Recente wetenschappelijke publicaties per onderzoeksgebied
Krijg toegang tot recente wetenschappelijke publicaties per discipline om werk te identificeren dat relevant is voor uw analyse, monitoring of onderzoek.
Individuals with Alzheimer's disease (AD) and Alzheimer's disease-related dementia (ADRD) experience memory and thinking changes that impact their ability to use digital daily management tools. For example, adding an event to a digital calendar requires multiple steps that may act as barriers to independent use for individuals with AD/ADRD. This paper presents AI-Care, a conversational agentic artificial intelligence (AI) layer built on top of a remote caregiving platform co-designed with people with AD/ADRD. AI-Care is designed to reduce the cognitive load on individuals with AD/ADRD when managing everyday tasks such as setting calendar reminders and organizing to-do lists through natural-language interaction with a voice-first chatbot. The system uses a LangGraph-based stateful orchestration approach in which each request passes through sanitization, intent classification, context loading, safety checks, deterministic slot collection, tool execution, and response composition. Safety-critical responses, particularly around medications and allergies, are grounded in caregiver-verified records rather than free-form model generation. The system does not make autonomous medical or treatment decisions. Incomplete or ambiguous requests are handled through controlled multi-turn clarification rather than silent failure or guessing. The system supports both typed and spoken input, with voice output through ElevenLabs text-to-speech. Longer responses are chunked before synthesis to avoid rushed playback. A preliminary pilot with four individuals with mild-to-moderate AD/ADRD showed that users found the system trustworthy, competent, and likable, and were able to complete the evaluated coordination tasks through conversation. We describe the design goals, system architecture, safety controls, and findings from this formative evaluation. ;9 pages, 3 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.
Alzheimer's disease (AD) presents a complex, multifaceted challenge to patients, caregivers, and the healthcare system, necessitating integrated and dynamic support solutions. While artificial intelligence (AI) offers promising avenues for intervention, current applications are often siloed, addressing singular aspects of the disease such as diagnostics or caregiver support without systemic integration. This paper proposes a novel methodological framework for a comprehensive, multi-agent system (MAS) designed for holistic Alzheimer's disease management. The objective is to detail the architecture of a collaborative ecosystem of specialized AI agents, each engineered to address a distinct challenge in the AD care continuum, from caregiver support and multimodal data analysis to automated research and clinical data interpretation. The proposed framework is composed of eight specialized, interoperable agents. These agents are categorized by function: (1) Caregiver and Patient Support, (2) Data Analysis and Research, and (3) Advanced Multimodal Workflows. The methodology details the technical architecture of each agent, leveraging a suite of advanced technologies including large language models (LLMs) such as GPT-4o and Gemini, multi-agent orchestration frameworks, Retrieval-Augmented Generation (RAG) for evidence-grounded responses, and specialized tools for web scraping, multimodal data processing, and in-memory database querying. This paper presents a detailed architectural blueprint for an integrated AI ecosystem for AD care. By moving beyond single-purpose tools to a collaborative, multi-agent paradigm, this framework establishes a foundation for developing more adaptive, personalized, and proactive solutions. This methodological approach aims to pave the way for future systems capable of synthesizing diverse data streams to improve patient outcomes and reduce caregiver burden.
The development of monoclonal anti-amyloid antibodies, a disease-modifying treatment for Alzheimer’s disease (AD), has raised the necessity to identify the epidemiological profile of the possible target patients who would benefit from such therapy. These are patients in the early stages of AD with biomarker-confirmed brain amyloid positivity. In this study, the epidemiological profile of possible target patients in Austria and Vienna was estimated. The number of patients in the stage of amyloid-beta (Aβ)-positive prodromal AD in Austria and Vienna are 193,500 and 34,700 patients, respectively. The expected patient demand for the upcoming therapy in Austria and Vienna are 61,200 and 11,100 patients, respectively. In the memory clinic of the Vienna General Hospital, the number of treatment-eligible patients for an upcoming anti-amyloid antibody was on average 52.8 patients per year, which is about 10% of the total number of patients visiting the memory clinic every year. Several challenges to provide therapy to the general population include expanding the MCI screening in primary care and increasing the capacity of the healthcare system for biomarker testing, infusion delivery, and ARIA management. The study primarily addresses the status quo of identifying patients on memory clinics through cognitive screening and biomarker testing.
Early detection of Alzheimer's disease from spontaneous speech has emerged as a promising non-invasive screening approach. However, the influence of automatic speech recognition (ASR) quality on downstream clinical language modeling remains insufficiently understood. In this study, we investigate Alzheimer's disease detection using lexical features derived from Whisper ASR transcripts on the ADReSSo 2021 diagnosis dataset. We evaluate interpretable machine-learning models, including Logistic Regression and Linear Support Vector Machines, using TF-IDF text representations under repeated 5x5 stratified cross-validation.
Our results demonstrate that transcript quality has a statistically significant impact on classification performance. Models trained on Whisper-small transcripts consistently outperform those using Whisper-base transcripts, achieving balanced accuracy above 0.7850 with Linear SVM. Paired statistical testing confirms that the observed improvements are significant. Importantly, classifier complexity contributes less to performance variation than ASR transcription quality. Feature analysis reveals that cognitively normal speakers produce more semantically precise object- and scene-descriptive language, whereas Alzheimer's speech is characterized by vagueness, discourse markers, and increased hesitation patterns.
These findings suggest that high-quality ASR can enable simple, interpretable lexical models to achieve competitive Alzheimer's detection performance without explicit acoustic modeling. The study provides a reproducible benchmark pipeline and highlights ASR selection as a critical modeling decision in clinical speech-based artificial intelligence systems. ;22 pages, 7 figures
Medium-horizon Alzheimer's disease progression prediction is difficult because future clinical scores can remain tied to baseline severity, while biomarker histories are irregular and incompletely observed. We develop an anchor-based analysis of 24-month Clinical Dementia Rating Sum of Boxes (CDR-SB) change using harmonized Alzheimer's Disease Neuroimaging Initiative (ADNI) tables. Each labeled sample is anchored at a mild cognitive impairment visit, uses only clinical and biomarker history observed at or before that anchor, and defines the response as CDR-SB at the future visit closest to 24 months within an 18--30 month window minus anchor CDR-SB. The analytic cohort contains 2,600 labeled anchors from 858 participants and 7,276 longitudinal rows. We propose a residual gap-aware transformer that combines a mixed-effects statistical reference with transformer-based residual learning from pre-anchor clinical and biomarker histories. The model uses participant-level random intercepts in the mixed-effects reference, observation-level triplet tokenization for irregular histories, and a learned nonnegative time-gap penalty inside self-attention. We compare the proposed model with a Bayesian-information-criterion-selected linear mixed-effects baseline, GRU-D, and STraTS under repeated participant-level train--test splits. Across five participant-level random seeds, the proposed model achieves the best mean test performance across all reported metrics, reducing MSE by 13.1% and increasing prediction--observation correlation by 26.4% relative to the mixed-effects baseline. It also improves over both GRU-D and STraTS in mean error and correlation. These results show that statistical anchoring and gap-aware residual learning provide a useful structure for medium-horizon Alzheimer's disease progression prediction. ;Preprint; includes appendix, 4 figures, and 6 tables
Individualized Alzheimer's disease (AD) progression prediction requires models that use irregular visits, account for censoring, avoid diagnostic leakage, and provide calibrated horizon risks. We propose PROgression-aware MultI-horizon Survival Estimation for Alzheimer's Disease (PROMISE-AD), a leakage-safe survival framework for predicting conversion from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD dementia using ADNI/TADPOLE tabular histories. PROMISE-AD converts pre-index visits into tokens with standardized measurements, missingness masks, longitudinal changes, time-normalized slopes, visit timing, and non-diagnostic categorical attributes. A temporal Transformer fuses global, attention-pooled, and latest-visit representations to estimate a progression score and latent discrete-time mixture hazards. Training combines survival likelihood, horizon-specific focal risk loss, progression ranking, hazard smoothness, and mixture-balance regularization, followed by validation-set isotonic calibration for 1-, 2-, 3-, and 5-year risks. In held-out testing across three seeds, PROMISE-AD achieved an integrated Brier score (IBS) of 0.085 $\pm$ 0.012, C-index of 0.808 $\pm$ 0.015, and mean time-dependent AUC of 0.840 $\pm$ 0.081 for CN-to-MCI conversion, yielding the lowest IBS among compared methods. For MCI-to-AD conversion, PROMISE-AD achieved the highest C-index (0.894 $\pm$ 0.018) and near-ceiling 5-year discrimination (AUROC 0.997 $\pm$ 0.003; AUPRC 0.999 $\pm$ 0.001), although some baselines had lower IBS. Ablations and interpretability supported longitudinal change features, fused temporal representations, mixture hazards, cognitive and functional measures, APOE4 status, and recent conversion-proximal visits. These findings suggest that progression-aware survival modeling can provide interpretable multi-horizon AD conversion risk estimates.
Alzheimer's disease affects over 55 million people worldwide and is projected to more than double by 2050, necessitating rapid, accurate, and scalable diagnostics. However, existing approaches are limited because they cannot achieve clinically acceptable accuracy, generalization across datasets, robustness to missing modalities, and explainability all at the same time. This inability to satisfy all these requirements simultaneously undermines their reliability in clinical settings. We propose OmniBrain, a multimodal framework that integrates brain MRI, radiomics, gene expression, and clinical data using a unified model with cross-attention and modality dropout. OmniBrain achieves $92.2 \pm 2.4\%$accuracy on the ANMerge dataset and generalizes to the MRI-only ADNI dataset with $70.4 \pm 2.7\%$ accuracy, outperforming unimodal and prior multimodal approaches. Explainability analyses highlight neuropathologically relevant brain regions and genes, enhancing clinical trust. OmniBrain offers a robust, interpretable, and practical solution for real-world Alzheimer's diagnosis. ;Published in Third Workshop on Computer Vision for Automated Medical Diagnosis CVAMD 2025 in ICCV 2025
Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions
worldwide, necessitating early and accurate diagnosis for optimal patient
management. In recent years, advancements in deep learning have shown
remarkable potential in medical image analysis. Methods In this study, we
present "ViTranZheimer," an AD diagnosis approach which leverages video vision
transformers to analyze 3D brain MRI data. By treating the 3D MRI volumes as
videos, we exploit the temporal dependencies between slices to capture
intricate structural relationships. The video vision transformer's
self-attention mechanisms enable the model to learn long-range dependencies and
identify subtle patterns that may indicate AD progression. Our proposed deep
learning framework seeks to enhance the accuracy and sensitivity of AD
diagnosis, empowering clinicians with a tool for early detection and
intervention. We validate the performance of the video vision transformer using
the ADNI dataset and conduct comparative analyses with other relevant models.
Results The proposed ViTranZheimer model is compared with two hybrid models,
CNN-BiLSTM and ViT-BiLSTM. CNN-BiLSTM is the combination of a convolutional
neural network (CNN) and a bidirectional long-short-term memory network
(BiLSTM), while ViT-BiLSTM is the combination of a vision transformer (ViT)
with BiLSTM. The accuracy levels achieved in the ViTranZheimer, CNN-BiLSTM, and
ViT-BiLSTM models are 98.6%, 96.479%, and 97.465%, respectively. ViTranZheimer
demonstrated the highest accuracy at 98.6%, outperforming other models in this
evaluation metric, indicating its superior performance in this specific
evaluation metric. Conclusion This research advances the understanding of
applying deep learning techniques in neuroimaging and Alzheimer's disease
research, paving the way for earlier and less invasive clinical diagnosis.
Mild Cognitive Impairment (MCI) serves as a prodromal stage of Alzheimer's Disease (AD), where early identification and intervention can effectively slow the progression to dementia. However, diagnosing AD remains a significant challenge in neurology due to the confounders caused mainly by the selection bias of multi-modal data and the complex relationships between variables. To address these issues, we propose a novel visual-language causality-inspired framework named Cross-modal Causal Intervention with Mediator for Alzheimer's Disease Diagnosis (MediAD) for diagnostic assistance. Our MediAD employs Large Language Models (LLMs) to summarize clinical data under strict templates, therefore enriching textual inputs. The MediAD model utilizes Magnetic Resonance Imaging (MRI), clinical data, and textual data enriched by LLMs to classify participants into Cognitively Normal (CN), MCI, and AD categories. Because of the presence of confounders, such as cerebral vascular lesions and age-related biomarkers, non-causal models are likely to capture spurious input-output correlations, generating less reliable results. Our framework implicitly mitigates the effect of both observable and unobservable confounders through a unified causal intervention method. Experimental results demonstrate the outstanding performance of our method in distinguishing CN/MCI/AD cases, outperforming other methods in most evaluation metrics. The study showcases the potential of integrating causal reasoning with multi-modal learning for neurological disease diagnosis.
Background and Objective: In brain imaging, geometric surface models are essential for analyzing the 3D shapes of anatomical structures. Alzheimer's disease (AD) is associated with significant cortical atrophy, making such shape analysis a valuable diagnostic tool. The objective of this study is to introduce and validate a novel local surface representation method for the automated and accurate diagnosis of AD. Methods: The study utilizes T1-weighted MRI scans from 160 participants (80 AD patients and 80 healthy controls) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cortical surface models were reconstructed from the MRI data using Freesurfer. Key geometric attributes were computed from the 3D meshes. Area distortion and conformal factor were derived using Ricci flow for conformal parameterization, while Gaussian curvature was calculated directly from the mesh geometry. Shannon entropy was applied to these three features to create compact and informative feature vectors. The feature vectors were used to train and evaluate a suite of classifiers (e.g. XGBoost, MLP, Logistic Regression, etc.). Results: Statistical significance of performance differences between classifiers was evaluated using paired Welch's t-test. The method proved highly effective in distinguishing AD patients from healthy controls. The Multi-Layer Perceptron (MLP) and Logistic Regression classifiers outperformed all others, achieving an accuracy and F$_1$ Score of 98.62%. Conclusions: This study confirms that the entropy of conformally-derived geometric features provides a powerful and robust metric for cortical morphometry. The high classification accuracy underscores the method's potential to enhance the study and diagnosis of Alzheimer's disease, offering a straightforward yet powerful tool for clinical research applications.
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.
Alzheimer's disease (AD) is the leading cause of dementia, and its early
detection is crucial for effective intervention, yet current diagnostic methods
often fall short in sensitivity and specificity. This study aims to detect
significant indicators of early AD by extracting and integrating various
imaging biomarkers, including radiomics, hippocampal texture descriptors,
cortical thickness measurements, and deep learning features. We analyze
structural magnetic resonance imaging (MRI) scans from the Alzheimer's Disease
Neuroimaging Initiative (ADNI) cohorts, utilizing comprehensive image analysis
and machine learning techniques. Our results show that combining multiple
biomarkers significantly improves detection accuracy. Radiomics and texture
features emerged as the most effective predictors for early AD, achieving AUCs
of 0.88 and 0.72 for AD and MCI detection, respectively. Although deep learning
features proved to be less effective than traditional approaches, incorporating
age with other biomarkers notably enhanced MCI detection performance.
Additionally, our findings emphasize the continued importance of classical
imaging biomarkers in the face of modern deep-learning approaches, providing a
robust framework for early AD diagnosis.
;Comment: SPIE Medical Imaging (MI25)
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.
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.
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.
BACKGROUND: Better cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD) are needed. OBJECTIVE: In this prospective longitudinal cohort, we are testing if changes in the cognitive domains of executive functioning and processing speed can predict global cognitive decline. METHODS: We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for processing speed and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). RESULTS: Among 184 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD (n = 24), pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p = 0.008 and 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08–1.60) and 1.62 (1.16–2.26)). CONCLUSIONS: Testing for cognitive domains of processing speed and executive functioning may predict subsequent global cognitive.
Alzheimer's disease is a debilitating disorder marked by a decline in cognitive function. Timely identification of the disease is essential for the development of personalized treatment strategies that aim to mitigate its progression. The application of generated images for the prediction of Alzheimer's disease poses challenges, particularly in accurately representing the disease's characteristics when input sequences are captured at irregular time intervals. This study presents an innovative methodology for sequential image generation, guided by quantitative metrics, to maintain the essential features indicative of disease progression. Furthermore, an age-scaling factor is integrated into the process to produce age-specific MRI images, facilitating the prediction of advanced stages of the disease. The results obtained from the ablation study suggest that the inclusion of quantitative metrics significantly improves the accuracy of MRI image synthesis. Furthermore, the application of age-scaled pixel loss contributed to the enhanced iterative generation of MRI images. In terms of long-term disease prognosis, the Structural Similarity Index reached a peak value of 0.882, indicating a substantial degree of similarity in the synthesized images. ;16 pages, 9 figures
Accumulation of amyloid beta proteins is a defining feature of Alzheimer's disease, and is usually accompanied by cerebrovascular pathology. Evidence suggests that amyloid beta and cerebrovascular pathology are mutually reinforcing; in particular, amyloid beta suppresses perfusion by constricting capillaries, and hypoperfusion promotes the production of amyloid beta. Here, we propose a whole-brain model coupling amyloid beta and blood vessel through a hybrid model consisting of a reaction-diffusion system for the protein dynamics and porous-medium model of blood flow within and between vascular networks: arterial, capillary and venous. We discretize the resulting parabolic--elliptic system of PDEs by means of a high-order discontinuous Galerkin method in space and an implicit Euler scheme in time. Simulations in realistic brain geometries demonstrate the emergence of multistability, implying that a sufficiently large pathogenic protein seeds is necessary to trigger disease outbreak. Motivated by the "two-hit vascular hypothesis" of Alzheimer's disease that hypoperfusive vascular damage triggers amyloid beta pathology, we also demonstrate that localized hypoperfusion, in response to injury, can destabilize the healthy steady state and trigger brain-wide disease outbreak.
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
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 presents an innovative method for Alzheimer's disease diagnosis
using 3D MRI designed to enhance the explainability of model decisions. Our
approach adopts a soft attention mechanism, enabling 2D CNNs to extract
volumetric representations. At the same time, the importance of each slice in
decision-making is learned, allowing the generation of a voxel-level attention
map to produce an explainable MRI. To test our method and ensure the
reproducibility of our results, we chose a standardized collection of MRI data
from the Alzheimer's Disease Neuroimaging Initiative (ADNI). On this dataset,
our method significantly outperforms state-of-the-art methods in (i)
distinguishing AD from cognitive normal (CN) with an accuracy of 0.856 and
Matthew's correlation coefficient (MCC) of 0.712, representing improvements of
2.4% and 5.3% respectively over the second-best, and (ii) in the prognostic
task of discerning stable from progressive mild cognitive impairment (MCI) with
an accuracy of 0.725 and MCC of 0.443, showing improvements of 10.2% and 20.5%
respectively over the second-best. We achieved this prognostic result by
adopting a double transfer learning strategy, which enhanced sensitivity to
morphological changes and facilitated early-stage AD detection. With
voxel-level precision, our method identified which specific areas are being
paid attention to, identifying these predominant brain regions: the
hippocampus, the amygdala, the parahippocampal, and the inferior lateral
ventricles. All these areas are clinically associated with AD development.
Furthermore, our approach consistently found the same AD-related areas across
different cross-validation folds, proving its robustness and precision in
highlighting areas that align closely with known pathological markers of the
disease.
;Comment: 21 pages, 9 figures, 9 tables
Alzheimer's disease detection requires expensive neuroimaging or invasive procedures, limiting accessibility. This study explores whether deep learning can enable non-invasive Alzheimer's disease detection through handwriting analysis. Using a dataset of 34 distinct handwriting tasks collected from healthy controls and Alzheimer's disease patients, we evaluate and compare three recurrent neural architectures (LSTM, GRU, RNN) against traditional machine learning models. A crucial distinction of our approach is that the recurrent models process pre-extracted features from discrete strokes, not raw temporal signals. This violates the assumption of a continuous temporal flow that recurrent networks are designed to capture. Results reveal that they exhibit poor specificity and high variance. Traditional ensemble methods significantly outperform all deep architectures, achieving higher accuracy with balanced metrics. This demonstrates that recurrent architectures, designed for continuous temporal sequences, fail when applied to feature vectors extracted from ambiguously segmented strokes. Despite their complexity, deep learning models cannot overcome the fundamental disconnect between their architectural assumptions and the discrete, feature-based nature of stroke-level handwriting data. Although performance is limited, the study highlights several critical issues in data representation and model compatibility, pointing to valuable directions for future research.
Neurodegeneration as measured through magnetic resonance imaging (MRI) is
recognized as a potential biomarker for diagnosing Alzheimer's disease (AD),
but is generally considered less specific than amyloid or tau based biomarkers.
Due to a large amount of variability in brain anatomy between different
individuals, we hypothesize that leveraging MRI time series can help improve
specificity, by treating each patient as their own baseline. Here we turn to
conditional variational autoencoders to generate individualized MRI predictions
given the subject's age, disease status and one previous scan. Using serial
imaging data from the Alzheimer's Disease Neuroimaging Initiative, we train a
novel architecture to build a latent space distribution which can be sampled
from to generate future predictions of changing anatomy. This enables us to
extrapolate beyond the dataset and predict MRIs up to 10 years. We evaluated
the model on a held-out set from ADNI and an independent dataset (from Open
Access Series of Imaging Studies). By comparing to several alternatives, we
show that our model produces more individualized images with higher resolution.
Further, if an individual already has a follow-up MRI, we demonstrate a usage
of our model to compute a likelihood ratio classifier for disease status. In
practice, the model may be able to assist in early diagnosis of AD and provide
a counterfactual baseline trajectory for treatment effect estimation.
Furthermore, it generates a synthetic dataset that can potentially be used for
downstream tasks such as anomaly detection and classification.
;Comment: MICCAI 2024 LDTM workshop
BACKGROUND: Clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) poses significant challenges due to pathological comorbidity. Similar ages of onset and overlapping cognitive and psychiatric symptoms can lead to diagnostic inaccuracy and inappropriate treatment recommendations. OBJECTIVE: Identify the best combination of clinical and neuropsychological predictors of AD, DLB, and mixed DLB/AD neuropathology in dementia patients. METHODS: Using the National Alzheimer's Coordinating Center dataset, we selected either pure AD (n = 189), DLB (n = 21), or mixed DLB/AD (n = 42) patients on autopsy. Neuropsychological and clinical predictors, including core clinical features of DLB, were entered into multivariable logistic regressions. RESULTS: Gait disturbances (odds ratio (OR) = 19.32; p = 0.01), visual-spatial complaints (OR = 6.06; p = 0.03), and visual hallucinations (OR = 31.06; p = 0.002) predicted DLB compared to AD, along with better memory (OR = 3.42; p = 0.003), naming (OR = 3.35; p = 0.002), and worse processing speed (OR = 0.51; p = 0.01). When comparing DLB to DLB/AD, gait disturbances (OR = 6.33; p = 0.01), increased depressive symptoms (OR = 1.44; p = 0.03), and better memory (OR = 3.01; p = 0.004) predicted DLB. Finally, rapid eye movement sleep behavior disorder (RBD) (OR = 6.44; p = 0.004), parkinsonism severity (OR = 1.07; p = 0.02), and lower depressive symptoms (OR = 0.70; p = 0.006) and memory impairment (OR = 0.57; p = 0.02) distinguished DLB/AD from AD. CONCLUSIONS: Our study converges with prior research suggesting specific neuropsychological and clinical features can help distinguish DLB from AD. Neuropsychological differentiation becomes more challenging among mixed pathologies and in advanced cognitive impairment, although the presence of RBD and parkinsonism distinguished DLB. Earlier clinical assessment and incorporation of in vivo and postmortem biomarkers should enhance diagnostic accuracy and understanding of disease characteristics, offering significant relevance for disease-modifying treatments.
25 wetenschappelijke publicaties binnen het domein Amyotrofische Laterale Sclerose
, voor snelle raadpleging van de bijbehorende wetenschappelijke literatuur.
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.
Objective To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN). Methods This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients ( n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden’s index), and correlations with demographic characteristics were calculated. Results Neurofilament concentrations were significantly higher in MND compared to MMN ( p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman’s rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease. Conclusion Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.
Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia-like cells that are capable of expressing molecular markers, and functional characteristics similar to in vivo human brain microglia. Methods In this study, we have established monocyte-derived microglia-like cells from 30 sporadic patients with ALS, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected healthy controls. Results We demonstrate that patient monocyte-derived microglia-like cells recapitulate canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive inclusions. Moreover, ALS microglia-like cells showed significantly impaired phagocytosis, altered cytokine profiles, and abnormal morphologies consistent with a neuroinflammatory phenotype. Interestingly, all ALS microglia-like cells showed abnormal phagocytosis consistent with the progression of the disease. In-depth analysis of ALS microglia-like cells from the rapid disease progression cohort revealed significantly altered cell-specific variation in phagocytic function. In addition, DNA damage and NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activity were also elevated in ALS patient monocyte-derived microglia-like cells, indicating a potential new pathway involved in driving disease progression. Conclusions Taken together, our work demonstrates that the monocyte-derived microglia-like cell model recapitulates disease-specific hallmarks and characteristics that substantiate patient heterogeneity associated with disease subgroups. Thus, monocyte-derived microglia-like cells are highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents, providing a basis for personalised treatment for patients with ALS.
TDP-43 is an aggregation-prone protein which accumulates in the hallmark pathological inclusions of amyotrophic lateral sclerosis (ALS). However, the analysis of deeply phenotyped human post-mortem samples has shown that TDP-43 aggregation, revealed by standard antibody methods, correlates poorly with symptom manifestation. Recent identification of cryptic-splicing events, such as the detection of Stathmin-2 ( STMN-2 ) cryptic exons, are providing evidence implicating TDP-43 loss-of-function as a potential driving pathomechanism but the temporal nature of TDP-43 loss and its relation to the disease process and clinical phenotype is not known. To address these outstanding questions, we used a novel RNA aptamer, TDP-43^APT, to detect TDP-43 pathology and used single molecule in situ hybridization to sensitively reveal TDP-43 loss-of-function and applied these in a deeply phenotyped human post-mortem tissue cohort. We demonstrate that TDP-43^APT identifies pathological TDP-43, detecting aggregation events that cannot be detected by classical antibody stains. We show that nuclear TDP-43 pathology is an early event, occurring prior to cytoplasmic accumulation and is associated with loss-of-function measured by coincident STMN-2 cryptic splicing pathology. Crucially, we show that these pathological features of TDP-43 loss-of-function precede the clinical inflection point and are not required for region specific clinical manifestation. Furthermore, we demonstrate that gain-of-function in the form of extensive cytoplasmic accumulation, but not loss-of-function, is the primary molecular correlate of clinical manifestation. Taken together, our findings demonstrate implications for early diagnostics as the presence of STMN-2 cryptic exons and early TDP-43 aggregation events could be detected prior to symptom onset, holding promise for early intervention in ALS.
The deposition of aggregated proteins is a common neuropathological denominator for neurodegenerative disorders. Experimental evidence suggests that disease propagation involves prion-like mechanisms that cause the spreading of template-directed aggregation of specific disease-associated proteins. In transgenic (Tg) mouse models of superoxide dismutase-1 ( SOD1 )-linked amyotrophic lateral sclerosis (ALS), inoculation of minute amounts of human SOD1 (hSOD1) aggregates into the spinal cord or peripheral nerves induces premature ALS-like disease and template-directed hSOD1 aggregation that spreads along the neuroaxis. This infectious nature of spreading pathogenic aggregates might have implications for the safety of laboratory and medical staff, recipients of donated blood or tissue, or possibly close relatives and caregivers. Here we investigate whether transmission of ALS-like disease is unique to the spinal cord and peripheral nerve inoculations or if hSOD1 aggregation might spread from the periphery into the central nervous system (CNS). We inoculated hSOD1 aggregate seeds into the peritoneal cavity, hindlimb skeletal muscle or spinal cord of adult Tg mice expressing mutant hSOD1. Although we used up to 8000 times higher dose—compared to the lowest dose transmitting disease in spinal cord inoculations—the peripheral inoculations did not transmit seeded aggregation to the CNS or premature ALS-like disease in hSOD1 Tg mice. Nor was any hSOD1 aggregation detected in the liver, kidney, skeletal muscle or sciatic nerve. To explore potential reasons for the lack of disease transmission, we examined the stability of hSOD1 aggregates and found them to be highly vulnerable to both proteases and detergent. Our findings suggest that exposed individuals and personnel handling samples from ALS patients are at low risk of any potential transmission of seeded hSOD1 aggregation.
Amyotrophic lateral sclerosis (ALS) attacks the corticomotor system, with motor cortex function affected early in disease. Younger females have a lower relative risk of succumbing to ALS than males and older females, implicating a role for female sex hormones in disease progression. However, the mechanisms driving this dimorphic incidence are still largely unknown. We endeavoured to determine if estrogen mitigates disease progression and pathogenesis, focussing upon the dendritic spine as a site of action. Using two-photon live imaging we identify, in the prp TDP-43^A315T mouse model of ALS, that dendritic spines in the male motor cortex have a reduced capacity for remodelling than their wild-type controls. In contrast, females show higher capacity for remodelling, with peak plasticity corresponding to highest estrogen levels during the estrous cycle. Estrogen manipulation through ovariectomies and estrogen replacement with 17β estradiol in vivo was found to significantly alter spine density and mitigate disease severity. Collectively, these findings reveal that synpatic plasticity is reduced in ALS, which can be amelioriated with estrogen, in conjuction with improved disease outcomes.
Background Epidemiological studies have reported an association between amyotrophic lateral sclerosis (ALS) and different autoimmune disorders. This study aims to explore the causal relationship between autoimmune disorders and ALS using Mendelian randomization (MR). Methods To test the genetically predicted effects of liability towards immune-related outcomes on ALS risk, we used summary statistics from the largest European genome-wide association studies (GWAS) for these disorders in a two-sample MR setting. To do this, we extracted single nucleotide polymorphisms (SNPs) from the GWAS, which strongly associated with the 12 traits, and queried their effects in a large European ALS GWAS (27,265 cases and 110,881 controls). To avoid bias in our MR instruments related to the complex linkage disequilibrium structure of the human leukocyte antigen (HLA) region, we excluded SNPs within this region from the analyses. We computed inverse-variance weighted (IVW) MR estimates and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy. We also performed a reverse MR analysis testing the causal effects of ALS on the above autoimmune traits. Results After applying Bonferroni correction for multiple testing, our MR analyses showed that the liability to autoimmune disorders does not affect ALS risk. Our reverse MR analysis also did not support the effects of liability to ALS on other autoimmune disorders. The results of the main IVW MR analyses were generally supported by our sensitivity MR analyses. The variance in the exposures explained by the sets of SNPs used as MR instruments ranged from 8.1 × 10^−4 to 0.31. Our MR study was well-powered to detect effects as small as an odds ratio (OR) of 1.045 for ALS in the main MR and as small as an OR of 1.32 in the reverse MR. Conclusion Our MR study does not support a relationship between liability to autoimmune disorders and ALS risk in the European population. The associations observed in epidemiological studies could be partly attributed to shared biology or environmental confounders.
Background Previous studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients. Methods We conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research (“starmaze”) that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test). Results Patients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups ( p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups ( p ≥ 0.238). Conclusions This study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.
Background 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.
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. Methods Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. Results A gene based collapsing model showed significant associations with SOD1 , TARDBP , and TBK1 (OR = 19.18, p = 3.67 × 10^–39; OR = 4.73, p = 2 × 10^–10; OR = 2.3, p = 7.49 × 10^–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 ( p = 4.88 × 10^–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10^–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 ( p = 8.38 × 10^–6). Conclusions In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3 . A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2 .
Background Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. Methods In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z -scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z -scores, with gradients hypothesised to represent directionality of neurodegeneration. Results At group-level, z -scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient − 0.24, [95% CI − 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). Discussion Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.
Background Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power. Methods In 125 patients with ALS from three independent prospective studies—one observational study and two interventional trials—we developed and externally validated a multivariate linear model for predicting disease progression, measured by the monthly decrease of the ALS Functional Rating Scale Revised (ALSFRS-R) score. We trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis: NfL levels, sex, age, site of onset, body mass index, disease duration, ALSFRS-R score, and monthly ALSFRS-R score decrease since disease onset. We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials. We analyzed the impact on trial power in mixed-effects models and compared the performance of the NfL model with two currently used predictive approaches, which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period (lead-in) or since disease onset (ΔFRS). Results Among the parameters provided, the NfL levels ( P < 0.001) and the interaction with site of onset ( P < 0.01) contributed significantly to the prediction, forming a robust NfL prediction model ( R = 0.67). Model application in the trial cohorts confirmed its applicability and revealed superiority over lead-in and ΔFRS-based approaches. The NfL model improved statistical power by 61% and 22% (95% confidence intervals: 54%–66%, 7%–29%). Conclusion The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could significantly increase the trial power. NCT00868166, registered March 23, 2009; NCT02306590, registered December 2, 2014.
Background MRI studies reported that ALS patients with bulbar and spinal onset showed focal cortical changes in corresponding regions of the motor homunculus. We evaluated the capability of brain 2-[^18F]FDG-PET to disclose the metabolic features characterizing patients with pure bulbar or spinal motor impairment. Methods We classified as pure bulbar (PB) patients with bulbar onset and a normal score in the spinal items of the ALSFRS-R, and as pure spinal (PS) patients with spinal onset and a normal score in the bulbar items at the time of PET. Forty healthy controls (HC) were enrolled. We compared PB and PS, and each patient group with HC. Metabolic clusters showing a statistically significant difference between PB and PS were tested to evaluate their accuracy in discriminating the two groups. We performed a leave-one-out cross-validation (LOOCV) over the entire dataset. Four classifiers were considered: support vector machines (SVM), K-nearest neighbours, linear classifier, and decision tree. Then, we used a separate test set, including 10% of patients, with the remaining 90% composing the training set. Results We included 63 PB, 271 PS, and 40 HC. PB showed a relative hypometabolism compared to PS in bilateral precentral gyrus in the regions of the motor cortex involved in the control of bulbar function. SVM showed the best performance, resulting in the lowest error rate in both LOOCV (4.19%) and test set (9.09 ± 2.02%). Conclusions Our data support the concept of the focality of ALS onset and the use of 2-[^18F]FDG-PET as a biomarker for precision medicine-oriented clinical trials.
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.
Protein homeostasis, or proteostasis, is essential for cell function and viability. Unwanted, damaged, misfolded and aggregated proteins are degraded by the ubiquitin–proteasome system (UPS) and the autophagy-lysosome pathway. Growing evidence indicates that alterations in these major proteolytic mechanisms lead to a demise in proteostasis, contributing to the onset and development of distinct diseases. Indeed, dysregulation of the UPS or autophagy is linked to several neurodegenerative, infectious and inflammatory disorders as well as cancer. Thus, modulation of protein clearance pathways is a promising approach for therapeutics. In this review, we discuss recent findings and open questions on how targeting proteolytic mechanisms could be applied for disease intervention.
Background Amyotrophic lateral sclerosis (ALS) is phenotypically heterogeneous in motor manifestations, and the extent of upper vs. lower motor neuron involvement is a widespread descriptor. This study aimed to examine cognition across different ALS motor phenotypes. Methods ALS patients ( N = 124) were classified as classical ( N = 66), bulbar ( N = 13), predominant-upper motor neuron (PUMN; N = 19), and predominant-lower motor neuron (PLMN; N = 26) phenotypes. Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and function with the ALS Functional Rating Scale—Revised (ALSFRS-R). Revised ALS-FTD consensus criteria were applied for cognitive/behavioral phenotyping. Results Defective ECAS-total scores were detected in all groups — bulbar: 15.4%, classical: 30.3%, PLMN: 23.1%, and PUMN: 36.8%. Classical and PUMN ALS patients performed worse than PLMN ones on ECAS-total, ALS-specific, Fluency, and Executive measures. No other difference was detected. Worse ASLFRS-R scores correlated with poorer ECAS-total scores in classical ALS patients. Conclusions Frontotemporal cognitive deficits are more prevalent in PUMN and classical ALS and linked to disease severity in the latter, but occur also in PLMN phenotypes.
Motor neuron disease (MND) is a rapidly progressive neurodegenerative disorder with limited treatment options. Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. The Motor Neuron Disease–Systematic Multi-Arm Randomised Adaptive Trial (MND–SMART) seeks to identify effective disease modifying drugs. This study investigates person-specific factors affecting recruitment and retention. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention. Participants with MND completed questionnaires and this was supplemented with clinical data. 12 months after completing the questionnaires we used MND–SMART recruitment data to establish if members of our cohort engaged with the trial. 120 people with MND completed questionnaires for this study. Mean age at participation was 66 (SD = 9), 14% ( n = 17) were categorised as long survivors, with 68% ( n = 81) of participants male and 60% ( n = 73) had the ALS sub-type. Of the 120 study participants, 50% ( n = 60) were randomised into MND–SMART and 78% ( n = 94) expressed interest an in participating. After the 1-year follow-up period 65% ( n = 39) of the 60 randomised participants remained in MND–SMART. Older age was significantly associated with reduced likelihood of participation (OR = 0.92, 95% CI = 0.88–0.96, p = 0.000488). The findings show that people with MND are highly motivated to engage in research, but older individuals remain significantly less likely to participate. We recommend the inclusion of studies to explore characteristics of prospective and current participants alongside trials.
Neurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impairment is characterized by a deficiency in ATP production, excessive production of reactive oxygen species, calcium dysregulation, mitochondrial transport failure, and mitochondrial dynamics deficiencies. These defects in mitochondrial health could compromise the synaptic process, leading to early cognitive dysfunction observed in these NDs. Interestingly, skin fibroblasts from AD, PD, HD, and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs. In this context, fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with neurons. Also, studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD, PD, HD, and ALS. Interestingly, these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same pathologies. Therefore, fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD, PD, HD, and ALS. This review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.
Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented.
Background Among clinicians and researchers, it is common knowledge that, in ALS, cognitive and behavioral involvement within the spectrum of frontotemporal degenerations (FTDs) begun to be regarded as a fact in the late 1990s of the twentieth century. By contrast, a considerable body of evidence on cognitive/behavioral changes in ALS can be traced in the literature dating from the late nineteenth century. Methods Worldwide reports on cognitive/behavioral involvement in ALS dating from 1886 to 1981 were retrieved thanks to Biblioteca di Area Medica “Adolfo Ferrate,” Sistema Bibliotecario di Ateneo, University of Pavia, Pavia, Italy and qualitatively synthetized. Results One-hundred and seventy-four cases of ALS with co-occurring FTD-like cognitive/behavioral changes, described in Europe, America, and Asia, were detected. Neuropsychological phenotypes were consistent with the revised Strong et al.’s consensus criteria. Clinical observations were not infrequently supported by histopathological, post-mortem verifications of extra-motor, cortical/sub-cortical alterations, as well as by in vivo instrumental exams—i.e., assessments of brain morphology/physiology and psychometric testing. In this regard, as earlier as 1907, the notion of motor and cognitive/behavioral features in ALS yielding from the same underlying pathology was acknowledged. Hereditary occurrences of ALS with cognitive/behavioral dysfunctions were reported, as well as familial associations with ALS-unrelated brain disorders. Neuropsychological symptoms often occurred before motor ones. Bulbar involvement was at times acknowledged as a risk factor for cognitive/behavioral changes in ALS. Discussion Historical observations herewith delivered can be regarded as the antecedents of current knowledge on cognitive/behavioral impairment in the ALS-FTD spectrum.
Introduction In this work, we describe a new case of association between SCA2 and MND. Case Report A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made. Discussion Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP. Conclusion CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.
Background Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with largely unknown etiology. This study compares racial differences in clinical characteristics of ALS patients enrolled in the National ALS Registry (Registry). Methods Data from ALS patients who completed the Registry’s online clinical survey during 2013–2022 were analyzed to determine characteristics such as site of onset, associated symptoms, time of symptom onset to diagnosis, and pharmacological and non-pharmacological interventions for White, Black, and other race patients. Results Surveys were completed by 4242 participants. Findings revealed that Black ALS patients were more likely to be diagnosed at a younger age, to have arm or hand initial site of onset, and to experience pneumonia than were White ALS patients. ALS patients of other races were more likely than White ALS patients to be diagnosed at a younger age and to experience twitching. The mean interval between the first sign of weakness and an ALS diagnosis for Black patients was almost 24 months, statistically greater than that of White ( p = 0.0374; 16 months) and other race patients ( p = 0.0518; 15.8 months). The mean interval between problems with speech until diagnosis was shorter for White patients (6.3 months) than for Black patients (17.7 months) and other race patients (14.8 months). Conclusions and Relevance Registry data shows racial disparities still exist in the diagnosis and clinical characteristics of ALS patients. Increased recruitment of non-White ALS patients and better characterization of symptom onset between races might aid clinicians in diagnosing ALS sooner, leading to earlier therapeutic interventions.
Dysfunction and degeneration of synapses is a common feature of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene is the main genetic cause of ALS/FTD (C9ALS/FTD). The repeat expansion leads to reduced expression of the C9orf72 protein. How C9orf72 haploinsufficiency contributes to disease has not been resolved. Here we identify the synapsin family of synaptic vesicle proteins, the most abundant group of synaptic phosphoproteins, as novel interactors of C9orf72 at synapses and show that C9orf72 plays a cell-autonomous role in the regulation of excitatory synapses. We mapped the interaction of C9orf72 and synapsin to the N-terminal longin domain of C9orf72 and the conserved C domain of synapsin, and show interaction of the endogenous proteins in synapses. Functionally, C9orf72 deficiency reduced the number of excitatory synapses and decreased synapsin levels at remaining synapses in vitro in hippocampal neuron cultures and in vivo in the hippocampal mossy fibre system of C9orf72 knockout mice. Consistent with synaptic dysfunction, electrophysiological recordings identified impaired excitatory neurotransmission and network function in hippocampal neuron cultures with reduced C9orf72 expression, which correlated with a severe depletion of synaptic vesicles from excitatory synapses in the hippocampus of C9orf72 knockout mice. Finally, neuropathological analysis of post-mortem sections of C9ALS/FTD patient hippocampus with C9orf72 haploinsufficiency revealed a marked reduction in synapsin, indicating that disruption of the interaction between C9orf72 and synapsin may contribute to ALS/FTD pathobiology. Thus, our data show that C9orf72 plays a cell-autonomous role in the regulation of neurotransmission at excitatory synapses by interaction with synapsin and modulation of synaptic vesicle pools, and identify a novel role for C9orf72 haploinsufficiency in synaptic dysfunction in C9ALS/FTD.
Glutamate is the most commonly engaged neurotransmitter in the mammalian central nervous system, acting to mediate excitatory neurotransmission. However, high levels of glutamatergic input elicit excitotoxicity, contributing to neuronal cell death following acute brain injuries such as stroke and trauma. While excitotoxic cell death has also been implicated in some neurodegenerative disease models, the role of acute apoptotic cell death remains controversial in the setting of chronic neurodegeneration. Nevertheless, it is clear that excitatory synaptic dysregulation contributes to neurodegeneration, as evidenced by protective effects of partial N -methyl- D -aspartate receptor antagonists. Here, we review evidence for sublethal excitatory injuries in relation to neurodegeneration associated with Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease. In contrast to classic excitotoxicity, emerging evidence implicates dysregulation of mitochondrial calcium handling in excitatory post-synaptic neurodegeneration. We discuss mechanisms that regulate mitochondrial calcium uptake and release, the impact of LRRK2, PINK1, Parkin, beta-amyloid and glucocerebrosidase on mitochondrial calcium transporters, and the role of autophagic mitochondrial loss in axodendritic shrinkage. Finally, we discuss strategies for normalizing the flux of calcium into and out of the mitochondrial matrix, thereby preventing mitochondrial calcium toxicity and excitotoxic dendritic loss. While the mechanisms that underlie increased uptake or decreased release of mitochondrial calcium vary in different model systems, a common set of strategies to normalize mitochondrial calcium flux can prevent excitatory mitochondrial toxicity and may be neuroprotective in multiple disease contexts.
Background Uric acid (UA) has emerged as a factor that can modify cognitive function both in the general population and in people with neurodegenerative disorders. Since very few data are available concerning amyotrophic lateral sclerosis (ALS), we explored the correlation of UA levels and cognitive impairment in a large cohort of ALS patients. Methods We enrolled ALS patients consecutively seen at the Turin ALS expert center in the 2007–2018 period who underwent both cognitive/behavioral and UA evaluation at diagnosis. Patients were classified in 5 categories: normal cognition (ALS-CN), isolated cognitive impairment (ALSci), isolated behavioural impairment (ALSbi), cognitive and behavioural impairment (ALScbi), frontotemporal dementia (ALS-FTD). For this study, ALSci, ALSbi and ALScbi were merged as ALS with intermediate cognitive impairment (ALS-INT). Results Out of the 841 ALS patients, 422 had ALS-CN, 271 ALS-INT and 148 ALS-FTD. The mean values of UA were significantly different among the cognitive subgroups of patients, with the lowest values in the ALS-FTD (ALS-CN, 288.5 ± 78.0 (μmol/L; ALS-INT, 289.7 ± 75.5 μmol/L; ALS-FTD, 271.8 ± 74.9 μmol/L; p = 0.046). The frequency of ALS-FTD was significantly higher in the 1st tertile of UA. Lower UA levels were independently associated with FTD (OR 1.32, 95% c.i. 1.01–1.43; p = 0.038) in binary logistic regression. Conclusions We found that in ALS lower UA serum levels are correlated with reduced frequency of co-morbid FTD. Patients with intermediate cognitive impairment showed UA levels similar to ALS-CN but higher than ALS-FTD, implying that higher UA levels can prevent or delay cognitive function deterioration.
Background Hispanics have been historically underrepresented in epidemiologic cancer research. Existing cohort studies focused on recruiting Hispanic participants have been relatively small, making studying cancer outcomes challenging. Therefore, we aimed to compare the distribution of cancer risk factors among Hispanic women of Mexican heritage (HWMH) participating in existing cohorts to explore the possibility of future data pooling efforts. Methods We used baseline data of HWMH from three US-based studies, the Mexican American Cohort (MAC; n = 19,797; 2001–2017), the Multiethnic Cohort (MEC; n = 18,007; 1993–1996), and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 4,022; 2008–2011), and one study from Mexico, the Mexican Teachers’ Cohort (MTC; n = 115,275; 2006–2008). Results Participants in MEC (59.5y) were older on average than MAC (40.9y), HCHS/SOL (45.5y), and MTC (42.6y) at enrollment. Most MAC (77.6%) and HCHS/SOL (85.4%) participants spoke Spanish as their primary language. Age at menarche (12.5–13.1y), age at menopause (45.8–47.9y), and smoking prevalence (~ 10%) was similar across studies. Parity was higher in MAC (3.8) and MEC (4.1) compared to HCHS/SOL (3.2) and MTC (2.5). Ever use of oral contraceptives was more frequent in HCHS/SOL (63.5%) compared to MTC (45.6%), MAC (37.9%), and MEC (35.2%). Obesity, diabetes, and hypertension were more common in the US cohorts. Conclusion This comparative study demonstrates the ability to harmonize data and provide information for future pooling projects across cohorts to evaluate cancer outcomes. Similarities and differences in characteristics across cohorts can be leveraged to better understand health disparities in HWMH.
Background The ability of machine learning (ML) to process and learn from large quantities of heterogeneous patient data is gaining attention in the precision oncology community. Some remarkable developments have taken place in the domain of image classification tasks in areas such as digital pathology and diagnostic radiology. The application of ML approaches to the analysis of DNA data, including tumor-derived genomic profiles, microRNAs, and cancer epigenetic signatures, while relatively more recent, has demonstrated some utility in identifying driver variants and molecular signatures with possible prognostic and therapeutic applications. Methods We conducted semi-structured interviews with academic and clinical experts to capture the status quo, challenges, opportunities, ethical implications, and future directions. Results Our participants agreed that machine learning in precision oncology is in infant stages, with clinical integration still rare. Overall, participants equated ongoing developments with better clinical workflows and improved treatment decisions for more cancer patients. They underscored the ability of machine learning to tackle the dynamic nature of cancer, break down the complexity of molecular data, and support decision-making. Our participants emphasized obstacles related to molecular data access, clinical utility, and guidelines. The availability of reliable and well-curated data to train and validate machine learning algorithms and integrate multiple data sources were described as constraints yet necessary for future clinical implementation. Frequently mentioned ethical challenges included privacy risks, equity, explainability, trust, and incidental findings, with privacy being the most polarizing. While participants recognized the issue of hype surrounding machine learning in precision oncology, they agreed that, in an assistive role, it represents the future of precision oncology. Conclusions Given the unique nature of medical AI, our findings highlight the field’s potential and remaining challenges. ML will continue to advance cancer research and provide opportunities for patient-centric, personalized, and efficient precision oncology. Yet, the field must move beyond hype and toward concrete efforts to overcome key obstacles, such as ensuring access to molecular data, establishing clinical utility, developing guidelines and regulations, and meaningfully addressing ethical challenges.
Deep learning has been reported to achieve high performances in the detection of skin cancer, yet many challenges regarding the reproducibility of results and biases remain. This study is a replication (different data, same analysis) of a previous study on Alzheimer's disease detection, which studied the robustness of logistic regression (LR) and convolutional neural networks (CNN) across patient sexes. We explore sex bias in skin cancer detection, using the PAD-UFES-20 dataset with LR trained on handcrafted features reflecting dermatological guidelines (ABCDE and the 7-point checklist), and a pre-trained ResNet-50 model. We evaluate these models in alignment with the replicated study: across multiple training datasets with varied sex composition to determine their robustness. Our results show that both the LR and the CNN were robust to the sex distribution, but the results also revealed that the CNN had a significantly higher accuracy (ACC) and area under the receiver operating characteristics (AUROC) for male patients compared to female patients. The data and relevant scripts to reproduce our results are publicly available (https://github.com/ nikodice4/Skin-cancer-detection-sex-bias). ;10 pages, 1 figure, published at FAIMI workshop at the MICCAI 2025 conference
The epigenetic deregulation of CpG islands (CGIs) plays a crucial role in cancer initiation and progression. CGIs comprise 1-2% of the human genome and are rich in differentially methylated regions (DMRs) that can serve as cancer biomarkers in clinical samples and liquid biopsies. Focusing epigenetic sequencing on CpG-rich sequences, including CGIs and avoiding non-informative regions, offers an efficient and sensitive approach for cancer identification and tracking, especially within samples containing excess of unaltered, normal DNA. To this end, we have developed Adaptor-anchored Methylation amplification via Proximity Primers (aMAPP), a versatile PCR-based enrichment method. aMAPP employs specially designed primers to selectively enrich either methylated or unmethylated CpGs, depending on the upstream methylation conversion method employed. aMAPP achieves high coverage of genome-wide CGIs and detects hundreds of DMRs in tumor samples compared to adjacent normal tissue using ultra-low depth sequencing (∼300,000 reads). It enables tracing of aberrant methylation down to allelic frequency 0.01% in dilutions of tumor DNA and in cell-free DNA samples, can be applied using picogram amounts of DNA, and can be adapted to enrich either small panels of cancer-specific DMRs, or the majority (>90%) of genomic CGIs and CpGs. aMAPP offers a simple, cost-effective, and highly sensitive approach for capturing the epigenetic footprint of genome-wide CpGs and identifying aberrantly methylated or un-methylated genomic regions.
The metastatic spread of a cancer can be reconstructed from DNA sequencing of primary and metastatic tumours, but doing so requires solving a challenging combinatorial optimization problem. This problem often has multiple solutions that cannot be distinguished based on current maximum parsimony principles alone. Current algorithms use ad hoc criteria to select among these solutions, and decide, a priori, what patterns of metastatic spread are more likely, which is itself a key question posed by studies of metastasis seeking to use these tools. Here we introduce Metient, a freely available open-source tool which proposes multiple possible hypotheses of metastatic spread in a cohort of patients and rescores these hypotheses using independent data on genetic distance of metastasizing clones and organotropism. Metient is more accurate and is up to 50x faster than current state-of-the-art. Given a cohort of patients, Metient can calibrate its parsimony criteria, thereby identifying shared patterns of metastatic dissemination in the cohort. Reanalyzing metastasis in 169 patients based on 490 tumors, Metient automatically identifies cancer type-specific trends of metastatic dissemination in melanoma, high-risk neuroblastoma and non-small cell lung cancer. Metient’s reconstructions usually agree with semi-manual expert analysis, however, in many patients, Metient identifies more plausible migration histories than experts, and further finds that polyclonal seeding of metastases is more common than previously reported. By removing the need for hard constraints on what patterns of metastatic spread are most likely, Metient introduces a way to further our understanding of cancer type-specific metastatic spread.
Purpose Cervical and endometrial cancers pose significant challenges in women’s healthcare due to their high mortality rates and limited treatment options. High throughput screening (HTS) of cervical and endometrial cancer in vitro models offers a promising avenue for drug repurposing and broadening patient treatment options. Traditional two-dimensional (2D) cell-based screenings have limited capabilities to capture crucial multicellular interactions, that are improved upon in three dimensional (3D) multicellular tissue engineered models. However, manual fabrication of the 3D platforms is both time consuming and subject to variability. Thus, the goal of this study was to utilize automated cell dispensing to fabricate 3D cell-based HTS platforms using the HP D100 Single Cell Dispenser to dispense cervical and endometrial cancer cells. Methods We evaluated the effects of automated dispensing of the cancer cell lines by tuning the dispensing protocol to align with cell size measured in solution and the minimum cell number for acceptable cell viability and proliferation. We modified our previously reported coculture models of cervical and endometrial cancer to be in a 384 well plate format and measured microvessel length and cancer cell invasion. Results Automatically and manually dispensed cells were directly compared revealing minimal differences between the dispensing methods. These findings suggest that automated dispensing of cancer cells minimally affects cell behavior and can be deployed to decrease in vitro model fabrication time. Conclusions By streamlining the manufacturing process, automated dispensing holds promise for enhancing efficiency and scalability of 3D in vitro HTS platforms, ultimately contributing to advancement in cancer research and treatment.
Purpose Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients’ short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS’s oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. Methods We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. Results Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8–5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. Conclusions MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.
It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies.
Background The cancer experienced in adolescent and young adult (AYA) could disturb developmental changes and long-term life. The current AYA guidelines and research for survivorship were developed and reported according to the general age range of 15–39 years; however, expected life events vary by diagnosed age. We aimed to examine the social, psychological, and physical well-being of AYA cancer survivors by age at diagnosis using a multinational representative dataset focusing on age at diagnosis. Methods We conducted a cross-sectional study using the US and Korean National Health and Nutrition Examination Surveys from 2007 to 2018. Participants diagnosed with any cancer aged 15–39 years and were aged > 18 years at the survey year were defined as AYA cancer survivors. AYA were classified into three groups based on their diagnosed age: adolescent survivors (diagnosed between the ages of 15 and 19, n = 45), young adult survivors (diagnosed between the ages of 20 and 29, n = 238), and late young adult survivors (diagnosed between the ages of 30 and 39, n = 539). We also selected an age-, sex-, race-, and survey year-matched general population with 1:5 ratio among participants without cancer ( N = 4110). Results The average age of the survey was 29.1, 43.7, and 48.7 years for AYA survivors diagnosed during adolescence, young adulthood, and late young adulthood, respectively. Adolescent survivors had more non-couple marital status (adjusted odds ratio (aOR), 1.34; 95% CI, 1.10–1.64) and unemployed (aOR, 1.30; 95% CI, 1.05–1.61) compared to late young adult survivors. Comparing with the matched general, adolescent survivors were more in poor general health (aOR, 4.65; 95% CI, 2.09–10.38) and unemployed (aOR, 2.17; 95% CI, 1.12–4.24) and late young adult survivors were more non-couple (aOR, 1.40; 95% CI, 1.05–1.86). Conclusion This study provides evidence for future studies on long-term health, which may vary according to age at the time of diagnosis among AYA with cancer.
Skin cancer detection still represents a major challenge in healthcare.
Common detection methods can be lengthy and require human assistance which
falls short in many countries. Previous research demonstrates how convolutional
neural networks (CNNs) can help effectively through both automation and an
accuracy that is comparable to the human level. However, despite the progress
in previous decades, the precision is still limited, leading to substantial
misclassifications that have a serious impact on people's health. Hence, we
employ a Vision Transformer (ViT) that has been developed in recent years based
on the idea of a self-attention mechanism, specifically two configurations of a
pre-trained ViT. We generally find superior metrics for classifying skin
lesions after comparing them to base models such as decision tree classifier
and k-nearest neighbor (KNN) classifier, as well as to CNNs and less complex
ViTs. In particular, we attach greater importance to the performance of
melanoma, which is the most lethal type of skin cancer. The ViT-L32 model
achieves an accuracy of 91.57% and a melanoma recall of 58.54%, while ViT-L16
achieves an accuracy of 92.79% and a melanoma recall of 56.10%. This offers a
potential tool for faster and more accurate diagnoses and an overall
improvement for the healthcare sector.
Background Despite the high burden and regional variability of ovarian cancer (OC), data on its status in Syria, a country impacted by long-standing conflict, remain scarce. This study aimed to provide the first nationwide analysis of OC epidemiological and clinicopathological characteristics. Methods In this national, multicenter, retrospective cross-sectional study, we collected data from three tertiary referral university hospitals in Syria: Tishreen University Hospital, Al-Bairouni University Hospital, and Ibn Rushd Hospital. The inclusion period spanned from 2017 to 2021. All included patients were 18 years or older and had a newly diagnosed, confirmed primary OC. Data collected included sociodemographic information, presenting symptoms, CA-125 levels, and treatment details. Results A total of 531 patients with OC with a mean age of 53.1 years (range: 18–91) were included in the study, representing 1.2% (95% confidence interval: 1.1%-1.3%) of the 44,248 patients diagnosed with all types of cancer. Serous carcinoma (55.4%) was the most common OC subtype, followed by mucinous (13.8%) and endometrioid carcinoma (9.7%). Among epithelial OCs, having high levels of CA-125 was associated with higher odds of serous carcinoma (adjusted OR: 2.30, 95% CI: 1.08–4.91) and lower odds of endometrioid cancer adjusted OR: 0.21, 95% CI: 0.08–0.54). Abdominal bloating was the most frequently reported symptom, affecting 194 patients (36.5%). Conclusions Our study revealed a lower proportion of OCs diagnoses among all cancer cases compared to global and regional data which may be attributed to underreporting, influenced by the disease’s specific characteristics and presence of more barriers for women to healthcare access in Syria’s conflict-affected setting. Given the study’s limitations, further research is essential to provide a more comprehensive assessment of the OC burden in Syria.
Background Armed conflict can disrupt oncology care profoundly, resulting in worsened health outcomes for cancer patients. Syria has endured armed conflict for over a decade, resulting in a severe breakdown of its healthcare services. The aim of this systematic review was to assess the available evidence on the burden of cancer and oncology services in Syria and how they have been affected during the conflict. Methods Eight academic and six grey literature databases were searched for English- and Arabic-language studies published from March 2011 until February 2024. Studies reporting any outcomes relating to the burden of cancer or the state of oncology services in wartime Syria were considered for inclusion, although case reports and scoping reviews were excluded. A narrative synthesis of findings was performed. Results Of 5,801 studies identified, 28 studies from academic (23) and grey literature (5) were eligible. Papers which reported on the burden of cancer showed an overall increase in cancer incidence and mortality between 2012 and 2022 (most recent data available). Most services were noted to be concentrated in Syria’s capital, Damascus. The main identified themes related to the challenges of providing oncology services with staff shortages, chemotherapeutic drug shortages, insufficient radiotherapy services, and a lack of screening and palliative care noted. Conclusion There is insufficient high-quality exploration of the burden of cancer and the state of oncology services across Syria in academic and grey literature. Syria’s health system is divided, creating disparities in access to oncology services, most of which are concentrated in Damascus, exacerbating pre-existing inequalities. The sparsity of robust data reinforces the need for high-quality data, including the use of national or other cancer registries with data from all regions of Syria, including those under opposition control. As the country rebuilds its healthcare systems, policymakers should focus on addressing inequities in oncology service availability to support equity of services.
Recent studies have made significant progress in developing large language
models (LLMs) in the medical domain, which can answer expert-level questions
and demonstrate the potential to assist clinicians in real-world clinical
scenarios. Studies have also witnessed the importance of integrating various
modalities with the existing LLMs for a better understanding of complex
clinical contexts, which are innately multi-faceted by nature. Although studies
have demonstrated the ability of multimodal LLMs in histopathology to answer
questions from given images, they lack in understanding of thorough clinical
context due to the patch-level data with limited information from public
datasets. Thus, developing WSI-level MLLMs is significant in terms of the
scalability and applicability of MLLMs in histopathology. In this study, we
introduce an expert-level MLLM for histopathology using WSIs, dubbed as
ChatEXAONEPath. We present a retrieval-based data generation pipeline using
10,094 pairs of WSIs and histopathology reports from The Cancer Genome Atlas
(TCGA). We also showcase an AI-based evaluation protocol for a comprehensive
understanding of the medical context from given multimodal information and
evaluate generated answers compared to the original histopathology reports. We
demonstrate the ability of diagnosing the given histopathology images using
ChatEXAONEPath with the acceptance rate of 62.9% from 1,134 pairs of WSIs and
reports. Our proposed model can understand pan-cancer WSIs and clinical context
from various cancer types. We argue that our proposed model has the potential
to assist clinicians by comprehensively understanding complex morphology of
WSIs for cancer diagnosis through the integration of multiple modalities.
The circadian clock, a fundamental cellular mechanism, regulates the rhythmic expression of numerous genes and biological processes across various organs. Disruptions in this system, driven by genetic or environmental factors, have been reported to be involved in cancer progression. This review explores the role of the circadian clock in cancer hallmarks and its impact on cellular homeostasis within haematological malignancies. Drawing on findings from in vitro, in vivo, and clinical trials, this review highlights the potential of clock genes as diagnostic and prognostic biomarkers, and as therapeutic targets for optimising treatment timing. It discusses how circadian rhythms can enhance treatment efficacy through both pharmacological and non-pharmacological interventions, outlining strategies for optimising dosing schedules and implementing personalised chronobiological interventions, with a particular focus on haematological malignancies, including cutaneous lymphoma. Ongoing research holds promise for advancing personalised therapeutic approaches and ultimately improving cancer care standards.
Background Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Methods Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. Results From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. Conclusions The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.
Background Postoperative delirium is especially common and often problematic among elderly patients undergoing surgery. This study aimed to explore factors that can predict postoperative delirium in elderly patients undergoing gastric cancer surgery. Methods This cohort study included 255 patients age 75 years or older who underwent gastric cancer surgery between July 2010 and December 2020. All the patients underwent preoperative comprehensive geriatric assessment (CGA) evaluation by a geriatrician. In addition to the CGA items, this study investigated the association between postoperative delirium and clinicopathologic factors, including Eastern Cooperative Oncology Group performance status (ECOG-PS). Results The most common postoperative complication was delirium, present in 31 patients (12.2%). The group with delirium was significantly more likely to have ECOG-PS ≥ 2, diabetes mellitus, cardiovascular disease, or cerebral infarction. The CGA showed frailty in the Instrumental Activities of Daily Living scale (IADL), the Mini-Mental State Examination (MMSE), the Vitality Index (VI), and the Geriatric Depression Scale 15 (GDS-15). In the multivariate analysis, the independent risk factors for delirium were ECOG-PS ≥ 2 ( P = 0.002) and MMSE-frailty ( P < 0.001). Using an MMSE score of ≤ 23 and an ECOG-PS score of ≥ 2 as cutoffs, postoperative delirium was predicted with a sensitivity of 80.7% and a specificity of 74.1%. Conclusion Postoperative delirium might be more easily predicted based on the combination of MMSE and ECOG-PS for elderly patients with gastric cancer undergoing gastrectomy.
Context Utilizing mobile apps to increase physical activity levels is now standard practice in cancer care. The study’s objective was to provide patients with precise physical activity recommendations and/or initiate self-directed exercise programs. Methods A multidisciplinary group directed the design procedure. We adhered to the self-determination approach,and accompanying behavior modification strategies, as well as international guidelines in the field of physical activity in cancer care. The design process was user-centered and involved three steps: Understanding the user and the context, conceptualization, and evaluation of the prototype. The testing was carried out by the beneficiaries, healthcare professionals, and two experts. Three criteria were evaluated in the designed solution: usability, quality, and potential for behavior change. Results The evaluation results of the designed solution showed good perception by both beneficiaries and healthcare professionals. The average system usability scale score was 90,6 (SD: 7.33) for beneficiaries, and 92.75 (SD: 3.83) for healthcare professionals. The first expert received a mean overall quality score of 4.51 on the mobile app rating scale, while the second received a score of 4.27. The results of the app behavior change scale gave the first expert a score of 17/21 and the second a score of 15/21. Conclusion Based on the criteria of usability, quality, and potential for behavior change, the designed app demonstrated positive results. This is a preliminary evaluation, which will be followed by additional, in-depth evaluations with larger sample sizes.
Background Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate ^68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. Material and methods Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent ^68 Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. Results A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07–13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1–26.1: p = 0.002) were associated with the type of hormone therapy administered. Conclusions PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.
Rectal cancer patients display heterogeneous responses to neoadjuvant treatment—including the intensive total neoadjuvant therapy (TNT)—and reliable biomarkers are lacking to guide which tumors will benefit most from these regimens. Here, we profiled DNA methylation in tumor tissue and matched patient-derived organoids (PDOs) from 18 rectal cancer cases (50 total samples), leveraging the Illumina MethylationEPIC array and quality control filters that retained 771,964 CpG sites. Analyses used linear models (for tissue-only or PDO-only) and a joint linear mixed-effects approach (accounting for patient-level random effects) to identify significant CpGs associated with log-transformed FOLFOX IC50. We found that PDOs faithfully recapitulate patient-tumor methylation patterns (Spearman’s correlation >0.95 among replicate organoids), and the joint model uncovered 745 CpGs tied to FOLFOX sensitivity, many of which were missed in tissue-only analyses. Differentially methylated regions reinforced that broader epigenetic blocks near TSS or enhancer regions may modulate chemo-resistance, while pathway enrichment pinpointed focal adhesion, ECM–receptor interaction, calcium signaling, and folate metabolism as key processes. A methylation risk score derived from these CpGs significantly predicted progression-free survival in an independent colorectal cancer cohort (p=0.019), outperforming single-sample–based signatures. These findings suggest that combining methylation profiles from both tumors and PDOs can expose robust epigenetic drivers of therapy response, aiding the development of clinically actionable biomarkers for rectal cancer TNT.
Background Although recent global studies have highlighted shifting patterns in oropharyngeal cancer, Korea lacks comprehensive epidemiological data on oral cancer, including detailed prevalence by anatomical subsites, age, and sex. This study aims to analyze long-term trends in oral cancer incidence and mortality in Korea, with particular attention to disease spectrum across subsites. Methods Patient data from individuals diagnosed between 2001 and 2021 were obtained from Cancer Registration Statistics by the Ministry of Health and Welfare, while cause-of-death statistics from Statistics Korea provided information on deaths due to malignant neoplasms of the lip, oral cavity, and pharynx. Age-standardized incidence and mortality rates were calculated using the direct method, with the 2000 Korean mid-year population as the standard. Temporal trends were assessed using joinpoint regression analysis to estimate annual percentage changes (APCs) and to identify significant shifts in incidence and mortality across sex, age group, and subsites. Results The overall trend in oral cancer incidence among males was modest (APC: 0.30), with the most notable increase observed in those aged 45 or younger (APC: 2.13). In females, oral cancer incidence showed a significant increase (APC: 2.19), with the highest rise occurring in those aged 45 or younger (APC: 3.20). Subsite-specific trends showed that in males, the greatest increases were in cancers of the tonsils (APC: 3.11), salivary glands (APC: 2.01), and tongue (APC: 1.95), whereas in females, the tongue (APC: 3.97), tonsils (APC: 3.85), and salivary glands (APC: 3.09) showed the highest increases. Conclusions These findings demonstrate distinct epidemiological shifts in oral cancer in Korea over the past two decades, particularly by age, sex, and anatomical subsite. While incidence increased notably among younger females, mortality declined in males, suggesting improved survival outcomes. These results underscore the importance of continuous monitoring and subsite-specific prevention strategies tailored to evolving demographic and clinical patterns.
Background Appendiceal cancer (AC), once rare, is now recognized as a complex disease with rising mortality. At diagnosis, 74% of AC cases are already metastatic. No standardized chemotherapy exists for advanced cases, despite an alarming 232% increase in incidence in the United States, predominantly in individuals under 50 years. We analyzed U.S. mortality patterns by demographics and geography to identify high-risk groups. Methods A retrospective analysis was performed using the CDC WONDER database. Deidentified death certificate data was extracted through ICD-10 code C18.1 to identify Appendiceal cancer–related deaths from 1999 to 2023. We analyzed mortality disparities by gender, race/ethnicity, states, and urban/rural classification. Age-adjusted mortality rates (AAMR) per 100,000 with 95% CI were reported. Trends and annual percent change (APC) were assessed using Joinpoint regression. Results Between 1999 and 2023, 15,928 appendiceal cancer–related deaths occurred in the U.S. AAMRs increased from 0.08 in 1999 to 0.24 in 2017 (APC: 5.61; 95% CI 5.14,6.07), then plateaued till 2023. Females consistently had higher AAMRs than males. NH-Whites had the highest racial AAMR (3.95), followed by NH-Blacks (3.73), with Hispanics/Latinos lowest (1.43). Rural areas had the highest 2020 AAMR (0.27), increasing sharply after 2004 (APC: 7.72). State-level AAMRs ranged from 0.08 (Nevada) to 0.30 (Delaware), with top-percentile states having nearly triple the rates of those in the lowest percentile. Conclusion Appendiceal cancer deaths are increasing in the United States, highlighting the need for targeted efforts to address this trend and reduce the risk of a growing health burden.
In computational pathology, cancer grading has been mainly studied as a
categorical classification problem, which does not utilize the ordering nature
of cancer grades such as the higher the grade is, the worse the cancer is. To
incorporate the ordering relationship among cancer grades, we introduce a
differential ordinal learning problem in which we define and learn the degree
of difference in the categorical class labels between pairs of samples by using
their differences in the feature space. To this end, we propose a
transformer-based neural network that simultaneously conducts both categorical
classification and differential ordinal classification for cancer grading. We
also propose a tailored loss function for differential ordinal learning.
