating approximately 750 hours of data. The mission has produced the first global UV emission maps of Earth and provided valuable insights into lightning phenomena and Transient Luminous Events (TLEs), such as elves, as well as artificial light sources and meteors. Notably, Mini-EUSO has conducted the first systematic space-based meteor survey, detecting over 22,000 meteors and identifying three interstellar candidates. Among the observed TLEs, the most interesting class of phenomena are elves, which appear as expanding ring-shaped structures occurring at $\sim$90 km altitude. Mini-EUSO has detected elves with varying structures and different numbers of concentric rings, from single-ring up to five rings. Thanks to its imaging capabilities, fast time resolution, and favorable observational geometry, Mini-EUSO is uniquely suited to studying this kind of lightning phenomena, providing unprecedented insight into their dynamics. Additionally, the instrument has demonstrated the capability of a space-based detector to identify short light transients resembling extensive air shower signals while distinguishing them from those produced by UHECRs. This contribution presents a comprehensive summary of the Mini-EUSO mission, its status, and main results.
Wave-optics effects in strongly lensed gravitational waves (GWs) provide a new interferometric probe of dark matter substructure. We compute the full diffraction integral for GWs propagating through statistically generated cold dark matter subhalo populations and quantify the resulting frequency-dependent amplification in the Laser Interferometer Space Antenna (LISA) band. We show that realistic galaxy-scale lenses generically produce percent-level amplitude and phase distortions in strongly magnified images, primarily induced by subhalos in the mass range $10^4$-$10^7\,M_{\odot}$. These signatures arise naturally within the standard cold dark matter paradigm and should be detectable in high signal-to-noise LISA events. Strongly lensed GWs thus offer a direct and complementary window on dark matter structure at subgalactic mass scales inaccessible to electromagnetic measurements. ;10 pages, 7 figures
The nuclear equation of state, which determines the structure and properties of neutron stars, remains subject to substantial theoretical uncertainties, leading to model dependence in predicted observables. Universal relations have emerged as a powerful tool to mitigate this dependence by linking neutron star observables in a framework-independent manner. In this work, we introduce a new universal relation that \emph{bridges} finite nuclei and neutron stars through the dimensionless quantity $ζ= β_{1.4}\tilde{L}^{-1}$, which couples the compactness of a $1.4~M_{\odot}$ neutron star to the slope of the nuclear symmetry energy at saturation. The relation is examined under a broad set of relativistic energy density functionals with point-coupling and meson-exchange interactions, as well as non-relativistic Skyrme functionals. We demonstrate that $ζ$ exhibits a strong exponential correlation with the electric dipole polarizability $α_D$ in finite nuclei across all considered equations of state. By exploiting experimental $α_D$ data for selected neutron-rich nuclei, we constrain $ζ$ and translate these constraints into equation-of-state independent bounds on the neutron star radius $R_{1.4}$ and the symmetry-energy slope $L$, providing insights into the properties of neutron star matter. ;v1: 10 pages, 4 figures, 4 tables; v2: 10 pages, 4 figures, 4 tables; matched published version in Physical Review C
A population of free-floating planets is known from gravitational microlensing surveys. None have a directly measured mass, owing to a degeneracy with the distance, but the population statistics indicate that many are less massive than Jupiter. We report a microlensing event -- KMT-2024-BLG-0792/OGLE-2024-BLG-0516, which was observed from both ground- and space-based telescopes -- that breaks the mass-distance degeneracy. The event was caused by an object with 0.219^{+0.075}_{-0.046} Jupiter masses that is either gravitationally unbound or on a very wide orbit. Through comparison with the statistical properties of other observed microlensing events and predictions from simulations, we infer that this object likely formed in a protoplanetary disk (like a planet), not in isolation (like a brown dwarf), and dynamical processes then ejected it from its birth place, producing a free-floating object. ;Published in Science. This is the authors' version. See the ancillary file for an animation associated with Fig. 2
We investigate the structure of strange dwarfs, modeled as hybrid compact stars composed of a self bound strange quark matter core surrounded by a white dwarf like crust, within a fully relativistic framework. Static configurations are constructed by solving the Tolman Oppenheimer Volkoff equations, and uniformly rotating configurations are modeled within the Hartle Thorne slow rotation expansion (to ${\cal O}(Ω^2)$). We therefore interpret results at large fractional spins conservatively, and use the Kepler frequency mainly as a reference scale for comparing different masses and models. The stellar matter is described using a hybrid equation of state, in which the crust is modeled by a degenerate electron ion system and the core by the MIT Bag Model. By comparing strange dwarfs with conventional white dwarfs across a range of rotation rates, we show that rotation inflates the radius and can reduce (in a quantifiable way) the separation between the two families in the $(M,R)$ plane, potentially masking structural signatures associated with the presence of a quark core. Our results highlight the importance of accounting for rotational effects when interpreting mass radius measurements and other global observables in the context of searches for exotic compact objects in current and future high precision surveys.
The presence of multi-phase outflows in low ionisation nuclear emission-line regions (LINERs) has been confirmed to be frequent, but the mechanisms that launch them are still under study. We aim to explore the connections between the ionised gas outflow, radio continuum structures and X-ray emission detected in the LINER NGC4438. We analyse L, C and X-band images (from 1.4 to 12 GHz) of the LINER NGC4438, combining high-resolution data from enhanced Multi Element Radio Linked Interferometer Network (e-MERLIN) and Karl G Jansky Very Large Array (VLA). We produce radio flux, spectral index maps, and an energetic model that allows us to characterise the source. We incorporate optical integral field spectroscopy (IFS) data (GTC/MEGARA) and Chandra X-ray data, with comparable resolution, to better trace the outflow, the AGN and their potential connection. We present new L, C, and X-band high-resolution, high-sensitivity radio images and spectral-index maps that probe $\sim$ 25 pc scales in NGC 4438. These data reveal a close morphological correspondence between the radio structures and the ionised gas bubble. Using a spatially resolved energetic model based on radio flux and spectral index, we disentangle the compact AGN emission from the extended bubble for the first time, establishing their distinct physical origins. We measure a kinetic power of $\sim 5\times 10^{44}$ erg s$^{-1}$ for the radio bubble, exceeding the power of the ionised outflow by more than three orders of magnitude. Our multi-wavelength analysis indicates that NGC 4438 is undergoing jet-mode feedback, where a low-luminosity, weakly collimated jet impacts the dense northern interstellar medium. This interaction drives shock-ionised gas, produces a moderate velocity outflow that removes material from the region, and generates thermal X-ray emission coincident with the radio and H$α$ cavity.
Background There has been a growing interest in studying the value of physical exercise in children with disabilities or chronic health conditions because of evidence of improvement in quality of life, social acceptance, and physical functioning. However, only scant evidence exists for routine sports activities in children requiring pediatric palliative care (PPC), and in most cases, such evidence has been collected in oncological patients. The Pediatric Hospice of Padua is the referral center for PPC in the Veneto region (northern Italy). Starting from the experience of this PPC center, this pilot study aims to describe the personal experience of children and young people who practice physical activity and their caregivers’ perspectives, focusing particularly on the emotional and social impact of exercise and sports practice. Methods Patients involved in at least one regular and structured sports activity were included in the pilot analysis. Two different ICF-CY (International Classification of Functioning, Disability and Health-Children and Youth Version) scales (“Body Function” and “Activity and Participation”) were filled out to assess the children’s global functional competence. Two online ad hoc questionnaires were created and administered to children, when able to respond, and caregivers. Results A total of 9% of patients reported being involved in a sports activity. All children who played sports did not have indications of cognitive retardation. The most practiced sport was swimming. The use of standardized methods such as ICF-CY shown that severe motor impairments do not limit sports accessibility. Questionnaires result suggest that sports are a positive experience for both children needing PPC and their parents. Children encourage other children to do sports and can find the positive side even in difficulties. Conclusion Since PPC is encouraged as early as the diagnosis of incurable pathologies, the inclusion of sports activities in the context of a PPC plan should be considered from the perspective of improving quality of life.
National Athletic Trainers AssociationMai 2018Sport
CONTEXT: : Return-to-sport criteria after anterior cruciate ligament (ACL) injury are often based on “satisfactory” functional and patient-reported outcomes. However, an individual's decision to return to sport is likely multifactorial; psychological and physical readiness to return may not be synonymous. OBJECTIVE: : To determine the psychosocial factors that influence the decision to return to sport in athletes 1 year post–ACL reconstruction (ACLR). DESIGN: : Qualitative study. SETTING: : Academic medical center. PATIENTS OR OTHER PARTICIPANTS: : Twelve participants (6 males, 6 females) were purposefully chosen from a large cohort. Participants were a minimum of 1-year postsurgery and had been active in competitive athletics preinjury. DATA COLLECTION AND ANALYSIS: : Data were collected via semistructured interviews. Qualitative analysis using a descriptive phenomenologic process, horizontalization, was used to derive categories and themes that represented the data. The dynamic-biopsychosocial model was used as a theoretical framework to guide this study. RESULTS: : Six predominant themes emerged that described the participants' experiences after ACLR: (1) hesitation and lack of confidence led to self-limiting tendencies, (2) awareness was heightened after ACLR, (3) expectations and assumptions about the recovery process influenced the decision to return to sport after ACLR, (4) coming to terms with ACL injury led to a reprioritization, (5) athletic participation helped reinforce intrinsic personal characteristics, and (6) having a strong support system both in and out of rehabilitation was a key factor in building a patient's confidence. We placed themes into components of the dynamic-biopsychosocial model to better understand how they influenced the return to sport. CONCLUSIONS: : After ACLR, the decision to return to sport was largely influenced by psychosocial factors. Factors including hesitancy, lack of confidence, and fear of reinjury are directly related to knee function and have the potential to be addressed in the rehabilitation setting. Other factors, such as changes in priorities or expectations, may be independent of physical function but remain relevant to the patient-clinician relationship and should be considered during postoperative rehabilitation.
BACKGROUND: Allergic diseases are common in the general population. Among the population of competitive athletes (hereafter referred to as athletes), previous studies have mostly focused on the prevalence of allergic diseases and further aspects of bronchial asthma. We aimed to examine the prevalence of allergic diseases and respective medication use in athletes in Germany.
METHODS: We performed a cross-sectional study in athletes from different sport disciplines between March 2012 and September 2013 in Munich, Bavaria. Allergic diseases and medication use were descriptively determined using the standardized Allergy Questionnaire for Athletes (AQUA). Allergic predisposition was defined at an AQUA score (range 0 to 35) of at least 5.
RESULTS: In total, 560 athletes (mean age 20.4 ± 6.7 years, males 73.4%, most frequent sport discipline soccer) were included in the analysis. The reported proportion of any allergic condition was 28%, and 46% of the athletes had an allergic predisposition. Sixteen percent of all athletes and 36% of athletes with an allergic predisposition reported the use of antiallergic or antiasthmatic medications.
CONCLUSIONS: Athletes had a high rate of allergic diseases, and almost half of them reported an allergic predisposition. Further research is needed to validate our results and investigate the impact of allergic diseases in athletes on the performance and specific aspects of their sport, such as training intensity and duration.
Female sports have recently seen a dramatic rise in participation and professionalism world-wide. Despite progress, the infrastructure and general sport science provisions in many female sports are behind their male counterparts. From a performance perspective, marked differences in physical and physiological characteristics can be seen between the sexes. Although physical preparation practices for male athletes are known, there are currently no published literature pertaining exclusively to female athletes. This information would provide invaluable data for both the researcher and practitioner alike. This survey therefore aimed to examine current practices utilized in female rugby codes (union, league, and sevens). A questionnaire assessing seasonal physical preparation practices, recovery, monitoring and sport science technology, and unique aspects in female rugby was developed. Thirty-seven physical preparation practitioners (32 males, 5 females) responded to the questionnaire. Most participants (78%) worked with national or regional/state level female athletes. Performance testing was more frequently assessed in the pre- (97%) and in-season (86%), than off-season (23%). Resistance, cardiovascular, sprint and plyometric training, and recovery sessions were all believed to be important to enhancing performance and implemented by most participants (≥ 89%). Sport science technologies were commonly (54%) utilized to inform current practice. Menstrual cycle phase was monitored by 22% of practitioners. The most frequently reported unique considerations in female rugby codes included psycho-social aspects (41%), the menstrual cycle (22%), and physical differences (22%). Practitioners working with female rugby can use the presented data to inform and develop current practices.
Introduction Primary patella resurfacing (PPR) in primary total knee arthroplasty (TKA) is a topic without clear clinical evidence. Using Patient Reported Outcome Measurements (PROM), previous work found TKA patients without PPR to have more pain postoperatively, but little is known whether this may impede patients from returning to their usual leisure sport. This observational study aimed at evaluating the treatment effect of PPR, with PROMs and return to sport (RTS). Materials and methods 156 primary TKA patients were retrospectively included from August 2019 to November 2020, from a single hospital in Germany. PROMs were measured with the Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the EuroQoL Visual Analog Scale (EQ-VAS), preoperatively and 1 year postoperatively. Leisure sport with three levels of intensity (never, sometimes, regular) were requested. The treatment effect of PPR was evaluated with a difference-in-difference (DiD) approach, with several confounders. Results Descriptively, the mean WOMAC total score and the mean WOMAC pain score were postoperatively better with PPR, ( – 4.8 points, – 1.1 points), then without PPR. The mean improvements of the WOMAC total score were better with PPR ( – 7.8 points). Mean improvements for the WOMAC pain score were also better with PPR ( – 1.2 points). Mean EQ-VAS were postoperatively similar, and the mean improvements were better with PPR (3.4 points). Rate of RTS was 93% for patients with PPR and 95% for patients without PPR. The DiD revealed minor differences in PROMs and RTS, not to result in statistically significant treatment effects. Conclusions There was no treatment effect for TKA with PPR, regarding PROMs and RTS, and descriptive differences were below published thresholds for clinical relevance. Rate of RTS was high for all patients, regardless of PPR. For the two endpoint categories, there was no measurable advantage of TKA with PPR over TKA without PPR.
Female breasts are vulnerable to direct blows or frictional injuries during sport; however, little research has investigated breast injuries experienced by female athletes. This study aimed to investigate the occurrence, causes and perceived performance effects of breast injuries in elite female athletes across a wide range of sports. A custom-designed survey was distributed to female athletes aged over 18 years who were competing nationally or internationally in their chosen sport. The survey included questions about breast injuries sustained during training and competition and any perceived performance effects of these injuries. 504 elite female athletes from 46 different sports completed the survey. 36% of participants (n = 182) reported experiencing breast injuries and 21% (n = 37) perceived that their breast injury negatively affected their performance. Contact breast injuries were reported by significantly more athletes involved in contact or combat sports and by athletes with larger breasts or a higher body mass index. Frictional breast injuries were reported by significantly more older athletes or those with larger breasts. Less than 10% of participants who experienced breast injuries reported their injury to a coach or medical professional and only half used any prevention strategies. Athletes, coaches and medical professionals associated with women’s sport need to be made aware of the occurrence and potential negative effects of breast injuries. It is critical to normalise conversations around breast health so that athletes can be encouraged to report and, when necessary, receive treatment for breast injuries. Further research is also required to better understand factors that affect breast injuries in sport in order to develop evidence-based breast injury prevention strategies.
Background The contribution of sport in non-specific low back pain (NS-LBP) remains unknown, due to a large heterogeneity in the methods applied in research. The aims of this scoping review (ScR) were to systematically map and summarize findings concerning studies reporting data on NS-LBP among athletes. Methods This ScR was developed referring to the 2020 version of the “Joanna Briggs Institute Methodological Guidance” and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. Five medical databases (Pubmed, Cochrane, Central, Embase, Pedro and Scopus) were searched up to November 2021. No limitations in terms of study design and language were applied. Results were presented numerically and thematically. Results A total of 4061 records were identified through the initial search; 114 articles met the inclusion criteria. Publications have increased over the years, since 1990. Most of the studies were conducted in the USA (17.5%), even if most research was conducted in Europe (53.5%). Analytic observational (42%) and cross-sectional studies (37%) were the most used designs, followed by case reports (12%) and systematic reviews (9%). Boating (7%), football, soccer, volleyball, running and gymnastics (4.4% each) were the most investigated, although the majority of the studies considered sports in general (36.8%). The overall sample size median was 181, mean age 22 ± 10.2; 68% of athletes were professional and 32% amateur. Most of the studies (38%) did not detail the frequency of training. Sport was reported as a risk factor for developing NS-LBP in 67.5% of cases, especially in those studies which assessed activities implying high or repeated loading on the spine. Conclusions This is the first ScR to provide a comprehensive overview on this topic. The increased number of publications on the association between sport practice and NS-LBP demonstrates a growing interest over the years on this topic. Some sport activities seem to be more involved than others in LBP development; however, research methods are extremely varied, thus more standardized observational research may focus on specific disciplines to properly contribute to research and clinical practice.
Too high demands, combined with a lack of resources, are often detrimental to athletic health and well-being. However, a valid and reliable instrument to investigate different dimensions of demands and resources in sport is currently unavailable. Therefore, the present study examines the psychometric properties of an existing and well-validated survey instrument on demands and resources at task-level that was adapted to sport. This instrument, the Demand-Induced Strain Compensation Questionnaire for Sport (DISQ-SPORT), was empirically tested among 1,101 athletes (416 females and 685 males) from a variety of sports and in different languages. Results supported the proposed six-factor structure of the instrument, consisting of physical, cognitive, and emotional demands and resources. Internal consistencies of all subscales were satisfactory and the instrument was invariant across type of sport, competitive level and language. Continued evaluation of the psychometric properties of the DISQ-SPORT, especially in terms of content validity and test-retest stability, is nevertheless warranted. Theoretical and practical implications as well as areas for future research are discussed.
BACKGROUND: Sudden death and catastrophic injuries during sport can be attenuated with the implementation of evidence-based health and safety policies. However, the extent of the implementation of these policies within secondary school athletics is unknown. PURPOSE: To provide an assessment of the implementation of health and safety policies pertaining to the leading causes of sudden death and catastrophic injuries in sport within secondary school athletics in the United States. STUDY DESIGN: Descriptive epidemiology study. METHODS: A rubric for evidence-based practices for preventing the leading causes of death and catastrophic injuries in sport was created. The rubric comprised 5 equally weighted sections for sudden cardiac arrest, head injuries, exertional heat stroke, appropriate medical coverage, and emergency preparedness. State high school athletic association (SHSAA) policies, enacted legislation, and Department of Education policies were extensively reviewed for all 50 states and the District of Columbia. States meeting the specific criteria in the rubric, which required policies to be mandated for all SHSAA member schools, were awarded credit; the weighted scores were tabulated to calculate an aggregate score. States were then ranked from 1 (best) to 51 (worst) based on the aggregate score achieved. RESULTS: The median score on the rubric was 47.1% (range, 23.00%-78.75%). States ranked 1 through 10 (from 78.75% to 56.98%) were North Carolina, Kentucky, Massachusetts, New Jersey, South Dakota, Missouri, Washington, Hawaii, Wisconsin, and Georgia, respectively. States ranked 11 through 20 (from 56.03% to 50.55%) were Arkansas, New York, Mississippi, West Virginia, Oregon, Illinois, Tennessee, Arizona, Texas, and District of Columbia, respectively. States ranked 21 through 30 (from 49.40% to 44.00%) were Virginia, Pennsylvania, Florida, New Mexico, Alabama, Maine, Rhode Island, Indiana, Nevada, and Utah, respectively. States ranked 31 through 40 (from 43.93% to 39.80%) were Ohio, Delaware, Alaska, Vermont, Louisiana, Maryland, Oklahoma, Connecticut, Idaho, and South Carolina, respectively. States ranked 41 through 51 (from 38.73% to 23.00%) were Michigan, North Dakota, Nebraska, New Hampshire, Kansas, Wyoming, Minnesota, Montana, Iowa, California, and Colorado, respectively. CONCLUSION: State scores ranged from 23.00% to 78.75% for the implementation of evidence-based best practices for preventing the leading causes of sudden death and catastrophic injuries (sudden cardiac arrest, traumatic head injuries, exertional heat stroke, and exertional sickling) in sport. Continued advocacy for the development and implementation of policies at the secondary school level surrounding sudden death and catastrophic injuries is warranted to optimize the health and safety of these student athletes.
BACKGROUND: Despite calf muscle strain injuries (CMSI) being problematic in many sports, there is a dearth of research to guide clinicians dealing with these injuries. The aim of this study was to evaluate the current practices and perspectives of a select group of international experts regarding the assessment, management and prevention of CMSI using in-depth semi-structured interviews. RESULTS: Twenty expert clinicians working in elite sport and/or clinician-researchers specialising in the field completed interviews. A number of key points emerged from the interviews. Characteristics of CMSI were considered unique compared to other muscle strains. Rigor in the clinical approach clarifies the diagnosis, whereas ongoing monitoring of calf capacity and responses to loading exposure provides the most accurate estimate of prognosis. Athlete intrinsic characteristics, injury factors and sport demands shaped rehabilitation across six management phases, which were guided by key principles to optimise performance at return to play (RTP) while avoiding subsequent injury or recurrence. To prevent CMSI, periodic monitoring is common, but practices vary and data are collected to inform load-management and exercise selection rather than predict future CMSI. A universal injury prevention program for CMSI may not exist. Instead, individualised strategies should reflect athlete intrinsic characteristics and sport demands. CONCLUSIONS: Information provided by experts enabled a recommended approach to clinically evaluate CMSI to be outlined, highlighting the injury characteristics considered most important for diagnosis and prognosis. Principles for optimal management after CMSI were also identified, which involved a systematic approach to rehabilitation and the RTP decision. Although CMSI were reportedly difficult to prevent, on- and off-field strategies were implemented by experts to mitigate risk, particularly in susceptible athletes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40798-021-00364-0.
Background Sports management and public health physical activity stakeholders need to understand changing patterns of participation to inform the development of sport and physical activity opportunities and strategies. This study investigated changes in the frequency and duration of participation in sport and physical activity in Australia from pre-COVID-19 to during-COVID-19, broken down by the specific type of activity and by gender, age and region. Methods During the first pandemic restrictions and lockdowns in Australia in May–June 2020, 6140 survey respondents provided information about the types, frequency and duration of the sport and physical activity they participated in prior to and during COVID-19 restrictions. Differences between mean values were analyzed. Results The greatest decline in participation during COVID-19 was in team sports, and the decline was greater for men than for women. Conclusion How will sport respond to getting these men back in the game, and women back from home-based yoga and Pilates?
OBJECTIVES: Recurrence rates have traditionally been used as a proxy for “failure” when comparing conservatively vs. operatively managed patients with anterior shoulder instability. Return to sport has been evaluated as an outcome proxy after surgical intervention, but no study has compared conservative vs. operative management using sustained return to sport as the main outcome measure. The purpose of this study was to compare the results between conservatively and operatively treated patients as to their ability to return a patient to uninterrupted sport in a subsequent season after an anterior instability event. METHODS: We identified and followed 179 scholastic athletes who were treated for a confirmed diagnosis of anterior shoulder instability. 97 were treated initially with conservative management, and 32 were managed surgically. Patients were excluded if they did not have remaining eligibility to play a subsequent season of athletics (high school seniors), or if they were treated with benign neglect (neither conservative nor operative treatment). “Ultimate success” was defined as return and completion of the subsequent season without time loss due to any shoulder related diagnosis. We substratified by age, sport, and type of instability event (subluxation vs. dislocation) using ANOVA and binary logistic regression. RESULTS: In the conservatively managed group, 85% met the definition of ultimate success by returning to play a subsequent season of scholastic athletics in the same sport without any time loss due to a shoulder condition. In the surgical group, 72% were able to achieve this status (p<0.05). Age did not differ between the two groups. Patients were 5x less likely to return to sport if they had sustained a dislocation requiring reduction compared to a subluxation confirmed as an anterior instability event (OR: 4.96, 95%CI= 1.2-9.6). CONCLUSION: Patients who were treated conservatively for an anterior shoulder instability event were far more likely to have a “successful” outcome than published results if the definition of outcome is changed from no recurrence to completion of a subsequent season in their same sport. Patients sustaining a subluxation were nearly uniformly successful in doing so. While surgical success using this definition was quite lower, there was likely a selection bias in the decision making process due to bone loss, surgeon preference or other factor. Nevertheless, this data would suggest that if a patient’s goal is to return to the same level of sport and “next season”, conservative management is highly effective. Further study to determine whether these results hold out with longer term follow up are warranted, but the routine fixation of the first time dislocator based on better outcomes, is called into question depending on what one’s definition of success is.
STUDY DESIGN: Case report BACKGROUND: Isolated, grade III lateral collateral ligament knee injuries are an uncommon traumatic injury with little guidance available in the literature for conservative management and prognosis for return to sport. The purpose of this case report is to describe the clinical decision-making in both differential diagnosis and physical therapy management of an isolated grade III lateral collateral ligament sprain in an adolescent multi-sport high school athlete. CASE DESCRIPTION: A 16 year-old male, high school, multi-sport athlete (cross country, wrestling, track and field) sustained a traumatic knee injury during a wrestling match when his involved lower extremity was forcefully externally rotated by his opponent. Initial clinical presentation revealed pain and increased laxity with varus stress testing of the left knee, which was subsequently identified via MRI as a complete lateral collateral ligament rupture (grade III). A conservative physical therapy program was developed targeting the active and neuromuscular subsystems, theorized to compensate for the lack of an intact lateral collateral ligament. OUTCOMES: The subject attended 18 visits of physical therapy over a period of 12 weeks. His rehabilitation program focused on functional strengthening of the posterolateral corner, enhancement of neuromuscular control, and graded progression to sports specific drills. Return to play decisions were based on a combination of lower extremity functional performance measures, condition specific outcome measures and subjective performance on sports specific tasks. At discharge from physical therapy, he reported 0/10 pain, scored a 76/80 on the Lower Extremity Functional Scale, and was able to return to competitive track and field events. DISCUSSION: Few descriptions in the literature exist for the conservative management of isolated, grade III lateral collateral ligament injuries. A program of selective functional strengthening, proprioceptive training, and graded sport specific activities may allow these individuals to return to sport with conservative management. LEVELS OF EVIDENCE: 4 (Single Case Report)
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Background: Only 65% of people return to a level of sport equivalent to that before after anterior cruciate ligament (ACL) surgery. Persisting apprehension may in part explain this observation. We aimed to describe characteristics of people with ACL-Return to Sport after Injury (RSI) scores ≥ 60/100 (low apprehension) at 6 months after injury and to identify variables independently associated with low apprehension at 6 months. Methods: We conducted a single-center retrospective study. People who had surgery for an ACL rupture and who participated in an outpatient post-operative rehabilitation program were included consecutively. The ACL-RSI questionnaire was self-administered at 6 months after injury. Baseline characteristics of people with ACL-RSI scores ≥ 60/100 and < 60/100 were described. Multiple logistic regression was performed to identify baseline variables associated with low apprehension at 6 months. Results: We included 37 participants: 13/37 (35.1%) were women and mean age was 27.2 (9.2) years. At 6 months, 21/37 (56.8%) had an ACL-RSI score ≥ 60/100. Participants who had an ACL-RSI score ≥ 60/100 more often received a preoperative rehabilitation (16/21 [76.2%] vs 5/16 [31.2%]), and had less often knee pain (7/21 [33.3%] vs 7/16 [43.7%]) and effusion (5/21 [23.8%] vs 8/16 [50.0%]) at 1 month after surgery, than participants who had an ACL-RSI score < 60/100. In the multivariate analysis, preoperative rehabilitation was associated with low apprehension at 6 months (OR [95% CI] = 0.107 [0.023 to 0.488], p = 0.002). Conclusions: Preoperative rehabilitation was independently associated with low apprehension at 6 months. Trial registration. Not applicable.
Elite sport offers a suitable setting to understand the ability to anticipate future events—a phenomenon that is central to animal life. Critically, however, whilst anticipation in sport has been studied for several decades, there have been few attempts to understand its development throughout childhood and adolescence. Additionally, whilst it is widely acknowledged that the need to anticipate emerges from temporal pressure, there has been no effort to understand the nonlinear effect that temporal demands have on the development of anticipatory skill. This is important as its consequences have different implications for sports authorities compared to an individual player. To bridge the gap in our understanding, this article draws attention to the mathematical concepts of concavity and convexity to explain the nonlinear relationship between temporal demands and the development of anticipatory skill. This viewpoint has implications for the design of junior sport, including the modification of rules, which has gained worldwide interest in recent years.
BACKGROUND: Research focused on mental health in sport has revealed a need to develop evidence-supported mental health practices that are sensitive to sport culture, particularly for non-elite athletes. A consensus statement was produced to assist effective mental health awareness in sport and guide programme implementation in this rapidly emerging field. METHOD: The AGREE Reporting Checklist 2016 was used in two international expert consultation meetings, followed by two online surveys. Experts from 10 countries and over 30 organisations contributed. RESULTS: Six objectives were agreed: (1) to define mental health awareness and service implementation constructs for inclusion in programmes delivered in sporting environments; (2) to identify the need to develop and use valid measures that are developmentally appropriate for use in intervention studies with sporting populations, including measures of mental health that quantify symptom severity but also consider causal and mediating factors that go beyond pathology (ie, well-being and optimisation); (3) to provide guidance on the selection of appropriate models to inform intervention design, implementation and evaluation; (4) to determine minimal competencies of training for those involved in sport to support mental health, those experiencing mental illness and when to refer to mental health professionals; (5) to provide evidence-based guidance for selecting mental health awareness and implementation programmes in sport that acknowledge diversity and are quality assured; and (6) to identify the need for administrators, parents, officials, coaches, athletes and workers to establish important roles in the promotion of mental health in various sports settings. CONCLUSION: This article presents a consensus statement on recommended psychosocial and policy-related approaches to mental health awareness programmes in sport.
The problem that the researcher poses in this study is regarding the success of handling ankle injuries in terms of Range of motion (ROM) with the sport massage frirage method. Ankle injuries have four movements, namely flexion, extension, inversion and eversion. The purpose of this study was to determine the success rate of sport massage frirage in handling ROM in badminton athletes’ ankle injuries and secondly to determine the management of sport massage frirage in handling ROM for badminton athletes with mild ankle injuries. The method used is pre-experimental design pretest-posttest one group with survey and test techniques. The population of this research is the badminton athletes of Universitas Pendidikan Indonesia as many as 32 people. The sampling technique used purposive sampling, totaling 11 people. The research instrument is a questionnaire and a goniometer. The research data analysis technique used paired t-test with the help of the SPSS software version 20.
OBJECTIVES: Athletes train and compete at the elite level during their reproductive years, yet sport policies that support pregnant athletes are lacking. The experiences of elite athletes during pregnancy are vastly under-represented, and such voices are needed to support evidence-informed policy. Thus, the purpose of this qualitative study was to describe the experiences of elite female athletes as they navigate pregnancy, and to identify sport policy considerations regarding participation during pregnancy. METHODS: Twenty athletes (mean age 35±5 years) who, within the last 5 years, had trained or competed at the elite level immediately prior to becoming pregnant were included. Data were generated via one-on-one semistructured interviews that were audio-recorded, transcribed verbatim and analysed through a process of content analysis. RESULTS: The findings of this study are represented by one overarching message: mother versus athlete, and five main themes: (1) pregnancy planning and fertility, (2) pregnancy disclosure and discrimination, (3) training pregnant athletic bodies, (4) safety concerns, and (5) supportive network and equitable funding. CONCLUSION: In-depth stories shared by participants highlight the many significant decisions athletes must make as they navigate pregnancy alongside elite sport participation. The shared experiences of pregnant athletes highlight clear challenges that should be considered in the development of sport policy and practices that are inclusive and supportive of female athletes.
OBJECTIVES: Knowledge of how physical activity (PA) and sport participation are related to mental health throughout adolescence is scarce. Our objective was to describe PA levels and sport participation in a population-based sample of adolescents, and to explore how they relate to mental health in different age groups. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: The adolescent part of the Nord-Trøndelag Health Study, a Norwegian population-based health survey, conducted from 2006 to 2008. Of 10 464 invited participants (age 13–19 years), 7619 (73%) participated, of whom 3785 (50%) were boys. OUTCOME MEASURES: Mental health outcomes included psychological distress assessed using a short version of the Hopkins Symptom Check List Five items, self-esteem assessed using a short version of the Rosenberg Self-Esteem Scale and life satisfaction assessed with a single-item satisfaction with life measure. METHOD: Logistic regression models were used to estimate the likelihood of psychological distress, low self-esteem and low life satisfaction, according to self-reported PA level and type of sport participation, stratified by gender and school level (junior vs senior high school). RESULTS: Fewer senior high school students participated in team sports compared with junior high school students (p<0.001). Physically active adolescents and participants in team sports had higher self-esteem and life satisfaction. A high PA level, compared with a low PA level, was associated with reduced odds of psychological distress among senior high school students (OR 0.63, 95% CI 0.46 to 0.86 for girls and OR 0.46, 95% CI 0.27 to 0.79 for boys). Team sport participation was associated with reduced odds of psychological distress in senior high school girls. CONCLUSION: A high PA level was favourably associated with various dimensions of mental health, especially for adolescents in senior high school. Team sport participation may have a positive impact on mental health and should, therefore, be encouraged.
Despite their prevalence, the longitudinal impacts of relative age effects (RAEs) on sport and other forms of physical activity (PA) are understudied. This study examined longitudinal participation patterns in organized sport (team and individual), unorganized PA, and non-participation with respect to RAEs in a prospective cohort of adolescents. Data from the first 24 cycles of the MATCH study were used for analyses. Elementary students (n = 929) were recruited from 17 schools in Atlantic Canada. Respondents self-reported PA three times/year. Mixed multilevel logistic models compared the likelihood of participating in each context across birth quarter. Chronological age and gender were considered, along with the interaction between chronological and relative age. Individuals born in Quarter 1/Quarter 2 were more likely to report participation in organized team sport but not individual sports. Relatively older participants born in Quarter 2 were more likely to report participation in unorganized PA. Increasing chronological age was associated with decreased participation in organized sport (particularly team-based) and increased non-participation. Gender was not associated with organized sport participation, but girls were under-represented in unorganized PA and more likely to report non-participation. The interaction parameters suggested that RAEs were consistent throughout adolescence in each context. Longitudinal analyses suggest RAEs are context dependent.
