Alzheimer's disease (AD) is a neurodegenerative disorder marked by memory loss and cognitive decline, making early detection vital for timely intervention. However, early diagnosis is challenging due to the heterogeneous presentation of symptoms. Resting-state functional magnetic resonance imaging (rs-fMRI) captures spontaneous brain activity and functional connectivity, which are known to be disrupted in AD and mild cognitive impairment (MCI). Traditional methods, such as Pearson's correlation, have been used to calculate association matrices, but these approaches often overlook the dynamic and non-stationary nature of brain activity. In this study, we introduce a novel method that integrates discrete wavelet transform (DWT) and graph theory to model the dynamic behavior of brain networks. Our approach captures the time-frequency representation of brain activity, allowing for a more nuanced analysis of the underlying network dynamics. Machine learning was employed to automate the discrimination of different stages of AD based on learned patterns from brain network at different frequency bands. We applied our method to a dataset of rs-fMRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, demonstrating its potential as an early diagnostic tool for AD and for monitoring disease progression. Our statistical analysis identifies specific brain regions and connections that are affected in AD and MCI, at different frequency bands, offering deeper insights into the disease's impact on brain function.
In the past two years, large language model (LLM)-based chatbots, such as ChatGPT, have revolutionized various domains by enabling diverse task completion and question-answering capabilities. However, their application in scientific research remains constrained by challenges such as hallucinations, limited domain-specific knowledge, and lack of explainability or traceability for the response. Graph-based Retrieval-Augmented Generation (GraphRAG) has emerged as a promising approach to improving chatbot reliability by integrating domain-specific contextual information before response generation, addressing some limitations of standard LLMs. Despite its potential, there are only limited studies that evaluate GraphRAG on specific domains that require intensive knowledge, like Alzheimer's disease or other biomedical domains. In this paper, we assess the quality and traceability of two popular GraphRAG systems. We compile a database of 50 papers and 70 expert questions related to Alzheimer's disease, construct a GraphRAG knowledge base, and employ GPT-4o as the LLM for answering queries. We then compare the quality of responses generated by GraphRAG with those from a standard GPT-4o model. Additionally, we discuss and evaluate the traceability of several Retrieval-Augmented Generation (RAG) and GraphRAG systems. Finally, we provide an easy-to-use interface with a pre-built Alzheimer's disease database for researchers to test the performance of both standard RAG and GraphRAG.
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.
Early detection of Alzheimer's disease (AD) requires models capable of integrating macro-scale neuroanatomical alterations with micro-scale genetic susceptibility, yet existing multimodal approaches struggle to align these heterogeneous signals. We introduce R-GenIMA, an interpretable multimodal large language model that couples a novel ROI-wise vision transformer with genetic prompting to jointly model structural MRI and single nucleotide polymorphisms (SNPs) variations. By representing each anatomically parcellated brain region as a visual token and encoding SNP profiles as structured text, the framework enables cross-modal attention that links regional atrophy patterns to underlying genetic factors. Applied to the ADNI cohort, R-GenIMA achieves state-of-the-art performance in four-way classification across normal cognition (NC), subjective memory concerns (SMC), mild cognitive impairment (MCI), and AD. Beyond predictive accuracy, the model yields biologically meaningful explanations by identifying stage-specific brain regions and gene signatures, as well as coherent ROI-Gene association patterns across the disease continuum. Attention-based attribution revealed genes consistently enriched for established GWAS-supported AD risk loci, including APOE, BIN1, CLU, and RBFOX1. Stage-resolved neuroanatomical signatures identified shared vulnerability hubs across disease stages alongside stage-specific patterns: striatal involvement in subjective decline, frontotemporal engagement during prodromal impairment, and consolidated multimodal network disruption in AD. These results demonstrate that interpretable multimodal AI can synthesize imaging and genetics to reveal mechanistic insights, providing a foundation for clinically deployable tools that enable earlier risk stratification and inform precision therapeutic strategies in Alzheimer's disease.
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.
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Background: Fluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25-35] peptide (Aβ25-35)-induced neurotoxicity in mice, a pharmacological model of Alzheimer's disease (AD) with high predictive value for drug discovery. Here, as drug infusion is likely to better reflect drug bioavailability due to the interspecies pharmacokinetics variation, we analyzed the efficacy of FENM after chronic subcutaneous (SC) infusion, in comparison with IP injections in two AD mouse models, Aβ25-35-injected mice and the transgenic APPswe/PSEN1∂E9 (APP/PS1) line.Methods: In Aβ25-35-treated mice, FENM was infused at 0.03-0.3 mg/kg/day during one week after Aβ25-35 injection. For comparison, FENM and MEM were administered IP daily at 0.03-0.3 mg/kg. In 10-month-old APP/PS1 mice, FENM was administered during four weeks by daily IP injections at 0.3 mg/kg or chronic SC infusion at 0.1 mg/kg/day. Memory deficits, spatial working memory and recognition memory, were analysed. Markers of neuroinflammation, apoptosis, oxidative stress, and amyloid burden in APP/PS1 mice, were quantified. Markers of synaptic plasticity such as PSD-95 and GluN2A/B/D subunits expression in hippocampus homogenates or synaptosomes were quantified in Aβ25-35-treated mice and synaptic long-term potentiation (LTP) in hippocampal slices was analysed in APP/PS1 mice.Results: Deficits in spontaneous alternation and object recognition in Aβ25-35 mice were prevented by infused FENM at all doses tested. Similar effects were observed with the daily FENM or MEM treatments. Animals infused with 0.1 mg/kg/day FENM showed prevention of Aβ25-35-induced neuroinflammation, oxidative stress and apoptosis. FENM infusion restored Aβ25-35-induced alterations in synaptosomal PSD-95, GluN2A and P-GluN2B levels. GluN2D levels were unchanged whatever the treatment. In APP/PS1 mice, FENM infused or administered IP alleviated spontaneous alternation deficits, neuroinflammation, increases in Aβ1-40/Aβ1-42 and hippocampal LTP alteration.Conclusion: These data confirmed the neuroprotective potential of FENM in the pharmacological Aβ25-35 and transgenic APP/PS1 mouse models of AD, with a superiority to MEM, and showed that the drug can be efficiently infused chronically.
The association of epileptic activity and Alzheimer's disease (AD) has been increasingly reported in both clinical and experimental studies, suggesting that amyloid-$β$ accumulation may directly affect neuronal excitability. Capturing these interactions requires a quantitative description that bridges the molecular alterations of AD with the fast electrophysiological dynamics of epilepsy. We introduce a novel mathematical model that extends the Barreto-Cressman ionic formulation by incorporating multiple mechanisms of calcium dysregulation induced by amyloid-$β$, including formation of $\mathrm{Ca}^{2+}$-permeable pores, overactivation of voltage-gated $\mathrm{Ca}^{2+}$ channels, and suppression of $\mathrm{Ca}^{2+}$-sensitive potassium currents. The resulting ionic model is coupled with the monodomain equation and discretized using a $p$-adaptive discontinuous Galerkin method on polytopal meshes, providing an effective balance between efficiency and accuracy in capturing the sharp spatiotemporal electrical wavefronts associated with epileptiform discharges. Numerical simulations performed on idealized and realistic brain geometries demonstrate that progressive amyloid-\textbeta{} accumulation leads to severe alterations in calcium homeostasis, increased neuronal hyperexcitability, and pathological seizure propagation. Specifically, high amyloid-$β$ concentrations produce secondary epileptogenic sources and spatially heterogeneous wavefronts, indicating that biochemical inhomogeneities play a critical role in shaping seizure dynamics. These results illustrate how multiscale modeling provides new mechanistic insights into the interplay between neurodegeneration and epilepsy in Alzheimer's disease.
Alzheimer's Disease is an incurable cognitive condition that affects
thousands of people globally. While some diagnostic methods exist for
Alzheimer's Disease, many of these methods cannot detect Alzheimer's in its
earlier stages. Recently, researchers have explored the use of
Electroencephalogram (EEG) technology for diagnosing Alzheimer's. EEG is a
noninvasive method of recording the brain's electrical signals, and EEG data
has shown distinct differences between patients with and without Alzheimer's.