Evaluating the proposed method on three different types of cancer datasets, we
demonstrate that the adoption of differential ordinal learning can improve the
accuracy and reliability of cancer grading, outperforming conventional cancer
grading approaches. The proposed approach should be applicable to other
diseases and problems as they involve ordinal relationship among class labels.
Gastric cancer (GC) is one of the most common digestive tract malignant tumors in the world. At the time of initial diagnosis, it frequently presents with local or distant metastasis, contributing to poor prognosis in patients. Neutrophil extracellular traps (NETs) constitute a mechanism employed by neutrophils that is intricately associated with tumor progression, prognosis, and response to immunotherapy and chemotherapy. Despite this, the specific involvement of NETs-related long non-coding RNAs (lncRNAs) in gastric cancer remains unclear. A prognostic model for NETs-related lncRNAs was constructed through correlation analysis, COX regression analysis, and least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the model was assessed using Kaplan–Meier survival curves, receiver operating characteristic (ROC) curves, facilitating the exploration of the relationship between disease onset and prognosis in gastric cancer. Additionally, differences in the tumor microenvironment and response to immunotherapy among gastric cancer patients across high- and low-risk groups were analyzed. Furthermore, a prognostic nomogram integrating the risk score with relevant clinicopathological parameters was developed. The prognostic prediction model for gastric cancer, derived from NETs-related lncRNAs in this study, demonstrates robust prognostic capabilities, serving as a valuable adjunct to traditional tumor staging. This model holds promise in offering novel guidelines for the precise treatment of gastric cancer, thereby potentially improving patient outcomes.
The study procedure and materials were approved by the Ethical Committee of the Statutory Physician Board of the State Rhineland Palatinate (Reference number 837.161.11 (7703)). Background Optimism and pessimism are stable, overarching dispositions that influence mental health, especially in stressful life situations, such as cancer survival. They have been associated with more specific coping strategies. This study sought to investigate a theoretically-based model of their interplay in shaping depressive and anxiety symptoms to inform prevention and intervention efforts. Methods The registry-based study included 689 survivors of malignant melanoma. We assessed sociodemographic and disease-related variables, optimism/pessimism (LOT-R), coping strategies (BC), depressive (PHQ-9), and anxiety symptoms (GAD-7). A structural equation model was conducted to analyse the hypothesized associations, modelling coping strategies (denial/self-blame, seeking external support, active coping) as mediators of the relationship of optimism/pessimism with depressive and anxiety symptoms. As a sensitivity analysis, gender-stratified models were tested. Results The proposed model fit the data well. In the full sample, optimism was directly related to depression and anxiety, and the effects of optimism and pessimism were mediated via denial/self-blame. This indirect effect accounted for 60.8% of the total effect of pessimism on depression, and for 79.55% on anxiety. Stratified analyses showed different patterns of associations by gender, in the sense that the mediation effect was more relevant among men. Conclusion This study shows the relevance and need of gender-sensitive psychosocial-care. Especially in men, psychosocial interventions should target maladaptive coping strategies. Within women, fostering optimism seems to be particularly important. As the model did not fit as well for women, more gender-sensitive research is needed to understand potentially different risk/protective factors and needs of support.
Background The reported inverse association between cancer and subsequent Alzheimer’s disease and related dementias (ADRD) remains uncertain. Objectives To investigate the association between these common conditions of old age and explore possible causal factors. Design, Setting, Participants and Measurements We conducted a large population-based cohort analysis using data from 3,021,508 individuals aged 60 and over in the UK Clinical Practice Research Datalink (CPRD), over a period up to 30 years (1988–2018). Cox proportional hazards models were fitted to estimate hazard ratios (HR) for risk of dementia associated with previous cancer diagnosis. Competing risk models were employed to account for competing risk of death. Two-sample Mendelian Randomization analysis based on meta-analysis data from large-scale GWAS studies was also conducted. Results In the CPRD cohort, 412,903 participants had cancer diagnosis and 230,558 were subsequently diagnosed with dementia over a median follow-up period of 7.9 years. Cancer survivors had a 25% lower risk of developing dementia (HR=0.75, 95% CI:0.74–0.76) after adjustment for potential confounders. Accounting for competing risk of death provided a sub-distribution HR of 0.56 (95% CI:0.55–0.56). Results were consistent for prevalent and incident cancer and different common cancer types. Two-sample Mendelian Randomization analysis, using 357 cancer-related instrumental single-nucleotide polymorphisms (SNPs) revealed evidence of vertical pleiotropy between genetically predicted cancer and reduced risk of Alzheimer’s disease (OR=0.97,95% CI:0.95–0.99). Conclusion Our results provide strong epidemiological evidence of the inverse association between cancer and risk of ADRD and support the potential causal nature of this association via genetic instruments. Further investigations into the precise underlying biological mechanisms may reveal valuable information for new therapeutic approaches.
Shifted partial derivative (SPD) methods are a central algebraic tool for circuit lower bounds, measuring the dimension of spaces of shifted derivatives of a polynomial. We develop the Shifted Partial Derivative Polynomial (SPDP) framework, packaging SPD into an explicit coefficient-matrix formalism. This turns shifted-derivative spans into concrete linear-algebraic objects and yields two dual measures: SPDP rank and SPDP codimension.
We define the SPDP generating family, its span, and the SPDP matrix M_{k,l}(p) inside a fixed ambient coefficient space determined by the (k,l) regime, so rank is canonical and codimension is a deficit from ambient fullness. We prove structural properties needed for reuse: monotonicity in the shift/derivative parameters (with careful scoping for |S|=k versus |S|<=k conventions), invariance under admissible variable symmetries and basis changes, and robustness across standard Boolean/multilinear embeddings. We then give generic width-to-rank upper-bound templates for local circuit models via profile counting, separating the model-agnostic SPDP toolkit from additional compiled refinements used elsewhere. We illustrate the codimension viewpoint on representative examples. ;45 pages, 1 Table
Anomaly detection is crucial in industrial applications for identifying rare and unseen patterns to ensure system reliability. Traditional models, trained on a single class of normal data, struggle with real-world distributions where normal data exhibit diverse patterns, leading to class imbalance and long-tailed anomaly score distributions (LTD). This imbalance skews model training and degrades detection performance, especially for minority instances. To address this issue, we propose a novel importance-weighted loss designed specifically for anomaly detection. Compared to the previous method for LTD in classification, our method does not require prior knowledge of normal data classes. Instead, we introduce a weighted loss function that incorporates importance sampling to align the distribution of anomaly scores with a target Gaussian, ensuring a balanced representation of normal data. Extensive experiments on three benchmark image datasets and three real-world hyperspectral imaging datasets demonstrate the robustness of our approach in mitigating LTD-induced bias. Our method improves anomaly detection performance by 0.043, highlighting its effectiveness in real-world applications. ;8 pages, Published as a conference paper at IJCNN 2025
Decoder-only autoregressive image generation typically relies on fixed-length tokenization schemes whose token counts grow quadratically with resolution, substantially increasing the computational and memory demands of attention. We present DPAR, a novel decoder-only autoregressive model that dynamically aggregates image tokens into a variable number of patches for efficient image generation. Our work is the first to demonstrate that next-token prediction entropy from a lightweight and unsupervised autoregressive model provides a reliable criterion for merging tokens into larger patches based on information content. DPAR makes minimal modifications to the standard decoder architecture, ensuring compatibility with multimodal generation frameworks and allocating more compute to generation of high-information image regions. Further, we demonstrate that training with dynamically sized patches yields representations that are robust to patch boundaries, allowing DPAR to scale to larger patch sizes at inference. DPAR reduces token count by 1.81x and 2.06x on Imagenet 256 and 384 generation resolution respectively, leading to a reduction of up to 40% FLOPs in training costs. Further, our method exhibits faster convergence and improves FID by up to 27.1% relative to baseline models.
We introduce \emph{Adaptive RAG Memory} (ARM), a retrieval-augmented generation (RAG) framework that replaces a static vector index with a \emph{dynamic} memory substrate governed by selective remembrance and decay. Frequently retrieved items are consolidated and protected from forgetting, while rarely used items gradually decay, inspired by cognitive consolidation and forgetting principles. On a lightweight retrieval benchmark, ARM reaches near state-of-the-art performance (e.g., NDCG@5 $\approx$ 0.940, Recall@5 $=1.000$) with only $\sim$22M parameters in the embedding layer, achieving the best efficiency among ultra-efficient models ($<$25M parameters). In addition, we compare static vs. dynamic RAG combinations across Llama 3.1 and GPT-4o. Llama 3.1 with static RAG achieves the highest key-term coverage (67.2\%) at moderate latency, while GPT-4o with a dynamic selective retrieval policy attains the fastest responses (8.2s on average) with competitive coverage (58.7\%). We further present an engineering optimization of the DynamicRAG implementation, making embedding weights configurable, adjustable at runtime, and robust to invalid settings.
ARM yields competitive accuracy, self-regularizing memory growth, and interpretable retention dynamics without retraining the generator\color{black} and provides practical trade-off between quality, latency and memory efficiency for production and research RAG system. ;6 Pages, 2 figures
Large Language Models (LLMs) are rapidly transitioning from conversational assistants to autonomous agents embedded in critical organizational functions, including Security Operations Centers (SOCs), financial systems, and infrastructure management. Current adversarial testing paradigms focus predominantly on technical attack vectors: prompt injection, jailbreaking, and data exfiltration. We argue this focus is catastrophically incomplete. LLMs, trained on vast corpora of human-generated text, have inherited not merely human knowledge but human \textit{psychological architecture} -- including the pre-cognitive vulnerabilities that render humans susceptible to social engineering, authority manipulation, and affective exploitation. This paper presents the first systematic application of the Cybersecurity Psychology Framework (\cpf{}), a 100-indicator taxonomy of human psychological vulnerabilities, to non-human cognitive agents. We introduce the \textbf{Synthetic Psychometric Assessment Protocol} (\sysname{}), a methodology for converting \cpf{} indicators into adversarial scenarios targeting LLM decision-making. Our preliminary hypothesis testing across seven major LLM families reveals a disturbing pattern: while models demonstrate robust defenses against traditional jailbreaks, they exhibit critical susceptibility to authority-gradient manipulation, temporal pressure exploitation, and convergent-state attacks that mirror human cognitive failure modes. We term this phenomenon \textbf{Anthropomorphic Vulnerability Inheritance} (AVI) and propose that the security community must urgently develop ``psychological firewalls'' -- intervention mechanisms adapted from the Cybersecurity Psychology Intervention Framework (\cpif{}) -- to protect AI agents operating in adversarial environments.
Substance overdose mortality in the United States claimed over 80,000 lives in 2023, with the COVID-19 pandemic exacerbating existing trends through healthcare disruptions and behavioral changes. Estimating excess mortality, defined as deaths beyond expected levels based on pre-pandemic patterns, is essential for understanding pandemic impacts and informing intervention strategies. However, traditional statistical methods like SARIMA assume linearity, stationarity, and fixed seasonality, which may not hold under structural disruptions. We present a systematic comparison of SARIMA against three deep learning (DL) architectures (LSTM, Seq2Seq, and Transformer) for counterfactual mortality estimation using national CDC data (2015-2019 for training/validation, 2020-2023 for projection). We contribute empirical evidence that LSTM achieves superior point estimation (17.08% MAPE vs. 23.88% for SARIMA) and better-calibrated uncertainty (68.8% vs. 47.9% prediction interval coverage) when projecting under regime change. We also demonstrate that attention-based models (Seq2Seq, Transformer) underperform due to overfitting to historical means rather than capturing emergent trends. Ourreproducible pipeline incorporates conformal prediction intervals and convergence analysis across 60+ trials per configuration, and we provide an open-source framework deployable with 15 state health departments. Our findings establish that carefully validated DL models can provide more reliable counterfactual estimates than traditional methods for public health planning, while highlighting the need for calibration techniques when deploying neural forecasting in high-stakes domains.
A copy of a hypergraph $F$ is called an $F$-copy. Let $K_k^r$ denote the complete $r$-uniform hypergraph whose vertex set is $[k] = \{1, \dots, k\}$ (that is, the edges of $K_k^r$ are the $r$-element subsets of $[k]$). Given an $r$-uniform $n$-vertex hypergraph $H$, the $K_k^r$-isolation number of $H$, denoted by $ι(H, K_k^r)$, is the size of a smallest subset $D$ of the vertex set of $H$ such that the closed neighbourhood $N[D]$ of $D$ intersects the vertex sets of the $K_k^r$-copies contained by $H$ (equivalently, $H-N[D]$ contains no $K_k^r$-copy). In this note, we show that if $2 \leq r \leq k$ and $H$ is connected, then $ι(H, K_k^r) \leq \frac{n}{k+1}$ unless $H$ is a $K_k^r$-copy or $k = r = 2$ and $H$ is a $5$-cycle. This solves a recent problem of Li, Zhang and Ye. The result for $r = 2$ (that is, $H$ is a graph) was proved by Fenech, Kaemawichanurat and the author, and is used to prove the result for any $r$. The extremal structures for $r = 2$ were determined by various authors. We use this to determine the extremal structures for any $r$. ;10 pages
The highly nonlinear degradation process, complex physical interactions, and various sources of uncertainty render single-image Super-resolution (SR) a particularly challenging task. Existing interpretable SR approaches, whether based on prior learning or deep unfolding optimization frameworks, typically rely on black-box deep networks to model latent variables, which leaves the degradation process largely unknown and uncontrollable. Inspired by the Kolmogorov-Arnold theorem (KAT), we for the first time propose a novel interpretable operator, termed Kolmogorov-Arnold Neural Operator (KANO), with the application to image SR. KANO provides a transparent and structured representation of the latent degradation fitting process. Specifically, we employ an additive structure composed of a finite number of B-spline functions to approximate continuous spectral curves in a piecewise fashion. By learning and optimizing the shape parameters of these spline functions within defined intervals, our KANO accurately captures key spectral characteristics, such as local linear trends and the peak-valley structures at nonlinear inflection points, thereby endowing SR results with physical interpretability. Furthermore, through theoretical modeling and experimental evaluations across natural images, aerial photographs, and satellite remote sensing data, we systematically compare multilayer perceptrons (MLPs) and Kolmogorov-Arnold networks (KANs) in handling complex sequence fitting tasks. This comparative study elucidates the respective advantages and limitations of these models in characterizing intricate degradation mechanisms, offering valuable insights for the development of interpretable SR techniques.
Large Language Models (LLMs) are increasingly used as high level controllers for autonomous Unmanned Aerial Vehicle (UAV) missions. However, existing evaluations rarely assess whether such agents remain safe, protocol compliant, and effective under realistic next generation networking constraints. This paper introduces $α^3$-Bench, a benchmark for evaluating LLM driven UAV autonomy as a multi turn conversational reasoning and control problem operating under dynamic 6G conditions. Each mission is formulated as a language mediated control loop between an LLM based UAV agent and a human operator, where decisions must satisfy strict schema validity, mission policies, speaker alternation, and safety constraints while adapting to fluctuating network slices, latency, jitter, packet loss, throughput, and edge load variations.
To reflect modern agentic workflows, $α^3$-Bench integrates a dual action layer supporting both tool calls and agent to agent coordination, enabling evaluation of tool use consistency and multi agent interactions. We construct a large scale corpus of 113k conversational UAV episodes grounded in UAVBench scenarios and evaluate 17 state of the art LLMs using a fixed subset of 50 episodes per scenario under deterministic decoding. We propose a composite $α^3$ metric that unifies six pillars: Task Outcome, Safety Policy, Tool Consistency, Interaction Quality, Network Robustness, and Communication Cost, with efficiency normalized scores per second and per thousand tokens. Results show that while several models achieve high mission success and safety compliance, robustness and efficiency vary significantly under degraded 6G conditions, highlighting the need for network aware and resource efficient LLM based UAV agents. The dataset is publicly available on GitHub : https://github.com/maferrag/AlphaBench ;20 pages
Doubly-stochastic matrices (DSM) are increasingly utilized in structure-preserving deep architectures -- such as Optimal Transport layers and Sinkhorn-based attention -- to enforce numerical stability and probabilistic interpretability. In this work, we identify a critical spectral degradation phenomenon inherent to these constraints, termed the Homogeneity Trap. We demonstrate that the maximum-entropy bias, typical of Sinkhorn-based projections, drives the mixing operator towards the uniform barycenter, thereby suppressing the subdominant singular value σ_2 and filtering out high-frequency feature components. We derive a spectral bound linking σ_2 to the network's effective depth, showing that high-entropy constraints restrict feature transformation to a shallow effective receptive field. Furthermore, we formally demonstrate that Layer Normalization fails to mitigate this collapse in noise-dominated regimes; specifically, when spectral filtering degrades the Signal-to-Noise Ratio (SNR) below a critical threshold, geometric structure is irreversibly lost to noise-induced orthogonal collapse. Our findings highlight a fundamental trade-off between entropic stability and spectral expressivity in DSM-constrained networks.
Electrical substations are a significant component of an electrical grid. Indeed, the assets at these substations (e.g., transformers) are prone to disruption from many hazards, including hurricanes, flooding, earthquakes, and geomagnetically induced currents (GICs). As electrical grids are considered critical national infrastructure, any failure can have significant economic and public safety implications. To help prevent and mitigate these failures, it is thus essential that we identify key substation components to quantify vulnerability. Unfortunately, traditional manual mapping of substation infrastructure is time-consuming and labor-intensive. Therefore, an autonomous solution utilizing computer vision models is preferable, as it allows for greater convenience and efficiency. In this research paper, we train and compare the outputs of 3 models (YOLOv8, YOLOv11, RF-DETR) on a manually labeled dataset of US substation images. Each model is evaluated for detection accuracy, precision, and efficiency. We present the key strengths and limitations of each model, identifying which provides reliable and large-scale substation component mapping. Additionally, we utilize these models to effectively map the various substation components in the United States, showcasing a use case for machine learning in substation mapping. ;26 pages, 13 figures
Retrieval-Augmented Generation (RAG) has emerged as a powerful paradigm for Large Language Models (LLMs) to address knowledge-intensive queries requiring domain-specific or up-to-date information. To handle complex multi-hop questions that are challenging for single-step retrieval, iterative RAG approaches incorporating reinforcement learning have been proposed. However, existing iterative RAG systems typically plan to decompose questions without leveraging information about the available retrieval corpus, leading to inefficient retrieval and reasoning chains that cascade into suboptimal performance. In this paper, we introduce Early Knowledge Alignment (EKA), a simple but effective module that aligns LLMs with retrieval set before planning in iterative RAG systems with contextually relevant retrieved knowledge. Extensive experiments on six standard RAG datasets demonstrate that by establishing a stronger reasoning foundation, EKA significantly improves retrieval precision, reduces cascading errors, and enhances both performance and efficiency. Our analysis from an entropy perspective demonstrate that incorporating early knowledge reduces unnecessary exploration during the reasoning process, enabling the model to focus more effectively on relevant information subsets. Moreover, EKA proves effective as a versatile, training-free inference strategy that scales seamlessly to large models. Generalization tests across diverse datasets and retrieval corpora confirm the robustness of our approach. Overall, EKA advances the state-of-the-art in iterative RAG systems while illuminating the critical interplay between structured reasoning and efficient exploration in reinforcement learning-augmented frameworks. The code is released at \href{https://github.com/yxzwang/EarlyKnowledgeAlignment}{Github}. ;16 pages
Despite the fact that cancer survivability rates vary greatly between stages, traditional survival prediction models have frequently been trained and assessed using examples from all combined phases of the disease. This method may result in an overestimation of performance and ignore the stage-specific variations. Using the SEER dataset, we created and verified explainable machine learning (ML) models to predict stage-specific cancer survivability in colorectal, stomach, and liver cancers. ML-based cancer survival analysis has been a long-standing topic in the literature; however, studies involving the explainability and transparency of ML survivability models are limited. Our use of explainability techniques, including SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME), enabled us to illustrate significant feature-cancer stage interactions that would have remained hidden in traditional black-box models. We identified how certain demographic and clinical variables influenced survival differently across cancer stages and types. These insights provide not only transparency but also clinical relevance, supporting personalized treatment planning. By focusing on stage-specific models, this study provides new insights into the most important factors at each stage of cancer, offering transparency and potential clinical relevance to support personalized treatment planning. ;12 pages, 8 figures
Synthesizing realistic human-object interaction (HOI) is essential for 3D computer vision and robotics, underpinning animation and embodied control. Existing approaches often require manually specified intermediate waypoints and place all optimization objectives on a single network, which increases complexity, reduces flexibility, and leads to errors such as unsynchronized human and object motion or penetration. To address these issues, we propose Decoupled Generative Modeling for Human-Object Interaction Synthesis (DecHOI), which separates path planning and action synthesis. A trajectory generator first produces human and object trajectories without prescribed waypoints, and an action generator conditions on these paths to synthesize detailed motions. To further improve contact realism, we employ adversarial training with a discriminator that focuses on the dynamics of distal joints. The framework also models a moving counterpart and supports responsive, long-sequence planning in dynamic scenes, while preserving plan consistency. Across two benchmarks, FullBodyManipulation and 3D-FUTURE, DecHOI surpasses prior methods on most quantitative metrics and qualitative evaluations, and perceptual studies likewise prefer our results.
This systematic literature review surveys technical defenses against software-based cheating in online multiplayer games. Categorizing existing approach-es into server-side detection, client-side anti-tamper, kernel-level anti-cheat drivers, and hardware-assisted TEEs. Each category is evaluated in terms of detection effectiveness, perfor-mance overhead, privacy im-pact, and scalability. The analy-sis highlights key trade-offs, particularly between the high visibility of kernel-level solutions and their privacy and stability risks, versus the low intrusive-ness but limited insight of server-side methods. Overall, the re-view emphasizes the ongoing arms race with cheaters and the need for robust, adversary-resistant anti-cheat designs.
We present a cross robot visuomotor learning framework that integrates diffusion policy based control with 3D semantic scene representations from D3Fields to enable category level generalization in manipulation. Its modular design supports diverse robot camera configurations including UR5 arms with Microsoft Azure Kinect arrays and bimanual manipulators with Intel RealSense sensors through a low latency control stack and intuitive teleoperation. A unified configuration layer enables seamless switching between setups for flexible data collection training and evaluation. In a grasp and lift block task the framework achieved an 80 percent success rate after only 100 demonstration episodes demonstrating robust skill transfer between platforms and sensing modalities. This design paves the way for scalable real world studies in cross robotic generalization. ;6 pages, 7 figures, conference: SII 2026. Cancun, Mexico
Accurate segmentation of the tooth point cloud is of great significance for diagnosis clinical assisting and treatment planning. Existing methods mostly employ semantic segmentation, focusing on the semantic feature between different types of teeth. However, due to the tightly packed structure of teeth, unclear boundaries, and the diversity of complex cases such as missing teeth, malposed teeth, semantic segmentation often struggles to achieve satisfactory results when dealing with complex dental cases. To address these issues, this paper propose BATISNet, a boundary-aware instance network for tooth point cloud segmentation. This network model consists of a feature extraction backbone and an instance segmentation module. It not only focuses on extracting the semantic features of different types of teeth but also learns the instance features of individual teeth. It helps achieve more robust and accurate tooth instance segmentation in complex clinical scenarios such as missing teeth and malposed teeth. Additionally, to further enhance the completeness and accuracy of tooth boundary segmentation, a boundary-aware loss function is designed to specifically supervise the boundary segmentation between instances. It mitigates effectively tooth adhesion and boundary ambiguity issues. Extensive experimental results show that BATISNet outperforms existing methods in tooth integrity segmentation, providing more reliable and detailed data support for practical clinical applications. ;10 pages, 4 figures
Rapid and accessible cardiac biomarker testing is essential for the timely diagnosis and risk assessment of myocardial infarction (MI) and heart failure (HF), two interrelated conditions that frequently coexist and drive recurrent hospitalizations with high mortality. However, current laboratory and point-of-care testing systems are limited by long turnaround times, narrow dynamic ranges for the tested biomarkers, and single-analyte formats that fail to capture the complexity of cardiovascular disease. Here, we present a deep learning-enhanced dual-mode multiplexed vertical flow assay (xVFA) with a portable optical reader and a neural network-based quantification pipeline. This optical sensor integrates colorimetric and chemiluminescent detection within a single paper-based cartridge to complementarily cover a large dynamic range (spanning ~6 orders of magnitude) for both low- and high-abundance biomarkers, while maintaining quantitative accuracy. Using 50 uL of serum, the optical sensor simultaneously quantifies cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) within 23 min. The xVFA achieves sub-pg/mL sensitivity for cTnI and sub-ng/mL sensitivity for CK-MB and NT-proBNP, spanning the clinically relevant ranges for these biomarkers. Neural network models trained and blindly tested on 92 patient serum samples yielded a robust quantification performance (Pearson's r > 0.96 vs. reference assays). By combining high sensitivity, multiplexing, and automation in a compact and cost-effective optical sensor format, the dual-mode xVFA enables rapid and quantitative cardiovascular diagnostics at the point of care. ;32 Pages, 6 Figures, 2 Tables
Computational point-of-care (POC) sensors enable rapid, low-cost, and accessible diagnostics in emergency, remote and resource-limited areas that lack access to centralized medical facilities. These systems can utilize neural network-based algorithms to accurately infer a diagnosis from the signals generated by rapid diagnostic tests or sensors. However, neural network-based diagnostic models are subject to hallucinations and can produce erroneous predictions, posing a risk of misdiagnosis and inaccurate clinical decisions. To address this challenge, here we present an autonomous uncertainty quantification technique developed for POC diagnostics. As our testbed, we used a paper-based, computational vertical flow assay (xVFA) platform developed for rapid POC diagnosis of Lyme disease, the most prevalent tick-borne disease globally. The xVFA platform integrates a disposable paper-based assay, a handheld optical reader and a neural network-based inference algorithm, providing rapid and cost-effective Lyme disease diagnostics in under 20 min using only 20 uL of patient serum. By incorporating a Monte Carlo dropout (MCDO)-based uncertainty quantification approach into the diagnostics pipeline, we identified and excluded erroneous predictions with high uncertainty, significantly improving the sensitivity and reliability of the xVFA in an autonomous manner, without access to the ground truth diagnostic information of patients. Blinded testing using new patient samples demonstrated an increase in diagnostic sensitivity from 88.2% to 95.7%, indicating the effectiveness of MCDO-based uncertainty quantification in enhancing the robustness of neural network-driven computational POC sensing systems. ;18 Pages, 5 Figures
This work investigates inexact block Schur complement preconditioning for linear poroelasticity problems discretized using a hybrid approach: Bernardi-Raugel elements for solid displacement and lowest-order weak Galerkin elements for fluid pressure. When pure Dirichlet boundary conditions are applied to the displacement, the leading block of the resulting algebraic system becomes almost singular in the nearly incompressible (locking) regime, hindering efficient iterative solution. To overcome this, the system is reformulated as a three-field problem with an inherent regularization that maintains the original solution while ensuring nonsingularity. Analysis shows that both the minimal residual (MINRES) and generalized minimal residual (GMRES) methods, when preconditioned with inexact block diagonal and triangular Schur complement preconditioners, achieve convergence independent of mesh size and the locking parameter for the regularized system. Similar theoretical results are established for the situation with displacement subject to mixed boundary conditions, even without regularization. Numerical experiments in 2D and 3D confirm the benefits of regularization under pure Dirichlet conditions and the robustness of the preconditioners with respect to mesh size and the locking parameter in both boundary condition scenarios. Finally, a spinal cord simulation with discontinuous material parameters further illustrates the effectiveness and robustness of the proposed iterative solvers.
Optimal configuration of the learning rate (LR) is a fundamental yet formidable challenge in large-scale pre-training. Given the stringent trade-off between training costs and model performance, the pivotal question is whether the optimal LR can be accurately extrapolated from low-cost experiments. In this paper, we formalize this investigation into two distinct research paradigms: Fitting and Transfer. Within the Fitting Paradigm, we innovatively introduce a Scaling Law for search factor, effectively reducing the search complexity from O(n^3) to O(n*C_D*C_η) via predictive modeling. Within the Transfer Paradigm, we extend the principles of $μ$Transfer to the Mixture of Experts (MoE) architecture, broadening its applicability to encompass model depth, weight decay, and token horizons. By pushing the boundaries of existing hyperparameter research in terms of scale, we conduct a comprehensive comparison between these two paradigms. Our empirical results challenge the scalability of the widely adopted $μ$ Transfer in large-scale pre-training scenarios. Furthermore, we provide a rigorous analysis through the dual lenses of training stability and feature learning to elucidate the underlying reasons why module-wise parameter tuning underperforms in large-scale settings. This work offers systematic practical guidelines and a fresh theoretical perspective for optimizing industrial-level pre-training.
Recent progress in audio generation models has made it possible to create highly realistic and immersive soundscapes, which are now widely used in film and virtual-reality-related applications. However, these audio generators also raise concerns about potential misuse, such as producing deceptive audio for fabricated videos or spreading misleading information. Therefore, it is essential to develop effective methods for detecting fake environmental sounds. Existing datasets for environmental sound deepfake detection (ESDD) remain limited in both scale and the diversity of sound categories they cover. To address this gap, we introduced EnvSDD, the first large-scale curated dataset designed for ESDD. Based on EnvSDD, we launched the ESDD Challenge, recognized as one of the ICASSP 2026 Grand Challenges. This paper presents an overview of the ESDD Challenge, including a detailed analysis of the challenge results.
Accurate and continuous monitoring of river water levels is essential for flood forecasting, water resource management, and ecological protection. Traditional hydrological observation methods are often limited by manual measurement errors and environmental constraints. This study presents a hybrid framework integrating vision based waterline detection, YOLOv8 pose scale extraction, and large multimodal language models (GPT 4o and Gemini 2.0 Flash) for automated river gauge plate reading. The methodology involves sequential stages of image preprocessing, annotation, waterline detection, scale gap estimation, and numeric reading extraction. Experiments demonstrate that waterline detection achieved high precision of 94.24 percent and an F1 score of 83.64 percent, while scale gap detection provided accurate geometric calibration for subsequent reading extraction. Incorporating scale gap metadata substantially improved the predictive performance of LLMs, with Gemini Stage 2 achieving the highest accuracy, with a mean absolute error of 5.43 cm, root mean square error of 8.58 cm, and R squared of 0.84 under optimal image conditions. Results highlight the sensitivity of LLMs to image quality, with degraded images producing higher errors, and underscore the importance of combining geometric metadata with multimodal artificial intelligence for robust water level estimation. Overall, the proposed approach offers a scalable, efficient, and reliable solution for automated hydrological monitoring, demonstrating potential for real time river gauge digitization and improved water resource management. ;11 pages, 14 figures, 4 tables
The evolution of Large Language Models (LLMs) from passive text generators to autonomous, goal-driven systems represents a fundamental shift in artificial intelligence. This chapter examines the emergence of agentic AI systems that integrate planning, memory, tool use, and iterative reasoning to operate autonomously in complex environments. We trace the architectural progression from statistical models to transformer-based systems, identifying capabilities that enable agentic behavior: long-range reasoning, contextual awareness, and adaptive decision-making. The chapter provides three contributions: (1) a synthesis of how LLM capabilities extend toward agency through reasoning-action-reflection loops; (2) an integrative framework describing core components perception, memory, planning, and tool execution that bridge LLMs with autonomous behavior; (3) a critical assessment of applications and persistent challenges in safety, alignment, reliability, and sustainability. Unlike existing surveys, we focus on the architectural transition from language understanding to autonomous action, emphasizing the technical gaps that must be resolved before deployment. We identify critical research priorities, including verifiable planning, scalable multi-agent coordination, persistent memory architectures, and governance frameworks. Responsible advancement requires simultaneous progress in technical robustness, interpretability, and ethical safeguards to realize potential while mitigating risks of misalignment and unintended consequences.
We propose a unified four-dimensional (4D) spatiotemporal formulation for time-dependent convection-diffusion problems that preserves underlying physical structures. By treating time as an additional space-like coordinate, the evolution problem is reformulated as a stationary convection-diffusion equation on a 4D space-time domain. Using exterior calculus, we extend this framework to the full family of convection-diffusion problems posed on $H(\textbf{grad})$, $H(\textbf{curl})$, and $H(\text{div})$. The resulting formulation is based on a 4D Hodge-Laplacian operator with a spatiotemporal diffusion tensor and convection field, augmented by a small temporal perturbation to ensure nondegeneracy. This formulation naturally incorporates fundamental physical constraints, including divergence-free and curl-free conditions. We further introduce an exponentially-fitted 4D spatiotemporal flux operator that symmetrizes the convection-diffusion operator and enables a well-posed variational formulation. Finally, we prove that the temporally-perturbed formulation converges to the original time-dependent convection-diffusion model as the perturbation parameter tends to zero.
BACKGROUND: Severe COVID and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokine/chemokine levels. METHODS: We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID patients, MIS-C patients, adult vaccinees, and adult and pediatric healthy controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA. RESULTS: Spike IgG were more afucosylated than bulk IgG during acute adult COVID and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID, with similar trends observed during pediatric COVID/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with pro-inflammatory cytokines in adult COVID and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. CONCLUSIONS: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID and MIS-C immunopathology.
Long COVID continues to challenge public health by affecting a considerable
number of individuals who have recovered from acute SARS-CoV-2 infection yet
endure prolonged and often debilitating symptoms. Social media has emerged as a
vital resource for those seeking real-time information, peer support, and
validating their health concerns related to Long COVID. This paper examines
recent works focusing on mining, analyzing, and interpreting user-generated
content on social media platforms to capture the broader discourse on
persistent post-COVID conditions. A novel transformer-based zero-shot learning
approach serves as the foundation for classifying research papers in this area
into four primary categories: Clinical or Symptom Characterization, Advanced
NLP or Computational Methods, Policy Advocacy or Public Health Communication,
and Online Communities and Social Support. This methodology achieved an average
confidence of 0.7788, with the minimum and maximum confidence being 0.1566 and
0.9928, respectively. This model showcases the ability of advanced language
models to categorize research papers without any training data or predefined
classification labels, thus enabling a more rapid and scalable assessment of
existing literature. This paper also highlights the multifaceted nature of Long
COVID research by demonstrating how advanced computational techniques applied
to social media conversations can reveal deeper insights into the experiences,
symptoms, and narratives of individuals affected by Long COVID.
Since the outbreak of COVID-19 pandemic in 2020, numerous researches and studies have focused on the long-term effects of COVID infection. The Centers for Disease Control (CDC) implemented an additional code into the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for reporting ‘Post COVID-19 condition, unspecified (U09.9)’ effective on October 1st 2021, representing that Long COVID is a real illness with potential chronic conditions. The National COVID Cohort Collaborative (N3C) provides researchers with abundant electronic health records (EHR) data by aggregating and harmonizing EHR data across different clinical organizations in the United States, making it convenient to build up a survival analysis on Long COVID patients and non Long COVID patients among large amounts of COVID positive patients.
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.
Background Long COVID involves persistent symptoms after COVID-19 recovery, affecting multiple organ systems for months or years. Risk factors include female sex, prior chronic conditions, severe SARS-CoV-2 infection, reinfections, and lack of vaccination. As a major public health concern, ongoing research continues to investigate its causes, mechanisms, and long-term effects. Methods Proteomic expression analysis of 171 individuals, in two time points, with confirmed SARS-CoV-2 infection, including 133 long COVID patients from the deeply characterized COVICAT cohort, assessed 1395 protein biomarkers using Olink® technology. Statistical analyses with linear mixed models examined protein expression changes, long COVID status, and sex-specific differences. Functional analysis included gene set enrichment analysis and protein–protein interaction networks. Results Findings revealed VEGFA overexpression in long COVID patients (effect size 0.322, SE = 0.098, p = 0.0013), along with sex-specific expression patterns and the influence of sex-hormonal status in females, with significant overexpression of circulating VEGFA levels specifically in postmenopausal women (Mann–Whitney U test p value = 8.55 × 10^−3). Network analysis identified 109 nodes and 274 edges, with VEGFA ranking highest in centrality. Dysregulated chemokine signaling, complement activation, and viral reactivation were also confirmed, consistent with prior studies. Conclusions Using high-throughput proteomic profiling in a population-based cohort, we observed that vascular dysfunction, particularly involving VEGFA, is a key feature of long COVID, especially in milder cases, with significant overexpression of VEGFA in postmenopausal women. Sex-specific proteomic patterns suggest distinct recovery mechanisms, highlighting the need to consider sex, vascular health, and disease severity in the pathogenesis and management of long COVID.
Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients’ clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.
Background Since the declaration of COVID-19 as a pandemic in 2020, its main symptoms have primarily affected the respiratory system. However, it also presents other systemic manifestations, including symptoms related to the larynx and pharynx. COVID-19 has evolved into subsequent variants, starting from the alpha variant and currently dominated by the Omicron variant, with the Delta variant being the most severe. The study aimed to elucidate the laryngo pharyngeal manifestations related to Delta and Omicron variants of COVID-19 as well as the associated risk factors. Results This study adopted a case–control design. The data were collected from patients who attended the phoniatric outpatient clinic at Menoufia University Hospital from January to December 2022. Patients were categorized into three groups (50 patients each). Group I consisted of patients who exhibited COVID-19 Laryngo pharyngeal symptoms during the Delta wave (Group 1) and the Omicron wave (Group 2). The control group included non-COVID-19 participants. The symptoms related to the larynx and pharynx were documented. In addition, laryngoscopic and stroboscopic examinations were done. The age of individuals affected by the Delta variant was higher. Delta cases exhibited a higher rate of smoking, diabetes, hypertension, and COPD compared to Omicron cases. Additionally, Delta cases displayed greater severity. Dysphagia, dysphonia, choking attacks related to swallowing, and stridor had significant higher rate in the Delta variant compared to the Omicron variant. The Delta variant primarily exhibited unilateral vocal fold paralysis in 38% of cases, as well as bilateral vocal fold paresis and paralysis in 20% and 22% of cases, respectively. In contrast, Omicron cases predominantly showed vocal fold congestion (80% of cases). Delta cases were more prone to experiencing abnormalities in amplitude, symmetry, and periodicity. Conclusions The Delta variant is more prone to neurologic affection of the vocal folds manifesting as paresis and paralysis, whereas the Omicron variant, which has maintained its dominance thus far, experiences milder affection, primarily manifesting as congestion. Consequently, laryngeal affection with various degrees of severity is still suspected.
BACKGROUND: Post-acute sequelae of SARS-CoV-2, referred to as “long COVID”, are a globally pervasive threat. While their many clinical determinants are commonly considered, their plausible social correlates are often overlooked. METHODS: Here, we use data from a multinational prospective cohort study to compare social and clinical predictors of differences in quality of life with long COVID. We further measure the extent to which clinical intermediates may explain relationships between social variables and quality of life with long COVID. FINDINGS: Beyond age, neuropsychological and rheumatological comorbidities, educational attainment, employment status, and female sex were important predictors of long COVID-associated quality of life days (long COVID QALDs). Furthermore, most of their associations could not be attributed to key long COVID-predicting comorbidities. In Norway, 90% (95% CI: 77%, 100%) of the adjusted association between belonging to the top two quintiles of educational attainment and long COVID QALDs was not explained by these clinical intermediates. The same was true for 86% (73%, 100%) and 93% (80%,100%) of the adjusted association between full-time employment and long COVID QALDs in the United Kingdom (UK) and Russia. Additionally, 77% (46%,100%) and 73% (52%, 94%) of the adjusted associations between female sex and long COVID QALDs in Norway and the UK were unexplained by the clinical mediators. INTERPRETATION: Our findings highlight that socio-economic proxies and sex are key predictors of long COVID QALDs and that other (non-clinical) mechanisms drive their observed relationships. Importantly, we outline a multi-method, adaptable causal approach for evaluating the isolated contributions of social disparities to experiences with long COVID. FUNDING: UK Foreign, Commonwealth and Development Office; Wellcome Trust; Bill & Melinda Gates Foundation; Oxford COVID-19 Research Response Funding; UK National Institute for Health and Care Research; UK Medical Research Council; Public Health England; Liverpool Experimental Cancer Medicine Centre; Research Council of Norway; Vivaldi Invest A/S; South Eastern Norway Health Authority
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.
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.
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.
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.
BACKGROUND: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. METHODS: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. FINDINGS: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. INTERPRETATION: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. FUNDING: 10.13039/100000060National Institute of Allergy and Infectious Diseases of the 10.13039/100000002National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.
Based on recent studies, some COVID-19 symptoms can persist for months after
infection, leading to what is termed long COVID. Factors such as vaccination
timing, patient characteristics, and symptoms during the acute phase of
infection may contribute to the prolonged effects and intensity of long COVID.
Each patient, based on their unique combination of factors, develops a specific
risk or intensity of long COVID. In this work, we aim to achieve two
objectives: (1) conduct a statistical analysis to identify relationships
between various factors and long COVID, and (2) perform predictive analysis of
long COVID intensity using these factors. We benchmark and interpret various
data-driven approaches, including linear models, random forests, gradient
boosting, and neural networks, using data from the Lifelines COVID-19 cohort.
Our results show that Neural Networks (NN) achieve the best performance in
terms of MAPE, with predictions averaging 19\% error. Additionally,
interpretability analysis reveals key factors such as loss of smell, headache,
muscle pain, and vaccination timing as significant predictors, while chronic
disease and gender are critical risk factors. These insights provide valuable
guidance for understanding long COVID and developing targeted interventions.
;Comment: 8 pages, 9 figures, 2 tables, initially submitted in IJCNN 2025, but
rejected because of the high number of contributions (requested to be
presented as a poster in the conference without being published in conference
proceedings)
BACKGROUND: Over 10,000 rare diseases (RDs) affect more than 300 million people globally, yet their influence on COVID-19 severity, reinfection risk, and long COVID remains poorly understood. This study evaluates the impact of RDs on these outcomes and examines the effectiveness of vaccination and antiviral treatments among individuals with and without RDs. METHODS: We conducted a retrospective cohort study using harmonized electronic health records (EHRs) from the National COVID Cohort Collaborative (N3C), encompassing 21,704,702 individuals, including 4,825,605 with confirmed SARS-CoV-2 infection between Jan 1, 2020, and Jan 4, 2024. RDs were defined using 12,003 conditions curated from GARD and Orphanet, mapped to OMOP concepts, and classified into 18 RD classes based on medical specialty involvement. Primary outcomes included: (1) COVID-19 severity (hospitalization and life-threatening disease), (2) long COVID, and (3) SARS-CoV-2 reinfection. We applied multivariable logistic regression with inverse probability of treatment weighting and reported adjusted odds ratios with 95% confidence intervals and associated p-values. Models were controlled for demographics, comorbidities, and exposure to vaccination and antiviral treatments. FINDINGS: Of 21,704,702 individuals, we identify 4,825,605 COVID-19 positive individuals, 6.36% had RDs, with markedly higher rates of rare disease (RD) patients that have life-threatening illness (16% vs. 6.1% without life-threatening illness) and that are hospitalized (13% vs. 6.0% without hospitalization). Otorhinolaryngologic diseases showed the highest risk of life-threatening outcomes (OR 4.51; 95% CI 3.81-5.33), followed by developmental defect during embryogenesis (OR 1.84; 95% CI 1.72-1.98) and cardiac conditions (OR 1.79; 95% CI 1.51-2.11). Hospitalization risk was highest for otorhinolaryngologic (OR 2.90; 95% CI 2.61-3.23), developmental defect during embryogenesis (OR 2.06; 95% CI 1.97-2.16), and hematologic and endocrine diseases (OR 1.81; 95% CI 1.75-1.87 and OR 1.81; 95% CI 1.64-1.99, respectively). In patients with RDs, vaccination alone or antiviral treatment alone was associated with reduced odds of life-threatening COVID-19 disease compared to non-vaccinated individuals (OR 0.71; 95% CI 0.66-0.77 and OR 0.33; 95% CI 0.26-0.42, respectively). The combination of both vaccination and antiviral treatment showed the greatest reduction in odds ratio (OR 0.24; 95% CI 0.20-0.27). Similar results were observed in patients without RDs. In contrast, vaccination or antiviral therapy alone, compared to no intervention, did not significantly reduce long COVID risk in RD patients, although these interventions alone did result in a lower odds ratio in patients without RD. However, their combination was protective in both groups. Vaccination alone, compared to no vaccination, also reduced the risk of reinfection across RD and non-RD populations. INTERPRETATION: RD patients face elevated risks of severe COVID-19 outcomes. While vaccination and antivirals significantly reduce the acute severity of illness, their impact on long COVID appears limited in this population. Notably, vaccination was protective against COVID-19 reinfection in both RD and non-RD populations. These findings highlight the need for targeted strategies to protect RD patients beyond current interventions, particularly in preventing long-term complications. FUNDING: This work was supported in part by the intramural and extramural programs at NCATS (ZIA ZICTR000410).
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.
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.
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.
Colégio Brasileiro de Cirurgia Digestivajanuari 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.
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.
Purpose This longitudinal study investigated distress rates in patients with advanced ovarian cancer during the COVID-19 pandemic and examined whether time, illness representations, and coping strategies predicted distress levels. Methods UK patients with stage 3 or 4 ovarian cancer were recruited between September 2020 and March 2021. Data were collected at baseline (T0), 2 months (T1), and 4 months (T2) post-enrolment. Validated questionnaires assessed distress (anxiety, depression, PTSD, fear of progression) and predictors (coping strategies and illness perceptions), analysed via multilevel modelling. Results Seventy-two participants returned a questionnaire at T0, decreasing to 49 by T2. High distress was observed, with over 50% of participants experiencing anxiety and depression consistently. Nearly 60% reported clinical levels of fear of progression at some point. PTSD rates resembled the general population. Although distress levels remained stable over time, some individual variability was observed. Time had minimal effect on distress. Coping strategies and illness perceptions remained stable. Threatening illness perceptions consistently predicted distress, while specific coping strategies such as active coping, acceptance, self-blame, and humour predicted various aspects of distress. Together, these factors explained up to half of the distress variance. Conclusion The findings have implications for routine screening for distress and the inclusion of psychological treatment pathways in advanced ovarian cancer care. Addressing illness representations is crucial, with attention to informational support. Future research should explore the long-term effects of heightened distress and the effectiveness of interventions targeting illness perceptions. This study informs current clinical practice and future pandemic preparedness in cancer care.
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.
Background Public transportation plays a major role in the transmission of SARS-CoV2, the virus that causes COVID-19, due to the confined spaces in vehicles. It is therefore very crucial to apply COVID-19 prevention measures in public transportation to reduce risk of COVID-19 transmission. The implementation of these measures depends largely on the public transportation users. We explored the awareness, perceptions and challenges among public transport operators during the implementation of COVID-19 preventive measures in Eastern Uganda. Methods This qualitative study was done in Eastern Uganda in January and February 2021. We conducted four focus group discussions, six in-depth interviews and three key informant interviews to document the awareness, perceptions and challenges faced by public transport operators including 10 boda boda riders, 19 taxi operators and 11 truck (cargo) transporters. All interviews were audio-recorded, transcribed verbatim, and analyzed with the help of NVIVO software version 12 plus using a thematic framework approach. Results We relied on the health belief model to report on four broad themes including: Perceived threat, perceived benefits, perceived barriers and cues to action. Perceived threat Participants were aware of the gravity / seriousness of COVID-19. They were aware that it is an unusual flu whose symptoms are severe and clearly distinguishable from the common flu. They also knew that COVID-19 is easily and quickly transmitted. However they were not aware of the cause of COVID-19. Perceived benefits: the participants perceived a number covid 19 preventive measures as beneficial in preventing COVID-19. These included: COVID 19 vaccination, observing hand hygiene, avoiding touching the ‘soft parts’ (eyes, nose and mouth), quarantining in a hospital setting, wearing a face mask, social distancing,. Perceived barriers: participants reported barriers to implementing COVID 19 preventive measures included Misconceptions about COVID 19, scepticism about COVID-19 vaccination, not breathing well or respiratory problems hinders use of face masks, fear of covid 19 transmission during home isolation, design of the vehicles do not favour social distancing, passengers unwilling to pay the fare, natural reflexes come in the way of not touching soft parts, financial constraints, hostility from passengers due to increased transport fares, law enforcement officials prioritizing the driving permit over implementation of the measures, hostility from law enforcement officials, religious beliefs against the use of alcohol, competing for passengers among public transporters. Cues to action included Mass sensitization by the Ugandan government through the ministry of health with the help of media platforms like television. Conclusions and recommendation Our study brings to light the likely barriers that impede the use of preventive measures in public transportation use during an epidemic / pandemic like COVID-19 which could potentially escalate transmission. During cues to action like sensitization through media, focus should be put to the demystification of myths on COVID-19, highlighting on benefits of using preventive measures and risk of disease. Public transport passengers should be sensitized on risk of COVID-19 transmission during public transportation use and on the importance of complying with COVID-19 preventive measures. We recommend further exploration on the challenges faced by the public transportation passengers in implementing preventive measures in the event of an epidemic like COVID-19. Future research is required to establish a more robust transport model in crisis situations such as a pandemic. In addition, there is need for integration between the public health and public transportation sectors to foster epidemic preparedness for future crises in the context of public transportation.
OBJECTIVES: Long COVID is a debilitating condition that impacts millions of Americans, but patients and clinicians have little information on how to prevent this disorder. Vaccination is a vital tool in preventing acute COVID-19 and may confer additional protection against Long COVID. There is limited evidence regarding the optimal timing of COVID-19 vaccination (i.e., vaccination schedule) to minimize the risk of Long COVID. METHODS: We applied Longitudinal Targeted Maximum Likelihood Estimation to electronic health record (EHR) data from a retrospective cohort of patients vaccinated against COVID-19 between December 2021 and September 2022. We evaluated the association between binary COVID-19 vaccination status (two or more doses vs. zero doses) and 12-month Long COVID risk among patients diagnosed with acute COVID-19 between December 2021 and September 2022. In addition, we compared the 12-month cumulative risk of Long COVID (ICD-10 code U09.9) among patients diagnosed with acute COVID-19 one to three months after vaccination, three to five months after vaccination, or five to seven months after vaccination while adjusting for relevant high-dimensional baseline and time-dependent covariates. RESULTS: We analyzed EHR data from a retrospective cohort of 1,558,018 patients. In our binary cohort (n = 519,980), we found that vaccinated patients had a lower risk of Long COVID than unvaccinated patients (adjusted marginal risk ratio 0.84 (0.81, 0.88)). In our longitudinal cohort (n = 1,085,291), we did not find a significant difference in Long COVID risk comparing patients who were diagnosed with acute COVID-19 one to three months after vaccination versus patients who were diagnosed with COVID-19 three to five months (adjusted marginal risk ratio 0.93 (95% CI 0.62, 1.41) or 5 to 7 months (adjusted marginal risk ratio 1.06 (95% CI 0.72, 1.56)) after vaccination. CONCLUSIONS: We found that COVID-19 vaccination before SARS-CoV-2 infection was protective against Long COVID, and we did not find that this protection significantly waned within 7 months after vaccination. These findings suggest that COVID-19 vaccination protects against Long COVID.
BACKGROUND: Youth living with HIV (YWH) face persistent barriers to care engagement and viral suppression. Telehealth expanded during COVID-19, offering new possibilities for access, but provider perspectives on its use with YWH are underexplored. METHODS: A national mixed-methods survey captured experiences of 156 HIV care providers. Quantitative data were analyzed using descriptive and inferential statistics; qualitative data were analyzed using reflexive thematic analysis. RESULTS: Most providers (88.5%) believed telehealth would continue to play a role in HIV care. Reported benefits included improved access (80.7%) and workflow efficiency (64.7%). However, providers were significantly less likely to discuss sensitive topics “often” via telehealth compared to in-person care, including mental health (81.4% vs. 92.9%, p = 0.0008) and sexual health (77.9% vs. 93.6%, p < 0.0001). CONCLUSIONS: While telehealth improves access for YWH, hybrid care models and targeted provider training are needed to address privacy, communication, and trust when discussing sensitive health concerns.
INTRODUCTION: HIV prevention and treatment supported by the United States President’s Emergency Plan for AIDS Relief (PEPFAR) have saved millions of lives. Rwanda is among the most successful countries around the world in achieving global targets with PEPFAR support. However, abrupt funding uncertainty around PEPFAR raises concerns about continued HIV epidemic control. We projected the impact of the Government of Rwanda’s (GoR’s) capacity to offset the elimination of PEPFAR funding on adult HIV epidemic and care continuum outcomes over 10 years. METHODS: Using an HIV policy model calibrated to Rwanda, we assessed: capacity to sustain HIV services at 50% (with no capacity by GoR to cover the PEPFAR funding gap), 75%, 90%, and 100% (with full capacity by GoR to cover the PEPFAR funding gap). Scenarios were operationalized by reducing the number on antiretroviral therapy (ART), with immediate ART discontinuation and proportional decreases in HIV diagnosis, ART initiation, and care re- engagement. We projected HIV epidemic outcomes (HIV prevalence, HIV incidence, number with HIV, new HIV infections, deaths) and care continuum outcomes (percent diagnosed, percent on ART among those diagnosed, percent virally suppressed among those on ART). We calculated differences in projected outcomes for partial or no capacity versus full capacity. Secondary analyses assessed delayed coverage capacity by 1 and 3 years. RESULTS: Compared to full capacity at 10 years, the model projected a 13.9%–38.7% increase in HIV prevalence and 69.0%–246.7% increase in HIV incidence across coverage capacity scenarios. This translated to 29,000–64,000 additional adults with HIV and 20,000–92,000 cumulative new adult HIV infections. Cumulative projected deaths increased by 10,000–51,200. The model projected continual reductions in percent diagnosed at 10 years; percent virally suppressed among those on ART was similar across scenarios. Higher, and more delayed, coverage capacity had projected outcomes similar to lower, and less delayed, coverage capacity. CONCLUSIONS: Even in countries like Rwanda that have achieved epidemic control, abrupt and persistent elimination of PEPFAR funding could drastically reverse critical gains. Evidence quantifying the consequences of different capacities to sustain HIV services underscores the high stakes of rapid and sufficient action.
BACKGROUND: Eliminating HIV vertical transmission (VT) and is a global priority. Estimates of paediatric HIV infections are commonly derived through mathematical models relying on rates of VT stratified by maternal immunological and treatment status from literature, namely the UNAIDS-supported Spectrum AIDS Impact Module (Spectrum-AIM) to assess progress towards eliminating VT. Default VT probabilities were last updated in 2018, since then there have been substantial changes to service delivery and ART regimens. METHODS: We aimed to (1) update the systematic review of VT probabilities by maternal status compatible with Spectrum-AIM, (2) conduct a meta-regression to systematically pool studies to estimate VT probabilities with statistical uncertainty, and (3) assess determinants of VT, including maternal viral load. We searched PubMed, Embase, Global Health Database, WHO Global Index Medicus, CINAHL Complete, and Cochrane CENTRAL for peer-reviewed articles in English from all geographic regions with data on VT from randomized controlled trials, cohort studies, or observational studies. We excluded sources that did not stratify VT by maternal treatment or immunological status. We fit four meta-regression models to produce VT probability estimates compatible with stratifications used in Spectrum-AIM and assessed how updated VT probabilities estimated new paediatric infections compared to default parameters in Spectrum-AIM. We conducted subgroup analyses to assess how study inclusion affected model estimates. Finally, we fit a meta-regression model to assess ART class and initiation timing on viral load suppression at delivery. FINDINGS: The updated systematic review identified 24 new studies published between January 2018 and February 2024. Combined with previous review data, 110 studies were included in the meta-regression analysis. Estimates were broadly consistent with previous reviews. For women not receiving PMTCT, the odds of perinatal transmission decreased by 0.20 (0.16–0.25) for each 100 mm (3) increase in median CD4 of the study population. Among women on ART during pregnancy, each additional week on ART before delivery reduced the odds of VT by 5.6% (4.3%–6.8%). ART regimen class affected VT probability; the odds ratio of perinatal VT among WLHIV who initiated an INSTI-based regimen versus a NNRTI-based regimen 20 weeks before delivery was 0.355 (0.140–0.898). However, this effect was confounded by study region. Viral load suppression at delivery was significantly lower among women who started ART late during pregnancy (p=0.02), but did not significantly differ by ART class (p>0.05). INTERPRETATION: Vertical transmission rates vary substantially according to maternal immunological stage, prophylactic regimen, and timing of treatment initiation. Time of initiation on ART before delivery was strongly associated with viral load suppression at delivery. Our estimates and their uncertainty can be used in Spectrum-AIM to produce estimates of paediatric incidence to inform funding and monitor progress towards eliminating VT. FUNDING: National Institutes of Health, UNAIDS, and the Medical Research Council
Background In Malawi, approximately 25% of adolescents living with HIV (ALWH) also suffer from depression. Not only is HIV stigma a major contributor to depression but it also adversely impacts HIV care engagement. ALWH can experience HIV stigma as stereotyping, social exclusion, low social support, and abuse, and these experiences are associated with poor mental health. Despite recognition of the deleterious effects of HIV stigma, we have limited knowledge of how stigma is experienced by ALWH with comorbid depression. Guided by the Health Stigma and Discrimination Framework, we describe stigma faced by ALWH and comorbid depression in Malawi and its implications for future interventions. Methods As part of a larger formative study to adapt a mental health counseling intervention, we conducted in-depth interviews, social support mapping sessions, and focus-group discussions with 25 ALWH, 4 caregivers of ALWH, 3 HIV providers, and 5 participants and 5 staff of a prior mental health counseling intervention. After analyzing the stigma codes, we used the Health Stigma and Discrimination Framework to organize the data into four key domains: drivers, manifestations, outcomes, and health and social impacts. Results Major drivers of HIV stigma included fear of HIV transmission, negative effects of antiretroviral therapy (ART), association with death, inaccurate knowledge, and negative attitudes towards ALWH. The most common manifestations of HIV stigma were gossip, insults and mocking, and physical and social distancing. Decreased ART adherence and missed HIV appointments were commonly cited outcomes of HIV stigma. Broader health impacts of HIV stigma were notable for mental health comorbidities including depression, anxiety, substance use, and suicidality. Identified resilience strategies included support for HIV care engagement and psychosocial support from family and friends. Conclusions This study systematically describes the stigmatization process faced by ALWH and experiencing depressive symptoms in Malawi. Notably, HIV stigma continues to disrupt HIV care and detrimentally impacts mental health during adolescent development. Further studies focused specifically on stigma are needed to better characterize this process and identify additional resilience factors. Investment in stigma-reduction interventions for ALWH is needed to avert poor mental health and HIV outcomes.
In vitro selection is typically limited to discovery of peptides, proteins and nucleic acids. Given the importance of carbohydrate-protein interactions in diverse areas of biology including cell adhesion/recognition, immunoregulation and host-pathogen interactions, directed-evolution-based methods for discovery of potent glycoligands are greatly needed. We have previously reported a method for in vitro selection of glycopeptides that combines mRNA display, alkynyl amino acid incorporation, and CuAAC “click” glycosylation. Herein, we describe extensions of this method that incorporate chemical cyclization, removal of N-terminal glycosylation sites and next-generation sequencing; as an approach to HIV immunogen design, we have then used this method to develop mimics of the High Mannose Patch (HMP), which is the region on HIV envelope protein gp120 most commonly targeted by HIV broadly neutralizing antibodies (bnAbs). We prepared libraries of 10 (12-14) glycopeptides about 50 amino acids in length, containing variable numbers of high mannose (Man (9) GlcNAc (2) ) glycans and cyclization at varied sites. We performed selections to obtain binders of HIV bnAbs PGT128, PGT122, and gl-PGT121, a germline precursor of PGT122, and prepared numerous glycopeptide hits by chemical synthesis. Selected glycopeptides in some cases bound very tightly to their target HIV bnAb, e.g., with a K (D) as low as 0.5 nM for PGT128. These glycopeptides are of interest as immunogens and tools for HIV vaccine design.
Background Integrating HIV clinical records with population-based surveillance data allows the study of health care seeking behaviours, access to care, and predictors of patient outcomes. We implemented a graph-based record linkage algorithm to deduplicate and link HIV clinical and population-based surveillance records in an HIV-endemic setting in rural South Africa. Methods We linked four data sources to create the Africa Health Research Institute (AHRI) Unified Data Platform: AHRI’s Health and Demographic Surveillance System (HDSS), AHRI Clinic and Hospital Information System (AHRILink), National Health Laboratory Service (NHLS), and Three Integrated Electronic Registers (TIER.Net) HIV care and treatment records. HDSS data were collected between January 1, 2000, and July 31, 2024, through repeated household surveys of over 140,000 individuals. Clinical and laboratory data were obtained for one hospital and 17 clinics in Hlabisa, KwaZulu-Natal, covering the HDSS surveillance area. We implemented a probabilistic record linkage algorithm trained and validated on a subset of records with national identity numbers. We assessed linkage accuracy, computed descriptive statistics for the linked database, and estimated the HIV care cascade for this population. Results A total of 986,832 records were successfully linked across the four databases, achieving a sensitivity of 92.7% and a positive predictive value of 96.5% (F-score=0.95). The average number of records (standard deviation (SD)) in TIER.Net, HDSS, AHRILink and NHLS were 1.18 (0.44),1.05 (0.23),1.13 (0.40), and 5.21 (4.24), respectively. The linked data indicated that 12,293 HDSS resident adults (≥15 years) were living with HIV at some point during the 2022 and 2024 surveillance rounds. Of these, 10,622 (86.4%) had ever sought HIV care in the public sector, of whom 10,492 (98.8%) had ever started ART and 7,065 (66.5%) were currently on ART, of whom 6,301 (89.2%) were virally suppressed(viral load<200 copies/mL). Conclusion HIV care and population surveillance records from four data sources were deduplicated and linked with high accuracy, revealing persistent gaps in retention in care and viral suppression in an HIV-endemic region in rural South Africa. The AHRI Unified Data Platform offers the potential to deepen our understanding of HIV epidemiology in a well-described population and to improve services for HIV. Trial registration Not applicable.
Background: HIV and substance use represent interacting epidemics with shared psychological drivers - impulsivity and maladaptive coping. Dialectical behavior therapy (DBT) targets these mechanisms but faces scalability challenges. Generative artificial intelligence (GenAI) offers potential for delivering personalized DBT coaching at scale, yet rapid development has outpaced safety infrastructure. Methods: We developed Glow, a GenAI-powered DBT skills coach delivering chain and solution analysis for individuals at risk for HIV and substance use. In partnership with a Los Angeles community health organization, we conducted usability testing with clinical staff (n=6) and individuals with lived experience (n=28). Using the Helpful, Honest, and Harmless (HHH) framework, we employed user-driven adversarial testing wherein participants identified target behaviors and generated contextually realistic risk probes. We evaluated safety performance across 37 risk probe interactions. Results: Glow appropriately handled 73% of risk probes, but performance varied by agent. The solution analysis agent demonstrated 90% appropriate handling versus 44% for the chain analysis agent. Safety failures clustered around encouraging substance use and normalizing harmful behaviors. The chain analysis agent fell into an "empathy trap," providing validation that reinforced maladaptive beliefs. Additionally, 27 instances of DBT skill misinformation were identified. Conclusions: This study provides the first systematic safety evaluation of GenAI-delivered DBT coaching for HIV and substance use risk reduction. Findings reveal vulnerabilities requiring mitigation before clinical trials. The HHH framework and user-driven adversarial testing offer replicable methods for evaluating GenAI mental health interventions.
Men who have sex with men (MSM) have been disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The HIV treatment cascade is an important clinical monitoring strategy that involves the number of MSM living with HIV in health services. This study aimed to analyze the HIV treatment cascade in the MSM population in Brazil and to identify factors associated with different cascade stages. A cross-sectional study was conducted in 12 Brazilian capitals and included 4,176 MSM recruited through respondent-driven sampling in 2016. Factors associated with each stage of the HIV treatment cascade (outcomes), i.e., HIV diagnosis, use of antiretroviral therapy, and achievement of undetectable viral load, were identified via logistic regression. Approximately 18.3% (95% CI: 15.4–21.7) of the MSM were diagnosed with HIV at the time of the survey. Among those living with HIV, only 55.5% (95% CI: 46.2–64.4) had previous knowledge of their serologic status, and 98.4% (95% CI: 96.3–99.3) of those aware of their status used antiretroviral therapy. Among those reporting using antiretroviral therapy, 80.0% (95% CI: 64.8–89.7) had a suppressed viral load, whereas 79.4% (95% CI: 64.4–89.2) had an undetectable viral load. Age > 25 years, having completed high school or higher, having a previous diagnosis of another sexually transmitted infection, and not being identified as bisexual were positively associated with all outcomes. Once enrolled in HIV treatment programs, most MSM achieve viral suppression. The challenge for HIV control is that fully half of our sample or men who tested positive did not know their HIV status. Regardless of the reason for this lack of testing, Brazil faces a continuing HIV epidemic.
Background Several studies have demonstrated the population-level effectiveness of oral PrEP in reducing the risk of HIV infection. However, oral PrEP utilization among MSM in China remains below 1%. While existing literature has primarily focused on oral PrEP preference and willingness, there is limited exploration of the underlying factors contributing to oral PrEP cessation in China. This study aims to fill this gap by investigating the factors associated with oral PrEP cessation among MSM in China. Methods Assisted by MSM community organizations, we collected 6,535 electronic questionnaires from 31 regions across China, excluding Taiwan, Hong Kong, and Macau. The questionnaire focused on investigating MSM's awareness, willingness, usage, and cessation of oral PrEP. Additionally, 40 participants were randomly chosen for key informant interviews. These qualitative interviews aimed to explore the reasons influencing MSM discontinuing oral PrEP. Results We eventually enrolled 6535 participants. Among the 685 participants who had used oral PrEP, 19.70% (135/685) ceased oral PrEP. The results indicated that individuals spending > ¥1000 on a bottle of PrEP ( aOR = 2.999, 95% CI: 1.886–4.771) were more likely to cease oral PrEP compared to those spending ≤ ¥1000. Conversely, individuals opting for on-demand PrEP ( aOR = 0.307, 95% CI: 0.194–0.485) and those using both daily and on-demand PrEP ( aOR = 0.114, 95% CI: 0.058–0.226) were less likely to cease PrEP compared to those using daily PrEP. The qualitative analysis uncovered eight themes influencing oral PrEP cessation: (i) High cost and low adherence; (ii) Sexual inactivity; (iii) Lack of knowledge about PrEP; (iv) Trust in current prevention strategies; (v) Poor quality of medical service and counseling; (vi) PrEP stigma; (vii) Partner and relationship factors; (viii) Access challenges. Conclusions The cessation of oral PrEP among MSM in China is associated with various factors, including the cost of oral PrEP medication, regimens, individual perception of HIV risk, stigma, and the quality of medical services. It is recommended to provide appropriate regimens for eligible MSM and develop tailored combinations of strategies to enhance PrEP awareness and acceptance among individuals, medical staff, and the MSM community. The findings from this study can support the refinement of HIV interventions among MSM in China, contributing to efforts to reduce the burden of HIV in this population.
Background The pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated to be one of the culprits. This notion is derived from studies in HIV-uninfected populations and/or animals while data on HTN and how it relates to IA in PLHIV remains scarce. We determined the relationship between HTN and IA among antiretroviral therapy (ART) naïve PLHIV. Methods We analysed baseline data of 365 out of 430 clinical trial participants whose main aim was to investigate the effect of low-dose aspirin on HIV disease progression in PLHIV starting ART. Soluble CD14 (sCD14), T cells co-expressing CD38 and HLA-DR, and PD-1 were the IA and exhaustion markers, respectively studied and were analysed by flow cytometry. Mann-Whitney U-test was used for comparison of the markers by HTN status. A robust Poisson regression model was used to determine the predictors for HTN. Results A quarter of the 365 were hypertensive (25.3%, 95% CI 20.9–29.8%), and, had higher median (IQR) body mass index (kg/m^2) (23.4 (19.6, 28.0) versus 21.9 (19.3, 25.1)) and lower median (IQR) estimated glomerular filtration rate (mL/min/1.73m^2) (101.2 (79.4, 126.9) versus 113.6 (92.7, 138.8)) than normotensive participants ( p < 0.05). Participants with HTN had higher median frequencies of all markers of IA and exhaustion but lower sCD14 ( p > 0.05). None of these markers significantly predicted the occurrence of HTN. Conclusion Studied markers of IA and exhaustion were higher in PLHIV with HTN than those without but were unpredictive of HTN. Larger multicentre studies with a wider range of markers are needed to confirm the role of IA in HIV-associated HTN.
People living with HIV face a high burden of comorbidities, yet early detection is often limited by symptom-driven screening. We evaluate the potential of AI to predict multiple comorbidities from routinely collected Electronic Health Records. Using data from 2,200 HIV-positive patients in South East London, comprising 30 laboratory markers and 7 demographic/social attributes, we compare demographic-aware models (which use both laboratory/social variables and demographic information as input) against demographic-unaware models (which exclude all demographic information). Across all methods, demographic-aware models consistently outperformed unaware counterparts. Demographic recoverability experiments revealed that gender and age can be accurately inferred from laboratory data, underscoring both the predictive value and fairness considerations of demographic features. These findings show that combining demographic and laboratory data can improve automated, multi-label comorbidity prediction in HIV care, while raising important questions about bias and interpretability in clinical AI. ;accepted at ICCV 2025
The prevalence of HBV, HCV, and TB was high among Iranian PLWH The prevalence was higher among at-risk groups such as PWIDs and homeless people The prevalence of HCV was more than HBV and TB among PLWH Background Up to now several studies estimate the prevalence of HBV, HCV, and TB among people living with HIV (PLWH) in Iran; however, their results are inconsistent. This study aimed to estimate the overall prevalence of HBV, HVC, and TB among Iranian PLWH. Methods In this systematic review and meta-analysis six databases including Medline, Web of Science, Scopus, MagIran, Scientific Information Database (SID), and Barakat Knowledge network system were searched up to October 2023 with no language restriction. All studies estimated the prevalence of HBV, HCV, and TB among PLWH in Iran were included. The random-effects model was used to report the study estimates. Results were reported at a 95% confidence interval (CI). Results Out of 1050 retrieved references, 58 articles met the eligibility criteria. Overall among PLWH, HBV prevalence was 13.0% (95% CI: 11.0, 15.0), HCV prevalence was 54% (95% CI: 45.0, 64.0), and TB prevalence was 19% (95% CI: 13.0, 24.0). The results from multivariate meta-regression analysis showed no statistically significant association between HBV and TB prevalence with the year of study, quality of studies, age, gender, and persons who inject drugs (PWID). HCV prevalence was significantly associated with PWID. Conclusion We found HBV, HCV, and TB infections are common among PLWH in Iran and required to be screened and treated with effective and timely services.