SIMPLE SUMMARY: Conformation assessment is the basis for the selection of horses for a specific sport. Traditional 100-point judging systems, linear scoring and basic measurements are simultaneously used in Poland for evaluation of the same warmblood sport horses. This study aimed to compare traditional 100-point judging systems and linear profiling and to find characteristic traits of specific sport types by analyzing the differences between warmblood mares that are qualified as dressage vs. jumping. The research showed that warmblood mares classified as different types varied in a few linear conformation traits, most significantly in the position of the shoulder, line of the loins or shape of the croup. Analyses of linear movement traits showed that dressage warmblood mares moved better in walking and more balanced canter than jumping ones. These differences were not evident in the overall 100-point system. Both point-scaling systems were correlated only between the same named traits—type, movement and gaits. Finding detailed, measured, objective characteristics for various sport types is important for breeding and judging. ABSTRACT: The aim of this study was to analyze the influence of factors on the results of 100-point judging systems, linear scoring and basic measurements, as well as differences between systems for dressage and jumping warmblood mares. The research covered official data on 1547 warmblood mares. Analysis of variance and phenotypic correlations (Pearson and partial) were used. The analysis showed that sport type significantly influenced 1/3 of biometric measurements, 2/9 traits on the 100-point system and 7/37 of linear scored traits. The influence of horse type evaluation is more significant in linear scoring than in the 100-point evaluation, which provides an argument for using the first system in breeding. In the linear evaluation for warmblood mares grouped as jumping or dressage, the most significant differences (p < 0.001) were noted between the traits of shoulder position, line of the loins and shape of the croup. In the point-based evaluation, differences (p < 0.05) were found in forelimbs and walking, as well as chest circumference in basic measurements. None of the traits in the two evaluation systems is identical to any other (r > 0.8). The comparison of systems showed meaningful correlations only between general traits. The differences between sport types of warmblood mares were smaller than expected. More objective traits should be discovered to increase accuracy in discriminating between horse types.
Background Timing for return to sport (RTS) after anterior cruciate ligament (ACL) injury is paramount for the avoidance of a secondary injury. A common criterion in RTS decision-making is the limb symmetry index (LSI) which quantifies (a)symmetries between the affected and unaffected limb. Limb dominance is one of many factors that may contribute to the recovery of the LSI after ACL reconstruction. The purpose of this study was to examine how limb dominance affects the LSI of functional performance tasks nine months following ACL reconstruction (time of RTS). Methods At time of return to sport, n = 100 patients ( n = 48 injured the dominant limb, n = 52 injured the non-dominant limb, n = 34 female, n = 66 male) with ACL reconstruction surgery performed isokinetic strength measurements of the knee extensors and flexors, and drop jumps (DJ), single leg hop for distance (SHD) and 6 m timed hop (6MTH) testings. Results The findings indicated that injury of the dominant leg led to significantly higher LSI values in maximal isokinetic knee extensor strength ( p = 0.030). No significant differences were observed for maximal isokinetic knee flexor strength, DJ, SHD or 6MTH performance. Stratifying for sex revealed no significant differences. Simple regression analyses demonstrated that LSI in maximal knee extensor strength significantly predicted LSIs in DJ and SHD while explaining 14% and 18% of the respective variance. Conclusions Given that limb dominance affects the LSI of muscle strength suggests that a differentiated interpretation of the LSI with respect to limb dominance should be considered for a safe return to sport. Monoarticular knee extensor strength and multiarticular hop test performance are interrelated and thus can show asymmetries which are not maladaptive but established during years of habituation or training.
Introduction: Sports psychiatry, a field of psychiatry, is a young medical discipline. The aim of this study was to gauge opinions on the following: sports psychiatry as a specialized subdiscipline, its areas of activity among professionals, the desire for interdisciplinary and interprofessional cooperation, and the need for specific sports psychiatry training. Methods: An online survey was performed to assess the views on sports psychiatry of German-speaking professionals in Switzerland, Germany, and Austria in the field of sports psychiatry. Results: Data from 183 professionals were included in the analysis. Most participants classified sports psychiatry as a field of psychiatry (89%), followed by sports medicine (61%) and child and adolescent psychiatry (49%). Mental health and disorders in competitive and elite sport (94%), sport and exercise for the prevention of and as therapy for mental disorders (84%), and sport-specific mental health problems and disorders in popular sport (80%) were reported by all the participants as areas of activity within sports psychiatry. Most of the participants stated the importance of interdisciplinary and interprofessional collaboration with sports psychiatry’s areas of activity. While 84% of the participants emphasized the necessity for specific training in sports psychiatry, a different picture emerged as to whether such training should be independent or integrated with postgraduate training for psychiatric or sports medicine. Conclusion: The results provide insight into sports psychiatry and its areas of activity and should be used for, and integrated with, the further development of the field.
OBJECTIVES: The prevalence of ulnar collateral ligament (UCL) injuries and their surgical treatment has risen significantly since the first treated by Dr. Jobe in 1974. The recent surgery, primarily amongst 15- to 25-year-olds involved in overhead sports, is concerning and necessitates refinement of and/or development of the most effective treatment options. The traditional surgical treatment has been UCL reconstruction, but more recently, the development of UCL repair techniques, particularly with the use of internal bracing, are an exciting potential alternative. Whereas previous work has examined early complications and early outcomes following UCL repair with internal brace, to our knowledge, few if any previous studies have compared mid-term outcomes between UCL repair and UCL reconstruction. Our study aimed to examine differences in mid-term outcomes between competitive athletes following UCL repair with internal brace or following UCL reconstruction from a single institution. Specifically, we compared patient-reported elbow and upper extremity function measures and return to preinjury sport between treatment groups. METHODS: Using CPT codes from an ongoing prospective data repository, we performed a retrospective search to identify patients that underwent either UCL repair with internal brace or UCL reconstruction between 2013 and 2021. We included those 15 to 45 years old that were at least 2-years post-operative and were competitive athletes at time of surgery. We excluded those with prior index elbow surgery, those with UCL repair without internal bracing. We performed detailed chart reviews using the electronic medical record and collected demographic information, injury data, and surgical details. We assessed patient-reported outcomes at follow-up using the following measures of elbow/upper extremity function: 1) American Shoulder and Elbow Surgeons Elbow assessment form (ASES-E; function subscale); 2) Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score (KJOC); 3) Andrews-Carson score. We further collected information on return-to-sport timing and success. We calculated summary statistics for demographic, injury, surgical, and outcomes data within both the UCL repair and reconstruction groups. We compared key demographic, injury, and surgical data between UCL repair and reconstruction groups using independent t-tests for continuous variables and chi-square tests for categorical data. For outcomes data, we used linear regression modeling (controlling for relevant demographic covariates) to compare patient-reported function measures (ASES-E; KJOC; Andrews-Carson) between groups. Lastly, we summarized return to preinjury sport (and reasons for the inability to return) and compared the proportions of successful return to preinjury sport between groups using a chi-square test. RESULTS: Clinical and outcomes data were successfully collected for 411 athletes with UCL injuries and surgical treatment (mean age at surgery=18.9±2.9 years; 93% male; mean follow-up time=4.9±2.2 years). Of the 411 UCL procedures, 265 (64%) were UCL repair with internal brace, and 146 (36%) were UCL reconstructions. The UCL repair group was younger (p=0.04), had shorter follow-up time (p<0.01), and had a higher proportion of females (p=0.02) when compared with the UCL reconstruction group (Table 1). Table 1 also shows primary sport at time of UCL injury and level of competition within both groups. Within the UCL repair group, there was a higher proportion of partial UCL tears and a lower proportion of complete UCL tears when compared with the UCL reconstruction group (p<0.01; Table 1). Additionally, within the UCL repair group, there was a lower proportion of concomitant ulnar nerve transpositions when compared with the UCL reconstruction group (p<0.01; Table 1). There were no differences between groups in the proportions of concomitant osteophyte excisions (Table 1). Outcomes-related data are shown in Table 2. Because of differences between groups in age and follow-up time, we controlled for these in comparisons of patient-reported outcomes between groups. After controlling for age and follow-up time, the groups did not differ in ASES-E, KJOC, nor Andrews-Carson scores at follow-up (Table 2). Of the 265 athletes in the repair group, 244 attempted to return to their preinjury sport (Table 2). Among the 244 that attempted to return, 237 (97%) were able to return to their preinjury sport, and 7 were unable to return due to limitations from their UCL repair (Table 2). Of the 146 athletes in the reconstruction group, 140 attempted to return to their preinjury sport (Table 2). Among the 140 that attempted to return, 137 (98%) were able to return to their preinjury sport, and 3 were unable to return due to limitations from their UCL reconstruction (Table 2). Other reasons for not attempting to return to preinjury sport within the 2 groups are shown in Table 2. The two groups did not statistically differ in the proportions that returned to preinjury sport (Table 2). CONCLUSIONS: In the current study, we found excellent elbow function and return-to-sport mid-term outcomes in a large cohort of both UCL repairs with internal brace and UCL reconstructions. Whereas the groups did differ in some demographic, injury, and concomitant surgical procedure variables, they did not differ in patient-reported outcomes nor in the ability to return to preinjury sport. These findings suggest that UCL repair with internal brace may be a viable option for the treatment of UCL injuries when clinically-indicated. Given the observational and retrospective nature of the current study, future research should evaluate randomized surgical intervention of UCL injuries.
OBJECTIVES: The relationship between psychological and physical readiness for return to sport after anterior cruciate ligament reconstruction (ACLR) is not well understood. Psychological stress and psychological readiness were therefore evaluated at six months following primary ACLR along with standard functional patient reported outcome (PRO) instruments and physical performance tests to understand the relationship between the physical and psychological readiness in young athletes. METHODS: Participants were evaluated at six months after ACLR with Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS), International Knee Documentation Committee Questionnaire (IKDC), PROMIS Psychological Stress Experience (PSE) and ACL Return to Sport After Injury Scale (ACL-RSI). Functional testing included gluteal, hamstring, and quadriceps strength testing, single leg hop (SLH), crossover hop, triple hop and timed 6-meter SLH. Patient characteristics and continuous and categorical variables were summarized. Pearson’s correlation coefficient and multivariable regression were used to determine associations between the limb symmetry index (LSI) on functional testing and PROs. Those with LSI deficits of less than 20% (better performance) were then compared to those with deficits greater than 20% (worse performance). RESULTS: 229 participants (89 male, 140 female) of median age 17 years (range 10.3 to 30.6 years) were enrolled. IKDC had a moderate negative correlation with PROMIS PSE (r=0.39 ; 95% CI=-0.49, -0.27; p<0.001) and a moderate positive correlation with ACL-RSI (r=0.55; 95% CI=0.46, 0.64; p<0.001) (Figure 1). 151 patients completed functional testing. ACL-RSI demonstrated a positive correlation with SLH LSI (r=0.21;95% CI=0.05, 0.35; p=0.01) and timed 6-meter SLH (r=0.28; 95% CI, 0.42; p=0.001) (Figure 2). When controlling for sex, age, and graft type, patients who had less than a 20% deficit on the SLH scored 17.9 points higher on ACL-RSI (p<0.001), and those with less than a 20% deficit on crossover hop testing scored average 13.9 points higher on ACL-RSI (p=0.04). CONCLUSIONS: At 6 months after ACLR, highe r psychological readiness for return to sport is associated with better performance and greater symmetry on hop testing, suggesting a potential link between physical and psychological recovery.
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.
BACKGROUND: This study aimed to describe the frequency of hypothyroidism phenotypes, clinical characteristics, and factors associated with nodular thyroid among hypothyroid patients at the University of Ghana Hospital in southern Ghana. METHODS: This study was a 6-year hospital-based retrospective study that extracted data from 221 patients with hypothyroidism from the archival records of the University of Ghana Hospital using a checklist. These include socio-demography (age, gender, marital status, residential status, educational level), lifestyle variables (anthropometry, smoking status, alcohol intake), and co-morbidities, as well as ultrasound imaging findings of the thyroid. Serum thyroid hormone levels were used to classify hypothyroidism phenotypes. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with nodular thyroid disease. RESULT: The frequency of primary, subclinical, and secondary hypothyroidism was 81.4%, 16.3%, and 2.3%, respectively. Fatigue [120(54.3%)], heavy menstrual loss [54/160(33.8%)], and cold intolerance [73(33.0%)], were predominant symptoms while 54/57 (94.7%) were overweight/obese, 23/32 (71.9%) had dyslipidaemia whereas 7/34 (20.6%) had hypertension. The odds of developing nodular thyroid disease were 2.11 times higher (95% CI: 1.07–4.17; p = 0.032) in males than in females. CONCLUSION: Our results provide insight into the frequency of hypothyroidism phenotypes, clinical characteristics, and factors associated with nodular thyroid, emphasizing male gender as an independent predictor of nodular thyroid disease. Our findings also emphasize the need for lifestyle adjustment as a mitigating strategy in the management of hypothyroidism. However, prospective studies are required to confirm the findings or investigate the histological characteristics of thyroid nodules in patients with hypothyroidism.
BACKGROUND: Iron is an essential element for thyroid function. However, no study focuses on the association between iron and thyroid in individuals with obesity. Our research aimed to investigate the iron status in relation to baseline thyroid hormone levels and after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 216 subjects with obesity were enrolled and divided into low and high iron groups depending on the median value. The association between iron and thyroid hormone was analyzed and compared before and after LSG at the 6-month follow-up in patients who underwent LSG. RESULTS: 1) In all, Total Triiodothyronine (TT3) was significantly higher in high iron than low iron group (P = 0.008). TT3 and thyroid stimulating hormone (TSH) were significantly higher in high iron than low iron group (1.92 ± 0.61 vs. 1.69 ± 0.28 nmol/l, P = 0.029; 2.93 ± 1.66 vs. 1.88 ± 1.03 mU/l, P = 0.002) in females while not in males (all P > 0.05). 2) Iron was significantly positively associated with free triiodothyronine (FT3), free thyroxine (FT4), TT3 and TSH (all P < 0.05). Adjusted for body mass index (BMI), total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and homeostatic model assessment of insulin resistance (HOMA-IR), FT3, FT4 and TSH were still significantly associated with iron (all P < 0.05). 3). Regression analysis showed that iron was significantly associated with FT4 (β = 0.338, P = 0.038). 3) LSG led to decreased FT3, FT3, TT3, total thyroxine (TT4) and TSH at 6 months follow-up (all P < 0.05). Changed FT4 was significantly associated with changed iron (r = 0.520, P = 0.009). Subjects with iron decreased had more significant decreased TT4 than subjects without iron decreased (P = 0.021). CONCLUSION: Serum iron overload is significantly associated with impaired thyroid function in subjects with obesity. LSG led to improved thyroid function which is associated with a change in iron. TRIAL REGISTRATION: NCT04548232 registration date is on October 9, 2022, registered in https://register.clinicaltrials.gov/.
Background Thyroid cancer has incidence continues to rise globally. Understanding the epidemiology of thyroid cancer and the future burden on public health systems is necessary. We aimed to investigate the prevalence, incidence, and mortality of thyroid cancer by age, sex, country in Asia in 2020 and its projection up to 2040. Methods The Global Cancer Observatory provided data on thyroid cancer incidence and mortality for the year 2020. By taking into account the sex, age group, and Asia region, the counts, rates, and mortality-to-incidence ratios (MIRs) were calculated. To estimate the projected number of new cancer cases or mortalities between 2025 and 2040 in a particular nation, the corresponding expected population for the years 2025 to 2040 was multiplied by the age-specific incidence or mortality rates calculated for 2020. Results In 2020, the 5-year prevalence rate, age-standardized incidence rate (ASIR), and age-standardized mortality rate (ASMR) for thyroid cancer were 24.60, 6.40, and 0.44 per 100,000 population in Asia, respectively. By country, the highest thyroid cancer 5-year prevalence rates and ASIRs were found in the Republic of Korea. The highest thyroid cancer ASMRs among both sexes combined were in the United Arab Emirates and Syrian Arab Republic. The highest incidence and mortality crude rates were in the 50–59 and 70 + age groups, respectively. Women had higher incidence and mortality rates than men. There were significant correlations between human development index and MIR and ASIR ( p < 0.001). The number of newly diagnosed thyroid cancer cases and mortalities are expected to rise by 26.6% and 77.8% up to 2040 in Asia, respectively. Conclusions Asia is experiencing rising rates of thyroid cancer incidence and mortality. It is imperative to prioritize strategies aimed at high-incidence regions, transitioning countries with limited resources, and younger adult populations to alleviate the global burden of thyroid cancer and resolve disparities in cancer management.
BACKGROUND: Hypothyroidism is a common thyroid disease affecting the health of the global population and oxidative stress and inflammation are involved in the pathophysiological process of hypothyroidism. Comprehensive dietary antioxidant index (CDAI), representing the overall dietary antioxidant capacity, has been proved to be associated with a variety of diseases. However, association between CDAI and hypothyroidism risk remains unclear. This study aims to evaluate the association of CDAI and hypothyroidism risk. METHODS: Data of this study were extracted from the National Health and Nutrition Examination Surveys (NHANES) database 2007–2012. CDAI, represents the overall dietary nutrients capacity, was calculated by selenium, zinc, magnesium, vitamin A, C and E. Thyroid stimulating hormone (TSH) > 5.6 mIU/L was defined as hypothyroidism. The weighted multivariate logistic regression models and propensity score matching (PSM) analysis were utilized to evaluate the relationship between CDAI and hypothyroidism, with odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analysis were further evaluated the relationship between CDAI and hypothyroidism. Moreover, the association between the components of CDAI and hypothyroidism was also explored. RESULTS: Totally, 7,959 subjects with information of complete dietary intake and thyroid function measurement were included. Of whom, 213 (2.68%) subjects had hypothyroidism. After adjusted all covariates, we observed high CDAI was related to low hypothyroidism risk (OR = 0.44, 95%CI: 0.27–0.71). This relationship was prominent in subjects with aged < 65 years old (OR = 0.32, 95%CI: 0.16–0.62), male (OR = 0.39, 95%CI: 0.15–0.99) and BMI ≥ 25 kg/m(2) (OR = 0.38, 95%CI: 0.19–0.76). The association between high CDAI and low hypothyroidism risk remained significant when subjects using thyroid hormones were excluded (OR = 0.47, 95%CI: 0.27–0.81). CONCLUSION: High CDAI was related to low hypothyroidism risk among U.S. adults. Our finding showed that the intake of an antioxidant-rich dietary is a potential method to reduce the risk of hypothyroidism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-024-01806-y.
BACKGROUND: Microwave ablation is a new, minimally invasive technique for the treatment of thyroid nodules. Hyperthyroidism due to destructive thyroiditis is a known risk of microwave ablation, though it occurs in only a minority of cases. We report a rare case of a patient diagnosed with Graves’ disease nearly six months after undergoing microwave ablation of a thyroid nodule. CASE PRESENTATION: On July 31, 2022, a 43-year-old male patient presented to our hospital with symptoms of pyrexia, excessive sweating, and palpitations lasting for 15 days. History inquiry revealed that the patient had undergone microwave ablation of right-sided thyroid nodule nearly five months ago at another hospital. The patient’s thyroid ultrasound suggested bilateral diffuse thyroid lesions, with a moderately echogenic mass observed on the right side of the thyroid gland, potentially indicative of thyroid nodule ablation. The patient had elevated serum thyroid hormone levels, decreased thyroid-stimulating hormone levels and positive associated thyroid antibodies. To control the symptoms of hyperthyroidism, the patient opted for oral antithyroid medication, and thyroid hormonal levels returned to normal after 3 months of treatment. The patient is now under regular follow-up. CONCLUSIONS: In this case, we presented the onset of Graves’ disease following microwave ablation in a patient with subclinical thyroid autoimmunity. While the causal relationship between microwave ablation and Graves’ disease remains unproven, this case suggests that preexisting autoimmune thyroid conditions may increase susceptibility to postoperative thyroid dysfunction. Procedural factors, such as thermal injury to surrounding tissues and potential involvement of the autonomic nervous system, are also potential contributors to the development of Graves’ disease following microwave ablation.
Thyroid ultrasound is the first-line exam for assessing thyroid nodules and determining whether biopsy is warranted. In routine reporting, radiologists produce two coupled outputs: a nodule contour for measurement and a TI-RADS risk category based on sonographic criteria. Yet both contouring style and risk grading vary across readers, creating inconsistent supervision that can degrade standard learning pipelines. In this paper, we address this workflow with a clinically guided multitask framework that jointly predicts the nodule mask and TI-RADS category within a single model. To ground risk prediction in clinically meaningful evidence, we guide the classification embedding using a compact TI-RADS aligned radiomics target during training, while preserving complementary deep features for discriminative performance. However, under annotator variability, naive multitask optimization often fails not because the tasks are unrelated, but because their gradients compete within the shared representation. To make this competition explicit and controllable, we introduce RLAR, a representation-level adversarial gradient regularizer. Rather than performing parameter-level gradient surgery, RLAR uses each task's normalized adversarial direction in latent space as a geometric probe of task sensitivity and penalizes excessive angular alignment between task-specific adversarial directions. On a public TI-RADS dataset, our clinically guided multitask model with RLAR consistently improves risk stratification while maintaining segmentation quality compared to single-task training and conventional multitask baselines. Code and pretrained models will be released.
BACKGROUND: The thyroid function test (free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH]) is one of the key determinant of glucose homeostasis by regulating the balance of insulin. Thyroid dysfunction alters glucose metabolism, leading to insulin resistance (IR). This study aimed to assess the association between thyroid function and IR in pregnant Sudanese women. METHOD: A cross-sectional study was conducted in Saad Abuelela Hospital, Khartoum-Sudan, from January to April 2021. Obstetric/sociodemographic characteristics were gathered through questionnaires. Serum TSH, FT3, FT4, fasting plasma glucose (FPG), and fasting insulin levels were measured and evaluated, and IR was estimated using the homeostatic model assessment for insulin resistance (HOMA-IR) equation. RESULTS: In total, the study included 127 pregnant women with a median age of 27.0 years (interquartile range [IQR] 23.0‒31.2) and a median gestational (IQR) age of 25.0 (IQR 25.0‒27.0) weeks. The medians (IQRs) of the TSH, FT3, and FT4 were 1.600 (1.162‒2.092) IU/ml, 2.020(1.772‒2.240) nmol/l, and 10.70 (9.60‒11.90) pmol/l, respectively. The median (IQR) of the FPG and fasting blood insulin level was [69.0 (62.00‒78.00) mg/dl] and [5.68(2.99‒11.66) IU/ml], respectively. The median (IQR) of the HOMA-IR level was 0.9407 (0.4356‒2.1410). There was a positive correlation between HOMA -IR and FT3 levels (r = 0.375; P < 0.001) and a negative correlation with FT4 levels (r= -0.312; P < 0.001). Also, a significant positive correlation was found between fasting insulin levels and FT3 levels (r = 0.438; P < 0.001) and a negative correlation with FT4 levels (r= -0.305; P < 0.001). CONCLUSIONS: This study indicated that FT3 has positive correlation with HOMA-IR, while FT4 has negative correlation among healthy pregnant women without a history of thyroid dysfunction. This may indicate screening of euthyroid pregnant women for thyroid dysfunction and IR. Further studies are needed.
The incidence of thyroid cancer has tripled in the last three decades, and papillary thyroid carcinoma is a major contributor to this increase. However, even though most patients with PTC can have excellent long-term prognosis, survival alone is not a sufficient measure for prognosis. In recent years, the primary focus of treatments and clinical diagnoses has shifted towards patient-centered care, with the preservation of quality of life being one of the most important associated areas. The present study is a cross-sectional epidemiological descriptive study investigating the quality of life and postoperative complications in patients undergoing surgery due to papillary thyroid carcinoma in the past 10 years in the hospitals of Velayat and Rajaei in Qazvin. The available information in the patient’s records, including demographic data and pathological diagnosis, was utilized. Additionally, during their visits, they were asked about their quality of life and surgical complications. The female preponderance frequency belonged to women with 71.7%. The minimum age of the individuals under study was 16 years, the maximum was 81 years, and the mean age with a standard deviation of 42.5 ± 13 years was reported. The female preponderance prevalence is related to women. There was no significant difference between gender and involvement of lymph nodes, pulmonary metastasis, voice hoarseness, postoperative neck swelling, the need for reoperation, postoperative hypocalcemia, and quality of life. There was no significant relation between age, the time of diagnosis, iodine therapy, and patients after surgery for papillary thyroid carcinoma. The findings of this study indicate that the female preponderance frequency is related to women. No significant relationship was found between age and the time of diagnosis and treatment in patients after surgery for papillary thyroid carcinoma. Due to limitations in the number of samples in this study, it is recommended that a study on the quality of life of patients after thyroid surgery be conducted with a larger sample size.
Background In this study, we observed the frequency of side effects encountered when the neural integrity monitor electromyogram endotracheal tube (NIM-EMG-ETT) was used in thyroidectomy and parathyroidectomy surgeries. Methods After obtaining hospital ethics committee approval, 239 cases affiliated with the American Society of Anesthesiologists (ASA II-IV) who used NIM EMG tubes in thyroid and parathyroid surgery were included in the prospective observational study. Tube and patient-related complications encountered with two different NIM EMG-ETT (silicone and polyvinyl chloride-PVC) were recorded. Results The average age of the patients is 49.50 ± 13.44 years, the average BMI is 28.25 ± 4.91 kg/m^2, the median surgery time is 115 (32–475) minutes, 75.7% are women, 97.5% are ASA II. Additional diseases other than thyroid and parathyroid problems were present in 77.3%. Thyroidectomy was performed in 73.2% of the patients. In our study, only 0.8% of patients with transient recurrent laryngeal nerve RLN paralysis were observed in thyroid and parathyroid surgeries performed using NIM-EMG tubes, 3 patient already had nerve involvement in the preoperative period. The most common complication was loss of stimulation response related to tubes and patient-related ventilation failure. There was no difference between the complications of silicone and PVC tubes except for irregular EMG response. Conclusions There was no significant difference in side effects other than irregular EMG response in the two different tubes we used in our study. It was observed that prolonging the surgical time increased the risk of irregular EMG response. It should not be forgotten that no matter which NIM-EMG tube is used, additional risks are encountered during the intubation and extubation process. In order to avoid negative consequences, it is necessary to follow the usage rules recommended by the manufacturer when using NIM-EMG tubes.
Purpose: Thyroid cancer has been a common cancer. Papillary thyroid cancer and follicular thyroid cancer are the two most common types of thyroid cancer. Follicular thyroid cancer lacks distinctive ultrasound signs and is more difficult to diagnose preoperatively than the more prevalent papillary thyroid cancer, and the clinical studies associated with it are less well established. We aimed to analyze the clinical data of follicular thyroid cancer based on a novel data mining tool to identify some clinical indications that may help in preoperative diagnosis. Methods: We performed a retrospective analysis based on case data collected by the Department of General Surgery of Peking University Third Hospital between 2010 and 2023. Unlike traditional statistical methods, we improved the association rule mining, a classical data mining method, and proposed new analytical metrics reflecting the malignant association between clinical indications and cancer with the help of the idea of SHAP method in interpretable machine learning. Results: The dataset was preprocessed to contain 1673 cases (in terms of nodes rather than patients), of which 1414 were benign and 259 were malignant nodes. Our analysis pointed out that in addition to some common indicators (e.g., irregular or lobulated nodal margins, uneven thickness halo, hypoechogenicity), there were also some indicators with strong malignant associations, such as nodule-in-nodule pattern, trabecular pattern, and low TSH scores. In addition, our results suggest that the combination of Hashimoto's thyroiditis may also have a strong malignant association. Conclusion: In the preoperative diagnosis of nodules suspected of follicular thyroid cancer, multiple clinical indications should be considered for a more accurate diagnosis. The diverse malignant associations identified in our study may serve as a reference for clinicians in related fields.
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.
The increasing prevalence of thyroid cancer globally has led to the development of various computer-aided detection methods. Accurate segmentation of thyroid nodules is a critical first step in the development of AI-assisted clinical decision support systems. This study focuses on instance segmentation of thyroid nodules using YOLOv5 algorithms on ultrasound images. We evaluated multiple YOLOv5 variants (Nano, Small, Medium, Large, and XLarge) across two dataset versions, with and without doppler images. The YOLOv5-Large algorithm achieved the highest performance with a dice score of 91\% and mAP of 0.87 on the dataset including doppler images. Notably, our results demonstrate that doppler images, typically excluded by physicians, can significantly improve segmentation performance. The YOLOv5-Small model achieved 79\% dice score when doppler images were excluded, while including them improved performance across all model variants. These findings suggest that instance segmentation with YOLOv5 provides an effective real-time approach for thyroid nodule detection, with potential clinical applications in automated diagnostic systems.
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.
Purpose Proper management of subcentimeter thyroid nodules remains challenging for both clinicians and patients. Conducting extensive sonographic research using a safe and inexpensive tool for identifying thyroid nodules is necessary. The aim of this study was to identify whether having the highest-risk ultrasound (US) characteristic suggests that US-guided fine-needle aspiration (FNA) biopsy of subcentimeter nodules is more appropriate for the identification of malignancy than active surveillance (AS) or surgery. Methods The data of patients with highly suspicious subcentimeter thyroid nodules and US characteristic data who underwent surgery were retrospectively examined. Results Among a total of 556 subcentimeter nodules, 223 (40.1%) were benign, and 333 (59.9%) were malignant, with a mean maximal nodule size of 8.1 mm. In addition to age younger than 45 years, several US features were significantly associated with malignancy: irregular margins, the presence of microcalcifications, and taller-than-wide shapes ( P < 0.001). Multivariate analysis also revealed that a taller-than-wide shape (OR = 8.988, P = 0.0015) was an independent factor associated with malignancy in subcentimeter thyroid nodules. The diagnostic performance of preoperative FNA was classified as a malignancy, with a sensitivity of 98.4%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9%. Conclusions This is one of the few reports based on actual data of the most suspicious US features in subcentimeter thyroid nodules. A taller-than-wide shape US feature is most significantly associated with malignancy. FNA is a simple, accurate, and reliable preoperative method for diagnosing malignant subcentimeter thyroid nodules with highly suspicious US characteristics. AS was less appropriate than FNA for subcentimeter nodules with a taller-than-wide shape, especially in patients ≤ 45 years of age.
BACKGROUND: Variation in thyroid function parameters within the normal range has been observationally associated with adverse health outcomes. Whether those associations reflect causal effects is largely unknown. METHODS: We systematically tested associations between genetic differences in thyrotropin (TSH) and free thyroxine (FT4) within the normal range and more than 1100 diseases and more than 6000 molecular traits (metabolites and proteins) in three large population-based cohorts. This was performed by combining individual and summary level genetic data and using polygenic scores and Mendelian randomization (MR) methods. We performed a phenome-wide MR study in the OpenGWAS database covering thousands of complex phenotypes and diseases. FINDINGS: Genetically predicted TSH or FT4 levels within the normal range were predominately associated with thyroid-related outcomes, like goitre. The few extra-thyroidal outcomes that were found to be associated with genetic liability towards high but normal TSH levels included atrial fibrillation (odds ratio = 0.92, p-value = 2.13 × 10(−3)), thyroid cancer (odds ratio = 0.57, p-value = 2.97 × 10(−4)), and specific biomarkers, such as sex hormone binding globulin (β = −0.046, p-value = 1.33 × 10(−6)) and total cholesterol (β = 0.027, p-value = 5.80 × 10(−3)). INTERPRETATION: In contrast to previous studies that have described the association with thyroid hormone levels and disease outcomes, our genetic approach finds little evidence of an association between genetic differences in thyroid function within the normal range and non-thyroidal phenotypes. The association described in previous studies may be explained by reverse causation and confounding. FUNDING: This research was funded by the 10.13039/501100001711Swiss National Science Foundation (P1BEP3_200041). The Fenland study (DOI 10.22025/2017.10.101.00001) is funded by the 10.13039/501100000265Medical Research Council (MC_UU_12015/1, MC_PC_13046 and MC_UU_00006/1). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the 10.13039/501100000265Medical Research Council (MR/N003284/1, MC-UU_12015/1, MC_PC_13048 and MC_UU_00006/1).
INTRODUCTION: Pheochromocytomas can present as a diagnostic challenge, given their diverse clinical manifestations. Though classically taught as presenting with headaches, palpitations and paroxysmal hypertension, only 1 in 4 present with such a triad. Catecholamines affect the myocardium in various ways, ranging from beta-adrenergic receptor-mediated myofibril dysfunction to direct myocardial injury by catecholamine oxidation products. CASE DESCRIPTION: We report the case of a 41-year-old female with no significant past medical history, who presented with acute coronary syndrome. She was found to have myocardial infarction with non-obstructive coronary arteries (MINOCA), and her clinical course was complicated by erratic blood pressure management. Laboratory findings and imaging findings confirmed the diagnosis of pheochromocytoma. Post-cardiac catheterisation, she developed a thyroid storm and fatal cardiac arrest. CONCLUSIONS: The combination of hyperthyroidism with pheochromocytoma is rare but often fatal; iodinated angiography contrast likely precipitated her thyroid storm. This case underscores the importance of considering pheochromocytoma early in patients with MINOCA, particularly in those with erratic blood pressure. Pheochromocytomas have been reported to be associated with MINOCA in rare cases and have significant mortality. Current guidelines do not include pheochromocytoma as a possible differential diagnosis; recognition and early diagnosis are crucial for improved outcomes. LEARNING POINTS: Pheochromocytoma and thyroid disease should be added as recommended differential diagnoses in patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA) despite current guidelines not including them in the routine work-up. For patients with erratic blood pressure and MINOCA, the possibility of a pheochromocytoma should be considered early, as a prompt diagnosis can result in favourable outcomes.
Objectives Thyroid cancer (TC) is commonly recognized as the most prevalent type of malignancy affecting the endocrine system. This study aimed to assess the incidence of TC and its trends in the Iranian population. Methods The incidence rate of TC in Iran was determined using data from the Iranian National Population-based Cancer Registry (INPCR). The INPCR registered all new cancer cases through various diagnostic methods, including pathology reports, clinical and paraclinical data, and death registry reports. Results From 2014 to 2018, a total of 27,530 cases of TC were recorded. Among these cases, 21,932 (79.7%) were female, and 5,598 (20.3%) were male. The age-standardized incidence rate (ASR) of TC was 6.17 (95% confidence interval [CI]: 6.09–6.25) per 100,000 person-years, showing an upward trend from 4.61 (95% CI: 4.45–4.77) per 100,000 population in 2014 to 8.17 (95% CI: 7.97–8.37) in 2018. The ASR of TC in women was nearly 3.7 times higher than that in men (9.79 vs. 2.59 per 100,000 person-years). The ASR of TC was highest in younger age groups among women (40–50 years) compared to men, who had higher rates in older age groups (65–75 years). Papillary thyroid carcinoma (PTC), including its follicular variant, was the predominant histological type of TC in the Iranian population, accounting for 82.19% ( n = 22,627) of cases, followed by follicular thyroid carcinoma (FTC) ( n = 859; 3.12%). Conclusions Our data suggest that thyroid cancer rate has increased in Iran though comprehending the underlying reasons for this phenomenon requires further research.
Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer. Despite recent advances in treating BRAFV600E-driven ATC, therapy resistance remains a significant challenge, often resulting in disease progression and death. Leveraging a focused CRISPR/KO screen in parallel with a CRISPR/activation screen, both tailored on response to BRAFV600E inhibitor treatment, we identified TAZ (encoded by the WWTR1 gene) deficiency as synthetically lethal with BRAF inhibitor in ATC. TAZ is overexpressed in ATC compared to well-differentiated thyroid tumors. We demonstrate that TAZ-deficient ATC cells display heightened sensitivity to BRAF inhibitors both in vitro and in vivo . Using gene essentiality score across a large panel of cancer cell lines, we found that BRAFV600E-driven cancers are highly sensitive to TAZ loss, unlike their counterparts with wild-type BRAF and non-BRAFV600E. Mechanistically, we demonstrate that dabrafenib triggers the Unfolded Protein Response (UPR) under ER stress and suppresses protein synthesis. TAZ loss represses the UPR, reverses the inhibition of protein synthesis, and triggers increased cell death by ferroptosis in dabrafenib-treated ATC. Collectively, our findings unveil TAZ as a new target to overcome resistance to BRAF inhibitors in undifferentiated thyroid cancer.
Ultrasound imaging is an essential technique for evaluating the risk of malignancy in thyroid nodules. Despite its usefulness, thyroid ultrasound is limited by its operator dependence, both for image acquisition and interpretation. As a result, many machine learning algorithms (which have had great success on natural and medical images) have been proposed to automatically interpret thyroid ultrasound images.The interest in this area stimulated by the promise of AI has led to an abundance of publications proposing algorithms for the detection, segmentation, and classification of thyroid nodules, as well as to the creation of multiple commercial products marketed to medical practitioners. Despite all of these tools, the actual impact on the daily practice of French endocrinologists and radiologists has been fairly minor; this limitation is largely due to the fact that most of these algorithms do not take into account the clinical context of thyroid ultrasound in France. The goal of this thesis is therefore to explore the unique aspects of thyroid ultrasound in France, in order to identify potential opportunities for improvement using machine learning. The first chapter consists of an examination of the inter-expert variability in the evaluation of thyroid ultrasound. A multicentric study using real ultrasound images acquired during the course of the clinical practice of four French experts gives an indication of which aspects of evaluation are difficult for clinicians. The results allow for the identification of ultrasound features of thyroid nodules whose description generates disagreement between practitioners and leads to consequences for the care of patients. The second chapter goes into more detail about one of the ultrasound features used by experts: echogenicity. Building on the previous chapter, the possibility using a machine learning tool to help non-expert practitioners distinguish between hyper-/isoechoic nodules and hypoechoic nodules is explored. Then, quantitative differences between images are investigated to examine the robustness of expert labels, and the reproducibility of the ultrasound examination. The third chapter addresses the difficulties of obtaining expert annotations for training and refining machine learning algorithms for thyroid ultrasound. Given the previous results, it is clear that obtaining expert consensus labels to create transparent algorithms is enormously time-consuming. In order to reduce the annotation burden for the development of these algorithms, active learning strategies to train neural networks with fewer labels are explored. This chapter presents the limitations of these strategies on real clinical data, and also proposes an active learning technique that blends classic selection criteria with the representative power of random sampling. Finally, the last chapter explores quantitative ultrasound as a future means to improve the evaluation of thyroid nodules. By using simulations of soft tissue and of a real ultrasound probe, neural networks are applied to map the nonlinear parameter of a propagation medium based on the raw signal received by the transducer. This strategy uses a combination of pulses to create a signal that is better suited to be analyzed by the network.The contributions of this thesis seek to better contextualize the use of machine learning for thyroid ultrasound, in order to allow these techniques to advance towards applications with a real, lasting impact on clinical practice.
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L'échographie est une technique indispensable pour l'évaluation du risque de malignité des nodules thyroïdiennes. Malgré son utilité, l'échographie thyroïdienne reste limitée par sa dépendance à l'expérience de l'opérateur, autant pour l'acquisition que pour l'interprétation. C'est pourquoi des algorithmes d'apprentissage automatique, ayant connu de grands succès sur des images naturelles et médicales, ont été proposés aussi pour l'interprétation des images échographiques thyroïdiennes. L'intérêt suscité dans ce domaine par la promesse de l'IA a mené à un grand nombre de publications proposant des algorithmes pour la détection, segmentation, et classification de nodules, ainsi qu'à la création de plusieurs produits commerciaux pour la pratique clinique. Malgré tous ces outils, l'impact réel sur la pratique des endocrinologues et radiologues français reste faible ; cette limitation correspond dans une large mesure au fait que la majorité de ces algorithmes ne prennent pas en compte le contexte clinique de l'échographie thyroïdienne en France. L'objet de cette thèse est donc d'explorer les particularités de l'échographie thyroïdienne en France, afin d'identifier les possibles pistes d'amélioration en utilisant les méthodes de l'apprentissage automatique. Le premier chapitre consiste à examiner la variabilité inter-expert en évaluation de l'échographie thyroïdienne. Une étude multicentrique utilisant des images échographiques acquises au fil de l'eau de la pratique clinique de quatre experts français donnent une indication des points de difficulté pour les médecins. Les résultats permettent d'identifier les caractéristiques échographiques des nodules thyroïdiens dont la description génère des différences significatives entre les praticiens, et entraîne des conséquences sur la prise en charge des patients. Le deuxième chapitre entre plus dans le détail de l'une des caractéristiques échographiques utilisées par les experts : l'échogénicité. En continuité du chapitre précédent, la possibilité de se servir d'un outil d'apprentissage automatique pour aider les praticiens non-experts à distinguer entre des nodules hyper-/isoéchogènes et nodules hypoéchogènes est explorée. Ensuite, les différences quantitatives entre les images sont étudiées pour évaluer la robustesse de la vérité terrain, et la reproductibilité de l'examen échographique. Le troisième chapitre s'intéresse à la difficulté d'obtenir des annotations expertes pour l'entraînement et le raffinement d'algorithmes d'apprentissage automatique en échographie thyroïdienne. Á partir des résultats précédents, il est évident que l'obtention d'un consensus sur les étiquettes des experts pour entraîner des algorithmes demanderait un temps considérable. Afin de réduire ce coût pour le développement des algorithmes, des stratégies d'apprentissage actif pour entraîner des réseaux de neurones avec moins d'annotations sont explorées. Ce chapitre présente les limitations de ces stratégies sur des vraies données cliniques, et propose aussi une technique d'apprentissage actif qui mélange des critères de sélection classiques avec la représentativité de l'échantillonnage au hasard. Le dernier chapitre explore l'échographie quantitative comme piste future pour améliorer l'évaluation des nodules thyroïdiens. En utilisant des simulations numériques de tissus mous et d'une vraie sonde échographique, des réseaux de neurones sont entrainés pour estimer le paramètre non linéaire d'un milieu de propagation à partir du signal brut reçu au niveau de la sonde. La stratégie utilise une combinaison de pulses pour créer un signal plus apte à être traité par le réseau. Les contributions de cette thèse cherchent à mieux contextualiser l'utilisation de l'apprentissage automatique dans l'échographie thyroïdienne, afin de permettre ces techniques d'avancer vers des applications ayant un vrai impact durable sur la pratique clinique.
BACKGROUND: Mitochondrial DNA (mtDNA) copy number is associated with tumor activity and carcinogenesis. This study was undertaken to investigate mtDNA copy number in papillary thyroid cancer (PTC) tissues and to evaluate the risk of PTC development. The clinicopathological features of patients and mtDNA copy number were correlated. The value of mtDNA copy number was evaluated as a biomarker for PTC. METHOD: DNA was extracted from 105 PTC tissues and 67 control thyroid tissues, and mtDNA copy number mtDNA oxidative damage were determined using qPCR techniques. RESULTS: Overall, the relative mtDNA copy number was significantly higher in PTC patients (p < 0.001). The risk of developing PTC increased significantly across the tertiles of mtDNA copy number (p trend < 0.001). The higher the mtDNA copy number tertile, the greater the risk of developing PTC. Patients with follicular variants had an odds ratio of 2.09 (95% CI: 1.78–2.44) compared to those with classical variants (p < 0.001). The level of mtDNA oxidative damage in PTC was significantly elevated compared to controls (p < 0.001). The ROC analysis of mtDNA copy number indicated an area under the curve (AUC) of 77.7% (95% CI: 0.71 to 0.85, p < 0.001) for the ability of mtDNA copy number z-scores in differentiate between PTC and controls. CONCLUSION: Our results indicated that the augmentation of mtDNA content plays a significant role during the initiation of thyroid cancer, and it might represent a potential biomarker for predicting the risk of PTC.
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
Introduction: Deep learning-based segmentation models are increasingly integrated into clinical imaging workflows, yet their robustness to adversarial perturbations remains incompletely characterized, particularly for ultrasound images. We evaluated adversarial attacks and inference-time defenses for thyroid nodule segmentation in B-mode ultrasound. Methods: Two black-box adversarial attacks were developed: (1) Structured Speckle Amplification Attack (SSAA), which injects boundary-targeted noise, and (2) Frequency-Domain Ultrasound Attack (FDUA), which applies bandpass-filtered phase perturbations in the Fourier domain. Three inference-time mitigations were evaluated on adversarial images: randomized preprocessing with test-time augmentation, deterministic input denoising, and stochastic ensemble inference with consistency-aware aggregation. Experiments were conducted on a U-Net segmentation model trained on cine-clips from a database of 192 thyroid nodules. Results: The baseline model achieved a mean Dice similarity coefficient (DSC) of 0.76 (SD 0.20) on unperturbed images. SSAA reduced DSC by 0.29 (SD 0.20) while maintaining high visual similarity (SSIM = 0.94). FDUA resulted in a smaller DSC reduction of 0.11 (SD 0.09) with lower visual fidelity (SSIM = 0.82). Against SSAA, all three defenses significantly improved DSC after correction, with deterministic denoising showing the largest recovery (+0.10, p < 0.001), followed by randomized preprocessing (+0.09, p < 0.001), and stochastic ensemble inference (+0.08, p = 0.002). No defense achieved statistically significant improvement against FDUA. Conclusion: Spatial-domain adversarial perturbations in ultrasound segmentation showed partial mitigation with input preprocessing, whereas frequency-domain perturbations were not mitigated by the defenses, highlighting modality-specific challenges in adversarial robustness evaluation. ;14 pages, 3 figures, 3 tables
Accurate thyroid nodule segmentation in ultrasound images is critical for diagnosis and treatment planning. However, ambiguous boundaries between nodules and surrounding tissues, size variations, and the scarcity of annotated ultrasound data pose significant challenges for automated segmentation. Existing deep learning models struggle to incorporate contextual information from the thyroid gland and generalize effectively across diverse cases. To address these challenges, we propose SSMT-Net, a Semi-Supervised Multi-Task Transformer-based Network that leverages unlabeled data to enhance Transformer-centric encoder feature extraction capability in an initial unsupervised phase. In the supervised phase, the model jointly optimizes nodule segmentation, gland segmentation, and nodule size estimation, integrating both local and global contextual features. Extensive evaluations on the TN3K and DDTI datasets demonstrate that SSMT-Net outperforms state-of-the-art methods, with higher accuracy and robustness, indicating its potential for real-world clinical applications.
Objective To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner. Methods This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients’ operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively. Results The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group ( P < 0.05). The differences in complication rate, intraoperative bleeding volume, 24-h postoperative pain index and recurrence rate were not statistically significant between the two groups ( P > 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up ( P < 0.05). The differences at the 6- and 12-month postoperative follow-ups were not statistically significant ( P > 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P < 0.05). The experimental group had better social adaptability, greater total medical costs, and better overall patient medical satisfaction than did the control group ( P < 0.05). The acceptance of TAWISL was greater than that of COACAS ( P < 0.05). Conclusion Compared with COACLAS, TAWISES is safe and effective and better meets the cosmetic, psychological and social adaptation needs of patients. TAWISES is also more cost effective and can be better utilized for the population in our region, filling the gap in surgical modalities for thyroid cancer in in our region.
Robot-assisted surgery has a permanent place in urological practice. With the signing of the Green Deal Healthcare 3.0, it is relevant to investigate the environmental impact of these treatments. No data are yet available for urological procedures. For the robot assisted hysterectomy, the total intraoperative greenhouse gas (GHG) emissions are almost three times higher compared to the open abdominal procedure. The largest contribution is made by the production, transport, use and processing of single-use instruments, whereas intra-operative energy use is only a fraction of the total use. This high intraoperative environmental impact may be compensated by shorter hospital stay and fewer complications. This seems to be true for the prostatectomy, but probably not for the cystectomy. Current recommendations for healthcare professionals are mainly to critically revise the usage of single-use materials and to optimize perioperative care. Robotgeassisteerde chirurgie heeft een vaste plek binnen de urologische praktijk. Met het tekenen van de Green Deal Zorg 3.0 is het relevant om de milieu-impact van deze behandelingen te onderzoeken. Over de impact van urologische ingrepen is nog weinig bekend. Voor de robotgeassisteerde hysterectomie geldt dat de totale intra-operatieve uitstoot van broeikasgassen (GHG) bijna driemaal zo hoog is als bij de open abdominale benadering. De grootste bijdrage wordt geleverd door de productie, het transport, het gebruik en de verwerking van single-use instrumenten. Peroperatief gebruik van energie draagt maar een fractie bij. Deze hoge intra-operatieve milieu-impact wordt mogelijk gecompenseerd door een kortere opnameduur en minder complicaties. Dit lijkt bij de prostatectomie te kloppen, maar bij de cystectomie waarschijnlijk niet. De huidige adviezen voor zorgprofessionals zijn vooral het kritisch omgaan met single-use materialen en het optimaliseren van perioperatieve zorg.
Our aim was to determine risk factors of enterococcal bacteraemia (EB) in urology. In a prospective study including all positive blood cultures (PBC) in urology for 18 months in five institutions, one hundred seventy-six PBC diagnosed, including 111 cases related to Gram negative bacilli (63%), 32 EB (18%) and 33 cases related to other pathogens (19%). The main characteristic of EB was their occurrence exclusively in male gender. In logistic regression, EB appeared to be associated with transurethral resection of the prostate: adjusted odds ratio (AOR) [95% CI]: 3.75 [1.30-10.78].
Introduction Concealed penis is a congenital anomaly that affects not only the appearance but also the function of the external genitalia in the male sex. Different surgical methods have been proposed to correct this disorder, including removal of the previous scar, penile shaft, penile trunk skin reconstruction with flap, penile skin fixation in penopubic and penoscrotal angles, and removal of extra pubic fat. In this study, we will discuss the results of definitive surgery in one stage using autogenous skin grafts and examine the details of this technique. Methods This study was conducted as a clinical trial in Hospitals related to the Isfahan University of Medical Sciences. Children over the age of 7 years old. A full-thickness graft with a length of 1.5 times the defect and a width of 1 cm was taken from the non-dominant thigh and defatted. The inguinal skin was chosen because it is hairless and next to the penis, and the resulting scar is easily hidden under clothing. Then, the graft was transferred to the operation site and fixed. Results and conclusion We proposed a method of treatment for concealed penis, using a full-thickness inguinal graft. Our technique showed promising results with minimal and negligible complications. To fully highlight each process’s benefits and limitations and evaluate them against one another, these procedures should, however, be tested on larger populations and compared comprehensively. Trial registration The study was conducted in accordance with the ethical standards of the Isfahan University of Medical Sciences Research Ethics Committee (ethical code: IR.MUI.MED.REC.1402.073) And was registered on 27/05/2023 as a clinical trial in Iranian registry of clinical trials. (IRCT code: IRCT20230513058160N1)
Background This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . Methods A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model’s utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients’ baseline characteristics ( $$Age$$ Age , body mass index ( $$BMI$$ BMI ), $$Gleason Score$$ GleasonScore , $$Grade$$ Grade , and $$Drug$$ Drug ) and two longitudinal endogenous covariates ( $$Platelets$$ Platelets and $$Bilirubin$$ Bilirubin ). Results The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. Conclusions The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.
Acute kidney injury (AKI) is a major global health problem, expensive to manage, and its associations with negative pediatric health outcomes have been clearly demonstrated. One of the most fundamental questions to consider as we use previous epidemiological information to advance research and care paradigms is the strength of the causal link between pediatric AKI and health outcomes. In this review, we apply the foundational framework of the Bradford Hill criteria to evaluate the extent to which a causal link exists between AKI and the associated adverse outcomes in children. Available data in children support a causal link between AKI and short-term outcomes including mortality, length of stay, and ventilation time. Clarifying the causal nature of longer term associations requires further high-quality observational studies in children, careful consideration of what defines the most meaningful and measurable longer term outcomes after pediatric AKI, and integration of evolving biological data related to mechanisms of disease. Preventing or mitigating AKI should lead to improved outcomes. Demonstrating such reversibility will solidify confidence in the causal relationship, improve child health, and highlight an aspect which is highly relevant to clinicians, scientists, and policy makers. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information
Background Prostate cancer is the most frequently diagnosed cancer among men in the world. Uganda and Zimbabwe have been reported to have highest incidence rates of prostate cancer in sub-Saharan Africa. There are no urologists and no prostate cancer diagnostic facilities in rural communities in south western Uganda. Men with lower urinary tract symptoms are treated with prostatectomy by midlevel healthcare workers and general surgeons without prior prostate cancer screening. Histological diagnosis relies on the prostate tissue retrieved during surgery and the results may take several months. Prostate cancer care in southwestern Uganda remains uncoordinated and has not been documented before. This study aimed to establish and document the burden of prostate cancer in rural southwestern Uganda as a basis for further research. Methods This was a retrospective study conducted in hospitals in rural southwestern Uganda. We used hospital records as primary source of data. Histology results of patients treated with prostatectomy during the five-year period (2019–2023) were retrieved and data extracted for analysis. 1013 patients were included in the study. Univariate data analysis was done with STATA version 17.0. The study received ethics clearance for Kabale university REC and Uganda National council of Science and Technology. Results The average age of patients in this study was 70.6 year (range 54–102 years). Prostate cancer was present in 232 (22.9%) patients. Seventeen (7.3%) patients with prostate cancer were below sixty years. Most (75.4%) of the patients with prostate cancer in this study had low to intermediate risk disease. Perineural tumor infiltration was present in 28.9% of prostate cancer patients. Conclusion More than 1 in 5 men (22.9%) with lower urinary tract symptoms treated with prostatectomy in the study period in southwestern Uganda had prostate cancer. Majority of patients (75.4%) had low to intermediate risk disease. These findings highlight the urgent need for systematic improvements in prostate cancer care, including sensitization of both health workers and the general population, establishment of early screening and regional diagnostic and treatment facilities to enhance patient outcomes in resource -limited rural communities in Uganda. Clinical trial number Not applicable.
Background The current literature still lacks robust real-life evidence to support the practical implications of telesurgery. We conduct the current study to evaluate the safety and effectiveness of telesurgery over a high-speed remote communication network (the 5G network) in the real world. Methods A total of 37 patients were enrolled across the participating hospitals from December 2023 to June 2024. Patients underwent various telesurgeries including radical prostatectomy, partial nephrectomy and other urological surgeries. The primary end point is the success rate of remote surgery. The secondary end points include network transmission status, robot-assisted surgery time, intraoperative blood loss, subjective evaluation of intraoperative experience, postoperative PSA level, positive surgical margin. Other evaluation index includes the surgeon’s physiological and psychological stress during surgery, equipment failure and adverse events as postoperative complications. Results The overall success rate for remote surgery was 100% [95% confidence interval (CI) 90.5–100, p = 0.019]. The mean network signal delay was 55.30 ± 39.64 ms. The total delay at the local and remote ends were 250.30 ± 39.64 ms and 249.78 ± 40.00 ms, respectively. The average packet loss rate was less than 0.01% at both ends. The evaluation of the remote surgeons’ intraoperative experience excellent. A total of 6 adverse events occurred and none were related to the instruments of robot. No postoperative complications of Clavien-Dindo grade III-IV occurred. No serious or repairable equipment failure occurred at either the remote or local end. Conclusions It is feasible to perform urological telesurgery over the 5G high-speed remote communication network to overcome geographical barriers and improve patient care.
Objective To evaluate the benefit of using platelet-rich plasma (PRP) covering layer in decreasing urethrocutaneous fistula rate post-distal penile hypospadias repair using the STAR technique. Methods This prospective randomized controlled trial included 44 boys with primary distal penile hypospadias. Patients were randomized into two groups: Group A ( n = 22) underwent repair using the STAR technique with an additional PRP layer over the neourethra, while Group B ( n = 22) received the STAR repair without PRP. PRP was prepared from autologous blood and applied as an intermediate layer before skin closure. Patients were followed for at least 4 weeks. The primary outcome was the incidence of urethrocutaneous fistula (UCF). Secondary outcomes included postoperative complications (edema, infection, meatal stenosis), operative time, and cosmetic outcome using the Hypospadias Objective Scoring Evaluation (HOSE). Results The two groups (22 patients per group) were similar in age (median ~ 20 months in each, p = 0.96) and other preoperative characteristics. The incidence of urethrocutaneous fistula was significantly lower in the PRP group (4.5% [1/22]) compared to the non-PRP group (27.3% [6/22], p = 0.039). Other postoperative complication rates showed no statistically significant differences: edema occurred in 4.5% of Group A vs 0% of Group B ( p = 1.00), meatal stenosis in 4.5% vs 0% ( p = 1.00), and no wound infections occurred in either group. Mean operative time was slightly longer with PRP (70.2 ± 16.5 min vs 61.1 ± 15.7 min without PRP) but did not reach statistical significance ( p = 0.068). Conclusion Incorporating PRP as a biological layer in distal hypospadias repair using the STAR technique significantly reduced urethrocutaneous fistula rates without increasing complications. PRP is a safe autologous adjunct that may improve surgical outcomes.
Objective Accurate midstream urine (MSU) collection is essential to minimise contamination and support correct diagnosis of urinary tract infection, yet contamination remains common despite routine verbal instruction. Persistent contamination can cause misdiagnosis, unnecessary antibiotics and delays before endourological procedures. This trial evaluated whether an educational video improves MSU collection compared with standard verbal instruction among elective urology patients. Materials and methods This prospective randomised controlled trial included adults admitted for elective urology surgery at a tertiary public hospital in Selangor, Malaysia (21 January–31 March 2025). Eligible patients (> 18 years, any sex, able to consent, English or Malay-speaking) were randomised 1:1 to standard verbal or educational video instruction on MSU collection. All participants completed a pre-intervention questionnaire, collected two urine samples (urinalysis and culture), and then completed a post-collection questionnaire. The primary outcome was urine sample contamination, defined as mixed growth of > 2 species or growth of typical skin/perineal/vaginal flora. Secondary outcomes were urinalysis indices, participant-reported knowledge and satisfaction, and a six-step correct practice score (0–6). Categorical outcomes were compared using Pearson’s chi-square tests; practice scores were compared using the Mann–Whitney U test. Results A total of 150 patients were randomised (75 per group; mean age 56.6 ± 13.8 years; 74.7% with comorbidities). Contamination was lower in the video than verbal group (24.0% vs. 38.7%; χ²=3.75, P = 0.053). Participants with diabetes had higher contamination than those without (42.9% vs. 24.5%; P = 0.019). Correct practice was high overall, but 88.0% of the video group versus 76.0% of the verbal group achieved a perfect score of 6; median (IQR) was 6.0 (0.0) in both groups, with a significant difference favouring video (z = − 2.101, P = 0.036). Conclusion Educational video instruction improved adherence to correct MSU collection steps and showed a non-significant trend towards reduced contamination compared with standard verbal instruction.
Introduction and hypothesis We evaluated a pilot multi-component reintegration intervention to improve women’s physical and psychosocial quality of life after genital fistula surgery. Methods Twelve women undergoing fistula repair at Mulago Specialized Women and Neonatal Hospital (Kampala, Uganda) anticipated in a 2-week multi-component intervention including health education, psychosocial therapy, physiotherapy, and economic investment. We assessed feasibility through recruitment, retention, and adherence, acceptability through intervention satisfaction, and preliminary effectiveness through reintegration, mental health, physical health, and economic status. We collected quantitative data at enrollment, 6 weeks, 3 months, and 6 months. We conducted in-depth interviews with six participants. Quantitative data are presented descriptively, and qualitative data analyzed thematically. Results Participants had a median age of 34.5 years (25.5–38.0), 50% were married/partnered, 42% were separated, 50$ had completed less than primary education, and 67% were unemployed. Mean number of sessions received was 12 for health education (range 5–15), 8 for counseling (range 8–9), and 6 for physiotherapy (range 4–8). Feasibility was demonstrated by study acceptance among all those eligible (100%); comfort with study measures, data collection frequency and approach; and procedural fidelity. Acceptability was high; all participants reported being very satisfied with the intervention and each of the components. Participant narratives echoed quantitative findings and contributed nuanced perspectives to understanding approach and content. Conclusions Our results suggest that the intervention and associated research were both feasible and acceptable, and suggested certain modifications to the intervention protocol to reduce participant burden. Further research to determine the effectiveness of the intervention above and beyond surgery alone with regard to the health and well-being of women with fistulas is warranted.
Background The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms’ tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. Methods Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. Results Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). Conclusions To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.
With increasing life expectancy there is also an increased need for the management of older (≥ 80 years) patients with the diagnosis of muscle-invasive bladder cancer. Radical cystectomy with urinary diversion is the state of the art treatment (with neoadjuvant chemotherapy, as long as the patient is fit enough). Choosing the best urinary diversion with respect to morbidity compared to functionality and quality of life remains a challenge in these patients. Physical age alone is not decisive for making a decision. A thorough preoperative assessment of medical features, physical and cognitive impairments is more important. Older patients are generally provided with an ileal conduit as an incontinent urinary diversion, as the intervention involves reduced operating times and complexity compared to continent urinary diversions; however, in the case of good health status with an adequate life expectancy and sufficient compliance, continent diversions may be considered even in aged candidates. In the case of multimorbid patients with a high perioperative risk, ureterostomy with permanent ureteric stents is an important alternative. Most importantly, a thorough preoperative counselling enables patients to reach an informed decision. Bei steigender Lebenserwartung gibt es zunehmend ältere (≥ 80 Jahre) PatientInnen mit der Diagnose eines muskelinvasiven Blasenkarzinoms. Therapie der Wahl ist die radikale Zystektomie mit Harnableitung (mit neoadjuvanter Chemotherapie, sofern belastbar). Die Auswahl der richtigen Harnableitung in Abwägung von Morbidität gegenüber Funktionalität und Lebensqualität stellt eine Herausforderung dar. Das kalendarische Alter allein ist nicht entscheidend. Wegweisend ist v. a. eine adäquate präoperative Begutachtung mit Blick auf medizinische Besonderheiten sowie physische und kognitive Einschränkungen. Standardmäßig wird bei älteren PatientInnen das Ileum-Conduit als inkontinente Harnableitung eingesetzt, da der Eingriff eine geringere Komplexität und Operationsdauer als eine kontinente Harnableitung aufweist. Fitte PatientInnen mit adäquater Lebenserwartung und ausreichender Compliance können jedoch auch im hohen Alter Kandidaten für kontinente Harnableitungen sein. Die Ureterokutaneostomie mit Harnleiterschienendauerversorgung ist eine wichtige Alternative für multimorbide PatientInnen mit hohem perioperativem Risiko. Wichtig ist v. a. eine gute präoperative Aufklärung, sodass PatientInnen eine informierte Entscheidung treffen können.
Purpose of Review To provide a primer for how augmented reality (AR)-guided surgical technology works at a fundamental level and discuss recent advances and limitations in a rapidly advancing field, including studies aiming to reduce current issues limiting wider adoption. Recent Findings Among the studies published within the last five years, AR-guided technologies have advanced from pre-operative planning to intraoperative use in procedures including robot-assisted radical prostatectomy, percutaneous nephrolithotomy, and renal transplantation. Artificial intelligence (AI) and deep learning techniques have allowed for development of automatic registration to address challenges with soft tissue deformation. Subspecialities which may benefit from further AR/MR adoption include reconstructive and andrology, which were underrepresented in our review. Summary Augmented reality refers to the process of superimposing digital information (e.g., preoperative imaging) on top of the physical world. Along with its interactive counterpart, mixed reality (MR), AR has become an area of sustained research interest in the urological surgery space. This technology has significant implications for surgical accuracy, efficiency, and medical education. As a result, it is critical for clinicians to both be aware of advancements in the field and understand the basics of this technology. We discuss articles published from March 2021 to February 2025, across a range of urologic procedures and applications, and discuss how recent trends point to a shift towards higher-powered, prospective studies incorporating intraoperative usage of AR/MR.
Introduction Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. Methods This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Results From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433–1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511–2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219–2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564–2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. Conclusion Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.
Purpose of Review To review the use of standardized letters of recommendation (SLORs) in urology residency match and to evaluate their impact on the selection process. Recent Findings We aimed to understand the current landscape of SLORs across medicine. We found 44 articles evaluating SLORs in various specialties, of which 5 focused on urology in the past 5 years. The use of SLORs have been shown to decrease gender and selection biases in urology. Currently, a new and improved peer-revised electronic SLOR format is being developed by the Society of Academic Urologists. Summary The use of SLORs can help alleviate biases that may develop with narrative letters of recommendation. There is limited information on optimal standardized formats for SLORs. Improving the structure and expanding the use of SLORs is fundamental for creating an efficient and fair match process.
Male patients undergoing urologic surgery under general anesthesia are more prone to developing catheter-related bladder discomfort (CRBD). Transcutaneous tibial nerve stimulation (TTNS) is an established intervention for lower urinary tract dysfunction. This study aimed to evaluate the impact of TTNS on the incidence of moderate-to-severe CRBD in male patients following urological surgery under general anesthesia. 124 male patients scheduled for urologic surgery from December 2023 to June 2024 were included and randomized to the TTNS or Control groups via stratified block group randomization. The TTNS group received 30 min of TTNS stimulation (200-μs pulses, 20/100 Hz alternating sparse-dense waves) in the post-anesthesia care unit, while the Control group received 30 min of sham stimulation. The degree of CRBD and VAS scores at 0 h, 1 h, 2 h, and 6 h after tracheal extubation, the Quality of Recovery-15 (QoR-15) score at 24 h postoperatively, length of hospitalization, rescue medication rates, and the incidence of adverse reactions were compared between the two groups. Compared with the Control group, a significant reduction was observed in the incidence of moderate-to-severe CRBD immediately after tracheal extubation (0 h) in the TTNS group [ P = 0.002, CI 0.190–0.741, RR 0.375]. The incidence of moderate-to-severe CRBD in the TTNS group was significantly lower than that in the Control group at 1 and 2 h after extubation ( P < 0.001, P = 0.002). Furthermore, the severity of CRBD at all time points was significantly lower than that in the TTNS group ( P = 0.017, P < 0.001, P < 0.001, and P < 0.001, respectively). The VAS scores of patients in the TTNS group were notably lower than those in the Control group at 0, 1, and 2 h after tracheal extubation ( P = 0.009, P = 0.012, P = 0.013, respectively). The QoR-15 scores at 24 h post-surgery in the TTNS group were significantly higher ( P < 0.001). The incidence rates of postoperative nausea and medication rescue were lower in the TTNS group than in the Control group ( P = 0.006, P < 0.001). Finally, the TTNS intervention was not associated with any adverse effects. TTNS effectively reduces the incidence of moderate-to-severe CRBD, enhances early postoperative analgesia, and improves recovery quality in male patients undergoing urologic surgery without significant safety concerns. Trial registration : This study was retrospectively registered and reviewed by a principal investigator (Xiangying Zheng) in the Chinese Clinical Trials Registry (registration number: ChiCTR2300078536) on December 12, 2023.
Transitioning from multi-port to single-port robotic systems in urologic surgery requires significant team adaptation; however, the experience of clinicians during this shift remains underexplored. Therefore, this study aims to examine the effect of single-port transition training on learning experiences and perceived readiness among healthcare providers, using Kolb’s experiential learning theory. Eleven physicians and 22 operating room nurses completed phased single-port transition training at a university hospital in Seoul (February–May 2025) and responded to open-ended questionnaires analyzed using Braun and Clarke’s thematic analysis. Most experiences aligned with Kolb’s learning cycle: concrete experience with single-port articulation, reflective comparison of single- and multi-port routines, abstract conceptualization of single-cannula principles, and active experimentation with collision prevention and workflow strategies. Some experienced physicians reported limited learning gains, suggesting that prior expertise reduces engagement. Nurses emphasized docking efficiency and spatial management, whereas physicians prioritized articulation control and technique refinement. Both groups reported greater confidence and interprofessional coordination. These findings suggest that integrating hands-on practice with structured reflection supports adaptation; however, the relationship between perceived readiness and clinical performance requires further investigation.
The endoscopic control system has remained similar in design for many decades The remit of advanced therapeutic endoscopy continues to expand requiring precision control and high cognitive workloads. Robotic systems are emerging, but all still require bimanual control and expensive and large new systems. Eye tracking is an exciting area that can be used as an endoscope control system. This is a study to establish the feasibility of an eye-controlled endoscope and compare its performance and cognitive demand to use of a conventional endoscope. An eye gaze-control system consisting of eye-tracking glasses, customised software and a small motor unit was built and attached to a conventional endoscope. Twelve non-endoscopists used both the eye gaze system and a conventional endoscope to complete a benchtop task in a simulated oesophagus and stomach. Completion of tasks was timed. Subjective feedback was collected from each participant on task load using the NASA Task Load Index. Participants were significantly quicker completing the task using iGAZE2 vs a conventional endoscope (65.02 ± 16.34s vs 104.21 ± 51.31s, p = 0.013) Participants were also significantly quicker completing retroflexion using iGAZE2 vs a conventional endoscope (8.48 ± 3.08 vs 11.38 ± 5.36s, p = 0.036). Participants reported a significantly lower workload (raw NASA-TLX score) when using iGAZE2 vs the conventional endoscope (152.1 ± 63.4 vs 319.6 ± 81.6, p = 0.0001) (Fig. 7). Users found iGAZE2 to have a significantly lower temporal demand, mental demand, effort, mental demand, physical demand, and frustration level. The eye gaze system is an exciting, small, and retrofittable system to any endoscope. The system shows exciting potential as a novel endoscopic control system with a significantly lower workload and better performance in novices suggesting a more intuitive control system.