In the past, Artificial Neural Networks (ANNs) have been used to predict
Alzheimer's from EEG data, but these models sometimes produce false positive
diagnoses. This study aims to compare losses between ANNs and Kolmogorov-Arnold
Networks (KANs) across multiple types of epochs, learning rates, and nodes. The
results show that across these different parameters, ANNs are more accurate in
predicting Alzheimer's Disease from EEG signals.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders worldwide. As it progresses, it leads to the deterioration of cognitive functions. Since AD is irreversible, early diagnosis is crucial for managing its progression. Mild Cognitive Impairment (MCI) represents an intermediate stage between Cognitively Normal (CN) individuals and those with AD, and is considered a transitional phase from normal cognition to Alzheimer's disease. Diagnosing MCI is particularly challenging due to the subtle differences between adjacent diagnostic categories. In this study, we propose EffNetViTLoRA, a generalized end-to-end model for AD diagnosis using the whole Alzheimer's Disease Neuroimaging Initiative (ADNI) Magnetic Resonance Imaging (MRI) dataset. Our model integrates a Convolutional Neural Network (CNN) with a Vision Transformer (ViT) to capture both local and global features from MRI images. Unlike previous studies that rely on limited subsets of data, our approach is trained on the full T1-weighted MRI dataset from ADNI, resulting in a more robust and unbiased model. This comprehensive methodology enhances the model's clinical reliability. Furthermore, fine-tuning large pretrained models often yields suboptimal results when source and target dataset domains differ. To address this, we incorporate Low-Rank Adaptation (LoRA) to effectively adapt the pretrained ViT model to our target domain. This method enables efficient knowledge transfer and reduces the risk of overfitting. Our model achieves a classification accuracy of 92.52% and an F1-score of 92.76% across three diagnostic categories: AD, MCI, and CN for full ADNI dataset.
This study estimates the association between blood levels of inflammatory markers and cognitive function in adults with Alzheimer’s disease or mild cognitive impairment. A systematic review and meta-analysis were conducted to synthesize data from studies examining the relationship between blood levels of inflammatory markers and cognitive function in adults with Alzheimer’s disease or mild cognitive impairment. The search strategy was applied to the Medline database through MEDLINE (OVID), WEB OF SCIENCE, SCOPUS, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies were selected based on predefined criteria. We included 84 studies in the qualitative synthesis, with 75 incorporated into the meta-analysis. In blood samples, subjects with Alzheimer’s disease showed significantly higher concentrations of IL-1β (mean difference 0.46 [95% CI: 0.35, 0.58]), IL-6 (3.41 [3.05, 3.78]), MCP-1 (26.20 [14.57, 37.82]), and TNF-α (6.68 [5.97, 7.39]), along with lower concentrations of IL-8 (− 1.46 [− 1.85, − 1.08]) and IL-10 (− 3.20 [− 4.21, − 2.20]). This systematic review and meta-analysis demonstrate significant alterations in inflammatory marker concentrations in blood samples of individuals with Alzheimer’s disease and mild cognitive impairment. Elevated levels of IL-1β, IL-6, MCP-1, and TNF-α, alongside reduced IL-8 and IL-10 levels, suggest a robust inflammatory response associated with Alzheimer’s disease.
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 (AD) is a neurodegenerative disorder characterized by
progressive memory and cognitive decline, affecting millions worldwide.
Diagnosing AD is challenging due to its heterogeneous nature and variable
progression. This study introduces a novel brain-aware readout layer (BA
readout layer) for Graph Neural Networks (GNNs), designed to improve
interpretability and predictive accuracy in neuroimaging for early AD
diagnosis. By clustering brain regions based on functional connectivity and
node embedding, this layer improves the GNN's capability to capture complex
brain network characteristics. We analyzed neuroimaging data from 383
participants, including both cognitively normal and preclinical AD individuals,
using T1-weighted MRI, resting-state fMRI, and FBB-PET to construct brain
graphs. Our results show that GNNs with the BA readout layer significantly
outperform traditional models in predicting the Preclinical Alzheimer's
Cognitive Composite (PACC) score, demonstrating higher robustness and
stability. The adaptive BA readout layer also offers enhanced interpretability
by highlighting task-specific brain regions critical to cognitive functions
impacted by AD. These findings suggest that our approach provides a valuable
tool for the early diagnosis and analysis of Alzheimer's disease.
BACKGROUND: Emerging evidence highlights the potential role of environmental factors, particularly air pollution, in the development and progression of Alzheimer's disease (AD). Air pollutants may contribute to neurodegenerative processes through mechanisms such as oxidative stress, neuroinflammation, and disruption of the blood–brain barrier. OBJECTIVE: This review aims to systematically evaluate global cohort studies investigating the association between long-term exposure to key air pollutants—specifically particulate matter (PM2.5), nitrogen dioxide (NO(2)), and ozone (O(3))—and the risk of AD. METHODS: A total of 31 peer-reviewed cohort studies were included based on a structured search strategy. We analyzed epidemiological outcomes, exposure assessment methodologies, and geographic trends. Additionally, a bibliometric analysis was conducted using VOSviewer to identify major contributors and emerging research themes. RESULTS: Findings indicate a consistent association between PM2.5 exposure and increased risk of AD, independent of genetic predisposition and lifestyle factors. Proposed biological mechanisms include oxidative stress, microglial activation, blood–brain barrier disruption, and amyloid-β accumulation. Bibliometric mapping revealed regional concentration of research in North America, Europe, and East Asia, with increasing global interest over the past decade. CONCLUSIONS: There is mounting evidence linking air pollution to Alzheimer's disease. Advances in exposure assessment have improved the accuracy of epidemiological findings. Public health policies targeting air quality control and further studies on molecular and early-life exposures are essential to mitigate the neurotoxic effects of environmental pollutants.
Early and reliable detection of Alzheimer's disease (AD) is crucial for timely clinical intervention and improved patient management. It also supports the evaluation of emerging therapeutic strategies. In this paper, we propose a Low-Rank Mixture of Experts (LoRA-MoE) deep learning framework for Alzheimer's disease diagnosis based on handwriting analysis. Handwriting signals provide a non-invasive and scalable digital biomarker that captures subtle cognitive-motor impairments associated with early AD progression. The proposed architecture allows multiple experts to specialize in different handwriting patterns while sharing a common base network. This design enables efficient learning of general representations while reducing interference between experts. Each expert is equipped with lightweight low-rank adapters. This mechanism significantly reduces the number of trainable parameters compared with standard Mixture of Experts (MoE) models and improves training stability. The proposed framework is evaluated on the Diagnosis AlzheimeR WIth haNdwriting (DARWIN) dataset. Extensive experiments are conducted, including ablation studies on key architectural parameters such as hidden dimension size, number of experts, and LoRA rank. The method is compared with multilayer perceptron (MLP) and conventional MoE architectures. In addition, stacking ensemble strategies (StackMean and StackMax) are investigated to improve robustness and predictive performance. Experimental results show that the LoRA-MoE framework achieves powerful diagnostic performance while activating significantly fewer parameters during inference. These results highlight the potential of the proposed approach as an accurate and computationally efficient solution for handwriting-based Alzheimer's disease screening and digital health applications. ;26 pages, 6 figures, and 17 tables
Early and accurate diagnosis of Alzheimer Disease is critical for effective clinical intervention, particularly in distinguishing it from Mild Cognitive Impairment, a prodromal stage marked by subtle structural changes. In this study, we propose a hybrid deep learning ensemble framework for Alzheimer Disease classification using structural magnetic resonance imaging. Gray and white matter slices are used as inputs to three pretrained convolutional neural networks such as ResNet50, NASNet, and MobileNet, each fine tuned through an end to end process. To further enhance performance, we incorporate a stacked ensemble learning strategy with a meta learner and weighted averaging to optimally combine the base models. Evaluated on the Alzheimer Disease Neuroimaging Initiative dataset, the proposed method achieves state of the art accuracy of 99.21% for Alzheimer Disease vs. Mild Cognitive Impairment and 91.0% for Mild Cognitive Impairment vs. Normal Controls, outperforming conventional transfer learning and baseline ensemble methods. To improve interpretability in image based diagnostics, we integrate Explainable AI techniques by Gradient weighted Class Activation, which generates heatmaps and attribution maps that highlight critical regions in gray and white matter slices, revealing structural biomarkers that influence model decisions. These results highlight the frameworks potential for robust and scalable clinical decision support in neurodegenerative disease diagnostics. ;18 pages, 4 figures
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 is a neurodegenerative condition characterized by
dementia and impairment in neurological function. The study primarily focuses
on the individuals above age 40, affecting their memory, behavior, and
cognitive processes of the brain. Alzheimer's disease requires diagnosis by a
detailed assessment of MRI scans and neuropsychological tests of the patients.