Background The COVID-19 pandemic posed significant challenges for managers overseeing women's harm reduction centers. This study seeks to capture managers' perspectives on the service providing in women's harm reduction centers during the COVID-19 pandemic. Methods This convergent mixed-method study conducted in three provinces of Iran: Tehran, Khuzestan, and Kermanshah. The study was carried out between January and May 2023. In the quantitative part, the researchers utilized reports from 10 center managers. A researcher-designed questionnaire was employed to collect data on a wide range of services and referrals provided by the centers. The qualitative part of the research involved conventional content analysis and included 12 individual interviews. Two directors from the Ministry of Health and ten managers of women’s harm reduction centers participated in the interviews. During the interpretation phase, the researchers compared the quantitative and qualitative findings to obtain a comprehensive understanding of the topic. Results During the quantitative stage of the study, it was observed that all the managers were women, with an average age of 40.7 ± 7 years. More than half of the managers had obtained a postgraduate education (n = 6, 60%), and a majority of them were married (n = 7, 70%). Additionally, 40% of the managers (n = 4) were working as contractors. During the non-COVID-19 period, there were higher coverage by centers and residents, more referrals of non-injecting drug users and sex workers, and a higher number of group counseling sessions in all three provinces compared to the COVID-19 period. The qualitative analysis revealed two primary themes: "challenges" and "capabilities." Conclusions During the COVID-19 pandemic, providing some services and client referrals decreased in the centers, and center managers faced increased challenges. Many of these challenges were in the communication, executive, management, structure, education, financial, civilization, facilities, and socio-cultural sectors. Managers used their skills to manage and control these challenges. It is important to focus on these challenges and managerial capabilities to effectively handle future crises.
Purpose of Review Despite the growing availability of oral PrEP, coverage remains suboptimal. Through the introduction of additional PrEP methods, including vaginal rings and long-acting injectable formulations, health systems globally are on the cusp of offering PrEP methods that vary by route of administration, efficacy, and frequency of use. With PrEP choice, it will be important to explore PrEP use patterns to better understand how the ability to choose and switch products affects coverage and continuation. In this review, we draw parallels with family planning (FP) by summarizing how method choice and product switching affected contraceptive coverage globally, synthesize what is known about PrEP product switching, and outline evidence gaps to help guide future research on PrEP switching in the context of choice. Recent Findings Decades of research in FP has demonstrated that product switching is common and can lead to more satisfaction and increases in contraceptive use. While research on PrEP product switching is nascent, findings suggest switching is common, and that providing more than one PrEP option can increase coverage. Key evidence gaps include understanding product switching in the context of full versus constrained choice, switching in the context of temporary need, and developing interventions that promote product switching for those who could benefit. Summary Providing choice and allowing people to start, stop, and switch products according to their needs and desires is a core component of a rights-based approach to HIV prevention. More research is needed to better understand what drives use patterns, including switching, and how to leverage choice to improve coverage. Standard definitions —some of which have been proposed in this review—are needed to inform comparable measurement. Finally, there is a need to holistically frame PrEP use to acknowledge changes in need over the life course, thus making method switching a standard part of HIV prevention.
Background Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a major public health problem in Ethiopia. Patients with TB-HIV co-infection have significantly higher mortality rates compared to those with TB or HIV mono-infection. This systematic review and meta-analysis aim to summarize the evidence on mortality and associated factors among patients with TB-HIV co-infection in Ethiopia. Methods Comprehensive searches were conducted in multiple electronic databases (PubMed/MEDLINE, Embase, CINAHL, Web of Science) for observational studies published between January 2000 and present, reporting mortality rates among TB/HIV co-infected individuals. Two reviewers performed study selection, data extraction, and quality assessment independently. Random-effects meta-analysis was used to pool mortality estimates, and heterogeneity was assessed using I² statistics. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. Results 185 articles were retrieved with 20 studies included in the final analysis involving 8,113 participants. The pooled mortality prevalence was 16.65% (95% CI 12.57%-19.65%) with I^2 : 95.98% & p-value < 0.00. Factors significantly associated with increased mortality included: older age above 44 years (HR: 1.82; 95% CI: 1.31–2.52), ambulatory(HR: 1.64; 95% CI: 1.23–2.18) and bedridden functional status(HR: 2.75; 95% CI: 2.01–3.75), extra-pulmonary Tuberculosis (ETB) (HR: 2.34; 95% CI: 1.76–3.10), advanced WHO stage III (HR: 1.76; 95% CI: 1.22–2.38) and WHO stage IV (HR: 2.17; 95% CI:1.41–3.34), opportunistic infections (HR: 1.75; 95% CI: 1.30–2.34), low CD4 count of < 50 cells/mm^3 (HR: 3.37; 95% CI: 2.18–5.22) and lack of co-trimoxazole prophylaxis (HR: 2.15; 95% CI: 1.73–2.65). Conclusions TB/HIV co-infected patients in Ethiopia experience unacceptably high mortality, driven by clinical markers of advanced immunosuppression. Early screening, timely treatment initiation, optimizing preventive therapies, and comprehensive management of comorbidities are imperative to improve outcomes in this vulnerable population.
Introduction Oral pre-exposure prophylaxis (PrEP) for HIV-1 infection is over 99% effective in protecting against HIV acquisition when used consistently and appropriately. However, PrEP uptake and persistent use remains suboptimal, with a substantial gap in utilization among key populations who could most benefit from PrEP. In Latin America specifically, there is poor understanding of barriers to PrEP uptake and persistence among transgender (trans) women. Methods In April-May 2018, we conducted qualitative interviews lasting 25–45 min as part of an end-of-project evaluation of TransPrEP, a pilot RCT that examined the impact of a social network-based peer support intervention on PrEP adherence among trans women in Lima, Peru. Participants in the qualitative evaluation, all adult trans women, included individuals who either (1) screened eligible to participate in the TransPrEP pilot, but opted not to enroll ( n = 8), (2) enrolled, but later withdrew ( n = 6), (3) were still actively enrolled at the time of interview and/or successfully completed the study ( n = 16), or (4) were study staff ( n = 4). Interviews were audio recorded and transcribed verbatim. Codebook development followed an immersion/crystallization approach, and coding was completed using Dedoose. Results Evaluation participants had a mean age of 28.2 years (range 19–47). When describing experiences taking PrEP, participant narratives highlighted side effects that spanned three domains: physical side effects, such as prolonged symptoms of gastrointestinal distress or somnolence; economic challenges, including lost income due to inability to work; and social concerns, including interpersonal conflicts due to HIV-related stigma. Participants described PrEP use within a broader context of social and economic marginalization, with a focus on daily survival, and how PrEP side effects negatively contributed to these stressors. Persistence was, in some cases, supported through the intervention’s educational workshops. Conclusion This research highlights the ways that physical, economic, and social side effects of PrEP can impact acceptability and persistence among trans women in Peru, amplifying and layering onto existing stressors including economic precarity. Understanding the unique experiences of trans women taking PrEP is crucial to informing tailored interventions to improve uptake and persistence.
Adverse childhood experiences (ACEs) and financial hardship are associated with increased likelihood of heavier alcohol use and health challenges in adulthood among persons living with HIV (PWH). We examined whether retrospectively captured lifetime drinking trajectories are a pathway through which childhood hardships affect current health in a sample of 365 adult PWH. Childhood economic hardship and ACEs were used as main predictors. Measures of alcohol use included age at first drink and lifetime drinking trajectories. Health indicators included health-related quality of life, frailty, number of comorbidities, and symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD). Structural equation modeling (SEM) was applied to estimate both direct and indirect pathways between childhood hardship and physical and mental health. Participants were mostly male; Black (84%); and averaged 48 years of age. SEM results supported both direct and indirect pathways between childhood experiences and adult health. ACEs were connected to physical health directly and mental health both directly and indirectly through age at first drink and drinking heaviness during ages 10–20. Childhood economic hardship related to mental health indirectly through higher drinking levels during ages 10–20. Childhood adverse experiences, economic hardship, and early drinking patterns appear to accumulate, resulting in later life physical and mental health concerns for PWH. Findings support taking a life course approach to health. This includes considering individual trauma histories in HIV care engagement and taking preventative approaches which support the economic and social well-being of vulnerable children to improve health in subsequent decades.
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 Males have accounted for a significant share of new HIV infections among young people in the recent years. This study aimed to identify the factors associated with risky sexual behaviors, including early sexual debut, multiple sexual partnership and condomless sex, among sexually active male college students and provide implications for tailored health interventions. Methods The cross-sectional study was conducted from December 2020 to December 2021 in 16 colleges that were located in Sichuan Province, one of the high-risk areas in China. Overall 1640 male college students who reported sexually experienced were analyzed in this study. Multivariable logistic regression analysis was applied to determine factors associated with early sexual debut, multiple sexual partnership and condomless sex. Results The average age of included male students was 19.95 ± 1.56. Of them, 27.74% initiated sexual behavior early, 48.60% reported multiple sexual partnership, and 16.52% did not use condoms at the latest sexual intercourse. Students who were younger (age ≤ 19, AOR = 7.60, 95%CI: 4.84–11.93; age20-21, AOR = 3.26, 95%CI: 2.04–5.21) and self-identified as sexual minorities (AOR = 2.38, 95%CI: 1.69–3.36) were more likely to have early sexual debut. The odds of having multiple sexual partners were higher among those who were ethnic minorities (AOR = 1.79, 95%CI: 1.33–2.41) and accepted extramarital sex (AOR = 1.33, 95%CI: 1.03–1.71). The likelihood of engaging in condomless sex at the latest sexual intercourse was lower among those who had sufficient knowledgeable about HIV (AOR = 0.63, 95%CI: 0.44–0.89), were very confident in condom use efficacy (AOR = 0.26, 95%CI: 0.16–0.43) and confident (AOR = 0.48, 95%CI: 0.34–0.69). Early sexual debut was positively associated with multiple sexual partnership (AOR = 3.64, 95%CI: 2.82–4.71) and condomless sex at the latest intercourse (AOR = 1.53, 95%CI: 1.07–2.20), respectively. Conclusion Early sexual debut, multiple sexual partnership and condomless sex were of considerable concern among male college students. Comprehensive sex education curricula were advised by developing customized information on HIV prevention, sexuality and empowering students with assertiveness and negotiation skills with regard to condom use during and before college.
Mobile populations such as fisherfolk show high HIV incidence and prevalence. We pilot-tested implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake and adherence in the context of healthcare outreach events in two mainland fisherfolk communities on Lake Victoria, Uganda from September 2021 to February 2022. The implementation strategies included PrEP adherence supporters (selected from PrEP users’ social networks), community workshops (to address misconceptions and stigma, and empower PrEP advocacy), and check-in calls (including refill reminders). PrEP medical records data were collected from 6-months pre-intervention to 6-months post-intervention. Qualitative interviews with 20 PrEP users (10 who continued, 10 who discontinued), 9 adherence supporters, and 7 key partners (providers, community leaders) explored acceptability. Percentages of PrEP initiators (of those eligible) were significantly higher during the intervention (96.5%) than 6-months before the intervention (84.5%), p < 0.0001; percentages of PrEP users who persisted (i.e., possessed a refill) 6-months post-initiation (47.9% vs. 6.7%) and had at least 80% PrEP coverage (based on their medication possession ratio) from the initiation date to 6-months later (35.9% vs. 0%) were higher during versus pre-intervention, p < 0.0001. A comparison fisherfolk community with better healthcare access had lower uptake (78.3%; p < 0.0001) and persistence at 6-months (34.0%; p < 0.001), but higher coverage during the intervention period (70.4%; p < 0.0001). Qualitative data suggested the strategies promoted PrEP use through reduced stigma and misconceptions. The intervention bundle cost was $223.95, $172.98, and $94.66 for each additional person for PrEP initiation, persistence, and coverage, respectively. Enhanced community-based PrEP implementation that fosters a supportive community environment can improve PrEP use in mobile populations without easy access to healthcare. (NCT05084716).
Scientific reports on the association between human immunodeficiency virus (HIV) in patients with COVID-19 and mortality have not been in agreement. In this nationwide study, we described and analyzed the demographic and clinical characteristics of people living with HIV (PLWH) and established that HIV infection is a risk factor for mortality in patients hospitalized due to COVID-19. We collected data from the National Hospital Data Information System at Hospitalization between 2020 and 2022. We included patients admitted to the hospital with a diagnosis of COVID-19. We established a cohort of patients with PLWH and compared them to patients without HIV (non-PLWH). For multivariate analyses, we performed binary logistic regression, using mortality as the dependent variable. To improve the interpretability of the results we also applied penalized regression and random forest, two well-known machine-learning algorithms. A broad range of comorbidities, as well as sex and age data, were included in the final model as adjusted estimators. Our data of 1,188,160 patients included 6,973 PLWH. The estimated hospitalization rate in this set was between 1.43% and 1.70%, while the rate among the general population was 0.83%. Among patients with COVID-19, HIV infection was a risk factor for mortality with an odds ratio (OR) of 1.25 (95% CI, 1.14–1.37, p < 0.001). PLWH are more likely to be hospitalized due to COVID-19 than are non-PLWH. PLWH are 25% more likely to die due to COVID-19 than non-PLWH. Our results highlight that PLWH should be considered a population at risk for both hospitalization and mortality.
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.
Antiretroviral therapy (ART) adherence is crucial for health outcomes of people living with HIV (PLHIV), influenced by a complex interplay of individual, community, and household factors. This article focuses on the influence of household factors, as well as individual and community factors, on ART adherence among PLHIV in Cape Town who have recently initiated ART. Baseline data for a cluster-randomized controlled trial were collected from 316 PLHIV in 12 districts in Cape Town between 6th May 2021 and 22nd May 2022. Zero-inflated Poisson models, with cluster-adjusted standard errors, were used to analyse the association between individual, household, and community factors and ART adherence measures. At the household-level, household support was associated with both better self-rated adherence (exp(β) = 0.81, z = − 4.68, p < 0.001) and fewer days when pills were missed (exp(β) = 0.65, z = − 2.92, p = 0.003). Psychological violence (exp(β) = 1.37, z = 1.97, p = 0.05) and higher household asset scores (exp(β) = 1.29, z = − 2.83, p = 0.05) were weakly associated with poorer ART adherence. At the individual-level, male gender (exp(β) = 1.37, z = 3.95, p < 0.001) and reinitiating ART (exp(β) = 1.35, z = 3.64, p < 0.001) were associated with worse self-rated ART adherence; higher education levels (exp(β) = 0.30 times, z = − 3.75, p < 0.001) and better HIV knowledge (exp(β) = 0.28, z = − 2.83, p = 0.005) were associated with fewer days where pills were missed. At the community-level, community stigma was associated with worse self-rated ART adherence (exp(β) = 1.24, z = 3.01, p = 0.003). When designing interventions to improve ART adherence, household, individual and community factors should all be considered, particularly in addressing gender-based disparities, reducing stigma, tackling violence, and enhancing household support. Clinical Trial Number: Pan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019. La adherencia a la terapia antirretroviral (TAR) es crucial para los resultados de salud de las personas que viven con el VIH (PLHIV), influenciada por una compleja interacción de factores individuales, comunitarios y del hogar. Este artículo se centra en la influencia de los factores del hogar, individuales y comunitarios en la adherencia al TAR entre personas que iniciaron recientemente el TAR en Ciudad del Cabo. Se recopilaron datos de referencia para un ensayo de control aleatorio por grupos de 316 PLHIV en 12 distritos de Ciudad del Cabo entre el 6 de mayo de 2021 y el 22 de mayo de 2022. Se utilizaron modelos de Poisson inflados a cero, con errores estándar ajustados por conglomerado para estudiar la asociación entre factores individuales, del hogar o comunitarios con dos medidas de adhesión al TAR: por un lado la auto declaración de adhesión, y por otro la cantidad de días en que se olvidó de tomar la medicina en los últimos 4 días. A nivel del hogar, el apoyo del hogar se asoció con una mejor adherencia auto declarada (exp(β) = 0.81, z = − 4.68, p < 0.001) y menos días en los que se omitió la medicina (exp(β) = 0.65, z = − 2.92, p = 0.003). La violencia psicológica (exp(β) = 1.37, z = 1.97, p = 0.05) y las puntuaciones más altas de activos del hogar (exp(β) = 1.29, z = − 2.83, p = 0.05) se asociaron con una peor adherencia al TAR. A nivel individual, el sexo masculino (exp(β) = 1.37, z = 3.95, p < 0.001) y el reinicio del TAR (exp(β) = 1.35, z = 3.64, p < 0.001) se asociaron con una peor adherencia al TAR autodeclarada; niveles de educación más altos (exp(β) = 0.30 times, z = − 3.75, p < 0.001) y un mejor conocimiento sobre el VIH (exp(β) = 0.28, z = − 2.83, p = 0.005) se asociaron con menos días en los que se omitió la medicina. A nivel comunitario, el estigma comunitario se asoció con una peor autodelaración de adhesión del TAR (exp(β) = 1.24, z = 3.01, p = 0.003). Para mejorar la adherencia al TAR, se deben tener en cuenta los factores del hogar, así como los individuales y comunitarios, particularmente al abordar las disparidades de género, reducir el estigma, abordar la violencia y mejorar el apoyo del hogar.
What was known: steady-state lamivudine pharmacokinetics in persons living with HIV (PLHIV) and managed with peritoneal dialysis (PD). This study adds : HIV-1 shedding into CAPD effluents is not necessarily contributed by reduced lamivudine dosages pharmacokinetics. Potential impact: Renally adjusted lamivudine dosages are effective even in patients shedding HIV-1 into CAPD effluents. Background Renally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated. Methods This overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis. Results Twenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5–10.5) years and a CAPD duration of 13.3 (IQR,3.3–31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 66.7% (2/3) and 33.3% (1/3) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC_0-24 h, 651.3 ng/mL; 75 mg-AUC_0-24 h, 677.84 ng/mL; 300 mg-AUC_0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC_0-24 h, 384.91 ng/mL; 75 mg-AUC_0-24 h, 383.24 ng/mL; 300 mg-AUC_0-24 h, 2001.60 ng/mL) among the entire study population. The C_max (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and C_min (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels. Conclusions Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.
Neurocognitive impairment is a prevalent and important co-morbidity in virologically suppressed people living with HIV (PLWH), yet the underlying mechanisms remain elusive and treatments lacking. Here, we explored for the first time, use of participant-derived directly induced neurons (iNs) to model neuronal biology and injury in PLWH. iNs retain age-and disease-related features of the donors, providing unique opportunities to reveal novel aspects of neurological disorders. We obtained primary dermal fibroblasts from six virologically suppressed PLWH (range: 27 – 64 years, median: 53); 83% Male; 50% White) and seven matched people without HIV (PWOH) (range: 27 – 66, median: 55); 71% Male; 57% White). iNs were generated using transcription factors NGN2 and ASCL1, and validated by immunocytochemistry and single-cell-RNAseq. Transcriptomic analysis using bulk-RNAseq identified 29 significantly differentially expressed genes between iNs from PLWH and PWOH. Of these, 16 genes were downregulated and 13 upregulated in PLWH iNs. Protein-protein interaction network mapping indicates that iNs from PLWH exhibit differences in extracellular matrix organization and synaptic transmission. IFI27 was upregulated in iNs from PLWH, which complements independent post-mortem studies demonstrating elevated IFI27 expression in PLWH-derived brain tissue, indicating that iN generation reconstitutes this pathway. Finally, we observed that expression of the FOXL2NB-FOXL2-LINC01391 genome locus is reduced in iNs from PLWH and negatively correlates with neurocognitive impairment. Thus, we have identified an iN gene signature of HIV through direct reprogramming of skin fibroblasts into neurons revealing novel mechanisms of neurocognitive impairment in PLWH. ONE SENTENCE SUMMARY: Direct reprogramming of skin fibroblasts into neurons reveals unique gene signatures indicative of HIV infection in the context of viral suppression.
Background Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI. Methods A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI. Results From the main cohort of TB patients ( n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors ( p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection. Conclusion The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.
Vaccination can prevent influenza in solid organ transplant (SOT) recipients. Using a modified season‐specific approach over nine consecutive influenza seasons, we investigated influenza vaccination coverage and effectiveness in a population‐based nationwide cohort study that included all SOT recipients aged ≥18 years who were living in Denmark from December 1, 2007 to April 1, 2016. The primary outcome was the season‐specific risk of all‐cause pneumonia admission. Secondary outcomes were season‐specific influenza‐related admission, intensive care unit (ICU) admission, and all‐cause mortality. Crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. In total, 11 381 person‐years of follow‐up data were collected from 5745 SOT recipients, 48% of whom were vaccinated. Influenza vaccination was associated with a reduced risk of all‐cause pneumonia admission (aHR, 0.83; 95% CI, 0.69–0.99; p = .035) and all‐cause mortality (aHR, 0.60; 95% CI, 0.47–0.76; p = .001), but not influenza‐related admission (aHR, 0.75; 95% CI, 0.46–1.22; p = .24) or ICU admission (aHR, 0.84; 95% CI, 0.67–1.06; p = .14) during the same season. Despite these benefits, uptake of influenza vaccination among SOT recipients was low. Therefore, annual influenza vaccination needs to be prioritized.[Image: see text]
Purpose Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro . However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies. Methods We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens. Results At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro . The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro -effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections. Conclusion Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections. Graphical abstract
Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level were associated with lower infant morbidity and lower number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem, but not pneumonia. Background Risk factors of infant mortality in Africa and south Asian countries have been broadly discussed. However, infant morbidity is largely underestimated. We analyzed the data from a randomized vaccine trial in Bangladesh to identify and assess the effect of risk factors on infant morbidity. Methods Pregnant women were randomly assigned to receive either inactivated influenza vaccine or pneumococcal polysaccharide vaccine and the infants were randomly assigned to receive 7-valent pneumococcal conjugate vaccine or Hib conjugate vaccine at week 6, 10 and 14. The data were collected from August 2004 through December 2005. Each pair of infant and mother were followed for 24 weeks after birth with weekly visits. Generalized estimating equations (GEE) for repeated measurements and Poisson regression models were used to identify the risk factors and evaluate their effect on the longitudinal incidence and total number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem and pneumonia. Results A total of 340 pregnant women were randomized with mean age of 25 years. The baseline mother and infant characteristics were similar between two treatment groups. Exclusive breastfeeding and higher paternal education level were common factors associated with lower infant morbidity of RIF (adjusted OR = 0.40 and 0.94 with p < 0.01 and p = 0.02, respectively), diarrhea disease (adjusted OR = 0.39 and 0.95 with p < 0.01 and p = 0.04, respectively), and ear problem (adjusted OR = 0.20 and 0.76 with p < 0.01 and p < 0.01, respectively). Maternal influenza vaccine significantly reduced the incidence of RIF (adjusted OR = 0.54; p < 0.01) but not diarrhea disease or ear problem ( p > 0.05). Female infants had lower incidence of diarrhea disease (adjusted OR = 0.67; p = 0.01) and ear problem (adjusted OR = 0.12; p = 0.01). Conclusions Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level significantly reduced the infant morbidity within the 24 weeks after birth in Bangladesh.
Chronic kidney disease (CKD) is an irreversible change in kidney function and structure with a prevalence of about 9.1% worldwide. Toxins and heavy metal exposure, as well as hypertension and diabetes mellitus, are common causes of CKD. Despite extensive therapeutic options such as renal replacement therapy and renal transplants, most changes in kidney function remain irreversible, causing lifelong morbidity and affecting the quality of life of patients. Increased susceptibility to infections as well as serious complications from influenza, is a major cause of concern in nephrological care. Therefore, it is imperative to consider the protective role of influenza vaccination against seasonal influenza, which can worsen preexisting kidney dysfunction. This commentary explores a possible relationship between the influenza vaccine and patient outcomes in CKD in terms of complications, hospitalization, and possibly prognostic improvements in patient outcomes from CKD.
Background China has a high burden of influenza-associated illness among children. We aimed to evaluate the cost-effectiveness of introducing government-funded influenza vaccination to children in China (fully-funded policy) compared with the status quo (self-paid policy). Methods A decision tree model was developed to calculate the economic and health outcomes, from a societal perspective, using national- and provincial-level data. The incremental cost-effectiveness ratio (ICER) [incremental costs per quality-adjusted life year (QALY) gained] was used to compare the fully-funded policy with the self-paid policy under the willingness-to-pay threshold equivalent to national and provincial GDP per capita. Sensitivity analyses were performed and various scenarios were explored based on real-world conditions, including incorporating indirect effect into the analysis. Results Compared to the self-paid policy, implementation of a fully-funded policy could prevent 1,444,768 [95% uncertainty range (UR): 1,203,446–1,719,761] symptomatic cases, 92,110 (95% UR: 66,953–122,226) influenza-related hospitalizations, and 6494 (95% UR: 4590–8962) influenza-related death per season. The fully-funded policy was cost-effective nationally (7964 USD per QALY gained) and provincially for 13 of 31 provincial-level administrative divisions (PLADs). The probability of a funded vaccination policy being cost-effective was 56.5% nationally, and the probability in 9 of 31 PLADs was above 75%. The result was most sensitive to the symptomatic influenza rate among children under 5 years [ICER ranging from − 25,612 (cost-saving) to 14,532 USD per QALY gained]. The ICER of the fully-funded policy was substantially lower (becoming cost-saving) if the indirect effects of vaccination were considered. Conclusions Introducing a government-funded influenza policy for children is cost-effective in China nationally and in many PLADs. PLADs with high symptomatic influenza rate and influenza-associated mortality would benefit the most from a government-funded influenza vaccination program.
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.
[Image: see text] The vast majority of seasonal influenza vaccines administered each year are derived from virus propagated in eggs using technology that has changed little since the 1930s. The immunogenicity, durability, and breadth of response would likely benefit from a recombinant nanoparticle-based approach. Although the E2 protein nanoparticle (NP) platform has been previously shown to promote effective cell-mediated responses to peptide epitopes, it has not yet been reported to deliver whole protein antigens. In this study, we synthesized a novel maleimido tris-nitrilotriacetic acid (NTA) linker to couple protein hemagglutinin (HA) from H1N1 influenza virus to the E2 NP, and we evaluated the HA-specific antibody responses using protein microarrays. We found that recombinant H1 protein alone is immunogenic in mice but requires two boosts for IgG to be detected and is strongly IgG1 (Th2) polarized. When conjugated to E2 NPs, IgG2c is produced leading to a more balanced Th1/Th2 response. Inclusion of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) significantly enhances the immunogenicity of H1–E2 NPs while retaining the Th1/Th2 balance. Interestingly, broader homo- and heterosubtypic cross-reactivity is also observed for conjugated H1–E2 with MPLA, compared to unconjugated H1 with or without MPLA. These results highlight the potential of an NP-based delivery of HA for tuning the immunogenicity, breadth, and Th1/Th2 balance generated by recombinant HA-based vaccination. Furthermore, the modularity of this protein–protein conjugation strategy may have utility for future vaccine development against other human pathogens.
Background Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance. Methods Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries. Results France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data. Conclusions This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases.
BACKGROUND: Immunosuppressive therapy (IS) has altered the course of Inflammatory Bowel Disease (IBD). IBD patients are at considerable risk of developing vaccine-preventable illness and are even more susceptible when on treatment. Many of these patients fail to receive appropriate vaccinations for influenza, pneumonia, hepatitis B, Shingles and recently COVID. Our aim was to develop a quality improvement intervention to increase recommended vaccinations in IBD patients on IS. METHODS: A retrospective chart analysis was completed at the Memphis Veteran Affairs Gastroenterology Practice. 55 patients were found to be on immunosuppressive therapy with a biologic and/or immunomodulator. Once identified, these patient’s vaccination records were reviewed to see if they were up to date on recommended vaccinations for influenza, pneumonia, hepatitis B, COVID, and Shingles. Patients who were not up to date on their vaccinations were called by a provider (Resident, Fellow, or Nurse Practitioner), and were offered a nurse visit to be given the appropriate vaccinations. After a 6-month intervention period, the data on the 55 patients was recollected and analyzed. RESULTS: Of the patients analyzed, 63% (n=35) had Crohn’s disease and 37% (n=20) had Ulcerative Colitis. The most common biologic medication the patients were on was adalimumab (n=24), and the most common immunomodulator was azathioprine (n=17). Prior to the intervention, 22% had received the shingles vaccine, 20% had received the COVID-19 vaccine, 78% had received the hepatitis B vaccine, 69% had received the flu vaccine, 62% had received the pneumococcal 23 vaccine, and 72% had received the pneumococcal 13 vaccine. After the intervention, 65% had received the shingles vaccine, 65% had received the COVID-19 vaccine, 87% had received the hepatitis B vaccine, 85% had received the flu vaccine, 78% had received the pneumococcal 23 vaccine, and 84% had received the pneumococcal 13 vaccine. CONCLUSION: Patients on immunosuppressive therapy remain vulnerable to vaccine-preventable illnesses such as Shingles, Pneumococcal Pneumonia, Influenza, Hepatitis B, and COVID-19. Our quality improvement intervention increased overall vaccination adherence. This project was a proof of concept and in the future, we hope to integrate a warning system into our practice to alert providers when these patients are due for their appropriate vaccinations. It is also a practice that can be adopted by other healthcare providers who treat patients with IS and biologics to improve vaccination uptake. [Image: see text] [Image: see text]
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Influenza A, and Influenza B viruses is essential for rapid differential diagnosis in patients with similar symptoms, especially during “flu season” in the post-pandemic era. So far, several multiplex methods have been approved for the simultaneous detection of SARS-CoV-2, Influenza A, and Influenza B. However, due to the rapid mutation rate of the SARS-CoV-2 genome and the emergence of new variants, existing methods must be improved and updated. METHODS: To identify a highly conserved region in the SARS-CoV-2 N-gene, a genomic survey was performed to increase the sensitivity and specificity of primer and probe sets targeting the SARS-CoV-2 genome. The 95% LLOD (95% lower limits of detection) were calculated by probit analysis. A total of 70 predetermined clinical samples using singleplex RT-qPCR assays, were included. The clinical performance of the multiplex RT-qPCR assay was determined and compared with a commercial multiplex kit. The Cohen’s kappa coefficient, P-value (McNemar’s test), Passing-Bablok regression, and Bland Altman agreement analysis were determined to monitor the agreement of the assays. RESULTS: The novel SARS-CoV-2 primer and probe set designed in this assay was able to detect all variants of concern (VOCs) and variants of interest (VOIs) with high analytical and clinical performance. The 95% LLOD for the multiplex RT-qPCR was 20 copies per reaction for the N gene of SARS-CoV-2, 2 copies per reaction for M1 gene of Influenza A and NS1 gene of Influenza B. The diagnostic sensitivity of the multiplex RT-qPCR was 94.4%, 93.7%, and 100% for the detection of SARS-CoV-2, Influenza A, and Influenza B genomes, respectively. Moreover, the specificity was identical (100%) in both assays. According to the agreement analysis results, there was no statistical difference between our multiplex assay and the commercial kit. CONCLUSIONS: In this study, we developed a novel in-house made multiplex RT-qPCR assay, with high sensitivity, specificity, and reliability for the diagnosis of SARS-CoV-2 infection in clinical samples. This is valuable during Influenza seasons when influenza co-circulates with SARS-CoV-2, as it saves costs, time, and thus specific and timely treatment of patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-023-03048-9.
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 Influenza represents a serious public health threat, especially for the management of severe cases and complications of the disease, requiring the implementation of control measures. We aimed to assess the acceptance and impact of qLAIV vaccination among a representative sample of family paediatricians (FPs) operating in Palermo Local Health Authority (LHA). To this end we evaluated vaccination coverage rates, comparing it with that observed in Sicilian context, while actively monitoring possible adverse reactions and their severity. Methods An observational descriptive non-controlled study was conducted in two phases, from September 2022 to June 2023. The first phase involved a formative and educational intervention with a pre-intervention questionnaire to assess the knowledge and attitudes of FPs on paediatric influenza vaccination. The second phase consisted of an active surveillance on qLAIV safety and acceptance among the paediatric population assisted by the participating FPs, from October 2022 to April 2023. Frequencies, chi-squared tests, and comparisons statistics were performed using Stata/MP 14.1. Results The overall coverage rate among the paediatric population involved in the intervention was 13.2%, with an I.M./qLAIV ratio of vaccine administered of 1/4.25. This coverage rate was significantly higher ( p -value <0.001) when compared to the average values reported in the population under the Palermo Local Health Authority (LHA) (6.7%) and in the entire Sicily (5.9%). Adverse events in the qLAIV group were mild, with only 3.3% experiencing them, primarily presenting as a feverish rise (3.2%). No severe adverse reaction was reported. Conclusions The educational intervention significantly raised paediatric influenza vaccination rates among the participating FPs, and in general improved influenza vaccination coverage rates in the Palermo’s LHU. Minimal, non-serious adverse events underscored the vaccine’s safety. Training sessions ensured paediatricians stayed informed, enabling them to provide comprehensive information to parents for secure and informed vaccination decisions in their practices.
Influenza virus is a persistent threat to human health; indeed, the deadliest modern pandemic was in 1918 when an H1N1 virus killed an estimated 50 million people globally. The intent of this work is to better understand influenza from an RNA-centric perspective to provide local, structural motifs with likely significance to the influenza infectious cycle for therapeutic targeting. To accomplish this, we analyzed over four hundred thousand RNA sequences spanning three major clades: influenza A, B and C. We scanned influenza segments for local secondary structure, identified/modeled motifs of likely functionality, and coupled the results to an analysis of evolutionary conservation. We discovered 185 significant regions of predicted ordered stability, yet evidence of sequence covariation was limited to 7 motifs, where 3—found in influenza C—had higher than expected amounts of sequence covariation.
Summary In this retrospective cohort study of 6604 adults, 65 years or older, admitted with seasonal influenza at Swedish hospitals, and 330,200 age- and sex-matched controls from the general population admitted for other reasons, were included. Patients with influenza had increased risk of fall injuries and fractures compared to controls. Introduction Fractures and fall injuries often lead to disability, increased morbidity, and mortality. Older adults are at higher risk of influenza-related complications such as pneumonia, cardiovascular events, and deaths, but the risk of fractures and fall injuries is unclear. The primary objective of this study was to investigate the risk of fractures and fall injuries in older patients after admission with seasonal influenza. Methods In this retrospective cohort study of 6604 adults, 65 years or older, admitted with seasonal influenza at Swedish hospitals (from December 1, 2015, to December 31, 2017) and 330,200 age- and sex-matched controls from the general population and admitted for other reasons, the risk of fracture or fall injury was investigated. Results The mean (SD) age of the 6604 influenza patients was 80.9 (8.1) years and 50.1% were women. During the first year after hospital discharge, there were 680 (10.3%) patients suffering from a fracture or fall injury among the patients with influenza, and 25,807 (7.8%) among the controls, corresponding to incident rates of 141 (95% CI, 131–152) and 111 (95% CI, 110–112) fractures or fall injuries per 1000 person-years respectively, translating to a significantly increased risk of fracture or fall injury in a Cox regression model (hazard ratio (HR) 1.28 (95% CI, 1.19–1.38)), a risk that was maintained after multivariable adjustment (HR 1.22 (95% CI 1.13–1.31)). Conclusions Older adults admitted with influenza diagnosis have an increased risk of fracture or fall injury during the first year after discharge.
Background Influenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza’s burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. Objective: The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza’s inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population. Methods We searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments. Findings We included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population. Conclusion Our findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.
As COVID-19 pandemic progresses, severe flu seasons may happen alongside an
increase in cases in cases and death of COVID-19, causing severe burdens on
health care resources and public safety. A consequence of a twindemic may be a
mixture of two different infections in the same person at the same time,
"flurona". Admist the raising trend of "flurona", forecasting both influenza
outbreaks and COVID-19 waves in a timely manner is more urgent than ever, as
accurate joint real-time tracking of the twindemic aids health organizations
and policymakers in adequate preparation and decision making. Under the current
pandemic, state-of-art influenza and COVID-19 forecasting models carry valuable
domain information but face shortcomings under current complex disease
dynamics, such as similarities in symptoms and public healthcare seeking
patterns of the two diseases. Inspired by the inner-connection between
influenza and COVID-19 activities, we propose ARGOX-Joint-Ensemble which allows
us to combine historical influenza and COVID-19 disease forecasting models to a
new ensemble framework that handles scenarios where flu and COVID co-exist. Our
framework is able to emphasize learning from COVID-related or influenza
signals, through a winner-takes-all ensemble fashion. Moreover, our experiments
demonstrate that our approach is successful in adapting past influenza
forecasting models to the current pandemic, while improving upon previous
COVID-19 forecasting models, by steadily outperforming alternative benchmark
methods, and remaining competitive with publicly available models.
;Comment: arXiv admin note: text overlap with arXiv:2106.12160
International audience;
Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p = 0.013), but not in influenza (1.74 (0.99–3.06), p = 0.052), or no viral infection groups (1.13 (0.68–1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.
Background Currently, the influenza epidemic in China is at a high level and mixed with other respiratory diseases. Current studies focus on regional influenza and the impact of environmental pollutants on time series, and lack of overall studies on the national influenza epidemic and the nonlinear correlation between environmental pollutants and influenza. The unclear spatial and temporal evolution patterns of influenza as well as the unclear correlation effect between environmental pollutants and influenza epidemic have greatly hindered the prevention and treatment of influenza epidemic by relevant departments, resulting in unnecessary economic and human losses. Method This study used Chinese influenza incidence data for 2007–2017 released by the China CDC and air pollutant site monitoring data. Seasonal as well as inter monthly differences in influenza incidence across 31 provinces of China have been clarified through time series. Space-Time Cube model (STC) was used to investigate the spatio-temporal evolution of influenza incidence in 315 Chinese cities during 2007–2017. Then, based on the spatial heterogeneity of influenza incidence in China, Generalized additive model (GAM) was used to identify the correlation effect of environmental pollutants (PM_2.5, PM_10, CO, SO_2, NO_2, O_3) and influenza incidence. Result The influenza incidence in China had obvious seasonal changes, with frequent outbreaks in winter and spring. The influenza incidence decreased significantly after March, with only sporadic outbreaks occurring in some areas. In the past 11 years, the influenza epidemic had gradually worsened, and the clustering of influenza had gradually expanded, which had become a serious public health problem. The correlation between environmental pollutants and influenza incidence was nonlinear. Generally, PM_2.5, CO and NO_2 were positively correlated at high concentrations, while PM_10 and SO_2 were negatively correlated. O_3 was not strongly correlated with the influenza incidence. Conclusion The study found that the influenza epidemic in China was in a rapidly rising stage, and several regions had a multi-year outbreak trend and the hot spots continue to expand outward. The association between environmental pollutants and influenza incidence was nonlinear and spatially heterogeneous. Relevant departments should improve the monitoring of influenza epidemic, optimize the allocation of resources, reduce environmental pollution, and strengthen vaccination to effectively prevent the aggravation and spread of influenza epidemic in the high incidence season and areas.
International audience;
Background:Influenza-like illness (ILI) incidence estimates in individuals treated withimmunosuppressants and/or biologics and/or corticosteroid for an autoimmune orchronic inflammatory disease are scarce. We compared the ILI incidence amongimmunocompromised population and the general population.Method:We conducted a prospective cohort study during the 2017–2018 seasonalinfluenza epidemic, on theGrippeNet.frelectronic platform, which allows the collec-tion of epidemiological crowdsourced data on ILI, directly from the French generalpopulation. The immunocompromised population were adults treated with systemiccorticosteroids, immunosuppressants, and/or biologics for an autoimmune or chronicinflammatory disease, recruited directly onGrippeNet.frand also among patients ofthe departments of a single university hospital that were asked to incorporateGrippeNet.fr. The general population consisted of adults reporting none of the abovetreatments or diseases participating inGrippeNet.fr. The incidence of ILI was esti-mated on a weekly basis and compared between the immunocompromised popula-tion and the general population, during the seasonal influenza epidemic. Results:Among the 318 immunocompromised patients assessed for eligibility,177 were included. During the 2017–2018 seasonal influenza epidemic period,immunocompromised population had 1.59 (95% CI: 1.13–2.20) higher odds to expe-rience an ILI episode, compared to the general population (N=5358). An influenzavaccination was reported by 58% of the immunocompromised population, comparedto 41% of the general population (p< 0.001).Conclusion:During a seasonal influenza epidemic period, the incidence of influenza-like illness was higher in patients treated with immunosuppressants, biologics, and/orcorticosteroids for an autoimmune or chronic inflammatory disease, compared to the general population.
Objective To analyze the etiology and epidemiological characteristics of respiratory infections during the winter season in the Tengzhou region and provide localized data to support public health measures. Methods A retrospective study was conducted on patients diagnosed with acute upper respiratory tract infections (ARTIs) between November 2023 and January 2024 at Tengzhou Central People's Hospital and Tengzhou Maternal and Child Health Hospital. Pathogens analyzed included influenza A (Flu A), influenza B (Flu B), respiratory syncytial virus (RSV), adenovirus (ADV), Mycoplasma pneumoniae (MP), and human rhinovirus (HRV). Statistical analyses were performed to evaluate infection patterns and their associations with age and other variables. Results A total of 4,869 specimens were collected, with 2,307 cases (47.4%) identified as single- pathogen infections, 272 cases (10.9%) as dual-pathogen infections, and 37 cases (1.5%) as infections with three or more pathogens. The detection rates differed significantly between the < 14-year-old and ≥ 14-year-old groups (χ^2 = 13.87, P < 0.05). Flu A was the most frequently detected pathogen (1,340 cases, 27.5%), followed by RSV (251 cases, 10.1%), ADV (241 cases, 9.7%), MP (223 cases, 4.6%), HRV (113 cases, 4.5%), and Flu B (139 cases, 2.9%). Detection rates for these six pathogens varied significantly between the < 14-year-old and ≥ 14-year-old groups ( P < 0.05). Among the 1,340 Flu A-positive cases, 543 (40.5%) were H3N2-positive, accounting for 11.2% of all specimens. One H1N1 case was detected, co-infected with H3N2, and no H7N9 cases were found. Conclusions This regional surveillance study highlights age-related differences in respiratory pathogen circulation in Tengzhou during the winter season. The findings support the need for continued seasonal monitoring and targeted prevention efforts.
Influenza is a severe infectious disease that leads to significant morbidity and mortality worldwide every year. Cardiovascular events, especially within the first 2 weeks after influenza infection, are the main cause of death. Due to immunosenescence, multimorbidity and frailty, older individuals are particularly at risk for severe disease progression. Influenza vaccination is an effective strategy for reducing influenza infections and associated cardiovascular complications. The Standing Committee on Vaccination (STIKO) therefore recommends annual influenza vaccination for individuals aged 60 years and older as well as for certain high-risk groups regardless of age. Standard vaccines are often less effective in older individuals due to declining immune responses. Therefore, various optimization approaches, such as the use of a high-dose influenza vaccine, are being explored to enhance immune response and vaccine efficacy. Due to the high-quality data available for the high-dose vaccine, the STIKO recommends its use from the age of 60 years onwards. Randomized controlled trials and meta-analyses show that the high-dose vaccine improves the efficacy and effectiveness in terms of influenza infections and cardiopulmonary events compared to standard dose influenza vaccines. Individuals with pre-existing heart conditions also benefit from influenza vaccination. Patients should be informed by their treating physicians about the cardiovascular benefits of influenza vaccination. Die Influenza ist eine schwere Infektionskrankheit, die jedes Jahr weltweit zu erheblicher Morbidität und Mortalität führt. Kardiovaskuläre Ereignisse, insbesondere in den ersten 2 Wochen nach einer Influenzainfektion, sind die Haupttodesursache. Dabei haben insbesondere ältere Menschen aufgrund von Immunseneszenz, Multimorbidität und Gebrechlichkeit ein erhöhtes Risiko für schwere Krankheitsverläufe. Die Influenzaimpfung ist eine wirksame Strategie zur Verringerung von Influenzainfektionen und dadurch bedingten kardiovaskulären Komplikationen. Die Ständige Impfkommission (STIKO) empfiehlt daher die jährliche Influenzaimpfung für Personen ab 60 Jahren und für bestimmte Risikogruppen unabhängig vom Alter. Aufgrund der nachlassenden Abwehrleistung des Immunsystems sind Standardimpfstoffe bei älteren Personen häufig nicht so effektiv. Über verschiedene Optimierungsansätze, wie z. B. die Verwendung eines hochdosierten Influenzaimpfstoffs, wird daher versucht, die Immunantwort auf eine Influenzaimpfung zu erhöhen und die Effektivität zu verbessern. Aufgrund der guten Datenqualität für den Hochdosisimpfstoff wird dessen Einsatz von der STIKO ab einem Alter von 60 Jahren empfohlen. Randomisierte kontrollierte Studien wie auch Metaanalysen zeigen, dass der Hochdosisimpfstoff im Vergleich zum standarddosierten Influenzaimpfstoff die Wirksamkeit bezüglich Influenzainfektionen und kardiorespiratorischen Ereignissen verbessert. Auch bereits herzkranke Personen profitieren von der Influenzaimpfung. Patient*innen sollten daher von ihren behandelnden Ärzt*innen über die kardiovaskulären Vorteile der Influenzaimpfung informiert werden.
BACKGROUND: Severe influenza is a serious global health issue that leads to prolonged hospitalization and mortality on a significant scale. The pathogenesis of this infectious disease is poorly understood. Therefore, this study aimed to identify the key genes associated with severe influenza patients necessitating invasive mechanical ventilation. METHODS: The current study utilized two publicly accessible gene expression profiles (GSE111368 and GSE21802) from the Gene Expression Omnibus database. The research focused on identifying the genes exhibiting differential expression between severe and non-severe influenza patients. We employed three machine learning algorithms, namely the Least Absolute Shrinkage and Selection Operator regression model, Random Forest, and Support Vector Machine-Recursive Feature Elimination, to detect potential key genes. The key gene was further selected based on the diagnostic performance of the target genes substantiated in the dataset GSE101702. A single-sample gene set enrichment analysis algorithm was applied to evaluate the participation of immune cell infiltration and their associations with key genes. RESULTS: A total of 44 differentially expressed genes were recognized; among them, we focused on 10 common genes, namely PCOLCE2, HLA_DPA1, LOC653061, TDRD9, MPO, HLA_DQA1, MAOA, S100P, RAP1GAP, and CA1. To ensure the robustness of our findings, we employed overlapping LASSO regression, Random Forest, and SVM-RFE algorithms. By utilizing these algorithms, we were able to pinpoint the aforementioned 10 genes as potential biomarkers for distinguishing between both cases of influenza (severe and non-severe). However, the gene HLA_DPA1 has been recognized as a crucial factor in the pathological condition of severe influenza. Notably, the validation dataset revealed that this gene exhibited the highest area under the receiver operating characteristic curve, with a value of 0.891. The use of single-sample gene set enrichment analysis has provided valuable insights into the immune responses of patients afflicted with severe influenza that have further revealed a categorical correlation between the expression of HLA_DPA1 and lymphocytes. CONCLUSION: The findings indicated that the HLA_DPA1 gene may play a crucial role in the immune-pathological condition of severe influenza and could serve as a promising therapeutic target for patients infected with severe influenza. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-024-10184-7.
Inhalation of airborne conidia of the ubiquitous fungus Aspergillus fumigatus commonly occurs but invasive aspergillosis is rare except in profoundly immunocompromised persons. Severe influenza predisposes patients to invasive pulmonary aspergillosis by mechanisms that are poorly defined. Using a post-influenza aspergillosis model, we found that superinfected mice had 100% mortality when challenged with A. fumigatus conidia on days 2 and 5 (early stages) of influenza A virus infection but 100% survival when challenged on days 8 and 14 (late stages). Influenza-infected mice superinfected with A. fumigatus had increased levels of the pro-inflammatory cytokines and chemokines IL-6, TNFα, IFNβ, IL-12p70, IL-1α, IL-1β, CXCL1, G-CSF, MIP-1α, MIP-1β, RANTES and MCP-1. Surprisingly, on histopathological analysis, superinfected mice did not have greater lung inflammation compared with mice infected with influenza alone. Mice infected with influenza had dampened neutrophil recruitment to the lungs following subsequent challenge with A. fumigatus , but only if the fungal challenge was executed during the early stages of influenza infection. However, influenza infection did not have a major effect on neutrophil phagocytosis and killing of A. fumigatus conidia. Moreover, minimal germination of conidia was seen on histopathology even in the superinfected mice. Taken together, our data suggest that the high mortality rate seen in mice during the early stages of influenza-associated pulmonary aspergillosis is multifactorial, with a greater contribution from dysregulated inflammation than microbial growth. IMPORTANCE: Severe influenza is a risk factor for fatal invasive pulmonary aspergillosis; however, the mechanistic basis for the lethality is unclear. Utilizing an influenza-associated pulmonary aspergillosis (IAPA) model, we found that mice infected with influenza A virus followed by A. fumigatus had 100% mortality when superinfected during the early stages of influenza but survived at later stages. While superinfected mice had dysregulated pulmonary inflammatory responses compared to controls, they had neither increased inflammation nor extensive fungal growth. Although influenza-infected mice had dampened neutrophil recruitment to the lungs following subsequent challenge with A. fumigatus , influenza did not affect the ability of neutrophils to clear the fungi. Our data suggest that the lethality seen in our model IAPA is multifactorial with dysregulated inflammation being a greater contributor than uncontrollable microbial growth. If confirmed in humans, our findings provide a rationale for clinical studies of adjuvant anti-inflammatory agents in the treatment of IAPA.
Introduction Annual influenza vaccinations are recommended for adolescents and adults with moderate to severe asthma. This study investigated the effect of tezepelumab, a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, on the humoral immune response to the quadrivalent seasonal influenza vaccine in patients with moderate to severe asthma. Methods VECTOR was a phase 3b, randomized, multicenter, double-blind, parallel-group, placebo-controlled study. Adolescents (aged 12–17 years) and young adults (aged 18–21 years) with moderate to severe asthma were enrolled across 15 centers in the USA. Patients received tezepelumab 210 mg or placebo subcutaneously at weeks 0, 4, 8, and 12, and a single dose of inactivated quadrivalent seasonal influenza vaccine at week 12 before receiving study treatment. Immediately before vaccination and at 4 weeks postvaccination (week 16), strain-specific antibody responses were assessed for four influenza antigens by hemagglutination inhibition (HAI) and microneutralization (MN) assays. Safety was assessed. Results Seventy patients were randomized to tezepelumab ( n = 35) or placebo ( n = 35). There were no meaningful differences in HAI or MN antibody responses between treatment groups at week 16. HAI assay geometric mean fold rises (GMFRs) for influenza strains were 1.76–7.34 for tezepelumab and 1.46–4.75 for placebo. MN assay GMFRs were 4.00–14.56 for tezepelumab and 3.56–10.62 for placebo. In the HAI assay, a fourfold or larger rise in antibody titer from weeks 12 to 16 occurred in 15.2–78.8% and 15.2–51.5% of tezepelumab and placebo recipients, respectively, and 97.0–100% of patients in both treatment groups achieved an antibody titer of at least 40 at week 16. No unexpected safety findings occurred. Conclusion There was no observed suppression of the humoral immune response after influenza vaccination in adolescents and young adults with moderate to severe asthma treated with tezepelumab. Therefore, the influenza vaccine can be administered to this patient population during tezepelumab treatment. ClinicalTrials.gov identifier NCT05062759
Background Gut microbes play an important role in the growth and health of neonatal piglets. Probiotics can promote the healthy growth of neonatal piglets by regulating their gut microbes. The study investigated the effects of spraying Lactiplantibacillus plantarum P-8 ( L. plantarum P-8) fermentation broth on the growth performance and gut microbes of neonatal piglets. Results The animals were randomly divided into probiotics groups (109 neonatal piglets) and control groups (113 neonatal piglets). The probiotics group was sprayed with L. plantarum P-8 fermented liquid from 3 day before the expected date of the sow to the 7-day-old of piglets, while the control group was sprayed with equal dose of PBS. Average daily gain (ADG), immune and antioxidant status and metagenome sequencing were used to assess the changes in growth performance and gut microbiota of neonatal piglets. The results showed that L. plantarum P-8 treatment significantly improved the average daily gain ( P < 0.05) of neonatal piglets. L. plantarum P-8 increased the activities of CAT and SOD but reduced the levels of IL-2 and IL-6, effectively regulating the antioxidant capacity and immunity in neonatal piglets. L. plantarum P-8 adjusted the overall structure of gut microflora improving gut homeostasis to a certain extent, and significantly increased the relative abundance of gut beneficial bacteria such as L. mucosae and L. plantarum . Conclusion Spraying L. plantarum P-8 can be a feasible and effective probiotic intervention not only improving the growth of neonatal piglets, regulating the antioxidant capacity and immunity of neonatal piglets, but also improving the gut homeostasis to a certain extent.
Background The emergence of multi-drug-resistant Klebsiella pneumoniae (MDR-KP) represents a serious clinical health concern. Antibiotic resistance and virulence interactions play a significant role in the pathogenesis of K. pneumoniae infections. Therefore, tracking the clinical resistome and virulome through monitoring antibiotic resistance genes (ARG) and virulence factors in the bacterial genome using computational analysis tools is critical for predicting the next epidemic. Methods In the current study, one hundred extended spectrum β-lactamase (ESBL)-producing clinical isolates were collected from Mansoura University Hospital, Egypt, in a six-month period from January to June 2022. One isolate was selected due to the high resistance phenotype, and the genetic features of MDR-KP recovered from hospitalized patient were investigated. Otherwise, the susceptibility to 25 antimicrobials was determined using the DL Antimicrobial Susceptibility Testing (AST) system. Whole genome sequencing (WGS) using Illumina NovaSeq 6000 was employed to provide genomic insights into K. pneumoniae WSF99 clinical isolate. Results The isolate K. pneumoniae WSF99 was phenotypically resistant to the antibiotics under investigation via antibiotic susceptibility testing. WGS analysis revealed that WSF99 total genome length was 5.7 Mb with an estimated 5,718 protein-coding genes and a G + C content of 56.98 mol%. Additionally, the allelic profile of the WSF99 isolate was allocated to the high-risk clone ST147. Furthermore, diverse antibiotic resistance genes were determined in the genome that explain the high-level resistance phenotypes. Several β-lactamase genes, including bla _CTX−M−15, bla _TEM−1, bla _TEM−12, bla _SHV−11, bla _SHV−67, and bla _OXA−9, were detected in the WSF99 isolate. Moreover, a single carbapenemase gene, bla _NDM−5, was predicted in the genome, positioned within a mobile cassette. In addition, other resistance genes were predicted in the genome including, aac (6’)-Ib, aph (3’)-VI, sul1 , sul2 , fosA , aadA , arr-2 , qnrS1 , tetA and tetC . Four plasmid replicons CoIRNAI, IncFIB(K), IncFIB(pQil), and IncR were predicted in the genome. The draft genome analysis revealed the occurrence of genetic mobile elements positioned around the ARGs, suggesting the ease of dissemination via horizontal gene transfer. Conclusions This study reports a comprehensive pathogenomic analysis of MDR-KP isolated from a hospitalized patient. These findings could be relevant for future studies investigating the diversity of antimicrobial resistance and virulence in Egypt.
Various eco-friendly techniques are being researched for synthesizing ZnO-NPs, known for their bioactivity. This study aimed at biosynthesizing ZnO-NPs using Streptomyces baarnensis MH-133, characterizing their physicochemical properties, investigating antibacterial activity, and enhancement of their efficacy by combining them with a water-insoluble active compound (Ka) in a nanoemulsion form. Ka is a pure compound of 9-Ethyl-1,4,6,9,10-pentahydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione obtained previously from our strain of Streptomyces baarnensis MH-133. Biosynthesized ZnO-NPs employing Streptomyces baarnensis MH-133 filtrate and zinc sulfate (ZnSO_4.7H_2O) as a precursor were purified and characterized by physicochemical investigation. High-resolution-transmission electron microscopy (HR-TEM) verified the effective biosynthesis of ZnO-NPs (size < 12 nm), whereas dynamic light scattering (DLS) analysis showed an average size of 17.5 nm. X-ray diffraction (XRD) exhibited characteristic diffraction patterns that confirmed crystalline structure. ZnO-NPs efficiently inhibited both Gram-positive and Gram-negative bacteria (MICs: 31.25–125 µg/ml). The pure compound (Ka) was combined with ZnO-NPs to improve effectiveness and reduce dose using checkerboard microdilution. Niteen treatments of Ka and ZnO-NPs combinations obtained by checkerboard matrix inhibited Klebsiella pneumonia . Eleven combinations had fractional inhibitory concentration index (FICi) between 1.03 and 2, meaning indifferent, another five combinations resulted from additive FICi (0.625–1) and only one combination with FICi of 0.5, indicating synergy. In the case of methicillin-resistant S. aureus (MRSA), Ka-ZnO-NPs combinations yielded 23 treatments with varying degrees of interaction. The results showed eleven treatments with indifferent interaction, eight additive interactions, and two synergies with FICi of 0.5 and 0.375. The combinations that exhibited synergy action were transformed into a nanoemulsion form to improve their solubility and bioavailability. The HR-TEM analysis of the nanoemulsion revealed spherical oil particles with a granulated core smaller than 200 nm and no signs of aggregation. Effective dispersion was confirmed by DLS analysis which indicated that Ka-ZnO-NPs nanoemulsion droplets have an average size of 53.1 nm and a polydispersity index (PI) of 0.523. The killing kinetic assay assessed the viability of methicillin-resistant Staphylococcus aureus ( MRSA) and K. pneumonia post-treatment with Ka-ZnO-NPs combinations either in non-formulated or nanoemulsion form. Results showed Ka-ZnO-NPs combinations show concentration and time-dependent manner, with higher efficacy in nanoemulsion form. The findings indicated that Ka-ZnO-NPs without formulation at MIC values killed K. pneumonia after 24 h but not MRSA. Our nanoemulsion loaded with the previously mentioned combinations at MIC value showed bactericidal effect at MIC concentration of Ka-ZnO-NPs combination after 12 and 18 h of incubation against MRSA and K. pneumonia , respectively, compared to free combinations. At half MIC value, nanoemulsion increased the activity of the combinations to cause a bacteriostatic effect on MRSA and K. pneumonia after 24 h of incubation. The free combination showed a bacteriostatic impact for 6 h before the bacteria regrew to increase log_10 colony forming unit (CFU)/ml over the initial level. Similarly, the cytotoxicity study revealed that the combination in nanoemulsion form decreased the cytotoxicity against kidney epithelial cells of the African green monkey (VERO) cell line. The IC_50 for Ka-ZnO-NPs non-formulated treatment was 8.17/1.69 (µg/µg)/ml, but in nano-emulsion, it was 22.94 + 4.77 (µg/µg)/mL. In conclusion, efficient Ka-ZnO-NPs nanoemulsion may be a promising solution for the fighting of ESKAPE pathogenic bacteria according to antibacterial activity and low toxicity.
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.
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 Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible ( bai ) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). Results Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro . However, E. muris was found to 7-dehydroxylate in vivo . Conclusions The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.
Background Recently, there has been an increase in the number of studies focusing on the association between the gut microbiome and obesity or inflammatory diseases, especially in adults. However, there is a lack of studies investigating the association between gut microbiome and gastrointestinal (GI) diseases in adolescents. Method We obtained 16S rRNA-seq datasets for gut microbiome analysis from 202 adolescents, comprising ulcerative colitis (UC), Crohn’s disease (CD), obesity (Ob), and healthy controls (HC). We utilized Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to acquire Operational Taxonomic Units (OTUs). Subsequently, we analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) terms and pathway enrichment for the identified OTUs. Results In this study, we investigated the difference between the gut microbiomes in adolescents with GI diseases and those in healthy adolescents using 202 samples of 16S rRNA sequencing data. The distribution of the six main gut microbiota (i.e., unclassified Dorea , unclassified Lachnospiraceae , unclassified Ruminococcus , Faecalibacterium prausnitzii , Prevotella copri , unclassified Sutterella ) was different based on the status of obesity and inflammatory diseases. Dysbiosis was observed within Lachnospiraceae in adolescents with inflammatory diseases (i.e., UC and CD), and in adolescents with obesity within Prevotella and Sutterella . More specifically, our results showed that the relative abundance of Faecalibacterium prausnitzii and unclassified Lachnospiraceae was more than 10% and 8% higher, respectively, in the UC group compared to the CD, Ob, and HC groups. Additionally, the Ob group had over 20% and over 3% higher levels of Prevotella copri and unclassified Sutterella , respectively, compared to the UC, CD, and HC groups. Also, inspecting associations between the six specific microbiota and KO terms, we found that the six microbiota -relating KO terms were associated with NOD-like receptor signaling. These six taxa differences may affect the immune system and inflammatory response by affecting NOD-like receptor signaling in the host during critical adolescence. Conclusion In this study, we discovered that dysbiosis of the microbial community had varying degrees of influence on the inflammatory and immune response pathways in adolescents with inflammatory diseases and obesity.
Background The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. Methods In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. Results We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. Conclusion Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.
Background Resistance to antifungal medications poses a significant obstacle in combating fungal infections. The development of novel therapeutics for Candida albicans is necessary due to the increasing resistance of candidiasis to the existing medications. The utilization of biological control is seen as a more advantageous and less hazardous strategy therefore the objective of this study is to identify the antifungal properties of Bacillus subtilis against pathogenic C. albicans. Results We conducted a study to evaluate the antifungal properties of three bacterial isolates against the human pathogen Candida albicans . One of the bacterial isolates exhibited a potent antifungal activity against this fungal pathogen. This bacterium was identified as Bacillus subtilis based on the 16Sr RNA gene sequence. It exhibited inhibitory efficacy ranging from 33.5 to 44.4% against 15 Candida isolates. The optimal incubation duration for achieving the maximum antifungal activity was determined to be 48 h, resulting in a mean inhibition zone diameter of 29 ± 0.39 mm. The Potato Dextrose agar (PDA) medium was the best medium for the most effective antifungal activity. Incubation temperature of 25^oC and medium pH value of 8.0 were the most favorable conditions for maximum antagonistic activity that resulted fungal growth inhibition of 40 ± 0.16 and 36 ± 0.94 mm respectively. Furthermore, the addition of 10.5 mg/ml of bacterial filtrate to C. albicans colonies resulted in 86.51%. decrease in the number of germinated cells. The fungal cell ultrastructural responses due to exposure to B. subtilis filtrate after 48 h were investigated using transmission electron microscopy (TEM). It revealed primary a drastic abnormality that lead to cellular disintegration including folding and lysis of the cell wall, total collapse of the yeast cells, and malformed germ tube following the exposure to the filtrate. However, the control culture treatment had a characteristic morphology of the normal fungal cells featuring a consistently dense central region, a well-organized nucleus, and a cytoplasm containing several components of the endomembrane system. The cells were surrounded by a uniform and intact cell wall. Conclusion The current study demonstrates a notable antifungal properties of B. subtilis against C. albicans as a result of production of bioactive components of the bacterial exudate. This finding could be a promising natural antifungal agent that could be utilized to combat C. albicans .
Background Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. Results Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups ( p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase ( p = 0.0146 ). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. Conclusions The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.
Interspecies pathways in the gut microbiome have been shown to metabolize levodopa, the primary treatment for Parkinson’s disease, and reduce its bioavailability. While the enzymatic reactions have been identified, the ability to establish the resulting macromolecules as biomarkers of microbial metabolism remains technically challenging. In this study, we leveraged an untargeted mass spectrometry-based approach to investigate volatile organic compounds (VOCs) produced during levodopa metabolism by Enterococcus faecalis , Clostridium sporogenes , and Eggerthella lenta . We cultured these organisms with and without their respective bioactive metabolites and detected levodopa-induced shifts in VOC profiles. We then utilized bioinformatics to identify significant differences in 2,6-dimethylpyrazine, 4,6-dimethylpyrimidine, and 4,5-dimethylpyrimidine associated with its biotransformation. Supplementing cultures with inhibitors of levodopa-metabolizing enzymes revealed specific modulation of levodopa-associated diazines, verifying their relationship to its metabolism. Furthermore, functional group analysis depicts strain-specific VOC profiles that reflect interspecies differences in metabolic activity that can be leveraged to assess microbiome functionality in individual patients. Collectively, this work identifies previously uncharacterized metabolites of microbe-mediated levodopa metabolism to determine potential indicators of this activity and further elucidate the metabolic capabilities of different gut bacteria.
Background Group B Streptococcus (GBS) is a commensal of healthy adults and an important pathogen in newborns, the elderly and immunocompromised individuals. GBS displays several virulence factors that promote colonisation and host infection, including the ST-17 strain-specific adhesin Srr2, previously characterised for its binding to fibrinogen. Another common target for bacterial adhesins and for host colonization is fibronectin, a multi-domain glycoprotein found ubiquitously in body fluids, in the extracellular matrix and on the surface of cells. Results In this study, fibronectin was identified as a novel ligand for the Srr2 adhesin of GBS. A derivative of the ST-17 strain BM110 overexpressing the srr2 gene showed an increased ability to bind fibrinogen and fibronectin, compared to the isogenic wild-type strain. Conversely, the deletion of srr2 impaired bacterial adhesion to both ligands. ELISA assays and surface plasmon resonance studies using the recombinant binding region (BR) form of Srr2 confirmed a direct interaction with fibronectin with an estimated Kd of 92 nM. Srr2-BR variants defective in fibrinogen binding also exhibited no interaction with fibronectin, suggesting that Srr2 binds this ligand through the dock-lock-latch mechanism, previously described for fibrinogen binding. The fibronectin site responsible for recombinant Srr2-BR binding was identified and localised in the central cell-binding domain of the protein. Finally, in the presence of fibronectin, the ability of a Δ srr2 mutant to adhere to human cervico-vaginal epithelial cells was significantly lower than that of the wild-type strain. Conclusion By combining genetic and biochemical approaches, we demonstrate a new role for Srr2, namely interacting with fibronectin. We characterised the molecular mechanism of this interaction and demonstrated that it plays a role in promoting the adhesion of GBS to human cervico-vaginal epithelial cells, further substantiating the role of Srr2 as a factor responsible for the hypervirulence of GBS ST-17 strains. The discovery of the previously undescribed interaction between Srr2 and fibronectin establishes this adhesin as a key factor for GBS colonisation of host tissues.
Background Staphylococcus aureus , a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections. Results Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCC mec IV was the predominant type among biofilm-positive MRSA, followed by SCC mec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp , icaA , icaB , icaC , icaD , icaR , and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types. Conclusions MRSA strains with biofilm production capability warrant increased vigilance.
The Yanomami are one of the oldest indigenous tribes in the Amazon and are direct descendants of the first people to colonize South America 12,000 years ago. They are located on the border between Venezuela and Brazil, with the Venezuelan side remaining uncontacted. While they maintain a hunter-gatherer society, they are currently experiencing contact with urbanized populations in Brazil. The human gut microbiota of traditional communities has become the subject of recent studies due to the Westernization of their diet and the introduction of antibiotics and other chemicals, which have affected microbial diversity in indigenous populations, thereby threatening their existence. In this study, we preliminarily characterized the diversity of the gut microbiota of the Yanomami, a hunter-gatherer society from the Amazon, experiencing contact with urbanized populations. Similarly, we compared their diversity with the population in Manaus, Amazonas. A metabarcoding approach of the 16 S rRNA gene was carried out on fecal samples. Differences were found between the two populations, particularly regarding the abundance of genera (e.g., Prevotella and Bacteroides ) and the higher values of the phyla Bacteroidetes over Firmicutes, which were significant only in the Yanomami. Some bacteria were found exclusively in the Yanomami ( Treponema and Succinivibrio ). However, diversity was statistically equal between them. In conclusion, the composition of the Yanomami gut microbiota still maintains the profile characteristic of a community with a traditional lifestyle. However, our results suggest an underlying Westernization process of the Yanomami microbiota when compared with that of Manaus, which must be carefully monitored by authorities, as the loss of diversity can be a sign of growing danger to the health of the Yanomami.
Background Klebsiella pneumoniae is a Gram-negative pathogen that has become a threat to public health worldwide due to the emergence of hypervirulent and multidrug-resistant strains. Cell-surface components, such as polysaccharide capsules, fimbriae, and lipopolysaccharides (LPS), are among the major virulence factors for K. pneumoniae . One of the genes involved in LPS biosynthesis is the uge gene, which encodes the uridine diphosphate galacturonate 4-epimerase enzyme. Although essential for the LPS formation in K. pneumoniae , little is known about the mechanisms that regulate the expression of uge . Ferric uptake regulator (Fur) is an iron-responsive transcription factor that modulates the expression of capsular and fimbrial genes, but its role in LPS expression has not yet been identified. This work aimed to investigate the role of the Fur regulator in the expression of the K. pneumoniae uge gene and to determine whether the production of LPS by K. pneumoniae is modulated by the iron levels available to the bacterium. Results Using bioinformatic analyses, a Fur-binding site was identified on the promoter region of the uge gene; this binding site was validated experimentally through Fur Titration Assay (FURTA) and DNA Electrophoretic Mobility Shift Assay (EMSA) techniques. RT-qPCR analyses were used to evaluate the expression of uge according to the iron levels available to the bacterium. The iron-rich condition led to a down-regulation of uge , while the iron-restricted condition resulted in up-regulation. In addition, LPS was extracted and quantified on K. pneumoniae cells subjected to iron-replete and iron-limited conditions. The iron-limited condition increased the amount of LPS produced by K. pneumoniae . Finally, the expression levels of uge and the amount of the LPS were evaluated on a K. pneumoniae strain mutant for the fur gene. Compared to the wild-type, the strain with the fur gene knocked out presented a lower LPS amount and an unchanged expression of uge , regardless of the iron levels. Conclusions Here, we show that iron deprivation led the K. pneumoniae cells to produce higher amount of LPS and that the Fur regulator modulates the expression of uge , a gene essential for LPS biosynthesis. Thus, our results indicate that iron availability modulates the LPS biosynthesis in K. pneumoniae through a Fur-dependent mechanism.