Background Gardnerella is a bacterial genera commonly present in the female urogenital tract, especially in bacterial vaginosis. Gardnerella are frequently detected in urine collected directly from the bladder and have been implicated in urinary incontinence and recurrent urinary tract infections. Understanding the contribution of Gardnerella to pathogenesis is complicated by its genetic heterogeneity and a shortage of data from in vivo models. One clinical isolate of Gardnerella triggered urothelial exfoliation and promoted urinary tract infection by uropathogenic E. coli in a mouse model. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with urinary tract persistence and pathogenesis. Methods Eighteen Gardnerella strains from the four main clades were inoculated transurethrally into female C57BL/6 mice. Bacteriuria was monitored by quantitative culturing and pathologic features were assessed in bladder tissues. Pan-genome phylogenetic analyses were performed to identify genes associated with in vivo phenotypes, including long- and short-term bacteriuria, urothelial exfoliation, and edema. Genes that were significantly associated to phenotype were matched against a pangenome analysis of 291 publicly available Gardnerella genomes to determine the conservation of these putative colonization and virulence factors across the genus. Results Clade 2 strains were more persistent, whereas the other three clades caused transient bacteriuria or were undetectable. Clade 2 and 4 strains induced urothelial exfoliation, and clades 2, 3 and 4 triggered edema. Forty-five genes were significantly associated with persistence and pathogenicity. Among the 291 publicly available genomes, clade 2 strains encoded more of the bacteriuria-associated genes than strains in the other three clades. Exfoliation-associated genes were present in most clade 4 strains. Clade 3 strains lack most of the in vivo associated genes, whereas clade 1 strains were more heterogeneous. Conclusions This study provides in vivo evidence for differential urinary tract colonization and pathogenesis by different clades/species within the genus Gardnerella and identifies new putative persistence and virulence factors. Pangenome analysis predicted that clade 2 Gardnerella are the most likely to persist in the urinary tract and that clades 2 and 4 have the highest uropathogenic potential. These findings inform future targeted screening and treatment approaches aimed at limiting harmful Gardnerella urinary tract exposures.
Non-technical skills (NTS) are crucial in healthcare, encompassing cognitive and social skills that support technical ability. Traditional NTS training is evolving with the emergence of artificial intelligence (AI) models that can intelligently converse with their users, known as large language models (LLMs). This study investigated the capabilities and limitations of a popular model named generative pre-trained transformer 4 (GPT-4) in NTS training, comparing its performance to that of human evaluators. Urology trainees identified NTS events in simulated scenarios and discussed them in blinded feedback sessions with AI and human consultants. Experts assessed the blinded interaction data, providing quantitative ratings and qualitative evaluations using annotated transcripts. Wilcoxon signed-rank tests compared pre- and post-intervention ratings, whilst Mann–Whitney U tests compared post-intervention ratings between AI and human feedback. Thematic analysis identified strengths, limitations, and differences between AI and human feedback approaches. The AI model demonstrated significant strengths in reinforcing knowledge gathering ( p = 0.04), providing accurate and evidence-based feedback ( p = 0.013), conveying empathy ( p = 0.021), and tailoring explanations to complexity ( p = 0.002). However, human feedback excelled in language terminology ( p = 0.003), complexity ( p = 0.020), and fact-based feedback ( p = 0.025). The study highlights the potential for AI to augment assessment of NTS training in healthcare. A blended approach utilising AI and human expertise may boost training efficacy.
Introduction and Hypothesis Pessary self-management offers benefits to women with no increased risk of complications. However, many are unwilling to self-manage, preferring clinician-led care. This study is aimed at exploring factors associated with willingness to self-manage a pessary. Methods Women attending pessary clinic at a UK hospital were asked to complete a questionnaire providing responses on pessary use, comorbidities, female genital self-image, self-management experience and willingness (or not) to learn self-management. Based upon statistical advice we aimed to recruit 90 women. Data were analysed using the non-parametric Kruskal–Wallis test and Chi-squared test. Free text data were analysed thematically. Results A total of 89 women completed the questionnaire. Thirty-three women (38%) had previously been taught pessary self-management. Of the remaining women, 12 (21%) were willing to learn, 28 (50%) were not willing and 16 (29%) were unsure. There was no correlation between female genital self-image and willingness to self-manage a pessary. Younger women were more willing to learn self-management ( p = < 0.001). Willing women were motivated by reduced follow-up visits. Self-managing women reported benefits including increased autonomy, cleanliness and giving their body “a break”. Reasons discouraging women from self-managing were a lack of confidence; feeling physically unable; wanting clinician-led care; fear of problems or previous problems with their pessary. Conclusions Most women were either unsure about pessary self-management or unwilling to self-manage. Age was the only factor we found that had a significant relationship with willingness to self-manage a pessary. With robust self-management teaching, support and follow-up, it is likely that many of the barriers women report can be overcome.
Introduction The European Board of Urology (EBU) In-Service Assessment (ISA) test evaluates urologists’ knowledge and interpretation. Artificial Intelligence (AI) chatbots are being used widely by physicians for theoretical information. This research compares five existing chatbots’ test performances and questions’ knowledge and interpretation. Materials and methods GPT-4o, Copilot Pro, Gemini Advanced, Claude 3.5, and Sonar Huge chatbots solved 596 questions in 6 exams between 2017 and 2022. The questions were divided into two categories: questions that measure knowledge and require data interpretation. The chatbots’ exam performances were compared. Results Overall, all chatbots except Claude 3.5 passed the examinations with a percentage of 60% overall score. Copilot Pro scored best, and Claude 3.5’s score difference was significant (71.6% vs. 56.2%, p = 0.001 ). When a total of 444 knowledge and 152 analysis questions were compared, Copilot Pro offered the greatest percentage of information, whereas Claude 3.5 provided the least (72.1% vs. 57.4%, p = 0.001 ). This was also true for analytical skills (70.4% vs. 52.6%, p = 0.019 ). Conclusions Four out of five chatbots passed the exams, achieving scores exceeding 60%, while only one did not pass the EBU examination. Copilot Pro performed best in EBU ISA examinations, whereas Claude 3.5 performed worst. Chatbots scored worse on analysis than knowledge questions. Thus, although existing chatbots are successful in terms of theoretical knowledge, their competence in analyzing the questions is questionable.
Introduction and Hypothesis To compare change in urgency urinary incontinence episodes (UUIEs) in women undergoing posterior tibial nerve stimulation (PTNS) plus mirabegron versus PTNS plus placebo for the treatment of refractory urgency urinary incontinence (UUI). The primary hypothesis was that combination therapy is superior to monotherapy. Methods A randomized controlled trial was performed in individuals identifying as female aged ≥ 18 years with UUI symptoms refractory to second-line treatment or who could not tolerate antimuscarinic medications. Both participants and providers were blinded to medication treatment allocation. Participants were randomized (1:1) to PTNS plus mirabegron or PTNS plus placebo. Participants completed a 3-day bladder diary prior to and after 12-week treatment. Validated symptom distress and impact questionnaires were obtained pre- and post-treatment. The primary outcome was change in mean number of UUIEs on a 3-day bladder diary pre- versus post-treatment between arms. Primary and secondary outcomes were analyzed via sample t tests. Results Fifty-four subjects were randomized, mean ± SD baseline age 56.2±15.6 years and body mass index 35.0±9.4 (kg/m^2); no differences were noted in any clinical–demographic characteristics. There was a significant difference between arms in mean pre- to post-treatment UUIEs, 9.4±3.9, mirabegron versus 5.3±5.5, placebo ( p =0.007). Significant differences were found pre- compared with post-treatment in urinary frequency, Overactive Bladder Questionnaire Short Form Symptom Bother and Symptom Health-Related Quality of Life scores. Conclusions In subjects undergoing PTNS treatment for refractory UUI and OAB-wet symptoms, the addition of a β-3 agonist produced significant improvement in both objective and subjective overactive bladder symptom outcomes compared with PTNS plus placebo.
Background The integration of artificial intelligence (AI) in medical education assessment remains largely unexplored, particularly in specialty-specific evaluations during clinical rotations. Traditional question development methods are time-intensive and often struggle to keep pace with evolving medical knowledge. This study evaluated the effectiveness of AI-generated questions in assessing urological competency among medical interns during a standardized clinical rotation. Methods Two state-of-the-art AI language models (ChatGPT and Gemini) generated 300 multiple-choice questions across six urological subspecialties. Seven experienced urologists, each with over 10 years of clinical practice and active involvement in resident training programs, independently evaluated the questions using a modified Delphi approach with standardized scoring rubrics. The evaluation criteria encompassed technical accuracy based on current clinical guidelines, clinical relevance to core rotation objectives, construct validity assessed through cognitive task analysis, and alignment with rotation objectives. Questions achieving consensus approval from at least five experts were retained, resulting in 100 validated questions. Results From the initial cohort of 45 eligible interns, 42 completed all three assessment points (93.3% completion rate). Performance improved significantly from baseline (mean: 45.2%, 95% CI: 42.6–47.8%) through mid-rotation (mean: 62.8%, 95% CI: 60.4–65.2%) to final assessment (mean: 78.4%, 95% CI: 76.5–80.3%). The technical accuracy was comparable between AI platforms (ChatGPT: 84.3%, Gemini: 83.8%, p = 0.86). Clinical scenario questions demonstrated better discrimination than recall questions (mean indices: 0.28 vs. 0.14, p < 0.001). Subspecialty performance varied, with highest scores in uro-oncology (mean: 82.6%, 95% CI: 80.2–85.0%) and endourology (mean: 79.4%, 95% CI: 77.0-81.8%). Conclusions AI-generated questions showed appropriate technical accuracy and difficulty levels for assessing clinical competency in urology. While promising for formative assessment, particularly with clinical scenarios, current limitations in discrimination capability suggest careful consideration for high-stakes testing. The strong correlation between clinical exposure and improved performance validates their effectiveness in measuring knowledge acquisition. These findings support the potential integration of AI-generated questions in specialty-specific assessment, though careful implementation with expert oversight and continuous validation remains essential. Clinical trial number Not applicable.
Veterinary systems biology is an innovative approach that integrates biological data at the molecular and cellular levels, allowing for a more extensive understanding of the interactions and functions of complex biological systems in livestock and veterinary science. It has tremendous potential to integrate multi-omics data with the support of vetinformatics resources for bridging the phenotype–genotype gap via computational modeling. To understand the dynamic behaviors of complex systems, computational models are frequently used. It facilitates a comprehensive understanding of how a host system defends itself against a pathogen attack or operates when the pathogen compromises the host’s immune system. In this context, various approaches, such as systems immunology, network pharmacology, vaccinology and immunoinformatics, can be employed to effectively investigate vaccines and drugs. By utilizing this approach, we can ensure the health of livestock. This is beneficial not only for animal welfare but also for human health and environmental well-being. Therefore, the current review offers a detailed summary of systems biology advancements utilized in veterinary sciences, demonstrating the potential of the holistic approach in disease epidemiology, animal welfare and productivity.
BACKGROUND: The veterinary care of cats and dogs is increasingly embracing innovations first applied to human health, including an increased emphasis on preventative care and precision medicine. Large scale human population biobanks have advanced research in these areas; however, few have been established in veterinary medicine. The MARS PETCARE BIOBANK™ (MPB) is a prospective study that aims to build a longitudinal bank of biological samples, with paired medical and lifestyle data, from 20,000 initially healthy cats and dogs (10,000 / species), recruited through veterinary hospitals over a ten-year period. Here, we describe the MPB protocol and discuss its potential as a platform to increase understanding of why and how diseases develop and how to advance personalised veterinary healthcare. METHODS: At regular intervals, extensive diet, health and lifestyle information, electronic medical records, clinicopathology and activity data are collected, genotypes, whole genome sequences and faecal metagenomes analysed, and blood, plasma, serum, and faecal samples stored for future research. DISCUSSION: Proposed areas for research include the early detection and progression of age-related disease, risk factors for common conditions, the influence of the microbiome on health and disease and, through genome wide association studies, the identification of candidate loci for disease associated genetic variants. Genomic data will be open access and research proposals for access to data and samples will be considered. Over the coming years, the MPB will provide the longitudinal data and systematically collected biological samples required to generate important insights into companion animal health, identifying biomarkers of disease, supporting earlier identification of risk, and enabling individually tailored interventions to manage disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-023-03691-4.
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.
OBJECTIVE: To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone‐iodine based protocols for surgical site infection (SSI) prevention in veterinary surgery. STUDY DESIGN: Systematic meta‐analytical review according to PRISMA‐P guidelines. SAMPLE POPULATION: Studies comparing preoperative skin asepsis protocols using chlorhexidine versus povidone‐iodine in veterinary surgery identified by systematic search between 1990 and 2020. METHODS: A search using MEDLINE/Pubmed, Web of Science and CAB Abstracts was performed, followed by secondary searches of Google Scholar, Proquest Dissertation and Theses, and relevant bibliographic articles. Primary and secondary outcome measures were the efficacy of skin asepsis protocols using chlorhexidine versus povidone‐iodine on SSI incidence and skin bacterial colonization, respectively. A meta‐analysis was performed with a random‐effect model, with effect size calculated as risk ratio (RR) or mean standard deviation (MSD) with 95% CI. Statistical significance was set at P < .05. RESULTS: Among 1067 publications that met the initial search criteria, 9 relevant studies were eligible for analysis. No difference in the incidence of postoperative SSI or skin bacterial colonization between preoperative asepsis protocols using chlorhexidine versus povidone‐iodine was found. Insufficient information and detail were frequent among studies and precluded a clear assessment of bias. CONCLUSION: This study showed that asepsis protocols using chlorhexidine were comparable to povidone‐iodine in preventing postoperative SSI and reducing skin bacterial colonization. CLINICAL SIGNIFICANCE: Given the limitations of the studies that were included in terms of both quality and quantity, more high‐quality randomized controlled trials are needed to confirm these conclusions.
International audience;
Passive surveillance is based on spontaneous reporting to veterinary authorities of disease suspicions by farmers and other stakeholders in animal production. Stakeholders are considered "actors" in sociology of organisations research. In veterinary public health, passive surveillance is considered to be the most effective method to detect disease outbreaks and to generate epidemiological information for decision-making on surveillance and control strategies. Nevertheless, under-reporting of cases is an inherent problem, reducing the ability of the system to rapidly detect infected animals. Previous studies have shown, for example, that passive surveillance for bovine brucellosis in France, through compulsory reporting of all bovine abortions, has limited sensitivity, with variability in reporting rates despite similar cattle farming profiles. Based on this observation and on sociological literature in health surveillance, we hypothesised that oversight organisational factors in different areas influence health actor contributions to passive surveillance. Therefore, to improve the efficiency of surveillance systems, we need to understand the organisational levers (supporting factors) and organisational drags (hindering factors) on the production and dissemination of health information. We conducted semi-structured interviews with the surveillance actors in two administrative geographic divisions in France (Departments A and B) with similar cattle farming profiles but contrasting abortion reporting rates (low and high, respectively). We assumed that these rates were related to health actor organisation in each administrative division. We mapped actor relationships and looked for behavioural recurrences and differences between the two departments. This analysis led to two socio-economic models explaining the configurations observed: pro-curative in Department A, and pro-preventive in Department B. These models showed a link between the level of competition endured by veterinarians on the sale of veterinary medicinal products and the overall contribution of the actors to health surveillance. The pro-preventive model had a higher contribution to surveillance than the pro-curative model. Importantly, the nature of the information produced in this configuration of actors corresponded to the needs of surveillance, providing collective and early information that circulated more readily between actors. We highlighted three characteristics that help to identify the configuration of a system of actors: 1) the pressure of competition exerted on veterinarian activities; 2) the dominant business model and form of organisation of veterinary clinics; and 3) the frequency of interactions between the main surveillance actors outside of crises. The first two characteristics affect the local contribution to data reporting for surveillance, and the third affects network responsiveness in a health crisis.
SIMPLE SUMMARY: In animals undergoing veterinary treatment, including therapeutic, quarantine and preventative medicine, their physiology and behaviour are derailed from their normal states and the animal’s choices and comfort are de facto limited. Traditional paradigms of animal welfare do not apply perfectly to animals under veterinary care, including quarantine and preventative medicine. A paradigm separating animal wellbeing from animal welfare is proposed in order to instil much needed clarity of thought and to guide actions in regard to the welfare of animals under human care. Using such a model, preventative medicine programs emerge as a cornerstone of zoo and aquarium animal welfare. Preventative medicine programs tailored to individual animals and organizations must weigh the expected benefits versus the risks inherent associated with veterinary procedures. As veterinary medicine and husbandry science continue to advance, preventative veterinary procedures can be carried out more safely and more frequently. The inclusion of operant conditioning to zoo veterinary practice allows the voluntary participation of the animals, thereby reducing the associated risks and costs. It also facilitates the collection of abundant and reliable physiological data, including the indicators of animal wellbeing, to help objectively evaluate the adequacy of the animal welfare. ABSTRACT: The overarching goal of a preventative medicine program is to minimize the chances of health problems developing and to maximize the chances of detecting health problems early, in a manner that best benefits the animals and the organization. The traditional paradigms of animal welfare, stemming from the five freedoms and being progressively fleshed out to five domains, the 24/7 approach and so forth do not apply perfectly to zoological collections and less so to animals undergoing veterinary treatments. The physiology and behaviour of animals undergoing veterinary treatments, including therapeutic, quarantine and preventative medicine, are derailed from their normal states and their choices and comfort are de facto limited. A paradigm separating animal wellbeing from animal welfare is necessary to instil clarity of thought and to guide actions in regard to the welfare of animals under human care. Using such a model, preventative medicine programs emerge as a cornerstone of zoo and aquarium animal welfare, all the more if it incorporates modern veterinary and husbandry techniques, including operant conditioning.
Background Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body’s cells’ alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process. Method AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-β, and TNF-α. Result It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-β and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced. Conclusion Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.
The English Bulldog has risen sharply in popularity over the past decade in the UK. However, its distinctive and extreme conformation has raised concerns because many of these physical features render the breed prone to serious health conditions. There are increasing international efforts to either reform the breed towards a more moderate conformation or, in the absence of such change, to ban the breeding of these dogs on welfare grounds. This VetCompass study explored random samples of anonymised veterinary clinical records from 2,662 English Bulldogs and 22,039 dogs that are not English Bulldogs from an overall population of 905,544 dogs under veterinary care during 2016 in the UK to identify all health disorders recorded for each dog during 2016. The most common disorders in each group were identified and the risks for the most common disorders overall was compared between the English Bulldogs and dogs that are not English Bulldogs. English Bulldogs were younger (2.65 years vs 4.42 years) and heavier (25.55kg vs 13.54kg) than dogs that are not English Bulldogs. English Bulldogs had 2.04 times the risk of diagnosis with at least one disorder during 2016 compared with dogs that are not English Bulldogs. English Bulldogs had increased risk for 24/43 (55.8%) disorders compared to dogs that are not English Bulldogs. The disorders with the highest risk in English Bulldogs included skin fold dermatitis (× 38.12), prolapsed nictitating membrane gland [cherry eye] (× 26.79), protruding lower jaw (× 24.32), brachycephalic obstructive airway syndrome [BOAS] (× 19.20) and interdigital cyst (× 12.96). Conversely, English Bulldogs had significantly reduced risk of 6/43 (14.0%) disorders compared to dogs that are not English Bulldogs. These included: retained deciduous [baby] tooth (× 0.02), lipoma [fatty mass] (× 0.06), dental disease (× 0.23), itchy skin (× 0.25) and flea infestation (× 0.40). The results of this study suggest that the overall health of the English Bulldog is much lower than dogs that are not English Bulldogs. Many of the disorder predispositions reported in this study are intrinsically related to the extreme conformation of English Bulldogs. Redefining the body-shape of the breed away from its current extreme conformation and towards a moderate conformation is advocated for urgent action to avoid the UK joining the growing list of countries where breeding of English Bulldogs is banned. Background The English Bulldog has risen sharply in popularity over the past decade but its distinctive and extreme conformation is linked to several serious health conditions. Using multivariable analysis of anonymised veterinary clinical data from the VetCompass Programme, this study compared the odds of common disorders between English Bulldogs and all remaining dogs in the UK during 2016. Results From 905,544 dogs under veterinary care during 2016, the analysis included a random sample of 2,662 English Bulldogs and 22,039 dogs that are not English Bulldogs. English Bulldogs had 2.04 times the odds of diagnosis with ≥ 1 disorder than dogs that are not English Bulldogs (95% confidence interval [CI] 1.85 to 2.25). At a specific-level of diagnostic precision, English Bulldogs had increased odds of 24/43 (55.8%) disorders. These included: skin fold dermatitis (odds ratio [OR] 38.12; 95% CI 26.86 to 54.10), prolapsed nictitating membrane gland (OR 26.79; 95% CI 18.61 to 38.58) and mandibular prognathism (OR 24.32; 95% CI 13.59 to 43.53). Conversely, English Bulldogs had significantly reduced odds of 6/43 (14.0%) disorders. These included: retained deciduous tooth (OR 0.02; 95% CI 0.01 to 0.17), lipoma (OR 0.06; 95% CI 0.01 to 0.40) and periodontal disease (OR 0.23; 95% CI 0.18 to 0.30). At a grouped-level of diagnostic precision, English Bulldogs had significantly increased odds of 17/34 (50.0%) disorders. These included: congenital disorder (OR 7.55; 95% CI 5.29 to 10.76), tail disorder (OR 6.01; 95% CI 3.91 to 9.24) and lower respiratory tract disorder (OR 5.50; 95% CI 4.11 to 7.35). Conversely, English Bulldogs had significantly reduced odds of 3/34 (8.8%) disorders. These were: dental disorder (OR 0.25; 95% CI 0.20 to 0.31), spinal cord disorder (OR 0.31; 95% CI 0.14 to 0.71) and appetite disorder (OR 0.43; 95% CI 0.20 to 0.91). Conclusions These results suggest that the health of English Bulldogs is substantially lower than dogs that are not English Bulldogs and that many predispositions in the breed are driven by the extreme conformation of these dogs. Consequently, immediate redefinition of the breed towards a moderate conformation is strongly advocated to avoid the UK joining the growing list of countries where breeding of English Bulldogs is banned.
SIMPLE SUMMARY: Research suggests that half of all veterinary clients fail to adhere to veterinarians’ dietary recommendations, which can lead to serious consequences for pet health. However, little is known about what clients’ resistance to such recommendations looks like in actual talk in veterinary consultations and how veterinarians respond. The present study aimed to fill this gap by using conversation analysis to investigate clients’ active resistance to veterinarians’ proposals for long-term changes to cats’ and dogs’ diets in 23 segments from 21 videotaped appointments in Ontario, Canada. Clients responded by suggesting that the proposals themselves or the nutritional modifications were potentially unnecessary, inappropriate, or unfeasible. Justifications were most frequently based on their pets’ food preferences, multi-pet feeding issues, their current use of equivalent health strategies, or their current enactment of the proposed changes. Thus, client resistance occurred when veterinarians did not first gather relevant diet- and patient-related information, solicit clients’ perspectives, or educate them about the benefits of the recommended changes before proposing them. Veterinarians subsequently accommodated clients’ resistance more often when barriers to adherence involved patient- or client-related issues rather than clients’ lack of medical knowledge. Findings provide valuable evidence for developing effective veterinary communication training and practice guidelines in nutritional assessment and shared decision-making. ABSTRACT: The impact of nutrition on animal health requires effective diet-related treatment recommendations in veterinary medicine. Despite low reported rates of veterinary clients’ adherence with dietary recommendations, little is known about how clients’ resistance to nutritional proposals is managed in the talk of veterinary consultations. This conversation-analytic study investigated clients’ active resistance to veterinarians’ proposals for long-term changes to cats’ and dogs’ diets in 23 segments from 21 videotaped appointments in Ontario, Canada. Clients’ accounts suggested the proposals themselves or nutritional modifications were unnecessary, inappropriate, or unfeasible, most often based on patients’ food preferences, multi-pet feeding issues, current use of equivalent strategies, or current enactment of the proposed changes. Resistance arose when veterinarians constructed proposals without first gathering relevant diet- and patient-related information, soliciting clients’ perspectives, or educating them about the benefits of recommended changes. Veterinarians subsequently accommodated clients’ concerns more often when resistance involved patient- or client-related issues rather than clients’ lack of medical knowledge. The design of subsequent proposals accepted by clients frequently replaced dietary changes in the initial proposals with nutritional or non-nutritional alternatives and oriented to uncertainty about adherence. This study provides evidence-based findings for developing effective communication training and practice guidelines in nutritional assessment and shared decision-making.
SIMPLE SUMMARY: Tumor histological grading systems are a tool widely used by human pathologists in oncology to support the assessment of tumor behavior and patient prognosis by clinical oncologists. In veterinary medicine, several tumor types already have a histological grading system used for these purposes, but some of these schemes lack reproducibility or correlation with clinical parameters, such as the correlation of the grade with survival time. This is the case for the grading systems proposed for canine bladder urothelial carcinoma. Over the years, some grading systems have been described for this type of tumor in dogs but without any routine use by pathologists and, consequently, without any application in clinical practice either. Based on this fact, the present study aimed to review the histological grading systems that exist in both human and veterinary medicine for bladder urothelial carcinoma, carrying out a critical analysis of their differences and thereby encouraging their real practical use and application in a relevant number of cases, prospectively. In this way, a histological grading system could be chosen or built from the existing ones and the knowledge about the behavior of this neoplasm in canine species could be improved, helping clinicians to establish a prognosis and personalized treatment for each patient with bladder urothelial carcinoma and also consider the predictive markers associated with treatment outcomes. ABSTRACT: The relationship between tumor morphology and clinical behavior is a key point in oncology. In this scenario, pathologists and clinicians play a pivotal role in the identification and testing of reliable grading systems based on standardized parameters to predict patient prognosis. Dogs with bladder urothelial carcinoma (BUC) were recently proposed as a “large animal” model for the study of human BUCs due to the similar morphology and metastasis locations. BUC grading systems are consolidated in human medicine, while in veterinary medicine, the BUC grading systems that have been proposed for canine tumors are not yet applied in routine diagnostics. These latter systems have been proposed, decade by decade, over the last thirty years, and the reason for their scarce application is mainly related to a lack of specific cutoff values and studies assessing their prognostic relevance. However, for any prognostic study, reliable grading is necessary. The aim of the present article was to give an overview of the BUC grading systems available in both human and veterinary pathology and provide an extensive description and a critical evaluation to support veterinary researchers in the choice of possible grading systems to apply in future studies on canine BUCs.
OBJECTIVE: To gather and evaluate validity evidence in the form of content and reliability of scores produced by 2 surgical skills assessment instruments, 1) a checklist, and 2) a modified form of the Objective Structured Assessment of Technical Skills (OSATS) global rating scale (GRS). STUDY DESIGN: Prospective randomized blinded study. SAMPLE POPULATION: Veterinary surgical skills educators (n =10) evaluated content validity. Scores from students in their third preclinical year of veterinary school (n = 16) were used to assess reliability. METHODS: Content validity was assessed using Lawshe's method to calculate the Content Validity Index (CVI) for the checklist and modified OSATS GRS. The importance and relevance of each item was determined in relation to skills needed to successfully perform supervised surgical procedures. The reliability of scores produced by both instruments was determined using generalizability (G) theory. RESULTS: Based on the results of the content validation, 39 of 40 checklist items were included. The 39‐item checklist CVI was 0.81. One of the 6 OSATS GRS items was included. The 1‐item GRS CVI was 0.80. The G‐coefficients for the 40‐item checklist and 6‐item GRS were 0.85 and 0.79, respectively. CONCLUSION: Content validity was very good for the 39‐item checklist and good for the 1‐item OSATS GRS. The reliability of scores from both instruments was acceptable for a moderate stakes examination. IMPACT: These results provide evidence to support the use of the checklist described and a modified 1‐item OSAT GRS in moderate stakes examinations when evaluating preclinical third‐year veterinary students' technical surgical skills on low‐fidelity models.
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.
SIMPLE SUMMARY: The arrival of the African swine fever (ASF) epizootic in the European continent has pushed public veterinary authorities to act immediately in order to contain its spread by applying the regulatory guidance of the current Animal Health Law of the European Union (Regulations EU 2016/429). Control and surveillance measures, in accordance with Regulations 2020/687 and 2023/594, have been implemented. Moreover, protection and surveillance areas have been created around the infected holdings and the wild boar cases. This paper analyzes the advantages and critical points of the legal framework for the control of ASF in wild boar, focusing on the role of official veterinary services in European Union Member States (EU MS). ABSTRACT: Recently, the African swine fever (ASF) epizootic has been reported in domestic pigs and wild boars in several European Union Member States (EU MS) and epidemiological evidence has accumulated which indicates that wild boar play a key role in maintaining and spreading the disease. Thanks to the experience gained when managing ASF outbreaks in Sardinia (Italy) and Eastern Europe, Directive 2002/60 CE was issued. This directive represented an important step forward in controlling the disease, particularly the risk of spreading the virus to wild animals. Since 2021, according to Regulation (EU) 2016/429, which is also called “Animal Health Law—AHL”, when the MS competent authority suspects or confirms ASF (a cat. A listed disease) in wild animals, it is mandatory to conduct surveillance in the wild boar population and implement the necessary control measures. Within AHL, Regulations (EU) 2020/687 and 2023/594 established special ASF control measures in kept and wild porcine animals, and their products and by-products, focusing on and underlying old and new responsibilities that vets (both public and private ones) have to accomplish under the new regulations. The new change in the legal framework deals with specific measures to be applied in the wild and represents a great challenge for MS veterinary services. Some of these measures have been well established in the last two decades, particularly those related to application in the farming system, while other measures are still new to veterinary health management and require a holistic approach in terms of intensity, considering all geographical, ecological, productive, cultural and social features of the involved EU MS. In this contribution, the authors intend to focus on specific measures which have been issued in order to limit or stop the spread of ASF in a wild, “boundless” ecosystem. These measures expand the field of competence of the official veterinary service to wild areas in addition to farm activity.
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.
Recently, with increasing interest in pet healthcare, the demand for
computer-aided diagnosis (CAD) systems in veterinary medicine has increased.
The development of veterinary CAD has stagnated due to a lack of sufficient
radiology data. To overcome the challenge, we propose a generative active
learning framework based on a variational autoencoder. This approach aims to
alleviate the scarcity of reliable data for CAD systems in veterinary medicine.
This study utilizes datasets comprising cardiomegaly radiograph data. After
removing annotations and standardizing images, we employed a framework for data
augmentation, which consists of a data generation phase and a query phase for
filtering the generated data. The experimental results revealed that as the
data generated through this framework was added to the training data of the
generative model, the frechet inception distance consistently decreased from
84.14 to 50.75 on the radiograph. Subsequently, when the generated data were
incorporated into the training of the classification model, the false positive
of the confusion matrix also improved from 0.16 to 0.66 on the radiograph. The
proposed framework has the potential to address the challenges of data scarcity
in medical CAD, contributing to its advancement.
International audience;
Public–private partnerships (PPPs) in the veterinary domain are joint approaches in which public veterinary services and private actors such as private veterinarians, producers' associations, or private companies work together to address complex animal health challenges. They are implemented worldwide and can help to strengthen the capacities of veterinary services, but few have been evaluated. None of the evaluations developed in the veterinary domain explicitly addressed PPPs, their complex program design, their evolving governance, and coordination system, and their impacts. This work represents the first application of the participatory impact pathway methodology for the evaluation of a PPP in the veterinary domain. The PPP evaluated aimed at developing the poultry sector in Ethiopia and improving poultry health service coverage, particularly in remote areas. The combination of semi-structured interviews ( n = 64) and collective reflection during three workshops ( n participants = 26, 48, 18), captured the viewpoints of public and private partners, actors who influenced the partnership, and actors impacted by it. The context of the PPP was analyzed, and the causal relationships between the PPP and its impacts were investigated. This work showed that collaboration between the public and private sector occurred at several administrative levels. The actors considered a variety of impacts, on the economy, business, trust, and health, which were then measured through different indicators. The actors also identified the added value of the PPP to enrich those impacts. The participatory impact pathway methodology helped to strengthen the engagement of actors in the PPP and to formulate recommendations at the policy level to favor positive results. This case study represents a milestone in building a participatory evaluation framework of PPP in the veterinary domain.
Pugs have become phenomenally popular in the UK over recent decades. The breed has a flat-faced look (brachycephalic) that many humans find highly attractive and ‘cute’ but this flat face is also linked to several serious health problems. Consequently, there is growing concern about the welfare issues associated with the popularity and health issues of Pugs. To get a better overall perspective on the health of Pugs, this study aimed to compare the risks of common disorders between Pugs and all remaining dogs. The study collected clinical information from first opinion veterinary practices in the UK that were participating in VetCompass. Dogs were grouped as either Pugs or non-Pugs. Information was gathered from the clinical records on all disorders diagnosed in each group during 2016 and a list of the most common disorders in each group was generated. From 905,544 dogs in the overall study, there were 16,218 (1.79%) Pugs and 889,326 (98.21%) non-Pugs. Pugs (2.36 years, interquartile range [IQR] 1.16–4.53) were generally younger than non-Pugs (4.44 years, IQR 1.90–8.12). Pugs (8.95 kg, IQR 7.80–10.17) were also generally lower in bodyweight than non-Pugs (14.07 kg, IQR 8.15–25.20). From a combined list of 40 common disorders among both groups of dogs, Pugs had increased risk for 23 (57.5%) but had reduced risk for 7 (17.5%) disorders compared to non-Pugs. The disorders with the highest relative risk in Pugs included brachycephalic obstructive airway syndrome (BOAS) (× 53.92 risk), narrowed nostrils (× 51.25), eye ulceration (× 13.01), and skin fold infection (× 10.98). Disorders with the lowest relative risk in Pugs included heart murmur (× 0.23), fatty lump (× 0.24), aggression (× 0.31), and wounds (× 0.53). The study provides a broad evidence base on the positive and negative aspects of the health of Pugs. Disease predispositions were more common than disease protections, confirming the hypothesis that there are many critical health-related welfare challenges to overcome for Pugs. The widely differing health profiles between Pugs and other dogs in the UK suggest that the Pug has now diverged to such an extent from mainstream dog breeds that it can no longer be considered as a typical dog from a health perspective. Background Pugs are a brachycephalic dog breed that has become phenomenally popular over recent decades. However, there is growing concern about serious health and welfare issues in the breed. To augment the evidence-base on the comparative health of Pugs, this study aimed to compare the odds of common disorders between Pugs and all remaining dogs under primary veterinary care in the UK during 2016. A cross-sectional study design of VetCompass clinical records was used to estimate the one-year (2016) period prevalence for the disorders most commonly diagnosed in Pugs and non-Pugs. Risk factor analysis applied multivariable logistic regression modelling methods to compare the odds of 40 common disorders between Pugs and non-Pugs. Results From a study population of 905,544 dogs, the analysis included random samples of 4308 Pugs and 21,835 non-Pugs. Pugs were younger (2.36 years, range 0.07–16.24 vs 4.44 years, range 0.01–20.46, p < 0.001) and lighter (8.95 kg, range 5.00–13.60 vs. 14.07 kg, range 1.41–85.00, p < 0.001) than non-Pugs. Pugs had 1.86 (95% confidence interval [CI] 1.72 to 2.01) times the adjusted odds of diagnosis with ≥1 disorder than non-Pugs. Pugs had significantly increased adjusted odds for 23/40 (57.5%) common disorders. These included: brachycephalic obstructive airway syndrome (odds ratio [OR] 53.92; 95% CI 36.22 to 80.28), stenotic nares (OR 51.25; 95% CI 24.93 to 105.37) and corneal ulceration (OR 13.01; 95% CI 10.50 to 16.11). Conversely, Pugs had significantly reduced adjusted odds of 7/40 (17.5%) common disorders compared to non-Pugs. These included: heart murmur (OR 0.23; 95% 0.13 to 0.14), lipoma (OR 0.24; 95% CI 0.11 to 0.55) and aggression (OR 0.31; 95% CI 0.21 to 0.47). Conclusions The current study highlights that predispositions outnumber protections between Pugs and non-Pugs for common disorders, suggesting some critical health welfare challenges to overcome for Pugs. Highly differing heath profiles between Pugs and other dogs in the UK suggest that the Pug has diverged substantially from mainstream dog breeds and can no longer be considered as a typical dog from a health perspective.