This project compares existing deep learning models in the pursuit of enhancing
the accuracy and efficiency of AD diagnosis, specifically focusing on the
Convolutional Neural Network, Bayesian Convolutional Neural Network, and the
U-net model with the Open Access Series of Imaging Studies brain MRI dataset.
Besides, to ensure robustness and reliability in the model evaluations, we
address the challenge of imbalance in data. We then perform rigorous evaluation
to determine strengths and weaknesses for each model by considering
sensitivity, specificity, and computational efficiency. This comparative
analysis would shed light on the future role of AI in revolutionizing AD
diagnostics but also paved ways for future innovation in medical imaging and
the management of neurodegenerative diseases.
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.
Recent advancements in generative AI have fostered the development of highly adept Large Language Models (LLMs) that integrate diverse data types to empower decision-making. Among these, multimodal retrieval-augmented generation (RAG) applications are promising because they combine the strengths of information retrieval and generative models, enhancing their utility across various domains, including clinical use cases. This paper introduces AlzheimerRAG, a Multimodal RAG application for clinical use cases, primarily focusing on Alzheimer's Disease case studies from PubMed articles. This application incorporates cross-modal attention fusion techniques to integrate textual and visual data processing by efficiently indexing and accessing vast amounts of biomedical literature. Our experimental results, compared to benchmarks such as BioASQ and PubMedQA, have yielded improved performance in the retrieval and synthesis of domain-specific information. We also present a case study using our multimodal RAG in various Alzheimer's clinical scenarios. We infer that AlzheimerRAG can generate responses with accuracy non-inferior to humans and with low rates of hallucination.
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 Analysis Model (ADAM) is a multi-agent reasoning large language model (LLM) framework designed to integrate and analyze multimodal data, including microbiome profiles, clinical datasets, and external knowledge bases, to enhance the understanding and classification of Alzheimer's disease (AD). By leveraging the agentic system with LLM, ADAM produces insights from diverse data sources and contextualizes the findings with literature-driven evidence. A comparative evaluation with XGBoost revealed a significantly improved mean F1 score and significantly reduced variance for ADAM, highlighting its robustness and consistency, particularly when utilizing human biological data. Although currently tailored for binary classification tasks with two data modalities, future iterations will aim to incorporate additional data types, such as neuroimaging and peripheral biomarkers, and expand them to predict disease progression, thereby broadening ADAM's scalability and applicability in AD research and diagnostic applications. ;12 pages, 7 figures
Springer Science and Business Media LLCJuly 2025Alzheimer's
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17 years' follow-up) of a range of diseases, including heart failure, chronic obstructive pulmonary disease, type 2 diabetes and Alzheimer's disease. Notably, having an especially aged brain posed a risk of Alzheimer's disease (hazard ratio (HR) = 3.1) that was similar to carrying one copy of APOE4, the strongest genetic risk factor for sporadic Alzheimer's disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2, independent of APOE genotype. Accrual of aged organs progressively increased mortality risk (2-4 aged organs, HR = 2.3; 5-7 aged organs, HR = 4.5; 8+ aged organs, HR = 8.3), whereas youthful brains and immune systems were uniquely associated with longevity (youthful brain, HR = 0.60 for mortality risk; youthful immune system, HR = 0.58; youthful both, HR = 0.44). Altogether, these findings support the use of plasma proteins for monitoring of organ health and point to the brain and immune systems as key targets for longevity interventions.
This case reports a 74-year-old female from eastern China presented with memory loss, dyscalculia, language disorders, diagnosed with Alzheimer's disease and underwent deep cervical venous lymphatic anastomosis. After rigorous preoperative evaluation, surgical treatment, and postoperative care, the patient had no postoperative care-related complications and showed obvious improvement in her language and self-care skills. The patient's Mini-Mental State Examination score improved three months after surgery compared to the preoperative period (5 versus 0). This case illustrates the potential of related surgery in the treatment of Alzheimer's disease and emphasizes that proper medical and nursing care are essential for better recovery.
Longitudinal modelling of Alzheimer's disease progression is clinically useful only if it can describe not just the most likely next diagnosis, but how a patient may evolve over time and how reliable that forecast is. Most deep learning approaches reduce this problem to single-step classification, treating cognitively normal, mild cognitive impairment, and dementia as flat categories while providing limited insight into how uncertainty accumulates across future visits. We propose a probabilistic framework that combines ordinal diagnosis prediction, multi-horizon trajectory generation, and decomposed uncertainty estimation. A Temporal Fusion Transformer encoder is adapted with a CORAL ordinal output layer, asymmetric loss weighting, and converter oversampling to respect disease-stage ordering and improve sensitivity to MCI-to-dementia transitions. Conditioned on the learned patient-context representation, an autoregressive Mixture Density Network generates five-year probabilistic trajectories for diagnosis state, CDR Sum of Boxes, MMSE orientation, and hippocampal volume. On ADNI, the model outperforms linear, recurrent, and transformer baselines for next-visit diagnosis prediction, with the strongest gains on MCI-versus-dementia discrimination. Generated trajectories achieve near-nominal 90% credible interval coverage, widening uncertainty across the forecast horizon, and biomarker dynamics consistent with expected Alzheimer's disease progression. We further separate aleatoric from epistemic uncertainty using analytic mixture variance and a five-member bootstrap ensemble, which provides the strongest encoder diversity and output-level epistemic signal. Epistemic uncertainty is higher for rare progression archetypes, MCI and dementia patients, and under external evaluation on OASIS-3, where it increases alongside prediction error.
Generative modeling frameworks have emerged as an effective approach to capture high-dimensional image distributions from large datasets without requiring domain-specific knowledge, a capability essential for disease progression modeling. Recent generative approaches have attempted to capture progression by mapping images to a latent space and guiding representations to generate follow-up images from previous time points. However, these methods impose constraints on distribution learning, resulting in latent spaces with limited controllability for generating follow-up images without paired subject-specific longitudinal guidance.
In order to enable controlled movements in the latent representational space and generate progression images from a previous time-point image without subject-specific guidance, we introduce a conditionable Diffusion Auto-encoder framework that forms a compact latent space capturing high-level semantics and providing means to control generation. Our approach leverages this latent space to condition and apply controlled shifts to the representations of previous time-point images by isolating progression and subject identity information for generating follow-up images. The shifts are implicitly guided by correlating with progression attributes and constraining to Alzheimer's disease specific regions, without paired longitudinal guidance. We validate the generations through image quality metrics, volumetric progression analysis, and downstream tasks in Alzheimer's disease datasets from different sources. This demonstrates the effectiveness of our approach for Alzheimer's progression modeling and longitudinal image generation. ;Accepted in IEEE Journal of Biomedical and Health Informatics ( https://ieeexplore.ieee.org/document/11579738 )
Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA’s neuroprotective action derives from animal models of Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases.
Background Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed. Methods Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared. Results 115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival ( P < 0.001). The cutoff duration was 20 months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20 months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group ( P = 0.047; P = 0.004; P = 0.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64 months and 26 months, respectively; P < 0.001). Conclusions A cutoff duration of 20 months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.