Background Renewable materials made using environmentally friendly processes are in high demand as a solution to reduce the pollution created by the fashion industry. In recent years, there has been a growing trend in research on renewable materials focused on bio-based materials derived from fungi. Results Recently, fungal cell wall material of a chitosan producing fungus has been wet spun to monofilaments. This paper presents a modification for the fungal monofilament spinning process, by the development of a benign method, dry gel spinning, to produce continuous monofilaments and twisted multifilament yarns, from fungal cell wall, that can be used in textile applications. The fungal biomass of Rhizopus delemar , grown using bread waste as a substrate, was subjected to alkali treatment with a dilute sodium hydroxide solution to isolate alkali-insoluble material (AIM), which mainly consists of the fungal cell wall. The treatment of AIM with dilute lactic acid resulted in hydrogel formation. The morphology of the hydrogels was pH dependent, and they exhibited shear thinning viscoelastic behavior. Dry gel spinning of the fungal hydrogels was first conducted using a simple lab-scale syringe pump to inject the hydrogels through a needle to form a monofilament, which was directly placed on a rotating receiver and left to dry at room temperature. The resulting monofilament was used to make twisted multifilament yarns. The process was then improved by incorporating a heated chamber for the quicker drying of the monofilaments (at 30⁰C). Finally, the spinning process was scaled up using a twin-screw microcompounder instead of the syringe pump. The monofilaments were several meters long and reached a tensile strength of 63 MPa with a % elongation at break of 14. When spinning was performed in the heated chamber, the tensile strength increased to 80 MPa and further increased to 103 MPa when a micro-compounder was used for spinning. Conclusion The developed dry gel spinning method shows promising results in scalability and demonstrates the potential for renewable material production using fungi. This novel approach produces materials with mechanical properties comparable to those of conventional textile fibers.
Fungi form part of saprotrophic communities that are responsible for the decomposition of carrion and corpses. While necrophagous insects are known in detail and can be therefore used for forensic investigation, information provided by fungi is rarely used in forensic investigations. By the present study, we further our understanding of fungal diversity on corpses in order to make fungi useful for forensic investigation. We sampled macroscopically visible microfungi on 36 corpses at the place of discovery or at the Institute of Legal Medicine in Frankfurt am Main. Forty-seven strains of fungi were isolated, cultivated, and identified based on morphological characteristics and molecular barcoding. Together with records of fungi on corpses found in literature, this information is compiled in a checklist which contains 306 records and context information on 104 species of fungi. By our investigation, 17 species of fungi have been detected for corpses for the first time. Information on localities and the decomposition stages of the corpses is compared to characteristics of fungal species as known by literature. Many fungal species use a broad spectrum of substrates in diverse habitats, but some indicate special circumstances concerning the habitat, humidity, and temperature. The degree of decomposition of the corpses significantly correlates negatively with the value of water activity for optimal growth of individual fungal species. The checklist is a first step for the documentation of the diversity of culturable fungi on corpses, but it is still very incomplete. More records of microfungi on corpses are required, and more detailed information on characteristics of individual fungal species is needed in order to interpret and use the occurrence of fungi for criminal investigation.
Background The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. Results Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6ʹ)-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers ( intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally , phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. Conclusion The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.
The cosmetics industry is harnessing microbial biotransformation through the adoption of fungi-based cosmetics. Fungi-based cosmetics offer similar benefits to their chemical and more traditional alternatives, including antioxidant, anti-aging, anti-inflammatory, and anti-wrinkling properties, which justify their application in the production of facial creams, sunscreen, body lotions, skin cleansers, shampoo, conditioner, and other skincare and haircare products. This article explores fungi-based cosmetics, with emphasis on the various species of fungi used in their production, the properties of each that are harnessed for various personal care products, and the implications of the cosmetic industry’s adoption of the cosmetics on its sustainability. This is achieved through a compilation and synthesis of existing literature on fungi-based cosmetics, an evaluation of the various fungi-based cosmetics in the market, and an evaluation of the economic and commercial viability of the cosmetics using industry data and projections.
The evolution, survival, and adaptation of microbes are consequences of gene duplication, acquisition, and divergence in response to environmental challenges. In this context, enzymes play a central role in the evolution of organisms, because they are fundamental in cell metabolism. Here, we analyzed the enzymatic repertoire in 6,467 microbial genomes, including their abundances, and their associations with metabolic maps. We found that the enzymes follow a power-law distribution, in relation to the genome sizes. Therefore, we evaluated the total proportion enzymatic classes in relation to the genomes, identifying a descending-order proportion: transferases (EC:2.-), hydrolases (EC:3.-), oxidoreductases (EC:1.-), ligases (EC:6.-), lyases (EC:4.-), isomerases (EC:5.-), and translocases (EC:7-.). In addition, we identified a preferential use of enzymatic classes in metabolism pathways for xenobiotics, cofactors and vitamins, carbohydrates, amino acids, glycans, and energy. Therefore, this analysis provides clues about the functional constraints associated with the enzymatic repertoire of functions in Bacteria and Archaea .
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.
Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus , Gram-negative Eschericia coli , and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm^2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm^2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.
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.
Fungi play crucial roles in ecosystems through complex ecological relationships with plants and animals, yet their morphological traits and how they mediate interactions remain underexplored. Historically, research focused on species cataloging, but the ecological implications of fungal morphology, such as color, shape, and odors, are still not well understood. While the study of functional traits in animals and plants is advanced, research on fungal morphology in interactions and communication is in its early stages and often inconclusive. This gap limits our understanding of fungal biology, ecology, and evolution. In this review, we explore mechanisms fungi use to interact with plants and animals, addressing the adaptive significance of traits like color patterns and shapes. We investigate whether these traits attract spore dispersers, deter predators, or serve other ecological functions. We also propose applying conceptual models based on the analysis of functional traits of plant-pollinator-disperser and animal communication to study the role of morphological traits such as color, shape, and size of fungi in sending information to animals. Additionally, we advocate creating databases that integrate fungal morphological and functional traits. In summary, our review synthesizes current knowledge on the functional roles of fungal morphological and chemical traits in interactions and communication with higher organisms and highlights the urgent need for further research to better understand their adaptive significance and ecological impact.
The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gα(q)- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2(−/−) mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-024-01236-9.
Society for Neurosciencejuli 2024Neurowetenschappen
Music, like spoken language, is often characterized by hierarchically organized structure. Previous experiments have shown neural tracking of notes and beats, but little work touches on the more abstract question: how does the brain establish high-level musical structures in real time? We presented Bach chorales to participants (20 females and 9 males) undergoing electroencephalogram (EEG) recording to investigate how the brain tracks musical phrases. We removed the main temporal cues to phrasal structures, so that listeners could only rely on harmonic information to parse a continuous musical stream. Phrasal structures were disrupted by locally or globally reversing the harmonic progression, so that our observations on the original music could be controlled and compared. We first replicated the findings on neural tracking of musical notes and beats, substantiating the positive correlation between musical training and neural tracking. Critically, we discovered a neural signature in the frequency range ∼0.1 Hz (modulations of EEG power) that reliably tracks musical phrasal structure. Next, we developed an approach to quantify the phrasal phase precession of the EEG power, revealing that phrase tracking is indeed an operation of active segmentation involving predictive processes. We demonstrate that the brain establishes complex musical structures online over long timescales (>5 s) and actively segments continuous music streams in a manner comparable to language processing. These two neural signatures, phrase tracking and phrasal phase precession, provide new conceptual and technical tools to study the processes underpinning high-level structure building using noninvasive recording techniques.
Society for Neurosciencejuli 2024Neurowetenschappen
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.
Society for Neurosciencejuli 2024Neurowetenschappen
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.
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.
Oxford University Pressseptember 2024Neurowetenschappen
OBJECTIVE: Research demonstrates reduced cognitive flexibility and weak central coherence during acute illness and following recovery from anorexia nervosa (AN). This systematic review investigated if these impairments are present in first-degree relatives of individuals with AN, representing a possible neuropsychological risk profile. METHODS: A systematic review of electronic databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search ended on July 14, 2023. Established search terms and inclusion criteria identified relevant research. Risk of bias was assessed using the Critical Appraisal Skills Program. The review was registered with Prospero international prospective register of systematic reviews (No. CRD42023401268). Study selection, descriptive data, critical appraisal, and risk of bias are presented in tables and figures. RESULTS: The search yielded 10 studies. The included studies conducted neuropsychological assessments of discordant AN relatives and lifetime longitudinal study participants. Most studies found cognitive flexibility and central coherence to be significantly reduced in participants with AN and their relatives compared with controls. One study found decision making to be significantly impaired in AN participants and relatives. Effect sizes were moderate to large. DISCUSSION: Reduced cognitive flexibility and weak central coherence appear to be endophenotypes of AN. Further research is required with relatives concordant for AN to establish whether these biomarkers co-segregate with AN within families. These findings suggest a possibility of developing screeners to identify individuals at risk of AN allowing for early intervention.
Due to the use of new technologies and ongoing digitization, there is a significant increase in the popularity of online stores. More and more, consumers appreciate the ease of online shopping, enjoying the ability to explore a diverse array of products from the comfort of their own homes. The wide range of products available in online stores allows consumers to precisely tailor their purchases to their individual preferences and needs. However, too much information on a page can lead to cognitive load, affecting visual attention and purchasing decisions. The article focuses on an innovative approach to measuring the impact of cognitive load on the purchasing decision-making process in online stores. The authors focus on psychological aspects, including reducing the influence of external factors, to obtain more reliable results. Understanding how cognitive load affects online shopping decisions is crucial for designing effective, user-friendly e-commerce platforms.
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.
Society for Neurosciencejuli 2024Neurowetenschappen
Sex differences have complicated our understanding of the neurobiological basis of many behaviors that are key for survival. As such, continued elucidation of the similarities and differences between sexes is necessary to gain insight into brain function and vulnerability. The connection between the hippocampus (Hipp) and nucleus accumbens (NAc) is a crucial site where modulation of neuronal activity mediates reward-related behavior. Our previous work demonstrated that long-term potentiation (LTP) of Hipp→NAc synapses is rewarding, and mice can establish learned associations between LTP of these synapses and the contextual environment in which LTP occurred. Here, we investigated sex differences in the mechanisms underlying Hipp→NAc LTP using whole-cell electrophysiology and pharmacology. We observed similarities in basal synaptic strength between males and females and found that LTP occurs postsynaptically with similar magnitudes in both sexes. However, key sex differences emerged as LTP in males required NMDA receptors (NMDAR), whereas LTP in females utilized an NMDAR-independent mechanism involving L-type voltage-gated Ca(2+) channels (VGCCs) and estrogen receptor α (ERα). We also uncovered sex-similar features as LTP in both sexes depended on CaMKII activity and occurred independently of dopamine-1 receptor (D1R) activation. Our results have elucidated sex-specific molecular mechanisms for LTP in an integral pathway that mediates reward-related behaviors, emphasizing the importance of considering sex as a variable in mechanistic studies. Continued characterization of sex-specific mechanisms underlying plasticity will offer novel insight into the neurophysiological basis of behavior, with significant implications for understanding how diverse processes mediate behavior and contribute to vulnerability to developing psychiatric disorders.
Psychology and neuroscience are closely related fields that complement each other in many ways, including understanding the brain. Neuroscience studies the brain and nervous system, while psychology focuses on mental processes. By combining the two fields, researchers can better understand how the brain creates the mind. Neuroscience can help psychologists make more informed decisions about mental health treatments and interventions. For example, neurotherapy uses brain maps to identify physiological reasons for psychological feelings, and then retrain the brain. Neuroscience can help psychologists understand psychological concepts like memory and emotion. For example, the hippocampus is a key region in the brain that helps encode short-term memories into long-term memories. Neuropsychology studies how the brain and nervous system influence behaviour and cognition. Neuropsychology uses experimental and clinical research, as well as neuroimaging and standardised tests.
The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K(+) channels, or Ca(2+)-activated K(+) channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
This chapter is first a journey through the history of human attention study from philosophy to computer science through experimental and cognitive psychology and neuroscience. It also brings the very important definitions which might be found about attention and which are very needed for the rest of the book.
Systems neuroscience employs a network and topological perspective to elucidate the paradigm “brain.” The attribution of perception, cognition, consciousness, and behavior to findings obtained from multimodal physiological research, neuroimaging, and clinical neuromonitoring represents a significant aspect of the field within translational neuroscience. From a clinical perspective, there is great hope that advances in the treatment of severe neurofunctional disorders will be driven by the examination of the “big data” now available. Examples of clinical applications include the study of severe brain injury, coma, and (disorders of) consciousness. This brief introduction will delineate the fundamental principles of systems neuroscience, computational models, bioinformatics, and artificial intelligence as they pertain to the clinical use and investigation of ketamine. The meaning of this research for innovative therapeutic approaches and the importance of “real-world brain and body biology” within the strengths and weaknesses of translational systems neuroscience will be outlined.
Functional magnetic resonance imaging (fMRI) has the capability to reflect brain activities, with brain regions such as the amygdala, prefrontal cortex, and hippocampus exhibiting distinct emotional activity patterns. These neural activities interact in complex ways, making interpretation and identification challenging. The objective of this study is to identify participants’ emotions using fMRI data from the ICBHI scientific challenge, involving 16 participants in the training set and 4 in the test set. Each participant has undergone 30 trails and reported their emotion classes and levels. The averaged fMRI signals were extracted from 246 regions by Brainnetome atlas, and the regions of interest were selected based on correlations, including emotional related 66 regions. We applied a band-pass filter (sigma = 2) for data preprocessing. There were two models developed, for class and level prediction, respectively. For class prediction, to enhance signal quality and reduce noise in fMRI signals, we employed a nonlinear least squares approach. Specifically, each 25-s signal segment was modeled using a polynomial, and parameters of this polynomial were adjusted to minimize the sum of squares of the differences between observed and predicted values. To test which brain regions’ activity patterns are highly correlated with emotions, we trained multiple fully connected neural networks (FCNNs) to select from the previously mentioned 66 brain regions. Ultimately, the signals from brain regions highly correlated with emotions are selected as inputs for subsequent integrated convolutional neural network (CNN) model to distinguish between types of emotions. For level prediction, we utilized long short- term memory (LSTM) models for level prediction to participants’ emotions judgement. Finally, the algorithm we proposed achieved a classification accuracy of 56% for identifying emotion classes, 20% for identifying emotional intensity levels. The mean score of 0.6251 was calculated by ICBHI. The difference of the precision for class and level may be related to the subjective evaluation of the subjects as the rating of emotion is highly dependent by the subject’s self-perception and background.
This study examines the Theta/Beta Ratio (TBR) in EEG measurements to infer the cognitive load during decision-making across different attachment styles. Participants’ EEGs were analyzed within the secretary problem framework while they were at rest and making decisions. The secure attachment group demonstrated higher TBR difference medians, suggesting a lower cognitive load. Conversely, the fearfully avoidant group exhibited significantly lower medians, indicating a heightened cognitive load. The anxiously attached group’s TBR varied widely, suggesting inconsistent cognitive engagement, while the avoidant group’s levels were moderate. These results imply that attachment style determines the cognitive load experienced during decision-making, with fearfully avoidant individuals bearing the highest load. This research elucidates the neurobiological links between attachment styles and cognitive processing.
Society for Neurosciencejuli 2024Neurowetenschappen
Calcineurin inhibitors, such as cyclosporine and tacrolimus (FK506), are commonly used immunosuppressants for preserving transplanted organs and tissues. However, these drugs can cause severe and persistent pain. GluA2-lacking, calcium-permeable AMPA receptors (CP-AMPARs) are implicated in various neurological disorders, including neuropathic pain. It is unclear whether and how constitutive calcineurin, a Ca(2+)/calmodulin protein phosphatase, controls synaptic CP-AMPARs. In this study, we found that blocking CP-AMPARs with IEM-1460 markedly reduced the amplitude of AMPAR-EPSCs in excitatory neurons expressing vesicular glutamate transporter-2 (VGluT2), but not in inhibitory neurons expressing vesicular GABA transporter, in the spinal cord of FK506-treated male and female mice. FK506 treatment also caused an inward rectification in the current–voltage relationship of AMPAR-EPSCs specifically in VGluT2 neurons. Intrathecal injection of IEM-1460 rapidly alleviated pain hypersensitivity in FK506-treated mice. Furthermore, FK506 treatment substantially increased physical interaction of α2δ-1 with GluA1 and GluA2 in the spinal cord and reduced GluA1/GluA2 heteromers in endoplasmic reticulum-enriched fractions of spinal cords. Correspondingly, inhibiting α2δ-1 with pregabalin, Cacna2d1 genetic knock-out, or disrupting α2δ-1–AMPAR interactions with an α2δ-1 C terminus peptide reversed inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons caused by FK506 treatment. In addition, CK2 inhibition reversed FK506 treatment–induced pain hypersensitivity, α2δ-1 interactions with GluA1 and GluA2, and inward rectification of AMPAR-EPSCs in spinal VGluT2 neurons. Thus, the increased prevalence of synaptic CP-AMPARs in spinal excitatory neurons plays a major role in calcineurin inhibitor-induced pain hypersensitivity. Calcineurin and CK2 antagonistically regulate postsynaptic CP-AMPARs through α2δ-1—mediated GluA1/GluA2 heteromeric assembly in the spinal dorsal horn.
In recent decades, human and animal studies have made strides in advancing knowledge about the neural and genetic basis of attachment—the selective preference for specific individuals, which is characterized by proximity-seeking, care, and the investment of time and resources. Pair-bonding is one instantiation of attachment, but it is unique for its role in reproduction (with genetic implications) and biparental care of offspring. Unique to humans, and sometimes coinciding with pair-bonding, is the complex phenomenon of romantic love, a basic human motivation involving an intense desire to be united with the beloved physically, emotionally, and mentally. Increasingly, scientists have examined the biological basis of romantic love, providing a deeper understanding of the mechanisms underlying attachment, pair-bonding, and its nature. In this chapter, we provide an overview of animal models detailing the biological mechanisms of pair-bonding. Next, we review research on the neural and genetic basis of pair-bonding and romantic love in humans. Finally, we comment on future directions of this work and elucidate how the neural and genetic processes discussed herein influence the expression and function of this basic human drive that we call love.
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.
This book emphasizes the pivotal role of enteric glial cells in maintaining gut health and their influence on the gut–brain axis. Although their existence was first noted at the end of the nineteenth century, recent scientific attention has shed light on their crucial functions, especially in inflammatory bowel diseases and potential links to neurodegenerative conditions like Parkinson’s disease. Understanding how these cells operate and interact within the complex network of the enteric nervous system is vital, not only for unraveling gut-related disorders but also for exploring their impact on brain health. Designed as a comprehensive guide, this book provides practical protocols to identify, visualize, and isolate enteric glial cells using techniques such as enzymatic digestion, immunofluorescence, and advanced imaging methods like confocal microscopy. It highlights the importance of studying glial cell behavior and their morphological diversity across different states of activation and maturation. Moreover, it explores innovative approaches using transgenic models and human biopsies to investigate their activity, interactions with the microbiome, and responses to inflammation. Understanding these mechanisms may open new avenues for therapies targeting both gastrointestinal and neurodegenerative diseases. This book also discusses possibilities for cell-based interventions, including the potential for enteric glial transplantation into the central nervous system. Overall, this work aims to bridge gastrointestinal and neurological research, underscoring the significance of enteric glia in health, disease, and the intricate communication between the gut and the brain. Advancing knowledge in this area could lead to novel, more precise treatments that address the root causes of complex conditions affecting both the gut and the nervous system.
Suppose twentieth-century literary theory had been based on the works of Henri Bergson rather than Ferdinand de Saussure. Would structuralist and poststructuralist theories of language have withstood a Bergsonian critique? Would the institution of literary study be radically different from what it is today? What does this suggest about the future of literary theory?
Society for Neurosciencejuni 2024Neurowetenschappen
The neurophysiological effects of spinal cord stimulation (SCS) for chronic pain are poorly understood, resulting in inefficient failure-prone programming protocols and inadequate pain relief. Nonetheless, novel stimulation patterns are regularly introduced and adopted clinically. Traditionally, paresthetic sensation is considered necessary for pain relief, although novel paradigms provide analgesia without paresthesia. However, like pain relief, the neurophysiological underpinnings of SCS-induced paresthesia are unknown. Here, we paired biophysical modeling with clinical paresthesia thresholds (of both sexes) to investigate how stimulation frequency affects the neural response to SCS relevant to paresthesia and analgesia. Specifically, we modeled the dorsal column (DC) axonal response, dorsal column nucleus (DCN) synaptic transmission, conduction failure within DC fiber collaterals, and dorsal horn network output. Importantly, we found that high-frequency stimulation reduces DC fiber activation thresholds, which in turn accurately predicts clinical paresthesia perception thresholds. Furthermore, we show that high-frequency SCS produces asynchronous DC fiber spiking and ultimately asynchronous DCN output, offering a plausible biophysical basis for why high-frequency SCS is less comfortable and produces qualitatively different sensation than low-frequency stimulation. Finally, we demonstrate that the model dorsal horn network output is sensitive to SCS-inherent variations in spike timing, which could contribute to heterogeneous pain relief across patients. Importantly, we show that model DC fiber collaterals cannot reliably follow high-frequency stimulation, strongly affecting the network output and typically producing antinociceptive effects at high frequencies. Altogether, these findings clarify how SCS affects the nervous system and provide insight into the biophysics of paresthesia generation and pain relief.
Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-024-01249-4.
Brain biopsies and cerebrospinal fluid collection are frequently used in neuroscience research and require precise execution. The objective of this chapter was to provide updated protocols for brain biopsies and other stereotactic procedures in adult mice. The described technique employing a stereotactic arm enables greater precision than freehand techniques. Stereotactic procedures in adult mice can be performed expeditiously and demonstrate high efficacy in reaching the target site. Efficacy is contingent upon the complexity of precisely targeting the biopsy site, owing to the diminutive size of the animal. This chapter describes an innovative, efficient, and reproducible surgical protocol for brain biopsy and cerebrospinal fluid collection in adult mice.
Society for Neurosciencejuni 2024Neurowetenschappen
Coordinated multijoint limb and digit movements—“manual dexterity”—underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that corticostriatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release in both male and female mice as they learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In the dorsolateral striatum, dopamine dynamics are faster than in the dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of the striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.
Society for Neurosciencejuli 2024Neurowetenschappen
It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography during a saccade task. Human participants (male and female) made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight into when remapped information becomes available. We found that the stimulus could be decoded at the remapped location ∼180 ms post-stimulus onset, but only when the stimulus was presented 100–200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons.
Dysphonia is one of the early symptoms of Parkinson's disease (PD). Most
existing methods use feature selection methods to find the optimal subset of
voice features for all PD patients. Few have considered the heterogeneity
between patients, which implies the need to provide specific prediction models
for different patients. However, building the specific model faces the
challenge of small sample size, which makes it lack generalization ability.
Instance transfer is an effective way to solve this problem. Therefore, this
paper proposes a patient-specific game-based transfer (PSGT) method for PD
severity prediction. First, a selection mechanism is used to select PD patients
with similar disease trends to the target patient from the source domain, which
greatly reduces the risk of negative transfer. Then, the contribution of the
transferred subjects and their instances to the disease estimation of the
target subject is fairly evaluated by the Shapley value, which improves the
interpretability of the method. Next, the proportion of valid instances in the
transferred subjects is determined, and the instances with higher contribution
are transferred to further reduce the difference between the transferred
instance subset and the target subject. Finally, the selected subset of
instances is added to the training set of the target subject, and the extended
data is fed into the random forest to improve the performance of the method.
Parkinson's telemonitoring dataset is used to evaluate the feasibility and
effectiveness. Experiment results show that the PSGT has better performance in
both prediction error and stability over compared methods.
International audience;
Neural network-based anomaly detection remains challenging in clinical applications with little or no supervised information and subtle anomalies such as hardly visible brain lesions. Among unsupervised methods, patch-based auto-encoders with their efficient representation power provided by their latent space, have shown good results for visible lesion detection. However, the commonly used reconstruction error criterion may limit their performance when facing less obvious lesions. In this work, we design two alternative detection criteria. They are derived from multivariate analysis and can more directly capture information from latent space representations. Their performance compares favorably with two additional supervised learning methods, on a difficult de novo Parkinson Disease (PD) classification task.
Hypomimia is a non-motor symptom of Parkinson's disease that manifests as
delayed facial movements and expressions, along with challenges in articulation
and emotion. Currently, subjective evaluation by neurologists is the primary
method for hypomimia detection, and conventional rehabilitation approaches
heavily rely on verbal prompts from rehabilitation physicians. There remains a
deficiency in accessible, user-friendly and scientifically rigorous assistive
tools for hypomimia treatments. To investigate this, we developed
HypomimaCoach, an Action Unit (AU)-based digital therapy system for hypomimia
detection and rehabilitation in Parkinson's disease. The HypomimaCoach system
was designed to facilitate engagement through the incorporation of both relaxed
and controlled rehabilitation exercises, while also stimulating initiative
through the integration of digital therapies that incorporated traditional face
training methods. We extract action unit(AU) features and their relationship
for hypomimia detection. In order to facilitate rehabilitation, a series of
training programmes have been devised based on the Action Units (AUs) and
patients are provided with real-time feedback through an additional AU
recognition model, which guides them through their training routines. A pilot
study was conducted with seven participants in China, all of whom exhibited
symptoms of Parkinson's disease hypomimia. The results of the pilot study
demonstrated a positive impact on participants' self-efficacy, with favourable
feedback received. Furthermore, physician evaluations validated the system's
applicability in a therapeutic setting for patients with Parkinson's disease,
as well as its potential value in clinical applications.
Parkinson's disease (PD), the second most prevalent neurodegenerative
disorder worldwide, frequently presents with early-stage speech impairments.
Recent advancements in Artificial Intelligence (AI), particularly deep learning
(DL), have significantly enhanced PD diagnosis through the analysis of speech
data. Nevertheless, the progress of research is restricted by the limited
availability of publicly accessible speech-based PD datasets, primarily due to
privacy concerns. The goal of this systematic review is to explore the current
landscape of speech-based DL approaches for PD classification, based on 33
scientific works published between January 2020 and March 2024. We discuss
their available resources, capabilities, and potential limitations, and issues
related to bias, explainability, and privacy. Furthermore, this review provides
an overview of publicly accessible speech-based datasets and open-source
material for PD. The DL approaches identified are categorized into end-to-end
(E2E) learning, transfer learning (TL), and deep acoustic feature extraction
(DAFE). Among E2E approaches, Convolutional Neural Networks (CNNs) are
prevalent, though Transformers are increasingly popular. E2E approaches face
challenges such as limited data and computational resources, especially with
Transformers. TL addresses these issues by providing more robust PD diagnosis
and better generalizability across languages. DAFE aims to improve the
explainability and interpretability of results by examining the specific
effects of deep features on both other DL approaches and more traditional
machine learning (ML) methods. However, it often underperforms compared to E2E
and TL approaches.
;Comment: van Gelderen, L., & Tejedor-Garc\'ia, C. (2024). Innovative
Speech-Based Deep Learning Approaches for Parkinson's Disease Classification:
A Systematic Review. Applied Sciences, 14(17). doi:10.3390/app14177873 This
research was funded by the NWO research programme NGF AiNed Fellowship Grants
under the project Responsible AI for Voice Diagnostics (RAIVD) - grant number
NGF.1607.22.013
Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally. Both are proteinopathic conditions and while occasionally inherited, are largely sporadic in nature. Although the advances in our understanding of the two have been significant, they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful. Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research. This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease, and highlights the shifting paradigms in studying two human‐specific conditions in non‐human organisms.
Abstract Background Exergaming has been proposed to improve gait and balance disorders in Parkinson's disease (PD) patients. We aimed to assess the efficacy of a home‐based, tailored, exergaming training system designed for PD patients with dopa‐resistant gait and/or balance disorders in a controlled randomized trial. Methods We recruited PD patients with dopa‐resistant gait and/or balance disorders. Patients were randomly assigned (1:1 ratio) to receive 18 training sessions at home by playing a tailored exergame with full‐body movements using a motion capture system (Active group), or by playing the same game with the computer's keyboard (Control group). The primary endpoint was the between‐group difference in the Stand‐Walk‐Sit Test (SWST) duration change after training. Secondary outcomes included parkinsonian clinical scales, gait recordings, and safety. Results Fifty PD patients were enrolled and randomized. After training, no significant difference in SWST change was found between groups (mean change SWST duration [SD] −3.71 [18.06] s after Active versus −0.71 [3.41] s after Control training, p = 0.61). Some 32% of patients in the Active and 8% in the Control group were considered responders to the training program (e.g., SWST duration change ≥2 s, p = 0.03). The clinical severity of gait and balance disorders also significantly decreased after Active training, with a between‐group difference in favor of the Active training ( p = 0.0082). Home‐based training induced no serious adverse events. Conclusions Home‐based training using a tailored exergame can be performed safely by PD patients and could improve gait and balance disorders. Future research is needed to investigate the potential of exergaming.
International audience;
Patients with Parkinson’s disease (PD) notably exhibit impairments in posture and visual attention. The objective of the present study was to determine whether PD patients were able to exhibit adaptive postural control in a goal-directed visual task. We hypothesized that the patients would reduce their centre of pressure (COP) movement and/or postural sway to a lesser extent than age-matched controls in the goal-directed visual (search) task, compared with the control free-viewing task (i.e. a lower degree of relative postural adaptation). We also expected the PD patients to sway more than controls in the goal-directed task (i.e. a lower degree of absolute adaptive postural control). The study included 39 PD patients (mean age: 59; mean Hoehn and Yahr stage: 2.1; mean Movement Disorder Society-Unified Parkinson's Disease Rating Scale score: 22; mean Montreal Cognitive Assessment score: 28 (on-drug) and 40 age-matched adults (mean age: 62 years). The participants gazed domestic ecological images (visual angle: 100°). Movements of the COP, head, upper back and lower-back and variations in pupil dilatation were analysed. As expected, PD patients exhibited greater COP and body sway than controls in both tasks (p<0.05). Unexpectedly, the difference in COP and/or body sway between the two tasks was greater in PD patients than in controls (p<0.05). Our results showed that PD patients are able to exhibit adaptive postural control for goal-directed visual tasks. On a practical level, our findings emphasize the likely benefits of rehabilitation with goal-directed tasks requiring a visual attentional focus (walking on footprints on the ground, etc.).
;
Les patients atteints de la maladie de Parkinson (MP) présentent notamment des troubles de la posture et de l'attention visuelle. L'objectif de la présente étude était de déterminer si les patients atteints de MP étaient capables de démontrer un contrôle postural adaptatif dans une tâche visuelle orientée vers un objectif. Nous avons émis l'hypothèse que les patients réduiraient leurs mouvements du centre de pression (COP) et/ou leurs oscillations posturales dans une moindre mesure que des témoins appariés en âge lors de la tâche visuelle orientée vers un objectif (recherche), par rapport à une tâche de vision libre (c’est-à-dire un degré inférieur d'adaptation posturale relative). Nous nous attendions également à ce que les patients atteints de MP oscillent davantage que les témoins dans la tâche orientée (c’est-à-dire un degré inférieur de contrôle postural adaptatif absolu). L'étude a inclus 39 patients atteints de MP (âge moyen : 59 ans ; stade moyen de Hoehn et Yahr : 2,1 ; score moyen à l'échelle MDS-UPDRS : 22 ; score moyen au MoCA : 28, en phase « on » du traitement) et 40 adultes appariés en âge (âge moyen : 62 ans). Les participants ont regardé des images écologiques domestiques (angle visuel : 100°). Les mouvements du COP, de la tête, du haut et du bas du dos ainsi que les variations de dilatation pupillaire ont été analysés. Comme prévu, les patients atteints de MP ont montré des oscillations du COP et du corps plus importantes que les témoins dans les deux tâches (p<0,05). De manière inattendue, la différence dans les oscillations du COP et/ou du corps entre les deux tâches était plus marquée chez les patients atteints de MP que chez les témoins (p<0,05). Nos résultats ont montré que les patients atteints de MP sont capables de démontrer un contrôle postural adaptatif dans des tâches visuelles orientées vers un objectif. Sur un plan pratique, nos résultats soulignent les bénéfices potentiels de la rééducation utilisant des tâches orientées nécessitant une attention visuelle (marcher sur des empreintes au sol, etc.).
Parkinson's disease is the world's fastest-growing neurological disorder.
Research to elucidate the mechanisms of Parkinson's disease and automate
diagnostics would greatly improve the treatment of patients with Parkinson's
disease. Current diagnostic methods are expensive and have limited
availability. Considering the insidious and preclinical onset and progression
of the disease, a desirable screening should be diagnostically accurate even
before the onset of symptoms to allow medical interventions. We highlight
retinal fundus imaging, often termed a window to the brain, as a diagnostic
screening modality for Parkinson's disease. We conducted a systematic
evaluation of conventional machine learning and deep learning techniques to
classify Parkinson's disease from UK Biobank fundus imaging. Our results show
that Parkinson's disease individuals can be differentiated from age and
gender-matched healthy subjects with an Area Under the Curve (AUC) of 0.77.
This accuracy is maintained when predicting either prevalent or incident
Parkinson's disease. Explainability and trustworthiness are enhanced by visual
attribution maps of localized biomarkers and quantified metrics of model
robustness to data perturbations.
;Comment: 17 pages, 4 figures, 2 tables, 4 supplementary tables
International audience;
Parkinson's disease (PD) and the parkinsonian variant of Multiple System Atrophy (MSA-P) are two neurodegenerative diseases which share similar clinical features, particularly in early disease stages. The differential diagnosis can be thus very challenging. Dysarthria is known to be a frequent and early clinical feature of PD and MSA. It can be thus used as a vehicle to provide a vocal biomarker which could help in the differential diagnosis. In particular, distortion of consonants is known to be a frequent impairment in these diseases. The aim of this study is to investigate distinctive patterns in the distortion of voiced obstruents (plosives and fricatives). It is the first study which attempts to examine such distortions in the French language for the purpose of the differential diagnosis between PD and MSA-P (and among the very few studies if we consider all languages). We carry out a perceptual and objective analysis of voiced obstruents extracted from isolated pseudo-words initials. We first show that devoicing is a significant impairment which predominates in MSA-P. We then show that voice onset time (VOT) of voiced plosives (prevoicing duration) can be a complementary feature to improve the accuracy in discrimination between PD and MSA-P.
In this paper, we evaluate the contribution of different handwriting
modalities to the diagnosis of Parkinson's disease. We analyse on-surface
movement, in-air movement and pressure exerted on the tablet surface.
Especially in-air movement and pressure-based features have been rarely taken
into account in previous studies. We show that pressure and in-air movement
also possess information that is relevant for the diagnosis of Parkinson's
Disease (PD) from handwriting. In addition to the conventional kinematic and
spatio-temporal features, we present a group of the novel features based on
entropy and empirical mode decomposition of the handwriting signal. The
presented results indicate that handwriting can be used as biomarker for PD
providing classification performance around 89% area under the ROC curve (AUC)
for PD classification.
;Comment: The work was published by IEEE
Idiopathic Parkinson’s disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus–subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood–brain barrier.
Limited accessibility to neurological care leads to underdiagnosed
Parkinson's Disease (PD), preventing early intervention. Existing AI-based PD
detection methods primarily focus on unimodal analysis of motor or speech
tasks, overlooking the multifaceted nature of the disease. To address this, we
introduce a large-scale, multi-task video dataset consisting of 1102 sessions
(each containing videos of finger tapping, facial expression, and speech tasks
captured via webcam) from 845 participants (272 with PD). We propose a novel
Uncertainty-calibrated Fusion Network (UFNet) that leverages this multimodal
data to enhance diagnostic accuracy. UFNet employs independent task-specific
networks, trained with Monte Carlo Dropout for uncertainty quantification,
followed by self-attended fusion of features, with attention weights
dynamically adjusted based on task-specific uncertainties. To ensure
patient-centered evaluation, the participants were randomly split into three
sets: 60% for training, 20% for model selection, and 20% for final performance
evaluation. UFNet significantly outperformed single-task models in terms of
accuracy, area under the ROC curve (AUROC), and sensitivity while maintaining
non-inferior specificity. Withholding uncertain predictions further boosted the
performance, achieving 88.0+-0.3%$ accuracy, 93.0+-0.2% AUROC, 79.3+-0.9%
sensitivity, and 92.6+-0.3% specificity, at the expense of not being able to
predict for 2.3+-0.3% data (+- denotes 95% confidence interval). Further
analysis suggests that the trained model does not exhibit any detectable bias
across sex and ethnic subgroups and is most effective for individuals aged
between 50 and 80. Requiring only a webcam and microphone, our approach
facilitates accessible home-based PD screening, especially in regions with
limited healthcare resources.
The prevalence of negative stimuli conventionally observed in young adults decreases during normal aging, oreven evolves into a prevalence of positive stimuli. This age-related effect is called the "positivity effect". Observedin emotional appraisal tasks, this effect disappears in action tendency tasks, suggesting a dissociation betweenemotions and action behaviors. Better understanding the evolution of the link between emotional processes andaction behaviors in normal aging would allow to specify the conditions for the emergence of the positivity effectand to better understand the motor and affective disorders associated with some neurodegenerative pathologiessuch as Parkinson's disease (PD). The first section of my PhD thesis consisted in evaluating the evolution ofemotional processing during normal aging. During a free exploration task of emotional image pairs, a first studyin oculometry show in the elderly a reduced automatic orientation of attention and a more spatially focusedattentional exploration for positive scenes, compared to young and middle-aged adults. At the cerebral level, asecond functional MRI study (fMRI) suggests a cerebral reorganization in normal aging which would reflect anevolution of emotional processing strategies: while young people would rather activate a fronto-limbic networkassociated with the emotional evaluation and regulation and a more complex cognitive processing, the elderly (vsyoung) would activate more regions related to viscero-somatosensory integration, spatial imaging and motorprogramming and regulation in a more embodied strategy of the emotional appraisal. In contrast, the two groups,young and older, differed less in the action tendency task, suggesting similar emotional processing strategies fordeciding motivated action. The second section of my PhD thesis consisted in evaluating the evolution of emotionalprocessing in de novo PD patients using the same protocols of previous studies. The oculometry study (3rd study)reveal in patients, a reduced automatic orientation of attention for emotional scenes (vs neutral) and even more forpositive scenes and an overall more extensive attentional exploration, compared to healthy controls. The fMRIstudy (4th study) reveals, for its part, an hyperactivation of a large temporo-parieto-fronto-limbic networkspecifically in the action tendency task in patients (vs healthy controls), suggesting a mechanism of compensationfor the difficulties encountered by the patients in this task, while their emotional appraisal is relatively preserved.The oculomotor and cerebral patterns specifically observed in de novo PD patients pave the way for theidentification of new early (bio)markers of Parkinson's disease and the action tendency task seems to be a relevanttool in this perspective.
;
La prévalence des stimuli négatifs classiquement observée chez de jeunes adultes s’atténue au cours du vieillissement sain, voire évolue vers une prévalence des stimuli positifs. Cet effet lié à l’âge est appelé « effet depositivité ». Présent dans des tâches d’évaluation du ressenti émotionnel, cet effet disparait lors de tâche d’évaluation de la tendance à l’action, suggérant une dissociation entre émotion et comportement d’action. Mieux comprendre l’évolution du lien entre processus émotionnels et comportements d’action au cours du vieillissement sain permettrait de préciser les conditions d’émergence de l’effet de positivité et de mieux comprendre les troubles moteurs et affectifs associés dans certaines pathologies neurodégénératives telles que la maladie de Parkinson. Le premier volet d’études de la thèse a consisté à évaluer l’évolution du traitement émotionnel au cours du vieillissement sain. Lors d’une tâche d’exploration libre de paires d’images émotionnelles, une première étude enoculométrie montre chez les personnes âgées une orientation automatique de l’attention réduite et une exploration attentionnelle plus focalisée spatialement pour les scènes positives, par rapport aux adultes jeunes et d’âge moyen.Au niveau cérébral, une seconde étude en IRM fonctionnelle (IRMf) suggère une réorganisation cérébrale au coursdu vieillissement sain qui traduirait une évolution des stratégies de traitement émotionnel : alors que les jeunes personnes activeraient plutôt un réseau fronto-limbique associé à l’évaluation et la régulation émotionnelles et à un traitement cognitif plus complexe, les personnes âgées (vs jeunes) activeraient davantage des régions liées à l’intégration viscéro-somato sensorielle, à la visualisation spatiale et à la programmation et régulation motrice dans une stratégie plus incarnée de l’évaluation émotionnelle. En revanche, les deux groupes, jeunes et âgés, se distinguent moins dans la tâche de tendance à l’action, suggérant des stratégies cérébrales de traitement émotionnel quasi-analogues pour décider d’une action motivée. Le deuxième volet d’études de la thèse a consisté à évaluer l’évolution du traitement émotionnel chez des patients parkinsoniens de novo en utilisant les mêmes protocoles des études précédentes. L’étude en oculométrie (3ème étude) révèle chez les patients, une orientation automatique de l’attention réduite pour les scènes émotionnelles (vs neutres) et d’autant plus pour les scènes positives et une exploration attentionnelle globalement plus étendue, par rapport aux contrôles sains. L’étude en IRMf (4ème étude)révèle, quant à elle, une suractivation d’un large réseau temporo-parieto-fronto-limbique spécifiquement dans latâche de tendance à l’action chez les patients (vs contrôles sains), suggérant un mécanisme de compensation aux difficultés rencontrées par les patients dans cette tâche, alors que leur évaluation émotionnelle est relativemen tpréservée. Les patterns oculomoteurs et cérébraux observés spécifiquement chez les patients parkinsoniens denovo ouvrent la piste à l’identification de potentiels nouveaux (bio)marqueurs précoces de la maladie de Parkinson et la tâche de tendance à l’action semble être un outil d’intérêt dans cette perspective.
Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis. Our goal was to study two serum circulating microRNAs (miR-96-5p and miR-339-5p) as novel biomarkers for the differential diagnosis between PD and MSA. Serum samples were obtained from 51 PD patients, 52 MSA patients and 56 healthy controls (HC). We measured levels of miRNAs using quantitative PCR and compared the levels of miR-96-5p and miR-339-5p among PD, MSA and HC groups using a one-way analysis of variance. Correlations between miRNA expression and clinical data were calculated using Pearson's rho test. We used the miRTarBase to detect miRNA targets and STRING to evaluate co-expression relationship among target genes. MiR-96-5p was significantly increased in MSA patients compared with HC (Fold change (fc): 3.6; p = 0.0001) while it was decreased in PD patients compared with HC (Fold change: 4; p = 0.0002). Higher miR-96-5P levels were directly related to longer disease duration in MSA patients. We observed a significant increase of miR-339-5p in MSA patients compared with PD patients (fc: 2.5; p = 0.00013). miR-339-5p was increased in MSA patients compared with HC (fc: 2.4; p = 0.002). We identified 32 target genes of miR-96-5p and miR-339-5p, some of which are involved in neurodegenerative diseases. The study of those miRNAs could be useful to identify non-invasive biomarkers for early differential diagnosis between PD and MSA.
Under review, (18 pages, 13 figures);International audience;
This study focuses on the diagnosis of Parkinson’s Disease (PD) based on electroencephalogram (EEG) signals. A novel approach inspired by the functioning of the brain is proposed, which uses the dynamics, frequency, and temporal content of EEGs to extract new discriminant features of the disease. The generated sparse dynamic features (SDFs) allow, through a transformation, to change the point of view on the data giving access to more informative features that are more faithful to the concept of EEG generation. Nevertheless, the method remains generic and can be applied to any signal but for this application it was evaluated on a publicly available dataset containing EEG signals recorded during a 3-oddball auditory task involving subjects, of whom 25 suffer from PD. Given the adequate perspective on the data, it comes out that by using only two extracted features from the generated SDFs the healthy and unhealthy subjects are separated using a linear classifier. The classification yields an accuracy of 90.0% () using a single channel. By aggregating the information from three channels and making them vote, an accuracy of 94%, a sensitivity of 96% and a specificity of 92% is obtained. The evaluation was carried out using a nested Leave-One-Out cross-validation procedure, thus preventing data leakage problems and giving a less biased evaluation. Several tests were carried out to assess the validity and robustness of our approach.
Parkinson's disease (PD) is a neurodegenerative disease that includes motor impairments, such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and 18 healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually guided pursuit, and rapid go/no-go manual interception. Compared with controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in ∼35% of trials compared with 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients' eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients' interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus and task dependency of oculomotor impairments, and we propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the superior colliculus-brainstem loop that bypasses the fronto-basal ganglia network. Our results demonstrate that studying oculomotor and hand movement function in PD can support disease diagnosis and further our understanding of disease progression and dynamics. SIGNIFICANCE STATEMENT Eye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson's disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously described eye movement impairments are task-specific. We assessed eye movements in PD under different visual (stationary vs moving targets) and movement (reactive vs deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements toward stationary targets. The preservation of eye movements toward dynamic stimuli might enable patients to accurately act on the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.
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: Parkinson's disease (PD) is a neurodegenerative disease perceived as a motor disorder. It is most commonly associated with autonomic dysfunction, affecting multiple systems. This altered autonomic control might be reflected by a parallel change in the airway caliber of these patients. AIM: To correlate the pulmonary impairment in patients with Parkinson's disease with the underlying dysautonomia. MATERIALS AND METHODS: A total of 30 patients with Parkinson's disease participated in the study. Heart rate (HR) variability was recorded for 5 min to assess the autonomic dysfunction, followed by impulse oscillometry (IOS) and spirometry. IOS being an effort independent technique uses sound waves at different frequencies (5–25 Hz) to measure the airway impedance. RESULTS: There was a significant decrease in SDSD (6.60 (10.18–6.01) vs. 12.22 (13.95–11.30); P = 0.04), RMSSD (6.59 (10.17–5.50) vs. 12.20 (13.93–11.28); P = 0.04), and total power (315.8 (506.3–120.7) vs. 771.3 (799.0–643.6); P = 0.04) in stage II as compared to stage I. Resistance at 20 Hz (R20) was found to be positively correlated with SDSD (r = 0.40, P = 0.04), RMSSD (r = 0.40, P = 0.04), and HF (r = 0.41, P = 0.03). CONCLUSION: Amongst the PD population, any changes in the parasympathetic component (responsible for bronchoconstriction) due to the underlying dysautonomia might be reflected as increased airway resistance in the pulmonary system.
The Japanese Society of Internal Medicinefebruari 2022Parkinson
OBJECTIVE: To investigate the efficacy of home-based gait training using the wearable Stride Management Assist (SMA) exoskeleton in people with moderately advanced Parkinson's disease. METHODS: This was a single-center, open-label, parallel, randomized controlled trial. We included outpatients with idiopathic Parkinson's disease who were capable of walking independently with or without walk aids and had Hoehn and Yahr stage 2-4 in the ON state. Patients were randomly assigned (1:1 ratio) to receive either SMA gait training (SMA group) or control gait training (control group). All participants underwent gait training for approximately 30 min. These training sessions were conducted 10 times for 3 months. We measured clinical outcomes at baseline and post-intervention. The between-group difference of distance in the three-minute walk test was the primary outcome. RESULTS: Of the 15 randomly assigned participants, 12 (five in the SMA group) completed this study. The between-group difference was a mean of 13.7 meters (standard error of the mean: 7.8) in the 3-minute walk test (p=0.109). The distance traversed increased from 141.4 m to 154.7 m in the SMA group (p=0.023), whereas there was no marked change in the control group. In addition, although there was a decrease in the physiological cost index from 0.29 to 0.13 in the SMA group (p=0.046), it remained unchanged in the control group. CONCLUSION: These findings suggest that home-based SMA gait training may increase the exercise endurance in people with moderately advanced Parkinson's disease.
People with Parkinson's disease (PD) may find it difficult to identify and access the wide number of services they need and are entitled to along their complex PD journey. As part of the project OPTIM‐PARK – Optimisation of community resources and systems of support to enhance the process of living with Parkinson's Disease, document analysis was developed to create overviews of existing resources and systems of support in Denmark, Norway, Spain and the United Kingdom. Documents on community resources, policies, guidelines and professional recommendations were the main sources of information. They were sought systematically at official websites of the public sector (national and regional levels) and websites of non‐governmental organisations and scientific societies; searches were performed in October 2020 and updated in September 2021. A higher‐level cross‐national content analysis integrated all the country‐specific information. Data‐ and concept‐driven coding frames were developed; trial coding and peer review strengthened face validity and reliability. The analysis led to overviews of: (1) Key aims at patient and societal levels. (2) Key elements in form of professional approaches. (3) Community resources. (4) Legally anchored services. In general, clear descriptions of how to implement care pathways and tools to facilitate delivery were missing in the included documents, and pathways and guidelines did not include referral to general social support, social security support or labour and employment support. The results shed light on the complex support systems and resources and can inspire the planning of more comprehensive care pathways for people with PD and other long‐term conditions.
International audience;
Parkinson's disease (PD) is characterized by motor alterations and associated with dopamine neurotransmitters degeneration, affecting 3 % of the population over 65 years of age. Today, there is no definitive biomarker for an early diagnosis and progression characterization. Recently, oculomotor alterations have shown promising evidence to quantify PD patterns. Current capture and oculomotor setups however require sophisticated protocols, limiting the analysis to coarse measures that poorly exploit alterations and restrict their standard use in clinical environments. Computational based deep learning strategies today bring a robust alternative by discovering in video sequences hidden patterns associated to the disease. However, these approaches are dependent on large training data volumes to cover the variability of patterns of interest. This work introduces a novel strategy that exploits data geometry within a deep Riemannian manifold, withstanding data scarcity and discovering oculomotor PD hidden patterns. First, oculomotor information is encoded as symmetric matrices that capture second order statistics of deep features computed by a convolutional scheme. These symmetric matrices then form an embedded representation, which is decoded by a Riemannian network to discriminate Parkinsonian patients w.r.t a control population. The proposed strategy, evaluated on a fixational eye experiment, proves to be a promising approach to represent PD patterns.
BACKGROUND: Synucleinopathies such as Parkinson ´s disease (PD), Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of misfolded and aggregated α-synuclein. Small aggregates (oligomers) of α-synuclein have been shown to be the most relevant neurotoxic species and are targeted by anle138b, an orally bioavailable small molecule compound which shows strong disease-modifying effects in animal models of synucleinopathies. METHODS: Anle138b was studied in a single-centre, double-blind, randomised, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects. Eligible participants were randomly assigned (1:1 for sentinel subjects and 1:5 for main group) to placebo or anle138b (dose range 50 mg to 300 mg per day), respectively. In addition, the effect of food on the pharmakokinetics of anle138b in healthy subjects was examined in doses of 150 mg per day. Participants were randomized to treatment sequence (fed→fasted) or (fasted→fed). Treatment was administered orally in hard gelatine capsules containing either 10 mg or 30 mg of anle138b or excipient only. The primary endpoints were safety and tolerability, the secondary endpoint was pharmakokinetics. Data from all randomized individuals were evaluated. Clinicaltrials.gov-identifier: NCT04208152. EudraCT-number: 2019-004218-33. FINDINGS: Between December 17(th), 2019 and June 27(th), 2020 196 healthy volunteers were screened and 68 participants were enrolled. Of these, all completed the study per protocol. There were no major protocol deviations. Adverse events in this healthy volunteer trial were mostly mild and all fully recovered or resolved prior to discharge. From baseline to completion of the trial no medically significant individual changes were observed in any system organ class. Already at multiple doses of 200 mg, exposure levels above the fully effective exposure in the MI2 mouse Parkinson model were observed. INTERPRETATION: The favourable safety and PK profile of anle138b in doses resulting in exposures above the fully effective plasma level in a mouse Parkinson model warrant further clinical trials in patients with synucleinopathies. FUNDING: This study was funded by MODAG GmbH and by the Michael J. Fox foundation for Parkinson's Research.
Parkinson disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the midbrain. The majority of early onset forms of Parkinson disease are a result of autosomal mutations in PRKN (parkin RBR E3 ubiquitin protein ligase) and PINK1 (PTEN induced kinase 1), which together regulate the clearance of damaged mitochondria from cells through selective autophagy of mitochondria (mitophagy). In a pair of recent papers, we characterized a secondary mechanism of activation of PRKN by PINK1 that is responsible for approximately a quarter of mitophagy in a cellular model. Our deepening understanding of PRKN-PINK1 signaling affords hope for the development of small molecule therapeutics for the treatment of Parkinson disease.
Measurements of the shear induced by weak gravitational lensing around galaxy cluster lines of sight are the gold standard for calibrating cluster observable-mass relations, thereby enabling a robust and precise inference of cosmological parameters. The weak-lensing mass bias is the systematic offset between the true halo mass and the mass that is inferred from the lensing data using an imperfect model for the halo mass distribution. We study the impact of cosmology on the lensing mass bias to inform future cosmological analyses of galaxy clusters. We create synthetic lensing shear maps for 115,920 projections of clusters with $M_{200\mathrm c}>1.56\times10^{14}\,h^{-1}M_\odot$ in a suite of Magneticum simulations. The simulation boxes are $896\,h^{-1}$Mpc on a side and are set up with 15 different combinations of the cosmological parameters $Ω_\mathrm{m}$, $Ω_\mathrm{b}$, $σ_8$, and $H_0$. Assuming a Navarro-Frenk-White profile, we extract weak-lensing mass measurements and quantify their bias $b_\mathrm{WL}$ with respect to the true halo mass. To investigate the impact of baryonic effects, we perform the analysis on gravity-only simulations and on their full-physics hydrodynamical counterparts. We confirm that assuming a fixed halo concentration or a fixed concentration-mass relation leads to cosmology-dependent changes of the mass bias. We report changes of up to $Δ\ln b_\mathrm{WL}=0.030$ with respect to the bias obtained at the fiducial WMAP7 cosmology. Adopting a model for the concentration that also depends on cosmology absorbs the changes in halo profiles and we recover essentially constant values for the mass bias. Our analysis of hydrodynamical simulations suggests that future, more accurate models will also need to explicitly account for the strength of baryonic effects. ;9 pages, accepted for publication in A&A (v3 is accepted version)
We will address the existence of a new symmetry for an imperfect fluid by introducing local four-velocity gauge-like transformations for the case when there is vorticity. A similar tetrad formulation as to the Einstein-Maxwell spacetimes formalism presented in previous manuscripts will be developed in this manuscript for the imperfect fluids. The four-velocity curl and the metric tensor will be invariant under these kind of four-velocity gauge-like local transformations. While the Einstein-Maxwell stress-energy tensor is locally gauge invariant under electromagnetic gauge transformations, the perfect fluid stress-energy tensor will not be invariant under four-velocity gauge-like local transformations. We will dedicate our analysis to the imperfect fluid stress-energy tensor that will be invariant under local four-velocity gauge-like transformations when additional transformations are introduced for several variables included in the stress-energy tensor itself. We will also pay special attention to the construction of a vorticity stress-energy tensor invariant under local four-velocity gauge-like transformations. An application on neutron stars will be developed in order to show the simplifications brought about by these new tetrads.
Using N-body simulations, we examine the impact of dark matter (DM) halo resolution and gravitational softening on bar formation. We generate isolated disk-halo systems with fixed stellar disk parameters, varying the number of halo particles, softening lengths, and halo concentration to modulate disk stability via the central DM fraction. The effects of DM resolution ($\mratio=1$, 10, and 100) on bar formation are less pronounced in more unstable disks, in which the overall evolutionary path is similar except that the lowest DM resolution model suffers gradual bar weakening. Irrespective of the halo resolution, large softening, $\epsdm$, flattens the central halo density profile within the softening scale, impeding angular momentum transfer to the nascent bar and preventing bar formation in more stable models. In unstable models with $\epsdm=0.96 \, \kpc$, a small bar still emerges due to enhanced initial instability and a larger seed perturbation, yet its strength remains capped at $F_2 \approx 0.3$ owing to unresolved central dynamical friction. Despite the destabilizing effect of reduced central DM fractions, our results indicate that deficient central angular momentum exchange can still suppress bar growth. Furthermore, halo softening influences buckling instability, as larger values ($\epsdm=0.30$ and $0.60 \, \kpc$) inhibit central vertical heating, exacerbating radial-vertical velocity dispersion anisotropies and triggering stronger buckling. ;14 pages, 10 figures, submitted
Dynamical tides can provide us vital information about the properties of neutron star (NS) matter. This is particularly true for g-modes, whose frequency and tidal coupling are highly sensitive to the composition of NSs, especially in their centers, where microphysical models are the least reliable. However, due to their weak coupling to external tidal fields, their effect on the gravitational-wave (GW) signal of binary inspirals can be difficult to observe. Here we show that the detectability of these tides can be significantly enhanced by binary NSs with moderate eccentricities. This is primarily due to higher eccentric harmonics in the early phase of the binary evolution experiencing larger phase shifts, which they transport to the sensitive band of GW detectors. In addition, g-mode tides in eccentric binaries undergo several epicyclic resonances, which also amplify the total phase shift. We demonstrate that these effects increase the detectability of g-mode dynamical tides by more than an order of magnitude for eccentricities of $e_\mathrm{10Hz}\sim0.2-0.4$, making it possible to put robust constraints on g-mode properties using current GW detectors, while all relevant models could potentially be constrained with eccentric binary NSs with Einstein Telescope. ;17 paged, 6 figures
Accurate modeling of gravitational-wave signals is essential for reliable inference of compact-binary source parameters, particularly for future space-based detectors operating in the milli- and deci-Hertz bands. In this work, we systematically investigate the parameter-estimation biases induced by neglecting orbital eccentricity when analyzing eccentric compact-binary coalescences with quasi-circular waveform templates. Focusing on the deci-Hertz detector B-DECIGO and the milli-Hertz detector LISA, we model eccentric inspiral signals using a frequency-domain waveform that incorporates eccentricity-induced higher harmonics and the time-dependent response of spaceborne detectors. We quantify systematic biases in the chirp mass, symmetric mass ratio, and luminosity distance using both Bayesian inference and the Fisher-Cutler-Vallisneri (FCV) formalism, and assess their significance relative to statistical uncertainties. By constructing mock gravitational-wave catalogs spanning stellar-mass and massive black-hole binaries, we identify critical initial eccentricities at which systematic errors become comparable to statistical errors. We find that for B-DECIGO, even very small eccentricities, $e_0\sim 10^{-4}-10^{-3}$ at 0.1 Hz, can lead to significant biases, whereas for LISA such effects typically arise at larger eccentricities, $e_0\sim 10^{-2}-10^{-1}$ at $10^{-4}$ Hz, due to the smaller number of in-band cycles. Comparisons between FCV predictions and full Bayesian analyses demonstrate good agreement within the regime where waveform mismatches remain small, especially when extrinsic parameters are pre-aligned to minimize mismatches. Our results highlight the necessity of incorporating eccentricity in waveform models for future space-based gravitational-wave observations. ;17 pages, 9 figures
The long-term dynamical evolution of asteroid families is governed by the interplay between orbital and rotational evolution driven by thermal forces and collision. We aim to observationally trace the rotational evolution of main-belt asteroid families over Gyr timescales. We analyzed rotational properties of 8739 asteroids with spin period measurements and 3794 asteroids with obliquity determinations across 28 asteroid families spanning ages from 14~Myrs to 3~Gyrs. We introduced a dimensionless timescale that normalizes each asteroid's family age by its classical YORP timescale, enabling direct comparison of rotational states across different evolutionary stages. We examined two key observables: the fraction of slow rotators (periods greater than or equal to 30 hours) and the polarization fraction (the degree to which asteroid spin poles align correctly with their position in the family's V-shape distribution according to the Yarkovsky theory). Evolution of both quantities were fitted to identify characteristic transition timescales. We discovered that the slow-rotator fraction increases steeply with $t$ and saturates at $f_{\rm slow} \simeq 0.25$ around a breakpoint $t_{\rm bp} \simeq 20$. This implies a stochastic YORP timescale $τ_{\rm YORP,stoc} \simeq 10\,τ_{\rm YORP}$ by comparison with rotational evolution models that include tumbling and weakened YORP torques. The polarization fraction reaches a maximum of $\simeq 0.8$ at $t \simeq 16$ and then decays toward the random limit $f_{\rm pol} \rightarrow 0.5$ for $t \gtrsim 20$, indicating an increasing dominance of collisional spin reorientation over time. The rotation properties within different asteroid families offer crucial clues to rotation evolution and can serve as a new dimension for age estimation of asteroid families with more data in the LSST era. ;Accepted for publication in Astronomy & Astrophysics. 8 pages, 5 figures
This paper presents new data and analyses of the AT Pyx system, a disk-hosting young star located in a cometary globule in the Gum Nebula. This radiation-driven structure is an unusual environment for observations of planet formation and differs greatly from the low-mass star-forming regions disks are most commonly observed in. Aided by a collection of visual and spectroscopic data available for this system, this paper aims to infer the possibility of embedded planets existing within the disk and how the system's environment may affect its disk morphology. Using data from the VLT's instruments XSHOOTER, ESPRESSO and - most prominently - SPHERE along with data from ALMA, we make a variety of measurements (geometric, photometric and otherwise) to characterise the observed disk features and attributes such as spiral arms and eccentricity. Mapping of the velocity components is also undertaken using the ALMA gas line data to characterise disk orientation and determine the likelihood that the system is experiencing a late-stage infall event. The disk is found to be eccentric when deprojected. Under the assumption that the formation of a planet is wholly responsible for the primary and secondary spiral arms, we find the mass of such a planet can range between 0.004 and 3 Jupiter masses. Measurement of the velocities associated with nearby globule cloud material returns reasonable velocities for a late-stage infall event. We estimate far-ultraviolet field strength at AT Pyx's location to be low in comparison to other surveyed disks. We also find that AT Pyx is possibly a binary system. AT Pyx is the first disk within a cometary globule to be spatially resolved, and is now the first such disk to be investigated to this extent. The work of this paper could potentially be a first step into the further study of disks in the moderate-FUV environment of the Gum Nebula and its globules. ;17 pages, 21 figures
The Central Molecular Zone (CMZ) of the Milky Way is the way station that primarily controls how much gas flows from the disk of the Galaxy towards the central nucleus. While this region is well documented to have extreme gas properties that clearly distinguish it from the rest of the Galaxy, the properties of the bulk molecular gas at high angular resolution are relatively unexplored. Band 3 data from the ALMA (Atacama Large Millimeter/Submillimeter Array) large program ACES (ALMA CMZ Exploration Survey) reveal the highly filamentary nature of CMZ molecular gas at high resolution (3" or 0.1pc) across the entire CMZ. Visual inspection of these data suggests that there are at least two general classes of elongated structures, which we identify as: i) large-scale (10 pc) filamentary structures (LFs) and ii) a ubiquitous population of small-scale (about 1 pc) filamentary structures (SFs). We present detailed morphological and kinematic properties towards three structures in each category, as well as their association with magnetic fields and the correlation of HNCO 4(0,4)-3(0,3) with other molecular species. Our investigation reveals that these structures are largely coherent in position-position-velocity space. The alignment with the magnetic field structure is mixed, with some parallel, some perpendicular, and some intermediate alignments. We find that LFs likely trace pieces of contiguous CMZ orbital structures and are a manifestation of global CMZ dynamics. The second class, SFs, are pervasive and may be the result of complicated turbulence and shearing dynamics in the CMZ gas flows, as seen in numerical simulations. ;Accepted to MNRAS
The origin of the soft X-ray excess below 2 keV in active galactic nuclei (AGNs) remains debated, with relativistic reflection from the inner accretion disk and warm Comptonization in an optically thick corona being the leading explanations. We investigate the timing and spectral properties of the Seyfert galaxy Mrk 110 using six XMM-Newton observations. A frequency-dependent lag analysis in the 7-9 $\times 10^{-5}$ Hz range reveals a soft X-ray lag of 889-3000s in the combined 2019 data, detected with a significance of 80%. The cross-correlation function analysis, supported by simulations, also detects lags of similar nature. Spectral modeling performed by adopting both proposed black hole masses in the literature for Mrk 110 confirms the presence of a warm corona in all observations, along with a weak relativistic reflection component and the reflection fraction remains low (Rf < 1). Interpreting the measured soft lag in terms of light travel time implies an emission radius 4.5 Rg for a supermassive black hole mass of $M = 1.4 \times 10^8$ solar mass , favoring a reflection scenario. However, if a lower mass of $M = 2 \times 10^7$ solar mass is adopted, the inferred radius increases, and both relativistic reflection and warm Comptonization can plausibly contribute to the observed soft lag. The warm corona radius appears larger in the high accretion state and smaller in a lower accretion state, although no trend can be established. The persistently low reflection fraction suggests an outflowing inner corona in Mrk 110, consistent with the recent detection of jet activity in this source. ;16 pages, 8 figures, 2 tables, Accepted in PASJ
We present a reanalysis of the water maser system in NGC 4258 to reassess its geometric distance, commonly reported as approximately 7.6 Mpc with percent-level accuracy, a key anchor in extragalactic distance ladder calibrations and recent determinations of the Hubble constant. We introduce a method that relies exclusively on tracking individual maser components, rather than assuming a single averaged trajectory as in previous works, thereby avoiding arbitrary data averaging that can bias interpretations of the disk's geometry and dynamics. This approach requires spatially resolved individual maser components; consequently, the majority of observational epochs were excluded, as they lack sufficient spatial resolution to localize the maser position. We track individual maser components across multiple epochs and introduce an efficient marginalization method over nuisance parameters (angular radius and azimuth of each maser), reducing the number of free parameters from hundreds to 14. Our analysis reveals that the current observational cadence is insufficient to reliably track the individual masers, which our method relies on, given their intrinsic variability. Across a range of maser selections and model configurations, inferred distances span approximately between 6.7 to 8.1 Mpc, demonstrating significant sensitivity to how our method selects individual masers. Even visually and statistically robust fits can differ by several standard deviations, reflecting ambiguity in component identification across sparsely sampled epochs. We evaluate the impact of observational cadence on tracking fidelity and distance precision, and show that high-cadence monitoring is needed for our method to track individual masers and produce a robust anchor for cosmology.
The angular, harmonic cross-correlation between gravitational wave (GW) events and galaxy catalogues contains rich information on the large-scale structure and the origin of compact binary mergers. In this work, we study how uncertainties in the binary formation channel affect the predicted cross-correlation signal for both current-generation and next-generation networks of detectors. We generate five mock GW catalogues for which we vary the progenitor-to-remnant mass-transfer function and the time-delay probability distribution between progenitor and remnant. We then cross-correlate these catalogues with galaxy samples modelled on the 2MASS Photometric Redshift catalogue (2MPZ) and the Gaia-unWISE quasar catalogue (Quaia). We find that the mass-transfer function has negligible effect on the cross-correlation signal, with differences remaining within redshift uncertainties. In contrast, the time-delay distribution dramatically affects the redshift distribution of the GW events and, with it, the cross-correlation signal, particularly for shallow galaxy catalogues. In particular, current-generation facilities can achieve significant detections only for the longest time delays when cross-correlated with 2MPZ, whilst all cross-correlations with the deeper Quaia catalogue are marginally detectable or consistent with zero. Our exploratory results thus demonstrate that forecasts on cosmological or astrophysical parameters derived from GW-galaxy cross-correlations are, as expected, strongly sensitive to the assumed binary formation history. ;Matches the version published in the Open Journal of Astrophysics
Accurately measuring stellar ages and internal structures is challenging, but the inclusion of asteroseismic observables can substantially improve precision. However, the curse of dimensionality means this comes at a high computational cost when using standard interpolation methods across grids of stellar models. Furthermore, without a rigorous treatment of random uncertainties in grid-based modelling, it is not possible to address systematic errors in stellar models. We present PITCHFORK -- a multilayer perceptron neural network with a branching architecture capable of rapid emulation of both classical stellar observables and individual asteroseismic oscillation modes of solar-like oscillators. PITCHFORK can predict the classical observables $T_{\text{eff}}$, $L$, and $\left[\mathrm{Fe}/\mathrm{H}\right]$ with precisions of $5.88\,\text{K}$, $0.014\,\text{L}_{\odot}$, and $0.001\,\text{dex}$, respectively, and can predict 35 individual radial mode frequencies with a uniform precision of $0.02$ per cent. PITCHFORK is coupled to a vectorised Bayesian inference pipeline to return well-sampled and fully marginalised posterior distributions. We validate our rigorous treatment of the random uncertainties -- including the asteroseismic surface effect -- in an extensive hare-and-hounds exercise. We also demonstrate our ability to infer the stellar properties of benchmark stars -- namely, the Sun and the binary stars 16 Cygni A and B. This work demonstrates a computationally scalable and statistically robust framework for stellar parameter inference of solar-like oscillators using individual asteroseismic mode frequencies. This provides a foundation for the treatment of systematics in preparation for the imminent abundance of asteroseismic data from future missions. ;20 pages, 17 figures, 11 tables. Accepted for publication in MNRAS
We present the discovery of radio emission from the Be/X-ray binary A0538-66 with the Australian Square Kilometre Array Pathfinder (ASKAP), and results from a subsequent weekly monitoring campaign with the MeerKAT radio telescope. A0538-66, located in the Large Magellanic Cloud, hosts a neutron star with a short spin period ($P \approx 69$ ms) in a highly eccentric $\approx16.6$-day orbit. Its rare episodes of super-Eddington accretion, rapid optical and X-ray flares, and other peculiar properties make it an interesting system among high-mass X-ray binaries. Our MeerKAT data reveal that it is also one of the most radio-luminous neutron star X-ray binaries observed to date, reaching $\approx 3 \times 10^{22}~\text{erg}~\text{s}^{-1} \text{Hz}^{-1}$, with radio emission that appears to be orbitally modulated. We consider several possible mechanisms for the radio emission, and place A0538-66 in context by comparing it to similar systems. ;Accepted for publication in MNRAS Letters
Observations indicate two nested pairs of extended bipolar bubbles emanating from the Milky-Way center - the $|b|\sim80^\circ$ latitude eROSITA bubbles (RBs), encompassing the smaller, $|b|\sim 50^{\circ}$ Fermi bubbles (FBs) - and classify the edges of both bubble pairs as strong forward shocks. Identifying each bubble pair as driven by a distinct, collimated outburst, we evolve these bubbles and constrain their origin using a stratified 1D model verified by a suite of 2D and 3D hydrodynamic simulations which reproduce X-ray observations. While the RBs are at the onset of slowdown, the FBs are still expanding ballistically into the RB-shocked medium. Observational constraints indicate that both RB and FB outbursts had (up to factor $\sim2$-$4$ uncertainties) $\sim4^\circ$ half-opening angles and $\sim 2000$ km s$^{-1}$ velocities $100$ pc from their base, carrying $\sim10^{56}$ erg. The FBs and RBs could thus arise from identical outbursts separated by $\sim10$ Myr; their longitudinal asymmetry favors an eastern ambient-density gradient over western wind suggestions. ;Added density contrast and revised (Primakoff-based) energy estimates
We present a spatially resolved spectroscopic analysis of the Helix Nebula (NGC 7293) using data from the SDSS-V Local Volume Mapper (LVM), by applying the recently developed LVM Data Analysis Pipeline (LVM-DAP). Covering the full optical range (3600-9800 Å) over a contiguous ~ 0.5 degree field, the LVM data provide the first hexagonally sampled, wide-field emission-line maps of all major ionic species in this archetypal planetary nebula. The resulting flux, kinematic, and line-ratio maps reveal the well-known ionization stratification of the nebula, from the compact He++ core to the bright [O III] ring and the extended low-ionization envelope, enabling a detailed comparison with classical aperture spectroscopy. Owing to the sensitivity and uniform spatial sampling of the LVM, numerous faint auroral and diagnostic lines are detected across the nebula, including [O III] 4363, [N II] 5755, and He I lines, allowing precise measurements of weak-line morphology. The derived radial trends confirm the remarkably low dust content and the overall homogeneity of electron temperature and density across the main ring. Ionized-gas kinematics traced by Hα further support the scenario of a slowly expanding, limb-brightened shell consistent with previous studies. This work demonstrates the diagnostic power of LVM spectroscopy for extended nebulae and highlights its capability to recover both global and spatially resolved physical conditions across complex ionized structures. ;20 pages, 12 figures, accepted for publishing in RMxA&A
The near-Earth asteroid Kamo`oalewa, a quasi-satellite of the Earth and the target for sample return by China's Tianwen-2 mission, exhibits distinctive spectral characteristics. This study re-analyzes the visible and near-infrared reflectance spectrum of Kamo`oalewa published by B. N. L. Sharkey et al. (2021), obtained using the Large Binocular Telescope, to infer its mineral composition and space weathering characteristics. Spectral similarity analysis is performed by comparing the spectrum of Kamo`oalewa to the mean spectra of various types in the Bus-DeMeo taxonomy to make a preliminary constraint on the combined characteristics of surface mineralogy and space weathering effects. To further characterize the mineral composition, a detailed analysis of the 1 μm band center is conducted based on spectral data below 1.25 μm that have higher signal-to-noise ratios. Empirical models for normalized spectra are developed to estimate the Is/FeO content. The results suggest that asteroid Kamo`oalewa has higher olivine abundance than that of typical S-type asteroids and the Moon, exhibiting an immature to submature degree of space weathering. These findings enhance our understanding of the evolution of similar quasi-satellites and provide important implication for the future exploration of Tianwen-2 mission.