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.
The rise of antibiotic-resistant bacteria is among the biggest challenges in human and veterinary medicine. One of the major factors that contributes to resistance is use of frontline clinical antibiotics in veterinary practices. To avoid this problem, searching for antimicrobials aimed at veterinary applications is becoming especially important. Thiopeptide micrococcin P1 and leaderless peptide EntEJ97s are two different bacteriocins that are very active against many gram-positive bacteria; however, sensitive bacteria can rapidly develop resistance towards those bacteriocins. To overcome this problem, we searched for synergy between those bacteriocins and conventional antibiotics against methicillin-resistant Staphylococcus pseudintermedius (MRSP): a common pathogen in animal skin infections. The two bacteriocins acted synergistically with each other and with penicillin G against MRSP clinical isolates in both planktonic and biofilm assays; they also prevented resistance development. The therapeutic potential was further validated in a murine skin infection model that showed that a combination of micrococcin P1, EntEJ97s and penicillin G reduced cell-forming units of MRSP by 2-log(10) CFU/g. Taken together, our data show that a combination of bacteriocins with conventional antibiotics can not only prevent resistance development but also pave the way to revitalize some old, less useful antibiotics, such as penicillin, which by itself has no effect on methicillin-resistant pathogens.
OBJECTIVES: In veterinary settings, high exposures to animal allergens and microbial agents can be expected. However, occupational exposure levels are largely unknown. The objective of this study was to estimate the allergen, endotoxin, and β-(1,3)-glucan concentrations in small animal practices and in the homes of practice employees. METHODS: Dust samples were collected using electrostatic dust fall collectors in diverse rooms of 36 small animal practices, as well as in employees’ homes. Major animal allergens (Fel d 1, Can f 1, Ory c 3, Cav p 1, Equ c 1, Bos d 2), domestic mite (DM) allergens, and β-(1,3)-glucan levels were measured using enzyme immunoassays. Endotoxin was determined using the Limulus amoebocyte lysate assay. Influences on exposure levels were analyzed using multilevel models. RESULTS: The levels of Can f 1, Fel d 1, Ory c 3, and Cav p 1 were up to 30 times higher in practices compared with homes without animals, but significantly lower compared with the homes with the respective pet. Although horses were not treated in the practices, Equ c 1 was found in 87.5% of samples, with the highest concentrations measured in changing rooms. DM levels were significantly lower in practices than in all private homes, and endotoxin levels were similar to those in homes with pets. In the practice itself, exposure levels were significantly influenced by animal presence, type of the room, and area per employee; whereas, room volume and diverse cleaning measures had mostly no effect. CONCLUSIONS: Exposure to animal allergens is high in veterinary practices, but it does not reach levels of households with pets. Domestic mite allergen and endotoxin exposure seem to be low for workers in veterinary practices. The high Equ c 1 detection rate strongly indicates dispersal of allergens, most likely through clothing and hair.
Public Library of Science (PLoS)Dezember 2021Tierarzt
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.
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.
Background: Limited universally-adopted data standards in veterinary medicine hinder data interoperability and therefore integration and comparison; this ultimately impedes the application of existing information-based tools to support advancement in diagnostics, treatments, and precision medicine.
Objectives: A single, coherent, logic-based standard for documenting breed names in health, production, and research-related records will improve data use capabilities in veterinary and comparative medicine. Methods: The Vertebrate Breed Ontology (VBO) was created from breed names and related information compiled from the Food and Agriculture Organization of the United Nations, breed registries, communities, and experts, using manual and computational approaches. Each breed is represented by a VBO term that includes breed information and provenance as metadata. VBO terms are classified using description logic to allow computational applications and Artificial Intelligence-readiness.
Results: VBO is an open, community-driven ontology representing over 19,500 livestock and companion animal breed concepts covering 49 species. Breeds are classified based on community and expert conventions (e.g., cattle breed) and supported by relations to the breed's genus and species indicated by National Center for Biotechnology Information (NCBI) Taxonomy terms. Relationships between VBO terms (e.g., relating breeds to their foundation stock) provide additional context to support advanced data analytics. VBO term metadata includes synonyms, breed identifiers/codes, and attributed cross-references to other databases.
Conclusion and clinical importance: The adoption of VBO as a source of standard breed names in databases and veterinary electronic health records can enhance veterinary data interoperability and computability.
Background Multidrug resistance in companion animals poses significant risks to animal and human health. Prolonged antimicrobial drug (AMD) treatment in animals is a potential source of selection pressure for antimicrobial resistance (AMR) including in the gastrointestinal microbiota. We performed a prospective study of dogs treated for septic peritonitis, pyometra, or bacterial pneumonia and collected repeated fecal samples over 60 days. Bacterial cultures and direct molecular analyses of fecal samples were performed including targeted resistance gene profiling. Results Resistant Escherichia coli increased after 1 week of treatment (D1:21.4% vs. D7:67.9% P < 0.001) and returned to baseline proportions by D60 (D7:67.9% vs D60:42.9%, P = 0.04). Dogs with septic peritonitis were hospitalized significantly longer than those with pneumonia or pyometra. Based on genetic analysis, Simpson’s diversity index significantly decreased after 1 week of treatment (D1 to D7, P = 0.008), followed by a gradual increase to day 60 (D1 and D60, P = 0.4). Detection of CTX-M was associated with phenotypic resistance to third-generation cephalosporins in E. coli (OR 12.1, 3.3–68.0, P < 0.001). Lincosamide and macrolide-resistance genes were more frequently recovered on days 14 and 28 compared to day 1 ( P = 0.002 and P = 0.004 respectively). Conclusion AMR was associated with prescribed drugs but also developed against AMDs not administered during the study. Companion animals may be reservoirs of zoonotic multidrug resistant pathogens, suggesting that veterinary AMD stewardship and surveillance efforts should be prioritized. Graphical abstract
The emergence and spread of multidrug-resistant bacteria are a global concern. The lack of new antibiotics in the pipeline points to the need for developing new strategies. In this sense, gold(III) complexes (G3Cs) could be a promising alternative due to their recently described antibacterial activity. The aim of this study was to evaluate the antimicrobial activity of G3Cs alone and in combination with colistin against pathogenic bacteria from veterinary sources. Minimal inhibitory concentration (MIC) values were determined by broth microdilution and compared with clinically relevant antibiotics. Antibiofilm activity was determined by crystal violet staining. Combinations of selected G3Cs with colistin and cytotoxicity in commercial human cell lines were evaluated. Four and seven G3Cs showed antibacterial effect against Gram-negative and Gram-positive strains, respectively, with this activity being higher among Gram-positive strains. The G3Cs showed antibiofilm activity against Gram-negative species at concentrations similar or one to four folds higher than the corresponding MICs. Combination of G3Cs with colistin showed a potential synergistic antibacterial effect reducing concentrations and toxicity of both agents. The antimicrobial and antibiofilm activity, the synergistic effect when combined with colistin and the in vitro toxicity suggest that G3Cs would provide a new therapeutic alternative against multidrug-resistant bacteria from veterinary origin.
Respiratorische Medizin, Immuno-Allergologie und Dermatologie
25 wissenschaftliche Veröffentlichungen im Bereich Respiratorische Medizin, Immuno-Allergologie und Dermatologie
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John Wiley and Sons Inc.September 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Even though the prevalence of allergies is increasing, population‐based data are still scarce. As a read‐out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society. METHODS: More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross‐sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE‐profiles based on unsupervised clustering were correlated with data of the health survey. FINDINGS: 42.6% of the participants reported a physician‐diagnosed allergy and 44% were found to be IgE‐positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25–34 years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi‐sensitization to respiratory sources. INTERPRETATION: Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care.
John Wiley and Sons Inc.Oktober 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill‐defined. OBJECTIVES: To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases. METHODS: Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to n = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (n = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round. RESULTS: The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients. CONCLUSIONS: The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum.
Lippincott Williams & WilkinsDezember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: The proteolytic activities of house dust mite (HDM) allergens are involved in the pathogenesis of asthma by cleaving T-junction protein complexes, increasing the permeability of airway epithelial cells, and enabling the allergens to reach the interstitial tissue. The human body contains natural protease inhibitors such as alpha-1 antitrypsin (AAT) with antiserine protease activity and cystatin C with anticysteine protease activity. OBJECTIVE: This study aimed to investigate the behavior of serum AAT and cystatin C levels in patients with HDM-allergic asthma. METHODS: Ten individuals with HDM-allergic asthma and 10 healthy volunteers participated in a cross-sectional study. The serum AAT and cystatin C inhibitory activities were measured using enzymatic assays. ELISA was used to determine the serum AAT and cystatin C concentrations. RESULTS: Serum AAT inhibitory activity (P = 0.445; P > 0.05), AAT concentration (P = 0.290; P > 0.05), and cystatin C concentration (P = 0.419; P > 0.05) did not significantly differ between the patient and control groups. However, serum cystatin C inhibitory activity in the asthmatic patient group was significantly higher than in the healthy subjects (P = 0.001; P < 0.05). There was no correlation between AAT inhibitory activity and AAT concentration or between cystatin C inhibitory activity and cystatin C concentration. CONCLUSION: These findings suggest that serum cystatin C activity is involved in asthma pathogenesis. Additional research is required to address this issue.
World Allergy OrganizationDezember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses. OBJECTIVE: To assess the comorbidity burden and healthcare resource utilization (HRU) associated with non-response to H1AH-based treatments; to identify predictors of non-response. METHODS: Optum® de-identified Electronic Health Record dataset (2007–2020) was used to identify adult patients with CSU who initiated a H1AH, alone or in combination with other oral non-biologics (index treatment). Based on twelve-month treatment patterns observed after index treatment initiation, patients were categorized as responders (continued index treatment or had only 1 next H1AH treatment without corticosteroids) or non-responders (continued corticosteroids or had 2 or more treatment switches). Patient characteristics and HRU were assessed in the 12 months before (baseline) and ≥12 months after (follow-up) index treatment initiation. Baseline predictors associated with non-response were identified using machine learning. RESULTS: There were 17 062 patients who met inclusion criteria, and 14824 (86.9%) were classified as non-responders. A higher proportion of non-responders had records of CSU-related symptoms, comorbidities, polypharmacy, and certain laboratory tests than responders at baseline. A higher proportion of non-responders than responders visited an allergist or dermatologist during follow-up (59.5% vs 53.0%). Non-responders had a larger increase in hospitalizations (15.7% vs −2.4%) than responders during follow-up vs baseline. Predictors of non-response included index and baseline treatment classes, types of specialists seen, chronic pulmonary disease, depression, and female sex. CONCLUSION: A large proportion of CSU patients treated with H1AH-based therapies had uncontrolled disease, contributing to increased HRU and patient burden. Non-responders had more comorbidities and HRU at baseline and follow-up, with steep increases in follow-up hospitalizations relative to baseline, highlighting an urgent need for early disease control.
Termedia Publishing HouseSeptember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
The term ‘proactive therapy’ refers to a long-term management of clinically intact skin in previously disease-affected areas. This method was initially implemented in atopic dermatitis to maintain the remission and decrease the risk of exacerbations. Proactive therapy aims to limit the need for reactive treatment and improve the patients’ quality of life. A proactive approach is likely to be adopted for other relapsing and inflammatory skin conditions in the future. This scoping review aims to identify dermatological conditions to be treated with the proactive approach, evaluate the available evidence for its efficacy and safety, as well as highlight the research gaps.
DoveJuni 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
Acute and chronic cough are common symptoms in patients with severe allergic asthma. Although asthma-related cough can be controlled by asthma-specific medications, both prescription and over-the-counter antitussives are often also necessary. The anti-immunoglobulin E monoclonal antibody omalizumab is an effective treatment for patients with moderate-to-severe asthma, but little is known about subsequent antitussive use patterns. This post hoc analysis examined data from the Phase 3 EXTRA study that included patients aged 12–75 years with inadequately controlled moderate-to-severe asthma. Baseline antitussive use was low overall (16/427, 3.7% for omalizumab and 18/421, 4.3% for placebo). Among patients with no baseline antitussive use (n = 411 omalizumab, n = 403 placebo), most patients (88.3% omalizumab, 83.4% placebo) reported not using antitussives during the 48-week treatment period. The percentage of patients using 1 antitussive was lower for patients treated with omalizumab than placebo (7.1% vs 13.2%), although the adjusted rate of antitussive use during the treatment period was similar for omalizumab and placebo (0.22 and 0.25). Non-narcotics were used more often than narcotics. In conclusion, this analysis found low use of antitussives in patients with severe asthma and suggests that omalizumab may have the potential to decrease antitussive use.
Termedia Publishing HouseJanuar 2024Respiratorische Medizin, Immuno-Allergologie und 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.
World Allergy OrganizationAugust 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. METHODS: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients’ demographic and clinical characteristics were further analyzed depending on the severity of the reaction. RESULTS: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25–75] age: 42 [33–52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1–7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1–6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5–17.0); p = 0.011, OR (CI) = 10.3 (1.6–63.3)]. CONCLUSION: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.
John Wiley and Sons Inc.Dezember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5‐grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass‐induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS(0‐36). METHODS: The data of the European population that participated in 3 Phase III, international, randomized double‐blind placebo‐controlled clinical trials were analyzed post hoc. RESULTS: A total of 864 patients randomized to 300 IR 5‐grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS(0‐36) between the 300 IR and placebo groups was statistically significant (point estimates: −2.51, CI(95%) [−3.88; −1.14], p < 0.0001 in clinical trial1; −2.31, CI(95%) [−3.39; −1.23], p < 0.0001 in CT2; and −2.31, CI(95%) [−3.58; −1.03], p = 0.0004 in CT3). The relative differences between the 300 IR 5‐grass tablet and placebo were −29.7%, −33.8%, and −26.3%, respectively. The results based on CSMS(0‐36) were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2‐point threshold of the CSMS(0‐36) for clinical relevance of AIT. CONCLUSION: Post hoc analysis of 3 CTs with the 300 IR 5‐grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen‐induced ARC with or without controlled asthma.
Lippincott Williams & WilkinsMärz 2025Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: MP-AzeFlu (Dymista; Meda Pharma GmbH & Co., KG), a formulation combining azelastine hydrochloride and fluticasone propionate in a single spray, is superior to fluticasone propionate alone in relieving symptoms and improving the quality of life of patients with allergic rhinitis. OBJECTIVES: In this study, we evaluated whether the effect of AzeFlu, a generic drug manufactured from China, is equivalent to that of MP-AzeFlu. METHODS: In total, 679 patients were recruited for a multicentre, randomized, double-blind, original drug-controlled, and parallel-group clinical trial. Overall, 339 and 340 patients were administered with AzeFlu and MP-AzeFlu, respectively. Efficacy was assessed by changes in the reflective total nasal symptom score, the area under the curve of reflective total nasal symptom score changes over time, changes from baseline in individual nasal symptom scores, and the Rhinoconjunctivitis Quality of Life Questionnaire. In addition, a safety evaluation was simultaneously performed. RESULTS: AzeFlu and MP-AzeFlu reduced the reflective total nasal symptom score from baseline (AzeFlu −6.7 [standard deviation, 2.59]; MP-AzeFlu −6.7 [standard deviation, 2.76]; P = 0.905) and improved nasal symptoms and quality of life (AzeFlu −62.3 [standard deviation, 33.59]; MP-AzeFlu −64.7 [standard deviation, 33.73]; P = 0.394) in patients with allergic rhinitis. Significant differences were not observed between groups. CONCLUSION: AzeFlu showed effects equivalent to those of MP-AzeFlu in this clinical trial and may benefit Chinese patients with allergic rhinitis. Registration number: CTR20190189 (chinadrugtrials.org.cn/index.html)
John Wiley and Sons Inc.Februar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: The impact of non‐pharmacological interventions (NPIs) on asthma prevention and management is insufficiently examined. We aim to comprehensively evaluate and synthesize existing evidence regarding the effectiveness of various NPIs throughout the life course. METHODS: We conducted a systematic search and screening of reviews that examined the effectiveness of various NPIs on asthma prevention and control in the Cochrane Library, PubMed, Embase, and Ovid databases. Data extraction was performed by considering the type of NPIs and the life course stages of the target population. Recommendations were provided by considering the quality of review assessed using the AMSTAR2 tool and the consistency of findings across reviews. RESULTS: We identified 145 reviews and mapped the evidence on the impact of 25 subtypes of NPIs on asthma prevention and control based on five stages of life course. Reviews indicated a shift of focus and various impacts of major NPIs on asthma prevention and control across life courses, while a few types of NPIs, such as physical exercise, appeared to be beneficial in children, adolescents and adults. Consistent and high‐level evidence was observed only for psychological intervention on asthma control and quality of life among adults and older adults. Potential benefit with high‐level evidence was reported on certain NPIs, such as vitamin D in reducing risk of developing asthma in offsprings in the prenatal stage, digital health interventions in improving asthma control from childhood to older adulthood, and breathing exercise in improving quality of life, asthma‐related symptoms and lung function in adulthood and older adulthood. CONCLUSION: This study emphasizes the significance of delivering NPIs to improve asthma prevention and management and highlights the heterogeneity regarding the impact of NPIs across life courses. High‐quality research is urgently needed to further strengthen the evidence base of NPIs and tailored interventions should be considered in guideline development.
BioMed CentralJuli 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Maternal probiotic supplementation has a promising effect on atopic dermatitis (AD) prevention in infancy. In the randomised controlled study, Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT), maternal probiotics reduced the cumulative incidence of AD in their offspring by 40% at 2 years of age. However, our understanding on how probiotics prevented AD is still limited, and the role of inflammatory proteins in infants following maternal probiotic supplementation is unclear. We hypothesised that maternal probiotics lowered pro-inflammatory proteins and increased anti-inflammatory proteins in their 2-year-old children as a mechanism of AD prevention. We aimed to explore this hypothesis and the association between these proteins and the presence of AD, severity of AD, and the degree of preventive effect of probiotics. METHODS: Plasma samples were collected from 2-year-old children (n = 202) during the ProPACT study, a randomised placebo-controlled trial of maternal probiotic supplementation. These samples were analysed for 92 inflammatory proteins using a multiplex proximity extension assay. Associations between inflammatory proteins and the presence and severity of AD, and the degree of preventive effect, was estimated individually using regression analysis and then collectively using unsupervised cluster analysis. RESULTS: Several proteins were observed to differ between the groups. The probiotic group had lower CCL11 and IL-17C, while children with AD had higher IL-17C, MCP-4, uPA, and CD6. Cytokine CCL20 and IL-18 had moderate correlation (r = 0.35 and r = 0.46) with the severity of AD. The cluster analysis revealed that children in the cluster of samples with the highest value of immune checkpoint receptors and inflammatory suppressor enzymes showed the greatest AD preventive effect from probiotics. CONCLUSIONS: The proteins associated with both maternal probiotic supplementation and the presence and severity of AD warrant attention because of their potential biological relevance. Cluster analysis may provide a new insight when considering which subgroups benefit from probiotic supplementation. Larger studies are needed to confirm the results. Trial registration number: The study was retrospectively registered at ClinicalTrials.gov (NCT00159523) on 12nd September 2005. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12948-023-00186-3.
Termedia Publishing HouseJanuar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: Concerns are growing in the aviation industry about occupational skin diseases like malignant melanoma (MM) among airline pilots (APs), due to the unique working environment that exposes them to various skin stressors. AIM: To compare five skin biophysical parameters in a group of 40 male APs, each matched in terms of age and service tenure (minimum of 5 years) with a control group of 40 male office workers (OWs). Considering the potential role of dermokine (DMKN) in skin barrier dysfunction and the pathogenesis of MM, we further analyzed the serum levels of this molecule and correlated them with the measured skin parameters. MATERIAL AND METHODS: Stratum corneum skin hydration, transepidermal water loss (TEWL), sebum content, erythema index (EI), and melanin index (MI) were quantified by non-invasive instruments in the cheek region. Serum DMKN levels were measured using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Compared with OWs, the skin of APs exhibited a decrease in hydration levels in the stratum corneum, coinciding with a higher TEWL. However, there was no significant variance in sebum content between the groups. MI was notably higher in APs than in OWs, as was EI. In APs, serum DMKN levels were independently associated with MI (β = 0.56, p < 0.05). CONCLUSIONS: We found a significant link between the profession of an airline pilot and changes in skin biophysical parameters. Further research into the interplay between serum DMKN levels and the risk of MM in APs is warranted.
Termedia Publishing HouseJuli 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: Chronic wounds are an increasing problem for health care all over the world. New treatment options for this illness are desired, especially antimicrobial agents. Silver nanoparticles (AgNPs) can be a potential substance that may be used in treatment of chronic wounds due to the growing antibiotic resistance. AIM: To synthetize silver nanoparticles that are stable, pure and effective against bacteria. MATERIAL AND METHODS: The synthesis was conducted with chemical methods using different coating factors. The antistaphylococcal properties were analysed with the microdilution method to determine minimal inhibition concentrations (MIC) value. AgNPs were purified by dialysis. Moreover, keratinocyte cytotoxic properties of AgNPs were also assessed. RESULTS: A method of synthesizing stable and efficient AgNPs has been developed. The type of the coating substance has a significant effect on AgNPs antimicrobial properties. Most of the silver nanoparticles, synthesized based on literature data, turned out to be durable during a few hours. This study has proven that depending on the coating factor, AgNPs stability ranges from 4 weeks to even 12 months. Unfortunately, the type of the stabilizer used also affects the cytotoxicity of AgNPs. It has been shown that dialysis is a substance purification method that is cheap, simple and easy to apply when dealing with high volume solutions. CONCLUSIONS: AgNPs could be an alternative to widely used antibiotics and disinfectants. Nevertheless, the introduction of those substances to health care requires detailed long-term research not only in the field of safe use, yet also durability and purity of AgNPs solutions used.
DoveSeptember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders, common variable immunodeficiency disorder (CVID) and X-linked agammaglobulinemia (XLA) are PIDs related to B-cell defect, characterized by reduced levels of immunoglobulins and immune dysregulation. Infections are the most common clinical manifestations, while underlying autoimmune and inflammatory conditions are present in some patients with CVID and XLA, leading to clinical misdiagnosis and diagnostic delay. Chronic diarrhea in patients with CVID and XLA, particularly complicated malabsorption and protein-energy malnutrition, is responsible for poor prognostic outcomes. METHODS: In this study, we described three PID adult patients (two with CVID and one with XLA) who presented with varying degrees of chronic diarrhea, weight loss, and protein-energy malnutrition. We suggest that villous blunting of the small intestine under capsule endoscopy may be an endoscopic feature of PID-related enteropathy, thus highlighting the application of capsule endoscopy in patients with CVID and XLA presenting with chronic diarrhea. CONCLUSION: We also summarize regular Ig supplementation is the basic treatment for CVID and XLA patients, proper enteral nutrition and probiotic therapy can be explored to use to alter gut microbiota and modulate intestinal immune response. However, vedolizumab is not helpful to PID-related enteropathy therapy, as it exacerbates the inflammatory response in extra-intestinal organs and ultimately causes poor clinical outcomes.
BioMed CentralJanuar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
H. pylori is a gram-negative bacterium that is usually acquired in childhood and can persistently colonize the gastric mucosa of humans, affecting approximately half of the world’s population. In recent years, the prevalence of H. pylori infection has steadily reduced while the risk of allergic diseases has steadily climbed. As a result, epidemiological research indicates a strong negative association between the two. Moreover, numerous experimental studies have demonstrated that eradicating H. pylori increases the risk of allergic diseases. Hence, it is hypothesized that H. pylori infection may act as a safeguard against allergic diseases. The hygiene hypothesis, alterations in gut microbiota, the development of tolerogenic dendritic cells, and helper T cells could all be involved in H. pylori’s ability to protect against asthma. Furthermore, Studies on mice models have indicated that H. pylori and its extracts are crucial in the management of asthma. We reviewed the in-depth studies on the most recent developments in the relationship between H. pylori infection and allergic diseases, and we discussed potential mechanisms of the infection’s protective effect on asthma in terms of microbiota and immunity. We also investigated the prospect of the application of H. pylori and its related components in asthma, so as to provide a new perspective for the prevention or treatment of allergic diseases.
Termedia Publishing HouseJuli 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. AIM: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. MATERIAL AND METHODS: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques. RESULTS: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96). CONCLUSIONS: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.
BioMed CentralJanuar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Resource utilization and costs can impede proactive assessment and de-labeling of penicillin allergy among inpatients. METHODS: Our pilot intervention was a proactive penicillin allergy de-labeling program for new inpatients with penicillin allergy. Patients deemed appropriate for a challenge with a low-risk penicillin allergy history were administered 250 mg amoxicillin and monitored for 1 h. We performed an explorative economic evaluation using various healthcare professional wages. RESULTS: Over two separate 2-week periods between April 2021 and March 2022, we screened 126 new inpatients with a penicillin allergy. After exclusions, 55 were appropriate for formal assessment. 19 completed the oral challenge, and 12 were directly de-labeled, resulting in a number needed to screen of 4 and a number needed to assess of 1.8 to effectively de-label one patient. The assessor’s median time in the hospital per day de-labeling was 4h08 with a range of (0h05, 6h45). A single-site annual implementation would result in 715 penicillin allergy assessments with 403 patients de-labeled assuming 20,234 annual weekday admissions and an 8.9% penicillin allergy rate. Depending on the assessor used, the annual cost of administration would be between $21,476 ($53.29 per effectively de-labeled patient) for a pharmacy technician and $61,121 ($151.67 per effectively de-labeled patient) for a Nurse Practitioner or Physician Assistant. CONCLUSION: A proactive approach, including a direct oral challenge for low-risk in-patients with penicillin allergy, appears safe and feasible. Similar programs could be implemented at other institutions across Canada to increase access to allergy assessment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00864-6.
Termedia Publishing HouseJuli 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: Autologous serum therapy (AST) is considered a potentially curative therapeutic option in the treatment of chronic urticaria, especially in the autoreactive type. AIM: To determine the ratio of patients with a positive autologous serum skin test (ASST) in chronic urticaria and the efficacy of AST. MATERIAL AND METHODS: A total of 77 (29 male and 48 female) patients with chronic urticaria were enrolled in the study. The autologous serum skin test (ASST) was performed for all patients and the patients were classified into two groups: ASST positive and ASST negative. Intramuscular injection of AST was administered and the total severity score (TSS) of the urticaria was calculated weekly for ten weeks. The TSS was calculated for another ten weeks without AST. RESULTS: There were 34 patients (11 men and 23 women) in the positive group and 43 (18 men and 25 women) in the negative group. Reduction of symptoms of urticaria begins in the fourth week of the study in both groups. At week 20, 21 (61.7%) patients of the ASST (+) group and 12 (27.2%) patients of the ASST (–) group showed complete clearance. The use of antihistamines decreased from 100% at baseline in both groups to 8.82% and 25.58% in the ASST (+) and ASST (–) groups, respectively, at the end of the study. CONCLUSIONS: AST is a low-cost, cost-effective and potentially curative treatment with no adverse effects in these patients. It can reduce the burden of antihistamines.
DoveSeptember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
INTRODUCTION: Previous studies on the outcomes of asthma and COVID-19 have shown inconsistent results. This study aimed to elucidate the association between asthma and COVID-19 outcomes. METHODS: We conducted a prospective study with a large health plan to compare the incidence of COVID-19 infection, hospitalization and ICU admission in a cohort of 41,282 patients with asthma and a 1:1 age-, sex-, and race-ethnicity-matched cohort without asthma across the following pandemic periods: pre-Delta (03/01/2020 to 05/31/2021), Delta (06/01/2021 to 12/31/2021), and Omicron (01/01/2022 to 08/13/2022). Demographic factors, comorbidities, COVID-19 test results, inpatient utilization, and COVID-19 vaccination status were collected from electronic health records. RESULTS: Subjects with asthma were more likely than controls to undergo COVID-19 testing during the three pandemic periods and were less likely to test positive in the Omicron period (fully adjusted odds ratio=0.92; 95% CI=0.86–0.98; p=0.01). Relative to controls, patients with asthma had an increased risk of hospitalization for COVID-19 (fully adjusted hazard ratio=1.33; 95% CI=1.08–1.64; p=0.01) and borderline significant (p=0.05) higher rates of ICU admissions in the pre-delta period but not during the delta or Omicron periods. The increased risk of COVID-19 hospitalization associated with asthma was more pronounced in patients with severe asthma and in women compared with men. None of the associations were significantly modified by vaccination status. CONCLUSION: Asthma was associated with a lower risk of COVID-19 infection but only during the Omicron period. Asthma was an independent risk factor for hospitalization for COVID-19 in the pre-delta period and this association was stronger for severe asthma and in women.
John Wiley and Sons Inc.März 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: The incidence of atopic dermatitis (AD) in children is increasing. Early exposure to stress factors may be associated with the AD development. This study aimed to summarize studies that reported an association between stress exposure and AD development in later life. METHODS AND FINDINGS: A comprehensive literature search was performed using online databases (PubMed, EMBASE, PsycINFO, and Web of Science) for articles published up to May 1, 2023. Eligible studies were screened and selected based on the inclusion criteria. We incorporated cohort or case‐control studies published in English which explored the relationship between stress experienced by parents or children and AD. The pooled odds ratio (OR) was calculated according to the type of stress using a random‐effects model. Twenty‐two studies were included. AD was related to maternal distress (OR 1.29, 95% Confidence Interval [CI]: 1.13–1.47), maternal anxiety (OR 1.31, 95% CI: 1.18–1.46), and negative life events (OR 2.00, 95% CI: 1.46–2.76). Maternal depression during pregnancy was associated with AD (OR 1.21, 95% CI: 1.09–1.33), whereas no significant association was found for postpartum depression. Research on stress experienced by paternal or children is scare. CONCLUSIONS: Early maternal stress may potentially elevate the risk of AD in their offspring. Importantly, rigorously designed studies are required to corroborate the link between maternal stress and AD in children. These studies should aim to gather insights about the impact of stress during specific trimesters of pregnancy, postnatal stress, and paternal stress, and to identify potential prevention strategies.
PubMed CentralMärz 2026Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Influenza is a highly contagious viral disease that infects the epithelial cells of the upper and lower respiratory tract. Among circulating viruses, influenza A and B strains are responsible for the majority of clinically significant disease and seasonal epidemics. SUMMARY: The severity of influenza infection and the effectiveness of vaccination are largely determined by the magnitude and quality of the host immune response. Both innate and adaptive immune mechanisms contribute to viral clearance, recovery, and the establishment of protective immunity. Although vaccination remains the most effective strategy to reduce influenza-related disease burden, its efficacy varies due to viral evolution, host factors, and immune response variability. KEY MESSAGES: Ongoing surveillance of circulating influenza strains and continued advancements in vaccine design are essential for improving preventive strategies and protecting public health. Further research into novel vaccine approaches and immune mechanisms is critical to enhance vaccine efficacy, address vaccine hesitancy, and ultimately reduce influenza-associated morbidity and mortality.
John Wiley and Sons Inc.Januar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: The American Bashkir Curly Horse is frequently advertised to horse‐allergic riders and claimed to be a so‐called hypoallergenic breed that elicits fewer symptoms. Previous studies quantifying selected allergens in different breeds did not find a reduced allergen content in Curly Horses. Here, we provide a comprehensive proteomic analysis of horse hair extracts and a molecular analysis of the major allergen Equ c 1 with the aim of identifying differences in the Curly Horse breed that might explain their presumed reduced allergenic potential. METHODS: Horse hair extracts were prepared from Curly and American Quarter Horse breeds, separated by gender and castration status, extracts from other breeds served as controls. Extracts and native Equ c 1 (nEqu c 1) were analyzed by mass spectrometry. IgE‐binding capacities of nEqu c 1 and its recombinant variants were tested by ELISA using sera of patients sensitized to horses. Structures and ligand binding abilities were analyzed by computational modeling and fluorescence quenching assays. RESULTS: All known respiratory horse allergens are present in hair extracts of Curly and Quarter Horses and share identical allergen‐specific peptides. Lipocalin allergens are the most abundant proteins in horse hair extracts and contain several post‐translational modifications. We identified two new variants of Equ c 1 that have similar IgE‐binding capacities but show structural differences in their binding cavities and altered ligand binding behavior. There are no differences in IgE‐binding of Equ c 1 derived from Curly Horses compared to other horse breeds. CONCLUSION: Our data do not support the claim that Curly Horses are less allergenic than other breeds.
John Wiley and Sons Inc.Januar 2024Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen‐specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters. METHODS: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder‐dnfp (PTAH) and placebo in the double‐blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut‐specific and peanut component–specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes. RESULTS: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double‐blind placebo‐controlled food challenge (DBPCFC). In PTAH‐treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components. CONCLUSIONS: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder‐dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02635776.