Background Amyotrophic lateral sclerosis (ALS) is characterized by a rapid disease course, with disease severity being associated with declining health-related quality of life (HRQoL) in persons living with ALS (pALS). The main objective of this study was to assess the impact of disease progression on HRQoL across King’s, Milano-Torino Staging (MiToS), and physician-judgement clinical staging. Additionally, we evaluated the impact of the disease on the HRQoL of care partners (cALS). Methods Data were sourced from the Adelphi ALS Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists, pALS and cALS presenting in a real-world clinical setting between July 2020 and March 2021 in Europe and the United States. Results Neurologists ( n = 142) provided data for 880 pALS. There were significant negative correlations between all three clinical staging systems and EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) utility scores and visual analogue scale (VAS) ratings. Although not all differences were significant, 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) scores showed a stepwise increase in HRQoL impairment at each stage of the disease regardless of the staging system. At later stages, high levels of fatigue and substantial activity impairment were reported. As pALS disease states progressed, cALS also experienced a decline in HRQoL and increased burden. Conclusions Across outcomes, pALS and cALS generally reported worse outcomes at later stages of the disease, highlighting an unmet need in this population for strategies to maximise QoL despite disease progression. Recognition and treatment of symptoms such as pain and fatigue may lead to improved outcomes for pALS and cALS.
Background Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient’s right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure ( p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved.
The nuclear RNA-binding protein TDP-43 forms abnormal cytoplasmic aggregates in the brains of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients and several molecular mechanisms promoting TDP-43 cytoplasmic mislocalization and aggregation have been proposed, including defects in nucleocytoplasmic transport, stress granules (SG) disassembly and post-translational modifications (PTM). SUMOylation is a PTM which regulates a variety of cellular processes and, similarly to ubiquitination, targets lysine residues. To investigate the possible regulatory effects of SUMOylation on TDP-43 activity and trafficking, we first assessed that TDP-43 is SUMO-conjugated in the nuclear compartment both covalently and non-covalently in the RRM1 domain at the predicted lysine 136 and SUMO-interacting motif (SIM, 106–110 residues), respectively. By using the SUMO-mutant TDP-43 K136R protein, we demonstrated that SUMOylation modifies TDP-43 splicing activity, specifically exon skipping, and influences its sub-cellular localization and recruitment to SG after oxidative stress. When promoting deSUMOylation by SENP1 enzyme over-expression or by treatment with the cell-permeable SENP1 peptide TS-1, the cytoplasmic localization of TDP-43 increased, depending on its SUMOylation. Moreover, deSUMOylation by TS-1 peptide favoured the formation of small cytoplasmic aggregates of the C-terminal TDP-43 fragment p35, still containing the SUMO lysine target 136, but had no effect on the already formed p25 aggregates. Our data suggest that TDP-43 can be post-translationally modified by SUMOylation which may regulate its splicing function and trafficking, indicating a novel and druggable mechanism to explore as its dysregulation may lead to TDP-43 pathological aggregation in ALS and FTD.
Background Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. Methods ALS patients diagnosed within 12 months and their spouses as healthy controls ( n = 150 couples) were screened. For eligible sALS and bALS patients ( n = 36) and healthy controls ( n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). Results sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes- ratio ( F/B- ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B- ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B- ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood ( r = 0.8006, P < 0.0001) and more severe symptoms ( r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B- ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood ( r = 0.9860, P < 0.0001) and greater disease severity ( r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. Conclusions We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.
Background Bulbar dysfunction is a cardinal feature of ALS with important quality of life and management implications. The objective of this study is the longitudinal evaluation of a large panel imaging metrics pertaining to bulbar dysfunction, encompassing cortical measures, structural and functional cortico-medullary connectivity indices and brainstem metrics. Methods A standardised, multimodal imaging protocol was implemented with clinical and genetic profiling to systematically appraise the biomarker potential of specific metrics. A total of 198 patients with ALS and 108 healthy controls were included. Results Longitudinal analyses revealed progressive structural and functional disconnection between the motor cortex and the brainstem over time. Cortical thickness reduction was an early feature on cross-sectional analyses with limited further progression on longitudinal follow-up. Receiver operating characteristic analyses of the panel of MR metrics confirmed the discriminatory potential of bulbar imaging measures between patients and controls and area-under-the-curve values increased significantly on longitudinal follow-up. C9orf72 carriers exhibited lower brainstem volumes, lower cortico-medullary structural connectivity and faster cortical thinning. Sporadic patients without bulbar symptoms, already exhibit significant brainstem and cortico-medullary connectivity alterations. Discussion Our results indicate that ALS is associated with multi-level integrity change from cortex to brainstem. The demonstration of significant corticobulbar alterations in patients without bulbar symptoms confirms considerable presymptomatic disease burden in sporadic ALS. The systematic assessment of radiological measures in a single-centre academic study helps to appraise the diagnostic and monitoring utility of specific measures for future clinical and clinical trial applications.
Background 5–10% of amyotrophic lateral sclerosis (ALS) patients presented a positive family history (fALS). More than 30 genes have been identified in association with ALS/frontotemporal dementia (FTD) spectrum, with four major genes accounting for 60–70% of fALS. In this paper, we aimed to assess the contribution to the pathogenesis of major and rare ALS/FTD genes in ALS patients. Methods We analyzed ALS and ALS/FTD associated genes by direct sequencing or next-generation sequencing multigene panels in ALS patients. Results Genetic abnormalities in ALS major genes included repeated expansions of hexanucleotide in C9orf72 gene (7.3%), mutations in SOD1 (4.9%), FUS (2.1%), and TARDBP (2.4%), whereas variants in rare ALS/FTD genes affected 15.5% of subjects overall, most frequently involving SQSTM1 (3.4%), and CHMP2B (1.9%). We found clustering of variants in ALS major genes in patients with a family history for “pure” ALS, while ALS/FTD related genes mainly occurred in patients with a family history for other neurodegenerative diseases (dementia and/or parkinsonism). Conclusions Our data support the presence of two different genetic components underlying ALS pathogenesis, related to the presence of a family history for ALS or other neurodegenerative diseases. Thus, family history may help in optimizing the genetic screening protocol to be applied.
Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. Case presentation A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. Conclusions We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% of all ALS cases is the accumulation of phosphorylated trans-activation response (TAR) DNA-binding protein 43 protein (pTDP-43) aggregates in the cytoplasm of neurons and glial cells within the central nervous system. Traditionally, it was believed that the accumulation of TDP-43 aggregates and subsequent neurodegeneration primarily occurs in motor neurons. However, contemporary evidence suggests that as the disease progresses, other systems and brain regions are also affected. Despite this, there has been a limited number of clinical studies assessing the non-motor symptoms in ALS patients. These studies often employ various outcome measures, resulting in a wide range of reported frequencies of non-motor symptoms in ALS patients. The importance of assessing the non-motor symptoms reflects in a fact that they have a significant impact on patients’ quality of life, yet they frequently go underdiagnosed and unreported during clinical evaluations. This review aims to provide an up-to-date overview of the current knowledge concerning non-motor symptoms in ALS. Furthermore, we address their diagnosis and treatment in everyday clinical practice.
Background When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na^+/K^+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na^+/K^+ ATPase elicits SD. Elevated K^+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.
Background This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic lateral sclerosis (ALS). Methods We included 265 newly diagnosed ALS patients during 2016–2022 in Stockholm and 207 ALS-free siblings and partners of the patients as controls. Information on body mass index (BMI), smoking, and history of head injuries, diabetes mellitus, hypercholesterolemia, and hypertension was obtained through the Euro-MOTOR questionnaire at recruitment. Patients were followed from diagnosis until death, invasive ventilation, or November 30, 2022. Results Higher BMI at recruitment was associated with lower risk for ALS (OR 0.89, 95%CI 0.83–0.95), especially among those diagnosed after 65 years. One unit increase in the average BMI during the 3 decades before diagnosis was associated with a lower risk for ALS (OR 0.94, 95%CI 0.89–0.99). Diabetes was associated with lower risk of ALS (OR 0.38, 95%CI 0.16–0.90), while hypercholesterolemia was associated with higher risk of ALS (OR 2.10, 95%CI 1.13–3.90). Higher BMI at diagnosis was associated with lower risk of death (HR 0.91, 95%CI 0.84–0.98), while the highest level of smoking exposure (in pack-years) (HR 1.90, 95%CI 1.20–3.00), hypercholesterolemia (HR 1.84, 95%CI 1.06–3.19), and hypertension (HR 1.76, 95%CI 1.03–3.01) were associated with higher risk of death, following ALS diagnosis. Conclusions Higher BMI and diabetes were associated with lower risk of ALS. Higher BMI was associated with lower risk of death, whereas smoking (especially in high pack-years), hypercholesterolemia, and hypertension were associated with higher risk of death after ALS diagnosis.