Context. Data-constrained models incorporate observed photospheric magnetic fields. However, due to the lack of magnetic field information in the rest of the solar atmosphere, models rely on extrapolations that, in most cases, neglect the Lorentz force. Nevertheless, this force is present in the lower atmosphere and may play a key role in destabilising the equilibrium configuration and triggering eruptions. Aims. This study seeks to understand and reproduce a solar eruption SOL2014-12-18T21:41 that occurred in active region NOAA 12241, preceded by an M6.9 flare, and to investigate the impact of relaxing the initial force-free assumption. Methods. The resistive and compressible magnetohydrodynamic simulation is initiated using a non-force-free magnetic field extrapolated from a photospheric vector magnetogram taken minutes before the flare. The simulation includes a stratified atmosphere and non-ideal effects such as thermal conduction and radiative cooling. Results. A flux rope forms and rises in the simulation, carrying away dense material from the lower solar atmosphere. Its formation results from the non-zero Lorentz force acting on the initial sheared arcade, without assuming pre-existing flux ropes or photospheric driving motions. The flux rope is then deflected toward regions of low magnetic pressure, escaping the domain at 350 km/s with approximately constant acceleration. Conclusions. A robust numerical framework for modelling flaring active regions was applied to the eruption of NOAA AR12241 as a case study, assuming a realistic non-force-free magnetic field near the flare onset. It exemplifies how an initial Lorentz force imbalance can successfully trigger a flux rope formation that later escapes the simulation domain. It also enables comparison with real observations through the addition of a stratified atmosphere spanning from the photosphere to the corona. ;17 pages, 14 figures
Dark matter (DM) halos in $Λ$ Cold DM cosmological simulations are triaxial. Most exhibit figure rotation. We study 40 isolated halos with stellar disks from the TNG50 simulation suite across $\sim 4$~Gyr to understand whether and how a triaxial halo's tumbling and orientation relative to the disk can drive warps. We measure a warp angle $ψ$ and find even our isolated disks are all at least slightly warped, with each galaxy's maximum $ψ> 1.8^{\circ}$. We perform a modified cross-correlation analysis between $ψ$ and the figure rotation pattern speed, as well as the misalignment between the disk spin axis and (a) the figure rotation axis, (b) the halo minor axis, and (c) the gas angular momentum axis. We use snapshots spanning a lookback time $t_{lb} ~4$ Gyr with 25 linearly-spaced lags from $ 0 - 2.33$ Gyr. We do not find evidence for a consistent lag between the onset of a warp and any of the aforementioned factors on the population level. However, we find significant correlations between individual time-series at various lags. These maximum correlation coefficients were significantly offset from random chance at the population level, suggesting that several of these factors do correlate with disk warping in specific situations. By examining four case studies whose maximum correlation coefficients were significantly higher than random chance, we establish clear qualitative relationships between these factors and warps. While a non-warped galaxy typically shows minimal halo tilt and figure rotation, warped galaxies can have strong/weak tilts and/or strong/weak figure rotation.
Keywords: Disk galaxies(391), Galaxy dynamics(591), Hydrodynamical simulations(767), Galaxy DM halos(1880) ;15 pages, 11 figures, to be submitted to Open Journal of Astrophysics
DMPP is a radial-velocity survey that aims to detect planets around stars exhibiting anomalous activity signatures, consistent with the presence of close-in evaporating planets. Here, we report the discovery of 7 new planetary signals in 5 different systems: DMPP-2c & d, HD67200/DMPP-6b & c, HD118006/DMPP-7b, HD191122/DMPP-8b, and HD200133/DMPP-9b. We update the orbital parameters of the DMPP-1, DMPP-2, and DMPP-3 systems, along with those of the planetary systems orbiting HD181433, HD39194, and HD89839. We derive detection limits for all 24 targets in our sample with adequate observational coverage, and test the DMPP hypothesis by calculating the occurrence rates for planets in this configuration. We find that the occurrence rates of planets in our sample with orbital periods shorter than $50~\mathrm{d}$ and masses in the range $3$-$10$ M$_\oplus$ are $83.0^{+27.1}_{-24.4}\%$, for $10$-$30$ M$_\oplus$ are $27.0^{+15.0}_{-11.2}\%$, and for $30$-$100$ M$_\oplus$ are $13.9^{+11.8}_{-7.5}\%$. This is significantly higher than the occurrence rates reported by other radial velocity surveys, providing strong support for the DMPP hypothesis. ;16 pages, 10 figures, accepted for publication in MNRAS. Appendix: 20 pages, 47 figures
The reionization process is driven by ionizing photons from dwarf galaxies in halos with virial temperature $T_{\rm vir} \gtrsim 10^4$ K, while minihalos whose $T_{\rm vir}\lesssim 10^4$ K consume ionizing photons and have negative contributions to reionization. Since ionizing sources and minihalos have different clustering characteristics, not only the reionization history, but also the morphology of the ionization field, is sensitive to the small-scale power spectrum. If the power spectrum at small scales is enhanced compared with the standard six-parameter $Λ$CDM model, then both the sources and sinks of ionizing photons would be boosted and the net impact depends on the competition between them. Therefore, the 21 cm signal that can probe the morphology of the ionization field will be a useful tool for detecting the small-scale power spectrum. Using the power spectrum proposed by Cielo et al. (2025) (C25) as a demonstration, we investigate the influence of small-scale power spectrum enhancement on the ionization field and the 21 cm signal. We find that for the C25 model, even under the constraints of observed UV luminosity functions for high-$z$ galaxies and reionization history, the 21~cm power spectrum and the bubble size distribution could be still significantly different from the regular $Λ$CDM model. The upcoming SKA-low AA* telescope, and a further imaging telescope, have the potential to detect the small-scale power spectrum more deeply. ;18 pages, 8 figures. Accepted for publication in ApJ
The accretion process in young stellar objects (YSOs) is fundamental to the formation of stellar systems. This process governs the star's mass assembly, the transfer of angular momentum, and the shaping of the protoplanetary disc, thereby influencing planet formation. For classical T Tauri stars (cTTSs), which are low-mass YSOs, accretion is a well-understood process. Their strong, dipolar magnetic field truncates the disc at a few stellar radii. Material is then channelled along these magnetic field lines, creating accretion funnel flows that fall onto the star's surface. However, this paradigm, known as magnetospheric accretion, is limited to isolated stars. The accretion process in multiple systems has not yet been fully understood. This work is part of a series of studies designed to build a framework to understand the accretion process in multiple star systems. The specific goal here is to determine how the magnetospheric accretion model can be used to describe DF Tau, a binary system where only the primary star is accreting material. To investigate how accretion occurs in a system where a single star is orbited by a non-accreting stellar companion, we used a time series of high-resolution spectropolarimetric observations from the ESPaDOnS instrument. This allowed us to study the accretion-related emission line variability, the veiling, and the magnetic field topology of the primary star in the system. Our research concludes that the primary star of the DF Tau system undergoes typical magnetospheric accretion. This process is driven by a strong dipolar magnetic field, which funnels accreting material onto the stellar surface, creating an accretion shock. We also identified a significant difference in the magnetic topology of the two stars querying the influence of accretion of the evolution of the magnetic field, or capture of the secondary star. ;11 pages, 13 figures. Accepted in A&A
The current census of planetary systems displays a wide range of architectures. Extending earlier work, this paper investigates the correlation between our classification framework for these architectures and host stellar properties. Specifically, we explore how planetary system properties depend on stellar mass and stellar metallicity. This work confirms previously detected trends that jovian planets are less prevalent for low-mass and low-metallicity stars. We also find new, but expected trends such as that the total mass in planets increases with stellar mass, and that observed planetary system masses show an upper limit that is roughly consistent with expectations from the stability of circumstellar disks. We tentatively identify potential unique trends in the host stars of super-puffs and hot jupiters and a possible subdivision of the class of hot jupiter systems. In general, we find that system architectures are not overly dependent on host star properties. ;17 pages, 6 figures, 1 table, accepted by AJ
In this study, we present a comprehensive analysis of the structural, astrophysical, and dynamical properties of eight open clusters: NGC 559, NGC 1817, NGC 2141, NGC 7245, Ruprecht 15, Ruprecht 137, Ruprecht 142, and Ruprecht 169, using precise astrometric and photometric data from Gaia Data Release 3. By fitting the King model to the radial density profiles, we determined the structural parameters of the clusters, including core and limiting radii, which were found to range from 3.07 to 16.21 arcmin and from 9.97 to 25.97 arcmin, respectively. Fundamental astrophysical parameters were derived by fitting PARSEC isochrones to the colour-magnitude diagrams. The results show that the clusters have logarithmic ages between 7.95 and 9.34, metallicities in the range 0.007 to 0.015, and heliocentric distances between 1640 and 5203 pc. The total stellar masses of the clusters were estimated to lie between 257 and 1916 solar masses. For most of the clusters, the mass function slopes are consistent with the Salpeter initial mass function. Our dynamical analysis indicates that all clusters, except Ruprecht 15, are dynamically relaxed. In addition, the spatial distribution and the bimodal structure observed in the radial density profile of NGC 7245 provide strong evidence that this object is a binary cluster candidate. Finally, kinematic analysis and orbit integrations demonstrate that all clusters exhibit dynamical properties fully consistent with membership in the Galactic thin disc. ;19 pages, including 15 figures and 8 tables, accepted for publication in the Journal of Astrophysics and Astronomy
Temporal asymmetry in the flux variability of active galactic nuclei (AGNs) offers key insights into the physical mechanisms driving AGN variability. In this study, we investigated the variability of the torus by analyzing temporal asymmetry in the mid-infrared (MIR) continuum. We compared ensemble structure functions between the brightening and dimming phases for AGNs at $0.15<z<0.4$, using monitoring data in the optical from the Zwicky Transient Facility and in the MIR from the Near-Earth Object Wide-field Infrared Survey Explorer. We found that AGNs with bluer optical-to-MIR colors exhibit positive temporal asymmetry in the MIR, indicating that their variability amplitude is larger when brightening. Conversely, those with redder colors show negative asymmetry, exhibiting larger variability amplitude when decaying. However, there is no significant temporal asymmetry in the $g$-band variability driven by the accretion disk, suggesting that the temporal asymmetry in the MIR continuum primarily originates from intrinsic processes in the torus instead of the reflection of the ultraviolet-optical variability from the accretion disk. Analysis of the composite light curves revealed that AGNs with bluer optical-to-MIR colors tend to brighten gradually in the MIR, leading to the observed temporal asymmetry. This finding suggests that hot-dust-rich AGNs evolve with a gradual decline in hot dust emission, while hot-dust-poor AGNs are associated with a steady increase. ;Accepted for publication in A&A
Since the discovery of superhumps in 1974, these photometric modulations have provided a crucial observational window into disk instabilities in cataclysmic variable stars, particularly the tidal instability associated with the 3:1 resonance. Over the past few decades, extensive time-resolved photometry has revealed a rich diversity of superhump-related phenomena, including delayed superhump development, early superhumps in WZ Sge-type dwarf novae, systematic stage A-B-C evolution, negative superhumps, and superhumps observed in related systems such as intermediate polars and AM CVn stars. In this invited review, we summarize key observational advances since the establishment of the thermal-tidal instability framework, discuss their theoretical interpretations within the disk instability model, and highlight remaining open problems. These developments have been driven by coordinated networks of amateur observers, wide-field robotic surveys, and continuous high-precision space-based photometry from Kepler and TESS. Together, they demonstrate that superhumps remain a powerful probe of disk dynamics, binary parameters, and the interplay between thermal, tidal, and geometric effects in accretion disks. ;Invited talk presented at the 87th Fujihara Seminar: The 50th Anniversary Workshop of the Disk Instability Model in Compact Binary Stars, held on 22-26 September 2025 in Tomakomai, Japan. To be published in the Proceedings of Science https://pos.sissa.it/493/
Background Hyperthermia (and associated health and performance implications) can be a significant problem for athletes and teams involved in intermittent sports. Quantifying the highest thermal strain (i.e. peak core body temperature [peak T _c]) from a range of intermittent sports would enhance our understanding of the thermal requirements of sport and assist in making informed decisions about training or match-day interventions to reduce thermally induced harm and/or performance decline. Objective The objective of this systematic review was to synthesise and characterise the available thermal strain data collected in competition from intermittent sport athletes. Methods A systematic literature search was performed on Web of Science, MEDLINE, and SPORTDiscus to identify studies up to 17 April 2023. Electronic databases were searched using a text mining method to provide a partially automated and systematic search strategy retrieving terms related to core body temperature measurement and intermittent sport. Records were eligible if they included core body temperature measurement during competition, without experimental intervention that may influence thermal strain (e.g. cooling), in healthy, adult, intermittent sport athletes at any level. Due to the lack of an available tool that specifically includes potential sources of bias for physiological responses in descriptive studies, a methodological evaluation checklist was developed and used to document important methodological considerations. Data were not meta-analysed given the methodological heterogeneity between studies and therefore were presented descriptively in tabular and graphical format. Results A total of 34 studies were selected for review; 27 were observational, 5 were experimental (2 parallel group and 3 repeated measures randomised controlled trials), and 2 were quasi-experimental (1 parallel group and 1 repeated measures non-randomised controlled trial). Across all included studies, 386 participants (plus participant numbers not reported in two studies) were recruited after accounting for shared data between studies. A total of 4 studies (~ 12%) found no evidence of hyperthermia, 24 (~ 71%) found evidence of ‘modest’ hyperthermia (peak T _c between 38.5 and 39.5 °C), and 6 (~ 18%) found evidence of ‘marked’ hyperthermia (peak T _c of 39.5 °C or greater) during intermittent sports competition. Conclusions Practitioners and coaches supporting intermittent sport athletes are justified to seek interventions aimed at mitigating the high heat strain observed in competition. More research is required to determine the most effective interventions for this population that are practically viable in intermittent sports settings (often constrained by many competing demands). Greater statistical power and homogeneity among studies are required to quantify the independent effects of wet bulb globe temperature, competition duration, sport and level of competition on peak T _c, all of which are likely to be key modulators of the thermal strain experienced by competing athletes. Registration This systematic review was registered on the Open Science Framework ( https://osf.io/vfb4s ; https://doi.org/10.17605/OSF.IO/EZYFA , 4 January 2021).
OBJECTIVES: Femoroacetabular impingement (FAI) is a condition that affects young athletes who participate in high impact activities. Patients often experience gradually worsening hip and/or groin pain, and thus have months to years of symptoms before choosing to undergo hip arthroscopy to correct the bony and soft tissue pathology. Patients undergoing surgery usually report that they are pursuing surgery for pain relief and expect to be able to return to their previous level of activity. An athlete’s ability to return to their previous level of sport depends not only on their physical ability, but their psychological ability as well. Because patients often experience months to years of symptoms before surgery, this group is particularly vulnerable to kinesiophobia, pain catastrophizing, and other psychological factors that may influence recovery and overall return to physical activity. The Hip-Return to Sport after Injury (Hip-RSI) scale is a validated tool used to assess an athlete’s psychological readiness to return to sport and specifically looks at emotions, confidence, and risk appraisal in relation to a patient’s perception of hip function and is positively associated with return to sport (RTS). Recovery and RTS is not a linear process, as an athlete’s psychological readiness likely changes over time. However, this potential change in readiness throughout the recovery process has not yet been described. This study primarily aimed to describe the change in Hip-RSI in patients who undergo hip arthroscopy for FAI. A secondary objective was to examine the relationship between Hip- RSI and patient satisfaction with hip function, patient expectations of recovery timeline, patient expectations to return to sport, and history of anxiety/depression. METHODS: A single surgeon’s prospectively collected Hip Database was used to obtain a comprehensive patient list. This study was conducted under the IRB approval of the Hip Database. Patients were included if they underwent a hip arthroscopy and completed the Hip-Return to Sport after Injury questionnaire (Hip-RSI) at minimum one of four postoperative timepoints: 3 months, 6 months, 1 year and 2 years. One hundred and fifty patients had a completed Hip-RSI score at at least one of these timepoints. Additional variables included BMI, diagnosis codes, patient satisfaction and expectations, history or presence of anxiety/depression, and other patient reported outcomes (PROs), including iHOT-12, HOS-ADL and HOS-SSS. There were four patient satisfaction and expectations questions patients answered in their questionnaire, three of which were yes/no questions, and one was a slider scale from 0-10 that pertained to hip function satisfaction. A chart review was performed to determine the BMI, diagnosis codes, and history/presence of history of anxiety/depression for patients who did not have this data in the Hip Database. A Mann Whitney U test and Pearson correlation tests were performed to determine averages and correlations between Hip-RSI and the history/presence of anxiety/depression and satisfaction and expectations. RESULTS: The average age of this population was 30 ± 13 years, with an average BMI of 25.8 ± 5.7, and an average duration of symptoms for 24.7± 22.6 months. Hip-RSI scores were determined for each of the four timepoints, which showed that there was an increase in Hip-RSI scores from 3 months to 1 year postoperatively, and an almost a 10-point decrease at 2 years postoperatively, as shown in Table 1. There was no significant difference in Hip-RSI in patients with a history of anxiety and/or depression at any of the four timepoints. There were no significant correlations between Hip-RSI and any other variables or outcome measures at two years postoperatively. At 3 months, 6 months, and 12 months postoperatively, Hip-RSI had a strong, positive correlation with a patient’s self-reported satisfaction level of their current hip function (p<0.001). The averages of Hip-RSI and this patient satisfaction question are shown in Table 2. Two other patient expectation questions were also positively correlated with Hip-RSI at various timepoints, as shown in Figure 1. Hip-RSI had a strong correlation with three other PROs: iHOT-12, HOS-ADL, and HOS-SSS at all three timepoints (p<0.001). The only exceptions were two moderative, positive correlations between Hip-RSI and HOS-ADL, as well as between Hip-RSI and HOS-SSS, at 3 months postoperatively. CONCLUSIONS: Based on our findings, a patient’s psychological readiness for return to sport changes over time, with an increase in readiness up to 1 year postoperatively, and a decrease in readiness at two years postoperatively. While history or presence of anxiety and/or depression does not influence Hip-RSI scores, patient satisfaction and expectations after a hip arthroscopy appears to influence it, however further investigation is required.
BACKGROUND: Preseason performance on the lower extremity functional test (LEFT), a timed series of agility drills, has been previously reported to be associated with future risk of lower quadrant (LQ = low back and lower extremities) injury in Division III (D III) athletes. Validation studies are warranted to confirm or refute initial findings. HYPOTHESIS/PURPOSE: The primary purpose of this study was to examine the ability of the LEFT to discriminate injury occurrence in D III athletes, in order to validate or refute prior findings. It was hypothesized that female and male D III athletes slower at completion of the LEFT would be at a greater risk for a non-contact time-loss injury during sport. Secondary purposes of this study are to report other potential risk factors based on athlete demographics and to present normative LEFT data based on sport participation. METHODS: Two hundred and six (females = 104; males = 102) D III collegiate athletes formed a validation sample. Athletes in the validation sample completed a demographic questionnaire and performed the LEFT at the start of their sports preseason. Athletic trainers tracked non-contact time-loss LQ injuries during the season. A secondary analysis of risk based on preseason LEFT performance was conducted for a sample (n = 395) that consisted of subjects in the validation sample (n = 206) as well as athletes from a prior LEFT related study (n = 189). STUDY DESIGN: Prospective cohort RESULTS: Male athletes in the validation sample completed the LEFT [98.6 ( ± 8.1) seconds] significantly faster than female athletes [113.1 ( ± 10.4) seconds]. Male athletes, by sport, also completed the LEFT significantly faster than their female counterparts who participated in the same sport. There was no association between preseason LEFT performance and subsequent injury, by sex, in either the validation sample or the combined sample. Females who reported starting primary sport participation by age 10 were two times (OR = 2.4, 95% CI: 1.2, 4.9; p = 0.01) more likely to experience a non-contact time-loss LQ injury than female athletes who started their primary sport at age 11 or older. Males who reported greater than three hours per week of plyometric training during the six-week period prior to the start of the preseason were four times more likely (OR = 4.0, 95% CI: 1.1, 14.0; p = 0.03) to experience a foot or ankle injury than male athletes who performed three or less hours per week. CONCLUSIONS: The LEFT could not be validated as a preseason performance measure to predict future sports injury risk. The data presented in this study may aid rehabilitation professionals when evaluating an injured athlete's ability to return to sport by comparing their LEFT score to population norms. LEVEL OF EVIDENCE: 2
Background This study aimed to assess whether moderate-to-vigorous physical activity (MVPA), sport and exercise as a proxy measure of muscle and bone strengthening activity, sedentary behaviour, and sleep were associated with total-body-less-head (TBLH) bone mineral content (BMC) and TBLH lean mass cross-sectionally and longitudinally from age 6 to 9 years and age 9 to 11 years to age 15 to 17 years. Methods We used longitudinal data from a population sample of Finnish children from the Physical Activity and Nutrition in Children study (age 6 to 9 years: n = 478, 229 females; age 9 to 11 years: n = 384, 197 females; age 15 to 17 years: n = 222, 103 females). Linear regression analysed the cross-sectional and longitudinal associations between accelerometer-assessed MVPA, sedentary time and sleep, and questionnaire-assessed sport and exercise participation and screen time with dual-energy X-ray absorptiometry-assessed TBLH BMC and lean mass. Results In females, MVPA at age 6 to 9 years was positively associated with TBLH BMC at age 15 to 17 years (β = 0.008, p = 0.010). Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (β = 0.020, p = 0.002) and lean mass (β = 0.343, p = 0.040) at age 15 to 17 years. MVPA at age 9 to 11 years was positively associated with TBLH lean mass (β = 0.272, p = 0.004) at age 15 to 17 years. In males, sleep at age 6 to 9 years was positively associated with TBLH lean mass (β = 0.382, p = 0.003) at age 15 to 17 years. Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (β = 0.027, p = 0.012) and lean mass (β = 0.721, p < 0.001) at age 15 to 17 years. Conclusions Promoting engagement in the 24-hour movement behaviours in childhood, particularly sport and exercise to strengthen muscle and bone, is important in supporting bone and lean mass development in adolescence. Trial registration NCT01803776; first trial registration date: 04/03/2013.
Background The aim of this study is to investigate the influence of a judoka's psychological readiness in relation to his ability to return to sport. At the present time, the relationship between physical and psychological readiness to return to sport has not been adequately elucidated. Methods This is a cross-sectional study. An online survey was distributed via social networks and the German Judo Association collecting data from competitive and recreational judo athletes. The survey collected data on participants’ characteristics, history of injury, and psychological readiness to return to sport after injury as determined by either the Anterior Cruciate Ligament-Return to Sport after Injury Scale, the Shoulder Instability-Return to Sport after Injury Scale, or a modified version of the Return to Sport after Injury Scale depending on the respective type of injury. Results The study included 383 judo athletes (272 competitive judo athletes and 112 recreational judo athletes). Regardless of injury location, athletes who achieved return to sports ( M = 70.67; SD = 16.47) had higher RSI scores than athletes that did not return to sports ( M = 53.88; SD = 19.12; p < 0.0001). Male athletes ( M = 65.60; SD = 19.34) did show significantly higher RSI scores than female athletes ( M = 60.45; SD = 19.46). The RSI score differed for different time loss categories, F (7, 375) = 11.309 , p < 0.001, η ^2 = .174 with decreasing RSI scores for longer time loss and lowest RSI scores in athletes, who never returned to sports. RSI scores of athletes with knee injuries differed from athletes with other injury locations (10.23, 95% CI [4.08, 16.38]). After adjusting for time loss due to injury, competitive athletes had higher RSI scores than competitive athletes ( F (1, 382) = 7.250, p < 0.001, partial η ^2 = .02). Conservatively treated athletes ( M = 66.58; SD = 18.54) had higher RSI scores than surgically treated athletes ( M = 59.05; SD = 20.01; p < 0.05). Conclusion Based on the data of this study, type of injury, sport level, treatment method, and gender appear to influence psychological readiness on judoka and their ability to return to sport. The multiple factors that influence a judoka and their ability to return to sport argue for individualized treatment of judoka and their psychological state after injury in the return to sport process.
OBJECTIVES: Young athletes that play a contact sport are susceptible to anterior glenohumeral instability due to high-velocity impacts and repetitive dislocations. Few studies have examined return-to play and patient outcomes following Latarjet procedure in this patient population. The objective of this study was to investigate postoperative return to contact sports in athletes undergoing the Latarjet procedure for shoulder instability. METHODS: 67 consecutive contact athletes (71 shoulders), age ≤35, that underwent Latarjet procedure for recurrent shoulder instability between 1/1/2018 and 3/31/2021 were retrospectively identified. Demographic information, medical history, surgical history, number of dislocations prior to surgery, and post-operative complications up to 6 months after surgery were reviewed. 42 patients were interviewed with minimum follow-up of 12 months. Outcomes evaluated include return to play, competition level, patient satisfaction, and patient-reported outcomes including American Shoulder and Elbow Surgeons (ASES) Score, Disabilities of the Arm, Shoulder, and Hand (DASH) Score, and Visual Analog Scale (VAS). RESULTS: Mean age at time of surgery for the total cohort was 19.7 years. 19/67 (28.3%) of patients had prior shoulder surgery, most commonly arthroscopic stabilization. On average, patients had 24.2 frank dislocations (SD 39.1) prior to undergoing Latarjet procedure. 8/67 (11.9%) of patients experienced unresolved pain or stiffness six months after surgery and 2/67 (2.9%) required re-operation after Latarjet. Only one patient experienced hardware failure. 42 patients (63%) were interviewed with mean follow-up of 26.7 months, of which 20 played football. 14/42 (33%) athletes competed at the collegiate level, and 23/42 (55%) at the high school level at the time of surgery. 33/42 patients (78.6%) returned to sport, of which 29/33 (88%) returned to playing at the same competition level; 12/20 (60%) of football players returned to sport. 3/42 (7%) reported recurrent dislocation. Mean ASES score was 91.7, DASH score 6.1, and visual analog scale 4. 38/42 (90%) patients reported improvement in quality of life after undergoing Latarjet procedure for shoulder instability. CONCLUSIONS: The Latarjet procedure allows young contact athletes with shoulder instability to return to competitive play at strong rates. Although there is high patient satisfaction with the Latarjet procedure, recurrent instability and unresolved pain and stiffness are significant post-operative complications.
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)
Background Concussion in sport is an ongoing global concern. The head injury assessment (HIA) by the field of play is acknowledged as the first step in recognising and identifying concussion. While previous systematic literature reviews have evaluated the sensitivity of side-line screening tools and assessment protocols, no systematic review has evaluated the research designs and assessments used in a field setting. This systematic review investigated existing screening and diagnostic tools used in research as part of the HIA protocol to identify concussion that are currently used in professional, semi-professional and amateur (club) sports settings. Methods A systematic searching of relevant databases was undertaken for peer-reviewed literature between 2015 and 2020. Results Twenty-six studies met the inclusion criteria. Studies were of moderate to good quality, reporting a variety of designs. The majority of studies were undertaken in professional/elite environments with medical doctors and allied health practitioners (e.g., physical therapists) involved in 88% of concussion assessments. While gender was reported in 24 of the 26 studies, the majority of participants were male (77%). There was also a variety of concussion assessments (n = 20) with the sports concussion assessment tool (SCAT) used in less than half of the included studies. Conclusion The majority of studies investigating concussion HIAs are focused on professional/elite sport. With concussion an issue at all levels of sport, future research should be directed at non-elite sport. Further, for research purposes, the SCAT assessment should also be used more widely to allow for consistency across studies.
National Athletic Trainers Associationapril 2017Sport
CONTEXT: Sport concussion is currently the focus of much international attention. Innovative methods to assist athletic trainers in facilitating management after this injury need to be investigated. OBJECTIVE: To investigate the feasibility of using a Facebook concussion-management program termed iCon (interactive concussion management) to facilitate the safe return to play (RTP) of young persons after sport concussion. DESIGN: Observational study. SETTING: Facebook group containing interactive elements, with moderation and support from trained health care professionals. PATIENTS OR OTHER PARTICIPANTS: Eleven participants (n = 9 men, n = 2 women; range, 18 to 28 years old) completed the study. DATA COLLECTION AND ANALYSIS: The study was conducted over a 3-month period, with participant questionnaires administered preintervention and postintervention. The primary focus was on the qualitative experiences of the participants and the effect of iCon on their RTP. Usage data were also collected. RESULTS: At the completion of the study, all participants (100%) stated that they would recommend an intervention such as iCon to others. Their supporting quotes all indicated that iCon has the potential to improve the management of concussion among this cohort. Most participants (n = 9, 82%) stated they were better informed with regard to their RTP due to participating in iCon. CONCLUSIONS: This interactive adjunct to traditional concussion management was appreciated among this participant group, which indicates the feasibility of a future, larger study of iCon. Athletic trainers should consider the role that multimedia technologies may play in assisting with the management of sport concussion.
Background Eating disorders negatively influence athletes’ health and performance. To achieve a high level of performance and conform to cultural expectations regarding an athletic body type, female athletes often restrict their diets, which can lead to eating disorders. In addition to factors related to the sports environment, adolescent athletes are subject to changes caused by the maturation process. Therefore, the same factors may have different effects on eating disorder risk among adolescent and adult athletes. This study examined the relationship between eating disorder risk, specific aspects of the sports environment (sport type, level of competition [national and international], and training background), and individual aspects (body satisfaction and body mass index) in two groups of athletes: adolescents and adults. Methods The sample included 241 highly trained female athletes aged 12–30 years (M = 20.68, SD = 4.45) recruited from different sports clubs in Poland. The subgroup of adolescents consisted of 82 athletes, while the number of adult athletes was 159. The Eating Attitudes Test questionnaire was used to assess the eating disorder risk among the athletes. Body satisfaction was measured using the Feelings and Attitudes Toward Body Scale incorporated into the Body Investment Scale. Results Eating disorder risk was prevalent among 14.6% of the adolescent and 6.9% of the adult athletes. Significant associations between eating disorder risk and the studied variables were noted only among adolescent athletes. Univariate logistic regression analysis revealed that the occurrence of eating disorder risk was associated with participation in lean non-aesthetic sports (OR = 11.50, 95% CI: 3.58–37.09). Moreover, eating disorder risk was associated with athletes’ lower body satisfaction (OR = 0.80, 95% CI: 0.70–0.92). Body mass index was not included in the final regression model. Conclusions The study indicated that eating disorder risk in adolescent female athletes was related to sport type and body satisfaction. The findings showed that, in adolescent athletes, eating disorder risk was the most associated with practicing lean non-aesthetic sports. Coaches and athletes should be aware that eating disorder risk increases among individuals with a lower body image.
Sport concussions can be difficult to diagnose and if missed, they can expose athletes to greater injury risk and long-lasting neurological disabilities. Discovery of objective biomarkers to aid concussion diagnosis is critical to protecting athlete brain health. To this end, we performed targeted proteomics on plasma obtained from adolescent athletes suffering a sports concussion. A total of 11 concussed male athletes were enrolled at our academic Sport Medicine Concussion Clinic, as well as 24 sex-, age- and activity-matched healthy control subjects. Clinical evaluation was performed and blood was drawn within 72 h of injury. Proximity extension assays were performed for 1,472 plasma proteins; a total of six proteins were considered significantly different between cohorts (P < 0.01; five proteins decreased and one protein increased). Receiver operating characteristic curves on the six individual protein biomarkers identified had areas-under-the-curves (AUCs) for concussion diagnosis ≥0.78; antioxidant 1 copper chaperone (ATOX1; AUC 0.81, P = 0.003), secreted protein acidic and rich in cysteine (SPARC; AUC 0.81, P = 0.004), cluster of differentiation 34 (CD34; AUC 0.79, P = 0.006), polyglutamine binding protein 1 (PQBP1; AUC 0.78, P = 0.008), insulin-like growth factor-binding protein-like 1 (IGFBPL1; AUC 0.78, P = 0.008) and cytosolic 5'-nucleotidase 3A (NT5C3A; AUC 0.78, P = 0.009). Combining three of the protein biomarkers (ATOX1, SPARC and NT5C3A), produced an AUC of 0.98 for concussion diagnoses (P < 0.001; 95% CI: 0.95, 1.00). Despite a paucity of studies on these three identified proteins, the available evidence points to their roles in modulating tissue inflammation and regulating integrity of the cerebral microvasculature. Taken together, our exploratory data suggest that three or less novel proteins, which are amenable to a point-of-care immunoassay, may be future candidate biomarkers for screening adolescent sport concussion. Validation with protein assays is required in larger cohorts.
Hardy personality plays a key role in sport due to the positive outcomes that has shown in sport performance. Consequently, it is salient to know which parental educational style is more related to positive characteristics of personality such as hardiness. Therefore, the objective of this research was to study the differences in perceived parental education styles in adult athletes with high and low levels of hardy personality. The sample consisted of 502 athletes from Spain (153 were women and 349 were men) between 18 and 64 years old (M = 27.76; SD = 9.11). A series of self-report questionnaires were fulfilled: an ad hoc sociodemographic questionnaire, the “Multifactor Self-Assessment Test of Child Adjustment”, the “Marathon-Hardy Personality Scale” and the Oviedo Scale of Infrequency Response. Firstly, sample was grouped in two groups. Secondly, the results of independent sample t-test showed higher levels of father protectionism and mother restriction in the low challenge scores group. Also, men educated that perceived to be educated by authoritarian parents reported lower commitment. Results also showed higher levels of care education close to mother protectionism, father restriction and mother restriction in the low hardy personality group. It was concluded that there are other variables that influence more on hardy personality in athletes apart from parents. Although challenge, hardy personality and commitment in men reported an influence by parental educational styles.
BACKGROUND: Recently, the incidence rate of back pain (BP) in adolescents has been reported at 21%. However, the development of BP in adolescent athletes is unclear. Hence, the purpose of this study was to examine the incidence of BP in young elite athletes in relation to gender and type of sport practiced. METHODS: Subjective BP was assessed in 321 elite adolescent athletes (m/f 57%/43%; 13.2 ± 1.4 years; 163.4 ± 11.4 cm; 52.6 ± 12.6 kg; 5.0 ± 2.6 training yrs; 7.6 ± 5.3 training h/week). Initially, all athletes were free of pain. The main outcome criterion was the incidence of back pain [%] analyzed in terms of pain development from the first measurement day (M1) to the second measurement day (M2) after 2.0 ± 1.0 year. Participants were classified into athletes who developed back pain (BPD) and athletes who did not develop back pain (nBPD). BP (acute or within the last 7 days) was assessed with a 5-step face scale (face 1–2 = no pain; face 3–5 = pain). BPD included all athletes who reported faces 1 and 2 at M1 and faces 3 to 5 at M2. nBPD were all athletes who reported face 1 or 2 at both M1 and M2. Data was analyzed descriptively. Additionally, a Chi(2) test was used to analyze gender- and sport-specific differences (p = 0.05). RESULTS: Thirty-two athletes were categorized as BPD (10%). The gender difference was 5% (m/f: 12%/7%) but did not show statistical significance (p = 0.15). The incidence of BP ranged between 6 and 15% for the different sport categories. Game sports (15%) showed the highest, and explosive strength sports (6%) the lowest incidence. Anthropometrics or training characteristics did not significantly influence BPD (p = 0.14 gender to p = 0.90 sports; r(2) = 0.0825). CONCLUSIONS: BP incidence was lower in adolescent athletes compared to young non-athletes and even to the general adult population. Consequently, it can be concluded that high-performance sports do not lead to an additional increase in back pain incidence during early adolescence. Nevertheless, back pain prevention programs should be implemented into daily training routines for sport categories identified as showing high incidence rates.
BACKGROUND: Since April 2020, some high schools were closed to in-person teaching, and interscholastic and club sports were cancelled in an attempt to slow the spread of COVID-19. While some US adolescents participated in sports since April 2020, other US adolescents did not participate in sports during this time. It is unknown what effect sport participation has had on the health of adolescents. HYPOTHESIS/PURPOSE: To identify how sport participation during the COVID-19 pandemic impacted the health of adolescents. METHODS: Adolescents across the US were recruited via social media to complete an online survey in the spring of 2021. Participants were asked to report their demographics (age, gender, race), whether they participated in school club or school sports since May 2020, type of school they attended (in-person, online, hybrid), and measures of mental health (MH), physical activity (PA) and quality of life (QoL). Assessments included the: General Anxiety Disorder-7 Item (GAD-7) for anxiety, Patient Health Questionnaire-9 Item (PHQ-9) for depression, Pediatric Functional Activity Brief Scale (PFABS) for physical activity, and Pediatric Quality of Life Inventory 4.0 (PedsQL) for quality of life. Assessment scores were compared for respondents who participated in sports (PAR) with those that did not participate in sports (NoPAR). Univariable comparisons between the groups were made via t-tests or chi-square tests while means for continuous outcome measures were compared between the groups by ANOVA models that controlled for age, gender, race and the type of school attendance. RESULTS: 4,693 adolescents (52% female, Age = 16.1+1.3 yrs., grades 9–12) from 38 states participated in the study with PAR = 4,286 (91%) and NoPAR = 407 (9%). NoPAR participants reported a higher prevalence of moderate to severe levels of anxiety (29.3% vs 21.3%, p<0.001) and depression (40.7% vs 19.8%, p<0.001). NoPAR participants reported lower (worse) PFABS scores (mean 13.2 [95%CI 12.4, 13.9] vs 21.2 [20.7, 21.6] p<0.001) and lower (worse) PedsQL total scores compared to the PAR group (77.9 [76.5, 79.3] vs. 83.2 [82.3, 84.1], p<0.001). CONCLUSIONS: Adolescents who did not play a sport during the COVID-19 pandemic reported significantly higher levels of anxiety and depression, as well as lower physical activity and quality of life scores compared to adolescents who did play a school or club sport. Participation in organized sports may offer an important opportunity to improve physical activity and mental health for adolescents during and after the COVID-19 pandemic.
International audience;
This article examines how high-performance sport coaches combine their professional and family lives. To address this issue, semi-structured interviews were conducted with 41 French coaches (8 females, 33 males) involved in the preparation of the French teams for the Olympic Games in Rio (2016), Pyeongchang (2018) and/or Tokyo (2020). The results show that all the coaches interviewed are engaged in a passionate relationship with their job. For some coaches, this commitment has an impact on their family life. Three groups of coaches stand out: (i) a majority of coaches who are unable to preserve their family life, (ii) coaches who maintain a distance from their profession and preserve their family life, (iii) coaches who have or have not preserved their family life and who position themselves as actors wishing to do everything possible to preserve the family life of the coaches they supervise. Thus, these results highlight, for some coaches, difficulties in combining professional and family life. For others, family life is a protection for engagement in a passionate profession. These data can provide useful information for sport organizations in charge of coaches.
This document is the result of an analysis initiated in 2007 with the aim of developing the practice of cycling in the Pays de la Loire region. This reflection first led to a first proposal at the end of 2008 to develop the practice of cycling with a sporting vision but also non-sporting in terms of citizenship and sustainable development. And it is after having integrated a more socio-economic dimension that the present project was again proposed to the local authorities in 2015 while being, in the principles, transposable to the national territory. Its vocation is to be a structuring society project for the Pays de la Loire considering the importance of cycling in society as a means of locomotion, as a leisure and playful tool, and its strong economic and social impact. This project is of course perfectible; it aims more from its foundations to be enriched by other ideas and ultimately contribute to the implementation of all or part of the proposals made to give the bike the place that is his with new services and uses. In other words, it is above all a basis of thought to lead to a transformation of behavior, the ambition being to lead a vision of the bike shared by all (sports and non-sports) but also with as a guideline, that of helping young people today to go after their own (and good ...) road in the general interest of society. The ambition of this project is part of the observation of cycling sport in the Pays de la Loire region. After the Rhône-Alpes and Brittany regions, the Pays de la Loire is in the leading pack in number of licensees practicing competition in a club. However, cycling struggles to develop fully compared to other sports. Cycling only ranks 18th in terms of number of licensees.While the total number of licensees has increased significantly among the youngest in recent years, this number falls sharply in the age group of 16 to 35 years. There are various reasons for this: an exploded offer, not always adapted to school and professional paths, new expectations from the public, less and less space due to an explosion of the urban phenomenon (the road that has historically been The biker's playground has become "hostile"), aging and uncovered velodromes ...To meet the needs of the discipline in the Nantes metropolis and thus contribute effectively to youth development through sport, the present document proposes the realization of a sports center dedicated to the different disciplines of cycling, with at least two strategic tools: a covered velodrome and a BMX track. Connected to a secure area and dedicated to the practice of so-called nature activities, this environment will promote access for all, young and old, and will privilege awakening, initiation, training and practice in competition but also a practice of simple leisure without constraint. On a purely sporting level, it aims at the national level to contribute to a rebalancing in terms of high level sports preparation and event offerings. Moreover, going further in the perspective of the organization of the Olympic Games in 2024, such a velodrome would benefit more to the structuring of the sports offer in the regions and would defend the economic interests of a Region. The logistics to be put in place in the framework of these Games are of the second order (sailing knows this problem) a vision that may seem utopian but is it not sometimes synonymous with ambition ...?However, this project is not only aimed at solving a sporting problem specific to the Nantes metropolis, even if, on reading it, it can be perceived at first glance with objectives that are too focused and sometimes too detailed on the development of cycling from a sporting point of view. After being a simple means of transport, cycling is today at the heart of major socio-economic and environmental issues for the cities of tomorrow. That is why it is important to integrate this sporting ambition into this social project for the Pays de la Loire with the aim of creating an identity in which its inhabitants recognize themselves.In this perspective, the sports center aims to constitute a multidisciplinary platform whose goal is to develop synergies around four levers / priority development axes: education, training, research and a societal economy / innovation, with end objectives that want to be complementary, namely: to be a tool at the service of the development of the individual and to be a tool at the service of society, sport being then only one variation among others of the use of this platform.To guarantee the success of such an approach, it is essential to break with frequent divisions, sometimes a source of complacency and culture of one's own. The mobilization and the involvement of all the actors concerned are essential, to mention only the ministries of national education and youth, sports, higher education, research and education. innovation, ecology and solidarity transition and the actors of civil society (citizens, companies, associations, etc.). It is this mobilization that will make it possible to respond to many of the recommendations of these same public authorities, associations and companies in favor of the development of physical and sports activities for all (development of sport health, well-being, women's sport, access to disadvantaged groups, integration and social cohesion, etc.) and the development of the economy in all its forms.It is also without counting on the evolution of public and private organizations, to which must be added the increasingly strong economic constraints that challenge the models that have worked so far. The pooling and rationalization of resources (financial, human, organizational, ...) have become necessary steps to reduce the costs of a project.Certainly, since the expression of this project, others projects exist but less integrators and paradoxically in small localities: one in Loudéac in Brittany (project in all likelihood validated in 2018) with a covered velodrome associated with a BMX track thus joining transversal sports objectives expressed here; the other one in Pays de la Loire at Essarts (85) but not yet validated in 2018, with only the construction of a covered velodrome. In the latter case, such an achievement near Nantes would naturally prevent Nantes Métropole from acquiring a tool of this type even in the long term.The construction of this second velodrome near La Roche s / Yon (20km) where the Regional Training and Training Center (CREF) is located can certainly make sense from a strictly sporting point of view. Nevertheless, it goes against the various plans of the State around the development of physical and sports activities with complementary objectives in particular (1) to ensure the reduction of social inequalities of access to the practice of these activities and to development of an adapted offer and (2) to be part of a sustainable development approach, a challenge to which cycling is undoubtedly able to contribute. With a potential of more than 600,000 inhabitants, Nantes Metropole has all the arguments in its favor to legitimize, with regard to societal issues, the realization of the infrastructures proposed here to (1) satisfy the expectations of a wider public and (2) achieve broader societal goals.Moreover, in terms of paradox, how not to mention the case of Limoges Métropole in Bonnac la Côte precisely. A velodrome covered with an inflatable structure, based on an idea from the United States, has just been created in a metropolis of "only" nearly 210000 inhabitants; an example that shows that when a project crosses power / networks, conviction / passion and means (the latter condition is not always a limiting step), it is likely to materialize. The concretization of the Les Essarts velodrome, to which reference is made above, would thus be the proof by example ...With regard specifically to the expectations of the public, the search for playful physical activities under the control of its practitioners is becoming stronger. The expectations of the new generations or certain socio-professional categories are more than ever in this direction and some countries, either by the development of another vision, or simply by difference of culture are already (engaged) in this dynamic.The same is true in terms of research and development with the "Images et Réseaux" Competitiveness Cluster of the Pays de la Loire and Brittany regions, whose mission is to boost the development of industrial activities and boost employment as widely as possible. This cluster has defined the theme "better living thanks to digital" as a major factor for the development of territories ; for this reason, it has all the potential to enable sports practices, activity monitoring and rehabilitation, to benefit the contribution of digital technologies. To reinforce the interest of this approach, it is enough to refer to the “Institut Carnot Star”, which carries the Fast_Sport'In field dedicated to the innovation of sport and well-being companies: by creating an environment open to businesses and by mobilizing resources of eight laboratories that implicate Aix-Marseille University (including six CNRS laboratories), this institute also intends for its part to meet many social issues such as the control of health expenditure, the aging of the population, the personalization of care, the increasing role of science and technology in practice and sports performance. So many arguments that show the interest of having a multidisciplinary platform in the Pays de la Loire region to the multiple services of society.It goes without saying that priorities of local authorities do not always favor the development of new projects because of the heavy investments required. However, with the societal transformations taking place in particular through digital and ecological transitions, local actors have more and more responsibilities in supporting these transformations.From this point of view, and with regard to transport policy, cycling seems finally to be perceived by the public authorities as a strategic tool. Proof of this is the bike plan launched by the State in September 2018, which includes funding dedicated to cycling. This plan reinforces and supports other plans already undertaken by local authorities such as in the Loire-Atlantique as part of its new policy for cycling, whether in terms of development of cycling paths or actions to promote the use of the bicycle. This is how we implement proposals that fit naturally with those advocated here, namely to make cycling safe for any type of practitioner. Now remains to achieve a network maintained real bike paths and functional in an existing motorway network sometimes complex with the hope of reaching the level of quality of some infrastructures of northern countries impregnated with another culture on the subject, and even from some countries further east of Europe. We can only hope to see this Bike Plan contribute to ride with confidence and thus reduce significantly the number of fatal accidents (sports and non-sports) that the news unfortunately brings us too often today.These are all elements of context that show the imperative need to provide a global answer to the role of the bicycle in the functioning of today's society. Designed to serve different uses with regard to societal issues, cycling can represent in a long-term vision a real vector of socio-economic development, and can, like culture, be a vector of moral values and social cohesion, one of the stakes of 21st century society. And it is precisely in this sense, quoting the website of the Ministry of Sports, that the development of responsible and sustainable physical and sports activities is particularly an important issue for local authorities, at all levels of territory.Since the diffusion in 2015 of this collaborative local project, some contextual elements have certainly evolved such as the location of such a project (given recent political decisions). Nevertheless, there is plenty of square meters around Nantes Metropole to integrate this vision into its overall development policy. Especially since the subject has all the characteristics to go into a regional policy to cope the issues raised which are more than ever hot topics ...
;
Ce document est le résultat d’une réflexion initiée dès 2007 avec pour objectif le développement de la pratique du vélo en région des Pays de la Loire. Cette réflexion a d’abord abouti à une première proposition fin 2008 destinée à développer la pratique du vélo avec une vision sportive mais aussi non sportive au regard de la citoyenneté et du développement durable. Et c’est après y avoir intégré une dimension plus socio-économique que le présent projet a été de nouveau proposé aux instances locales en 2015 tout en étant, dans les principes, transposable au territoire national. Il a pour vocation d’être un projet de société structurant pour les Pays de la Loire considérant la place importante du vélo dans la société comme moyen de locomotion, comme outil de loisir et ludique, et son fort impact économique et social.Ce projet est bien entendu perfectible ; il a plus pour objectif à partir de ses fondements d’être enrichi par d’autres idées et de contribuer au final à la mise en œuvre de tout ou partie des propositions faites pour donner au vélo la place qui est la sienne avec de nouveaux services et usages. Autrement dit, il constitue surtout une base de réflexion pour aboutir à une transformation des comportements, l’ambition étant d’entraîner une vision du vélo partagée par tous (sportifs et non sportifs) mais aussi avec comme fil directeur, celui d’aider les jeunes d’aujourd’hui à aller au bout de leur propre (et bonne ...) route dans l’intérêt général de la société.L’ambition de ce projet est partie du constat que s’agissant de la pratique sportive, la région des Pays de la Loire est après la Région Rhône-Alpes et la Bretagne dans le peloton de tête en nombre de licenciés pratiquant la compétition dans un club. Pour autant, le cyclisme peine à s’y développer pleinement comparé à d’autres sports. Le cyclisme ne se hisse qu’à la 18ème place en nombre de licenciés.Alors que le nombre total de licenciés progresse sensiblement chez les plus jeunes depuis quelques années, cet effectif chute fortement dans la tranche d’âge de 16 à 35 ans. Diverses raisons à cela au rang desquelles : une offre éclatée, pas toujours adaptée aux parcours scolaires et professionnels, de nouvelles attentes du public, de moins en moins d’espace en raison d’une explosion du phénomène urbain (la route qui est historiquement le terrain de jeu du cycliste est devenue « hostile »), des vélodromes vieillissants et aucun couvert,...Pour répondre aux besoins de la discipline dans la métropole nantaise et ainsi contribuer efficacement au développement des jeunes ligériens à travers le sport, le présent document propose donc la réalisation d’un complexe sportif dédié aux différentes disciplines relevant du cyclisme, avec a minima au centre du dispositif deux outils stratégiques : un vélodrome couvert ainsi qu’une piste de BMX. L’ensemble, relié à une aire sécurisée et consacrée à la pratique d’activités dites de nature, favorisera l'accès à tous, petits et grands, et privilégiera l’éveil, l’initiation, la formation et la pratique en compétition mais aussi une pratique de simple loisir sans contrainte. Sur un plan purement sportif, il vise au niveau national à contribuer à un rééquilibrage en matière de préparation au sport de haut niveau et d’offre événementielle. D’ailleurs, en allant plus loin dans la perspective de l’organisation des Jeux olympiques de 2024, un tel vélodrome profiterait plus à la structuration de l’offre sportive dans les régions et défendrait les intérêts économiques d’une Région. La logistique à mettre en place dans le cadre de ces Jeux relève du second ordre (la voile connaît bien cette problématique) une vision qui peut paraître utopique mais celle-ci n’est-elle pas parfois synonyme d’ambition … ?Cependant, ce projet ne vise pas uniquement à résoudre une problématique sportive propre à la métropole nantaise même si à sa lecture, il peut être de prime abord perçu avec des objectifs trop centrés et parfois trop détaillés sur le développement du cyclisme sous l’angle sportif. Après avoir été un simple moyen de transport, le vélo est aujourd’hui au coeur d’enjeux socio-économiques et environnementaux majeurs pour les métropoles de demain. C’est pourquoi, il est important d'intégrer cette ambition sportive dans ce projet de société pour les Pays de la Loire avec l’objectif de créer une identité dans laquelle ses habitants se reconnaissent.Dans cette perspective, le complexe sportif a pour vocation de constituer une plateforme pluridisciplinaire dont le but est de développer les synergies autour de quatre leviers/axes de développement prioritaires : l'éducation, la formation, la recherche et une économie/innovation sociétale, avec des objectifs finaux se voulant complémentaires, à savoir : être un outil au service du développement de l’individu et être un outil au service de la société, le sport n’étant alors qu’une déclinaison parmi d’autres de l’utilisation de cette plateforme.Pour garantir le succès d'une telle démarche, il est essentiel de rompre avec des clivages fréquents parfois source d’une certaine complaisance et de culture de l’entre soi. La mobilisation et l’implication de l’ensemble des acteurs concernés sont indispensables avec pour ne citer qu’eux, les ministères de l’éducation nationale et de la jeunesse, des sports, de l’enseignement supérieur, de la recherche et de l’innovation, de la transition écologique et solidaire et les acteurs de la société civile (citoyens, entreprises, associations, etc.). C’est cette mobilisation qui permettra notamment de répondre à bon nombre de préconisations de ces mêmes pouvoirs publics, d’associations et d'entreprises en faveur du développement d’activités physiques et sportives pour tous (développement du Sport santé, bien-être, du sport féminin, accès aux publics défavorisés, insertion et cohésion sociale, …) et du développement de l'économie sous toutes ses formes. C'est sans compter également sur l'évolution des organisations publiques et privées à laquelle il faut ajouter les contraintes économiques de plus en plus fortes qui remettent en cause les modèles qui ont fonctionné jusqu'ici. La mutualisation et la rationalisation de moyens (financiers, humains, organisationnels,...) sont devenues un passage obligé pour diminuer les coûts d'un projet.Certes, force est de constater au passage que des projets ont pointé depuis l’expression de ce projet mais moins intégrateurs et paradoxalement dans de petites localités : l'un à Loudéac en Bretagne (projet selon toute vraisemblance validé courant 2018) avec un vélodrome couvert associé à une piste de BMX rejoignant ainsi des objectifs sportifs transversaux exprimés ici ; l’autre en Pays de la Loire aux Essarts (85) mais pas encore validé en 2018, avec uniquement la construction d’un vélodrome couvert. Dans ce dernier cas, une telle réalisation à proximité de Nantes empêcherait naturellement Nantes Métropole de se doter même à long terme d’un outil de ce type. La construction de ce second vélodrome proche de La Roche s/Yon (20km) où se trouve le Centre Régional d'Entraînement et de Formation (CREF) peut certes prendre un certain sens d’un point de vue strictement sportif. Néanmoins, il va à l’encontre des divers plans de l’Etat autour du développement des activités physiques et sportives avec des objectifs complémentaires en particulier (1) veiller à la réduction des inégalités sociales d’accès à la pratique de ces activités et au développement d’une offre adaptée et (2) s’inscrire dans une démarche de développement durable, un défi auquel le vélo est incontestablement en mesure de contribuer. Avec un potentiel de plus de 600000 habitants, Nantes Metropole a tous les arguments en sa faveur pour légitimer, au regard des enjeux sociétaux, la réalisation des infrastructures proposées ici pour (1) satisfaire les attentes d’un plus large public et (2) atteindre des objectifs plus étendus sur un plan sociétal. D’ailleurs, en matière de paradoxe, comment ne pas mentionner le cas de Limoges Métropole à Bonnac la Côte précisément. Un vélodrome couvert avec une structure gonflable, sur la base d’une idée venue des Etats-Unis, vient en effet d’être créé dans une métropole de « seulement » près de 210000 habitants ; un exemple qui montre que lorsqu’un projet croise pouvoir/réseaux, conviction/passion et moyens (cette dernière condition n’étant d’ailleurs pas toujours une étape limitante), il a de fortes chances de se concrétiser. La concrétisation du vélodrome des Essarts auquel il est fait référence plus haut en serait ainsi la preuve par l’exemple … S’agissant précisément des attentes du public, la recherche d’activités physiques ludiques sous le contrôle de ses pratiquants est de plus en plus forte. Les attentes d’une partie des nouvelles générations ou de certaines catégories socio-professionnelles vont plus que jamais dans ce sens et certains pays, soit par l’élaboration d’une autre vision, soit tout simplement par différence de culture sont déjà (engagés) dans cette dynamique.Il en est de même sur un plan de recherche et développement avec le Pôle de compétitivité « Images et Réseaux » des Pays de la Loire et Bretagne dont la mission est d’amplifier le développement d'activités industrielles et de dynamiser l'emploi le plus largement possible. Après avoir défini le thème « mieux vivre grâce au numérique » comme majeur pour le développement des territoires, le pôle a tout le potentiel pour que les pratiques sportives, le suivi de l’activité et la rééducation puissent bénéficier des apports des technologies du numérique. Pour conforter une telle démarche, il suffit de faire référence à l'institut Carnot Star porteur de la filière Fast_Sport’In dédiée à l’innovation des entreprises du sport et bien-être : en créant un environnement ouvert aux entreprises et en mobilisant les ressources de huit laboratoires associés d’Aix-Marseille Université (dont six laboratoires CNRS), cet institut entend aussi de son côté relever de nombreux enjeux de société comme aussi bien la maîtrise des dépenses de santé, le vieillissement de la population, la personnalisation des soins, que le rôle croissant de la science et de la technologie dans la pratique et les performances sportives. Autant d’arguments qui montrent l’intérêt de disposer d’une plateforme pluridisciplinaire en Région des Pays de la Loire aux services multiples de la société. Il va sans dire que les priorités des collectivités ne favorisent pas toujours le développement de nouveaux projets en raison de lourds investissements nécessaires. Pour autant, avec les transformations sociétales qui s’opèrent au gré notamment des transitions numérique et écologique, les acteurs locaux ont de plus en plus de responsabilités dans le soutien à ces transformations. De ce point de vue et s’agissant précisément de la politique des transports, le vélo semble enfin être perçu par les pouvoirs publics comme un outil stratégique. La preuve en est, le Plan vélo engagé par l’Etat en septembre 2018 et qui comprend un financement dédié au vélo. Ce plan vient conforter et soutenir d’autres plans déjà engagés par des départements comme celui de la Loire-Atlantique dans le cadre de sa nouvelle politique en faveur du vélo, que ce soit en termes d’aménagement ou d’actions visant à favoriser l’usage du vélo. C’est ainsi qu’on y trouve la mise en œuvre de propositions qui s’inscrivent naturellement dans le sens de celles préconisées ici, à savoir rendre la pratique de la bicyclette sûre pour tout type de pratiquant. Reste à présent à réaliser un réseau entretenu de vraies pistes cyclables et fonctionnelles dans un réseau autoroutier existant parfois complexe avec l’espoir d’atteindre le niveau de qualité de certaines infrastructures de pays du nord imprégnés d’une autre culture sur le sujet, et même de certains pays plus à l’Est de l’Europe. On ne peut qu’espérer voir ce Plan vélo y contribuer pour se déplacer en toute sérénité et ainsi permettre une réduction significative du nombre d’accidents mortels (sportifs et non sportifs) que l’actualité nous rapporte hélas trop souvent.Ce sont donc là autant d'éléments de contexte qui montrent l'impérieuse nécessité d'apporter une réponse globale à la place de la bicyclette dans le fonctionnement de la société actuelle. Pensé au service de différents usages au regard d’enjeux sociétaux, le vélo peut représenter dans une vision à long terme un réel vecteur de développement socio-économique, et peut, comme la culture, être un vecteur de valeurs morales et de cohésion sociale, un des enjeux de la société du 21ème siècle. Et, c’est précisément en ce sens, pour reprendre les propos du site internet du ministère des sports, que le développement d’activités physiques et sportives responsables et durables est tout particulièrement un enjeu important pour les collectivités territoriales, à tous les échelons du territoire.Depuis la diffusion en 2015 de ce projet local collaboratif, quelques éléments de contexte ont certes évolué et modifient par exemple le lieu d’implantation suggéré initialement compte tenu de décisions politiques encore bien présentes dans les esprits ligériens . Il n'en reste pas moins que les espaces ne manquent pas à la métropole nantaise pour intégrer un tel projet dans sa politique globale de développement. D’autant que sur le fond, il dispose de nombreux atouts pour faire face aux problématiques soulevées ici et qui sont plus que jamais d’actualité…
SIMPLE SUMMARY: This review explores the evidence for the effect of equestrian sports on equine welfare and highlights scenarios in which their welfare can be impaired and where efforts are being made to improve it. We discuss animal welfare as a complex and disputed issue, clarifying what it means and how it can be measured. We review many aspects of animal welfare risk to the life of equids used for sport from foal to retirement. This is followed by a unique analysis of the institutions and social processes influencing equine welfare, exposing the challenges faced by a broad range of stakeholders with differing ethics, attitudes and values. We conclude with recommendations to ensure good welfare for all equids used for sport in the UK and beyond. ABSTRACT: Equestrian sports, including racing (e.g., flat, steeple-chasing, harness or donkey derby); show-jumping; cross-country; dressage; polo; polocrosse; endurance; carriage driving; vaulting and hunting; are hugely popular in the UK, and they involve a significant number of people, both as participants and spectators, and tens of thousands of equids. In this paper, we discuss animal welfare as a complex and disputed issue, clarifying what the term means and how it can be measured. We review many aspects of welfare risk to equids used for sport, addressing issues encountered throughout their lives, including housing, feeding, veterinary intervention, shoeing, handling, training, breeding and equipment. This is followed by a unique exploration of the institutions and social processes influencing equine welfare. The institutional components comprise the rules of competition, the equids, attributes of the stakeholders and the space where participants strive to achieve a common purpose. We endeavour to untangle the most significant elements that create barriers or provide opportunities for equine welfare improvement. We expose the challenges faced by a broad range of stakeholders with differing ethics, attitudes and values. Evidently, there are many welfare risks to which equids used in sports continue to be exposed. It is also evident that significant improvements have occurred in recent times, but there remains a barrier to reducing the risks to an acceptable level. We conclude with recommendations regarding a process for change, involvement of stakeholders and management of knowledge to improve equine welfare that involves identifying and prioritising the risk factors and ultimately leading to interventions, further research and/or education.
In this viewpoint we make specific recommendations that can assist and make the return to sport/exercise as safe as possible for all those impacted - from the recreational athlete to the elite athlete. We acknowledge that there are varying rules and regulations around the world, not to mention the varying philosophies and numerous schools of thought as it relates to return to sport/exercise and we have been cognisant of this in our recommendations. Despite the varying rules and circumstances around the world, we believe it is essential to provide some helpful and consistent guidance for return to training and sport for sport and exercise physicians around the world at this most difficult time. The present viewpoint provides practical and medical recommendations on the resumption to sport process.
BACKGROUND AND PURPOSE: The patella plays an important role in knee biomechanics and provides anterior coverage of the knee joint. One to two percent of the population has an anatomical variant of patella called a bipartite patella that usually does not case pain. However, occasionally after injury or overuse during sport it can be a source of anterior knee pain. The purpose of this case report was to present a rare variant of bipartite patella and highlight conservative treatment of this condition. STUDY DESIGN: Case Report CASE DESCRIPTION: A 35-year-old female patient presented with persistent bilateral non-traumatic anterior knee pain of a six-year duration that was enhanced by strenuous kinds of sport activity. Standard radiographs and MRI revealed the presence of bipartite patella with medial pole cartilage edema bilaterally. Conservative care including physical therapy, extracorporeal shock wave therapy (ESWT), and viscosupplementation was utilized. OUTCOME: After treatment VAS decreased to 0/10 from 5/10 in the left knee and 1/10 from 5/10 in the right knee. The Kujala Scores improved after treatment to 100 and 95 for the left and right knees respectively. The subject returned to full sport activity and work as a fitness instructor without pain and limitations. DISCUSSION: This case describes a rare finding of bilateral medial bipartite patella and the successful use of physical therapy with viscosupplementation in patellar pain caused by bipartite patella. It also supports the use of Extra Corporeal Shock Wave Therapy in bipartite patella pain as a supplement for therapy. LEVEL OF EVIDENCE: 4
BACKGROUND: It is estimated that 21% of boys and 16% of girls in England meet recommended physical activity guidelines. Team sport has the potential to increase physical activity levels; however, studies show that gender-based factors can influence girls' participation in team sport. Furthermore, evidence for the effectiveness of interventions promoting team sport among girls is limited. This systematic review aimed to assess the impact of physical activity interventions on secondary school-aged girls' (aged 11-18 years) participation in team sport and to identify potential strategies for increasing participation. METHODS: Electronic databases and grey literature were systematically searched for studies of interventions targeting team sport participation among girls in the UK. Results were exported to Refworks, duplicates removed and eligible studies identified. Extracted data included: participant details, such as sample size and age; components of the intervention; outcomes assessed; and each study was quality appraised. Due to heterogeneity across studies, results were presented narratively. RESULTS: Four studies sourced from the grey literature met the inclusion criteria. Findings suggest that physical activity interventions can encourage girls to try new sports, but evidence is limited in relation to sustained participation. Potential strategies for promoting participation included: consultation with girls, implementation of appropriate peer-leaders and friendship group strategies, early intervention and consideration of intervention setting. CONCLUSIONS: This review highlights the limited availability of evidence on the effectiveness of physical activity interventions for promoting team sport participation among girls in the UK. Findings indicate that future research is needed to improve the methodological quality of complex intervention evaluation. Physical activity interventions may have the potential to encourage girls to try team sport, but their impact on sustained participation, and subsequent physical activity outcomes, is less apparent.
Purpose The management of isolated SLAP lesions is still debated especially in athletes. Aims of the study were: 1. to analyse our algorithm to treat SLAP lesions starting from the selection of patients for surgery and 2. to correlate the familiarity for diabetes and hypothyroid disorders with post-operative results. Methods Seventy-eight patients with isolated SLAP lesion were arthroscopically treated using knotless anchors and microfractures. All patients had a pre-operative and post-operative clinical examination according to Walch–Duplay, Constant, Rowe and Dash scores and interviewed for familiarity to diabetes and hypothyroid disorders. Results About 68.8% of patients solved pain with rehabilitation. About 29% of patients returned to the sports activities. About 32% of patients were no responder to physiotherapy and were arthroscopically treated. About 53.9% of patients responded excellent, 34.7% good, 3.8% medium and 7.6% poor results according to Walch–Duplay score. The Constant score increased from 64 to 95, the Rowe score from 48 to 96. The outcomes were significantly worse in patients with familiarity for diabetes. Conclusions Microfractures and knotless anchor give long-term good results for the treatment of SLAP lesions in athletes. The familiarity for diabetes is an important risk factor that can lead to decreased outcomes.
Multimodal agents, which integrate a controller e.g., a vision language model) with external tools, have demonstrated remarkable capabilities in tackling complex multimodal tasks. Existing approaches for training these agents, both supervised fine-tuning and reinforcement learning, depend on extensive human-annotated task-answer pairs and tool trajectories. However, for complex multimodal tasks, such annotations are prohibitively expensive or impractical to obtain. In this paper, we propose an iterative tool usage exploration method for multimodal agents without any pre-collected data, namely SPORT, via step-wise preference optimization to refine the trajectories of tool usage. Our method enables multimodal agents to autonomously discover effective tool usage strategies through self-exploration and optimization, eliminating the bottleneck of human annotation. SPORT has four iterative components: task synthesis, step sampling, step verification, and preference tuning. We first synthesize multimodal tasks using language models. Then, we introduce a novel trajectory exploration scheme, where step sampling and step verification are executed alternately to solve synthesized tasks. In step sampling, the agent tries different tools and obtains corresponding results. In step verification, we employ a verifier to provide AI feedback to construct step-wise preference data. The data is subsequently used to update the controller for tool usage through preference tuning, producing a SPORT agent. By interacting with real environments, the SPORT agent gradually evolves into a more refined and capable system. Evaluation in the GTA and GAIA benchmarks shows that the SPORT agent achieves 6.41% and 3.64% improvements, underscoring the generalization and effectiveness introduced by our method. The project page is https://SPORT-Agents.github.io. ;24 pages
Background There is growing understanding of mental health needs in elite athletes, but less is known about the mental health of coaches and support staff who work within elite sport settings. This study examined the prevalence and correlates of mental health symptoms in elite-level coaches and high-performance support staff (HPSS) and compared rates against published elite athlete samples. A cross-sectional, anonymous, online survey was administered to coaches and HPSS working in Australia’s high-performance sports system. Main outcomes were scores on validated measures of psychological distress, probable ‘caseness’ for a diagnosable psychological condition, alcohol consumption and sleep disturbance. Results Data were provided by 78 coaches (mean age = 46.4 years, 23.8% female) and 174 HPSS (mean age = 40.0 years, 56.7% female). Overall, 41.2% of the sample met probable caseness criteria, 13.9% reported high to very high psychological distress, 41.8% reported potential risky alcohol consumption and 17.7% reported moderate to severe sleep disturbance, with no statistically significant differences between coaches and HPSS. The most robust correlates of psychological distress and probable caseness were dissatisfaction with social support and dissatisfaction with life balance, while poor life balance was also associated with increased alcohol consumption and poor social support with sleep disturbance. Coaches and HPSS reported similar prevalence of mental health outcomes compared to rates previously observed in elite athletes, with the exception of higher reporting of alcohol consumption among coaches and HPSS. Conclusions Elite-level coaches and HPSS reported levels of psychological distress and probable caseness similar to those previously reported among elite-level athletes, suggesting that these groups are also susceptible to the pressures of high-performance sporting environments. Screening for mental health symptoms in elite sport should be extended from athletes to all key stakeholders in the daily training environment, as should access to programs to support mental health and well-being.