BioMed CentralDezember 2023Respiratorische Medizin, Immuno-Allergologie und Dermatologie
BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. CASE PRESENTATION: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00859-3.
The impact of volcanic airborne products on airway epithelium homeostasis is largely unknown. This study assessed the effects of volcanic Fumarole Condensates (FC) alone or combined with Cigarette Smoke Extracts (CSE) on airway epithelial cells (16HBE and A549). Chemical composition of FC was analyzed by gas chromatography and HPLC. Cells were exposed to FC and IL-33 and IL-8 were assessed. The effects of FC and CSE on cell injury were evaluated assessing cell metabolism/cell viability, mitochondrial stress, cell apoptosis/cell necrosis, and cell proliferation. FC contained: water vapor (70–97%), CO_2 (3–30%), acid gases (H_2S, SO_2, HCl, HF) around 1%. FC increased the intracellular IL-33 but differently modulated IL-33 and IL-8 gene expression and IL-8 release in the tested cell lines. FC without/with CSE: (a) increased cell metabolism/cell viability in 16HBE, while decreased it in A549; (b) increased mitochondrial stress in both cell types. FC with CSE increased cell necrosis in A549 in comparison to CSE alone. CSE reduced cell proliferation in 16HB,E while increased it in A549 and FC counteracted these effects in both cell types. Overall, FC induce a pro-inflammatory profile associated to a metabolic reprogramming without a relevant toxicity also in presence of CSE in airway epithelial cells.
Merapi volcano is located on Java Island, Indonesia. It exhibits a typical subduction andesitic volcano morphology and activity: steep vegetated slopes with a volcanic activity of effusive viscous lava dome emplacement and growth alternating with explosive, sometimes very destructive events. Assessing the location, shape, thickness, and volume of viscous domes is crucial to evaluate the hazards associated with likely sudden pyroclastic density currents for the numerous surrounding crops, villages, and cities.In this thesis, we take advantage of the capabilities of radar and optical satellite images to track for surface changes at Merapi to better and safely quantify volcanic hazard.We use both high and medium resolution satellite images to follow the evolution of Merapi summit activity since 2017 up to the end of 2023, with a double target of improving the near-real time monitoring and the understanding of volcanic processes at stake.Two main methodological advances have been carried on to improve the monitoring of Merapi : first, a new and efficient tropospheric delay correction strategy for Sentinel-1 (radar) has been tested based on the local GNSS network, and compared with several commonly used tropospheric correction strategies (empirical, global weather models). Secondly, we showed the robust complementarity between high resolution on-demand TanDEM-X (radar) and Pléiades (optical) derived Digital Elevation Models (DEMs), thus allowing to fill the gaps in spatial and temporal information from their respective limitations.Regarding lava domes hazard assessment, 53 TanDEM-X and 11 Pléiades derived DEMs were produced over the summit area of Merapi, between July 2018 and September 2023. DEM differences with respect to a reference DEM from 2013 allowed to track for topographic changes. Uncertainties are quantified for each dataset over stable areas. Not only the DEMs derived from TanDEM-X show very good agreement with the DEMs calculated from Pleiades, but they are also very consistent with survey drone measurements made by the BPPTKG, in charge of monitoring the volcano. The dataset allows to quantitatively track lava volumes and effusion rates during the last two episodes of dome construction, in 2018-2019 and 2021-2023 respectively.We show that the 2018-2019 dome was hosted in the crater and reached a maximum volume of ~0.64 Mm3 in 5 months, before undergoing a phase of balanced lava supply and gravitational destabilization leading to no apparent change in volumes.We also show that the last eruption of 2021 was different from the prior in many aspects: an additional dome appeared on the southwest flank. Both the crater and flank domes show ~3 Mm3 volumes, which is ~3 times higher than in 2018-2019. Moreover, thanks to additional Sentinel-1 displacement timeseries and Pléiades horizontal image correlation timeseries, we show that prior to the 2021 lava domes, starting from summer 2020, several major changes occurred in the summit area, mainly on the western flank.First, we detected a rapid sliding of 3 blocks of several meters before November 2020, reaching 15 m by the end of 2023 (Pleiades). This process was going along a sliding of the entire western flank of about 15 cm in the Line of Sight (LOS) between August-December 2020, continuing up to 50 cm at least by the end of 2023 (Sentinel-1). Sentinel-1 also show a transient inflation on the eastern flank of 7 cm in the LOS between August-December 2020. Moreover, DEM differences displayed the removal of a southwest block in August 2020, creating a 50 m pit co-located with the 2021 flank dome. We interpret all these flank modifications, going from cm to m scale, as potential precursors of the 2021 lava domes eruption : we argue that the rising of shallow magma triggered the destabilization of the entire western flank. The creation of a pit to the south-west probably favored the exit of the lava at this point, allowing the growth of an external flank dome.
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Le volcan Mérapi est situé à Java, en Indonésie. Son activité volcanique est typique des stratovolcans andésitiques de subduction : elle se manifeste par la croissance de dômes de lave visqueuse, alternant avec des événements explosifs parfois très destructeurs. Il est crucial de déterminer la localisation et le volume de ces dômes pour évaluer les aléas associés aux nuées ardentes, susceptibles d'affecter les populations environnantes. Dans cette thèse, nous tirons parti des images satellites radar et optiques pour suivre les changements de surface du Mérapi. L'utilisation jointe d'images satellites à haute et moyenne résolutions a permis de suivre l'évolution de l'activité sommitale du Mérapi de 2018 à 2023, avec le double objectif d'améliorer la surveillance opérationnelle et de mieux comprendre les processus volcaniques en jeu.Deux avancées méthodologiques principales sont ici proposées pour améliorer la surveillance du Mérapi : premièrement, une nouvelle stratégie de correction des délais troposphériques pour Sentinel-1 (radar) a été testée en utilisant le réseau GNSS local, et comparée à d'autres stratégies existantes (empiriques, modèles météorologiques globaux). Deuxièmement, nous avons démontré la complémentarité robuste entre les Modèles Numériques de Terrain (MNT) dérivés des satellites haute résolution TanDEM-X (radar) et Pléiades (optique), permettant ainsi de dépasser leurs limitations respectives.Concernant l'évaluation de l'aléa volcanique lié à la croissance du dôme de lave, 53 MNT dérivés de TanDEM-X et 11 MNT dérivés de Pléiades ont été produits sur la zone sommitale du Merapi, entre 2018 et 2023. Les différences de MNT par rapport à un MNT de référence datant de 2013 ont permis de suivre les changements de topographie. Non seulement les MNT dérivés de TanDEM-X montrent un très bon accord avec les MNT calculés avec Pléiades, mais aussi avec les mesures de drone effectuées par le BPPTKG (observatoire du Mérapi). L'ensemble des données permet de suivre quantitativement les volumes de lave et les taux d'effusion pendant les deux derniers épisodes de construction de dômes, en 2018-2019 et 2021-2023.Nous montrons que le dôme de 2018-2019, situé à l'intérieur du cratère sommital, a atteint un volume maximum d'environ 0,64 Mm³ en 5 mois, avant d'entrer dans une phase d'équilibre entre l'apport de lave et la déstabilisation gravitationnelle, expliquant l'absence de changement apparent de volume. La dernière éruption de 2021 est différente de la précédente à bien des égards, avec l'apparition d'un autre dôme sur le flanc Sud-ouest. Le volume des dômes de cratère et de flanc a atteint ~3 Mm³, soit environ 3 fois plus qu'en 2018-2019. Grâce aux séries temporelles de déplacements Sentinel-1 et aux corrélations d'images Pléiades, nous montrons qu'à partir de l'été 2020, plusieurs changements majeurs ont eu lieu dans la zone sommitale, principalement sur le flanc Ouest. Tout d'abord, nous avons détecté un glissement rapide de 3 blocs sommitaux de plusieurs mètres avant novembre 2020, atteignant jusqu'à 15 m fin 2023. Ce processus a été accompagné d'un glissement de tout le flanc Ouest d'environ 15 cm dans la ligne de visée du satellite (LOS) entre août et décembre 2020, atteignant au moins 50 cm fin 2023. Sentinel-1 montre également une inflation transitoire sur le flanc Est de 7 cm dans la LOS entre août et décembre 2020. De plus, les différences de MNT ont montré la destruction d'un bloc au Sud-ouest en août 2020, créant un trou de 50 m coïncidant avec le dôme du flanc de 2021. Ces modifications de flancs, allant de l'échelle centimétrique à métrique, peuvent être interprétés comme des précurseurs potentiels de l'éruption des dômes de 2021 : l'ascension du magma superficiel a probablement déclenché la déstabilisation de tout le flanc Ouest. La création d'un déficit de topographie au Sud-ouest a probablement favorisé la sortie de lave à cet endroit, permettant ainsi la croissance d'un dôme externe sur le flanc.
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Mass controls two major processes in volcanic islands: large-scale collapse and vertical movements. Therefore, large islands like Hawaii are gradually subsiding and have undergone massive landsliding. What if the mass is much smaller, and there is good evidence that the vertical movement is more complex than simple loading-related subsidence? Here, we show that small volcanic islands, seemingly stable because of the small mass, can undergo sector collapses that can affect the vertical movement of the island. Santa Maria Island (Azores) is ca. 170 times smaller than Hawaii; however, it has collapsed more than once, as inferred from new onshore and marine geophysical data. From the vertical distribution of submarine and subaerial lavas, we can infer a complex subsidence and uplift history (seamount-island-seamount-island, meaning that Santa Maria has been an island twice), which is most likely the consequence of alternating volcanic construction (loading = subsidence) and large-scale destruction by sector collapse (unloading = uplift). Given the age difference between Santa Maria and the underlying oceanic crust, the island likely sits on several hundred meters of marine sediments that could behave as a weak layer (detachment) under shear. We evaluate the likely collapse mechanism by numerical modelling and conclude that small volcanic islands can collapse when both the edifice and its substrate are weak. The proximity of Santa Maria to the East Azores Fault, active during the volcanic lifetime of Santa Maria, may point to the trigger mechanism of the flank collapses. The inferred instability factor, a weak substrate, could be responsible for similar evolutions in other volcanic ocean islands sitting on sediments overlying the igneous oceanic crust.
We present X-ray observations of the upper atmospheric density disturbance
caused by the explosive eruption of the Hunga Tonga-Hunga Ha'apai (HTHH)
volcano on 15 January 2022. From 14 January to 16 January, the Chinese X-ray
astronomy satellite, Insight-HXMT, was observing the supernova remnant
Cassiopeia A. The X-ray data obtained during Earth's atmospheric occultations
allowed us to measure neutral densities in the altitude range of ~90-150 km.
The density profiles above 110 km altitude obtained before the major eruption
are in reasonable agreement with expectations by both GAIA and NRLMSIS 2.0
models. In contrast, after the HTHH eruption, a severe density depletion was
found up to ~1,000 km away from the epicenter, and a relatively weak depletion
extending up to ~7,000 km for over 8 hr after the eruption. In addition,
density profiles showed wavy structures with a typical length scale of either
~20 km (vertical) or ~1,000 km (horizontal). This may be caused by Lamb waves
or gravity waves triggered by the volcanic eruption.
;Comment: 14 pages, 4 figures, accepted for publication in Geophysical Research
Letters
The explosive volcanism of Petite-Terre (Mayotte, Comoros Archipelago, Western Indian Ocean) is the westernmost subaerial expression of a 60 km volcanic chain (the Eastern Mayotte Volcanic Chain, EMVC), whose eastern submarine tip has been the site of the 2018-2020 eruption of 6.5 km3 of magma giving birth to a new volcano, Fani Maoré. The scattered recent volcanic activity and the persistence of deep seismic activity along the volcanic chain require constraining the origin of past activity as a proxy for possible future volcanic activity on land as it highlighted the existence of significant volcanic hazards in an area long thought to be extinct.Through geomorphology, stratigraphy, grain size and componentry data we show that Petite-Terre tuff-rings and tuff-cones are likely formed by several closely spaced eruptions forming a monogenetic volcanic complex. The eruptive sequences are composed of few, relatively thin (cm-dm) coarse and lithic-rich pumice fallout layers containing abundant ballistic clasts, and fine-ash rich deposits mostly emplaced by dilute pyroclastic density current (PDCs).All deposits are dominated by juvenile clasts (pumice, dense clasts, and obsidian) and include non-juvenile clasts from older mafic scoria cones, coral reef and the volcanic shield of Mayotte as well as mantle xenoliths. We conclude that phonolitic magma ascended directly and rapidly from the mantle and first experienced a purely magmatic fragmentation at depth (> 1 km deep). The fragmented pyroclasts underwent a second shallower hydromagmatic fragmentation when they interacted with liquid water, producing fine ash and building the tuff-ring and tuff-cone morphologies.The location of Petite-Terre, at the intersection of the old (20 - 0.1 Ma) extinct shield volcanoes of Grande-Terre (Mayotte) and the currently active Eastern Mayotte Volcanic Chain raises the question of its affiliation to one or the other system. Using the petrological and geochemical characteristics of lava and pyroclastic samples from the subaerial volcanism of Petite-Terre, we investigate the link between the phonolites and basanites of Petite-Terre. Major and trace elements along with the peculiar mineralogy (fayalite-magnetite-alkali feldspar) show that Petite-Terre phonolites do not belong to any of the magmatic series defined on Grande-Terre but rather to the magmatic series of the EMVC. Petite-Terre basanites are similar to the ones found in the northern and north-east shield of Grande-Terre but might also represent parental magmas for Petite-Terre and EMVC phonolites, both series having be produced by similar partial melting degrees of a similar source, likely a metasomatized mantle.The presence of harzburgite xenoliths in the phonolites indicates that the phonolites evolved in the lithospheric mantle (Cpx-Opx thermobarometry: 400 MPa/ 1015 °C). Xenocrysts of Fe-rich biotite and amphibole along with syenitic xenoliths show that these hot phonolites (K-feldspar-melt thermometry: 950 °C) crossed the path of a more or less solidified syenitic lens (biotite- and amphibole-only thermobarometry, 200 - 400 MPa, 780 °C). These phonolites also evolved under very reducing conditions (∆NNO = - 2.3 log unit) which would explain their high iron content (up to 6 wt.%).These results show that the recent explosive phonolitic volcanism on Petite-Terre Island, and likely all the submarine volcanic chain east of Mayotte, is not related to the old shield activity that built Mayotte Island and is still potentially active. This recent volcanism takes place in a very dynamic system where most of the magmatic evolution happens at mantle depths (> 17 km) and can produce sub-plinian eruptions. It also shows that recent magmas erupting in the area can interact with melt lenses stored at shallower levels, potentially remobilizing them, with significant implications for the style and dynamics of possible eruptive scenarios.
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Le volcanisme explosif de Petite-Terre (Mayotte, archipel des Comores, océan Indien occidental) est l'expression subaérienne la plus occidentale d'une chaîne volcanique de 60 km (la chaîne volcanique orientale de Mayotte, EMVC), dont la pointe sous-marine orientale a été le site de l'éruption 2018-2020 de Fani Maoré. La répartition de l'activité volcanique récente et la persistance de l'activité sismique profonde le long de la chaîne volcanique nécessitent de contraindre l'origine de l'activité passée en vue d'une éventuelle activité volcanique future sur terre, la zone étant depuis longtemps considérée comme éteinte. Nous montrons que les anneaux de tuf de Petite-Terre ont probablement été formés par plusieurs éruptions formant un complexe volcanique monogénétique. Les séquences éruptives sont composées de niveaux relativement minces de retombées de ponces grossières et lithiques contenant des blocs balistiques, et de dépôts riches en cendres fines, principalement mis en place par des courants pyroclastiques dilués.Les dépôts sont dominés par des clastes juvéniles (ponce, clastes denses et obsidienne) et comprennent des clastes non juvéniles provenant de cônes de scories mafiques plus anciens et de corail ainsi que des fragments du manteau. Nous concluons que le magma phonolitique est monté directement et rapidement du manteau et a subi une fragmentation magmatique (> 1 km de profondeur). Les pyroclastes fragmentés ont subi une seconde fragmentation, moins profonde lorsqu'ils ont interagi avec de l'eau liquide, produisant des cendres fines et construisant les morphologies d'anneaux de tuff. La localisation de Petite-Terre, à l'intersection des anciens volcans boucliers éteints de Grande-Terre et de la chaîne volcanique orientale de Mayotte (EMVC) actuellement active, soulève la question de son appartenance à l'un ou l'autre système. Les éléments majeurs et traces ainsi que la minéralogie particulière (fayalite-magnétite-feldspath alcalin) montrent que les phonolites de Petite-Terre n'appartiennent à aucune des séries magmatiques définies sur l'ile Grande-Terre mais plutôt à la série magmatique de l'EMVC. Les basanites de Petite-Terre sont similaires à celles trouvées dans le bouclier nord et nord-est de la Grande-Terre et représentent des équivalents aux magmas parentaux des phonolites de Petite-Terre et de l'EMVC, les deux séries ayant été produites par un degré de fusion partielle similaire de la même source, probablement un manteau métasomatisé.La présence de xénolithes d'harzburgite dans les phonolites indique que les phonolites ont évolué dans le manteau lithosphérique (thermobarométrie Cpx-Opx : 400 MPa/ 1015 °C). Des xénocristaux de biotite et d'amphibole riches en Fe, ainsi que des xénolithes syénitiques, montrent que ces phonolites chaudes (thermométrie felspath-alcalin - liquide : 950 °C) ont croisé le chemin d'une lentille syénitique plus ou moins solidifiée (thermobarométrie biotite-seule et amphibole-seule, 200 - 400 MPa, 780 °C). Ces phonolites ont également évolué dans des conditions très réductrices (∆NNO = - 2,3 log unité), ce qui expliquerait leur teneur élevée en fer (jusqu'à 6 % en poids).Ces résultats montrent que le volcanisme phonolitique explosif récent de l'île de Petite-Terre, et probablement de toute la chaîne volcanique sous-marine à l'est de Mayotte, n'est pas lié à l'ancienne activité du bouclier qui a construit l'île de Mayotte et qui est encore potentiellement active. Ce volcanisme récent s'inscrit dans un système très dynamique où l'essentiel de l'évolution magmatique se produit à des profondeurs mantelliques (> 17 km) et peut produire des éruptions sub-pliniennes. Il montre également que les magmas entrant en éruption dans la région peuvent interagir avec les lentilles de liquide magmatique stockées à des niveaux moins profonds, en les remobilisant potentiellement, avec des implications significatives pour le style et la dynamique des scénarios éruptifs possibles.
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The characterisation of tephra deposits resulting from almost simultaneous sedimentation and wind remobilisation is complex, and multidisciplinary strategies are required in order to accurately constrain associated processes and eruptive parameters. We present a multifaceted study that aims to characterise the recent eruptive activity and the subsequent aeolian remobilisation of tephra deposits at Sabancaya volcano (Peru), which started erupting in November 2016 with frequent and relatively small explosions (plume heights <6 km above the vent). First, we estimated the bulk volume of tephra deposit produced between November 2016 and August 2018 at 0.04 ± 0.02 km 3 , and the dense rock equivalent (DRE) volume at 0.02 ± 0.01 km 3 . This corresponds to a tephra production rate of 1.1 ± 0.5 × 10 -3 km 3 DRE per month. Second, continuous sampling in a dedicated tephra collector network between April 2018 and November 2019 allowed estimation of the tephra volume at 2.3 ± 1.1 × 10 -5 km 3 DRE per month, indicating a significant decrease in the mass eruption rate since 2018. Third, by characterising the pulsatory activity through the repose interval between explosions and magma characteristics, Sabancaya's activity was classified as Vulcanian. Finally, aeolian remobilisation phenomena were studied using high-resolution videos, measurements of the airborne concentration of particulate matter with a diameter of ≤10 μm (PM 10 ) and particle physical characterisation. Subtle morphological differences are identified between remobilised particles and those in primary deposits, and we found that particles moving at ground level and above 1.5 m have grainsizes transportable by saltation and suspension, respectively.
Coronal pseudostreamer flux systems have a specific magnetic configuration
that influences the morphology and evolution of coronal mass ejections (CMEs)
from these regions. Here we continue the analysis of the Wyper et al. (2024,
ApJ 975, 168) magnetohydrodynamic simulation of a CME eruption from an
idealized pseudostreamer configuration through the construction of synthetic
remote-sensing and in-situ observational signatures. We examine the
pre-eruption and eruption signatures in extreme ultraviolet and white-light
from the low corona through the extended solar atmosphere. We calculate
synthetic observations corresponding to several Parker Solar Probe-like
trajectories at $\sim$10$R_\odot$ to highlight the fine-scale structure of the
CME eruption in synthetic WISPR imagery and the differences between the in-situ
plasma and field signatures of flank and central CME-encounter trajectories.
Finally, we conclude with a discussion of several aspects of our simulation
results in the context of interpretation and analysis of current and future
Parker Solar Probe data.
;Comment: 29 pages, 12 figures, 2 tables. Accepted for publication
International audience;
Discussions continue about whether Middle Eocene magmatism in the Eastern Pontides is associated with collision or subduction. This paper presents new whole-rock geochemistry, Sr-Nd isotopic and 40Ar-39Ar age data for Middle Eocene volcanic rocks from the Bayburt area of the Eastern Pontides (NE Turkey) to investigate their sources and evolutionary history. The new 40Ar–39Ar ages reveal that these volcanic rocks erupted between 44.6 ± 0.1 Ma and 43.5 ± 0.1 Ma, within the Lutetian (Middle Eocene). The studied volcanic rocks are composed of basalt, andesite, basaltic andesite and minor dacite lava and pyroclastic rocks. These rocks consist of plagioclase, amphibole, pyroxene, olivine, biotite, sanidine and minor quartz phenocrysts with Fe-Ti oxides. They have microlithic, hyalo-microlithic, porphyritic and rarely glomeroporphyritic textures. The volcanic rocks have low to high-K calc-alkaline affinities. They display enrichment in large-ion lithophile elements and depletion in high-field strength elements with high Th/Yb ratios, which indicate that the magmas forming the volcanic rocks were derived from lithospheric mantle sources enriched by mostly slab-derived fluids in the spinel stability field. 87Sr/86Sr(i) values vary between 0.70485 and 0.70551 and 143Nd/144Nd(i) values vary between 0.51255 and 0.51267. These data correspond to the mantle array on the isotope ratio diagram. The main solidification processes consist of fractional crystallization with minor assimilation. In light of the data obtained in this study together with data from previous studies, petrogenetic character of the Middle Eocene magmas from the southern parts of the Eastern Pontides may be explained by melting of an enriched lithospheric mantle source initially metasomatized by subduction fluids in a post-collisional extensional-related tectonic setting.
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Changes in the emission rate of volcanic sulphur dioxide (SO2) are crucial parameters for identifying volcanic unrest and forecasting the eruptive activity. Ground-based ultraviolet (UV) remote sensing provides a near continuous record of the SO2 emission rate, with Differential Optical Absorption Spectroscopy (DOAS) being the preferred method for quantifying SO2 absorption from recorded spectra. However, retrieving accurate column amounts of SO2 using DOAS requires a complex fitting procedure that relies on user expertise for selecting suitable fit parameters and visually inspecting the fit results. We explore an alternative approach that exploits the well-defined spatial frequencies present in sky-scattered UV spectra. We use wavelet coherence to compare UV spectra recorded with calibration cells of known SO2 concentration in the wavelength–spatial frequency plane. Our findings reveal that the Magnitude-Squared Wavelet Coherence (MSWC) is inversely proportional to the SO2 concentration, suggesting that this relationship could be used to quantify volcanic SO2 in natural spectra. To validate this approach, we analyze UV spectra recorded by scanning-DOAS instruments from the Network of Volcanic and Atmospheric Change (NOVAC) at Masaya volcano, Nicaragua, and Soufrière Hills volcano, Montserrat. We observe a favourable comparison between the MSWC values we calculate and the slant column densities (SCDs) of SO2 obtained using the DOAS and iFit algorithms, respectively. We demonstrate the MSWC to be a robust indicator of SO2 which may potentially serve as a proxy for differential SCDs of volcanic SO2. The straightforward computation of the wavelet coherence between spectra offers an efficient means to identify spectra which contain the signature of the volcanic plume and an objective approach to validate results obtained using traditional fitting routines.
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Rapid and simple estimation of the mass eruption rate (MER) from column height is essential for real-time volcanic hazard management and reconstruction of past explosive eruptions. Using 134 eruptive events from the new Independent Volcanic Eruption Source Parameter Archive (IVESPA, v1.0), we explore empirical MER-height relationships for four measures of column height: spreading level, sulfur dioxide height, and top height from direct observations and as reconstructed from deposits. These relationships show significant differences and highlight limitations of empirical models currently used in operational and research applications. The roles of atmospheric stratification, wind, and humidity remain challenging to detect acrossthe wide range of eruptive conditions spanned in IVESPA, ultimately resulting in empirical relationships outperforming analytical models that account for atmospheric conditions. This finding highlights challenges in constraining the MER-height relation using heterogeneous observations and empirical models, which reinforces the need for improved eruption source parameter data sets and physics-based models.
CCSD;University of Sydney Oceania PublishingJanuar 2025Vulkanologie
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This paper presents a detailed overview of archaeological research undertaken on Epi and Tongoa, in central Vanuatu. These islands were previously connected to one another and respectively formed the western and eastern portions of Kuwae, one of the largest islands in the Vanuatu archipelago, until the catastrophic Tombuk volcanic eruption separated them in the mid‐fifteenth century AD. Oral traditions and insights drawn from previous ethnographic, linguistic and genetic research provide context for the archaeological data. We begin to address questions about the extent to which impacts of the major Tombuk eruption were experienced across the entirety of the former Kuwae landmass, and the role of this and other volcanic events in the complex transformations of the physical and cultural landscapes of central Vanuatu.
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Cet article présente un résumé détaillé des recherches archéologiques conduites sur Epi et Tongoa, deux îles situées dans le centre du Vanuatu. Ces îles étaient autrefois reliées l'une à l'autre, formant les parties occidentale et orientale de Kuwae, l'une des plus grandes îles de l'archipel de Vanuatu, jusqu'à ce que l’éruption volcanique dite de Tombuk les sépare, au milieu du XVème siècle après J.‐C. Les traditions orales et les données issues de recherches ethnographiques, linguistiques et génétiques antérieures permettent de contextualiser ces données archéologiques. Nous nous interrogeons en particulier sur l’étendue de l'impact de cette éruption sur l'ancienne masse terrestre de Kuwae et sur l'influence qu'a eu cette éruption ainsi que d'autres événements volcaniques sur les transformations complexes des paysages physiques et culturels du centre de Vanuatu.
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The French Massif Central represents one of the rare occurrences in Europe where lower Pleistocene fossil deposits are associated to a substantial volcanic activity. Thanks to the abundance of volcanic zircons in the differentiated products of the Monts-Dore/Gu´ery stratovolcano, we were able for the first time to use U/Pb geochronology on zircon to precisely date lower Pleistocene fossil deposits. Zircon, a weathering-proof heavy mineral, was dispersed over the landscape through Plinian eruptions, and quickly reworked in fossil-bearing sedimentary deposits. Five Villafranchian fossil sites in the Upper Allier River valley (French Massif Central) have been precisely dated: Chilhac (MNQ17b, 2.285 ± 0.046 Ma), Mont Coupet (2.274 ± 0.032 Ma), Sen`eze (reference locality for MNQ18, 2.100 ± 0.029 Ma, confirming the previously determined 2.18–2.10 Ma 40Ar/39Ar ages), Blassac-La Girondie (MNQ19, 1.946 ± 0.029 Ma), and Vazeilles (1.843 ± 0.028 Ma). These new chronological data constrain the duration of the MNQ18 in central France to about 200 ka. The confirmation of an old age for the Blassac-La Girondie deposit indicates that the MNQ19 biozone started significantly earlier thanpreviously thought.
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Deformation bands in porous volcaniclastics are little studied structural heterogeneities despite their relevance for constraining the modalities of deformation development and related fluid-rock interactions in volcanic areas.We document a dense network of normal-sense Deformation Bands (Normal-sense Compactional Shear Bands (NCSBs) affecting upper Pliocene felsic glassy tuffites in Milos, Greece. NCSBs probably formed between 300 and 500 m of burial depth, in response to NE-SW directed extension which is related to volcanic rift development in the area. They accommodate mm-to m-shear-offsets, trend either N105 ± 10° or N070 ± 10°, and show mutual cross-cutting relations. The NCSB fault rock is made of ultracataclasite in which the cataclastic mechanisms have affected both the mineral fraction and the volcanic glass. Minerals are fractured along their cleavages whereas pumices are interestingly fractured along their vesicles.The development of chemical alteration (dissolution and cementation) essentially into the ultracataclasite is expressed through glass-hosted corrosion gulfs and smectites filling the intergranular porosity. These observations support that NCSBs preferentially retained water, have been the seat of greater fluid flow, and are the locus of ongoing phyllosilicate self-sealing in the vadose zone. A significant decrease (up to one order of magnitude) in porosity is measured within the studied NCSBs
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Porphyritic lava and mineral fragments include plagioclase, diopside, augite and enstatite, as well as magnesio-hornblende and ferri-tschermakite. Geothermobarometry based on clinopyroxene and amphibole reveal the dominant role of upper crustal magma reservoirs. Ferri-tschermakite from 93 and 167.5 mbsf (~410 and 856 ka, respectively) records contributions from lower crustal, hot magma reservoirs. These temperature estimates are supported by Ti-in-zircon data. O-isotope ratios and trace elements in zircon reflect magmatic activity typical for an evolved island arc system. The bathymetry of the Grenada basin, the composition of lava clasts and minerals, scarcity of altered lava fragments, the narrow maximum age population of detrital zircon, and the O-isotope and trace element data on zircon suggest that the majority of U1398B volcaniclastic turbidites originated from the island of Dominica. The thick volcaniclastic units are most likely related to major eruption periods of andesitic magma that ascended from crustal reservoirs. Debris avalanche-related processes seem to be less important in U1398B at ≤ 170 mbsf. Mineral chemistry and O-isotope data obtained from plagioclase, pyroxene, amphibole, zircon and glass, separated from deep marine volcaniclastic turbidites, provide a chronostratigraphic frame for the sedimentary succession, and helps to complete knowledge about the volcanic and magmatic evolution of the neighboring volcanic islands. While this is documented here for the well-constrained Pleistocene history of the central Lesser Antilles, the applied methods may also be used to characterize ancient marine volcaniclastic mass flow deposits and to reconstruct their volcanic source areas.
Sulfur is a volatile element that outgasses from magmas. Its role in volcanology and mantle geochemistry, therefore, needs to be assessed through primitive magmas, to exclude the influence of magma evolution process and degassing. In my thesis, the primary goal is to find these primitive magmas, and characterize their volatile element concentrations and sulfur isotopic compositions. My research covers two important processes of the sulfur cycle in a subduction zone. 1) First, the transport of material from the subducting plate (slab) to the mantle wedge, because the nature of the sulfur dissolved in the fluids escaping from the slab, as well as its speciation and sulfur isotopic composition, remain poorly constrained. 2) Second is the degassing of primitive magma during its ascent, prior to eruption at arc volcanoes, because this process is critical in understanding the observed global discrepancies between total sulfur masses discharged and dissolved sulfur in magmas estimated by petrology, commonly referred to as "excess degassing of sulfur". Melt inclusions of Aso volcano (Japan) allows to identify the primitive mafic magma responsible for the deep volatile element flux in a mature volcano, providing petrological constraints on (1) the depths of the magma reservoirs, as well as (2) the origin of the observed volcanic gases. In this study, I analyzed melt inclusions and phenocrysts of Holocene basaltic eruptions, and reported their concentrations of major and volatile elements. The samples showed clear evidences of magma mixing, such as reverse mineral zonation, and highly variable mineral and glass compositions. I found that the pre-eruptive storage depths were 2 km and 4 km below the edifice, for the Strombolian eruption and the sub-Plinian eruption, respectively. The most volatile-rich primitive magma, which is one of the magmas participating in the mixing, originates from a deeper level (>10 km). I determined the initial volatile element concentrations of the primitive magma: >4.68 wt% H2O, 400 - 750 ppm CO2, 3750 ppm S, 716 ppm Cl and 324 ppm F. I then studied melt inclusions trapped in olivines from nine volcanoes on Kyushu Island, Japan to understand the systematics of sulfur behavior in the primary magmas along this arc segment. I measured major, trace, and volatile elements as well as sulfur isotopes in olivine melt inclusions from tephra of Oninomi, Yufu, Kuju, and Aso, to southern Kyushu with Kirishima (2 cones), Sumiyoshi-ike, and Kaimon, and one back-arc volcano, Fukue. For each edifice, I identified the least degassed compositions and selected melt inclusions from the primary magma. Sr/Y ratios highlight a compositional dichotomy between volcanoes in northern Kyushu (Sr/Y>20) and southern Kyushu (Sr/Y<20), separated by the Kyushu-Palau ridge. Trace element systematics records a stronger slab melt signature, with residual garnet, in northern Kyushu. Two volcanoes, Fukue and Oninomi, lie outside these two groups and are interpreted as originating from a mantle wedge with weak slab inputs. The δ34S in melt inclusions range from -0.32±0.79 ‰ to +9.43±0.47 ‰ (2σ) and trace the source of magma from the different volcanoes, rather than degassing or crustal fractionation processes. The δ34S variation is not controlled by the nature of the fluid (aqueous or silicate liquid) metasomatizing the mantle wedge. Rather, this study highlights the need for a component with a high δ34S, such as seawater sulfates in the agent metasomatizing the mantle wedge.