Background The present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients. Methods N = 88 ALS patients without frontotemporal dementia were assessed for FI—Katz’s Basic ADL Scale (BADL) and Lawton-Brody’s Instrumental ADL Scale (IADL)—, cognition—Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders—i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King’s and Milano-Torino stages. Results Higher scores on the ECAS-Language were associated with higher IADL scores ( p = 0.005), whilst higher apathetic features—as measured by the Dimensional Apathy Scale (DAS)—were inversely related to the BADL ( p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language ( p = 0.023) and DAS ( p = 0.008) scores were more functionally dependent than those without. Discussion Among non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.
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 devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal cord. As in many other neurodegenerative disorders, the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal transport. Notably, sensory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2 (HSAN2) and spastic paraplegia 30 (SPG30) share several causative genes with ALS, as well as having common clinical phenotypes. KIF1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors (SVPs) and dense core vesicles and has been reported as a causative gene for HSAN2 and SPG30. Methods Here, we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ALS. Results We identified rare damage variants (RDVs) in the KIF1A gene associated with ALS and delineated the clinical characteristics of ALS patients with KIF1A RDVs. Clinically, these patients tended to exhibit sensory disturbance. Interestingly, the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A protein. Functional examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A, VAMP2, and synaptophysin. Expression of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A motor. Conclusions Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS, indicating KIF1A as an important player in the oligogenic scenario of ALS.
Background This article comprises a systematic review of the literature that aims at researching and analyzing the frequently applied guidelines for structuring national databases of epidemiological surveillance for motor neuron diseases, especially Amyotrophic Lateral Sclerosis (ALS). Methods We searched for articles published from January 2015 to September 2019 on online databases as PubMed - U.S. National Institutes of Health’s National Library of Medicine, Scopus, Science Direct, and Springer. Subsequently, we analyzed studies that considered risk factors, demographic data, and other strategic data for directing techno-scientific research, calibrating public health policies, and supporting decision-making by managers through a systemic panorama of ALS. Results 2850 studies were identified. 2400 were discarded for not satisfying the inclusion criteria, and 435 being duplicated or published in books or conferences. Hence, 15 articles were elected. By applying quality criteria, we then selected six studies to compose this review. Such researches featured registries from the American (3), European (2), and Oceania (1) continent. All the studies specified the methods for data capture and the patients’ recruitment process for the registers. Discussions From the analysis of the selected papers and reported models, it is noticeable that most studies focused on the prospect of obtaining data to characterize research on epidemiological studies. Demographic data (ID01) are present in all the registries, representing the main collected data category. Furthermore, the general health history (ID02) is present in 50% of the registries analyzed. Characteristics such as access control, confidentiality and data curation. We observed that 50% of the registries comprise a patient-focused web-based self-report system. Conclusion The development of robust, interoperable, and secure electronic registries that generate value for research and patients presents itself as a solution and a challenge. This systematic review demonstrated the success of a population register requires actions with well-defined development methods, as well as the involvement of various actors of civil society.
Background Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally. Methods We conducted an observational study to define the initial sites of disease onset and the clinical progression (‘spreading patterns’) of motor deficits in a cohort of 910 ALS patients in Germany. Results Mean age of ALS onset was 59.0 ± 12.6 years for males and 61.2 ± 10.5 years for females, the mean ALSFRS-R was 35.1 ± 9.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar/upper limb in 26.8%/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71/244 bulbar onset patients reported spreading pattern to the legs, and 17/339 lumbar onset patients reported spreading secondarily to the bulbar region. Discussion Our results indicate that, although the phenotype of so-called ‘spinal’ or ‘intraspinal’ spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a ‘spinal’ or an ‘intraspinal’ pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS.
Background There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis. Methods We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations. Results Creatinine significantly correlated with LMN damage ( r = 0.38), active ( r = 0.18) and chronic ( r = 0.24) denervation and baseline ALSFRS-R ( r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active ( r = 0.35, r = 0.27, r = 0.24) and chronic ( r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score ( r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride ( r = −0.19) and potassium levels ( r = −0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57–0.86)], creatinine [HR 0.86 (95% CI 0.81–0.92)], chloride [HR 0.95 (95% CI 0.92–0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99–0.99)], and AST [HR 1.02 (95% CI 1.01–1.02)] were independently associated with survival. Conclusions Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival.
Background Actigraphy has been proposed as a measure for tracking functional decline and disease progression in patients with Motor Neuron Disease (MND). There is, however, little evidence to show that wrist-based actigraphy measures correlate with functional decline, and no consensus on how best to implement actigraphy. We report on the use of wrist actigraphy to show decreased activity in patients compared to controls, and compared the utility of wrist- and hip-based actigraphy for assessing functional decline in patients with MND. Methods In this multi-cohort, multi-centre, natural history study, wrist- and hip-based actigraphy were assessed in 139 patients with MND (wrist, n = 97; hip, n = 42) and 56 non-neurological control participants (wrist, n = 56). For patients with MND, longitudinal measures were contrasted with clinical outcomes commonly used to define functional decline. Results Patients with MND have reduced wrist-based actigraphy scores when compared to controls (median differences: prop. active = − 0.053 [− 0.075, − 0.026], variation axis 1 = − 0.073 [− 0.112, − 0.021]). When comparing wrist- and hip-based measures, hip-based accelerometery had stronger correlations with disease progression (prop. active: τ = 0.20 vs 0.12; variation axis 1: τ = 0.33 vs 0.23), whereas baseline wrist-based accelerometery was better related with future decline in fine-motor function (τ = 0.14–0.23 vs 0.06–0.16). Conclusions Actigraphy outcomes measured from the wrist are more variable than from the hip and present differing sensitivity to specific functional outcomes. Outcomes and analysis should be carefully constructed to maximise benefit, should wrist-worn devices be used for at-home monitoring of disease progression in patients with MND.
Background Drug development for neurodegenerative disorders (NDDs) is a long, complex, and expensive enterprise. Methods to optimize drug development for NDDs are needed. Basket trials have been widely used in oncology and have been promoted by the Food and Drug Administration as a means of enhancing the efficiency of drug development. Discussion We reviewed clinical trials for NDDs registered on clinicaltrials.gov in the past 10 years. We identified 59 basket trials assessing the impact of treatment on more than one NDD in the trial. Forty-one of the trials were for 25 agents addressing symptoms of NDD such as motor impairment, hypotension, or psychosis. Eighteen of the trials assessed 14 disease-modifying therapies; the principal targets were mitochondrial function, tau biology, or alpha-synuclein aggregation. Basket trials are most common in phase 2 but have been conducted in phase 1, phase 3, and phase 4. The duration and size of the basket trials are highly variable depending on their developmental phase and the intent of the trial. Parkinson’s disease was the most common disorder included in basket trials of symptomatic agents, and Alzheimer’s disease was the most common disorder included in basket trials of disease-modifying therapies. Most of the basket trials of symptomatic agents were sponsored by pharmaceutical companies (29 of 41 trials); similarly, most of the basket trials investigating DMTs in basket trials were sponsored by the biopharmaceutical industry (11/17 trials). Conclusions Basket trials may increase drug development efficiency by reducing redundancy in trial implementation, enhancing recruitment, sharing placebo groups, and using biomarkers relevant to the mechanism of action of the treatment across NDDs. There have been relatively few basket trials including multiple NDDs in the same trial conducted over the past 10 years. The use of the basket trial strategy may represent an opportunity to increase the efficiency of development programs for agents to treat NDDs.
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 Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. Aim/hypothesis We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. Methods We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. Results 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. Conclusions Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO registration CRD42020223648.
Objective Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of ^18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results. Methods We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans. Results ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC. Interpretation Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits.