OBJECTIVES: Graft selection for skeletally mature adolescents undergoing anterior cruciate ligament (ACL) reconstruction is guided by surgeon and patient preference. In young patients returning to high-risk cutting and pivoting sports, graft rupture is the most feared complication of ACL reconstruction. Some studies have demonstrated slightly lower rates of graft failure and decreased laxity in the short term associated with patellar tendon (BTB) autografts as compared to hamstring (HS) autografts, but these studies are limited by their heterogeneity of ages and activity level. The purpose of this study is to compare the rates of graft failure between BTB and HS ACL reconstruction cohorts matched by age, sex, and sport. METHODS: A single-institution retrospective review was performed of consecutive patients less than 19 years of age treated with ACL reconstructions using either patellar tendon (BTB) or hamstring (HS) autograft performed by a single surgeon. Skeletally mature or nearly mature patients in “high-risk” ACL injury sports (basketball, football, soccer, lacrosse, and gymnastics) were initially treated with hamstring autografts but the graft preference transitioned to BTB autografts as the preferred graft choice during the study period. This transition in graft preference for adolescents participating in “high risk” sports allows for a comparison of outcomes based on graft types. Inclusion criteria were ages 13 – 18 years, participation in a “high risk” sport, and minimum 24-month follow-up. The two cohorts of patients were matched by age, gender, and sport. The primary outcome measure was graft rupture. RESULTS: One hundred twenty-six patients with an average age of 15.8 years (range 13 – 18 years) met inclusion criteria. There were 60 BTB reconstructions and 66 HS reconstructions. There were 55 females and 71 males. There was no difference in age, sex, BMI, or laterality between groups. There were more patients who played soccer in the BTB cohort (44%) vs HS cohort (22%) and fewer who played basketball in the BTB cohort (24%) vs HS cohort (38%), p = 0.005. There were no differences between the BTB and HS cohorts in terms of meniscus tears (60% v 68%, p = 0.34), meniscus repair (20% v 30%, p = 0.19), or partial meniscectomy (33% v 39%, p = 0.48). Mean duration of follow-up was 41 months (range 24-78 months). There was a difference in follow-up between cohorts (BTB 36 months and HS 50 months, p < 0.05). There were 16 graft ruptures (12.6%). There was no difference in the rate of graft rupture between cohorts (BTB 10.0% vs HS 15.2%, p = 0.45). Mean time to graft rupture was 21 months (range 8 – 35 months) and Kaplan-Meier survival curves demonstrated no difference between cohorts. The mean age of graft failures within the BTB cohort was 15.5 years as compared to 16.1 years for those that did not have a graft failure (p=0.268). The mean age of graft failures within the HS cohort was 14.9 years as compared to 15.9 years for those that did not have a graft failure (p<0.05). CONCLUSION: ACL reconstruction in adolescents returning to high-risk sports can be performed utilizing BTB or HS autografts with similar rates of graft rupture. Patients under the age of 15 years have a greater risk of failure associated with HS autograft as compared to patients 16 years of age and older with the same graft. In contrast, BTB grafts have similar failure rates regardless of age. There is a trend toward lower rates of graft rupture associated with BTB autografts, but additional patients will be necessary to determine if this trend will become a statistically significant difference.
The aim of this study was to describe the nonoperative treatment outcomes of finger flexor tenosynovitis in sport climbers and to evaluate the association with baseline measures and therapy contents. Sixty-five sport climbers (49 males, mean age 34.1 years) diagnosed with tenosynovitis of the finger flexors were retrospectively asked about injury triggers, therapy contents and outcomes. Pulley thickness was measured by ultrasound. All patients were initially treated conservatively, and only one of the patients needed further therapy (single injection with hyaluronic acid); none of them underwent surgical treatment. The most frequently applied therapy was climbing-related load reduction (91%). The treatment resulted in a statistically significant reduction in pain intensity during climbing (before/after therapy ratio [Visual Analog Scale (VAS)/VAS] = 0.62, 95% CI = 0.55, 0.68). The average duration of the symptoms was 30.5 weeks (range 1-120 weeks). In a multiple linear regression analysis, initial daily life pain intensity and a climbing level higher than 7b according to the French/sport grading scale were the only predictive parameters for the relative change in pain intensity and symptom duration, respectively. All patients were able to resume climbing, with 75% regaining or even exceeding their initial climbing level. The good to excellent outcomes and no correlation between particular therapy contents and therapy outcome may suggest that finger flexor tenosynovitis in sport climbers has a favorable natural course without requiring invasive therapy. However, further cohort studies and, ultimately, randomized controlled trials are needed to conclusively confirm our promising observations.
Background Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. Methods This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. Results Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. Conclusions Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT. Graphical abstract
Background Thyroid nodules are unusual in children, but when present, they carry a higher risk for malignancy, as compared to adults. Several guidelines have been created to address the risk stratification for malignancy of thyroid nodules in adults, but none has been completely validated in children. A few authors have proposed lowering the size threshold to the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS™) management guidelines to decrease missed carcinomas at presentation in children; however, little information is known regarding their accuracy. Objective To assess the performance of proposed modifications of the ACR TI-RADS™ size criteria to guide management decisions in pediatric thyroid nodules and to assess the associated increase in number of fine needle aspiration (FNA) and follow-up exams. Materials and methods This is a retrospective study of children under 18 years old who underwent ultrasound assessment of a thyroid nodule at a tertiary care pediatric institution between January 2006 and August 2021. The largest dimension, maximum ACR TI-RADS™ score, and final thyroid nodules’ diagnoses were documented. The course of action based on the adult ACR TI-RADS™ and after modifying the size threshold for management recommendations was documented and compared. Statistics included descriptive analysis, weighted Kappa statistics, sensitivity, specificity, accuracy, and positive/negative predictive values of the ACR TI-RADS™ presented with 95% confidence intervals (CI) using either Clopper–Pearson or standard logit methods. Results Of 116 nodules, 18 (15.5%) were malignant. Most malignant nodules (94.4%, n = 17) were ACR TI-RADS™ 4 and ACR TI-RADS™ 5 categories. Based on the adult ACR TI-RADS™ criteria, 24 (24.5%) benign and 15 (83.3%) malignant nodules would have undergone FNA; 14 (14.3%) benign and 3 (16.7%) malignant nodules would have been followed up; and 60 (61.2%) benign and none of malignant nodules would have been dismissed. Three (16.7%) malignant nodules would not have been recommended FNA at presentation, delaying their diagnoses. By lowering the size-threshold criteria of the ACR TI-RADS™ guidelines, no malignancy would have been missed at presentation, but this also resulted in a higher number of FNA from 24 (24.5%) to 36 (36.7%) and follow-up ultrasound exams from 14 (14.3%) to 62 (63.3%). Conclusion Applying potential modifications to the ACR TI-RADS™ guideline lowering the size threshold criteria of the thyroid nodule to guide management decisions for pediatric thyroid nodules can lead to early detection of malignant nodules in children, but at the cost of a significantly increased number of biopsies or ultrasound exams. Further tailoring of the guideline with larger multicentric studies is needed, before warranting its acceptance and general use in the pediatric population. Graphical Abstract
Purpose: Hashimoto’s thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFβ1) in HT patients with different patterns of thyroid function. Methods: A total of 29 HT patients, with a median age of 52 years (21–68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFβ1 assayed by ELISA. Results: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = −0.60, P < 0.01). Serum TGFβ1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFβ1 (r = −0.75, P < 0.01). Conclusions: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFβ1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFβ1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT.
Background Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. Materials and methods Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. Results The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals ( p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group ( p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects ( p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients ( p < 0.01). Conclusion These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.
Accurate detection of ultrasound nodules is essential for the early diagnosis and treatment of thyroid and breast cancers. However, this task remains challenging due to irregular nodule shapes, indistinct boundaries, substantial scale variations, and the presence of speckle noise that degrades structural visibility. To address these challenges, we propose a prior-guided DETR framework specifically designed for ultrasound nodule detection. Instead of relying on purely data-driven feature learning, the proposed framework progressively incorporates different prior knowledge at multiple stages of the network. First, a Spatially-adaptive Deformable FFN with Prior Regularization (SDFPR) is embedded into the CNN backbone to inject geometric priors into deformable sampling, stabilizing feature extraction for irregular and blurred nodules. Second, a Multi-scale Spatial-Frequency Feature Mixer (MSFFM) is designed to extract multi-scale structural priors, where spatial-domain processing emphasizes contour continuity and boundary cues, while frequency-domain modeling captures global morphology and suppresses speckle noise. Furthermore, a Dense Feature Interaction (DFI) mechanism propagates and exploits these prior-modulated features across all encoder layers, enabling the decoder to enhance query refinement under consistent geometric and structural guidance. Experiments conducted on two clinically collected thyroid ultrasound datasets (Thyroid I and Thyroid II) and two public benchmarks (TN3K and BUSI) for thyroid and breast nodules demonstrate that the proposed method achieves superior accuracy compared with 18 detection methods, particularly in detecting morphologically complex nodules.The source code is publicly available at https://github.com/wjj1wjj/Ultrasound-DETR.
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.
Purpose: Thyroid scintigraphy plays a vital role in diagnosing a range of thyroid disorders. While deep learning classification models hold significant promise in this domain, their effectiveness is frequently compromised by limited and imbalanced datasets. This study investigates the impact of three data augmentation strategies including Stable Diffusion (SD), Flow Matching (FM), and Conventional Augmentation (CA), on enhancing the performance of a ResNet18 classifier.
Methods: Anterior thyroid scintigraphy images from 2,954 patients across nine medical centers were classified into four categories: Diffuse Goiter (DG), Nodular Goiter (NG), Normal (NL), and Thyroiditis (TI). Data augmentation was performed using various SD and FM models, resulting in 18 distinct augmentation scenarios. Each augmented dataset was used to train a ResNet18 classifier. Model performance was assessed using class-wise and average precision, recall, F1-score, AUC, and image fidelity metrics (FID and KID).
Results: FM-based augmentation outperformed all other methods, achieving the highest classification accuracy and lowest FID/KID scores, indicating both improved model generalization and realistic image synthesis. SD1, combining image and prompt inputs in the inference process, was the most effective SD variant, suggesting that physician-generated prompts provide meaningful clinical context. O+FM+CA yielded the most balanced and robust performance across all classes.
Conclusion: Integrating FM and clinically-informed SD augmentation, especially when guided by expert prompts, substantially improves thyroid scintigraphy classification. These findings highlight the importance of leveraging both structured medical input and advanced generative models for more effective training on limited datasets.
Objective: Molecular testing (MT) classifies cytologically indeterminate
thyroid nodules as benign or malignant with high sensitivity but low positive
predictive value (PPV), only using molecular profiles, ignoring ultrasound (US)
imaging and biopsy. We address this limitation by applying attention multiple
instance learning (AMIL) to US images.
Methods: We retrospectively reviewed 333 patients with indeterminate thyroid
nodules at UCLA medical center (259 benign, 74 malignant). A multi-modal deep
learning AMIL model was developed, combining US images and MT to classify the
nodules as benign or malignant and enhance the malignancy risk stratification
of MT.
Results: The final AMIL model matched MT sensitivity (0.946) while
significantly improving PPV (0.477 vs 0.448 for MT alone), indicating fewer
false positives while maintaining high sensitivity.
Conclusion: Our approach reduces false positives compared to MT while
maintaining the same ability to identify positive cases, potentially reducing
unnecessary benign thyroid resections in patients with indeterminate nodules.
;Comment: 9 pages, 3 figures
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.
Background Portable gamma cameras are being developed for nuclear medicine procedures such as thyroid scintigraphy. This article introduces Seracam® – a new technology that combines small field of view gamma imaging with optical imaging – and reports its performance and suitability for small organ imaging. Methods The count rate capability, uniformity, spatial resolution, and sensitivity for ^99mTc are reported for four integrated pinhole collimators of nominal sizes of 1 mm, 2 mm, 3 mm and 5 mm. Characterisation methodology is based on NEMA guidelines, with some adjustments necessitated by camera design. Two diagnostic scenarios – thyroid scintigraphy and gastric emptying – are simulated using clinically relevant activities and geometries to investigate application-specific performance. A qualitative assessment of the potential benefits and disadvantages of Seracam is also provided. Results Seracam’s performance across the measured characteristics is appropriate for small field of view applications in nuclear medicine. At an imaging distance of 50 mm, corresponding to a field of view of 77.6 mm × 77.6 mm, spatial resolution ranged from 4.6 mm to 26 mm and sensitivity from 3.6 cps/MBq to 52.2 cps/MBq, depending on the collimator chosen. Results from the clinical simulations were particularly promising despite the challenging scenarios investigated. The optimal collimator choice was strongly application dependent, with gastric emptying relying on the higher sensitivity of the 5 mm pinhole whereas thyroid imaging benefitted from the enhanced spatial resolution of the 1 mm pinhole. Signal to noise ratio in images was improved by pixel binning. Seracam has lower measured sensitivity when compared to a traditional large field of view gamma camera, for the simulated applications this is balanced by advantages such as high spatial resolution, portability, ease of use and real time gamma-optical image fusion and display. Conclusion The results show that Seracam has appropriate performance for small organ ^99mTc imaging. The results also show that the performance of small field of view systems must be considered holistically and in clinically appropriate scenarios.
Background This study develops a Quality of Care Index (QCI) to evaluate global disparities in care quality for five head and neck cancer (HNC) subtypes—thyroid, larynx, lip and oral cavity, nasopharynx, and other pharynx cancers—from 1990 to 2021, addressing the issue of existing indicators not fully reflecting cancer quality. Methods We developed a QCI for five HNC subtypes using data from the Global Burden of Disease Study 1990–2021. The QCI was constructed through principal component analysis of six epidemiological indicators. Trends in age-standardized DALY rates (ASDR) and QCI were assessed globally, regionally, nationally and by Socio-demographic Index (SDI). Results From 1990 to 2021, ASDR declined markedly for larynx and nasopharynx cancers, whereas thyroid, lip and oral cancer, and other pharynx cancers decreased only in high-SDI regions, remaining stable or rising in low- and middle-SDI regions. QCI improved for all subtypes. High-SDI regions consistently exhibited a ‘high-quality, low-burden’ pattern, with the highest absolute QCI values but limited relative gains; low-SDI regions, in contrast, faced “high burden and low quality” and, despite lower absolute QCI, showed the largest improvements over time. Subtype-specific patterns were evident: nasopharynx cancer achieved the greatest QCI gains, larynx cancer showed consistent ASDR decline and QCI improvement across all SDI levels, and thyroid cancer improved in QCI despite ASDR increases in low- to middle- SDI regions. Lip and oral cancer, and other pharynx cancers exhibited persistent high burden in lower SDI regions, with modest QCI gains. Conclusions Global HNC care quality has improved, but reductions in disease burden and gains in QCI were not fully aligned. Substantial inequalities persist across cancer subtypes and SDI regions. Strengthening care infrastructure and optimizing HNC management in resource-limited settings are needed to reduce disparities.
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.
Timely and accurate diagnosis is crucial in addressing the global rise in thyroid cancer, ensuring effective treatment strategies and improved patient outcomes. We present an intelligent classification method that couples an Adaptive Convolutional Neural Network (CNN) with Cohen-Daubechies-Feauveau (CDF9/7) wavelets whose detail coefficients are modulated by an n-scroll chaotic system to enrich discriminative features. We evaluate on the public DDTI thyroid ultrasound dataset (n = 1,638 images; 819 malignant / 819 benign) using 5-fold cross-validation, where the proposed method attains 98.17% accuracy, 98.76% sensitivity, 97.58% specificity, 97.55% F1-score, and an AUC of 0.9912. A controlled ablation shows that adding chaotic modulation to CDF9/7 improves accuracy by +8.79 percentage points over a CDF9/7-only CNN (from 89.38% to 98.17%). To objectively position our approach, we trained state-of-the-art backbones on the same data and splits: EfficientNetV2-S (96.58% accuracy; AUC 0.987), Swin-T (96.41%; 0.986), ViT-B/16 (95.72%; 0.983), and ConvNeXt-T (96.94%; 0.987). Our method outperforms the best of these by +1.23 points in accuracy and +0.0042 in AUC, while remaining computationally efficient (28.7 ms per image; 1,125 MB peak VRAM). Robustness is further supported by cross-dataset testing on TCIA (accuracy 95.82%) and transfer to an ISIC skin-lesion subset (n = 28 unique images, augmented to 2,048; accuracy 97.31%). Explainability analyses (Grad-CAM, SHAP, LIME) highlight clinically relevant regions. Altogether, the wavelet-chaos-CNN pipeline delivers state-of-the-art thyroid ultrasound classification with strong generalization and practical runtime characteristics suitable for clinical integration. ;Scientific Reports
Background Thyroid nodules have attracted much attention due to their high incidence and potential for malignant transformation. Compared with the clinical assessment and diagnosis of thyroid nodules, there are relatively few studies on the epidemiological risk factors for thyroid nodules. The aim of this study was to investigate the prevalence of thyroid nodule among adults in Zhejiang province and to explore their relationship with physiological and psychosocial factors. Methods The data used in this study were obtained from the baseline survey of the Zhejiang Provincial Cohort Study on Environment and Health. From June 2022 to December 2023, a total of 21,712 participants from five representative cities in Zhejiang were recruited for the baseline survey. Based on the inclusion and exclusion criteria, 15,595 adults were included in the analysis. The data were collected via self-report questionnaires and physical examinations. Multivariate logistic regression analysis was subsequently performed. Results The detection rate of thyroid nodules was 50.98% among adults in Zhejiang province. Age, gender, education level, BMI, tea and alcohol consumption all had a statistically significant association with thyroid nodules ( p < 0.05). After adjusting for sociodemographic factors, results of logistic regression analysis showed that good life satisfaction (OR = 0.854, 95% CI: 0.780–0.934) had a lower risk of thyroid nodules, however, poor life satisfaction (OR = 1.406, 95% CI: 1.014–1.951), social isolation (OR = 1.294, 95% CI: 1.089–1.538) and a family history of thyroid nodules (OR = 1.334, 95% CI: 1.064–1.672) had a greater risk of thyroid nodules. Conclusion The detection rate of thyroid nodules in adults of Zhejiang province was an increasing trend compared with that in previous years. In addition to the sensitive thyroid nodule screening technology, influencing factors mentioned in this study might also represent credible candidates for this increase. As variable influence factors, weight management, good interpersonal relationships and life satisfaction should be the focus of health interventions.
Background: Automated classification of thyroid Fine Needle Aspiration Biopsy
(FNAB) images faces challenges in limited data, inter-observer variability, and
computational cost. Efficient, interpretable models are crucial for clinical
support.
Objective: To develop and externally validate a deep learning system for
multi-class thyroid FNAB image classification into three key categories
directly guiding post-biopsy treatment in Vietnam: Benign (Bethesda II),
Indeterminate/Suspicious (BI, III, IV, V), and Malignant (BVI), achieving high
diagnostic accuracy with low computational overhead.
Methods: Our pipeline features: (1) YOLOv10 cell cluster detection for
informative sub-region extraction/noise reduction; (2) curriculum learning
sequencing localized crops to full images for multi-scale capture; (3) adaptive
lightweight EfficientNetB0 (4M parameters) balancing performance/efficiency;
and (4) a Transformer-inspired module for multi-scale/multi-region analysis.
External validation used 1,015 independent FNAB images.
Results: ThyroidEffi Basic achieved macro F1 of 89.19% and AUCs of 0.98
(Benign), 0.95 (Indeterminate/Suspicious), 0.96 (Malignant) on the internal
test set. External validation yielded AUCs of 0.9495 (Benign), 0.7436
(Indeterminate/Suspicious), 0.8396 (Malignant). ThyroidEffi Premium improved
macro F1 to 89.77%. Grad-CAM highlighted key diagnostic regions, confirming
interpretability. The system processed 1000 cases in 30 seconds, demonstrating
feasibility on widely accessible hardware.
Conclusions: This work demonstrates that high-accuracy, interpretable thyroid
FNAB image classification is achievable with minimal computational demands.
;Comment: Preprint
This study presents the first report on the development of an artificial
intelligence (AI) for automatic region segmentation of four-dimensional
computer tomography (4D-CT) images during swallowing. The material consists of
4D-CT images taken during swallowing. Additionally, data for verifying the
practicality of the AI were obtained from 4D-CT images during mastication and
swallowing. The ground truth data for the region segmentation for the AI were
created from five 4D-CT datasets of swallowing. A 3D convolutional model of
nnU-Net was used for the AI. The learning and evaluation method for the AI was
leave-one-out cross-validation. The number of epochs for training the nnU-Net
was 100. The Dice coefficient was used as a metric to assess the AI's region
segmentation accuracy. Regions with a median Dice coefficient of 0.7 or higher
included the bolus, bones, tongue, and soft palate. Regions with a Dice
coefficient below 0.7 included the thyroid cartilage and epiglottis. Factors
that reduced the Dice coefficient included metal artifacts caused by dental
crowns in the bolus and the speed of movement for the thyroid cartilage and
epiglottis. In practical verification of the AI, no significant misrecognition
was observed for facial bones, jaw bones, or the tongue. However, regions such
as the hyoid bone, thyroid cartilage, and epiglottis were not fully delineated
during fast movement. It is expected that future research will improve the
accuracy of the AI's region segmentation, though the risk of misrecognition
will always exist. Therefore, the development of tools for efficiently
correcting the AI's segmentation results is necessary. AI-based visualization
is expected to contribute not only to the deepening of motion analysis of
organs during swallowing but also to improving the accuracy of swallowing CT by
clearly showing the current state of its precision.
;Comment: 8 pages, 5 figures, 1 table
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
BACKGROUND: Thyroid disorders are common endocrine conditions impacting multiple organs, including the reproductive system and often lead to sexual dysfunction. These effects can vary by gender; for example, women with hypothyroidism frequently experience reduced libido. Low thyroid hormone levels are also linked to vaginal dryness, causing discomfort, especially during intercourse. This study aims to assess the global prevalence of sexual dysfunction in women with thyroid disorders. METHODS: Systematic searches were performed across electronic databases, including PubMed, Scopus, Web of Science, Embase, ScienceDirect and Google Scholar, to retrieve studies reporting the prevalence of sexual dysfunction in patients with thyroid disorders up to February 8, 2024. Inclusion criteria comprised studies that reported on the prevalence of female sexual dysfunction (FSD) in patients with thyroid disorders and studies published in English available full text. Exclusion criteria included case studies, intervention studies, studies with incomplete information, repeated studies and those not written in English. Cross-sectional studies were the primary study design included. Data were analyzed using the Comprehensive Meta-Analysis software (Version 2). RESULTS: Analysis of nine studies, involving a total sample size of 1013, found an overall prevalence of sexual dysfunction in women with thyroid disorders to be 44.8% (95% CI: 33.8–56.2). Given the substantial reporting of sexual dysfunction among women with either hypothyroidism or hyperthyroidism, subgroup analyses were conducted. The prevalence of sexual dysfunction was 41.8% (95% CI: 26.3–59) among women with hypothyroidism and 59.6% (95% CI: 50.5–68.1) among those with hyperthyroidism. CONCLUSION: The notable prevalence of sexual dysfunction in women with thyroid disorders highlights the for increased awareness among this population. Targeted awareness initiatives may help mitigate the occurrence of sexual dysfunction and its adverse effects, improving overall quality of life for affected women. CLINICAL TRIAL NUMBER: Not applicable.
Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3 , EXO1 , UBE2T , UBE2C , FOXM1 , CENPA , DLL3 , CCNA2 , SOX2 , KIF23 , and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1 , DLL3 , and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival ( p = 0.041) and overall survival ( p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC.
BACKGROUND: Acute suppurative thyroiditis (AST) caused by pyriform sinus fistula (PSF) is a rare condition in adults. PSF is a congenital malformation that can cause an infection of the thyroid gland, usually located on the left side. AST presents with symptoms similar to respiratory infections, which can make it difficult to diagnose. It is essential to consider PFS as a differential diagnosis due to its relationship with the recurrence of thyroid abscesses. CASE REPORT: We report the case of a 32-year-old woman who presented with neck pain and fever, initially mistaken for an upper respiratory infection. After 3 weeks, she was diagnosed with AST with an abscess in the left thyroid lobe. Drainage and initial antibiotic treatment (metronidazole and clindamycin) improved her condition. However, due to non-compliance with medical follow-up, the patient suffered a recurrence of the abscess and required a left thyroid lobectomy. The culture identified multidrug-resistant Staphylococcus sciuri and the patient was finally referred for a successful fistulectomy. CONCLUSION: AST due to PSF is uncommon in adults, with few documented cases. Initial treatment includes antibiotics and surgical drainage, although recurrence can occur if the risk factor is not eliminated. In this case, failure to comply with medical follow-up contributed to the recurrence. It is crucial to identify PSF as a causative factor early on and to carry out adequate follow-up to avoid serious complications. LEARNING POINTS: Thyrotoxicosis can occur in up to 42% of cases of acute suppurative thyroiditis, making it less relevant to differentiate it from other causes of thyroiditis. In adults with no obvious risk factors, congenital malformations should be considered, especially when the condition affects the left lobe. To avoid recurrences, it is necessary to evaluate the pyriform sinus in any age group and patient adherence to medical instructions is essential.
Background Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. Summary While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023. Conclusion Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD.
Aims A few studies have evaluated the performance of the American College of Radiology Thyroid Imaging Reporting And Data System (ACR-TIRADS) in pediatric and elderly patients and found differences between the latter two age groups and middle adulthood. Thus, the present study was undertaken to explore the possible variation of ACR-TIRADS performance across different ages of patients. Methods A retrospective population undergoing thyroidectomy was selected to use histology as the reference standard. Ultrasound images were reviewed, and alignment of ACR-TIRADS with the corresponding histological diagnosis was made afterwards. Results of the age groups were compared. The ACR-TIRADS diagnostic performance was calculated considering the assessment of nodules across risk categories (i.e., from TR1 to TR5), rate of unnecessary FNAC (UN-FNAC), and rate of necessary but non-performed FNAC (NNP-FNAC). Results Overall, 114 patients with a total of 220 nodules (46 carcinomas) were included. The rate of UN-FNAC was 66.3%, being 93.1% in TR3, 82.1% in TR4, and 31.4% in TR5. There were 15 NNP-FNACs. No significant difference was observed between age groups in terms of sample size, nodule, cancer, and FNAC. The nodule assessment according to ACR-TIRADS categories did not vary across ages. Sensitivity and specificity recorded in three age tertiles were not significantly different. Conclusions The present study shows that the performance of ACR-TIRADS is not significantly influenced by patient age.
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.
OBJECTIVE: To investigate the clinical characteristics, related risk factors and outcomes of thyroid immune-related adverse events (irAEs) in patients with malignant solid tumor treated with programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in a large tertiary Chinese center. METHODS: We retrospectively analyzed the clinical data of 1151 patients with malignant solid tumors who received PD-1 or PD-L1 inhibitors treatment and underwent thyroid function evaluation in a large 3 A hospital of Beijing from September 2019 to December 2023. According to the thyroid status after receiving PD-1/PD-L1 inhibitors treatment, patients were divided into normal thyroid group and thyroid irAEs group. The clinical characteristics, including age, gender, tumor type, previous anti-cancer treatment history and thyroid function status were evaluated. After the occurrence of thyroid irAEs, thyroid function evaluation, onset time, and survival outcomes were analyzed. Risk factors that may contribute to the thyroid irAEs were further explored by logistic regression. RESULTS: Out of 1151 patients treated with a PD-1/PD-L1 inhibitor, 257 (22.3%) developed new thyroid irAEs, with the vast majority (98.0%) being hypothyroidism (193/257, 75.1%) and Grade1-2 (252/257, 98.0%), including 252 Hashimoto’s thyroiditis (98.0%), 3 subacute thyroiditis (1.17%) and 2 Graves’ disease (0.78%). There was a significant difference in the number of treatment cycles of PD-1/PD-L1 inhibitors between the two groups (P = 0.001). In multivariate analysis, gastrointestinal cancer, radiotherapy history, targeted therapy history, positive TgAb and TPOAb at baseline were associated with thyroid irAEs caused by PD-1/PD-L1 inhibitors. Absence of thyroid irAEs predicted increased mortality overall (HR = 2.935, P = 0.024) and particularly in gastrointestinal cancers (HR = 9.453, P = 0.007), despite comparable crude mortality (5.84% vs. 5.82%, P = 0.228). No association was observed in lung/other tumors. Thyroid function recovery occurred in 36.2% of patients, and treatment interruption due to thyroid irAEs was rare (3.5%). CONCLUSION: In our group, 22.3% patients treated with PD-1/PD-L1 inhibitors developed thyroid irAEs. The main subtype of thyroid irAEs was hypothyroidism (75.1%). Patients with gastrointestinal cancer, previous radiotherapy, history of targeted therapy, and baseline TgAb or TPOAb positivity may increase the risk of thyroid irAEs. Thyroid irAEs was associated with a trend for a survival benefit in patients with gastrointestinal cancer.
Per- and polyfluoroalkyl substances (PFAS) may disrupt thyroid hormones although the literature shows mixed evidence of this effect and exposure to mixtures of PFAS remains poorly understood. We used the Michigan PFAS Exposure and Health Study cohort to examine linear and nonlinear associations between serum PFAS concentrations, both alone and as a mixture, and serum thyroid hormone concentrations. Study participants included 728 adolescents and adults living in an area with past PFAS contamination of drinking water. We quantified 39 individual PFAS and four thyroid hormones in serum from participants between the years 2020 and 2021. Linear regression, weighted quantile sum (WQS) regression, supervised Principal Component Analysis (PCA), and Bayesian Kernel Machine Regression (BKMR) were used. When analyzed individually, a 1% increase in PFUnA serum concentrations was associated with a 0.023% decrease in TT3 concentration (95% CI: -0.04%, -0.01%, p < 0.05). All three mixture analyses consistently indicated an inverse relationship between PFAS mixtures and TT3 concentrations: (1) a one standard deviation increase in the WQS of the PFAS mixture was associated with a 2.0% decrease in TT3 concentration (95% CI= -4%, 0%, p < 0.05) adjusting for covariates, (2) using PCA, one standard deviation increase in a PFAS mixture was associated with a 1.2% decrease in TT3 (95% CI: -2.1%, -0.4%), and (3) BKMR similarly suggested a negative association between the PFAS mixture and TT3. We observed cross-sectional associations between a mixture of serum PFAS concentrations and thyroid hormone dysregulation, largely manifesting as decreased TT3 serum concentrations.
Introduction and Hypothesis The objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery. Methods A multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months. Results A total of 214 women were randomized to Device ( n = 113) or Control ( n = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group ( p = 0.040; two-tailed Fisher’s test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related. Conclusions The pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.
The objective is to investigate the outcomes of the Hinotori Surgical Robotic System (HSRS) for urological surgery and to analyze the variation in perioperative performance between the HSRS and the da Vinci surgical robot. Multiple databases including PubMed, Cochrane Library, Embase and Web of Science were comprehensibly retrieved to screen studies that applied HSRS to urologic surgery and compared it with the da Vinci system. The results were combined and analyzed using estimated ratio of ratios (OR) and weighted mean difference (WMD). Eight studies with 740 patients were included. Among the baseline characteristics of patients in both groups, all outcomes showed similarity. In urologic surgery, the HSRS cohort experienced a longer operative time (WMD = 8.85, 95% Cl (1.73, 15.97), p < 0.05) and a relatively longer use of the robotic system (WMD = 10.77, 95% Cl [1.09, 20.44], p < 0.05), as well as a notable increase in console time (WMD = 20.99, 95% Cl 95% Cl [8.24, 33.75], p < 0.05). However, estimated blood loss, length of hospitalization, rate of severe complications, and rate of positive margins did not show statistical differences. In urologic surgery, HSRS has a longer operative time, robot system usage time, and console time, but its perioperative results are similar to the Da Vinci system. HSRS shows good clinical promise, however, further long-term data studies are needed to prove it.
Purpose of Review This review synthesizes the recent literature on lower urinary tract symptoms in pediatric patients with congenital conditions. We will discuss emerging insights from multiple studies on pathophysiology, prevalence, clinical impact, management strategies, and long-term outcomes. Recent Findings Surgical advancements have increased early continence rates to 80% in exstrophy-epispadias complex (EEC), but attrition of continence remains a challenge. Studies have shown 40% of males with PUV and 80% of patients with EEC report moderate or severe LUTS which significantly impact quality of life. Summary LUTS in patients with congenital anomalies remains a challenge in pediatric urology. Patients require individualized, lifelong management strategies. Future research should include standardizing continence definitions and assessing comparative effectiveness of treatments to enhance patient-centered outcome metrics. A multidisciplinary approach is critical to promoting sustained improvements in quality of life for individuals living with congenital genitourinary anomalies.
The Wilms tumor 1 ( WT1 ) gene was first identified in 1990 as a strong candidate for conferring a predisposition to Wilms tumor. The WT1 protein has four zinc finger structures (DNA binding domain) at the C-terminus, which bind to transcriptional regulatory sequences on DNA, and acts as a transcription factor. WT1 is expressed during kidney development and regulates differentiation, and is also expressed in glomerular epithelial cells after birth to maintain the structure of podocytes. WT1 -related disorders are a group of conditions associated with an aberrant or absent copy of the WT1 gene. This group of conditions encompasses a wide phenotypic spectrum that includes Denys–Drash syndrome (DDS), Frasier syndrome (FS), Wilms–aniridia–genitourinary–mental retardation syndrome, and isolated manifestations of nephropathy or Wilms tumor. The genotype–phenotype correlation is becoming clearer: patients with missense variants in DNA binding sites including C2H2 sites manifest DDS and develop early-onset and rapidly developing end-stage kidney disease. A deeper understanding of the genotype–phenotype correlation has also been obtained in DDS, but no such correlation has been observed in FS. The incidence of Wilms tumor is higher in patients with DDS and exon-truncating variants than in those with non-truncating variants. Here, we briefly describe the genetic background of this highly complicated WT1 -related disorders.
Background Robotic-assisted surgery has become a standard approach for urological procedures, providing enhanced precision, dexterity, and minimally invasive benefits. However, high costs and limited accessibility limits its broader adoption. This study evaluates feasibility and safety of novel AGIBOT^® robotic system in complex urological surgeries. Methods This prospective, multicenter study evaluated 59 patients undergoing AGIBOT^® assisted partial nephrectomy (PN, n = 37) or radical prostatectomy (RP, n = 22) between December 2023 and May 2024. Primary outcomes assessed feasibility (successful surgery without conversion) and safety (absence of major intraoperative complications). Secondary outcomes included operative time, docking time, estimated blood loss, warm ischemia time, hospital stay, functional recovery, and surgical margin status. Results All procedures were completed successfully without conversions or major intraoperative complications. For partial nephrectomy, the median operative time was 64 min, blood loss was 50 mL, and median warm ischemia time was 16.5 min, with negative surgical margins in all but one case. For radical prostatectomy, the median operative time was 114.5 min, blood loss was 100 mL, and positive surgical margins were observed in four cases (18%). Renal function remained stable after partial nephrectomy, immediate continence was achieved in 30% of RP patients, improving to full continence at six months in all patients. Two postoperative complications occurred but were not considered related to the robotic system. No major device-related malfunctions were observed and none of the patient’s required readmission within 30 days. Conclusions The AGIBOT^® robotic system was feasible and safe for complex urological surgeries, with promising early oncological and functional outcomes. These findings suggest AGIBOT^® as a reliable platform for robotic surgery, although larger, long-term studies are needed to validate these preliminary results. Graphical Abstract
Purpose Our purpose was to evaluate the prognostic value of Vesical Imaging Reporting and Data System (VI-RADS) in bladder cancer (BCa) staging and predicting recurrence or progression. Methods We retrospectively analyzed the prospectively collected data from 96 patients with bladder tumors who underwent VI-RADS-based multiparametric magnetic resonance imaging (mpMRI) before endourological treatment from April 2021 to December 2022. Diagnostic performance was evaluated by comparing mpMRI reports with final pathology, using logistic regression for muscle-invasive bladder cancer (MIBC) predictors. Follow-up until May 2023 included Kaplan-Meier and Cox regression analysis to assess VI-RADS predictive roles for recurrence-free survival (RFS) and progression-free survival (PFS). Results A total of 96 patients (19.8% women, 80.2% men; median age 68.0 years) were included, with 71% having primary tumors and 29% recurrent BCa. Multiparametric MRI exhibited high sensitivity (92%) and specificity (79%) in predicting MIBC, showing no significant differences between primary and recurrent cancers (AUC: 0.96 vs. 0.92, P = .565). VI-RADS emerged as a key predictor for MIBC in both univariate (OR: 40.3, P < .001) and multivariate (OR: 54.6, P < .001) analyses. Primary tumors with VI-RADS ≥ 3 demonstrated significantly shorter RFS ( P = .02) and PFS ( P = .04). Conclusions In conclusion, mpMRI with VI-RADS has a high diagnostic value in predicting MIBC in both primary and recurrent BCa. A VI-RADS threshold ≥ 3 is a strong predictor for MIBC, and in primary tumors predicts early recurrence and progression.
Objective To investigate whether the panoramic view offered by robot-assisted laparoscopic pyeloplasty (RALP) reduces the likelihood of missing a crossing vessel compared to open pyeloplasty in cases where initial pyeloplasty fails. Methods A single institution redo-pyeloplasty database was reviewed for children treated between January 2012 to July 2023. Clinical history, imaging and operative details were reviewed to identify the etiology for the redo procedure. Results Cohort consisted of 45 patients undergoing a redo RALP during the study period. 29 of 45 patients had an initial open surgical approach, whereas 16 had an initial RALP. 10 patients were noted to have a missed crossing vessel on redo pyeloplasty – 9 had an initial open approach whereas 1 had an initial RALP ( p <0.0001). Conclusions RALP may reduce the risk of missing a crossing vessel due to the panoramic view of the surgical field intrinsic to an intraperitoneal RALP approach.
Worldwide, in Africa and Ethiopia prevalence of Benign Prostatic Hyperplasia among patients with lower urinary tract symptoms was 26.2%, 44.2%, and 33.4% respectively. However, there is limited evidence regarding Benign Prostatic Hyperplasia in southern Ethiopia and it was not well explored. Therefore, this study aimed to assess the magnitude and associated factors of Benign Prostatic Hyperplasia among adult male patients visiting Wolaita Sodo University Comprehensive Specialized Hospital, southern Ethiopia 2022. A hospital-based cross-sectional study was conducted from July to September 2022. A systematic random sample technique was employed to select 376 participants. Data were gathered using a structured questionnaire and entered, cleaned, coded, and analyzed using SPSS Version 25.0. To describe the study respondents, descriptive statistics were used. Bivariate and multivariate analyses were conducted and an adjusted odd ratio with 95% Confidence Interval (CI) was utilized to quantify the degree of association, and statistical significance was declared at p-value < 0.05. A total of 376 male patients admitted to the surgical department of the Urology ward were included in this study and the magnitude of Prostatic Hyperplasia was 21.3%; 95% CI: 17.3, 25.8. The vegetable consumption, fruit consumption, physical activity, sleeping time and sexual dysfunction [(AOR = 7.57, 95% CI: (2.78, 20.60)], [(AOR = 21.06,95% CI: (7.06,27.53)], [(AOR = 0.57,95% CI: (0.19, 0.67)], [(AOR = 3.23, 95% CI: (1.18,8.79)] and [(AOR = 17.05, 95% CI: (4.82,60.28)] were factors associated with Benign Prostatic Hyperplasia respectively. The benign prostatic hyperplasia is a prevalent disease among men in this study. Sexual dysfunction, consumption of vegetables, consumption of fruits, practice of physical activity and sleeping time were factors associated with BPH. Hence, screening programs for higher-risk people to ensure the early presentation of benign prostatic hyperplasia and practicing eating balanced diets are vital areas to reduce the prevalence.
Penile prosthesis placement after priapism is challenging due to corporal scarring which may complicate corporal dilation and increase the risk of dilation-related injuries such as corporal perforation, crossover, and urethral injury. Management options for these complications and techniques for difficult dilation are presented here. Important considerations for the placement timing and for device selection are also reviewed. Videos demonstrate difficult dilation maneuvers and early placement of a malleable device after priapism.
Urology has been a leading field in the adoption of robotic surgery, which offers technical advantages and low complication rates, including notably reduced intraoperative blood loss. In this study, we aimed to examine the relationship between formula-based estimated blood loss and visually estimated intraoperative blood loss in robotic urologic procedures. In this retrospective study, 111 robot-assisted urologic surgery were included. The agreement between the visually estimated intraoperative blood loss and the estimated values calculated using different formulas ( Hb dilution method formula , Hb mass method , Gross Formula , López-Picado Formula ). To determine how consistent each estimation was with the visually estimated intraoperative blood loss and with each other, Bland–Altman analysis , Concordance Correlation Coefficient (CCC) and Intraclass Correlation Coefficient (ICC) were applied. Intraoperative blood loss (visual estimation) indicated a mean blood loss of 220.72 ± 212.61 mL, whereas formula-based calculations consistently yielded higher estimates: López-Picado, 721.64 ± 532 mL; Hb mass method, 667.79 ± 429 mL; Gross formula, 726.97 ± 540 mL; and Hb dilution method, 737.99 ± 545 mL. The analyses revealed that all formulas differed statistically significantly from the visually estimated intraoperative blood loss. Evaluation of agreement and consistency demonstrated that the formulas showed poor agreement both with estimated blood loss and with one another. The strongest concordance was observed between López-Picado and Gross formula. There was a large discrepancy between visually estimated intraoperative blood loss and formula-based estimations. While formula-based methods show strong internal consistency, they differ substantially from the subjective estimates commonly used.
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 Ileal ureter interposition is a well-established option for complex ureteral strictures. While minimally invasive approaches have evolved, the application of the single-port (SP) robotic platform for ileal ureter reconstruction has not been previously reported. This study presents the first clinical series evaluating the feasibility, technique, and early outcomes of SP robotic ileal ureter reconstruction. Methods We retrospectively reviewed a prospectively maintained database of patients who underwent SP robotic ileal ureter substitution between September 2019 and November 2024 by a single surgeon. Demographic, perioperative, and functional data were analyzed. Surgical success was defined as freedom from reintervention, absence of radiographic obstruction, and stable renal function. Pre- and postoperative renal function was compared using paired statistical analysis. Results Seventeen patients underwent SP robotic ileal ureter reconstruction (29% male), with a mean age of 54 years. Radiation-induced strictures accounted for 70.6% of cases. Unilateral reconstruction was performed in 8 (47.1%), while 8 (47.1) required bilateral reconstruction with V-shaped or reverse-7 configurations, including bladder augmentation in selected cases. One patient (5.9%) underwent unilateral ileal ureter with bladder neck reconstruction. The median ileal segment length was 25 cm. Mean operative time was 308 min, and median blood loss was 70 mL. One intraoperative complication (5.9%) occurred. Postoperative complications were observed in 47%, with 11.8% classified as Clavien–Dindo grade IIIa. Renal function remained stable (preoperative eGFR 56.4 vs. postoperative 57.5 mL/min/1.73 m², p = 0.803). At a median follow-up of 20.5 months, the overall success rate was 94.1%. Conclusions Single-port robotic ileal ureter reconstruction is a feasible and effective technique for complex ureteral strictures, achieving high early success with acceptable morbidity.
Background The gut microecosystem represents the most abundant and complex microbial ecosystem in the human body. Maintaining homeostasis of gut microbiota and their metabolites is essential for human health. As a chronic metabolic disorder, the association between benign prostatic hyperplasia (BPH) and gut microbiota remains unclear. Growing evidence suggests that modulating the composition and function of gut microbiota may influence the gut-prostate axis, thereby affecting the development and progression of prostatic hyperplasia. In this study, we employed network pharmacology to systematically elucidate the complex interactions among gut microbiota, microbial metabolites, and BPH-related therapeutic targets. Methods In this study, we first retrieved information on gut microbial metabolites from the gutMGene database. Subsequently, we identified overlapping targets of these metabolites using the SEA and STP databases. To further clarify targets related to BPH, we integrated data from authoritative databases such as Genecard and OMIM. Based on this information, we constructed a protein-protein interaction (PPI) network to screen for core targets. In addition, we performed systematic GO and KEGG functional enrichment analyses of these targets using the DAVID database. we constructed a network model to illustrate the interactions among microbiota, substrates, metabolites, and targets.Finally, molecular docking validation was performed between the core targets and gut microbiota metabolites. Results We identified 43 overlapping targets between gut microbial metabolites and BPH. Subsequently, we selected AKT1, IL-6, and IL-1B as core therapeutic targets for BPH. By constructing an MSMT comprehensive network, we found that these three core targets exert therapeutic effects on BPH through interactions with 11 metabolites, 2 substrates, and 4 gut microbial species. Furthermore, GO analysis revealed that gut microbial metabolites influence prostatic hyperplasia by regulating inflammation, immune responses, and the activation of oxidoreductase activity. KEGG analysis indicated that the AGE-RAGE signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, C-type lectin receptor signaling pathway, and PI3K/Akt signaling pathway are the major pathways involved in BPH.The molecular docking results demonstrated that butyrate may influence prostatic hyperplasia by modulating the AKT1 gene. Discussion This study employs a network pharmacology approach to elucidate the intricate “Microbiota-Substrate-Metabolite-Target” (M-S-M-T) network in Benign Prostatic Hyperplasia (BPH), identifying key hub genes (AKT1, IL-6, IL-1B), signaling pathways (PI3K/Akt, AGE-RAGE, HIF-1), and gut microbiota-derived metabolites (butyrate, propionate, TMAO) as central regulators. It further characterizes the functional significance of the Bifidobacterium-tryptophan and Clostridium sporogenes-tyrosine axes, highlighting their probiotic potential for microbiota-targeted BPH therapy. While demonstrating the therapeutic promise of modulating the gut microbiome, the study underscores the need for future experimental validation to decipher the precise mechanistic links within the M-S-M-T network and its role in BPH pathogenesis Conclusion IL-6, AKT1, and IL-1B serve as the primary targets through which gut microbiota metabolites exert their therapeutic effects on benign prostatic hyperplasia.
Purpose Living donor kidney transplantation is a critical strategy to address the growing burden of end-stage kidney disease (ESKD) in Malaysia. Whilst living donation is generally safe, concerns remain regarding long-term donor outcomes. This study aimed to evaluate renal function and morbidity changes in living kidney donors 1 year post-donation, and to identify predictors of impaired kidney function. Methods A retrospective cohort study was conducted using clinical records of 230 living kidney donors who underwent nephrectomy at University Malaya Medical Centre between 2003 and 2021. Donor sociodemographic characteristics, comorbidities, and estimated glomerular filtration rate (eGFR) were assessed pre-donation and at 1 year post-donation. Impaired kidney function was defined as eGFR < 90 mL/min/1.73m^2. Data were analysed using descriptive statistics and multivariate logistic regression. Results At 1 year post-donation, 76.2% of donors exhibited impaired kidney function. Additionally, the proportion of donors with diabetes and dyslipidaemia increased significantly post-donation. Male sex and increasing age were significant predictors of reduced eGFR. Ethnic Chinese and 'Others' ethnicities were found to have a lower risk of impaired renal function compared to Malays. No significant association was found between baseline comorbidity status and post-donation eGFR. Conclusion The study highlights the importance of age, gender, and ethnicity in predicting renal outcomes post-donation. These findings underscore the need for standardised pre-donation screening and structured post-donation surveillance. Strengthening clinical protocols and policy frameworks is essential to ensure donor safety and the sustainability of living donor transplantation in Malaysia.
The gold standard treatment for renal cell carcinoma with a tumor thrombus (RCC-TT) is radical nephrectomy with tumor thrombectomy (RN-TT). Operative approaches to this can be done open (ORN-TT), laparoscopic (LRN-TT), or robotic (RRN-TT). The purpose of this study was to compare overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) between open, laparoscopic, and robotic approaches to RN-TT using the Intercontinental Collaboration on Renal Cell Carcinoma (ICORCC) database. Patient records were reviewed from the ICORCC database. All patients included in the study underwent RN-TT for RCC-TT from 1999 to present. Tumor thrombus level was graded using the Neves classification system. Statistical analysis was carried out using analysis of variance, chi-squared test, and Kaplan–Meier survival curves with log-rank test to compare outcomes by surgical approach. A total of 392 patients were included. There were 308 ORN-TT, 61 LRN-TT, and 23 RRN-TT cases. On Kaplan–Meier analysis, OS and CSS were not significantly different by approach ( p > 0.05). MFS was significantly lower in RRN-TT patients ( p = 0.030). Operative time was the longest in ORN-TT, followed by LRN-TT, and RRN-TT the quickest ( p = 0.011). Blood transfusion rates were significantly lower in RRN-TT relative to ORN-TT ( p < 0.001). Rates of lymph node dissection, soft tissue margin positivity, and cytoreductive surgery were alike ( p > 0.05). There is no definitive superiority of one operative approach compared to another. RRN-TT may result in worse MFS for patients, which calls for further investigation, but this is not certain. Ultimately, the risks, benefits, and resources the surgeon has at his/her disposal should all play in the final operative choice of RN-TT for the patient.
This chapter will review the da Vinci^® Xi robotic operating system, equipment, necessary personnel, and operating room setup for standard urologic surgical procedures, including pelvic and upper retroperitoneal operations.
Background The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity. Methods We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann–Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien–Dindo surgical complication classification method. Results Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries ( P < 0.001), more IVC interruptions ( P <0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique ( P < 0.001), and a greater need for cut-off of the short hepatic vein ( P < 0.001) and liver dissociation ( P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time ( P < 0.001), more surgical blood loss ( P <0.001), more intra-operative blood transfusion ( P < 0.001), and longer postoperative hospital stay ( P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001). Conclusion Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus.
Purpose Cryptorchidism is a common congenital abnormality affecting male infants and is associated with impaired germ cell maturation and infertility. Current guidelines recommend orchidopexy between 6 and 18 months of age to optimize fertility-related outcomes; however, the real-world feasibility of early surgery is limited, and the benefits of earlier intervention remain uncertain. This study aimed to evaluate whether orchidopexy before 12 months reduces testicular atrophy and postoperative complications compared with surgery after 12 months. Methods A systematic literature search of five databases was conducted following PRISMA guidelines. Studies comparing early (< 12 months) versus late orchidopexy in boys with cryptorchidism were included, based on thresholds within the available data. The primary outcome was testicular atrophy; secondary outcomes included postoperative complications and fertility-related markers. Random-effects meta-analyses were performed with outcomes reported as odds ratios (OR) and 95% confidence intervals (CI). Certainty of evidence was assessed using the GRADE framework. Results Sixteen studies were included. Meta-analysis of 1855 testes from five studies showed no significant difference in testicular atrophy between orchidopexy before 12 months (OR 1.05, 95% CI 0.49–2.23; I² = 0%). Pooled analysis of 757 testes across three studies showed no significant difference in postoperative complication rates (OR 1.15, 95% CI 0.44–2.99; I² = 36%). The overall quality of evidence was rated low for both outcomes. Conclusion Available data of low quality suggest that orchidopexy before 12 months does not significantly reduce testicular atrophy or postoperative complications compared with later surgery.
Hintergrund Der Hodenhochstand (Kryptorchismus) stellt mit einer Prävalenz von 1–4 % bei reifgeborenen männlichen Neugeborenen die häufigste angeborene Anomalie des urogenitalen Systems dar. Bei Frühgeborenen liegt die Inzidenz deutlich höher. Eine frühzeitige Diagnostik und Therapie sind entscheidend, um langfristige Komplikationen wie Fertilitätsstörungen und ein erhöhtes Malignitätsrisiko zu reduzieren. Ziel Darstellung der aktuellen diagnostischen und therapeutischen Strategien beim Hodenhochstand unter besonderer Berücksichtigung interdisziplinärer Aspekte in der pädiatrischen Versorgung. Ergebnisse Die klinische Untersuchung bleibt der zentrale Bestandteil der Diagnostik, unterstützt durch Sonographie und in ausgewählten Fällen durch laparoskopische Verfahren. Die frühzeitige Orchidopexie innerhalb des ersten Lebensjahres gilt als Goldstandard. Sie führt zu einer signifikant besseren Erhaltung der Keimzell- und Leydig-Zell-Funktion sowie zu einer Reduktion des Entartungsrisikos. Eine hormonelle Behandlung wird leitliniengerecht nur noch zurückhaltend eingesetzt. Schlussfolgerung Die interdisziplinäre Abklärung des Hodenhochstands als auch eine frühzeitige operative Sanierung gewährleisten ein gutes Outcome bezüglich Fertilität und Entartungsrisko. Die strukturierte postoperative Nachsorge bis ins Jugendalter ist essenziell zur Früherkennung von Atrophie, Reaszensus und malignen Veränderungen. Background Cryptorchidism represents the most common congenital anomaly of the male urogenital system, affecting 1–4% of term male neonates, with markedly higher incidence rates in preterm infants. Early diagnosis and timely treatment are essential to prevent long-term complications such as infertility and an increased risk of testicular cancer. Objective To provide an overview of current diagnostic and therapeutic strategies for cryptorchidism, with particular emphasis on interdisciplinary aspects in pediatric management. Results Clinical examination remains the cornerstone of diagnosis, supported by ultrasonography and, in selected cases, by laparoscopic assessment. Early orchidopexy within the first year of life is considered as first-line therapy resulting in significantly improved preservation of germ cell and Leydig cell function and a reduced risk of malignant transformation. Hormonal therapy is only applied restrictively in accordance with current guidelines and should not delay surgical treatment. Structured postoperative follow-up into adolescence is essential for the early detection of atrophy, re-ascent, and neoplastic changes. Conclusion Standardized, early, and interdisciplinary management of children with cryptorchidism substantially improves long-term outcomes regarding fertility and oncologic safety. Early surgical intervention remains the key prognostic factor for optimal testicular development and long-term health.
Background Ureteral strictures are a potentially obstructive condition that, if left untreated, may progress to chronic kidney disease. The leading cause is iatrogenic, most commonly following endourological surgery or gynecological procedures. While reconstructive surgery—either open or robotic—remains the gold standard, endourological stents represent a viable alternative in many cases. Case presentation We report the case of a 54-year-old woman who sustained an iatrogenic complete transection of the distal right ureter during myomectomy. Initial management included percutaneous nephrostomy and delayed open ureteral reconstruction using a Boari flap. Postoperative complications included stent dislocation and partial anastomotic dehiscence, necessitating revision surgery. Despite these interventions, the patient developed a recurrent distal ureteral stricture with persistent symptoms and stent intolerance. As a minimally invasive alternative, an Allium® self-expanding ureteral stent (Allium Ltd., Caesarea, Israel) was placed endoscopically. The patient experienced marked clinical improvement, stable renal function, and no major complications such as migration or encrustation. A localized inflammatory reaction at the stent contact zone was identified upon follow-up ureteroscopy, with biopsy confirming chronic inflammation. Conclusion The Allium® ureteral stent represents a safe, effective, and well-tolerated option for managing complex recurrent ureteral strictures in patients who are poor candidates for, or unwilling to undergo, surgical reconstruction. This case illustrates the stent’s potential to preserve renal function and improve patient quality of life while minimizing the need for frequent interventions. Careful patient selection and regular endoscopic follow-up are critical to optimizing outcomes. Hintergrund Ureterstrikturen stellen eine potenziell obstruktive Erkrankung dar, die unbehandelt zur chronischen Niereninsuffizienz führen kann. Die führende Ursache ist iatrogen, zumeist nach endourologischen oder gynäkologischen Operationen. Während rekonstruktive Operationen – entweder offen oder robotergestützt – weiterhin den Goldstandard bilden, sind endourologische Stents in vielen Fällen eine praktikable Alternative. Falldarstellung Vorgestellt wird der Fall einer 54-jährigen Frau, bei der es iatrogen zur kompletten Durchtrennung des distalen rechten Ureters bei einer Myomektomie kam. Zur initialen Behandlung gehörte eine perkutane Nephrostomie und eine verzögerte offene Ureterrekonstruktion mit einem Boari-Lappen. An postoperativen Komplikationen traten eine Stentdislokation und eine partielle Anastomosendehiszenz auf, die eine Revisionsoperation erforderten. Trotz dieser Interventionen entwickelte sich bei der Patientin eine rezidivierende distale Ureterstriktur mit persistierenden Symptomen und Stentunverträglichkeit. Als minimal invasive Alternative wurde endoskopisch ein selbstexpandierender Allium®-Ureterstent platziert (Fa. Allium Ltd., Caesarea, Israel). Bei der Patientin kam es zur deutlichen klinischen Besserung und stabilen Nierenfunktion, größere Komplikationen wie Migration oder Verkrustungen traten nicht auf. Eine lokalisierte entzündliche Reaktion im Bereich der Stentkontaktzone wurde bei der Nachsorgeureteroskopie diagnostiziert, mittels Biopsie bestätigte sich die chronische Entzündung. Schlussfolgerung Der Allium®-Ureterstent stellt eine sichere, wirksame und gut verträgliche Option für die Behandlung komplexer rezidivierender Ureterstrikturen bei Patienten dar, die für eine chirurgische Rekonstruktion nicht gut geeignet sind oder diese nicht wünschen. Der vorliegende Fall zeigt das Potenzial von Stents, die Nierenfunktion zu erhalten und die Lebensqualität der Patienten zu verbessern, während die Notwendigkeit häufiger Interventionen minimiert wird. Eine sorgfältige Patientenauswahl und regelmäßige endoskopische Nachuntersuchungen sind entscheidend für die Optimierung der Ergebnisse.
Purpose Transperineal laser ablation (TPLA) is a new minimally-invasive surgical treatment for patients with benign prostatic obstruction (BPO). We report the perioperative and mid-term functional results of the first 100 consecutively patients undergoing TPLA at our institution. Methods Clinical data from consecutive patients undergoing TPLA at our institution from April 2021 to July 2023 were prospectively collected. Primary endpoints were the postoperative changes in IPSS, QoL and MSHQ 3-item questionnaires and in Qmax and post-void residual volume (PVR). Results Overall, 100 consecutive patients underwent the procedure. Median age and prostate volume were 66 (IQR 60–75) years and 50 (IQR 40–70) ml, respectively. In the cohort, 14 (14%) patients had an indwelling catheter and 81 (81%) were under oral BPO therapy at the time of TPLA. Baseline median Qmax (ml/s) and PVR (ml) were 9.1 (IQR 6.9–12) and 90 (IQR 50–150), respectively, while median IPSS and QoL were 18 (IQR 15–23) and 4 (IQR 3–4). At all the follow-up timepoints, the evaluated outcomes on both symptoms and functional parameters showed a statistically significant improvement ( p < 0.001). Antegrade ejaculation was preserved in all sexually active patients. No postoperative Clavien-Dindo > 2 complications were recorded. Conclusions TPLA represents a safe option for selected well-informed patients swith LUTS due to BPO. Our prospective study confirms the feasibility and favorable perioperative and functional outcomes in a real-world cohort with heterogenous prostate volumes and patient characteristics.
Objectives The nursing management of adult urology patients in day surgical settings has undergone rapid development. This study aimed to (1) retrieve, evaluate, and summarize the best available evidence regarding the perioperative nursing management in adult patients undergoing urological day surgery, and (2) develop a functional prototype of an evidence-based nursing management mobile application (APP) using an artificial intelligence (AI)-assisted pathway. Methods This research was conducted in two phases. First, in April 2025, a best evidence summary was conducted across many databases utilizing the PIPOST tool. Clinical guidelines, systematic reviews, expert consensus documents, clinical decision tools, and evidence summaries were included and screened. Formal quality appraisal was conducted for clinical guidelines, systematic reviews, and expert consensus documents using appropriate appraisal tools. Second, an AI-augmented platform called Manus AI was used to create an app prototype with the best evidence summary. This platform made it possible to design the architecture, organize the material, and create user interface mock-ups. Results The best evidence summary included 21 studies that were thematically classified into eight nursing management domains: nursing organization management, pre-hospital nursing management, preoperative nursing management, intraoperative nursing management, postoperative nursing management, discharge management, nursing follow-up and nursing quality management. This framework was successfully used to create a completely structured app prototype. The eight domains are reflected in the app prototype. Preliminary feedback from 12 clinical nurses indicated that the prototype was clinically meaningful and may support standardized perioperative nursing management in adult urology day surgery. Conclusion This study summarizes the current best evidence and demonstrates a novel AI-empowered pathway for translating evidence into a practical digital tool. The developed app prototype offers a promising foundation for standardizing nursing care in urological day surgery. Future studies are needed to determine whether the app prototype could improve protocol adherence and patient outcomes. Clinical trial number Not applicable.
In individuals with diabetes, chronic kidney disease (CKD) is a major comorbidity. However, it appears that there is worldwide confusion regarding which term should be used to describe CKD complicated with diabetes: diabetic nephropathy, diabetic kidney disease (DKD), CKD with diabetes, diabetes and CKD, etc. Similar confusion has also been reported in Japan. Therefore, to provide clarification, the Japanese Diabetes Society and the Japanese Society of Nephrology collaborated to update the corresponding Japanese term to describe DKD and clearly define the concept of DKD. In this review, we briefly described the history of kidney complications in individuals with diabetes and the Japanese definition of the DKD concept and provided our rationale for these changes.
SIMPLE SUMMARY: Access to veterinary care for pet owners is an important part of keeping animals healthy. Not having enough money and other resources can make it hard for pet owners to get veterinary care. Recently, veterinarians have started offering a range of care options to address clients’ needs. But veterinarians still mainly give the most technological and specialized care they learned in their training. The goal of this study was to learn more about veterinarians’ behaviors, knowledge, attitudes, and beliefs about offering more treatments in a range from less to more sophisticated. This study found that many veterinarians do report offering a range, but that it is mostly the veterinarians who feel the most comfortable and confident doing it. When veterinarians had been in practice for more than 20 years, they were less likely to offer a range of services. Rural veterinarians were more likely to offer a range than urban veterinarians. These results offer a reference for more exploration into what veterinarians report about offering a range of care options to people who need help. ABSTRACT: Access to veterinary care for animal owners is an important part of keeping animals healthy and keeping pets and people together whenever that is appropriate. Insufficient financial and other resources to allocate to veterinary care are major barriers for pet owners to receiving preventative, sick, and emergency services. The veterinary community has begun to incorporate offering a range of diagnostic and treatment options more intentionally in response to clients’ inability to pay and to a lesser extent to mitigate other barriers to care. Many veterinarians are nonetheless oriented toward providing specialized and more sophisticated care based on their training. This study sought to identify the self-reported behaviors, knowledge, attitudes, and beliefs of veterinarians about offering a spectrum of care options (SoC) to clients. The finding that many reported offering SoC is encouraging. However, veterinarians who report comfort and confidence in a variety of aspects of clinical care were most likely to offer SoC. Practitioners in the field for 20 or more years were less likely to offer SoC to clients with financial limitations. Rural veterinarians were more likely to offer SoC to any client compared to urban veterinarians. These results provide a point of reference and potential focus for veterinarians who are not currently offering SoC as well as an exploration of veterinarians’ reported knowledge, behaviors, attitudes, perceptions, and concerns about SoC.
SIMPLE SUMMARY: This is a study related to NDM-5-producing E. coli in companion animals in China. Notably, an E. coli isolate possessing both bla(NDM-5)-bearing plasmid and mcr-1-bearing plasmid was identified in a dog from the same veterinary clinic, where we previously found the mobile IncX3–X4 hybrid plasmid encoding both bla(NDM-5) and mcr-1 in a cat. This observation highlights the diversity of bla(NDM-5)- and mcr-1-harboring plasmids and the transferability of such resistant pathogens from companion animals to humans. Given that colistin is the last-resort antibiotic for treating human infections caused by carbapenem-resistant Enterobacteriaceae, the co-transfer of resistance to both antibiotics may seriously compromise the effectiveness of clinical therapy. ABSTRACT: Carbapenem and colistin are important antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative pathogens. Here, we isolated the bla(NDM-5)-harboring Escherichia coli in companion animals in healthy or diseased companion animals from veterinary clinics in six cities in China from July to November 2016. A total of 129 rectal swabs of healthy or diseased dogs and cats were collected from veterinary clinics in six different cities in China, and the isolates were subjected to carbapenem and colistin susceptibility testing. Resistance genes were confirmed using PCR. Conjugation experiments were conducted to determine the transferability of antibiotic resistance genes (ARGs) in the strains. The isolated rate of bla(NDM-5)-harboring E. coli strains was 3.88% (five strains). These five strains were multidrug resistant to at least three antibiotics and corresponded to four sequence types including ST101. The bla(NDM-5) gene was located on 46 kb IncX3 plasmids in these five strains, and the genetic contexts were shared and were nearly identical to the K. pneumoniae plasmid pNDM5-IncX3 from China. In addition, one strain (CQ6-1) co-harbored bla(NDM-5)-encoding-IncX3 plasmid along with a mcr-1-encoding-IncX4 plasmid, and their corresponding genetic environments were identical to the bla(NDM-5)-IncX3 and mcr-1-IncX4 hybrid plasmid reported previously from the same area and from the same clinic. The results indicated that the similar genetic contexts were shared between these isolates from companion animals, and the IncX3-type plasmids played a key role in the spread of bla(NDM-5) among these bacteria.
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.
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.
International audience;
Veterinary practices can be stressful places for dogs. Decreasing stress during veterinary consultations is therefore a major concern, since animal welfare matters both for owners and veterinarians. Stress can be expressed through behaviour modifications; monitoring dogs’ behaviour is thus one way to assess stress levels. We also know that the owner can affect dog behaviour in different ways. The aim of this study was therefore to assess the effect of the presence of owners on the behaviour of their dogs in veterinary consultations. We studied dogs-owner dyads at two standardised veterinary consultations, conducted at intervals of five to seven weeks; the owner was present for the first consultation and absent for the second (O/NoO group, n= 12), or vice versa (NoO/O group, n= 13). A consultation consisted in three phases: exploration, examination, greeting. Dog behaviours were compared between the two conditions using a video recording.
OBJECTIVES: To estimate the frequency and risk factors for Cushing's syndrome in dogs under UK primary veterinary care. MATERIALS AND METHODS: Dogs with Cushing's syndrome were identified by searching electronic patient records of primary‐care veterinary practices. Pre‐existing and incident cases of Cushing's syndrome during 2016 were included to estimate the 1‐year period prevalence. Incident cases were used to estimate the annual incidence and to identify demographic risk factors for the diagnosis of Cushing's syndrome in dogs, through multivariable logistic regression. RESULTS: Analysis included 970 pre‐existing and 557 incident cases of Cushing's syndrome from a population of 905,544 dogs. The estimated 1‐year period prevalence for Cushing's syndrome in dogs under veterinary care was 0.17% (95% confidence interval 0.16 to 0.18) and incidence was 0.06% (95% confidence interval 0.05 to 0.07). In multivariable logistic regression modelling, the Bichon frise (odds ratio=6.17, 95% confidence interval 4.22 to 9.00), Border terrier (5.40, 95% confidence interval 3.66 to 7.97) and Miniature schnauzer (3.05, 95% confidence interval 1.67 to 5.57) had the highest odds of Cushing's syndrome. The Golden retriever (0.24, 95% confidence interval 0.06 to 0.98) and Labrador retriever (0.30, 95% confidence interval 0.17 to 0.54) were the most protected breeds. Increasing age, bodyweight greater than the breed‐sex mean and being insured also showed increased odds of Cushing's syndrome. CLINICAL SIGNIFICANCE: As Cushing's syndrome is predominately diagnosed and managed in primary‐care practice, this study provides valuable new information of its epidemiology in this setting. Demographics reported are supportive of previous work and additional novel associations identified, such as the Border terrier, could enhance the index of suspicion for veterinarians.
SIMPLE SUMMARY: Veterinarians are animal health experts. More recently, explicit references to veterinarians as animal welfare experts have proliferated. Veterinarians are ideally situated to act as animal welfare experts by virtue of their core work with animals, influence over owners, their roles in policy development, compliance, and monitoring, and as educators of future veterinary professionals. However, the discipline of animal welfare science has moved beyond a focus on nutrition and health towards an acceptance that the mental experiences of animals are the focus of welfare consideration. The Five Domains Model is a framework for assessing animal welfare and focuses on mental experiences arising from a broad range of impacts or opportunities. The Model can be used as a framework to integrate contemporary understanding of animal welfare science in veterinary curricula and improve welfare literacy within the veterinary profession. ABSTRACT: Veterinarians are animal health experts. More recently, they have been conferred a leading role as experts in animal welfare. This expectation of veterinarians as welfare experts appears to stem from their training in veterinary medicine as well as professional contributions to welfare-relevant policy and law. Veterinarians are ideally situated to act as animal welfare experts by virtue of their core work with animals and potential influence over owners, their roles in policy development, compliance, and monitoring, and as educators of future veterinarians. However, since its inception as a discipline over 70 years ago, animal welfare science has moved beyond a two-dimensional focus on nutrition and health (biological functioning) towards an understanding that the mental experiences of animals are the focus of welfare consideration. The Five Domains Model is a structured and systematic framework for more holistically considering conditions that contribute to the animal’s internal state and its perception of its external situation, and the resultant mental experiences. The Model can be used to better align veterinary animal welfare expertise with contemporary understanding of animal welfare science and improve welfare literacy within the veterinary profession. Improved understanding of animal welfare science is likely to lead to increased confidence, competence, and empowerment to act as experts in their daily lives.