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Le soufre est un élément volatile qui dégaze des magmas. Son rôle en volcanologie et en géochimie du manteau doit donc être évalué à partir des magmas primitifs pour exclure l'influence du processus d'évolution du magma et du dégazage. Dans ma thèse, l'objectif principal est de trouver les magmas primitifs, et de caractériser leurs concentrations en éléments volatils et leurs compositions isotopiques en soufre. Mes recherches portent sur deux processus importants du cycle du soufre dans une zone de subduction. 1) Le premier est le transport de matériel de la plaque plongeante vers le coin mantellique, car la nature du soufre dissout dans les fluides s'échappant de cette dernière, ainsi que sa spéciation et sa composition isotopique, restent mal connues. 2) Le second est le dégazage du magma primitif au cours de son ascension, avant l'éruption au niveau des volcans d’arc, car ce processus est essentiel pour comprendre les écarts mondiaux observés entre les masses totales de soufre évacuées et le soufre dissout dans les magmas estimés par la pétrologie, communément appelé "excès de soufre dégazé".Les inclusions magmatiques du volcan Aso (Japon) permettent d'identifier le magma mafique primitif responsable du flux profond d'éléments volatils dans ce volcan mature, fournissant des contraintes pétrologiques sur (1) les profondeurs des réservoirs magmatiques, ainsi que sur (2) l'origine des gaz volcaniques observés. Dans cette étude, j'ai analysé des inclusions magmatiques et des phénocristaux provenant d'éruptions basaltiques holocènes, et j'ai rapporté leurs concentrations en éléments majeurs et volatils. Les échantillons présentaient des signes évidents de mélange magmatique, comme une zonation minérale inversée, et des compositions minérales et vitreuses très variables. J'ai déterminé des profondeurs de stockage pré-éruptif de 2 km et 4 km sous l'édifice, pour l'éruption strombolienne et l'éruption sub-plinienne, respectivement. Le magma primitif le plus riche en éléments volatils, qui est l'un des magmas participant au mélange, provient d'un niveau plus profond (>10 km). J'ai déterminé les concentrations initiales en éléments volatils du magma primitif : >4,68 % en poids de H2O, 400 - 750 ppm de CO2, 3750 ppm de S, 716 ppm de Cl et 324 ppm de F.J'ai ensuite étudié les inclusions magmatiques piégées dans les olivines de neuf volcans de l'île de Kyushu, au Japon, afin de comprendre la systématique du comportement du soufre dans les magmas primaires le long de ce segment d'arc. J'ai mesuré les éléments majeurs, traces et volatils ainsi que les isotopes du soufre dans les inclusions magmatiques d'olivines provenant des téphras d'Oninomi, Yufu, Kuju et Aso, du sud de Kyushu avec Kirishima (2 cônes), Sumiyoshi-ike et Kaimon, et d'un volcan de l'arrière-arc, Fukue. Pour chaque édifice, j'ai identifié les compositions les moins dégazées et sélectionné les inclusions magmatiques du magma primaire. Les rapports Sr/Y mettent en évidence une dichotomie de composition entre les volcans du nord de Kyushu (Sr/Y>20) et du sud de Kyushu (Sr/Y<20), séparés par la crête Kyushu-Palau. La systématique des éléments traces enregistre une signature de fusion de la plaque plongeante plus forte, avec du grenat résiduel, dans le nord de Kyushu. Deux volcans, Fukue et Oninomi, se situent à l'extérieur de ces deux groupes et sont interprétés comme provenant d'un coin mantellique avec de faibles apports de la plaque plongeante. Les δ34S dans les inclusions de fusion varient de -0,32±0,79 ‰ à +9,43±0,47 ‰ (2σ) et retracent la source du magma des différents volcans, plutôt que des processus de dégazage ou de fractionnement crustal. La variation du δ34S n'est pas contrôlée par la nature du fluide (aqueux ou liquide silicaté) métasomatisant le coin mantellique. Cette étude met plutôt en évidence la nécessité d'un composant avec un δ34S élevé, comme les sulfates d'eau de mer, dans l'agent métasomatisant le coin mantellique.
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We analyze the volcanic plume from the April 2015 Calbuco eruption over a 35‐day period using simulations from Meso‐NH, a non‐hydrostatic mesoscale atmospheric model. A dedicated parameterization of the deep injection of the plume into the stratosphere ensures a realistic representation when compared to Infrared Atmospheric Sounding Interferometer satellite observations. During the first 12 hr of the eruption, on 22 April 2015, SO 2 mixing ratio reached 29 ppmv between 15 and 18 km for the first eruption pulse, and 38 ppmv between 12 and 16 km for the second. Most SO 2 was injected directly into the stratosphere, with a stratospheric load reaching 308 ktS (kilotons of atomic sulfur, i.e. 616 kilotons of SO 2 ) after the eruption. After 1 month, both stratospheric and tropospheric SO 2 loads returned to near‐background levels. During analysis, the chemical conversion of SO 2 into H 2 SO 4 removed a part of SO 2 from the stratosphere. During the long‐range advection, the co‐location between the subtropical jet stream and the Calbuco plume led to three significant stratospheric intrusions on 24, 26 and 28 April 2015. These events transferred stratospheric SO 2 into the troposphere, SO 2 mixing ratios in the upper troposphere reaching 15 ppmv, 26 and 15 ppbv, respectively. SO 2 is gradually oxidized into H 2 SO 4 , with up to 5 ktS of gaseous H 2 SO 4 in the stratosphere on 30 April, but dynamical processes dominate the SO 2 atmospheric budget over chemical transformations. This study demonstrates that stratospheric intrusions can play a critical role in the removal of volcanic material from the stratosphere following a major eruption.
International audience;
We estimated the subsidence rate of the lava flow formed during the 2012–2013 eruption of Tolbachik volcano from satellite radar interferometry with using Sentinel-1 satellite images between 2017 and 2019. The maximum subsidence values were 285 mm/yr in 2017, 249 mm/yr in 2018, and 261 mm/yr in 2019. The subsidence rate increases with the flow thickness. This trend is observed for most of locations except a small area in the vicinity of the active vent where the subsidence is anomalously high. We show that the main observed trend can be well explained by a thermal compaction with a 1D mathematical model that takes into account the latent heat of crystallization, temperature dependences of physical parameters (heat capacity, thermal conductivity, density), temperature dependence of crystal concentration in the melt volume, and the percentage of uncrystallized material (glass or melt), porosity and lava layer formation rate. The much faster subsidence rates observed close to the vent can be explained by contraction of buried lava tubes that is not accounted in the thermal model.
Cette thèse est sous embargo jusqu’au 04/02/2025.;
Landscape evolution on volcanic islands is driven by complex interactions between volcano growth and destruction by a variety of processes (explosive eruptions, landslides, riverine erosion, weathering). Major climate changes, may impact the dynamics of degradation processes at different spatial and temporal scales. For example, extreme rain can produce an immediate hydrological response causing important destruction. Changes in weathering rates, sensitive to precipitation and temperature, can trigger changes in soil fertility but also modify global carbon cycling.The Azores volcanic islands provide an ideal setting to study these interactions, with both scientific and societal significance, especially in the context of ongoing global warming. Located in the Central North Atlantic, they are under the influence of major climatic drivers. Most of them had pulses of volcanic activity over the past 1 Myr, a period characterized by high-amplitude glacial-interglacial transitions with major climatic changes. While global climatic variations have been relatively well-studied for this period, reconstructing the atmospheric paleoclimate and its effects at local/regional scales remains challenging. Paleosols (PSs) are fossil soils formed by weathering at surface, and later incorporated into the geological record. Their geochemistry provides valuable insights into past environmental conditions, while the geochronology of volcanic products “bracketing” PSs allows their temporal constraint.In this work, we reconstructed mean annual precipitations (MAP) and air temperature (MAAT) over the last 1 Myr in the Azores region through a combined geochemical-geochronological study of PSs. Two proxies based on PSs’ major element were used: the weathering index (CIA-K) and the Clayeyness, both validated in other volcanic settings. The precise dating of volcanic units by either unspiked K-Ar on lava flow groundmass separates or ⁴⁰Ar/³⁹Ar on single K-feldspar of trachytic fallout evidence “pulses” of soil-formation within only a few kyr. This occurred especially after glacial terminations (MIS 21, 19, 11, 9e, 5e and 1), under wet and warm conditions. Fast paleoenvironmental changes were recorded in PSs’ geochemistry, and MAAT reconstructions (12-28 ᵒC) agree with previously published Sea Surface Temperatures, pointing to a tight ocean-atmosphere teleconnection. Those “pulses” suggest sustained weakening phases for the Azores High, allowing humid air currents (Westerlies) to reach further to the south.Our data also show contrasted rates of vertical soil development (3-180 mm/kyr). Weathering was favored by the structure and texture of parental materials, as PSs formed under lower MAP in pyroclastic deposits than in lava flows (~500 and ~800 mm/yr thresholds). This highlights the influence of fragmentation on weathering’s kinetics due to higher specific surface area. Enhanced weathering at surface and along geological discontinuities may have promoted mechanical weakening, favoring erosion and landslides. Notably, high MAPs (up to 1500 mm/yr) obtained around the Eemian interglacial stage are coincident in time with the initiation of a large slide complex on the southern flank of Pico. Intense precipitation may have led to increased water infiltration favoring enhanced hydromagmatic interactions. Drastic increase in pore pressure may then have triggered the initiation of the flank movement along listric faults that are still active. Current conditions in the Azores are wetter and slightly warmer than during the last Myr. Increased infiltration along faults could partly control subsequent movement and yield to detachment of the outer flank of Pico, with potentially dramatic consequences.More generally, present temperature and humidity increase on volcanic islands points to intense weathering, resulting in fast landscape evolution, increased lixiviation and elementary export and high atmospheric CO₂ uptaking, with local, regional and global impacts.
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L'évolution des îles volcaniques résulte d'interactions complexes entre croissance des volcans et processus de destruction (éruptions explosives, glissements de terrain, érosion fluviale, altération). Les changements climatiques peuvent influencer ces processus sur des échelles variées. A l’échelle événementielle, des précipitations intenses peuvent engendrer des épisodes érosifs extrêmes. Sur le long-terme, des variations des taux d'altération, sensibles aux précipitations et à la température, peuvent impacter la fertilité des sols et le cycle global du carbone.Les îles volcaniques des Açores offrent un cadre idéal pour étudier ces interactions, avec une grande importance scientifique et sociétal, en particulier dans le contexte actuel du réchauffement climatique. Au centre de l'Atlantique Nord, elles sont influencées par des facteurs climatiques majeurs. Ces îles ont eu des pulses d'activité volcanique au cours du dernier million d'années (Ma), une période marquée par d’importants changements climatiques liés aux cycles glaciaires-interglaciaires. Si les variations des conditions globales ont été bien documentées sur cette période, la reconstruction paléoclimatique aux échelles locales/régionales reste un défi. Les paléosols (PSs) sont des anciens sols inclus dans le registre géologique. Leur géochimie fournit des informations précieuses sur les conditions paléo-environnementales, et la géochronologie des produits volcaniques les encadrant permet leur contrainte temporelle.Dans ce travail, nous avons reconstruit les conditions moyennes annuelles de précipitation (MAP) et de température de l’air (MAAT) aux Açores au cours du dernier Ma. Deux proxies basés sur la composition en éléments majeurs des PSs ont été utilisés : l’indice d'altération CIA-K et l’argilosité, tous deux validés dans d'autres milieux volcaniques. La datation précise des unités volcaniques par K-Ar sur mésostase séparée (laves) et par ⁴⁰Ar/³⁹Ar sur monocristaux de feldspath potassique (dépôts pyroclastiques), révèle des «pulses» d‘altération sur quelques milliers d’années, notamment après les terminaisons glaciaires (MIS 21, 19, 11, 9e, 5e et 1). La géochimie des PSs montre des changements environnementaux rapides et des MAATs (12-28 ᵒC) en accord avec les données de température marine de surface établies à partir d’archives océaniques. Cette concordance indique une étroite relation océan-atmosphère. Ces «pulses» suggèrent en outre des phases d'affaiblissement de l'anticyclone des Açores, permettant aux courants d'air humides d'atteindre des secteurs plus au sud.Les taux moyens de formation des sols (3-180 mm/kyr) ont été influencés par la structure et la texture du substrat rocheux. Des PSs se sont formés lors de MAPs plus faibles dans les dépôts pyroclastiques que dans les coulées de lave (seuils de ~500 et ~800 mm/an). Cette différence supporte une cinétique favorisée par la fragmentation et une surface spécifique élevée. L’altération accrue en surface et le long des discontinuités géologiques de sub-surface peut avoir favorisé l'érosion par glissements de terrain. Des MAPs élevées (jusqu'à 1500 mm/an) sont notamment obtenues autour du stade interglaciaire de l’Eemien, qui coïncide avec l’initiation d’un glissement complexe sur le flanc Sud de Pico. Des MAPs intenses ont pu accélérer l’infiltration des eaux et favoriser les interactions hydromagmatiques. L’augmentation associée de pression interstitielle a ainsi pu déclencher la mise en mouvement du flanc le long de failles listriques toujours actives. Les conditions actuelles aux Açores sont plus humides et légèrement plus chaudes qu’au cours du dernier Ma, ce que pourrait favoriser le détachement du flanc externe de Pico, avec des conséquences potentiellement drastiques.Plus généralement, l’altération accrue favorise l’évolution rapide du paysage sur de telles îles et engendre des flux élémentaires et une absorption de CO₂ atmosphérique croissantes, ce qui a impacts locaux, régionaux et globaux.
CCSD;Geological Society of AmericaJanuar 2022Vulkanologie
International audience;
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.
International audience;
This work investigates the relationships between partial melting, melt extraction, pluton growth and silicic volcanism in garnet-bearing felsic volcanic rocks that were extruded in the Iberian Pyrite Belt, at ca. 345 Ma. The garnets are of peritectic origin, displaying textural and chemical features of disequilibrium crystallization during partial melting reactions involving biotite at high temperatures (up to 870 °C) in the middle-lower crust. Major element composition suggests compositional equilibrium with the entrained and pinitized peritectic cordierite, but reveals some subsequent homogenization by diffusion. Trace element maps and spot analyses of garnet show, nonetheless, significant trace element variations, reflecting biotite and Y-REE-P-rich accessory phase breakdown during partial melting reactions. Peritectic garnet and cordierite growth resulted in the preservation of Th- and Y-rich prograde suprasolidus monazite, which constrains the timing of partial melting of the metapelitic protolith at ca. 356.8 ± 2.4 Ma. The zircon cargo further shows that a significant amount of zircon crystals from previously crystallized felsic melts were also remobilized and erupted. These were likely stored in an upper crustal pluton that grew episodically since ca. 390 Ma during voluminous melt generation periods within the middle to lower crust, which also resulted in voluminous volcanism. The geochemical trends of the felsic volcanic rocks reflect the entrainment of xenoliths of peritectic garnet, cordierite and feldspar, and as such, the garnet-bearing felsic volcanic rocks represent an erupted mixture of a lower-temperature (ca. 770 °C) silicic melt and autocrysts, and peritectic phases and zircon crystals from previously crystallized and stored felsic melts.
CCSD;AGU and the Geochemical SocietyApril 2026Vulkanologie
International audience;
Abstract Many intraplate volcanic chains are explained as hotspot trails formed by plate motion over mantle plumes, yet some deviate from this model. The Rodrigues Ridge, a volcanic lineament extending eastward from the Réunion hotspot track toward the Central Indian Ridge (CIR), is one such case. To assess its origin, we integrated field studies with zircon U‐Pb and (U‐Th)/He geo‐/thermochronology, groundmass K‐Ar dating, and major and trace element analyses of volcanic rocks from Rodrigues Island. Our results reveal that Rodrigues Island experienced a prolonged subaerial volcanic history from 4.1 to 1.1 Ma, 2.7 million years longer than previously thought. This history shows two episodes of volcanic construction: (a) a circular volcano construction between 4.1 and 2.5 Ma, followed by erosion, subsidence, and coral reef development and (b) fissural volcanism from 2.3 to 1.1 Ma, which shaped the island's elongated morphology. Subaerial lavas are more alkalic and enriched in incompatible elements than older submarine ridge lavas. This geochemical evolution suggests an eastward migration of partial melting, with oceanic accretion driving magmatism along the Rodrigues Ridge. Combined with magnetic anomalies of the oceanic lithosphere, the chronology points to at least two propagation episodes toward the CIR (≥9.9–7.9 Ma and 4.1–0.4 Ma). We conclude that the Rodrigues Ridge originated as a fracture in the oceanic lithosphere, driven by plume‐related buoyancy forces and asthenospheric flow beneath the CIR, without any direct contribution from the Réunion plume to the partial melting degree. These findings emphasize the role of lithospheric stresses and oceanic accretion in shaping off‐axis volcanic chains.
We propose a new ``helicity-pumping'' method for energizing coronal
equilibria that contain a magnetic flux rope (MFR) toward an eruption. We
achieve this in a sequence of magnetohydrodynamics relaxations of small
line-tied pulses of magnetic helicity, each of which is simulated by a suitable
rescaling of the current-carrying part of the field. The whole procedure is
``magnetogram-matching'' because it involves no changes to the normal component
of the field at the photospheric boundary. The method is illustrated by
applying it to an observed force-free configuration whose MFR is modeled with
our regularized Biot--Savart law method. We find that, in spite of the bipolar
character of the external field, the MFR eruption is sustained by two
reconnection processes. The first, which we refer to as breakthrough
reconnection, is analogous to breakout reconnection in quadrupolar
configurations. It occurs at a quasi-separator inside a current layer that
wraps around the erupting MFR and is caused by the photospheric line-tying
effect. The second process is the classical flare reconnection, which develops
at the second quasi-separator inside a vertical current layer that is formed
below the erupting MFR. Both reconnection processes work in tandem with the
magnetic forces of the unstable MFR to propel it through the overlying ambient
field, and their interplay may also be relevant for the thermal processes
occurring in the plasma of solar flares. The considered example suggests that
our method will be beneficial for both the modeling of observed eruptive events
and theoretical studies of eruptions in idealized magnetic configurations.
;Comment: 9 pages, 3 figures, new comments and references added, relative
magnetic helicity calculated, fig. 2 modified, typos corrected, accepted to
ApJ
CCSD;Presses Universitaires de StrasbourgFebruar 2022Vulkanologie
International audience;
Gas and particulate matter (PM) emissions from Masaya volcano, Nicaragua, cause substantial regional volcanic air pollution (VAP). We evaluate the suitability of low-cost SO2 and PM sensors for a continuous air-quality network. The network was deployed for six months in five populated areas (4-16 km from crater). The SO2 sensors failed and recorded erroneous values on multiple occasions, likely due to corrosion, requiring significant maintenance commitment. The PM sensors were found to be robust but data required correction for humidity. SO2 measurements could not be used as stand-alone tools to detect occurrence of VAP episodes (VAPE), but SO2/PM correlation reliably achieved this at near-field stations, as confirmed by meteorological forecasts and satellite imagery. Above-background PM concentrations reliably identified VAPE at both near-field and far-field stations. We suggest that a continuous network can be built from a combination of low-cost PM and SO2 sensors with a greater number of PM-only sensors.
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Las emisiones de gases y partículas (PM) del volcán Masaya, Nicaragua, causan una importante contaminación atmosférica volcánica regional (VAP). Evaluamos la idoneidad de los sensores de SO2 y PM de bajo coste para una red continua de calidad del aire. La red se desplegó durante seis meses en cinco zonas pobladas (a 4–16 km del cráter). Los sensores de SO2 fallaron y registraron valores erróneos en múltiples ocasiones, probablemente debido a la corrosión, lo que requirió un importante compromiso de mantenimiento. Los sensores de PM resultaron ser robustos, pero los datos requerían una corrección en función de la humedad. Las mediciones de SO2 no pudieron utilizarse como herramientas independientes para detectar la aparición de episodios de VAP (VAPE), pero una correlación SO2/PM lo consiguió de forma fiable en las estaciones cercanas, como confirmaron las previsiones meteorológicas y las imágenes por satélite. Las concentraciones de PM por encima del fondo identificaron de forma fiable los VAPE tanto en las estaciones de campo cercano como en las de campo lejano. Sugerimos que se puede construir una red continua a partir de una combinación de sensores de PM y SO2 de bajo coste con un mayor número de sensores sólo de PM.
International audience;
Volcanic eruptions in basaltic systems represent the most frequent expression of volcanic activity in the World, whose surface manifestations range from effusive lava flows to more explosive events. Their eruptive dynamics and style are largely controlled by the degassing of magma. In this study, we analyze seismic tremors recorded during 23 eruptions that occurred at Piton de la Fournaise volcano (La Réunion, France) during 2014–2021 and show that their properties are strongly linked to the magma degassing. We apply the network covariance matrix method to build a catalog of tremor sources associated with all 23 eruptions, to measure their time-frequency properties, and to locate their sources. We then conduct a multi-disciplinary analysis by comparing the seismic tremor observations with images of the eruptive sites, lava flow rate measurements, impulsive earthquakes, as well as deformation and magma composition data. The tremor depth distribution is found to be well correlated with magma gas content, indicating that the tremor generating mechanism is largely controlled by the shallow magma degassing under the eruptive site. The resulting seismic tremor signals analysis enable to track changes in degassing regimes and associated eruptive styles at the surface, thus improving monitoring and knowledge of the eruptive dynamics of the studied volcano.
Soil organic carbon (SOC) plays a crucial role in agriculture and soil health, as well as in the fight against climate change. In this context, methods are needed to assess the biogeochemical stability of SOC quickly and at low cost. The aim of this PhD thesis is to study the potential of thermal fractionation based on Rock-Eval® analysis results to assess the biogeochemical stability of SOC. I carried out this assessment on the scale of mainland France using surface samples (0–30 cm) collected as part of the first campaign of the French « Réseau de mesures de la qualité des sols » (RMQS1; 2000–2009). Firstly, I conducted a literature review to verify the validity of thermal analysis methods for assessing the biogeochemical stability of SOC, by comparing the results of measurements from thermal analyses with measurements from five classes of standard methods of SOC stability assessment (biological respiration, chemical fractionation, physical fractionation, isotopic measurements, SOC gradient). This review confirms the ability of thermal analysis methods, and in particular Rock-Eval® thermal analysis, to effectively estimate the biogeochemical stability of SOC. I then used the samples from the RMQS first campaign to draw up an inventory of the elemental stoichiometry and thermal stability of COS in mainland France. This study showed that the SOC of cropland and vineyard soils is more thermally stable than the SOC of forests and grasslands, with a higher oxygen index (proxy for the O/C ratio of soil organic matter) and a lower hydrogen index (proxy for the H/C ratio of organic matter). The large number (ca. 2000) and even distribution of sites throughout France mean that a national interpretation reference system can be built for these indicators in surface soils. I then used the Rock-Eval® analysis results as input variables for the PARTYSOC learning model to calculate the quantities of century-scale stable SOC (Cs) and active SOC (Ca) (mean residence time (MRT) of ca. 30 years). I compared these fractions with the results of physical fractionations used to separate SOC into particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) fractions previously carried out on around 1000 RMQS1 samples. The study of these fractions and their determinants led to the conclusion that the two techniques are complementary. Indeed, they differ both in their MRTs and in their quantities. However, the determinants for the two most stable compartments (Cs and MAOC) are very similar, as are those for the most labile compartments (Ca and POC): the quantity of stable carbon depends mainly on soil variables, while the quantity of carbon in the most labile fractions is conditioned by climate and plant cover, i.e. by carbon inputs. Finally, I sought to investigate the relationships between clay mineralogy and the quantity of pyrogenic carbon (PyC) and the quantity of stable carbon (Cs). This work on the drivers of Cs is currently at a preliminary stage. This PhD thesis work validated the potential of Rock-Eval® thermal analysis combined with the use of the PARTYSOC model to assess the biogeochemical stability of SOC on large sample sets. Estimating the biogeochemical stability of SOC on a national scale will enable a more detailed assessment of the potential for storage and the risks of SOC losses. Finally, this work could provide input for future studies linking SOC stability and soil health indicators.
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Le carbone organique des sols (COS) joue un rôle crucial pour l’agriculture et la santé des sols ainsi que dans la lutte contre le changement climatique. Dans ce cadre, il est nécessaire de pouvoir disposer de méthodes permettant d’évaluer la stabilité biogéochimique du COS rapidement et à moindre coût. Cette thèse vise à étudier les potentialités d’un fractionnement thermique basé sur des résultats d’analyse Rock-Eval® pour évaluer la stabilité biogéochimique du COS. J’ai réalisé cette évaluation à l’échelle de la France métropolitaine en bénéficiant des échantillons de surface (0–30 cm) collectés dans le cadre de la campagne 1 du Réseau de mesures de la qualité des sols (RMQS1 ; 2000–2009). Dans un premier temps, j’ai mené une revue bibliographique afin de vérifier la validité des méthodes d’analyse thermique pour évaluer la stabilité biogéochimique du COS, en comparant les résultats de mesures issues d’analyses thermiques avec des mesures issues de cinq classes de méthodes usuelles d’évaluation de la stabilité du COS (respiration biologique, extraction chimique, fractionnement physique, mesure isotopique, gradient de COS). Cette revue confirme la capacité des méthodes d’analyse thermique et notamment l’analyse thermique Rock-Eval® à estimer efficacement la stabilité biogéochimique du COS. J’ai ensuite utilisé les échantillons de la campagne 1 du RMQS pour dresser un état des lieux de la stoechiométrie élémentaire et de la stabilité thermique du COS en France métropolitaine. Cette étude a mis en évidence que le COS des sols de grandes cultures et de vignes présentent une stabilité thermique plus importante que celui des forêts et des prairies, ainsi qu’un indice oxygène (proxy du rapport O/C de la matière organique des sols) plus élevé et un indice hydrogène (proxy du rapport H/C de la matière organique) plus faible. Le nombre élevé (env. 2000) et la répartition homogène des sites sur l’ensemble du territoire français permettent de construire un référentiel national d’interprétation pour ces indicateurs dans les sols de surface. J’ai ensuite utilisé ces résultats d’analyse Rock-Eval® comme variables d’entrées du modèle d’apprentissage PARTYSOC pour calculer les quantités de COS stable à l’échelle du siècle (Cs) et de COS actif (Ca) (temps de résidence moyen (MRT) de l’ordre de 30 ans). J’ai comparé ces fractions aux résultats de fractionnements physiques permettant de séparer le COS en fractions carbone organique particulaire (POC) et carbone organique associé aux minéraux (MAOC) précédemment réalisés sur environ 1000 échantillons RMQS1. L’étude de ces fractions et de leurs déterminants a permis de conclure à la complémentarité des deux techniques. En effet, elles diffèrent tant par leurs MRT que par leurs tailles. Toutefois, les déterminants pour les deux compartiments les plus stables (Cs et MAOC) sont très similaires, de même que pour les compartiments les plus labiles (Ca et POC) : la quantité de carbone stable dépend principalement de variables pédologiques tandis que la quantité de carbone dans les fractions les plus labiles est conditionnée par le climat et le couvert végétal, c’est-à-dire par les entrées de carbone. Enfin, j’ai cherché à investiguer les relations entre la minéralogie des argiles et la quantité de carbone pyrogénique (PyC) et la quantité de carbone stable (Cs). Ce travail sur les déterminants du Cs est pour l’instant à un stade préliminaire. Ce travail de thèse a permis de valider le potentiel de l’analyse thermique Rock-Eval® associée à l’utilisation du modèle PARTYSOC pour évaluer la stabilité biogéochimique du COS sur de gros jeux d’échantillons. L’estimation de la stabilité biogéochimique du COS à l’échelle nationale permettra d’apprécier plus finement les potentialités de stockage et les risques de pertes de COS. Enfin, ce travail pourra alimenter de futures études liant stabilité du COS et indicateurs de la santé des sols.
International audience;
Fifty per cent of European peatlands are in a damaged state. While intact peatlands are natural carbon sinks, degraded sites release important amounts of greenhouse gases into the atmosphere, contributing to global warming. Restoration of the hydrological functionality of peatlands has proved to be an efficient tool to avoid these emissions. In France, Tuffnell and Bignon's ministerial report (2019) emphasized the need for peatlands 'integration into the National Low Carbon Strategy, targeting carbon neutrality by 2050. However, current knowledge regarding French peatlands' distribution and carbon stocks is insufficient and does not allow decision makers and managers to prioritize areas for restoration. The most complete database to date is the 1949 Atlas, an inventory of exploitable peat deposits that was conducted during WWII for peat exploitation as fuel. Until its digitalization, the latter database was archived and never used in a scientific study. It provides detailed information about peatland surfaces, peat thicknesses and carbon contents at that time. We estimated peat carbon stocks from French peatlands to be 111 Mt C in 1949 for 63,290 ha identified as peaty sites, the equivalent of 3% of the organic carbon contained in the upper 30 centimetres of French soils. 34% of this stock was held in Lower Normandy (37.7 Mt C) and 12% in the Picardy's region (13.0 Mt C), in large lowland peatlands. However, not all peatlands were prospected in the 1949 inventory and the characteristics of the prospected peatlands may have changed with anthropic disturbances of the last decades, such as draining or climate change. These first results highlight the need for a recent inventory of French peatlands and carbon stocks based on local data aggregation. Data from the 1949 Atlas could help constituting this new inventory but should be validated before being used to describe the present.
International audience;
Radiocarbon ( 14 C) is a critical tool for understanding the global carbon cycle. During the Anthropocene, two new processes influenced 14 C in atmospheric, land and ocean carbon reservoirs. First, 14 C-free carbon derived from fossil fuel burning has diluted 14 C, at rates that have accelerated with time. Second, ‘bomb’ 14 C produced by atmospheric nuclear weapon tests in the mid-twentieth century provided a global isotope tracer that is used to constrain rates of air–sea gas exchange, carbon turnover, large-scale atmospheric and ocean transport, and other key C cycle processes. As we write, the 14 C/ 12 C ratio of atmospheric CO 2 is dropping below pre-industrial levels, and the rate of decline in the future will depend on global fossil fuel use and net exchange of bomb 14 C between the atmosphere, ocean and land. This milestone coincides with a rapid increase in 14 C measurement capacity worldwide. Leveraging future 14 C measurements to understand processes and test models requires coordinated international effort—a ‘decade of radiocarbon’ with multiple goals: (i) filling observational gaps using archives, (ii) building and sustaining observation networks to increase measurement density across carbon reservoirs, (iii) developing databases, synthesis and modelling tools and (iv) establishing metrics for identifying and verifying changes in carbon sources and sinks. This article is part of the Theo Murphy meeting issue 'Radiocarbon in the Anthropocene'.
HAL CCSD;European Geosciences UnionJanuar 2022Klimawissenschaft
International audience;
Changes in soil organic carbon (SOC) stocks are a major source of uncertainty for the evolution of atmospheric CO2 concentration during the 21st century. They are usually simulated by models dividing SOC into conceptual pools with contrasted turnover times. The lack of reliable methods to initialize these models, by correctly distributing soil carbon amongst their kinetic pools, strongly limits the accuracy of their simulations. Here, we demonstrate that PARTYSOC, a machine-learning model based on Rock-Eval® thermal analysis, optimally partitions the active- and stable-SOC pools of AMG, a simple and well-validated SOC dynamics model, accounting for effects of soil management history. Furthermore, we found that initializing the SOC pool sizes of AMG using machine learning strongly improves its accuracy when reproducing the observed SOC dynamics in nine independent French long-term agricultural experiments. Our results indicate that multi-compartmental models of SOC dynamics combined with a robust initialization can simulate observed SOC stock changes with excellent precision. We recommend exploring their potential before a new generation of models of greater complexity becomes operational. The approach proposed here can be easily implemented on soil monitoring networks, paving the way towards precise predictions of SOC stock changes over the next decades.
Sugarcane is an important crop for tropical countries and to accurately inventory its greenhouse gas (GHG) emissions baseline measurements are needed. In Colombia, sugarcane is one of the most important crops in terms of cultivated area and, paradoxically, scientific information reporting GHG emissions based on field measurements is almost nonexistent. The objective of this work was to quantify the direct emissions of carbon dioxide (CO_2) and nitrous oxide (N_2O) in the sugarcane-soil system of the Cauca river valley, Colombia. For this purpose, a field experiment was established in a typic haplustert soil cropped with sugarcane. The effects of nitrogen (N) fertilization and sampling site on its GHG emissions were tested using the closed static chamber method over a period of 211 days. The main cumulative emissions were 765.14 ± 34.1 g CO_2–C m^−2 and 125.4 ± 22.6 mg N_2O–N m^−2. Overall, GHG emissions were modified by N fertilization, the sampling site, and their interaction. Nitrogen fertilization with urea increased mean and cumulative CO_2 and N_2O emissions, especially at the row sampling site. This paper highlights the importance of considering these factors when the quantification of GHGs or a reduction of their associated uncertainties are required. This work reportss the first GHG emissions data for a typical sugarcane agroecosystem in Colombia.
CCSD;Association canadienne des sciences géomatiquesDezember 2025Klimawissenschaft
International audience;
<div><p>Fires across sub-Saharan Africa (SSA) are a dominant source of global carbon emissions, yet their true magnitude remains uncertain due to the limitations of coarse-resolution satellite products. In this study, we developed a high-resolution fire emission inventory prototype for SSA using active fire detections from the VIIRS sensor (375 m) and a top-down approach based on fire radiative power (FRP). Emissions were estimated through the integration of FRP to fire radiative energy (FRE), conversion to dry matter burned using biome-specific combustion coefficients, and application of emission factors for carbon dioxide. A parallel MODIS-based dataset was also produced using the same methodology to isolate sensor-specific effects. To evaluate detection and modelling differences, the VIIRS-based product (VIIRS-EM) was compared against six widely used global fire emission inventories. In addition, a subset of emissions from small fires (defined as FRP < 10 MW) was derived and assessed separately. Over the period 2013-2022, VIIRS-EM estimated average annual carbon emissions of 3.0 Pg C, which is 50-75 % higher than most MODIS-based inventories. Emission hotspots were identified in agricultural and savanna regions, particularly in West and Central Africa. Small fires contributed significantly to early and late fire-season emissions and revealed widespread underestimation in existing products. Our findings underscore the importance of high-resolution detection and FRP-based modelling for capturing the full extent of African fire activity. The VIIRS-EM inventory provides improved spatial and temporal resolution, with implications for atmospheric composition modelling, greenhouse gas accounting, and regional fire policy development.</p></div>
Frontiers Research FoundationNovember 2021Klimawissenschaft
Echinopsis chiloensis is an endemic cactus from Chile, distributed in a temperature and rainfall gradient between 30° and 35° South latitude, with mean temperatures increasing and precipitation decreasing toward the north. It is the main host of the mistletoe Tristerix aphyllus, a holoparasite completely dependent on the cactus for water, carbon, and minerals. In this study, we investigated the consequences of parasitism over the fitness and physiology of this cactus throughout its distribution range and how it is affected by the environment. We measured five functional traits in eight populations latitudinally distributed, the first three only for the host: reproductive fitness, stomatal traits (density and size), and photosynthesis (during winter and summer); and the last two for the host and parasite: stable isotopes (∂13C and ∂15N), and nutrients (carbon and nitrogen content). The results showed a negative effect of parasitism over fitness of infected cacti. However, the higher nitrogen concentrations in cactus tissues toward the south improved overall fitness. Regarding photosynthesis, we only observed a negative effect of parasitism during the dry season (summer), which is also negatively affected by the increase in summer temperatures and decrease in winter rainfall toward the north. There were no differences in nutrient concentration or in the isotopic signature of healthy and infected cacti. Conversely, we observed a higher carbon and lower nitrogen concentration in mistletoes than in cacti regardless of latitude. The loss of temperature seasonality toward the north increases the C:N ratio, and the values between the parasite and its host diverge. ∂15N was similar between parasites and hosts while ∂13C of the parasite was enriched when compared to its host. Overall, the infection by T. aphyllus affects Echinopsis chiloensis fitness but showed no strong effects over the cactus physiology, except for the summer photosynthesis. Therefore, our data revealed that E. chiloensis response to T. aphyllus infection is sensitive to environmental changes in a way that could be strongly impacted by the desertification projected for this area due to climate change.