Dysphagia is common in motor neurone disease (MND) and associated with negative health and psychosocial outcomes. Although largely considered a motor disease, a growing body of evidence suggests that MND can also affect the sensory system. As intact sensation is vital for safe swallowing, and sensory changes can influence the clinical management of dysphagia in people living with MND, this review evaluated and summarised the current evidence for sensory changes related to swallowing in MND. Of 3,481 articles originally identified, 29 met the inclusion criteria. Of these, 20 studies reported sensory changes, which included laryngeal sensation, taste, gag reflex, cough reflex, tongue sensation, smell, palatal and pharyngeal sensation, silent aspiration, and undefined sensation of the swallowing mechanism. Sensory changes were either described as decreased ( n = 16) or heightened ( n = 4). In the remaining nine studies, sensory function was reported as unaffected. The presence of changes to sensory function related to swallowing in MND remains inconclusive, although an increasing number of studies report sensory changes in some sensory domains. Future research is needed to evaluate the prevalence of sensory changes in MND and how such changes may influence dysphagia and its management.
Purpose Amyotrophic lateral sclerosis (ALS) is a progressive motor impairment leading to early death. Religiousness is one of the factors potentially alleviating the psychological burden of patients. However, its role might vary according to cultural context. Our study aimed to analyze religiosity, and its clinical, psychological and socio-demographic correlates in ALS patients and controls, comparing two European countries with different cultural backgrounds. Methods 268 Polish and German ALS patients, including 18 with locked-in syndrome (LIS) and 198 healthy controls (HC) were interviewed about religiousness, quality of life (Qol), depression, functional status and pain. A follow-up was conducted on 71 patients. Results Polish subjects had a significantly higher level of public, private and general religiosity than the German sample. Importantly, we found no difference in total and public religiousness between ALS patients and HC within either population. Only the private religiousness was significantly higher in German patients compared to controls. In the same sample, private religiousness correlated with functional impairment due to disease progression. In ALS groups and LIS patients, religiousness did not correlate with any disease-associated factors: disease duration, pain, Qol or depression. Follow-up comparisons in the ALS group revealed worsening functional status, increased depression and no significant change in religiosity. Conclusions Religiosity was linked to the cultural background rather than ALS. Generally, it did not correlate with clinical, psychological and socio-demographic parameters and was stable throughout disease progression. The only exception was the relationship between the functional decline and private religiosity among German patients.
Accurate classification of histological subtypes of non-small cell lung
cancer (NSCLC) is essential in the era of precision medicine, yet current
invasive techniques are not always feasible and may lead to clinical
complications. This study presents a multi-stage intermediate fusion approach
to classify NSCLC subtypes from CT and PET images. Our method integrates the
two modalities at different stages of feature extraction, using voxel-wise
fusion to exploit complementary information across varying abstraction levels
while preserving spatial correlations. We compare our method against unimodal
approaches using only CT or PET images to demonstrate the benefits of modality
fusion, and further benchmark it against early and late fusion techniques to
highlight the advantages of intermediate fusion during feature extraction.
Additionally, we compare our model with the only existing intermediate fusion
method for histological subtype classification using PET/CT images. Our results
demonstrate that the proposed method outperforms all alternatives across key
metrics, with an accuracy and AUC equal to 0.724 and 0.681, respectively. This
non-invasive approach has the potential to significantly improve diagnostic
accuracy, facilitate more informed treatment decisions, and advance
personalized care in lung cancer management.
Young adult cancer survivors, defined as persons aged 18–39 who have completed primary curative treatment, constitute a unique group, as they are in a particular life phase forming the foundations of their lives. As a result, they face distinct age-specific challenges in their everyday life related to education, work, and social activities, which negatively impact their quality of life. Rehabilitation may address these challenges, however there is a lack of rehabilitation programmes specifically tailored for young adult cancer survivors. This paper describes the co-production and development of an age-specific and municipality-based cancer rehabilitation programme to improve young adult cancer survivors’ self-efficacy and health-related quality of life. The development included the following steps: (1) reviewing existing literature on cancer rehabilitation programmes for young adults and consulting with relevant stakeholders to gain insights into the target population and the context for implementation; (2) conducting four workshops involving 2–6 young adults, 3–4 professionals, and two researchers and one workshop with 20 young adults and two researchers to co-produce the programmes name, component content, delivery methods, and potential outcomes; and (3) Refine of the programme description. The co-produced programme, Young Adults Taking ACtion, includes one mandatory session for needs identification and goal setting that guides which of the following sessions the young adult cancer survivors will receive: (1) Everyday life, (2) Physical activity, (3) Psychological issues, (4) Education and work, (5) Sexuality and relationships, (6) Funding and grant, and (7) Family and friends. Background Young adult cancer survivors, defined as individuals aged 18–39 who have completed primary curative treatment, face numerous age-specific biopsychosocial late effects that impact health-related quality of life negatively. Rehabilitation can enhance participation in life roles, work, leisure activities and health-related quality of life. However, there is a lack of age-specific cancer rehabilitation for this population, leaving many young adults with diminished self-efficacy in managing their challenges, resulting in unmet needs. This study aimed to co-produce and develop an age-specific, municipality-based cancer rehabilitation intervention programme to improve young adults’ self-efficacy and health-related quality of life. Methods The development process was completed between September 2019 and June 2023 and followed Hawkins et al.’s three-staged framework for co-production: (1) A literature review and stakeholder consultations; (2) four workshops with 2–6 young adult cancer survivors, 3–4 professionals, and two researchers and one workshop with 20 young adult cancer survivors and two researchers to co-produce the name, component content, delivery methods and potential outcomes; and (3) Refinement of the programme and its programme theory. Key findings from each stage informed the subsequent stages. Results The Young Adults Taking ACtion programme was developed. It applies a person-centred approach and is grounded in social cognitive theory and experiential learning theory. It comprises one mandatory component, a needs assessment and goal setting that tailor which of the following seven components the young adults will receive: (1) everyday life, (2) physical activity, (3) psychological issues, (4) education and work, (5) sexuality and relationships, (6) funds and grants, and (7) family and friends. The programme is primarily group-based and will be delivered by an interdisciplinary team over 16 weeks. Conclusions We co-produced a comprehensive, goal-oriented, and peer-based rehabilitation programme for young adult cancer survivors. The engagement of young adults and professionals ensured that the programme aligned with the population’s needs and preferences and was context specific. Thus, it is likely that the programme will be more realistic and feasible to implement in clinical practice.
Background Many patients with cancer want to be involved in healthcare decisions. For adequate participation, awareness of one’s own desires and preferences and sufficient knowledge about medical measures are indispensable. In order to support patient participation, a decision guide for patients with cancer was developed as part of a larger project called TARGET, which specifically aims to improve the care of patients with rare cancer. Methods The development of the decision guide took place from 08.2022 to 03.2023. The decision guide is a single component of a complex intervention that aims to facilitate decision support in cancer care for patients. For the development, existing development and evaluation studies of Question Prompt Lists (QPLs) were identified through systematic literature searches in the MEDLINE via PubMed, PsycInfo, and CINAHL databases. The decision guide was pre-tested for feasibility, usability, completeness and acceptance with the target groups through guided individual interviews. Sociodemographic data were collected anonymously. An expert review was conducted. The verbatim transcribed interviews were analysed using content analysis according to Kuckartz with MAXQDA. The guide has been iteratively optimized based on the results. Results A generic decision guide for patients with cancer for diagnostic or treatment decisions was developed in both PDF web-based formats, based on the Ottawa Personal Decision Guide. It was supplemented with decision-related questions from QPLs for patients with cancer. The pre-test comprised seven expert reviews of (psych)oncologists and experts in evidence-based health information and ten interviews with cancer patients ( n = 7), family relatives ( n = 2), and one caregiver. The results were coded into nine main categories. The results indicated a good feasibility, usability and acceptability of the guide. The tool was perceived as comprehensive and appropriate. Individual elements were identified as modifiable for better comprehensibility. The target audience appreciated the decision guide as a good support option. Conclusion The decision guide is potentially a useful support option for patients with cancer facing medical decisions in their further course of treatment. In the TARGET project, it will be made available to patients and can be supplemented with decision coaching. Further steps for implementation into healthcare structures are necessary. Clinical trial number Not applicable.