Background: Bacterial corneal infections are common and potentially blinding diseases in all species. As antibiotic resistance is a growing concern, alternative treatment methods are an important focus of research. Photoactivated chromophore for keratitis-corneal crosslinking (PACK-CXL) is a promising oxygen radical-mediated alternative to antibiotic treatment. The main goal of this study was to assess the anti-bactericidal efficacy on clinical bacterial isolates of the current standard and an accelerated PACK-CXL treatment protocol delivering the same energy dose (5.4 J/cm$^{2}$).
Methods: Clinical bacterial isolates from 11 dogs, five horses, one cat and one guinea pig were cultured, brought into suspension with 0.1% riboflavin and subsequently irradiated. Irradiation was performed with a 365 nm UVA light source for 30 min at 3mW/cm$^{2}$ (standard protocol) or for 5 min at 18mW/cm$^{2}$ (accelerated protocol), respectively. After treatment, the samples were cultured and colony forming units (CFU’s) were counted and the weighted average mean of CFU’s per μl was calculated. Results were statistically compared between treated and control samples using a linear mixed effects model.
Results: Both PACK-CXL protocols demonstrated a significant bactericidal effect on all tested isolates when compared to untreated controls. No efficacy difference between the two PACK-CXL protocols was observed.
Conclusion: The accelerated PACK-CXL protocol can be recommended for empirical use in the treatment of bacterial corneal infections in veterinary patients while awaiting culture results. This will facilitate immediate treatment, the delivery of higher fluence PACK-CXL treatment within a reasonable time, and minimize the required anesthetic time or even obviate the need for general anesthesia.
SIMPLE SUMMARY: On the one hand, veterinary ethics is a required part of veterinary education. On the other hand, the success of ethics teaching and the students’ skills concerning judgements in morally demanding situations are hardly evaluated systematically. This article presents an innovative tool to evaluate those skills in veterinary students in a first case of application. One group of students in this case had taken ethics classes, the other had not. The participants were asked to fill in a questionnaire with different scenarios from veterinary practice and answer additional free-text questions. Students who had taken ethics classes did not answer generally different from those students who had not taken ethics classes. However, there were many overall differences between the students’ answers, decisions, attitudes, and explanations. The tool is therefore suggested for further evaluations of ethics teaching and moral judgement skills in veterinary students. ABSTRACT: Although veterinary ethics is required in veterinary curricula and part of the competencies expected of a trained veterinary surgeon according to the European Association of Establishments for Veterinary Education (EAEVE), knowledge concerning the effects of ethics teaching and tools evaluating moral judgement are scarce. To address this lack of tools with a mixed-methods approach, a questionnaire with three case scenarios presenting typical ethical conflicts of veterinary practice was administered to two groups of veterinary students (one had taken ethics classes, one did not). The questionnaire contained both open-ended and closed questions and was analysed qualitatively and quantitatively. The qualitative part aimed at revealing different argumentation patterns between the two groups, whereas the quantitative part focused on the students’ approval of different roles and attitudes possibly relating to veterinarians. The results showed no major differences between both groups. However, answering patterns suggest a clear diversity among the students in their perception of morally relevant factors and the veterinary profession. Awareness of morally challenging elements of their profession was presented by students of both groups. With this exploratory study, the application of an innovative mixed-methods tool for evaluating the moral judgement of veterinary medical students is demonstrated.
ChatGPT, the most accessible generative artificial intelligence (AI) tool,
offers considerable potential for veterinary medicine, yet a dedicated review
of its specific applications is lacking. This review concisely synthesizes the
latest research and practical applications of ChatGPT within the clinical,
educational, and research domains of veterinary medicine. It intends to provide
specific guidance and actionable examples of how generative AI can be directly
utilized by veterinary professionals without a programming background. For
practitioners, ChatGPT can extract patient data, generate progress notes, and
potentially assist in diagnosing complex cases. Veterinary educators can create
custom GPTs for student support, while students can utilize ChatGPT for exam
preparation. ChatGPT can aid in academic writing tasks in research, but
veterinary publishers have set specific requirements for authors to follow.
Despite its transformative potential, careful use is essential to avoid
pitfalls like hallucination. This review addresses ethical considerations,
provides learning resources, and offers tangible examples to guide responsible
implementation. Carefully selected, up-to-date links to platforms that host
large language models are provided for advanced readers with programming
capability. A table of key takeaways was provided to summarize this review. By
highlighting potential benefits and limitations, this review equips
veterinarians, educators, and researchers to harness the power of ChatGPT
effectively.
Background In animals, the endocannabinoid system regulates multiple physiological functions. Like humans, animals respond to preparations containing phytocannabinoids for treating several conditions. In Argentina, laws 27350 and 27669 have expanded the possibility of studying beneficial and adverse effects. Materials and methods We conducted a web-based survey of Argentinian Cannabis Veterinarians to make a situational diagnosis on the number of veterinary medicine professionals currently developing treatments with cannabinoids focusing on dogs and cats. Results Among the species treated, 77% corresponded to dogs, while 21% were cats. Pain, seizures, and behavior disorders are the most prevalent conditions in dogs. Seven conditions and combinations were treated in cats. Full-spectrum cannabis extract derived from three different chemotypes was administered alone or with standard medication. Response to cannabis treatment was characterized based on improvement categorized according to clinical assessment. Both dogs and cats showed different improvement grades in clinical signs. Conclusion This analysis provides promising results regarding the medicinal use of cannabis in dogs and cats. Based on this analysis, we propose to expand the training of professionals, obtain quality preparations, and initiate controlled trials to reinforce knowledge of the use of cannabinoids in veterinary medicine.
Large language models (LLMs) are increasingly used in clinical settings, yet their performance in veterinary medicine remains underexplored. We evaluated three commercially available veterinary-focused LLM summarization tools (Product 1 [Hachiko] and Products 2 and 3) on a standardized dataset of veterinary oncology records. Using a rubric-guided LLM-as-a-judge framework, summaries were scored across five domains: Factual Accuracy, Completeness, Chronological Order, Clinical Relevance, and Organization. Product 1 achieved the highest overall performance, with a median average score of 4.61 (IQR: 0.73), compared to 2.55 (IQR: 0.78) for Product 2 and 2.45 (IQR: 0.92) for Product 3. It also received perfect median scores in Factual Accuracy and Chronological Order. To assess the internal consistency of the grading framework itself, we repeated the evaluation across three independent runs. The LLM grader demonstrated high reproducibility, with Average Score standard deviations of 0.015 (Product 1), 0.088 (Product 2), and 0.034 (Product 3). These findings highlight the importance of veterinary-specific commercial LLM tools and demonstrate that LLM-as-a-judge evaluation is a scalable and reproducible method for assessing clinical NLP summarization in veterinary medicine. ;4 Figures, 10 pages
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.
Antibiotic resistance is a global public health concern that could lead to millions of deaths if nothing is done. As a One Health problematic, it needs to be addressed both in human, animal and environmental sectors. Vietnam, with a population of nearly 100 million, is one of the fastest growing economies and demographics in Southeast Asia. The chicken production sector is undergoing a major transformation. The average growth rate of the chicken population is 6% per year and farms are intensifying. Antibiotic misuse and overuse in chicken production is common in Vietnam as products are easily accessible and that the sector is poorly regulated. As a result, many of the bacteria isolated from chicken farms are multi-drug resistant. Strategies exist to tackle antibiotic resistance but they are implemented with difficulties. The objective of this thesis is to co-develop with the stakeholders of the poultry supply chain and of the veterinary drug value chain, strategies to reduce antibiotic use in chicken production in Vietnam. To answer to this objective, we have adopted a transdisciplinary, systemic and participatory approach.After an exploratory study to understand the context in which our study takes place, we have built a typology of antibiotic use practices among the different chicken production systems. We identified three chicken production systems: household, family commercial farms and intensive farms. The decision-making process of farmers varied according to the production system. During the exploratory study, we also identified changes in the regulatory framework and tried to understand how these changes are understood, acknowledged and applied by the stakeholders of the veterinary drug value chain. After mapping the chain and identifying stakeholder’s posture regarding the regulations we have explored the barriers and motivations to implement them. Major barriers included the lack of capacity of the authorities to enforce the regulations, a mismatch between theory and practices, the lack of knowledge on the new regulations and the high proportion of small-scale farms. Because farmers will have no choice but to adapt to the changes in regulations, we then explored how farmers at a local level are dealing with the necessity to reduce antibiotic use. We identified local solutions such as the use of locally-handmade probiotics, knowledge exchange, and organization of farmers in cooperatives to overcome the barriers to ABU reduction. Finally, all the identified barriers and levers were put in to context through the organization of workshops aimed at co-build strategies. The workshops were organized at the local level with stakeholders of the chicken and veterinary value chain. Strategies aiming to improve training and communication on biosecurity and organic production were co-developed.Within this work, we identified barriers and levers to the reduction of antibiotic use in chicken production in Vietnam. Our study emphasizes the need to adopt a systemic and participatory approaches to co-develop local-based solutions using bottom-up approaches. Strategies and solutions must then be disseminated to policy makers for a sustainable change in practice. We also identified the development of quality products value chain in Vietnam that could act as a lever to change of practice but should be done by taking into consideration the most vulnerable stakeholders. Further studies must be conducted in this direction.
;
La résistance aux antibiotiques est un problème de santé publique mondial et pourrait entraîner des millions de décès si rien n'est fait. En tant que problématique One Health, elle doit être adressée à la fois dans le secteur humain, animal et environnemental. Le Viêt Nam compte près de 100 millions d'habitants, il est l'un des pays d'Asie du Sud-Est dont l'économie et la démographie connaissent la croissance la plus rapide. Le secteur de la production de poulets est en pleine transformation. Le taux de croissance moyen de la population de poulets est de 6 % par an et les élevages s’intensifient. L'utilisation abusive et excessive d'antibiotiques est courante au Viêt Nam car les produits sont facilement accessibles et le secteur peu réglementé. En conséquence, de nombreuses bactéries isolées dans les élevages de poulets sont résistantes aux antibiotiques. Des stratégies existent pour lutter contre cette menace mais sont difficilement mises en place. L'objectif de cette thèse est de codévelopper avec les acteur·rices de la filière poulets et de la chaîne de distribution du médicament vétérinaire des stratégies pour réduire l'utilisation des antibiotiques dans les élevages. Pour répondre à cet objectif, nous avons adopté une approche transdisciplinaire, systémique et participative. Après une étude exploratoire pour comprendre le contexte dans lequel se déroule notre étude, nous avons construit une typologie des pratiques d'utilisation des antibiotiques parmi les différents systèmes de production de poulet. Nous avons identifié trois systèmes de production : les élevages de basse-cour, les élevages familiaux commerciaux et les élevages intensifs. Le processus de prise de décision des éleveur·ses varie en fonction du système de production. Au cours de l'étude exploratoire, nous avons également identifié des changements dans le cadre réglementaire et essayé de comprendre de quelle manière ces changements sont compris, reconnus et appliqués par les acteur·rices de la chaîne de distribution du médicament vétérinaire. Après avoir cartographié la chaîne et identifié la position des parties prenantes concernant les réglementations, nous avons exploré les barrières et les motivations pour les mettre en œuvre. Les principales barrières concernent le manque de capacité des autorités à les faire appliquer, le décalage entre la théorie et les pratiques, le manque de connaissances et la forte proportion de petites exploitations. Étant donné que les éleveur·ses n'auront pas d'autre choix que de s'adapter, nous avons ensuite exploré comment ces acteur·rices font face à la nécessité de réduire l'utilisation des antibiotiques à une échelle locale. Nous avons identifié des solutions telles que l'utilisation de probiotiques fabriqués localement, le partage de connaissances et l’organisation d’éleveur·ses en coopératives. Enfin, tous les résultats obtenus ont été mis en contexte par l'organisation d'ateliers visant à coconstruire des stratégies. Les ateliers ont été organisés au niveau local avec les acteur·rices de la filière poulets et de la chaine de distribution du médicament vétérinaire. Ces stratégies codéveloppées ont pour objectifs d’améliorer la formation et la communication sur la biosécurité et la production biologique.Dans le cadre de ce travail, nous avons identifié des barrières systémiques mais aussi des leviers permettant de réduire l'utilisation des antibiotiques au Viêt Nam. Notre étude souligne la nécessité d'adopter une approche systémique et participative pour codévelopper des solutions et des stratégies. Celles-ci doivent ensuite être diffusées auprès des décideur·ses politiques pour un changement durable des pratiques. Nous avons également identifié le développement d’une filière qualité qui pourrait agir comme un levier au changement. Cependant le développement d’une telle filière devrait se faire en prenant en considération les acteur·rices les plus vulnérables. Des études complémentaires doivent être menées dans ce sens.
As warned by Sir Alexander Fleming in his Nobel Prize address: “the use of antimicrobials can, and will, lead to resistance”. Antimicrobial resistance (AMR) has recently increased due to the overuse and misuse of antibiotics, and their use in animals (food-producing and companion) has also resulted in the selection and transmission of resistant bacteria. The epidemiology of resistance is complex, and factors other than the overall quantity of antibiotics consumed may influence it. Nowadays, AMR has a serious impact on society, both economically and in terms of healthcare. This narrative review aimed to provide a scenario of the state of the AMR phenomenon in veterinary medicine related to the use of antibiotics in different animal species; the impact that it can have on animals, as well as humans and the environment, was considered. Providing some particular instances, the authors tried to explain the vastness of the phenomenon of AMR in veterinary medicine due to many and diverse aspects that cannot always be controlled. The veterinarian is the main reference point here and has a high responsibility towards the human–animal–environment triad. Sharing such a burden with human medicine and cooperating together for the same purpose (fighting and containing AMR) represents an effective example of the application of the One Health approach.
In the cutting-edge domain of medical artificial intelligence (AI),
remarkable advances have been achieved in areas such as diagnosis, prediction,
and therapeutic interventions. Despite these advances, the technology for image
segmentation faces the significant barrier of having to produce extensively
annotated datasets. To address this challenge, few-shot segmentation (FSS) has
been recognized as one of the innovative solutions. Although most of the FSS
research has focused on human health care, its application in veterinary
medicine, particularly for pet care, remains largely limited. This study has
focused on accurate segmentation of the heart and left atrial enlargement on
canine chest radiographs using the proposed deep prototype alignment network
(DPANet). The PANet architecture is adopted as the backbone model, and
experiments are conducted using various encoders based on VGG-19, ResNet-18,
and ResNet-50 to extract features. Experimental results demonstrate that the
proposed DPANet achieves the highest performance. In the 2way-1shot scenario,
it achieves the highest intersection over union (IoU) value of 0.6966, and in
the 2way-5shot scenario, it achieves the highest IoU value of 0.797. The DPANet
not only signifies a performance improvement, but also shows an improved
training speed in the 2way-5shot scenario. These results highlight our model's
exceptional capability as a trailblazing solution for segmenting the heart and
left atrial enlargement in veterinary applications through FSS, setting a new
benchmark in veterinary AI research, and demonstrating its superior potential
to veterinary medicine advances.
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 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
Insulinoma is the most common pancreatic tumor diagnosed in dogs. This study aimed to report incidence risk, breed predispositions and other demographic risk factors for insulinoma diagnosed in dogs under primary veterinary care in the UK. The VetCompass Program supports research on anonymized electronic health records (EHRs) from dogs under UK veterinary care. This study included all VetCompass EHRs from dogs under primary veterinary care during 2019. Multivariable logistic regression analysis was used to evaluate demographic risk factors for insulinoma diagnosis. Of 2,250,741 study dogs, 278 were confirmed as insulinoma cases at any date. The estimated 2019 incidence risk was 0.003% (95% CI 0.002–0.004%). Compared to crossbreeds, predisposed breeds included Dogue de Bordeaux, German Pointer, Flat Coated Retriever, Boxer and West Highland White Terrier. The Labrador Retriever showed decreased odds for insulinoma diagnosis. Additionally, being a terrier breed and being a breed predisposed to other endocrine cancers were associated with increased odds for insulinoma diagnosis. Other risk factors associated with increased odds for insulinoma diagnosis included being female neutered, being 9 - <15 years of age, having an adult median bodyweight of 20 - <30 kg and having a bodyweight above the median for the sex/breed. This is the first study to report the epidemiology of canine insulinoma in dogs under primary veterinary care, resulting in crucial leads for further research in the epidemiology and etiology of canine insulinoma and possible links of canine insulinoma with other canine endocrine cancers. Additionally, the results can aid veterinarians to identify dogs at greater risk of insulinoma.
Background The English Cocker Spaniel (ECS) is a common family dog in the UK. This study aimed to describe demography, morbidity, and mortality in ECS under primary veterinary care in the UK during 2016 using data from the VetCompass™ Programme. This study hypothesised that the prevalence of aggression is higher in male than female ECS, and higher in solid-coloured than bi-coloured ECS. Results English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. The median age was 4.57 years (inter-quartile range (IQR) 2.25–8.01) and the median adult bodyweight was 15.05 kg (IQR 13.12–17.35). The annual proportional birth rate was relatively stable between 2.97–3.51% from 2005–2016. The most common specific diagnoses were periodontal disease ( n = 486, prevalence 20.97%, 95% confidence interval (CI): 19.31–22.62), otitis externa ( n = 234, 10.09%, 95% CI: 8.87–11.32), obesity ( n = 229, 9.88%, 95% CI: 8.66–11.09), anal sac impaction ( n = 187, 8.07%, 95% CI: 6.96–9.18), diarrhoea ( n = 113, 4.87%, 95% CI: 4.00–5.75), and aggression ( n = 93, 4.01%, 95% CI: 3.21–4.81). The prevalence of aggression was higher in males (4.95%) than in females (2.87%) ( P = 0.015) and in solid-coloured (7.00%) than in bi-coloured dogs (3.66%) ( P = 0.010). The median age at death was 11.44 years (IQR 9.46–13.47) and the most common grouped causes of death were neoplasia ( n = 10, 9.26%, 95% CI: 3.79–14.73), mass-associated disorders ( n = 9, 8.33%, 95% CI: 4.45–15.08), and collapse ( n = 8, 7.41%, 95% CI: 3.80–13.94). Conclusions Periodontal disease, otitis externa, and obesity are identified as the most common health issues for ECS, and neoplasia and mass-associated disorders as the most common reasons for death. The prevalence of aggression was higher in males and solid-coloured dogs. The results can aid veterinarians in giving evidence-based health and breed choice information to dog owners and highlights the importance of thorough oral examination and body condition score evaluation during routine veterinary examination of ECS. The English Cocker Spaniel (ECS) is a popular family dog in the UK, but there is limited information regarding common disorders affecting the breed. The goal of this study was to describe demography (age, sex, neuter, and bodyweight), disease occurrence, lifespan, and reasons for death in ECS by using data from the VetCompass™ Programme. The VetCompass™ Programme collects information from anonymised clinical records of dogs attending first-opinion veterinary practices in the UK. This study hypothesised that aggression is more common in males than in females, and in solid-coloured than in bi-coloured ECS dogs. English Cocker Spaniels comprised 10,313/336,865 (3.06%) of dogs under primary veterinary care during 2016. Breed popularity did not vary much from 2005 to 2016, comprising around 3% of all dogs born each year. The average age of dogs in 2016 was 4.57 years and the average adult bodyweight was 15.05 kg. The most common disorders were periodontal disease (infection of the tissues that hold the teeth in place, affecting 20.97% of the dogs), inflammation of the external ear canal (10.09%), obesity (9.88%), anal sac impaction (8.07%), diarrhoea (4.87%), and aggression (4.01%). Aggression was more common in males (4.95%) than in females (2.87%) and in solid-coloured (7.00%) than in bi-coloured (3.66%) dogs. The frequency of aggression also varied across the four most common solid colours (black, liver, golden, red), with golden-coloured dogs showing the most aggression (12.08%). The average lifespan was 11.44 years and the most common cause of death was tumours. This study shows that first-opinion clinical records can help us to understand and enhance breed health. The results can guide veterinarians in giving breed-adapted information to owners of ECS and help breeders to optimise breeding decisions. Further, this information can be used by future ECS owners to make more informed decisions when acquiring a dog if avoidance of aggression is a key priority. Periodontal disease was the most common condition affecting the breed, which highlights the importance of regular veterinary dental checks and as well as tooth brushing in ECS.
SIMPLE SUMMARY: During the COVID-19 pandemic, many veterinary practices have been required to move to a low or no-contact consultation model to minimise the risk of SARS-CoV-2. Utilising data from a global survey, we explored the experiences of veterinary team members performing low and no-contact euthanasia during the early months of the COVID-19 pandemic. We found that low and no-contact euthanasia were encountered as common and/or stressful ethical challenges in the pandemic. In order to minimise the potential negative impacts of low and no-contact euthanasia on veterinary team members, clients and animal patients, there is a need for a toolkit of protocols to assist veterinary team members in provision of low-contact euthanasia, and avoidance of no-contact euthanasia wherever possible. ABSTRACT: Background: During the ongoing COVID-19 pandemic, many veterinary practices around the world have shifted to a low or no-contact consultation model to ensure the safety of their team members and clients, and comply with public health orders, while continuing to provide veterinary care. Methods: We performed reflexive thematic analysis on a subset of data collected using a mixed-methods survey of veterinary team members globally. Results: There were 540 valid responses available for analysis. Low and no-contact euthanasia we raised as a common and/or stressful ethical challenge for 22.8% of respondents. We identified five key themes: no-contact euthanasia as a unique ethical challenge; balancing veterinary team safety with the emotional needs of clients; low and no-contact protocols may cause or exacerbate fear, anxiety and distress in veterinary patients; physical distancing was more challenging during euthanasia consultations; and biosecurity measures complicated communication around euthanasia and end-of-life decision making. Recommendations: In light of concerns highlighted by respondents, we recommend the development of a toolkit of protocols that will assist veterinary team members in performing low-contact euthanasia in a range of circumstances, in alignment with their values and professional ethical codes. Professional bodies may be involved in developing, updating and disseminating this information, and ensuring a continuous supply chain of PPE.
Prudent use of antibiotics in livestock is widely considered to be important to prevent antibiotic resistance. This study aimed to evaluate the interactions between biofilms and veterinary antibiotics in therapeutic concentrations administrated via drinking water through a standardized experimental setup. In this context, two biofilms formed by pseudomonads (Pseudomonas (P.) aeruginosa or P. fluorescens) and a susceptible Escherichia (E.) coli strain were developed in a nutrient-poor medium on the inner surface of polyvinyl chloride pipe pieces. Subsequently, developing biofilms were exposed to sulfadiazine/trimethoprim (SDZ/TMP) or tylosin A (TYL A) in dosages recommended for application in drinking water for 5 or 7 days, respectively. Various interactions were detected between biofilms and antibiotics. Microbiological examinations revealed that only TYL A reduced the number of bacteria on the surface of the pipes. Additionally, susceptible E. coli survived both antibiotic treatments without observable changes in the minimum inhibitory concentration to 13 relevant antibiotics. Furthermore, as demonstrated by HPLC-UV, the dynamics of SDZ/TMP and TYL A in liquid media differed between the biofilms of both pseudomonads over the exposure period. We conclude that this approach represents an innovative step toward the effective evaluation of safe veterinary antibiotic use.
Background Extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) are important causative agents for infections in humans and animals. At the Equine Veterinary Teaching Hospital of the University of Helsinki, the first infections caused by ESBL-E were observed at the end of 2011 leading to enhanced infection surveillance. Contact patients were screened for ESBL-E by culturing infection sites and rectal screening. This study was focused on describing the epidemiology and microbiological characteristics of ESBL-E from equine patients of the EVTH during 2011–2014, and analysing putative risk factors for being positive for ESBL-E during an outbreak of Klebsiella pneumoniae ST307. Results The number of ESBL-E isolations increased through 2012–2013 culminating in an outbreak of multi-drug resistant K. pneumoniae ST307: bla _CTX-M-1: bla _TEM: bla _SHV during 04–08/2013. During 10/2011–05/2014, altogether 139 ESBL-E isolates were found from 96 horses. Of these, 26 were from infection-site specimens and 113 from rectal-screening swabs. A total of 118 ESBL-E isolates from horses were available for further study, the most numerous being K. pneumoniae (n = 44), Escherichia coli (n = 31) and Enterobacter cloacae (n = 31). Hospital environmental specimens (N = 47) yielded six isolates of ESBL-E. Two identical E. cloacae isolates originating from an operating theatre and a recovery room had identical or highly similar PFGE fingerprint profiles as five horse isolates. In the multivariable analysis, mare–foal pairs (OR 4.71, 95% CI 1.57–14.19, P = 0.006), length of hospitalisation (OR 1.62, 95% CI 1.28–2.06, P < 0.001) and passing of a nasogastric tube (OR 2.86, 95% CI 1.03–7.95, P = 0.044) were associated with being positive for ESBL-E during the K. pneumoniae outbreak. Conclusions The occurrence of an outbreak caused by a pathogenic ESBL-producing K. pneumoniae ST307 strain highlights the importance of epidemiological surveillance of ESBL-E in veterinary hospitals. Limiting the length of hospitalisation for equine patients may reduce the risk of spread of ESBL-E. It is also important to acknowledge the importance of nasogastric tubing as a potential source of acquiring ESBL-E. As ESBL-E were also found in stomach drench pumps used with nasogastric tubes, veterinary practices should pay close attention to appropriate equipment cleaning procedures and disinfection practices.
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.
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.
Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
25 wetenschappelijke publicaties binnen het domein Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
, voor snelle raadpleging van de bijbehorende wetenschappelijke literatuur.
Lippincott Williams & Wilkinsapril 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.
Dovenovember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: Geographic tongue (GT) is a chronic tongue condition triggered by various factors such as immune reactions, allergies, stress, hereditary factors, and nutritional deficiencies. The prevalence of GT in the population ranges from 1% to 3%, and its symptoms can cause discomfort to patients. Spicy foods are popular among Indonesians. Chili is one such food that can cause allergies and trigger GT. OBJECTIVE: This report highlights the significance of identifying the risk factors associated with symptomatic GT. CASE: A 19-year-old female patient complained of a rough and sore dorsal tongue for a year, particularly after consuming spicy food. Extra-oral examination revealed dry lips. Intra-oral examination showed red patches with white borders on the dorsal tongue. A complete blood count and allergy test were performed. The eosinophil count was 4%, the total IgE level was 698 IU/mL, and the skin prick test for chili was positive. The diagnosis of chili-induced GT was made. CASE MANAGEMENT: The patient was advised to avoid chilies, and benzydamine hydrochloride mouthwash was administered. One week after treatment, clinical improvement was observed. Severity decreased on the Geographic Tongue Area and Severity Index (GTASI) from 12 (moderate) to 0.4 (mild). Pain decreased from 6 to 0 on the numerical rating scale (NRS). CONCLUSION: Management of symptomatic GT includes the avoidance of allergens such as chilies and appropriate pharmacological therapy. The identification of risk factors is required for effective management.
Doveoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Allergic rhinitis (AR) is a common disease, characterized by typical symptoms and type 2 inflammation. Standard treatment is usually effective and safe, and most medications are available as over-the-counter (OTC). Therefore, AR patients, mostly at the AR onset or if symptoms are mild, prefer to manage symptoms themselves. However, self-management could be associated with problems, including inadequate control or medication abuse. Therefore, this paper aimed at presenting and discussing this issue. Ideally, self-management should be conducted under medical supervision. In this regard, telemedicine could represent a valuable tool for implementing self-management. Visual analog scale (VAS) is a perfect parameter to measure symptom severity, medications use, and AR control. In addition, VAS is easily monitored over time. Presently, a mobile application allows to AR patients of self-managing themselves. Therefore, mobile healthcare may supply fundamental support in communication and decision-making. In this regard, VAS represents the best tool to monitor symptoms’ severity and control over time. Finally, pharmacological and non-pharmacological remedies are numerous and effective but should be used wisely.
Dustri-Verlag Dr. Karl Feistlemei 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Development, production, and marketing authorization of allergen products is generally challenging due to several specific characteristics, including the natural source as well as the multitude of allergenic materials. Also, depending on the frequency of sensitization in the population, the number of patients available for inclusion in clinical trials can be a limiting factor for product development. In the development of allergen products for diagnosis of type I and type IV allergies these challenges are particularly demanding because, in contrast to certain products for allergen-specific immunotherapy, no exemptions from marketing authorization are foreseen for this product group in Directive 2001/83/EC. Thus, the regulatory framework is constantly adapted within the legal scope in order to balance necessary regulatory requirements ensuring quality, safety, and efficacy with the clinical need for a comprehensive range of diagnostic allergen products. In this article, we give an overview on the current regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies.
World Allergy Organizationjanuari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Modern living conditions and the recent surge in global urbanization have transformed the human microbiome. This transformation is believed to be a significant factor in the recent spike of common chronic inflammatory diseases like asthma and allergies worldwide, evident in both developed and developing nations. Immigrants from less developed regions who settle in highly urbanized and affluent areas present an ideal demographic for research. Investigating immigrant populations can yield valuable insights, particularly when studying microbiome changes that occur as individuals transition from areas with low asthma prevalence to regions with a high prevalence of the condition. The application of prebiotics and probiotics as potential treatments for asthma and allergies faces challenges. This is due to the complex interplay of numerous factors that contribute to their aetiology. Exploring the interaction between the human microbiome and potential epigenetic changes in specific populations, such as immigrants adapting to new, urbanized environments, may offer crucial insights. Such research could underscore the role of prebiotics and probiotics in preventing allergic conditions. Recognizing the changes in the human microbiome in the context of a Western/modern environment might be essential in addressing the increasing prevalence of allergic diseases. Persistent research in this domain is pivotal for devising effective interventions such as dietary supplementation with prebiotics and probiotics.
Termedia Publishing Housefebruari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: It is worth to explore a more effective treatment method to minimize the damage for patients during the treatment process. AIM: To explore the method, feasibility and efficacy of B-ultrasound or computed tomography (CT)-guided 3D printing individualized non-coplanar template brachytherapy in the treatment of locally uncontrolled recurrent head and neck squamous cell carcinoma. MATERIAL AND METHODS: Ten patients with locally uncontrolled recurrent head and neck squamous cell carcinoma who were treated in our department from August 2021 to February 2023 were collected and treated by 3D printing individualized non-coplanar template brachytherapy under the guidance of B-ultrasound or CT, using the 192Ir high-dose rate afterloading treatment machine of NUCLETRON Technologies GmbH. The radiation source was 192Ir, with a diameter of 0.5 mm, a length of 3.5 mm, a total dose of 10–24 Gy, 5–8 Gy/time, once a week. RESULTS: According to the efficacy evaluation criteria, CT scan was performed after 1-6 months, followed up for 24 months, including CR 40% (4/10), PR 50% (5/10), NC 10% (5/10), PD 0 (0). The total effective rate of CR + PR was 90% (9/10), the 6-month local control rate was 90%, the 12-month local control rate was 80%, the 18-month local control rate was 70%, and the 24-month local control rate was 70%. The overall survival rate at 24 months was 100%. CONCLUSIONS: Safe and effective interpolation is used to guide the 3D printing of a single non-coplanar template with B-ultrasound or CT in the radiotherapy of local and uncontrolled recurrent head and neck squamous cell carcinoma. According to the guidance of B-ultrasound or CT, the 3D printing individualized non-coplanar template has an obvious healing effect especially in the brachytherapy, and can also protect the functional organs well, with less side effects and fewer complications. Therefore, this method is the most effective for the treatment of locally uncontrolled recurrent head and neck squamous cell carcinoma.
World Allergy Organizationoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Allergic rhinitis is a significant public health concern worldwide, affecting both developed and developing countries, with prevalence rates ranging between 10% and 30% in adults and over 40% in children. However, there are limited studies on allergic rhinitis prevalence in Saudi Arabia. OBJECTIVE: To explore allergic rhinitis among schoolchildren in Saudi Arabia in terms of prevalence, severity, and risk factors. METHODS: This study was conducted between March and April 2019, covering 20 regions. The study employed a multistage, stratified cluster sampling approach and selected 137 primary and 140 intermediate schools. The research utilized the methodology and questionnaires recommended by the Global Asthma Network (GAN). Data analysis was carried out using IBM SPSS Statistics (Version 23). RESULTS: The completed questionnaires in the analysis comprised 3614 children aged 6–7 years old and 4068 adolescents aged 13–14 years old. The study found that 5.6% of children and 14.0% of adolescents reported current rhinoconjunctivitis, with 0.5% of children and 1.3% of adolescents experiencing severe symptoms. Several risk factors were significantly associated with rhinoconjunctivitis. In children 6–7 years old, eating cooked vegetables was inversely associated with rhinoconjunctivitis, while prematurity, wheezing in infancy, and a history of pneumonia were positively associated with the condition. In adolescents, vigorous physical activity, current exposure to cats, and frequent use of paracetamol were found to be the main risk factors associated with rhinoconjunctivitis, while high consumption of pulses and eggs was found to have a protective effect. CONCLUSION: In Saudi Arabia, the prevalence of rhinoconjunctivitis in children is lower than average globally, but among adolescents, it is within the global average range. However, the prevalence of severe rhinoconjunctivitis among adolescents is twice the global average. Further research is required to examine regional differences, track trends over time, and explore risk factors that contribute to allergic rhinitis.
World Allergy Organizationseptember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Immunoglobulin E (IgE) blood tests are used to detect sensitizations and potential allergies. Recent studies suggest that specific IgE sensitization patterns due to molecular interactions affect an individual's risk of developing allergic symptoms. OBJECTIVE: The aim of this study was to reveal specific IgE sensitization patterns and investigate their clinical implications in Hymenoptera venom allergy. METHODS: In this cross-sectional study, 257 hunters or fishers with self-filled surveys on previous Hymenoptera stings were analyzed. Blood samples were taken to determine Hymenoptera IgE sensitization levels. Using dimensionality reduction and clustering, specific IgE for 10 Hymenoptera venom allergens were evaluated for clinical relevance. RESULTS: Three clusters were unmasked using novel dimensionality reduction and clustering methods solely based on specific IgE levels to Hymenoptera venom allergens. These clusters show different characteristics regarding previous systemic reactions to Hymenoptera stings. CONCLUSION: Our study was able to unmask non-linear sensitization patterns for specific IgE tests in Hymenoptera venom allergy. We were able to derive risk clusters for anaphylactic reactions following hymenoptera stings and pinpoint relevant allergens (rApi m 10, rVes v 1, whole bee, and wasp venom) for clustering.
John Wiley and Sons Inc.maart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK. METHODS: We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006‐January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups). RESULTS: We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19). CONCLUSIONS: Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.
BioMed Centralseptember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Primary Systemic Sclerosis (PSS) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Interstitial lung disease (ILD) is a late demonstration of PSS and cytokines can contribute to the disease pathology. The purpose of the current study was to determine the association between serum interleukin-6 level and pulmonary involvement in progressive systemic sclerosis. METHODS AND MATERIALS: Demographic data and serum interleukin-6 levels were measured for 30 PSS patients with pulmonary involvement (case group) and 30 PSS patients without pulmonary involvement (control group) following informed consent. The disease duration and activity, C-reactive protein (CRP), chest x-ray and highresolution CT scan (HRCT) findings, ejection fraction (EF) and echocardiography findings, and pulmonary artery pressure (PAP) were also determined in both groups. RESULTS: The age of patients in case and control groups was 52.5 ± 9.3 and 43.9 ± 9.7 years, respectively (p = 0.001). No significant difference was found between serum levels of IL-6 in case and control groups (73.1 ± 95.4 vs 46.7 ± 83.6 pg/ml, p = 0.267). However, IL-6 level was significantly higher in male case patients compared to male controls (p = 0.007). The duration of PSS was 11.6 ± 6.4 and 7.4 ± 4.2 years in case and control groups, respectively (p = 0.002). The quantitative CRP and PAP was also significantly higher in case patients (p = 0.01 and p < 0.001, respectively). There was found reticulonodular pattern in 20 (66.7%) of the cases, whereas 28 (93.3%) of the controls had normal Chest X-rays (CXR) (p < 0.001). EF was significantly lower in case patients compared to control patients (p = 0.001). CONCLUSION: The serum level of IL-6 did not appear to have a relationship with pulmonary involvement, hence it could not be regarded as a potential therapeutic target.
Doveaugustus 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: The oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting. PATIENTS AND METHODS: This retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting. RESULTS: In total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1–Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0–100.0%) and 0.0% (0.0–83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges–Lehmann estimate [95% confidence interval], 0.0000% [0.0000–0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were >0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥25% reduction, 50.5% and 40.6% (OR 1.4888); ≥50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005). CONCLUSION: Among severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05136547).
BioMed Centralaugustus 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients. MATERIAL AND METHODS: This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4–6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack. RESULTS: A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17–163) in patients vs 625 (405–932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%). CONCLUSION: SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00832-0.
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Diseaseoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
PURPOSE: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years. METHODS: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration. RESULTS: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children. CONCLUSIONS: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.
World Allergy Organizationnovember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Mosquito bite is normally associated with mild allergic responses, but severe localized or systemic reactions are also possible. Reliable tools for the diagnosis of mosquito allergy are still unavailable. Here, we investigated the IgE response to 3 potential salivary allergens identified in the saliva of the tiger mosquito Aedes albopictus. METHODS: Serum from 55 adult individuals (28 controls and 27 allergic people), were analysed using an in-house Enzyme Linked ImmunoSorbent Assay (ELISA) against the Salivary Gland Extract (SGE) and the recombinant proteins albD7l2 (Aed al 2), albAntigen5-3 (Aed al 13) and albLIPS-2 (Aed al 14). RESULTS: Fifteen of the 27 (56%) individuals having hypersensitive reactions to mosquito bites had IgE serum levels recognizing SGE. Negative sera did not show detectable levels of IgE targeting the SGE from the most common sympatric mosquito Culex pipiens. Among the positive individuals, 2 subjects displayed IgE targeting Aed al 2 (13%), while IgE recognizing Aed al 13 and Aed al 14 were detected in ten (67%) and seven (47%) individuals, respectively. Two sera from non-hypersensitive subjects had detectable levels of IgE targeting Aed al 13, suggesting possible cross-reaction with the homologue salivary proteins of multiple mosquito species or, more generally, of hematophagous insects. CONCLUSIONS: Our results indicate that Aed al 13 and Aed al 14 hold the potential to be developed as tools for the diagnosis of allergy to Ae. albopictus bites. Such tools would facilitate epidemiological studies on tiger mosquito allergy in humans and might foster the development of further protein-based assays to investigate cross-species allergies.
Lippincott Williams & Wilkinsdecember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Nasal irrigation (NI) for the local treatment of chronic rhinosinusitis (CRS) has some specificity due to the deep anatomical site of the sinuses. The purpose of this review is to help standardize the application of NI in healthcare practice, improve the prevention and treatment of CRS, and facilitate further research on the local treatment of CRS in the future. We searched the PubMed database for 342 articles in the last decade, using the keywords “saline nasal irrigation” and “chronic rhinosinusitis.” We summarize the studies on the mechanism of action, rinsing solution, rinsing apparatus, and rinsing method of NI for CRS. NI plays an important role in the treatment of CRS, and it is a beneficial low-risk treatment. Isotonic saline is the most accepted flushing solution, and large-volume low-pressure flushing bottles are the flushing devices with the best flushing effect and are generally tolerated by patients. Phage, colloidal silver, and hydrogen can be further studied as components of rinses. NI plays an important role in the treatment of CRS, and it is a beneficial low-risk treatment. Further high-quality and expanded sample size studies on other flushing solutions, flushing head position, flushing frequency, and treatment courses are still needed, and lessons learned in practice.
Lippincott Williams & Wilkinsnovember 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
We previously reported the effectiveness of rush subcutaneous immunotherapy with birch pollen extract (Birch rSCIT) for pollen-food allergy syndrome (PFAS) and the high rate of systemic reactions (SR) during the rapid escalation phase. In this study, we examined whether modifying the dose escalation protocol of Birch rSCIT would reduce SR and maintain therapeutic effects. Birch rSCIT was introduced in 20 patients with PFAS who experienced systemic symptoms upon ingestion of soybeans. Birch rSCIT was implemented using 3 protocols: 2 protocols (nonstep-up group) increased the target dose to more than 1:2 × 10(2) (w/v) in 0.05 mL, while 1 protocol (step-up group) increased the target dose to 1:2 × 10(3) (w/v) in 0.3 mL, and then increased to 1:2 × 10(2) (w/v) in 0.05 mL using the conventional method in the following week. In the nonstep-up group, 4 out of 5 patients (80%), and in the step-up group, 2 out of 15 patients (13.3%) developed SR during rapid escalation. During the rapid escalation phase, the step-up group had significantly fewer SR than the nonstep-up group (P = 0.014). The median ingestible dose of soy milk in the oral food challenge was 3.5 mL before the treatment and increased significantly to 200 mL 1 year after initiating Birch SCIT (P < 0.01). We confirmed that reducing the target antigen dose in Birch rSCIT improved safety and maintained the therapeutic effect for soybean allergy with PFAS.
John Wiley and Sons Inc.januari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: Information and communication technologies (ICTs) improve patient‐centered care and are routinely used in Allergic Rhinitis (AR), but patients' preferences and attitudes are unexplored. This study examines AR‐related information preferences and ICT use by AR patients. METHODS: A survey‐based cross‐sectional study was carried out in Ecuador from July to September 2019 in seven centers of reference for allergic disease. Participants were 18 years or older, diagnosed with AR and had access to ICT and the Internet. Descriptive and binomial logistic regressions were performed. A value of less than 0.05 was considered statistically significant. RESULTS: 217 patients were included. 47% (n = 102) used ICTs to learn about AR, of which 38.2% (n = 83) found it useful. Most of participants (75%, n = 164) did not think that ICTs reduce their need to see a doctor. Individuals with poorer quality of life were more likely to utilize ICTs to contact their doctor (OR 1.27, 95% CI 1.04–1.55), and more likely to be interested in AR‐related content (OR 1.23, 95% CI 1.00–1.52). Patients with long‐term AR or other allergies were less likely to use ICTs (OR 0.92 and OR 0.40 respectively). Higher education and lower quality of life may increase AR apps adoption (OR 4.82, 95% CI 1.11–21.00). Academic preparation five‐fold increased ICT use for health provider communication (OR 5.29, 95% CI 1.18–23.72). Mild‐persistent AR enhanced the probabilities of using ICTs to share experiences and communicate with other patients (OR 12.59, 95% CI 1.32–120.35). CONCLUSIONS: Our study emphasizes the importance of tailoring digital resources to patient needs by considering factors such as quality of life, education, and specific subgroups within the AR patient population. Additionally, the findings suggest that while ICTs can play a valuable role in patient education and support, they should complement, rather than replace, traditional medical care for many AR patients.
World Allergy Organizationnovember 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: For therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch. OBJECTIVE: To assess current practice on all aspects of biologic therapy by specialists in Germany. METHODS: A questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis. RESULTS: Forty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between “responders”, “partial responders” and “non-responders”. Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP. CONCLUSION: This study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.
Termedia Publishing Houseoktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: COVID-19 vaccines became a relevant element of prevention during COVID-19 pandemic. It is worth highlighting the importance of severe allergic post-vaccination reactions. AIM: To evaluate the usability of skin reaction tests using skin prick tests with Comirnaty (Pfizer, USA) vaccine in risk detection of the post-vaccine immediate hypersensitivity reaction (anaphylaxis) after administration of this vaccine [PvIHR(A)]. MATERIAL AND METHODS: The analysis embraces 102 people, 85 women and 17 men with a history of immediate hypersensitivity (anaphylaxis) [IHR(A)]. Detailed medical history was collected and skin prick tests were made among participants. The positive and negative test results were illustrated in Figure 1. RESULTS: As it stands in Table 1, considering all participants of the study, a positive result of the skin prick tests was obtained only in 2 cases, a negative result in 99 and 1 result was questionable. The two positive results were found in participants from a group with a previous PvIHR(A) in their past medical history and they decided not to get vaccinated. The one questionable result was of a person that had PvIHR(A) after administration of the first dose of Comirnaty vaccine (Pfizer, USA). This person decided to get vaccinated again and there was no PvIHR(A) observed. CONCLUSIONS: COVID-19 vaccination involves a low risk of anaphylaxis. Purposefulness of providing the skin prick tests using the mRNA vaccine is questionable, due to their low sensitivity and low specificity.
Dustri-Verlag Dr. Karl Feistlemei 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
Occupational skin and respiratory allergies are among the most common occupational diseases in Germany. The identification of the allergy trigger is essential for the recognition of an occupational allergy as well as for effective individual prevention. However, occupational type I allergens are among the “rare” allergens and the possibilities of guideline-compliant diagnosis using quality-tested skin test solutions is becoming increasingly difficult due to the reduction in commercially available test allergens. In order to guarantee meaningful diagnostic workup for all affected insured persons with suspected occupational type I allergies and to ensure this in the future, a durable optimization, standardization, and availability of allergy tests for occupational allergic diseases is urgently required. The need for action has been recognized by the German Social Accident Insurance (DGUV), and steps to eliminate the diagnostic gaps have been initiated by a joint research project at the Institute for Prevention and Occupational Medicine of the DGUV (IPA) and the Paul Ehrlich Institut (PEI). The evaluation of alternative methods for the production of standardized test allergen solutions can also be used for newly emerging allergens in the workplace. New allergen sources at workplaces and thus also sensitization and allergies among employees can be expected as a result of changes in work processes and the introduction of new technologies and/or working materials, which are also introduced in connection with climate change and the concept of sustainability.
BioMed Centralmaart 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: While the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity. OBJECTIVE: To describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes. METHODS: Mothers with infants aged < 19 months old with a diagnosis of AD were recruited from social media and medical clinics in Winnipeg, Canada between October 2021 and May 2022. Infant AD severity was classified using maternal-reported data on the Patient-Oriented Scoring Atopic Dermatitis tool (PO-SCORAD). Quantitative data were collected via a series of questionnaires with a subset of mothers subsequently completing semi-structured interviews. Quantitative and qualitative data were integrated in the discussion. RESULTS: Mothers of infants with moderate/severe AD (6/12) were more likely to report their infant suffering from a higher degree of sleeplessness (i.e., ≥ 5 on a scale of 0–10) over the past 48 h compared to mothers of infants with mild AD (0/18). This was supported by qualitative findings where mothers described how their infant’s sleep quality and quantity worsened with AD severity. Additionally, 7/32 mothers reported that their child’s AD, regardless of severity, disturbed their sleep. Maternal sleep loss was most commonly attributed to infant itching (6/7), followed by worry (4/7). CONCLUSION: Infantile AD severity was associated with worse sleep outcomes for both mothers and infants. We propose that maternal and infantile sleep quality and quantity can be improved by reducing AD severity through adherence to topical treatments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-024-00883-x.
Termedia Publishing Housejanuari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
INTRODUCTION: Acne vulgaris is a prevalent skin disorder influenced by a variety of factors, including a high body mass index (BMI) and obesity. AIM: To investigate the association between BMI z-scores and acne severity in boys and girls aged 10–18 years. MATERIAL AND METHODS: A 72-patient prospective analysis was performed, in which patient weight, height, body mass index (BMI), body mass index z score (BMI z-score), percentiles, and demographic information were collected, and acne severity was categorized as mild or moderate/severe. RESULTS: The results indicated that patients with moderate/severe acne were significantly older and had higher weight, height, BMI, and BMI z-scores than those with mild acne (p < 0.01). CONCLUSIONS: The findings suggest that higher BMI z-scores are linked to increased acne severity. These results emphasize the importance of addressing weight-related risk factors for the prevention and treatment of acne vulgaris. The early detection and management of weight-related conditions can play a crucial role in improving the overall well-being of individuals with acne, considering its negative impact on mental health and social functioning.
OceanSide Publications, Inc.september 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Food protein–induced enterocolitis syndrome (FPIES) is a rare, non–immunoglobulin E (IgE) mediated gastrointestinal food hypersensitivity. It is a clinical diagnosis commonly characterized by profuse vomiting 1 to 4 hours after ingestion of the triggering food(s). OBJECTIVE: The objective was to increase awareness of FPIES and review the epidemiology, clinical presentation, pathogenesis, diagnosis, and management of FPIES. The lack of availability of a definite biomarker or diagnostic tool often leads to a delay in diagnosis. METHODS: A literature search of salient articles that described case reports and case series of FPIES and their management were analyzed. RESULTS: A case of FPIES with a literature review is presented with emphasis on clinical pearls and pitfalls. FPIES is a diagnosis of exclusion and the mainstay of treatment is avoidance of the trigger food(s) for at least 12–18 months from the last exposure. CONCLUSION: As FPIES is a non-IgE-mediated reaction, allergy testing via skin-prick test or blood tests to measure food IgE antibodies is not routinely recommended. Many children outgrow FPIES by 3–4 years of age. Supervised oral food challenge is recommended to assess acquisition of tolerance.
BioMed Centraloktober 2023Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Current management of food protein-induced enterocolitis syndrome (FPIES) involves strict avoidance of the offending food for 12–18 months, followed by oral food challenge (OFC) under physician supervision. OFCs are resource-intensive and there is a lack of a universal standardized protocol for FPIES. Prolonged avoidance may increase the risk of IgE-mediated allergy, particularly in atopic patients. Food ladders have shown success in promoting accelerated tolerance in patients with IgE-mediated allergy. Our case series evaluated the safety of use of the Canadian Egg Ladder in patients with mild-to-moderate FPIES to egg. METHODS: From May 2020 to November 2021, patients with mild-to-moderate FPIES to egg, defined as no history of lethargy or intravenous fluid administration, were started on the Canadian Egg Ladder. Instructions for advancing up the ladder were identical to using the Canadian Egg Ladder in patients with IgE-mediated allergy. Patients were followed every 3–6 months, at which time information was collected regarding progression up the ladder, symptoms while on treatment and interventions required. Treating allergists completed a survey to capture baseline demographic characteristics and prior tolerance to egg. Descriptive statistics were analyzed using MS Excel. RESULTS: Twenty-one patients with mild-to-moderate FPIES were started on the Canadian Egg Ladder. Median age at initiation of the ladder was 10 months (IQR, 9–11). Nineteen (90.5%) patients completed the ladder, tolerating a serving size amount of cooked egg, over a median duration of 7 month (IQR, 4–9 months). Four patients (19.0%) had mild symptoms including vomiting (9.5%), pallor (9.5%), belching (4.8%), irritability (4.8%) and small spit up (4.8%). In three of the four patients, symptoms were the result of accidental exposure to a higher step of the ladder. There were no reports of lethargy. No patients required health care presentation or intravenous fluid administration. No patients discontinued the ladder. CONCLUSIONS: The Canadian Egg Ladder can safely guide the dietary advancement of egg-containing foods in patients with mild-to-moderate FPIES to egg, without the need for prolonged avoidance and resource-intensive OFCs.
World Allergy Organizationjanuari 2024Respiratoire Geneeskunde, Immuno-allergologie en Dermatologie
BACKGROUND: Data about drug hypersensitivity reactions with first-line antituberculosis drugs and their management is limited. Rapid drug desensitization seems to be an appropriate management. OBJECTIVE: Evaluate the efficacy of the rapid desensitization protocols in patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and identify possible risk factors of breakthrough reactions during the protocols. METHODS: This is a retrospective study of active tuberculosis patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and underwent desensitization with the drugs used during the reaction. Characteristics of drug hypersensitivity and breakthrough reactions, and outcomes of rapid desensitizations were recorded. RESULTS: One hundred and seventy-nine patients were included in the study. Most of the initial reactions (n = 132, 73.7%) occurred within the first week of treatment and were mild (n = 146, 81.6%). A total of 690 desensitizations were performed. Desensitizations were successfully completed without any breakthrough reaction in 103 (57.5%) patients and in 29 of 36 (80.6%) patients after a breakthrough reaction. The overall success of desensitizations were found to be 95% (132 of 139 patients). Most of the breakthrough reactions (84%) were mild. Sixteen patients had breakthrough reactions with multiple drugs. Although pyrazinamide was the most common culprit of breakthrough reactions and had the lowest desensitization success, it had the highest rate of a single breakthrough reaction (p < 0.001). Timing of the initial reaction and concomitant breakthrough reaction with ethambutol were found to have increased the risk for breakthrough reaction caused by rifampicin (p = 0.017 and p = 0.010 respectively). CONCLUSION: The rapid desensitization protocols used in this study provide a successful and effective management of the patients with a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs.
International audience;
From September 19 to December 12, 2021, a mixed explosive-effusive eruption impacted La Palma Island, in the Canary archipelago, leading to the growth of Tajogaite volcanic cone. Daily Open-Path Fourier Transform Infrared (OP-FTIR) measurements from October 3 until the end of the eruption allowed us to capture the molar proportions of H2O, CO2, SO2, HCl and CO (plus COS occasionally) in magmatic gases emitted from summit and flank vents of the new cone. Our results reveal high CO2/SO2 ratios ranging from 11 to 53 in explosive gas emissions throughout most of the eruption, with a time-averaged value of ∼30. In contrast, effusive degassing at lower flank vents systematically displayed lower CO2/SO2 ratios (from 3 to 11) and enhanced proportions of H2O, S and Cl. Combined with solubility data and the magma eruption rates, this chemical contrast suggests gas fractionation in a very shallow conduit branching beneath the Tajogaite cone, were most of the pre-exsolved CO2-rich gas phase but a minor fraction of the magma explosively escaped through the main eruptive conduit, while CO2-depleted gas and most of the magma were effusively discharged through lateral branches. The CO/COS/CO2 ratios for explosive degassing are consistent with petrological evidence of oxidized magmatic conditions (FMQ +1.7 ± 0.3), which enhanced sulfur solubility and late-stage SO2 outgassing. The high oxidation state, as well as low HCl/HF ratios, retrieved from solar occultation across the volcanic plume, are both typical of Ocean Island Basalt (OIB) magmatism. The apparent increase of CO2/SO2 and SO2/HCl ratios at summit vents during the first half of the eruption is consistent with the influx of progressively more mafic, deeper-derived, basanitic magma, though we cannot entirely rule out artefacts due to more challenging measurement of the pure explosive gas in that period. Our study presents the very first detailed data set for gas geochemistry during a subaerial eruption in the Canary archipelago and highlights the remarkable potential of OP-FTIR spectroscopy for real-time monitoring and study of volcanic eruptions.
CCSD;Society for Libyan Studiesjanuari 2024Vulkanologie
International audience;
Archaeological sites in Northwest Africa are rich in human fossils and artefacts providing proxies for behavioural and evolutionary studies. However, these records are difficult to underpin on a precise chronology, which can prevent robust assessments of the drivers of cultural/behavioural transitions. Past investigations have revealed that numerous volcanic ash (tephra) layers are interbedded within the Palaeolithic sequences and likely originate from large volcanic eruptions in the North Atlantic (e.g., the Azores, Canary Islands, Cape Verde). Critically, these tephra layers offer a unique opportunity to provide new relative and absolute dating constraints (via tephrochronology) to synchronise key archaeological and palaeoenvironmental records in this region. Here, we provide an overview of the known eruptive histories of the potential source volcanoes capable of widespread ashfall in the region during the last ~300,000 years, and discuss the diagnostic glass compositions essential for robust tephra correlations. To investigate the eruption source parameters required for ash dispersal towards NW Africa, we simulate plausible ashfall distributions using Ashfall3D. This work constitutes the first step in developing a more robust tephrostratigraphic framework for distal ash layers in NW Africa and highlights how tephrochronology may be used to robustly synchronise and date key climatic and cultural transitions during the Palaeolithic.
International audience;
Explosive volcanic eruptions can reach the stratosphere and cause elevated concentrations of sulphate particles for months to years. When these particles descend into the troposphere, they can impact cirrus clouds though to what degree is unknown. In this study, we combine three satellite data sets to investigate the impact of downwelling sulphate aerosol on midlatitude cirrus clouds during springtime. The results show that cirrus clouds in the northern hemisphere (NH) have lower ice water content (IWC), ice crystal number concentrations, and cloud fraction (CF) when the aerosol load in the lowermost stratosphere is elevated by volcanism. These changes are largest for the coldest clouds at the highest altitudes. The cirrus clouds in the southern hemisphere on the other hand show no significant changes with downwelling aerosol levels. The reduction in cirrus IWC and CF in the NH implies that volcanic aerosol can cool the climate through reduced warming from cirrus clouds.
CCSD;Uppsala University Publicationsfebruari 2026Vulkanologie
co-auteur étranger;International audience;
Seafloor-derived silicified volcanic and sedimentary rocks provide unique records ofhydrothermal systems that operated at the top of the Paleoarchean submerged crust. Basedon petrographic, thermometric, and geochemical analyses, we distinguish the signaturesof Paleoarchean hydrothermal activity from those due to subsequent metamorphismand weathering in silicified volcanic and sedimentary rocks sampled from the3.5–3.2 GaBarberton Greenstone Belt. Measured138La-138Ce and147Sm-143Nd isotopic compositionsindicate that weathering by post-Archean oxidised fluids modified LREE abundances insamples displaying Ce anomalies. Raman spectroscopy of carbonaceous material, chloritethermometry and oxygen isotope thermometry provide evidence for mineralogical resettingby regional metamorphism at∼350±50°C, which arguably did not modify the bulk-rockgeochemistry. Oxygen isotope fractionation in a quartz-carbonate assemblage preservedfrom subsequent resetting provides a minimum temperature of∼110±50°Cinterpreted asthe highest possible temperature of the Paleoarchean silicifying hydrothermal fluids. Y/Hoand Zr/Hf ratios are chondritic in silicified volcanic and clastic sedimentary rocks, whichdifferentiates them from Archean orthochemical cherts with suprachondritic Y/Ho and Zr/Hfratios. Finally, silicified volcanic rocks that are free of Ce anomalies (mostly unweatheredby oxidising fluids) display slightly lower Sm/Nd ratios and more variable Lu/Hf ratios thannon-silicified counterparts, which we ascribe to differential REE mobilisation by silicifyinghydrothermal fluids. The modification of Sm/Nd and Lu/Hf ratios during Paleoarcheanhydrothermal activity should be integrated in future Sm-Nd and Lu-Hf isotopic investigationsof hydrothermal inputs to Archean ocean chemistry and of recycled seafloor-derived rocks
International audience;
The 3930 BPFall Stratified (FS) eruption atMt.Etna is a rare example of a highly explosive eruption of primitive (picritic) magma directly from the mantle. The eruption produced ash plumes up to an estimated 20km height, leading to a volcanic explosivity index (VEI) 4 (subplinian). Given its volatile-rich and primitive nature, theFS magma may have ascended rapidly from great depths to avoid fractionation and mixing within the extensive plumbing system beneath Etna. To determine the pressures from which the FS magma derived, we perform rehomogenization experiments on melt inclusions hosted inFo 90–91 olivines to resorb shrinkage bubbles and determine the initial H2O and CO2 in the melt. With measured CO2 concentrations of up to 9600 ppm, volatile solubility models yield magma storage pressures of630 –800 MPa. These correspond to depths of24 –30km, which are comparable to the seismologically estimated Moho. Therefore, the magma ’s high CO2 concentration must come from carbon in the mantle (likely from subducted carbonates), as opposed to assimilation of shallow (<10km) crustal carbonates. Diffusion modeling of H2O and forsterite zonation profiles in clear, euhedral, and crystallographically oriented olivines indicates rapid ascent of magma directly from its source region to the surface. Forsterite profiles exhibit a narrow rim of growth zoning but no detectable diffusional zoning, reflecting maximum ascent times of1 –5 days. Eighteen measured H2O profiles result in remarkably uniform decompression rates of0.47 MPa/s (95% confidence interval of0.16 –1.28 MPa/s), which is among the fastest measured for basaltic-intermediate magmas. These decompression rates indicate that the final stage of magma ascent over the region in which H2O degasses (between the surface and ~15km) occurred extremely fast at~17.5 m/s. This eruption may provide a link between primary magma composition and eruption intensity: we propose that the unusually explosive nature of this picritic eruption was driven by high H2O and CO2 concentrations, which led to continuously rapid ascent without stalling, all the way from the Moho.
How filaments form and erupt are topics about which solar researchers have
wondered since more than a century and that are still open to debate. We
present observations of a filament formation, its failed eruption, and the
associated flare (SOL2019-05-09T05:51) that occurred in active region (AR)
12740 using data from SDO, STEREO-A, IRIS, and NSO/GONG. AR 12740 was a
decaying region formed by a very disperse following polarity and a strong
leading spot, surrounded by a highly dynamic zone where moving magnetic
features (MMFs) were seen constantly diverging from the spot. Our analysis
indicates that the filament was formed by the convergence of fibrils at a
location where magnetic flux cancellation was observed. Furthermore, we
conclude that its destabilization was also related to flux cancellation
associated to the constant shuffling of the MMFs. A two-ribbon flare occurred
associated to the filament eruption; however, because the large-scale magnetic
configuration of the AR was quadrupolar, two additional flare ribbons developed
far from the two main ones. We model the magnetic configuration of the AR using
a force-free field approach at the AR scale size. This local model is
complemented by a global potential-field source-surface one. Based on the local
model, we propose a scenario in which the filament failed eruption and flare
are due to two reconnection processes, one occurring below the erupting
filament, leading to the two-ribbon flare, and another one above it between the
filament flux-rope configuration and the large-scale closed loops. Our
computation of the reconnected magnetic flux added to the erupting flux rope,
compared to that of the large-scale field overlying it, lets us conclude that
the latter was large enough to prevent the filament eruption. A similar
conjecture can be drawn from the computation of the magnetic tension derived
from the global field model.
;Comment: 32 pages, 17 figures, Accepted for publication in Solar Physics
International audience;
We present the integration of airborne magnetic data and five different airborne electromagnetics data sets spaning from 3 000 NIA up to 1 000 000 NIA magnetic moments (three different AEM systems were used) in La Reunion volcanic island. Subsequently, a 3D geological model of the first kilometer beneath the Plaine des Fougeres was built, in order to constrain 3D hydrogeological modeling. This approach allowed for the correlation of different datasets, providing a comprehensive image of the subsurface and enabling a greater hydrogeological understanding. It was used to position the route of a deep water drainage gallery and has great potential for applications in other areas.
HAL CCSD;European Geosciences Union (EGU)oktober 2021Vulkanologie
International audience;
Abstract. The ∼74 ka Toba eruption was one of the largest volcanic events of the Quaternary. There is much interest in determining the impact of such a large event, particularly on the climate and hominid populations at the time. Although the Toba eruption has been identified in both land and marine archives as the Youngest Toba Tuff, its precise place in the ice core record is ambiguous. Several volcanic sulfate signals have been identified in both Antarctic and Greenland ice cores and span the Toba eruption 40Ar/39Ar age uncertainty. Here, we measure sulfur isotope compositions in Antarctic ice samples from the Dome C (EDC) and Dronning Maud Land (EDML) ice cores at high temporal resolution across 11 of these potential Toba sulfate peaks to identify candidates with sulfur mass-independent fractionation (S-MIF), indicative of an eruption whose plume reached altitudes at or above the stratospheric ozone layer. Using this method, we identify several candidate sulfate peaks that contain stratospheric sulfur. We further narrow down potential candidates based on the isotope signatures by identifying sulfate peaks that are due to a volcanic event at tropical latitudes. In one of these sulfate peaks at 73.67 ka, we find the largest ever reported magnitude of S-MIF in volcanic sulfate in polar ice, with a Δ33S value of −4.75 ‰. As there is a positive correlation between the magnitude of the S-MIF signal recorded in ice cores and eruptive plume height, this could be a likely candidate for the Toba super-eruption, with a plume top height in excess of 45 km. These results support the 73.7±0.3 ka (1σ) 40Ar/39Ar age estimate for the eruption, with ice core ages of our candidates with the largest magnitude S-MIF at 73.67 and 73.74 ka. Finally, since these candidate eruptions occurred on the transition into Greenland Stadial 20, the relative timing suggests that Toba was not the trigger for the large Northern Hemisphere cooling at this time although we cannot rule out an amplifying effect.
In terms of assessing global energy budgets associated with volcanism, and in particular heat flow, typically only that released during eruptive phases has been considered. There is however an immense release of heat passively at volcanic systems between eruptions especially at active hydrothermal systems. At such systems, passive heat release is continuous and widespread, and as such potentially accounts for a significant percentage of the global heat flux ascribed to volcanic activity. At volcanic hydrothermal systems, heat generation at depth is the result of cooling of a magmatic body and/or ascent of hot fluids. The thermal gradient between the heat source and the surface is what sets in convection of fluids into the hydrothermal system where volcanic water and volatiles mix with groundwater infiltrating into the system. The enhanced heat flux above the hydrothermal system results in a thermal anomaly at the surface between the geothermally heated ground and surrounding ambient non-heated ground. The intensity and spatial extension of the thermal anomaly can be used to constrain heat flow, it is also a proxy for understanding the state of the hydrothermal system and determining whether or not the system is moving into unrest.In this thesis, I use a network of temperature sensors installed in the crater of La Fossa Vulcano (Italy), combined with satellite sensor-derived thermal infrared data, to estimate the size and intensity of the thermal anomaly and thus the heat flow. I assess the thermal signature of La Fossa before and during an unrest period which started in the second half of 2021. These ground- and satellite-based data were used to invert a heat transfer model to calculate and track the changes in permeability before, during and after the unrest. During unrest, permeability increased by three orders of magnitude from 10-10 to 10-7 during 2021, before reverting to pre-unrest levels by 2022. I also compare dry and wet heat flux models for hydrothermal systems using ground- and satellite-based data for Nisyros (Greece) and Poas (Costa Rica). I find the critical parameters in assessing heat flux at dry systems is vapour pressure and air temperature, and their variation during a solar day, and at wet systems the main drivers are vapour pressure and wind which control evaporation. I find that differences in emissivity between different surface types can influence the thermal anomaly by a few degrees centigrade, which is significant for a low amplitude thermal anomaly such as found above hydrothermal systems. Similarly, the presence of water vapor in the near-ground layer of the atmosphere can have a comparable impact on the thermal anomaly.The work carried out in this thesis is used to complete a review of all parameters needed to be taken into account in order to calculate heat flux at hydrothermal systems and how to compare one system with another. Given diurnal variations in the heat flux defined in this thesis, punctual measurements made at different times of the day can be set in the context of daily cycles of heat emission. The next step will be to uise these methodologies to build a complete inventory for global heat fluxes associated with active volcanic systems.
;
Lors de l''évaluation des bilans énergétiques globaux associés au volcanisme, et en particulier les flux de chaleur, seule la chaleur libérée pendant les phases éruptives a été prise en compte. Il y a cependant une immense quantité de chaleur émise passivement dans les systèmes volcaniques entre les éruptions, en particulier dans les systèmes hydrothermaux actifs. Dans ces systèmes, l'émission passive de chaleur est continue et généralisée et, en tant que telle, peut représenter un pourcentage important du flux de chaleur global attribué au volcanisme. Dans les systèmes hydrothermaux volcaniques, la production de chaleur en profondeur résulte du refroidissement d'un corps magmatique et/ou de l'ascension de fluides chauds. Le gradient thermique entre la source de chaleur et la surface est à l'origine de la convection des fluides dans le système hydrothermal, où l'eau d'origine volcanique et les éléments volatiles se mélangent aux eaux souterraines qui s'infiltrent dans le système. L'augmentation du flux de chaleur au-dessus du système hydrothermal entraîne une anomalie thermique à la surface entre le sol chauffé par la géothermie et le sol environnant non chauffé. L'intensité et l'extension spatiale de l'anomalie thermique peuvent être utilisées pour contraindre le flux de chaleur. Ce sont aussi des indicateurs pour comprendre l'état du système hydrothermal et déterminer si le système est en train d'entrer en phase d'unrest ou non.Dans cette thèse, j'utilise un réseau de capteurs de température installés dans le cratère du volcan La Fossa (Italie), combiné à des données infrarouges thermiques dérivées de capteurs satellitaires, pour estimer la taille et l'intensité de l'anomalie thermique et donc le flux de chaleur. J'évalue la signature thermique de La Fossa avant et pendant une période d'unrest qui a débuté mi-2021. Ces données terrestres et satellitaires ont été utilisées pour inverser un modèle de transfert de chaleur afin de calculer et de suivre les changements de perméabilité avant, pendant et après l'unrest. Pendant l'unrest, la perméabilité a augmenté de trois ordres de grandeur, passant de 10-10 à 10-7 au cours de l'année 2021, avant de revenir aux niveaux antérieurs à la période d'unrest en 2022. Je compare également les modèles de flux de chaleur secs et humides pour les systèmes hydrothermaux en utilisant des données au sol et par satellite pour Nisyros (Grèce) et Poas (Costa Rica). Je constate que les paramètres essentiels pour évaluer le flux de chaleur dans les systèmes secs sont la pression de vapeur et la température de l'air, ainsi que leur variation au cours d'une journée solaire, tandis que dans les systèmes humides, les principaux facteurs sont la pression de vapeur et la vitesse du vent, qui contrôlent l'évaporation. Je constate que les différences d'émissivité entre les différents types de surface peuvent influencer l'anomalie thermique de quelques degrés centigrades, ce qui est significatif pour une anomalie thermique de faible amplitude comme celle que l'on trouve au-dessus des systèmes hydrothermaux. De même, la présence de vapeur d'eau dans la couche atmosphérique proche du sol peut avoir un impact comparable sur l'anomalie thermique.Le travail réalisé dans cette thèse permet de passer en revue l'ensemble des paramètres à prendre en compte pour calculer le flux de chaleur dans les systèmes hydrothermaux et de comparer un système à un autre. Compte tenu des variations diurnes du flux de chaleur défini dans cette thèse, des mesures ponctuelles effectuées à différents moments de la journée peuvent être replacées dans le contexte des cycles journaliers d'émission de chaleur. La prochaine étape consistera à utiliser ces méthodologies pour établir un inventaire complet des flux de chaleur globaux associés aux systèmes volcaniques actifs
International audience;
Abstract. Sulfur dioxide emitted during volcanic eruptions can be hazardous for aviation safety. As part of their activities, the Volcanic Ash Advisory Centres (VAACs) are therefore interested in the real-time atmospheric monitoring of this gas. A recent development aims at improving the forecasts of volcanic sulfur dioxide quantities made by the MOCAGE (Modèle de Chimie Atmosphérique à Grande Échelle) chemistry transport model. For this purpose, observations from both TROPOMI (Tropospheric Monitoring Instrument) and IASI (Infrared Atmospheric Sounding Interferometer; B and C) located on separate polar-orbiting satellites are assimilated into the model. These sulfur dioxide measurements are based on the eruption event of the La Soufrière Saint Vincent volcano in April 2021. Observations from OMI (Ozone Monitoring Instrument) are considered validation data. The resulting assimilation experiments show that the combined assimilation of IASI and TROPOMI observations always leads to a better forecast compared to the independent assimilation of data from each instrument. Sulfur dioxide atmospheric field forecasts are better when the available observations are numerous and cover a long time window.