International audience;
Peatlands store organic carbon available for decomposition and transfer to neighboring water bodies, which can ultimately generate carbon dioxide (CO<sub>2</sub>) emissions. The objective of this study was to clarify the biogeochemical functioning of open‐water peatland pools and their influence on carbon budgets at the ecosystem and global scale. Continuously operated automated equipment and monthly manual measurements were used to describe the CO<sub>2</sub> and CH<sub>4</sub> dynamics in boreal ombrotrophic peatland pools and porewater (Québec, Canada) over the growing seasons 2019 and 2020. The peat porewater stable carbon isotope ratios (δ<sup>13</sup>C) for both CO<sub>2</sub> (median δ<sup>13</sup>C‐CO<sub>2</sub> : −3.8‰) and CH<sub>4</sub> (median δ<sup>13</sup>C‐CH<sub>4</sub> : −64.30‰) suggested that hydrogenotrophic methanogenesis was the predominant degradation pathway in peat. Open‐water pools were supersaturated in CO<sub>2</sub> and CH<sub>4</sub> and received most of these dissolved carbon greenhouse gases (C‐GHG) from peat porewater input. Throughout the growing season, higher CO<sub>2</sub> concentrations and fluxes in pools were measured when the water table was low—suggesting a steady release of CO<sub>2</sub> from deep peat porewater. Higher CH<sub>4</sub> ebullition and diffusion occurred in August when bottom water and peat temperatures were the highest. While this study demonstrates that peatland pools are chimneys of CO<sub>2</sub> and CH<sub>4</sub> stored in peat, it also shows that the C‐GHG concentrations and flux rates in peat pools are comparable to other aquatic systems of the same size. Although peatlands are often considered uniform entities, our study highlights their biogeochemical heterogeneity, which, if considered, substantially influences their net carbon balance with the atmosphere.
Soils store twice the amount of carbon that is found in atmosphere and vegetation combined. They act as a buffer between solid earth and atmosphere and exercise a major control on the atmospheric concentration of CO2 through the release or sink of greenhouse gases. Organic carbon in soils in the form of organic matter is essential to soil health and fertility, to nutrient availability and water quality. The performance of the most valuable tool at our disposal for understanding and predicting the evolution of this reservoir, soil organic carbon (SOC) dynamics models, is currently limited by a missing key: the ability to estimate the proportion of SOC that will remain unchanged over projection-relevant timescales. This important amount of carbon present in soils for centuries or millennia, and therefore considered “stable”, can vary greatly from one location to another. The goal of my thesis was to explore a new approach based on thermal analysis and machine learning, to characterise SOC, estimate the proportion of “stable” carbon in soil samples, and use this information to improve the accuracy of SOC dynamics models. In a second step, I focused on the thermal analysis technique in the heart of this approach to understand better the important information it offers, based on model laboratory experiments. Finally, the main results of my thesis consist of a complete and validated operational approach improving the accuracy of SOC models with a clear and significant value for “climate-smart” soil management, while the experimental part offers new insights into the working principle, limitations and possibilities of the thermal analysis technique at the heart of this approach.
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A la croisée de la terre solide et de l'atmosphère, les sols forment le plus grand réservoir terrestre de carbone organique, contenant deux fois plus de carbone que l'atmosphère et la végétation réunies, et constituant un contrôle majeur sur le flux des gaz à effet de serre. En outre, le carbone organique des sols (COS) est essentiel pour leur santé et fertilité, ainsi que pour la qualité de l'eau. La précision de l'outil le plus précieux dont nous disposons pour prédire l'évolution de ce réservoir, les modèles de dynamique du COS, est limitée par notre capacité à estimer la proportion du COS qui persistera sur le long terme. Cette quantité importante de carbone présente dans les sols depuis des siècles ou des millénaires, considérée comme « stable », peut varier fortement d'un endroit à l'autre. L'ambition de ma thèse était d’explorer une nouvelle approche basée sur l'analyse thermique et l’apprentissage automatique, pour caractériser le COS, estimer la proportion du carbone « stable » dans les échantillons de sol et ensuite utiliser cette nouvelle information pour améliorer la précision des modèles de dynamique du COS. Dans un deuxième temps, je me suis concentrée sur la technique de l'analyse thermique pour comprendre mieux les informations qu'elle offre, à la base des expériences modèles en laboratoire. Enfin, les résultats principaux de ma thèse consistent en une approche opérationnelle améliorant la précision des modèles du COS avec une valeur claire et significative pour une gestion « intelligente » des sols et, en des nouveaux aperçus sur le principe de fonctionnement, les limites et les possibilités de la technique d'analyse thermique au cœur de cette approche.
The epipelagic and mesopelagic oceans play a key role in the production, recycling, and transfer of both organic and mineral matter to the deep ocean. Rhizaria (including Radiolaria and Phaeodaria) are planktonic protists thriving in these layers throughout the world ocean. They can display either mixotrophic or heterotrophic feeding behavior, and some of them form silica skeletons. Furthermore, these organisms can aggregate detrital material around them, forming fast-sinking particles. Sampling these fragile organisms is challenging, but advances in in situ imaging techniques have improved estimates of their abundance and roles in element fluxes. Still, due to a lack of measurements at the cellular level, our understanding of their global carbon biomass and their roles in biogeochemical processes remains limited. To fill this gap, the carbon content of diverse rhizarian taxa was measured, covering a broad size spectrum, and an allometric relationship was established, revealing an overall low carbon density compared to smaller protists. Using boosted regression trees and a global Underwater Vision Profiler (UVP) 5 dataset, including >167,000 rhizarian images recorded all over the world ocean, global carbon biomass of >600-μm Rhizaria was reestimated to be 1.7% of the total mesozooplankton biomass within the upper 500 m of the water column. This biomass was found to be 10-fold higher in the mesopelagic than in the epipelagic layer. Subsequently, mesopelagic flux-feeder Phaeodaria were estimated to intercept 3.8-9.2% of the gravitational POC flux exported out of the euphotic zone. In the Southern Ocean, where their abundance was previously shown to be low, this interception rate can reach as high as 11.2-23.4%. In addition, biogenic silica (bSi) production rates of Phaeodaria were estimated, being the first quantification of bSi production in the mesopelagic layer. As the sole bSi producers in this layer, they play a significant role in its recycling, co-dominating the silicon cycle along with diatoms and sponges. Lastly, a new methodology to measure the sinking speed of marine particles using the UVP6 mounted on a sediment trap was introduced. After collecting approx. 9,000 measurements of particle sinking speeds in the North Atlantic, no strong relationships were found between morphological measurements provided by the UVP6 and sinking speeds. Instead, it was observed that sinking speeds increased with depth and were influenced by environmental conditions. These results highlight the importance of considering community composition, including both phytoplankton and zooplankton, for speed estimation and to refine flux estimates using in situ imaging.
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Les océans épipélagique et mésopélagique jouent un rôle clé dans la production, le recyclage et le transfert de la matière organique et minérale vers l’océan profond. Les Rhizaria (comprenant les Radiolaria et les Phaeodaria) sont des protistes planctoniques qu’on retrouve dans ces couches de l’océan mondial. Ils peuvent être mixotrophes ou hétérotrophes, et certains d’entre eux forment des squelettes de silice. De plus, ces organismes peuvent agréger du matériel détritiques autour d’eux, formant ainsi des particules sédimentant rapidement. L’échantillonnage de ces organismes fragiles est difficile par le biais de méthodes traditionnelles comme les filets à plancton, mais les avancées en imagerie in situ ont amélioré les estimations de leur abondance et de leur rôle dans les flux élémentaires. Cependant, en raison du manque de mesures au niveau cellulaire, notre compréhension de leur biomasse mondiale en carbone et de leur rôle dans les processus biogéochimiques reste limitée. Pour combler ces lacunes, le contenu en carbone de divers taxons de Rhizaria a été mesuré, couvrant un large spectre de tailles, et une relation allométrique a été établie, révélant une densité de carbone globalement faible par rapport aux protistes plus petits. À l’aide de boosted regression trees et d’un ensemble de données global collecté à l’aide de l’Underwater Vision Profiler (UVP) 5, comprenant plus de 167 000 images de Rhizaria enregistrées dans le monde entier, la biomasse mondiale en carbone des Rhizaria >600 μm a été ré-estimée à 1,7 % de la biomasse totale du mésozooplancton dans les 500 premiers m de la colonne d’eau. Cette biomasse s’est révélée être dix fois plus élevée dans la zone mésopélagique que dans la zone épipélagique. Ensuite, il a été estimé que les Phaeodaria mésopélagiques, se nourrissant du flux de particules, peuvent intercepter de 3,8 à 9,2 % du flux de carbone particulaire exporté de la zone euphotique. Dans l’océan Austral, où leur abondance était précédemment considérée faible, ce taux d’interception est de 11,2-23,4 %. De plus, les taux de production de silice biogénique (bSi) des Phaeodaria ont été estimés, constituant la première quantification de la production de bSi dans la zone mésopélagique. En tant que seuls producteurs de bSi dans cette zone, ils jouent un rôle significatif dans son recyclage, co-dominant le cycle du silicium aux côtés des diatomées et des éponges. Enfin, une nouvelle méthodologie pour mesurer la vitesse de sédimentation des particules marines à l’aide de l’UVP6 monté sur un piège à sédiments a été introduite. Après la collecte d’environ 9 000 valeurs de vitesse de sédimentation dans l’Atlantique Nord, aucune relation forte n’a été trouvée entre les mesures morphologiques fournies par l’UVP6 et celles-ci. Au lieu de cela, il a été observé que les vitesses de sédimentation augmentent avec la profondeur et sont influencées par les conditions environnementales. Ces résultats mettent en évidence l’importance de prendre en compte la composition des communautés phytoplanctoniques et zooplanctoniques, pour estimer la vitesse et affiner les estimations de flux qui utilisent l’imagerie in situ.
Background The farmyard manure application maintains quality of arable soils, provides nutrients, mitigates climate change by soil carbon sequestration. Biochar and other complex carbon rich amendments may stabilize organic matter derived by composting and decelerate organic carbon mineralization. However, how the combined utilization of biochar, humic substances and manure effects on soil chemical and biological properties have been least explored, especially their effect on soil basal and substrate induced respirations are needed to be further explored. Therefore, the potential of biochar and Humac (a commercial humic substances product) in combination with manure to improve the soil properties and plant growth was investigated in this experiment using barley under a short-term (12 weeks) and maize under long-term (following 12 weeks, a total of 24 weeks) cultivation. Results In the early phase of cultivation (12 weeks) Humac- or biochar-enriched manures (M + H, M + B, respectively) enhanced the contents of nutrient elements (carbon + 5.6% and + 7%, nitrogen + 6.7% and − 5%, sulphur − 7.9% and + 18.4%), the activity of enzymes including (β-glucosidase + 32% and + 9.6%, phosphatase + 11% and 6.3%), and dry aboveground biomass (+ 21% and + 32%), compared to the control and manure-treated soil. However, these impacts of M + H and M + B manures were reduced under longer period, i.e., at the experiment end (24 weeks). After 24 weeks of cultivation, a decrease in absolute values of all determined enzyme activities indicated putative reduction of mineralization rate due to presumed higher recalcitrance of manure-derived organic matter, with Humac, biochar amendments. Increased stability of soil organic matter reduced microbial activity due to lower availability of nutrients. Possibly, the shortened period of manure maturation could help preserve a higher amount of less degraded organic matter in the enriched manures to counteract these observed features. Conclusions We summarized that the biochar and humic substances combined with manure have the potential to improve the soil characteristics, plant biomass and soil health indicators but the improvements faded away in a cultivation time-dependent manner. Further studies are required to explore the structure and functioning of microbial activities under long-term experimental conditions. Graphical abstract
International audience;
Humic thermokarst lakes of permafrost peatlands in Western Siberia Lowland (WSL) are major environmental controllers of carbon and nutrient storage in inland waters and greenhouse gases emissions to the atmosphere in the subarctic. In contrast to sizable former research devoted to hydrochemical and hydrobiological (phytoplankton) composition, zooplankton communities of these thermokarst lakes and thaw ponds remain poorly understood, especially along the latitudinal gradient, which is a perfect predictor of permafrost zones. To fill this gap, 69 thermokarst lakes of the WSL were sampled using unprecedented spatial coverage, from continuous to sporadic permafrost zone, in order to assess zooplankton (Cladocera, Copepoda, Rotifera) diversity and abundance across three main open water physiological seasons (spring, summer and autumn). We aimed at assessing the relationship of environmental factors (water column hydrochemistry, nutrients, and phytoplankton parameters) with the abundance and diversity of zooplankton. A total of 74 zooplankton species and taxa were detected, with an average eight taxa per lake/pond. Species richness increased towards the north and reached the maximum in the continuous permafrost zone with 13 species found in this zone only. In contrast, the number of species per waterbody decreased towards the north, which was mainly associated with a decrease in the number of cladocerans. Abundance and diversity of specific zooplankton groups strongly varied across the seasons and permafrost zones. Among the main environmental controllers, Redundancy Analysis revealed that water temperature, lake area, depth, pH, Dissolved Inorganic and Organic Carbon and CO<sub>2</sub> concentrations were closely related to zooplankton abundance. Cladocerans were positively related to water temperature during all seasons. Copepods were positively related to depth and lake water pH in all seasons. Rotifers were related to different factors in each season, but were most strongly associated with DOC, depth, CH<sub>4</sub>, phytoplankton and cladoceran abundance. Under climate warming scenario, considering water temperature increase and permafrost boundary shift northward, one can expect an increase in the diversity and abundance of cladocerans towards the north which can lead to partial disappearance of copepods, especially rare calanoid species.
International audience;
<div><p>The carbon sink in pantropical biomes play a crucial role in modulating the inter-annual variations of global terrestrial carbon balance and is threatened by extreme climate events. However, it has not been carefully examined whether an increase in tropical gross primary productivity (GPP) can compensate the decrease during precipitation anomalies. Using the asymmetry index (AI) and multiple GPP products, we assessed responses of pantropical GPP to precipitation anomalies during 2001-2022. Positive AI indicates that GPP increases are greater than GPP decreases during precipitation anomalies, and vice versa. Our results showed an average negative pantropical GPP asymmetry, that is, GPP decreases exceeded the GPP increases during precipitation anomalies. In addition, a positive AI was found in tropical hyper-arid and arid regions, which is opposite to the negative AI observed in tropical semi-arid, sub-humid, and humid regions. This suggest that tropical GPP asymmetry changes from positive to negative as the moisture increases. Notably, a significant decreasing trend of negative AI was observed over the entire tropical region, indicating that the negative effect of inter-annual precipitation variations on pantropical vegetation productivity has enhanced. Considering the model predicted increasing climate variability and extremes, the negative impact of precipitation variability on tropical carbon cycle may continue to intensify. Lastly, the divergence in AI estimates among multiple GPP products highlight the need to further improve our understanding of the response of tropical carbon cycle to climate changes, especially for the tropical humid regions.</p><p>Plain Language Summary Tropical biomes play an essential role in controlling the global carbon balance but has been threatened by extreme climate events recently. Whether the increase in tropical GPP can compensate the GPP decrease during precipitation anomalies is still poorly known. In this study, we found an average negative asymmetric GPP response to precipitation anomalies over the entire tropics during 2001-2022, that is, GPP decreases exceeded the GPP increases during precipitation anomalies. Meanwhile, we found that the tropical GPP was shifted from positive asymmetry to negative asymmetry as the moisture increases. Besides, a significantly decreasing trend of GPP asymmetry was observed over the study period, suggesting that the negative effect of inter-annual precipitation variations on pantropical GPP has intensified.</p></div>
International audience;
Estimating SOC stocks and stability, as well as modeling their response to rising temperatures, is crucial for predicting climate change impacts. This is particularly true in mountainous regions, where low temperatures slow down SOC decomposition, resulting in higher SOC stocks compared to soils at lower elevations. However, these stocks are also more vulnerable to warming, increasing the risk of SOC depletion. Such conditions create the potential for a positive feedback loop in which warming accelerates SOC losses, further amplifying climate change impacts on these sensitive ecosystems.To better understand the factors controlling SOC stocks and stability in mountain soils, we sampled 170 soil profiles along 29 elevation gradients in the western Alps from 280 to 3160 m a.s.l. We assessed SOC stocks and chemical composition using mid-infrared spectroscopy method and SOC stability with Rock-Eval® thermal analysis. Our findings, based on an unprecedented dataset, reveal a clear elevational pattern in SOC properties. SOC stocks increase with elevation up to the montane belt (1200–1500 m a.s.l.), remain relatively stable through the subalpine zone, and then decline beyond the subalpine/alpine boundary (2200–2400 m a.s.l.). Notably, this transition is also marked by a significant drop in SOC stability, suggesting a shift in the dominant stabilization processes at higher elevations. Our results also indicate that SOC stocks and stability are influenced by a complex interplay of factors.At higher elevations, climate emerges to be the dominant factor, whereas lithology and weathering play a more significant role at lower elevations. These results suggest that at high-elevations, harsh climatic conditions favor stabilization of SOC, while less developed soils limit organo-mineral interactions. In contrast, at warmer, lower elevations with higher carbon fluxes, more developed soils facilitate organo-mineral interactions, thereby enhancing SOC stability in the long term. Consequently, alpine grasslands, which contain substantial stocks of labile carbon stabilized by climatic conditions, appear to be particularly vulnerable to the effects of climate warming.
American Chemical SocietyJuli 2023Klimawissenschaft
[Image: see text] Dissolved inorganic carbon (DIC) is a key component of the global carbon cycle and plays a critical role in ocean acidification and proliferation of phototrophs. Its quantification at a high spatial resolution is essential for understanding various biogeochemical processes. We present an analytical method for 2D chemical imaging of DIC by combining a conventional CO(2) optode with localized electrochemical acidification from a polyaniline (PANI)-coated stainless-steel mesh electrode. Initially, the optode response is governed by local concentrations of free CO(2) in the sample, corresponding to the established carbonate equilibrium at the (unmodified) sample pH. Upon applying a mild potential-based polarization to the PANI mesh, protons are released into the sample, shifting the carbonate equilibrium toward CO(2) conversion (>99%), which corresponds to the sample DIC. It is herein demonstrated that the CO(2) optode–PANI tandem enables the mapping of free CO(2) (before PANI activation) and DIC (after PANI activation) in complex samples, providing high 2D spatial resolution (approx. 400 μm). The significance of this method was proven by inspecting the carbonate chemistry of complex environmental systems, including the freshwater plant Vallisneria spiralis and lime-amended waterlogged soil. This work is expected to pave the way for new analytical strategies that combine chemical imaging with electrochemical actuators, aiming to enhance classical sensing approaches via in situ (and reagentless) sample treatment. Such tools may provide a better understanding of environmentally relevant pH-dependent analytes related to the carbon, nitrogen, and sulfur cycles.
An impact of climate change is the increase in frequency and intensity of
extreme precipitation events. However, confidently predicting the likelihood of
extreme precipitation at seasonal scales remains an outstanding challenge.
Here, we present an approach to forecasting the quantiles of the maximum daily
precipitation in each week up to six months ahead using the temporal fusion
transformer (TFT) model. Through experiments in two regions, we compare TFT
predictions with those of two baselines: climatology and a calibrated ECMWF
SEAS5 ensemble forecast (S5). Our results show that, in terms of quantile risk
at six month lead time, the TFT predictions significantly outperform those from
S5 and show an overall small improvement compared to climatology. The TFT also
responds positively to departures from normal that climatology cannot.
International audience;
The use of cover crops (CCs) is a promising cropland management practice with multiple benefits, notably in reducing soil erosion and increasing soil organic carbon (SOC) storage. However, the current ability to represent these factors in land surface models remains limited to small scales or simplified and lumped approaches due to the lack of a sediment-carbon erosion displacement scheme. This precludes a thorough understanding of the consequences of introducing a CC into agricultural systems. In this work, this problem was addressed in two steps with the spatially distributed CE-DYNAM model. First, the historical effect of soil erosion, transport, and deposition on the soil carbon budget at a continental scale in Europe was characterized since the early industrial era, using reconstructed climate and land use forcings. Then, the impact of two distinct policy-oriented scenarios for the introduction of CCs were evaluated, covering the European cropping systems where surface erosion rates or nitrate susceptibility are critical. The evaluation focused on the increase in SOC storage and the export of particulate organic carbon (POC) to the oceans, compiling a continental-scale carbon budget. The results indicated that Europe exported 1.95 TgC/year of POC to the oceans in the last decade, and that CCs can contribute to reducing this amount while increasing SOC storage. Compared to the simulation without CCs, the additional rate of SOC storage induced by CCs peaked after 10 years of their adoption, followed by a decrease, and the cumulative POC export reduction stabilized after around 13 years. The findings indicate that the impacts of CCs on SOC and reduced POC export are persistent regardless of their spatial allocation adopted in the scenarios. Together, the results highlight the importance of taking the temporal aspect of CC adoption into account and indicate that CCs alone are not sufficient to meet the targets of the 4‰ initiative. Despite some known model limitations, which include the lack of feedback of erosion on the net primary productivity and the representation of carbon fluxes with an emulator, the current work constitutes the first approach to successfully couple a distributed routing scheme of eroded carbon to a land carbon model emulator at a reasonably high resolution and continental scale.
Los bosques pantanosos amazónicos eliminan grandes cantidades de dióxido de carbono (CO_2) pero producen metano (CH_4). Ambos son importantes gases de efecto invernadero (GEI). La sequía y el cultivo reducen las emisiones de CH_4 pero pueden liberar CO_2. La variación del contenido de oxígeno en los suelos ricos en nitrógeno produce óxido nitroso (N_2O), que es el tercer GEI más importante. A pesar de los enormes cambios potenciales, las emisiones de GEI del suelos de los humedales bajo diferentes usos de la tierra y condiciones ambientales rara vez se han comparado en la Amazonía. Medimos las características ambientales y las emisiones de CO_2, CH_4 y N_2O de la superficie del suelo con cámaras opacas manuales en tres sitios cerca de Iquitos, Perú, de septiembre de 2019 a marzo de 2020: un bosque pantanoso de turba prístino, un bosque joven y un campo de yuca de talado y quemado. El campo de yuca mostró una respiración moderada del suelo y emisión de N_2O. Los bosques pantanosos de turba con un ligero descenso del nivel freático emitieron grandes cantidades de CO_2 y CH_4. Una fuerte lluvia posterior a la sequía creó un momento caliente de N_2O en el bosque pantanoso prístino, probablemente producido por nitrificantes. Endefinitiva, incluso pequeños cambios en la humedad del suelo pueden crear momentos calientes de emisiones de GEI de los suelos de los humedales amazónicos y, por lo tanto, deben monitorearse cuidadosamente. Amazonian swamp forests remove large amounts of carbon dioxide (CO_2) but produce methane (CH_4). Both are important greenhouse gases (GHG). Drought and cultivation cut the CH_4 emissions but may release CO_2. Varying oxygen content in nitrogen-rich soil produces nitrous oxide (N_2O), which is the third most important GHG. Despite the potentially tremendous changes, GHG emissions from wetland soils under different land uses and environmental conditions have rarely been compared in the Amazon. We measured environmental characteristics, and CO_2, CH_4 and N_2O emissions from the soil surface with manual opaque chambers in three sites near Iquitos, Peru from September 2019 to March 2020: a pristine peat swamp forest, a young forest and a slash-and-burn manioc field. The manioc field showed moderate soil respiration and N_2O emission. The peat swamp forests under slight water table drawdown emitted large amounts of CO_2 and CH_4. A heavy post-drought shower created a hot moment of N_2O in the pristine swamp forest, likely produced by nitrifiers. All in all, even small changes in soil moisture can create hot moments of GHG emissions from Amazonian wetland soils, and should therefore be carefully monitored.
International audience;
Abstract. Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based fCO2 products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. Additional lines of evidence on land and ocean sinks are provided by atmospheric inversions, atmospheric oxygen measurements, and Earth system models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and incomplete understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2022, EFOS increased by 0.9 % relative to 2021, with fossil emissions at 9.9±0.5 Gt C yr−1 (10.2±0.5 Gt C yr−1 when the cement carbonation sink is not included), and ELUC was 1.2±0.7 Gt C yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 11.1±0.8 Gt C yr−1 (40.7±3.2 Gt CO2 yr−1). Also, for 2022, GATM was 4.6±0.2 Gt C yr−1 (2.18±0.1 ppm yr−1; ppm denotes parts per million), SOCEAN was 2.8±0.4 Gt C yr−1, and SLAND was 3.8±0.8 Gt C yr−1, with a BIM of −0.1 Gt C yr−1 (i.e. total estimated sources marginally too low or sinks marginally too high). The global atmospheric CO2 concentration averaged over 2022 reached 417.1±0.1 ppm. Preliminary data for 2023 suggest an increase in EFOS relative to 2022 of +1.1 % (0.0 % to 2.1 %) globally and atmospheric CO2 concentration reaching 419.3 ppm, 51 % above the pre-industrial level (around 278 ppm in 1750). Overall, the mean of and trend in the components of the global carbon budget are consistently estimated over the period 1959–2022, with a near-zero overall budget imbalance, although discrepancies of up to around 1 Gt C yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows the following: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living-data update documents changes in methods and data sets applied to this most recent global carbon budget as well as evolving community understanding of the global carbon cycle. The data presented in this work are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023).
Data assimilation will be essential for the management and expansion of
geological carbon storage operations. In traditional data assimilation
approaches a fixed set of geological hyperparameters, such as mean and standard
deviation of log-permeability, is often assumed. Such hyperparameters, however,
may be highly uncertain in practical CO2 storage applications where
measurements are scarce. In this study, we develop a hierarchical data
assimilation framework for carbon storage that treats hyperparameters as
uncertain variables characterized by hyperprior distributions. To deal with the
computationally intractable likelihood function in hyperparameter estimation,
we apply a likelihood-free (or simulation-based) inference algorithm,
specifically sequential Monte Carlo-based approximate Bayesian computation
(SMC-ABC), to draw posterior samples of hyperparameters given dynamic
monitoring well data. In the second step we use an ensemble smoother with
multiple data assimilation (ESMDA) procedure to provide posterior realizations
of grid-block permeability. To reduce computational costs, a 3D recurrent
R-U-Net deep learning-based surrogate model is applied for forward function
evaluations. A rejection sampling (RS) procedure for data assimilation is
applied to provide reference posterior results. Detailed posterior results from
SMC-ABC-ESMDA are compared to those from the reference RS method. Close
agreement is achieved with 'converged' RS results, for two synthetic true
models, in all quantities considered. Importantly, the SMC-ABC-ESMDA procedure
provides speedup of 1-2 orders of magnitude relative to RS for the two cases. A
modified standalone ESMDA procedure is introduced for comparison purposes. For
the same number of function evaluations, the hierarchical approach is shown to
provide superior results for posterior hyperparameter distributions and
monitoring well pressure predictions.
Earth’s drylands store large amounts of organic carbon and thus play an important role in regulating atmospheric CO2 concentrations and mitigating climate change. However, little is known about the magnitude and the drivers of organic carbon stocks because of limited data, in particular in desert ecosystems. To fill this gap, we surveyed 763 plots and collected 5091 soil samples from 170 sites covering grassland and desert ecosystems across the drylands of China. The results show that 10.96 Pg organic carbon is stored in these ecosystems (7.07 Pg in grasslands and 3.89 Pg in deserts). The effects of environmental variables on carbon density were found to be contingent on ecosystem type and soil depth. Mean annual precipitation had a strong positive effect on the spatial distributions of vegetation carbon density in both types of ecosystems. The spatial variations of surface (0–40 cm) and subsurface (40–100 cm) soil organic carbon (SOC) density in grasslands were mainly correlated with plant productivity and mean annual temperature (MAT), respectively, while in desert ecosystems, they were mainly correlated with soil salinity (electrical conductivity). The spatial sensitivities (linear regression slopes) of the surface SOC density versus MAT increased from dry subhumid to semi-arid regions and then gradually shifted to decrease from semi-arid to hyper-arid regions, indicating that the surface SOC stock is more sensitive to temperature in semi-arid regions. This study provides a comprehensive survey of ecosystem carbon stocks in China’s drylands, fills a gap in our knowledge about carbon stocks in deserts, complements estimates of ecosystem carbon stocks throughout China, and provides insights into our understanding of the carbon cycle in drylands.
Arbuscular mycorrhizal (AM) symbioses in plants are broadly significant because of their capacity to facilitate water and nutrient acquisition and thus, to promote vigorous growth and development among host plants. Many horticultural plants, especially citrus plants, are highly dependent on AM fungi. In return, AM fungi receive sugars and lipids from their host plants. The sugars (mainly sucrose) are transported from the aerial parts of host plants to the roots and thus, form a mycorrhizal carbon pool. In roots, sucrose is converted to hexoses, which are then taken up by AM fungal intraradical hyphae and converted to trehalose and glycogen for growth and storage in extraradical hyphae and potentially participate in the soil carbon cycle through as the glomalin-related soil proteins. Therefore, the root mycorrhizal carbon pool influences the sugar (mainly sucrose) metabolism of plants, providing a guarantee for mycorrhizal plants to maintain better plant growth, stress resistance, fruit quality, lateral root development, and soil carbon sequestration. Thus, sugar metabolism is a player in the dialog between AM fungi and plants. This review briefly summarizes the processes of sucrose synthesis, transport, and metabolism, and highlights the relationship between AM fungi and plant sugars with an emphasis on AM-carbon pools, osmotic adjustment, fruit quality, and sugar-associated gene expression. Future research prospects are discussed.
CCSD;American Association for the Advancement of Science (AAAS)Januar 2022Klimawissenschaft
International audience;
The enhanced seasonal amplitude of atmospheric CO2 has been viewed so far primarily as a Northern Hemisphere phenomenon. Yet, analyses of atmospheric CO2 records from 49 stations between 1980 and 2018 reveal substantial trends and variations in this amplitude globally. While no significant trends can be discerned before 2000 in most places, strong positive trends emerge after 2000 in the southern high latitudes. Using factorial simulations with an atmospheric transport model and analyses of surface ocean Pco2 observations, we show that the increase is best explained by the onset of increasing seasonality of air-sea CO2 exchange over the Southern Ocean around 2000. Underlying these changes is the long-term ocean acidification trend that tends to enhance the seasonality of the air-sea fluxes, but this trend is modified by the decadal variability of the Southern Ocean carbon sink. The seasonal variations of atmospheric CO2 thus emerge as a sensitive recorder of the variations of the Southern Ocean carbon sin
Mitigating climate change requires transforming agriculture to minimize
environ mental impact and build climate resilience. Regenerative agricultural
practices enhance soil organic carbon (SOC) levels, thus improving soil health
and sequestering carbon. A challenge to increasing regenerative agriculture
practices is cheaply measuring SOC over time and understanding how SOC is
affected by regenerative agricultural practices and other environmental factors
and farm management practices. To address this challenge, we introduce an
AI-driven Soil Organic Carbon Copilot that automates the ingestion of complex
multi-resolution, multi-modal data to provide large-scale insights into soil
health and regenerative practices. Our data includes extreme weather event data
(e.g., drought and wildfire incidents), farm management data (e.g., cropland
information and tillage predictions), and SOC predictions. We find that
integrating public data and specialized models enables large-scale, localized
analysis for sustainable agriculture. In comparisons of agricultural practices
across California counties, we find evidence that diverse agricultural activity
may mitigate the negative effects of tillage; and that while extreme weather
conditions heavily affect SOC, composting may mitigate SOC loss. Finally,
implementing role-specific personas empowers agronomists, farm consultants,
policymakers, and other stakeholders to implement evidence-based strategies
that promote sustainable agriculture and build climate resilience.
International audience;
Salt marshes are blue carbon (C) ecosystems characterized by intense atmospheric CO2 uptake and C sequestration but also by organic and inorganic C exports through the tide. However, uncertainties about the main biotic factors controlling these vertical and horizontal C fluxes imply studying terrestrial and aquatic metabolisms simultaneously at small timescales (diurnal and tidal) to distinguish their contributions to net ecosystem CO2 exchange (NEE). In a temperate salt marsh, four sampling 24 h cycles were performed to measure all water C biogeochemical parameters (including CO2 partial pressures, pCO2), nutrients, and aquatic metabolism simultaneously to NEE from high tide during marsh immersion (imported coastal waters influenced by the continental shelf) to low tide during marsh emersion (exported channel waters influenced by the marsh drainage). At high tide, water CO2 oversaturation (water pCO2 > air pCO2) due to marsh aquatic heterotrophy and CO2-concentrated water inputs from the coastal end-member induced water–air CO2 emissions during marsh immersion. At low tide, water pCO2 in the channel were also mainly controlled by the marsh aquatic metabolism, inducing a water CO2 oversaturation in winter due to dominant heterotrophy and a water CO2 undersaturation in spring and summer due to dominant autotrophy. In winter, the greatest increases in dissolved inorganic carbon (DIC; from 2354 to 3963 µmol kg−1), total alkalinity (TA; from 2508 to 4016 µmol kg−1) and dissolved inorganic nitrogen (DIN; from 27.7 to 68.4 µM) were measured simultaneously during low tide at night, probably due to intense aerobic/anaerobic microbial respiration of organic matter in channel waters and/or sediments resulting in the greatest water pCO2 increase (from 533 to 1461 ppmv). On the contrary, in spring and summer, large water pCO2 decreases (down to 83 ppmv) and dissolved organic carbon (DOC) increases (up to 1040 µM) from high to low tide could be related to intense autochthonous and allochthonous marsh primary production, including benthic microalgae, phytoplankton and macroalgae. This study suggests that the horizontal exchanges of coastal waters with the salt marsh significantly modify water C dynamics and associated water CO2 sink/source state in the channel due to an intense marsh metabolism (production and respiration). At the daily scale, plant and phytoplankton metabolism rates played a major and a minor role, respectively, in the marsh CO2 sink measured by atmospheric eddy covariance at the ecosystem scale (NEE), even during immersion where emerged plants located on the highest marsh levels can maintain a low CO2 uptake, despite aquatic heterotrophy and associated water–air CO2 emissions.
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