Purpose To systematically review the proportion and incidence of CVAD-associated complications in pediatric patients with cancer. Methods PubMed, Embase, and the Cumulative Index of Nursing and Allied Health Literature were searched from 2012 to 2022. Cohort studies and the control arm of randomized controlled trials, which reported CVAD-associated complications in pediatric patients aged 0–18 years, were included. CVAD complications were defined as CVAD failure, central line–associated bloodstream infection (CLABSI), local infection, occlusion, CVAD-associated venous thromboembolism, dislodgement/migration, breakage/rupture, and dehiscence. The pooled proportion and incidence rate (IR) for each CVAD-associated complication were reported. Results Of 40 included studies, there was mixed quality of methods and reporting. Approximately 31.4% (95% confidence interval [CI] 22.5–41.1; 6920 devices) of devices experienced a CVAD-associated complication, and 14.8% (95% CI 10.2–20.1; 24 studies; 11,762 devices) of CVADs failed before treatment completion (incidence rate (IR) of 0.5 per 1000 catheter days (95% CI 0.3–0.8; 12 studies; 798,000 catheter days)). Overall, 21.2% (95% CI 14.3–28.9; 26 studies; 5054 devices) of CVADs developed a CLABSI, with an IR of 0.9 per 1000 catheter days (95% CI 0.6–1.3; 12 studies; 798,094 catheter days). Tunneled central venous catheters (TCVC) and peripherally inserted central catheters (PICCs) were associated with increased complications in comparison to totally implanted venous access devices (TIVADs). Conclusion CVAD complication rates in this population remain high. TCVCs and PICCs are associated with increased complications relative to TIVADs. Insufficient evidence exists to guide device selection in this cohort, necessitating further research to determine the role of PICCs in pediatric cancer care. PROSPERO: CRD42022359467. Date of registration: 22 September 2022.
Background Oral contraceptive (OC) use is widespread globally. Despite their significant benefits, concerns persist about a potential rise in breast cancer risk linked to their use. Genetic predisposition also influences breast cancer risk; however, its interaction with OC use remains inconclusive. This study aims to explore the association between OC use and breast cancer risk in women with varying genetic predispositions to breast cancer, as measured by polygenic risk scores (PRS). Method A total of 257,185 white female participants from the UK Biobank were included. Time-varying Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) to examine the association between OC and invasive breast cancer events, stratified by PRS. Age was used as the primary time scale, and analyses were adjusted for year of birth, Townsend Deprivation Index, body mass index, smoking status, age at menarche, menopausal status, family history of breast cancer, parity, hormone replacement therapy use, history of hysterectomy, as well as genetic principal components. Results Current use of OC was associated with an increased risk of breast cancer, with a HR of 1.21 (95% CI: 1.03–1.41). In contrast, previous use showed no association (HR = 0.99, 95% CI: 0.92–1.05). Genetic risk, as measured by the PRS, was strongly associated with breast cancer risk ( P < 0.001). Individuals in the highest PRS decile had approximately three times higher risk compared to those in the mid deciles. Importantly, for the association between current OC use and breast cancer risk, a statistically significant trend was observed across both PRS deciles ( P = 0.04) and tertiles ( P = 0.05), with decreasing HRs as genetic risk increased. Specifically, the HR for current OC use was 1.43 (95% CI: 1.02–2.01) in the lowest PRS tertile, 1.14 (95% CI: 0.89–1.45) in the middle tertile, and 0.96 (95% CI: 0.80–1.14) in the highest tertile. Conclusion Both OC use and a high PRS increase the risk of breast cancer. There is a trend toward a decreased relative risk associated with OC use among those with higher genetic predisposition. Therefore, there is no evidence to suggest that women with a high genetic risk for breast cancer are more adversely affected by OC use.
Patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) face a much poorer prognosis than those with differentiated thyroid cancers. Around 25% of PDTCs and 35% of ATCs carry the BRAFV600E mutation, which constitutively activates the MAPK pathway, a key driver of cell growth. Although combining BRAF and MEK inhibitors can shrink tumors, resistance often develops. The exact cause of this resistance remains unclear. We previously found that in PDTC and ATC cells the BRAFV600E mutation is strongly linked to the expression of ETV5, a transcription factor downstream of the MAPK pathway. In the current study, we observed a significant association between ETV5 expression and the activation of p38, a central component of the MAPK14 pathway. Upon reduction of ETV5 levels, p38 expression and activation decreased, along with its upstream regulators MKK3/MKK6. This suggests that the MAPK and p38/MAPK14 pathways are interconnected and that p38 has oncogenic properties in these cancers. Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. We then tested this combination in a genetically engineered mouse model (GEMM) of ATC. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.
Background The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. There may be differences in pathological characteristics and epidemiological trends between different subgroups of EOCRC, which warrants further investigation. Materials We utilized the Surveillance, Epidemiology, and End Results (SEER) 17 database and the Global Burden of Disease (GBD) 2021 data to analyze clinical, prognostic, and epidemiological differences by dividing EOCRC into Very Early Onset Colorectal Cancer (VEOCRC, ages 15–29) and Mid-Aged Early Onset Colorectal Cancer (MAEOCRC, ages 30–49) over the past 15 years. Statistical analyses included Kaplan-Meier survival analysis, joinpoint regression, average annual percentage change (AAPC) analysis, decomposition analysis. Results The VEOCRC group had a significantly higher proportion of mucinous adenocarcinoma/signet ring cell carcinoma (MA/SRCC) (18.1% vs. 8.7%) and more advanced histologic grades III and IV (32.2% vs. 18.9%) compared to MAEOCRC. There were no significant pathological differences between MAEOCRC and Late-onset CRC (LOCRC). VEOCRC had a worse prognosis than MAEOCRC, especially at stage III. From 2006 to 2021, the age-standardized incidence rate (ASIR) for VEOCRC grew faster than for MAEOCRC globally (AAPC: 0.78 vs. 0.63), notably in high-middle Socio-demographic Index (SDI) countries (AAPC: 2.01 vs. 1.44). Excluding carcinoid tumors, the incidence of VEOCRC in high SDI countries has remained stable over the past 15 years, whereas in high-middle SDI countries, it surpassed high SDI countries as early as 2013, reaching the highest globally. Decomposition analysis revealed that in high-middle SDI countries, epidemiological changes contributed more to the increase in VEOCRC compared to MAEOCRC. Conclusions VEOCRC and MAEOCRC differ significantly in clinical characteristics, prognosis, and epidemiology, with VEOCRC showing worse pathology and prognosis. In the past 15 years, the global incidence of VEOCRC has risen faster than MAEOCRC, warranting particular attention from policymakers, especially in high-middle SDI countries.
Background Cytological screening remains a high-impact practice, particularly in low-resource settings, for preventing cervical cancer. The examination of screening practices over time and the prevalence of epithelial abnormalities have not been investigated in longitudinal studies in one of the largest countries in the Middle East and Africa. Methods Routine healthcare data, between March 1981 and December 2022, were extracted from the database of the Early Cancer Detection Unit in a tertiary referral university hospital in the Greater Cairo Region, Egypt. Cervical smears were obtained using a standardized technique and sent to the cytopathology laboratory for conventional cytology examination by expert pathologists. The anonymous data were analyzed to determine the temporal trend of the number of women screened each year and the prevalence of epithelial abnormalities. Results Data included the results of satisfactory smears from 95120 women. The mean age (SD) of the women at the time of screening was 38.5 (10.5). None of the included women received an HPV vaccine. Abnormal epithelial cells were reported in 5174 women (5.44%). Of these epithelial abnormalities, the majority were low-grade squamous intraepithelial lesions in 4144 women (4.36%). Other abnormalities included atypical squamous cells in 378 women (0.40%), high-grade squamous intraepithelial lesions in 226 women (0.24%), atypical glandular cells not otherwise specified in 184 women (0.19%), adenocarcinoma in 165 women (0.17%), squamous cell carcinoma in 70 women (0.07%), and atypical glandular cells favoring neoplasms in 7 women (0.01%). Women who were at an early age at first intercourse, those who opted for routine cervical cytology screening, and those who were older at screening were more likely to have epithelial abnormalities. The yearly number of screened women was positively associated with the detection of low-grade squamous intraepithelial lesions (correlation coefficient [95% CI] = 0.84 [0.72, 0.91]) and negatively associated with the detection of squamous cell carcinoma (correlation coefficient [95% CI] = -0.55 [-0.73, -0.29]). Conclusions The small number of annually screened Egyptian women and the temporal trend in epithelial abnormalities critically demonstrate the need for establishing and scaling up a structured population-based program to achieve the goal of eliminating cervical cancer.