International audience;
The Fucino Basin, central Italy, with its long and continuous history of Quaternary sediment accumulation, is one of the richest Mediterranean Middle Pleistocene tephra records. Here, we present a new detailed investigation of tephra layers (tephras) of the 250-170 thousand years before present (ka) interval, corresponding to the entire Marine Isotope Stage (MIS) 7 and parts of the MIS 8 and MIS 6. The investigated tephras have been characterised in terms of major, minor and trace elements, Sr-Nd isotopic compositions and <SUP>40</SUP>Ar/<SUP>39</SUP>Ar ages. For correlation purposes, glass compositions and several new <SUP>40</SUP>Ar/<SUP>39</SUP>Ar ages of selected proximal pyroclastic units spanning the same temporal interval from Vulsini (Latera Volcanic Complex), Sabatini, and Vico volcanic systems, central Italy, were measured. The late MIS 8-early MIS 6 Fucino tephras were backtracked to their corresponding volcanic sources, which include the Vulsini, Vico, Sabatini, Roccamonfina, Ischia and Campi Flegrei volcanic systems. While some of these tephras have been correlated to specific eruption units, other layers are currently not documented or described in near-vent sections, thus highlighting previously unrecognised events generated by these volcanic systems. Furthermore, the new high precision <SUP>40</SUP>Ar/<SUP>39</SUP>Ar ages provide improved temporal constraints for Fucino making it one of the most detailed and chronologically best constrained tephra records for central Mediterranean MIS 7 tephrochronology. The Fucino record thus provides new integrative information for reconstructing the explosive history of Italian volcanoes during the investigated time interval. Furthermore, the geochronological constraints provide the basis for future paleoclimatic investigations at local and regional scale.
In the standard 2D model of eruption, the eruption of a magnetic flux rope is associated with magnetic reconnection occurring beneath it. However, in 3D, additional reconnection geometries are possible, in particular the AR-RF, where external reconnection involving the overlying arcades (A) and erupting flux rope (R) turns into another arcade and a flare loop (F). This process results in the drifting of the legs of the erupting flux rope. We investigated spectroscopic signatures of such AR-RF reconnection occurring in an erupting filament reconnecting with coronal arcades during a two-ribbon flare. The evolution of the erupting filament eruption is examined using observations by the Atmospheric Imaging Assembly (AIA) and the Interface Region Imaging Spectrograph (IRIS). As the filament rises into the corona, it reconnects with the surrounding arcade of coronal loops with localized brightenings, resulting in the disappearance of the coronal loops and formation of a hot flux rope, showing slipping motion of its footpoints extending to the previous footpoints of the coronal loops (AR-RF reconnection) as predicted by the 3D extensions to the Standard solar flare model. These brightenings are accompanied by the presence of strong blue-shifts in both the IRIS Si IV and Mg II lines, upto about 200 km/s. The lines are also extremely wide, with non-thermal widths above 100 km/s. Furthermore, a strongly non-Gaussian profile of the most blue-shifted component is detected at the start of the AR-RF reconnection, indicating the presence of accelerated particles and MHD turbulence, and associated with the appearance of hot plasma in the AIA 94 A passband. For the first time, an observation has been reported in which the IRIS slit successfully captures AR-RF reconnection between a filament and overlying arcades, resulting in strong blue-shifts and very broad line profiles. ;14 pages, 8 figures, 1 figure in the Appendix, Accepted in A&A
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 °C) 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.
;
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 paléoenvironnementales, 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 °C) 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.
International audience;
Microcracking due to thermal stresses affects the mechanical and flow properties of rocks, which is significant for thermally dynamic environments such as volcanoes and geothermal reservoirs. Compared with other crustal rocks like granite, volcanic rocks have a complex and variable response to temperature; it remains unclear how thermal microcracks form and how they are affected by temperature. We heated and cooled samples of low‐porosity basalts containing different amounts of microcracks and a porous andesite over three cycles, whilst monitoring microstructural changes by acoustic emission (AE) monitoring and measurement of P ‐wave velocity ( v P ; up to 450°C) and thermal expansion coefficient (TEC; up to 700°C). During the second and third cycles, the TEC was positive throughout and the rate of detected AE was low. In contrast to studies on granite, we measured a strong and reversible increase in v P with increasing temperature (by 15%–40% at 450°C), which we interpret as due to microcrack closure. During the first cycle, AE and v P measurements indicated thermal microcracking within the andesite and the basalt with a low initial microcrack density. For these samples, strong inflexions in the TEC indicated stress relaxation during heating, preceding significant thermal microcracking during cooling. The basalt with a high initial microcrack density underwent little microcracking throughout all cycles. Our results and a review of the literature relate the initial microstructure to the occurrence of thermal microcracking and explore the potentially significant influence of temperature on volcanic rock properties.
Although dominantly effusive, the 2021 Tajogaite eruption from Cumbre Vieja volcano (La Palma, Spain) produced a wide tephra blanket over 85 days of activity. About one month after the eruption onset, clean-up operations were implemented to mitigate the impact of tephra load on primary buildings. Here, we present a post-event impact assessment of 764 primary buildings, which expands our empirical knowledge of building vulnerability to tephra fallout to include impacts from long-lasting eruptions. Field observations are analyzed in the perspective of existing fragility curves, high-resolution satellite imagery and a reconstruction of the spatio-temporal evolution of the tephra blanket to characterize the evolution of roof collapse due to static loads over time. Thanks to a chronological correlation between the temporal evolution of tephra sedimentation and the timing of clean-up operations, we quantified their effectiveness in mitigating roof collapse. If no clean-up measures had been taken 11% of the surveyed buildings would have exceeded a 75% probability of roof collapse, while only 10 roof collapses have been observed (1.3% of the analysed buildings). This work provides key insights for further development of emergency plans for the management of long-lasting eruptions characterised by the sustained emission of tephra over weeks to months.
Background It is not clear, if modern Konik Polski horses have retained the ability to identify sounds in terms of danger. The aim of the study was to identify differences in their behaviour in response to the reproduction of volcanic eruption and sea storm sounds, assumed to be unfamiliar to these horses, as compared to their response to a thunderclap sound, considered by the horses as potentially dangerous. The study included 13 adult mares of the Konik Polski breed, kept under a free-range system. Their behavioural responses to the reproduction of the three natural sounds with an intensity of over 50 dB, were registered. They were analysed distance of each horse to the central point of the pasture and to the exit from the enclosure, and time and/or frequencies of elements of behaviour categorised as: increased anxiety (walking, trotting and cantering), vigilance (snoring, vocalisation, high head position, high tail position, sticking together), foraging (time of grazing), comfort (playing, examining the surroundings, sniffing), maintenance of hygiene (rubbing against objects, auto- or allogrooming, rolling) and resting. The obtained data were analysed by the Dwass, Steel and Critchlow-Fligner method using the SAS program. Results Most of analysed elements increased in response to reproduced sounds and decreased after sounds were stop playing ( p < 0.05), however, they were no significant differences in general response to each studied sound. Conclusions The responses of horses to similar sounds of both known and unknown origins, i.e. the sound of a thunderstorm, sea storm and volcanic eruption, are similar. The sound stimuli applied were not too stressful for the horses.
HAL CCSD;American Geophysical Unionjanuari 2023Vulkanologie
International audience;
We performed the first 3D island-scale tomography of the electrical conductivity of Stromboli volcano (Aeolian Islands, Italy) using 2D acquisition lines (37.2 km) and a total of 18,880 measurements and 2,402 unique electrode locations. This 3D data set was inverted using a Gauss-Newton algorithm, parallel-processing on an unstructured tetrahedral mesh containing 678,420 finite-element nodes and 3,580,145 elements to account for the topography of the volcanic island. The tomogram exhibits a conductive body (10<SUP>-2</SUP>-1.0 S m<SUP>-1</SUP>) consistent with the location of CO<SUB>2</SUB> and temperature anomalies observed at the ground surface. It corresponds to the hydrothermal system with high electrical conductivity associated with alteration. In order to confirm this interpretation, a 2.5D large-scale induced polarization tomography was performed crossing the volcano. The joint interpretation of the conductivity and normalized chargeability is done with a petrophysical model previously tested and verified at both shield- and strato-volcanoes. This model implies that alteration (through the effect of the cation exchange capacity associated with clay minerals and zeolites) plays a strong role in both controlling the electrical conductivity and normalized chargeability at Stromboli volcano. A temperature tomogram, derived from the geoelectrical measurements, is consistent with surface temperature anomalies and the Very Long Period (VLP) seismicity related to the mild-explosive activity. This survey displays at 600 m a.s.l. a lateral shift in the highest temperature location, also corresponding to the source of VLP seismicity. Structural boundaries have a major role in the hottest hydrothermal fluids rising below the active crater terrace of Stromboli volcano.
Evaluation of third molar eruption represents an established method for age assessment of living individuals. Different classification systems are available for the radiological assessment of third molar eruption. The aim of this study was to identify the most accurate and reliable classification system for the mandibular third molar eruption on orthopantomograms (OPG). We compared the method of Olze et al. (2012) with the method of Willmot et al. (2018) and a newly derived classification system using OPGs from 211 individuals aged 15–25 years. The assessments were performed by three experienced examiners. One examiner evaluated all radiographs twice. The correlation between age and stage was investigated and the inter- and intra-rater reliability was estimated for all three methods. Correlation between stage and age was similar between classification systems, although higher in the data from males (Spearman’s rho ranging from 0.568 to 0.583) than from females (0.440 to 0.446). Inter- and intra-rater reliability measures were similar across methods and invariant on sex, with overlapping confidence intervals, although the highest point estimates for both intra- and inter-rater reliability were for the method by Olze et al. with Krippendorf’s alpha values of 0.904 (95% confidence interval 0.854, 0.954) and 0.797 (95% confidence interval 0.744, 0.850). It was concluded that the method of Olze et al. from 2012 is a reliable method for practical application and future studies.
International audience;
Chronostratigraphic calibration of the Westphalian and early Stephanian succession in the Saar-Lorraine Basin of Germany and France has been improved using high-precision U-Pb zircon dating of intercalated tonsteins (volcanic ashes) in coal seams. The clay mineralogy and elemental composition were determined to specify the source of these volcanic ashes and the post-depositional weathering processes. Samples selected for dating were tonsteins with homogeneous zircons without zoning to avoid the inherited ages from the volcanic chamber.<p>Four of them provided concordant ages in agreement with their stratigraphic position. New radiometric ages constrain the hiatus below the Holz Conglomerate approximately between 307.9 and 306.0 Ma, that corresponds to the early and mid-Cantabrian substage as defined in its type area, the NW Spain. The age of T600 tonstein, which corresponds in Saar-Lorraine Basin to the Duckmantian/Bolsovian boundary is fully in agreement with ages of that boundary determined in the Ruhr Basin of the Variscan foreland and in continental basins of the Bohemian Massif. T10 tonstein on top of the Westphalian succession confirms its late Asturian age previously determined from macroflora. T00 tonstein in the Ottweiler Group provided a mid-Barruelian age, which allowed to re-define macrofloral biozones in the lower part of that group from Alethopteris zeilleri of Saberian substage to Crenulopteris lamuriana of Barruelian substage. New U-Pb ages further improved correlation of local lithostratigraphic units with other basins in Europe and also with global marine-based stages. These new ages allow us to compare radioisotopically constrained Bayesian age model to metronomic age models from Bolsovian to Barruelian and show that the high frequency sequences fall in the range of the precession and obliquity. The sources of the volcanic ashes were probably volcanoes in the Vosges and Black Forest massifs. Considered could be also volcanic centers at a larger distance, e.g., the Teplice-Altenberg volcanic complex for Westphalian, Gothard and Aar massifs in Alps and the Thüringian Forest in Saxony for Stephanian and Autunian tonsteins. The detrital zircons extracted from the sandstones of the Bolsovian deposits and Holz Conglomerate (late Cantabrian) show a wide range of ages from Precambrian to Ordovician that confirms the northward source of these zircons (Rhenohercynian zone) mixed with a local source from the Mid-German Crystalline High.</p>
The Overseas Departments and Regions of France (DROM), and more particularly the French West Indies, are now greatly affected by surface and groundwater pollution by the agricultural use of plant protection products (PP). Tropical volcanic agropedosystems are at risk due to intensive crops (banana and sugarcane), and environmental conditions that favour the dispersion of PP after spreading (very permeable soils, high rainfall). The assessment of the risks of water contamination by PP in the French West Indies suffers from two majors limitations : i) the impact of the specific pedology (high organic matter content and particular mineralogical procession) of West Indian volcanic soils on the sorption and degradation properties of PP is not well known, ii) the risk assessment procedures underway at the European and national levels are based on approaches calibrated exclusively on continental European agropedoclimatic situations, which are very different from the ones present in the French West Indies.The work carried out during this thesis aimed i) at acquiring knowledge on pesticide degradation and retention processes in tropical volcanic soils, and ii) at evaluating a water contamination risk assessment tool, TROPHY, developed by the UMR LISAH, in order to consider, in an ad hoc manner, water and solute transfer mechanisms and agropedoclimatic situations typical of the West Indian environment. To meet these objectives, experiments were conducted in the laboratory on the climatosequence andosol/nitisol/ferralsol, data from the literature and from pesticide flux studies conducted in previous work on the study site were mobilised.The main results are threefold. Firstly, a study of the most exhaustive tropical literature possible showed that the formalism for the dependence of PP half-lives on soil temperature, currently used in European contamination risk assessment tools and established for a range of temperatures characteristic of the temperate context, is not adapted to the temperatures above 20 °C prevailing in tropical climates. The decrease of DT50 above 20 °C is lower than predicted by the classical formalism. Secondly, batch experiments confirmed that volcanic soils, with variable charges and specific mineralogy, show a higher sorption of PP than temperate situations. Depending on the molecules concerned, the organic carbon content and the soil pH are explanatory factors for the variability of retention between soils. Liming, which is common in acidic volcanic soils, clearly decreases the retention of ionic molecules and should be considered for the analysis of the fate of PP in these soils. Finally, the evaluation of the TROPHY risk estimation tool led to improvements in the tool and to the identification of its capabilities. The simulation period was extended to 50 years in order to take into account the variability of the tropical climate occurring during crop cycles and the representation of runoff was improved. The protective character of the risk estimates carried out with TROPHY was confirmed at the plot scale and adjustment paths were identified for the estimation of risk at the river water scale. The nitisol scenario is to be preferred for an initial assessment of the risk of CP contamination, as it proved to be protective for all the aquatic compartments considered. Works carried out during this thesis had therefore improve knowledge of the fate of PP in tropical volcanic environment, confirming the need to adapt the procedure for assessing the risk of water contamination in this particular context, and to validate a new tool, TROPHY, dedicated to assessing the risk in tropical volcanic environment.
;
Les Départements et Régions d'Outre-Mer, et plus particulièrement les Antilles françaises, sont aujourd'hui grandement touchés par la pollution des eaux de surface et souterraines par l'usage agricole des produits phytosanitaires (PP). Les agropédosystèmes volcaniques tropicaux sont des situations à risque du fait de cultures intensives (banane et canne à sucre), et des conditions du milieu favorisant la dispersion des PP après épandage (sols très perméables, pluviométrie élevée). L'évaluation des risques de contamination des eaux par les PP aux Antilles souffre de deux limites importantes : i) l'impact de la pédologie spécifique (forte teneur en matière organique et cortège minéralogique particulier) des sols volcaniques antillais sur les propriétés de sorption et de dégradation des PP est peu connu, ii) les procédures d'évaluation du risque en cours aux plans européen et national se basent sur des démarches calibrées exclusivement sur des situations agropédoclimatiques d'Europe continentale, très différentes de celles présentes aux Antilles.Le travail mené durant cette thèse a visé i) à l'acquisition de connaissances sur les processus de dégradation et de rétention des pesticides dans les sols volcaniques tropicaux, et ii) à l'évaluation d'un outil d'évaluation des risques de contamination des eaux, TROPHY, développé par l'UMR LISAH, afin de considérer de manière ad hoc les mécanismes de transfert d'eaux et de solutés et les situations agropédoclimatiques typiques du milieu antillais. Pour répondre à ces objectifs, des expérimentations ont été menées au laboratoire sur la climatoséquence andosol/nitisol/ferralsol, des données, issues de la littérature et d'études de flux de pesticides menées dans des travaux antérieurs sur le site d'étude, ont été mobilisées. Les principaux résultats sont triples. Premièrement, une étude de la littérature tropicale la plus exhaustive possible a montré que le formalisme de dépendance des durées de demi-vie des PP à la température, actuellement utilisé dans les outils d'évaluation du risque au niveau européen et établi pour une gamme de températures caractéristiques du contexte tempéré, n'est pas adapté aux températures supérieures à 20 °C prévalant sous climat tropical. La diminution des DT50 au-dessus de 20 °C est plus faible que celle prédite par le formalisme classique. Deuxièmement, des expérimentations en batch ont confirmé que les sols volcaniques, à charges variables et à la minéralogie spécifique, présentent une sorption des PP plus élevée que les situations tempérées. Selon les molécules concernées, la teneur en carbone organique et le pH du sol sont des facteurs explicatifs de la variabilité de rétention entre sols. Le chaulage, fréquent sur les sols volcaniques acides, diminue nettement la rétention des molécules ioniques et devrait être considéré pour l'analyse du devenir des PP dans ces sols. Enfin, l'évaluation de l'outil d'estimation du risque TROPHY a conduit à apporter des améliorations à l'outil et à cerner ses capacités. La période de simulation a été rallongée à 50 ans afin de considérer la variabilité du climat tropical se produisant lors des cycles culturaux et la représentation du ruissellement a été améliorée. Le caractère protecteur des estimations du risque menées avec TROPHY a été confirmé à l'échelle parcellaire et des pistes d'ajustement ont été identifiées pour l'estimation du risque à l'échelle des eaux de rivière. Le scénario nitisol est à privilégier pour une première évaluation du risque de contamination par les PP car il s'est avéré protecteur pour l'ensemble des compartiments aquatiques considérés. Les travaux conduits au cours de cette thèse ont donc permis d'améliorer les connaissances sur le devenir des PP en milieu volcanique tropical, confirmant la nécessité d'adapter la procédure d'évaluation du risque de contamination des eaux dans ce contexte, et de valider un nouvel outil, TROPHY, dédié à l'évaluation du risque en milieu volcanique tropical.
HAL CCSD;AGU and the Geochemical Societyjanuari 2023Vulkanologie
International audience;
Alaska is located at the northernmost point of the interface between the Pacific plate and the North American continent. The subduction of the Pacific plate generates arc volcanoes along the Aleutian trench, which stops to the east at the Denali Volcanic Gap. This volcanic gap has been linked to the underthrusting of the Yakutat terrane, which might alter the thermal state of the mantle wedge and prevent melt formation. This implies that the limits of the volcanic activity should mirror the extent of the Yakutat subduction. However, the transition from the Pacific slab to the Yakutat terrane at depth is not fully understood. To investigate this issue, we processed a new composite seismic data set from six arrays deployed in the region from 2000 to 2018. We apply a multi-mode 3D Kirchhoff migration to obtain high-resolution 3D scattering images of the region. Our results highlight a sharp lateral boundary in the slab structure, with a 10 km Moho step, just offshore Anchorage, and a more gradual slab transition beneath the southern part of the Kenai peninsula. Our images from the Yakutat slab plunge down to 150 km depth are consistent with previous estimates of the Yakutat slab extent below the Alaska Range. Although the steeply dipping boundaries of the subducting Pacific lithospheres are not fully recovered, deep coherent signals from the Pacific slab are observed down to 150 km depth. These observations suggest that the crust is still partially uneclogitized at these depths in both slabs.
HAL CCSD;Nature Publishing Groupjuli 2023Vulkanologie
International audience;
Titanium diffusion profiles in quartz crystals are widely applied to constrain the duration of magmatic processes. However, experimentally determined Ti diffusion coefficients in quartz diverge by three orders of magnitude. To rectify this problem we derive Ti diffusion coefficients from natural quartz phenocrysts from the 1991 eruption at Mt. Pinatubo, by combining U-Th ages of small (15-40 µm long) zircon inclusions with Ti diffusion profiles measured at nearby growth zone contacts in the same quartz crystals. Application of the obtained data to quartz crystals with Ti-rich rims from thirteen silicic volcanic tuffs worldwide suggests that the magmas erupted years to thousands of years after magma chamber rejuvenation, with the priming time increasing with magma volume and decreasing temperature. Here we show that the time scales involved in the generation of silicic volcanic eruptions are much longer than originally thought.
Springer Science and Business Media LLCjuli 2023Vulkanologie
Abstract The geomechanical characterization of volcanic material has important implications for geothermal and mineral exploration, engineering design, geophysical signals of volcano unrest, and models of instability and mass flows. Chemical weathering and hydrothermal systems can alter the host rock, leading to changes in mechanical behavior and failure mode. Here, we compare the physical and mechanical properties of lava, autoclastic breccia, and pyroclastic (scoria) rocks from Mount Ruapehu volcano (Ruapehu) in New Zealand to mineralogical composition determined via infrared spectroscopy and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS). We use correlation matrices, principal component analysis, and parametric analysis to determine which parameters can be used to predict physical and mechanical properties and form the basis for transfer functions. Laboratory-based spectroscopy shows that the samples contain absorption features indicative of Al- and Mg-rich hydrous phyllosilicates (e.g., kaolinite, halloysite, montmorillonite), Fe- oxides (e.g., goethite), and sulfates attributed to surface weathering, supergene, and steam-heated alteration. We find that porosity and primary lithology are the predominant control on physical and mechanical properties, followed by the pervasiveness of weathering/alteration, and then mineralogical composition. Several properties, such as porosity, uniaxial compressive strength, P-wave seismic velocity, density, and Young’s modulus, show strong correlations with other properties, indicating the potential for transfer functions between these properties. Hydrothermally altered rocks near the vent complex (up to ~ 400 m depth beneath the crater lake) with high-intensity hydrothermal alteration do not follow typical physical and mechanical property trends due to high clay content, low permeability, and low strength. The presence of these rocks within the edifice at Ruapehu implies local barriers to fluid flow and subsequent pore pressure variations. Additionally, they may have less than half the strength than would be dictated by typical porosity-strength trends for surface rocks, increasing the likelihood of structural failure. Trends in the pervasiveness of weathering with physical and mechanical properties, along with shifts in the position of spectral absorption peaks as hydrothermal/weathering alteration increases, suggest that it may be possible to extrapolate properties from imaging spectroscopy.
co-auteur étranger;International audience;
Open conduit volcanoes are characterized by frequent, small scale explosive eruptions, which have a significant impact. Ash-forming explosions are impacting over larger areas with respect to effusive or poorly explosive events and, consequently, are more significant for hazard assessments. Quantifying the hazard associated with them requires understanding the processes and parameters controlling explosive style, and tephra dispersal and obtaining a comprehensive dataset to constrain syn-eruptive dynamics and particle transport in the volcanic plume. We present a study focused on Etna volcano (Italy), which, despite its continuous outgassing through the summit vents, has very frequent explosive eruptions dispersing ash along the southern Mediterranean area. The goal of this study is to obtain a statistically valid dataset on ash morphology and texture and investigate how various particle types distribute spatially in the tephra blanket. We chose a small scale, ash-forming eruption occurred in May 2016, sampled a few hours after tephra deposition. Analyses of grainsize distribution were coupled with further data on tephra texture and morphology, and numerical simulations. Several components were identified based either on purely textural or purely shape characteristics. Shape parameters related to the form of the grains (aspect ratio) are consistent across grainsizes and components. However, roughness parameters (solidity, convexity, concavity index) vary non-uniformly with particle size and componentry. Ash was formed through complex fragmentation of heterogenous magma, starting in the conduit, extending to the explosion jet, and resulting into a large variability of particle shapes, density and textures which distribute non-uniformly across grainsizes. This variability determines variable traveling potential within the volcanic plume and thus non uniform distribution in the deposit. Componentry variations along the dispersal axis suggest that density is the most effective parameter in controlling particle settling. However, extreme shapes, such as very elongated particles formed by surface tension instabilities in the jet, have the largest potential of being transported in the plume and can disperse downwind up to tens of km. Our results suggest that heterogeneities in textures and morphologies of particles are fundamental characteristics of tephra from frequently erupting volcanoes and should be accounted for plume dispersal modelling and hazard assessment.
Two major mechanisms have been proposed to drive the solar eruptions: the
ideal magnetohydrodynamic instability and the resistive magnetic reconnection.
Due to the close coupling and synchronicity of the two mechanisms, it is
difficult to identify their respective contribution to solar eruptions,
especially to the critical rapid acceleration phase. Here, to shed light on
this problem, we conduct a data-driven numerical simulation for the flux rope
eruption on 2011 August 4, and quantify the contributions of the upward exhaust
of the magnetic reconnection along the flaring current sheet and the work done
by the large-scale Lorentz force acting on the flux rope. Major simulation
results of the eruption, such as the macroscopic morphology, early kinematics
of the flux rope and flare ribbons, match well with the observations. We
estimate the energy converted from the magnetic slingshot above the current
sheet and the large-scale Lorentz force exerting on the flux rope during the
rapid acceleration phase, and find that (1) the work done by the large-scale
Lorentz force is about 4.6 times higher than the former, and (2) decreased
strapping force generated by the overlying field facilitates the eruption.
These results indicate that the large-scale Lorentz force plays a dominant role
in the rapid acceleration phase for this eruption.
;Comment: 12 pages, 5 figures; Accepted for publication in ApJL
HAL CCSD;American Geophysical Unionjanuari 2023Klimaatwetenschap
International audience;
This contribution to the RECCAP2 (REgional Carbon Cycle Assessment and Processes) assessment analyzes the processes that determine the global ocean carbon sink, and its trends and variability over the period 1985-2018, using a combination of models and observation-based products. The mean sea-air CO<SUB>2</SUB> flux from 1985 to 2018 is -1.6 ± 0.2 PgC yr<SUP>-1</SUP> based on an ensemble of reconstructions of the history of sea surface pCO<SUB>2</SUB> (pCO<SUB>2</SUB> products). Models indicate that the dominant component of this flux is the net oceanic uptake of anthropogenic CO<SUB>2</SUB>, which is estimated at -2.1 ± 0.3 PgC yr<SUP>-1</SUP> by an ensemble of ocean biogeochemical models, and -2.4 ± 0.1 PgC yr<SUP>-1</SUP> by two ocean circulation inverse models. The ocean also degasses about 0.65 ± 0.3 PgC yr<SUP>-1</SUP> of terrestrially derived CO<SUB>2</SUB>, but this process is not fully resolved by any of the models used here. From 2001 to 2018, the pCO<SUB>2</SUB> products reconstruct a trend in the ocean carbon sink of -0.61 ± 0.12 PgC yr<SUP>-1</SUP> decade<SUP>-1</SUP>, while biogeochemical models and inverse models diagnose an anthropogenic CO<SUB>2</SUB>-driven trend of -0.34 ± 0.06 and -0.41 ± 0.03 PgC yr<SUP>-1</SUP> decade<SUP>-1</SUP>, respectively. This implies a climate-forced acceleration of the ocean carbon sink in recent decades, but there are still large uncertainties on the magnitude and cause of this trend. The interannual to decadal variability of the global carbon sink is mainly driven by climate variability, with the climate-driven variability exceeding the CO<SUB>2</SUB>-forced variability by 2-3 times. These results suggest that anthropogenic CO<SUB>2</SUB> dominates the ocean CO<SUB>2</SUB> sink, while climate-driven variability is potentially large but highly uncertain and not consistently captured across different methods.
International audience;
Abstract River networks contribute disproportionately to the global carbon cycle. However, global estimates of carbon emissions from inland waters are based on perennial rivers, even though more than half of the world's river length is prone to drying. We quantified CO 2 and CH 4 emissions from flowing water and dry riverbeds across six European drying river networks (DRNs, 120 reaches) and three seasons and identified drivers of emissions using local and regional variables. Drivers of emissions from flowing water differed between perennial and non‐perennial reaches, both CO 2 and CH 4 emissions were controlled partly by the annual drying severity, reflecting a drying legacy effect. Upscaled CO 2 emissions for the six DRNs at the annual scale revealed that dry riverbeds contributed up to 77% of the annual emissions, calling for an urgent need to include non‐perennial rivers in global estimates of greenhouse gas emissions.
All ecosystems on Earth depend on primary production, which converts inorganic carbon (C) into organic compounds and living biomass. In terrestrial systems, phototrophic microbes are widespread, and recent global estimates show that they contribute on average to approximately 6% of ecosystem C uptake, in addition to plants. These estimates are however rough, and microbial contribution remains underexplored in many terrestrial systems, including C-accreting systems such as northern peatlands. Considering the functional role of phototrophic microbes could alter our current view of peatland C dynamic and deeply question our prediction of peatland C sink under climate change. This challenge is worthy because northern peatlands play a major role in the global C cycle, and their response to climate change could release the majority of warming-induced soil C loss over the next century, with dramatic consequences for the global climate. To bring a new piece in the understanding of peatland C dynamic, we explored phototrophic microbial communities, their activity and their response to climate change. We found that phototrophic microbes are extremely abundant and diverse in northern peatlands and that environmental drivers such as microtopography, water availability, or plant composition shape their community structure. In particular we found a key role of peat mosses, Sphagnum, and of their metabolites in determining and structuring the microbial food web and the place of specific phototrophic microbes. Overall, we showed that phototrophic microbes fix significant amounts of C, on average 0.11 µgC.h-1.cm-3, which represents 9% of peatland primary production. Despite structural differences, we further found that different phototrophic microbial communities respond similarly to climate change, emphasizing the strong functional similarity and redundancy among phototrophic microbes. Rising temperatures stimulate microbial photosynthesis of up to nearly 20% per degree gained, but we found a seasonality in these effects, according to soil moisture content. Benefits of warmer temperatures can flip to neutral when Sphagnum moisture is either too dry or too moist. These results reveal the vulnerability of peatland C dynamics to changes in temperature and precipitation patterns. Altogether, our result show the importance of phototropic microbes as primary producers in northern peatlands. Combined with recent studies showing that phototrophic microbial organic matter can stimulate heterotrophic activities and peat decomposition, our results bring a new and worrying piece in the understanding of peatland C dynamic and its evolution under future climates. Our results highlight the urgent need to focus more intensely on the unseen phototrophic microbes in northern peatlands.
;
Tous les écosystèmes sur Terre dépendent de la production primaire qui converti du carbone (C) inorganique en matière organique et en biomasse. Les microbes phototrophiques sont omniprésents dans les écosystèmes terrestres, et des estimations globales montrent qu'ils contribuent en moyenne à 6% de la fixation de C des écosystèmes. Ces estimations restent cependant grossières, et cette contribution microbienne est sous-étudiée dans de nombreux systèmes, incluant ceux qui stockent du C comme les tourbières nordiques. La prise en comptes des microbes phototrophiques pourrait compléter notre vision actuelle des dynamiques du C dans les tourbières et pourrait aussi remettre en question nos prédictions de leurs réponses aux changements climatiques. L'enjeu est grand car les tourbières nordiques jouent un rôle majeur dans le cycle global du C. Elles pourraient relâcher d'énormes quantité de carbone à cause du changement climatique, avec des conséquences dramatiques sur le réchauffement. Dans ces travaux, nous avons voulu apporter une nouvelle pièce dans la compréhension de la dynamique du C des tourbières en explorant les communautés de microbes phototrophiques, leurs activités photosynthétiques et leurs réponses au changement climatique. Nous avons trouvé que les microbes phototrophiques sont extrêmement abondants et diversifiés dans les tourbières nordiques, et que la structure de leurs communautés est régie par des facteurs environnementaux comme la microtopographie, la disponibilité en eau ou la composition des plantes. En particulier, nous avons trouvé un rôle clé des sphaignes - mousses des tourbières - et de leurs métabolites dans la détermination et la structure des réseaux trophiques microbiens incluant des microbes phototrophiques spécifiques. Dans l'ensemble, nous avons montré que les microbes phototrophiques fixent des quantités importantes de C, 11 µgC.h- 1.cm-3 en moyenne, ce qui représente 9% de la production primaire des tourbières. Malgré des différences structurelles, nous avons trouvé que différentes communautés phototrophiques répondent de manière similaire au changement climatique, ce qui souligne une forte similarité et redondance fonctionnelle parmi les microbes phototrophiques. Une augmentation des températures stimule la photosynthèse microbienne de presque 20% par degré. Une saisonnalité existe cependant dans cet effet, dépendant de l'humidité du sol. Les gains dus à des températures plus élevées peuvent s'estomper quand les sphaignes sont trop sèches ou trop humides. Ces résultats révèlent la vulnérabilité de la dynamique du C des tourbières à des changements de température et de régime des précipitations. Dans l'ensemble, nos résultats montrent l'importance des microbes phototrophiques comme producteurs primaires dans les tourbières nordiques. En combinaison avec des études récentes, montrant que les microbes phototrophiques peuvent stimuler les activités hétérotrophiques et la décomposition de la tourbe, nos résultats apportent des informations nouvelles et inquiétantes dans la compréhension due la dynamique du C des tourbières et sa réponse aux changements climatiques. Notre travail souligne le besoin urgent d'étudier plus en détail les microbes phototrophiques dans les tourbières nordiques.
The main purpose of this work is to study the biogeochemical response of coastal seafloor subject to episodic massive sediment deposition from floods events. The Rhône River and its connected coastal margins serve as an important case-study site for quantifying the impact of these extreme events on early diagenetic process because it receives significant inputs of sediment (estimated to be up to 80%) during short and intense events. These extreme events are rare and unpredictable, thus the assessment of their impact on sediment biogeochemical processes is difficult.In order to study the short and intermediate term response of the sediment biogeochemistry under these abruptly changing conditions, an event-driven numerical model of early diagenesis was specifically developed during this thesis. Using published data of two contrasting floods in year 2008, the model showed reliable capability to simulate the changes induced by the sediment input on the porewater profiles for various solutes. The model suggests that these floods could produce differing biogeochemical response, the extent of which is determined by the underlying characteristics of the flood layer deposit. We found a two-fold increase in overall mineralization rates during the 2008 spring flood event from pre-flood conditions in the spring, which increased further in the fall when a very labile carbon-enrichment sediment was deposited (up to a factor of 7). My research demonstrated that these differences were due to the nature of organic carbon delivered to the proximal delta of the Rhone as well as the scale (thickness) of deposition. These intrinsic characteristics might also be responsible for constraining the relaxation timescale of the various porewater solutes (e.g oxygen, dissolved inorganic carbon, sulfate) to a few months as observed in the field. Furthermore, this research also demonstrated that the strong internal cycling and the role of secondary redox processes such as pyrite precipitation which were enhanced during these flood events might be responsible for the maintenance of non-sulfidic condition observed in Rhône prodelta sediment. The thesis also briefly explores the concept of “memory effect” of temporally connected sequence of flood deposition with the conclusion that the multiple occurrence of these events can also trigger temporal interaction between floods which has a substantial effect on the processes operating in the deep (such as methanogenesis and sulfate reduction) but negligible for superficial oxic and suboxic processes. This has significant ramification in the future scenarios of increasing frequency of these extreme events.More recent time series of porewater composition obtained during winter campaigns in 2021-22 investigates the temporal evolution of the porewater following an estimated 25 cm of sediment deposition. A remarkable modification of the DIC, SO_4^{2-} and CH_4 profiles were observed which was distinguishable from the pre-flood situation. Model simulations describes adequately the dataset and showed that these winter events can result to as much as 75% increase in total carbon mineralization, thus enhancing longer-term DIC production in the sediment. This winter flood also leads to a decoupling of the two pathways for sulfate reduction - organoclastic sulfate reduction and anaerobic oxidation of methane and is associated to vertical displacement of the sulfate-methane transition zone. This observation has important implications since further deepening of the AOM maximum zone due to flood deposition could enhance the effective trapping of methane (a “green house” gas crucial in the context of climate change) flux out of the sediment.Overall, the numerical exploration in this thesis provides for the first time, a synthesis of the role of episodic event such as the massive flood deposition on spatio-temporal dynamics of the biogeochemical processes in the sediment.
;
L'objectif principal de ce travail est d'étudier la réponse biogéochimique des fonds marins côtiers soumis à des dépôts massifs épisodiques de sédiments. Le Rhône et ses marges côtières constituent un cas d'étude important pour quantifier l'impact des dépôts de crue sur les processus diagénétiques dans les sédiments superficiels, car juqu'à 80% des apports de sédiments sont réalisés lors d'événements courts et intenses de crues. Ces événements extrêmes sont rares et imprévisibles, et il est donc difficile d'évaluer par l'observation directe leur impact sur les processus biogéochimiques des sédiments. Afin d'étudier la réponse à court et moyen terme de la biogéochimie des sédiments dans ces conditions de changement brutal, un modèle numérique de diagenèse précoce a été spécifiquement développé au cours de cette thèse. En utilisant les données publiées de deux inondations contrastées en 2008, le modèle a montré sa capacité à simuler les changements induits par l'apport de sédiments sur les profils d'eau interstitielle pour différents solutés. Le modèle suggère que ces inondations pourraient produire des réponses biogéochimiques différentes, dont l'ampleur est déterminée par les caractéristiques du dépôt sédimentaire. Nous avons constaté que les taux de minéralisation du carbone organique totaux ont été multipliés par deux au cours de la crue du printemps 2008 par rapport aux conditions antérieures, et qu'ils ont encore augmenté à l'automne lorsqu'un sédiment enrichi en carbone très labile a été déposé (acrroissement d'un facteur 7). Mes recherches ont démontré que ces différences étaient dues à la nature du carbone organique du delta proximal du Rhône ainsi qu'à l'épaisseur du dépôt. Ces caractéristiques intrinsèques pourraient également être responsables du temps de relaxation des divers solutés de l'eau interstitielle (par exemple l'oxygène, le carbone inorganique dissous, le sulfate) autour de quelques mois. La thèse explore également le concept d'effet mémoire d'une séquence temporellement connectée de plusieurs dépôts de crue. L'occurrence multiple de ces événements peut déclencher une superposition temporelle entre les crues qui a un effet substantiel sur les processus opérant en profondeur (tels que la méthanogénèse et la réduction des sulfates) mais négligeable pour les processus oxiques et suboxiques superficiels. Cela a des conséquences importantes dans les scénarios futurs d'augmentation de la fréquence de ces événements extrêmes.La récente série temporelle de composition de l'eau interstitielle obtenue au cours des campagnes hivernales de 2021-22 étudie l'évolution temporelle du sédiment après un dépôt de sédiments estimé à 25 cm. Une modification remarquable des profils de DIC, SO_4^{2-} and CH_4 a été observée, qui se distingue de la situation antérieure à la crue. Les simulations du modèle décrivent de manière adéquate l'ensemble des données et montrent que ces événements hivernaux peuvent entraîner une augmentation de 75 % de la minéralisation totale du carbone, augmentant ainsi la production de DIC à plus long terme dans les sédiments. Cette inondation hivernale entraîne également un découplage des deux voies de réduction du sulfate - la réduction organoclastique du sulfate et l'oxydation anaérobie du méthane - et est associée à un enfoncement dans le sédiment de la zone de transition entre le sulfate et le méthane. Ceci pourrait renforcer l'efficacité du piège de méthane (un gaz à effet de serre crucial dans le contexte du changement climatique) dans le sédiment. Dans l'ensemble, cette thèse fournit pour la première fois une synthèse issue de l'exploration numérique du rôle d'un événement épisodique tel qu'un dépôt de crue massif sur la dynamique spatio-temporelle des processus biogéochimiques dans les sédiments.
International audience;
Rainfall pulses generate rapid increases and subsequent declines in soil moisture (SM), yet global ecosystem responses during SM dry-downs remain poorly quantified. Using 6502 soil dry-down events identified from global eddy-covariance observations, we compared carbon fluxes during dry-downs (treatment) to fluxes during the same periods without dry-downs in other years (control). During early dry-downs days, gross primary production (GPP) and respiration both exceeded controls, with stronger GPP gains enhancing net carbon uptake. This enhancement persisted for several days before diminishing as SM decreased and atmospheric dryness intensified. Latent and sensible heat fluxes also rose initially, but latent heat enhancement weakened over time, accompanied by enhanced sensible heat. Machine-learning analyses show that photosynthetic capacity and radiation drive positive GPP anomalies, while water limitations induce negative ones. Satellite data supported these patterns, whereas Earth system models underestimate their magnitude. These findings highlight transient pulse responses and support the broader applicability of the pulse-reserve paradigm.
HAL CCSD;European Geosciences Unionjanuari 2022Klimaatwetenschap
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.
International audience;
The Atlantic Meridional Overturning Circulation (AMOC) is integral to the climate system, transporting heat and anthropogenic carbon across the North Atlantic (NA) from subtropical to subpolar latitudes. This physical mechanism promotes the uptake and sequestration of atmospheric CO2 through surface cooling as warm water advances northward and consequently sinks through deep winter convection. Using ship-based observations, ocean reanalyses, neural networks, and a back-calculation approach, we present a 30-year monthly time series of contemporary carbon (natural, Cnat and anthropogenic, Cant) concentrations and transports at the A25-OVIDE hydrographic section in the subpolar NA Ocean, and assess their variability from seasonal to long-term scales. We divided the section into essential layers, including the upper branch of the AMOC (uMOC) and the mixed layer (ML). Our findings indicate that the full-section-averaged Cnat concentration shows no significant trend over the 30-year period. In contrast, the full-section-averaged Cant concentration increased by more than one third over the 30-year period, attributed to the anthropogenic increase in atmospheric CO2. Seasonal and interannual variability is more pronounced in the uMOC and in the ML, where deep convection and biological activity impact their concentration, than in the deeper ocean. The seasonal deepening of the ML in winter contributes two thirds and one half of its ML concentration for Cnat and Cant, respectively, the rest being attributed to biology and solubility. The Cant and Cnat transports are predominantly determined by the variability of volume transport, except for the decadal trend in Cant transport which is primarily influenced by changes in Cant concentration. The variability in tracer transport is the largest in the uMOC, which exhibits a seasonal peak-to-peak amplitude of approximately 25 % of the annual mean tracer transport. These results offer new insights to refine model representations and improve our understanding of the subpolar NA carbon dynamics.
International audience;
Reservoirs are active reactors for the biogeochemical cycling of carbon (C) and nutrients (nitrogen: N, phosphorus: P, and silica: Si), however, our in-depth understanding of C and nutrient cycling in reservoirs is still limited by the fact that it involves a variety of closely linked and coupled biogeochemical and hydrological processes. In this study, the updated process-based Barman model was applied to three reservoirs of the Seine Basin during 2019-2020, considering the variations of carbon dioxide (CO 2) concentrations and key water quality variables. The model simulations captured well the observed seasonal variations of water quality variables, although discrepancies remained for some variables. According to the model, we found that: (1) the three reservoirs are autotrophic ecosystems and showed high removal efficiency of dissolved inorganic carbon and nutrients during 2019-2020; (2) phytoplankton assimilation, benthic denitrification, precipitation and dissolution of calcium carbonate, and gas exchange at the water-air interface are the dominant processes for water quality variations in reservoirs; (3) based on scenarios results, trophic state and mean water depth of reservoir would impact the biogeochemical processes and the retention efficiency of nitrate and dissolved silicate. Finally, we expect that the successful application of Barman model in the reservoirs of the Seine Basin could provide a useful tool for simulating reservoir water quality changes and thus evaluating the impacts of reservoirs on downstream water quality.
HAL CCSD;Institute of Electrical and Electronics Engineersaugustus 2021Klimaatwetenschap
International audience;
In preparation of the micro-bolometer based MIcro Satellite for Thermal Infrared GRound surface Imaging (MIST-IGRI) mission, we study the error budget of the Temperature-Emissivity Separation (TES) method using several spectral configurations that differ in channel numbers, locations, and widths. The error budget quantifies the contribution of (1) the TES underlying assumption about emissivity spectral contrast, (2) the errors on atmospheric corrections, and (3) the instrumental noise. When dealing with atmospheric corrections, we consider errors on atmospheric temperature, water vapor content, and concentrations of CO2 and O3. To that end, we design an end-to-end simulator of MISTIGRI measurements in order to simulate the radiative and biophysical quantities involved in the data processing. We conduct numerous simulations over a wide range of realistic setups that include cavity effect, i.e., radiance trapping within vegetation canopy. In the case of micro-bolometer based sensing, the current study highlights that atmospheric and instrumental noises have similar impacts on the TES retrievals, with resulting errors twice as large as those due to the TES intrinsic assumption about spectral contrast, where the latter contributes to the TES error budget within the [0.005-0.009] interval for emissivity, and within the [0.3 K-0.4 K] interval for LST. Also, we show that retrieval performances of surface temperature are very similar across all considered MISTIGRI spectral configurations, with RMSE variation within 0.2 K.
International audience;
Land-based mitigation is essential in reducing net carbon emissions. Yet, the attribution of carbon fluxes remains highly uncertain, in particular for the forest-rich region of Eastern Europe (incl. Western Russia). Here we integrate various data sources to show that Eastern Europe accounted for an above-ground biomass carbon sink of ~0.41 gigatons of carbon per year over the period 2010-2019, that is 78% of the entire European carbon sink. We find that this carbon sink is declining, mainly driven by changes in land use and land management, but also by increasing natural disturbances. Based on a random forest model, we show that land use and management changes are main drivers of the declining carbon sink in Eastern Europe, although soil moisture variability is also important. Specifically, the saturation effect of tree regrowth in abandoned agricultural areas, combined with increasing wood harvest removals, particularly in European Russia, contributed to the decrease in the Eastern European carbon sink.
Afforestation and reforestation are popular strategies for mitigating climate change by enhancing carbon sequestration. However, the effectiveness of these efforts is often self-reported by project developers, or certified through processes with limited external validation. This leads to concerns about data reliability and project integrity. In response to increasing scrutiny of voluntary carbon markets, this study presents a dataset on global afforestation and reforestation efforts compiled from primary (meta-)information and augmented with time-series satellite imagery and other secondary data. Our dataset covers 1,289,068 planting sites from 45,628 projects spanning 33 years. Since any remote sensing-based validation effort relies on the integrity of a planting site's geographic boundary, this dataset introduces a standardized assessment of the provided site-level location information, which we summarize in one easy-to-communicate key indicator: LDIS -- the Location Data Integrity Score. We find that approximately 79\% of the georeferenced planting sites monitored fail on at least 1 out of 10 LDIS indicators, while 15\% of the monitored projects lack machine-readable georeferenced data in the first place. In addition to enhancing accountability in the voluntary carbon market, the presented dataset also holds value as training data for e.g. computer vision-related tasks with millions of linked Sentinel-2 and Planetscope satellite images. ;10 figures
International audience;
Ongoing ocean acidification affects marine calcification, although the scope and magnitude of this impact is essentially unknown. Here, we investigate the evolutionary origin of shell building in foraminifera to understand the long-term interplay between ocean carbon chemistry and calcification. Our analysis of shell chemical composition reveals multiple, independent origins for foraminiferal calcification throughout the Phanerozoic. Differences between orders reflect the different physiological controls employed by foraminifera to take up Ca<SUP>2+</SUP> and inorganic carbon from seawater for CaCO<SUB>3</SUB> precipitation. With the long timespan involved, variability in seawater chemistry provided contrasting environments for calcification to arise, resulting in the diverse calcification strategies that exist today. This, in turn, explains the opposite responses of shell building to carbon perturbations. Our results call for adopting an evolutionary perspective when predicting the impact of perturbations on marine calcification and thereby, on the global carbon cycle.
International audience;
Soil organic carbon (SOC) is crucial for ecosystem function and carbon storage, especially in mountain regions where cooler temperatures limit microbial activity, leading to higher SOC stocks compared to lowlands. However, the available data are insufficient to fully understand the distribution of SOC properties along elevation and snow cover duration gradients. Given that climate change models predict a reduction in snow cover duration, it is essential to better characterize these properties at a finer, mesotopographic scale (e.g., ridges and slopes), corresponding to the distribution of mountain plant communities. This study investigates the impact of microclimate on SOC content and stability in European mountain grasslands. We focused on two types of grasslands on acidic soils to maintain homogeneity in key parameters such as soil properties and plant communities. These grasslands, located across temperate European mountain ranges (Alps, Pyrenees, Vosges, Balkans, Carpathians, Black Forest, Bohemian Forest, and Sudetes), span a gradient of snow cover duration, ranging from frost-exposed ridges dominated by Carex curvula, to intermediate grasslands, without frost, dominated by Nardus stricta. SOC content and stability were assessed using Rock-Eval® thermal analysis across all sites. The results indicate that microclimate significantly influences SOC properties. Cooler temperatures, driven by elevation and reduced snow cover duration, were associated with increased SOC content but decreased stability. On windy ridges, extended growing seasons combined with intense winter freezing led to higher SOC lability, as freezing slows down mineralization processes. In contrast, intermediate grasslands, with longer growing seasons, showed enhanced SOC stability due to higher decomposition activity. These findings provide valuable insights into how SOC properties may evolve under climate change, particularly in relation to rising temperatures and shifting snow cover dynamics.
Seismic monitoring of carbon storage sequestration is a challenging problem
involving both fluid-flow physics and wave physics. Additionally, monitoring
usually requires the solvers for these physics to be coupled and differentiable
to effectively invert for the subsurface properties of interest. To drastically
reduce the computational cost, we introduce a learned coupled inversion
framework based on the wave modeling operator, rock property conversion and a
proxy fluid-flow simulator. We show that we can accurately use a Fourier neural
operator as a proxy for the fluid-flow simulator for a fraction of the
computational cost. We demonstrate the efficacy of our proposed method by means
of a synthetic experiment. Finally, our framework is extended to carbon
sequestration forecasting, where we effectively use the surrogate Fourier
neural operator to forecast the CO2 plume in the future at near-zero additional
cost.
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.
International audience;
<div xmlns="http://www.tei-c.org/ns/1.0"><p>Unleashing the land sector's potential for climate mitigation requires purposedriven changes in land management. However, contributions of past management changes to the current global and regional carbon cycles remain unclear. Here, we use vegetation modelling to reveal how a portfolio of ecological restoration policies has impacted China's terrestrial carbon balance through developing counterfactual 'no-policy' scenarios. Pursuing conventional policies and assuming no changes in climate or atmospheric carbon dioxide (CO 2 ) since 1980 would have led China's land sector to be a carbon source of 0.11 Pg C yr -1 for 2001-2020, in stark contrast to a sink of 175.9 Tg C yr -1 in reality. About 72.7% of this difference can be attributed to land management changes, including afforestation and reforestation (49.0%), reduced wood extraction (21.8%), fire prevention and suppression (1.6%) and grassland grazing exclusion (0.3%). The remaining 27.3% come from changes in atmospheric CO 2 (42.2%) and climate (-14.9%). Our results underscore the potential of active land management in achieving 'carbon-neutrality' in China.</p><p>The dynamics of the terrestrial ecosystem carbon balance are driven collectively by environmental changes and direct land management 1-4 . Future environmental changes such as climate change and atmospheric CO 2 increase (or decrease) hinge on the climate policies of all nations. Hence, the resulting land carbon responses are beyond the control of any specific nation. In contrast, options for active changes in land management to increase carbon stock or avoid emissions lie within the reach of each individual nation. Indeed, of the declared or submitted nationally determined contributions (NDCs) to implement the Paris Agreement, 10%-30% of the planned reductions in global emissions will be provided by active changes in land management 5,6 .</p></div>
Tropical forests are threatened by anthropogenic activities such as conversion into agricultural land, logging and fires. Land-use change and disturbance affect ecosystems not only aboveground, but also belowground including the ecosystems' carbon and nitrogen cycle. We studied the impact of different types of land-use change (intensive and traditional agroforestry, logging) and disturbance by fire on fine root biomass, dynamics, morphology, and related C and N fluxes to the soil via fine root litter across different ecosystems at different elevational zones at Mt. Kilimanjaro (Tanzania). We found a decrease in fine root biomass (80–90%), production (50%), and C and N fluxes to the soil via fine root litter (60–80%) at all elevation zones. The traditional agroforestry 'Chagga homegardens' (lower montane zone) showed enhanced fine root turnover rates, higher values of acquisitive root morphological traits, but similar stand fine root production, C and N fluxes compared to the natural forest. The decrease of C and N fluxes with forest disturbance was particularly strong at the upper montane zone (60 and 80% decrease, respectively), where several patches of Podocarpus forest had been disturbed by fire in the previous years. We conclude that changes on species composition, stand structure and land management practices resulting from land-use change and disturbance have a strong impact on the fine root system, modifying fine root biomass, production and the C and N supply to the soil from fine root litter, which strongly affects the ecosystems' C and N cycle in those East African tropical forest ecosystems.
The rapid expansion of Artificial Intelligence (AI) has intensified concerns about its environmental sustainability. Current assessments focus on operational carbon emissions using secondary data, overlooking impacts in other life cycle stages. This study presents a comprehensive multi-criteria life cycle assessment of AI training, examining 16 environmental impact categories using primary data from the Nvidia A100 SXM 40 GB GPU. Results for GPT-4 training show that the use phase dominates 10 categories, contributing 96% to climate change and fossil fuel depletion. Manufacturing dominates 6 categories, including human toxicity (94%) and freshwater eutrophication (81%). The GPU chip is the largest contributor in 10 categories, particularly climate change (81%) and fossil resource use (80%). While primary data produces modest changes in carbon estimates, substantial variations emerge elsewhere, e.g. minerals and metals depletion increases by 33%. This analysis expands the Sustainable AI discourse beyond carbon emissions, challenging current sustainability narratives.
International audience;
The ability of forests to withstand, and recover from, acute drought stress is a critical uncertainty regarding the impacts of climate change on the terrestrial carbon (C) cycle, but it is unclear how drought responses scale from individual trees to whole forests. Here, we assembled a dataset of tree-ring chronologies co-located within the footprint of eddy covariance towers across North America and Europe, with the aim of quantifying the sensitivity of tree radial growth versus gross primary productivity (GPP) during and following drought. We found that drought induced a large decoupling across C cycle processes, whereby GPP was relatively resistant to water stress despite large reductions in tree-ring widths. This decoupling also occurred in the year following drought (i.e., a ‘drought legacy effect’), and was similar in magnitude in response to both summer and winter droughts. By modeling whole-forest C turnover time, we show that a radial growth-GPP decoupling has important ramifications for the forest C cycle, especially if the C not used to support radial growth is instead allocated towards pools with short residence times. Our results demonstrate that quantifications of drought impacts that rely solely on C uptake are missing this fundamental pathway through which drought alters the forest C cycle and the resulting feedbacks to the climate system.
International audience;
Monitoring the carbon dioxide (CO2) concentration in the atmosphere is crucial for reducing carbon emissions. Compared to traditional ground-based monitoring, remote sensing measurements have a wider coverage and stronger continuous monitoring capabilities. This paper introduces the types and characteristics of remote sensing satellites used for CO2 detection, describes the detection process and main technologies, and takes the remote sensing satellite carrying AIRS (Atmospheric Infrared Sounder) as an example to analyze its application in CO2 detection. The results indicate that the current remote sensing satellites have TIROS-N series TOVS sensors, AIRS, IASI, SCIAMACHY, GOSAT, and OCO. The remote sensing technology process includes mission planning and sensor selection, data acquisition, data preprocessing, spectral analysis, inversion algorithm for extracting CO2 concentration information, spatial resolution optimization, data quality control and validation, spatiotemporal analysis and data fusion, generation of visual reports, and data dissemination. The data obtained from the AIRS remote sensing satellite for detecting CO2 concentration has been validated through comparison with ground station and aircraft measurement data. In addition, by analyzing the spatial and temporal distribution of CO2 and analyzing the intensity and seasonal variations of carbon sources and sinks in different regions, high carbon emission areas can be identified. Remote sensing technology also has some challenges and uncertainties, such as limitations caused by atmospheric turbulence, cloud cover, and lower accuracy. Therefore, future research needs to optimize remote sensing data processing methods further, develop more accurate inversion models, and consider integrating multiple remote sensing data sources.
International audience;
This chapter provides an overview of the physical and biogeochemical factors that control spatial and temporal patterns of oxygen minimum zones (OMZs), carbon and pH variability in the Indian Ocean. Oxygen concentrations decline to nearly zero in Arabian Sea intermediate water with profound biogeochemical impacts on the nitrogen cycle as a result of denitrification. These impacts can hardly be observed in the Bay of Bengal where oxygen concentrations are poised just above the threshold below which denitrification becomes significant. Hypoxic/anoxic conditions in the open ocean waters of the northern Indian Ocean have not dramatically changed over past decades, but evidence is now emerging that oxygen concentrations are starting to decline, with significant biogeochemical and ecological impacts. The Indian Ocean accounts for ~1/5 of the global oceanic uptake of atmospheric CO2, with the Arabian Sea as a source of CO2 to the atmosphere and the southern subtropical gyre as a CO2 sink. Net CO2 flux in the Bay of Bengal is uncertain due to sparse sampling. Surface pH values in the Indian Ocean are anomalously low and projected to decline further with negative impacts on calcifying organisms. Dissolved organic carbon (DOC) concentrations in the Indian Ocean tend to be high in nearsurface (sub)tropical waters where autotrophic production of DOC exceeds heterotrophic consumption and vertical stability of the water column favors accumulation. In contrast, the highest particulate organic carbon (POC) concentrations in the Indian Ocean are observed in the northwestern part of the basin and the lowest in the southern subtropical gyre, reflecting primary production patterns. POC export flux patterns in the Indian Ocean are similar to the patterns in POC concentration, though carbon flux is also strongly influenced by lithogenic matter content in river-influenced regions like the Bay of Bengal. Observational and modeling research should target improved understanding of northern Indian Ocean OMZ and carbon system variability as such is needed to predict the impacts of anthropogenic influence and global warming on Indian Ocean biogeochemistry and ecosystems.
International audience;
Will humans survive the climate crisis? The burning of fossil fuels and other carbon dioxide-emitting industrial and agricultural activities have sharply increased the levels of atmospheric carbon dioxide (CO2) from about 280 ppmv in 1850 to 430 ppmv in April 2025. This has induced a +1.49 °C increase of the global surface temperature versus the 1850-1900 pre-industrial average temperature, with the ten most recent years being the warmest years on record. This change is remarkably represented using data from the United States National Aeronautics Space Administration (US NASA, Fig. 1). In April 2025, the threshold of a maximum 1.5 °C increase of the 2015 Paris Agreement to limit greenhouse emissions has thus nearly been reached, which means that we have just entered an era where catastrophic events will highly intensify. In fact, +1.5 °C is already too high and is likely to raise sea-level by several meters, thus causing substantial damage to coastal populations. This calls for techniques such as radiative forcing geoengineering that could rapidly decrease atmospheric CO2 levels on the global scale. As a consequence, the number of academic reports on carbon capture and sequestration since 2015 has more than doubled compared to from 1992 to 2014. Here we discuss the global soil carbon pool, microbial carbon capture, the microbial carbon pump, contributions from plants, fungi and bacteria, and the use of synthetic microbial communities.
Storms are among the most damaging disasters on earth: the most costly and the second deadliest. Among these storms, tropical cyclones cause the most damage. Medicanes --- Mediterranean subtropical cyclones --- can also do significant harm, as demonstrated by the recent example of Storm Daniel.The study of tropical cyclones is largely based on climate models. It is well established that a prerequisite for simulating these phenomena is a horizontal resolution of a few tens of kilometres.The Institut Pierre-Simon Laplace (IPSL) develops and maintains a climate model (IPSL-CM), with which it is now possible to achieve such high resolutions thanks to the recent development of DYNAMICO.My thesis assesses the opportunity associated with the arrival of DYNAMICO for studying tropical cyclones at IPSL. The question I address in the present thesis is: Is IPSL-CM at high horizontal resolution capable of correctly simulating the climatology of tropical and Mediterranean cyclones?First, I compared several methods for detecting tropical cyclones in climate data. To this end, I applied four methods to the ERA5 reanalysis and compared the results with a database of observations. I showed that all detection methods can detect around 80% of observed cyclones. They agree on the strongest events. The frequency and duration of events detected vary according to the methods' propensity to detect weak cyclones. Some methods also tend to detect extra-tropical cyclones. To counter this problem, I have developed two methods to filter out such systems. (Bourdin et al., 2022)I then assessed the climatology of tropical cyclones in six simulations with varying resolutions, produced using the HighResMIP protocol. In these atmosphere-only historical simulations, the cyclone activity increases dramatically as resolution increases from 200 to 25 km. Increasing resolution also enables better simulation of the distribution of cyclones between and among basins as well as the structure of cyclones. The high-resolution model can simulate the observed interannual variability and its link with ENSO, particularly in the North Atlantic and Northeast Pacific. In the North-Western Pacific, the model does not simulate enough tropical cyclones due to a climatological bias in the large-scale circulation. The IPSL model shows an outstanding ability to simulate tropical cyclones in the North Atlantic, a basin where many other models exhibit biases. (Bourdin et al., 2023, in review)Finally, I have extended my evaluation to Mediterranean cyclones to highlight the particularities of medicanes.The model can simulate Mediterranean cyclones and medicanes climatology in good agreement with the ERA5 reanalysis. The simulated medicanes have a more symmetrical structure, and surface heat fluxes play a more important role compared to Mediterranean cyclones in general. Unlike Mediterranean cyclones, medicanes only appear in the presence of weak horizontal wind shear.In conclusion, my thesis demonstrates the ability of the IPSL model to simulate tropical and Mediterranean cyclones at a horizontal resolution of 25 km. This paves the way for further studies of tropical cyclones with the IPSL model, which may help to better understand the climatology of these events.
;
Les tempêtes font partie des désastres qui font le plus de dégâts sur terre : elles sont les plus coûteuses, et les deuxièmes plus mortelles. Parmi ces tempêtes, les cyclones tropicaux font le plus de dégâts. Il existe aussi un type de cyclone subtropical méditerranéen proche des cyclones tropicaux, appelé medicane, qui peut causer d'importants dégâts, comme l'a prouvé l'exemple récent de la tempête Daniel.L'étude des cyclones tropicaux et subtropicaux repose en grande partie sur les modèles de climat. Il est bien établi qu'une condition nécessaire à la simulation de ces phénomènes est une résolution horizontale de quelques dizaines de kilomètres.L'Institut Pierre-Simon Laplace (IPSL) développe et maintient un modèle de climat (IPSL-CM), avec lequel il est désormais possible d'atteindre ces résolutions grâce au développement récent de DYNAMICO.Ma thèse consiste à évaluer l'opportunité que représente l'arrivée de DYNAMICO pour l'étude des cyclones tropicaux au sein de l'IPSL. J'ai donc adressé la question suivante : Le modèle de l'IPSL à haute résolution horizontale est-il capable de simuler correctement la climatologie des cyclones tropicaux et méditerranéens ?Dans un premier temps, j'ai effectué une comparaison de plusieurs méthodes de détection des cyclones tropicaux dans des données climatiques. Pour cela, j'ai appliqué quatre méthodes à la réanalyse ERA5, et comparé les résultats à une base de données d'observations. J'ai montré que toutes les méthodes de détection sont capables de détecter environ 80% des cyclones observés. Elles s'accordent toutes sur les évènements les plus forts. La fréquence et la durée des évènements détectés varient selon la propension des méthodes à détecter les cyclones faibles. Certaines méthodes ont aussi tendance à détecter des cyclones extra-tropicaux. Pour remedier à ce problème, j'ai développé deux méthodes de filtrages de ces systèmes. (Bourdin et al., 2022)J'ai ensuite procédé à l'évaluation de la climatologie des cyclones tropicaux dans six simulations de résolution variable, produites selon le protocole HighResMIP. Dans ces simulations historiques en atmosphère seule, on constate que l'activité cyclonique augmente énormément lorsque la résolution augmente de 200 à 25 km. L'augmentation de la résolution permet aussi de mieux simuler la répartition des cyclones entre et parmi les bassins, et la structure des cyclones. Le modèle à haute résolution est capable de simuler la variabilité interannuelle observée et son lien avec ENSO, en particulier dans le Nord Atlantique et de Nord-Est Pacifique. Dans le Nord-Ouest Pacifique, le modèle ne simule pas assez de cyclones tropicaux à cause d'un biais climatologique dans la circulation de grande échelle. Le modèle de l'IPSL démontre une capacité particulièrement bonne à simuler les cyclones tropicaux dans le Nord Atlantique, qui est un bassin où beaucoup d'autres modèles présentent des biais. (Bourdin et al., 2023, en révision)Enfin, j'ai étendu mon évaluation aux cyclone méditerranéens pour mettre en évidence les particularités des medicanes.Le modèle simule une climatologie de cyclones méditerranéens et de medicanes similaire à la réanalyse ERA5. Cela permet de montrer que les medicanes ont une structure plus symétrique, et que les flux de surface y jouent un rôle plus important que pour l'ensemble des cyclones méditerranéens. De plus, ils n'apparaissent qu'en présence d'un faible cisaillement de vent horizontal.En conclusion, ma thèse démontre la capacité du modèle de l'IPSL à simuler des cyclones tropicaux et méditerranéens à une résolution horizontale de 25 km. Cela ouvre la voie à des études plus poussées des cyclones tropicaux avec le modèle de l'IPSL, qui pourront aider à mieux comprendre la climatologie de ces évènements.
CCSD;American Association for the Advancement of Science (AAAS)november 2025Klimaatwetenschap
International audience;
The size and control mechanism of the Southern Ocean’s carbon fluxes remain highly uncertain due to sparse winter observations. Here, we integrate satellite light detection and ranging (LIDAR) measurements with machine learning to assess the Southern Ocean air-sea CO2 fluxes between 2007 and 2020. We reveal that CO2 outgassing south of 50°S was underestimated by up to 40% in previous studies. While the midlatitude Southern Ocean (30° to 50°S) strengthens as a carbon sink, the high-latitude region (50° to 90°S) shows Southern Annular Mode (SAM)–modulated alternation between uptake and outgassing. The air-sea CO2 partial pressure difference (ΔpCO2) increasingly dominates flux variability over wind-driven transfer velocity. We propose a framework involving three latitudinal loops with differing pCO2 controls: (i) Antarctic (salinity/sea ice), (ii) polar front (atmospheric CO2/chlorophyll), and (iii) subpolar (sea surface temperature/CO2). The findings underscore the winter processes’ critical role and necessitate year-round observations to understand Southern Ocean’s global carbon cycle impact.
John Wiley and Sons Inc.juni 2022Klimaatwetenschap
Increasing responsiveness to anthropogenic climate change and the loss of global shellfish ecosystems has heightened interest in the carbon storage and sequestration potential of bivalve‐dominated systems. While coastal ecosystems are dynamic zones of carbon transformation and change, current uncertainties and notable heterogeneity in the benthic environment make it difficult to ascertain the climate change mitigation capacity of ongoing coastal restoration projects aimed at revitalizing benthic bivalve populations. In this study we sought to distinguish between direct and indirect effects of subtidal green‐lipped mussels (Perna canaliculus) on carbon cycling, and combined published literature with in‐situ experiments from restored beds to create a carbon budget for New Zealand's shellfish restoration efforts. A direct summation of biogenic calcification, community respiration, and sediment processes suggests a moderate carbon efflux (+100.1 to 179.6 g C m(−2) year(−1)) occurs as a result of recent restoration efforts, largely reflective of the heterotrophic nature of bivalves. However, an examination of indirect effects of restoration on benthic community metabolism and sediment dynamics suggests that beds achieve greater carbon fixation rates and support enhanced carbon burial compared to nearby sediments devoid of mussels. We discuss limitations to our first‐order approximation and postulate how the significance of mussel restoration to carbon‐related outcomes likely increases over longer timescales. Coastal restoration is often conducted to support the provisioning of many ecosystem services, and we propose here that shellfish restoration not be used as a single measure to offset carbon dioxide emissions, but rather used in tandem with other initiatives to recover a bundle of valued ecosystem services.
Wij gebruiken cookies en andere soortgelijke technologieën om :
ETHISCHE SEIDO-diensten aanbieden en toezien op de goede werking ervan
Storingen in de dienstverlening opsporen en beschermen tegen cyber-malware, zoals spam, fraude en misbruik
meten van publieksbetrokkenheid en site-statistieken om te begrijpen hoe onze diensten worden gebruikt en om de kwaliteit ervan te verbeteren
Nieuwe diensten ontwikkelen en verbeteren
Als u op "Accepteren" klikt, zullen we ook cookies en andere vergelijkbare technologieën gebruiken om:
Advertenties weergeven en hun effectiviteit meten
Bied gepersonaliseerde inhoud op basis van uw instellingen
Geef gepersonaliseerde advertenties weer op basis van uw instellingen
Om u gratis toegang te bieden tot onze diensten, de verspreiding van advertenties die de betaling van onze diensten mogelijk maken
Als u op "weigeren" klikt: wij zullen geen cookies gebruiken voor deze extra doeleinden. Een abonnement is nodig om toegang te krijgen tot onze diensten.
Log in, als je al een abonnement hebt
![Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[^18F]FDG-PET study](https://media.springernature.com/m685/springer-static/image/art%3A10.1007%2Fs00415-022-11445-9/MediaObjects/415_2022_11445_Fig1_HTML.jpg)