Background Sarcopenia is characterized by the loss of muscle strength and mass and is associated with poorer clinical outcomes in women with breast cancer. However, no specific tool is capable of assessing the risk of sarcopenia in this population. Therefore, the aim of the present study was to compare the performance of SARC-F, SARC-CalF, and BMI-adjusted SARC-CalF as screening tools for the risk of sarcopenia in women with breast cancer. Methods An observational cross-sectional study was conducted involving women with breast cancer diagnosed in the previous 12 months. The risk of sarcopenia was identified by SARC-F, SARC-CalF, and BMI-adjusted SARC-CalF. As proposed by the EWGSOP2, sarcopenia was defined as low muscle strength (grip strength: <23.0 kg) and appendicular skeletal muscle mass index < 6.38 kg/m^2 (determined by dual-energy X-ray absorptiometry). The performance of the screening tools was assessed by calculating specificity, sensitivity, positive and negative predictive values, and area under the ROC curve (AUC). AUC values were compared using DeLong’s test. Results This study included 168 women with a mean age of 54.8 ± 11.3 years. The prevalence of sarcopenia risk ranged from 10.1 to 36.6%, depending on the screening tool employed. The prevalence of sarcopenia was 8.3%. Using the presence of sarcopenia as reference, the SARC-F had an AUC of 0.550 [(0.396–0.703) p = 0.54], sensitivity of 21.4%, and specificity of 85.7%; the SARC-CalF had an AUC of 0.790 [(0.654–0.927) p < 0.001], sensitivity of 42.8%, and specificity of 92.2%; the BMI-adjusted SARC-CalF had an AUC of 0.521 [(0.385–0.658) p = 0.08], sensitivity of 28.6%, and specificity of 63.0%. Therefore, the SARC-CalF tool had low sensitivity and high specificity. Conclusion SARC-CalF performed the best compared to the alternatives provided. However, based on the current results, it may be necessary to reconsider the use of either of these instruments as a screening option for sarcopenia risk in women with breast cancer.
Purpose With cancer diagnoses increasing worldwide and the number of cancer survivors rising, family physicians are being increasingly relied upon to provide post-cancer treatment care and/or survivorship care. This mixed-method study explores and evaluates barriers and facilitators to optimizing family physician-led survivorship care in the largely rural Interior of British Columbia (BC), Canada. Methods A mixed-method approach consisting of quantitative surveys and qualitative interviews was utilized to explore family physician and oncologist perspectives on the current state of survivorship care for breast, lung, prostate, and colorectal cancers within the BC Interior. Results Concerns about family physician knowledge in some aspects of survivorship care were identified by both groups, with mixed responses regarding geographical factors, resources, and communication networks. Success was dependent on information from oncologists with more common cancer sites fitting the model better. There was significant concern for individuals with no family physician. Five frequently discussed facilitators were identified: (1) providing accessible survivorship guidelines, (2) standardized discharge summaries (i.e., survivorship care plans), (3) clear points-of-contact at cancer care centers, (4) more educational opportunities, and (5) compatible electronic supports between care providers. Conclusions Overall, the model of family physician–led survivorship care was supported by family physicians and oncologists within the BC Interior, although success was dependent on several factors. Identifying the perspectives of physicians directly involved in the survivorship care pathway will be instrumental in developing and implementing solutions that will succeed within the BC Interior and similar regions. Implication to for Cancer Survivors We hope that the improvements to interprofessional cooperation driven by our research may improve the quality and continuity of care received by cancer survivors in British Columbia and beyond. Implication to Cancer Survivors We hope that the improvements to interprofessional cooperation driven by our research may improve the quality and continuity of care received by cancer survivors in British Columbia and beyond.
Skin cancer is the most common cancer type in the USA, with over five million annually treated cases and one in five Americans predicted to develop the disease by the age of 70. Skin cancer can be classified as melanoma or non-melanoma (NMSC), the latter including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC). Development of BCC and SCC is impacted by environmental, behavioral, and genetic risk factors and the incidence is on the rise, with the associated number of deaths surpassing those caused by melanoma, according to recent reports. Substantial morbidity is related to both BCC and SCC, including disfigurement, loss of function, and chronic pain, driving high treatment costs, and representing a heavy financial burden to patients and healthcare systems worldwide. Clinical presentations of BCC and SCC can be diverse, sometimes carrying considerable phenotypic similarities to benign lesions, and underscoring the need for the development of disease-specific biomarkers. Skin biomarker profiling plays an important role in deeper disease understanding, as well as in guiding clinical diagnosis and patient management, prompting the use of both invasive and non-invasive tools to evaluate specific biomarkers. In this work, we review the known and emerging biomarkers of BCC and SCC, with a focus on molecular and histologic biomarkers relevant for aspects of patient management, including prevention/risk assessments, tumor diagnosis, and therapy selection.
Residents are actively involved in patient assessment and all aspects of patient care, and they are critical in providing nutritional support education and treatment for patients with cancer. This study aims to assess the nutritional knowledge and performance of resident physicians, providing insights into existing gaps in awareness and practices related to cancer nutrition. A total of 300 resident physicians undergoing standardized residency training in China participated in this study. An anonymous online questionnaire covering demographic characteristics, nutritional knowledge, clinical practice, and training requirements was designed and administered through the “Wenjuanxing” platform. Data were collected from June 1, 2023, to July 31, 2023. Among the participants, only 40.00% demonstrated adequate knowledge of cancer nutrition, and merely 32.00% exhibited proficient performance in nutritional care. Socio-demographic analysis revealed that residents without affiliations and those specializing in obstetrics and gynecology had superior knowledge, while surgery specialists showed significantly worse performance. Most participants expressed a lack of exposure to cancer nutrition education during academic and standardized residency training. The study highlights the demand for enhanced education and the preference for case-based teaching methods. The findings underscore an urgent need for comprehensive oncology nutrition education within China’s standardized residency training. Targeted interventions and curriculum enhancements are essential to improve medical talent development and enhance patient care outcomes in oncology. The study emphasizes the critical role of practical, case-based teaching methods in addressing identified gaps in nutritional knowledge and practices among resident physicians.
Automated segmentation of cancer on medical images can aid targeted
diagnostic and therapeutic procedures. However, its adoption is limited by the
high cost of expert annotations required for training and inter-observer
variability in datasets. While weakly-supervised methods mitigate some
challenges, using binary histology labels for training as opposed to requiring
full segmentation, they require large paired datasets of histology and images,
which are difficult to curate. Similarly, promptable segmentation aims to allow
segmentation with no re-training for new tasks at inference, however, existing
models perform poorly on pathological regions, again necessitating large
datasets for training. In this work we propose a novel approach for promptable
segmentation requiring only 24 fully-segmented images, supplemented by 8
weakly-labelled images, for training. Curating this minimal data to a high
standard is relatively feasible and thus issues with the cost and variability
of obtaining labels can be mitigated. By leveraging two classifiers, one
weakly-supervised and one fully-supervised, our method refines segmentation
through a guided search process initiated by a single-point prompt. Our
approach outperforms existing promptable segmentation methods, and performs
comparably with fully-supervised methods, for the task of prostate cancer
segmentation, while using substantially less annotated data (up to 100X less).
This enables promptable segmentation with very minimal labelled data, such that
the labels can be curated to a very high standard.
;Comment: Accepted at Medical Image Understanding and Analysis (MIUA) 2025
The Mar Menor, Europe’s largest saltwater lagoon in the Mediterranean basin (Murcia, southeastern Spain), is an ecosystem facing severe pollution, anoxia events, and marine biodiversity loss. This exploratory study examines the association between residential proximity to the Mar Menor and childhood cancer incidence in Murcia from 2000 to 2018. In our case–control study of 594 cancer cases and 3564 controls, matched by birth year and sex, participants were categorized by proximity to the lagoon (G1 ≥ 20 km, G2 = 10–20 km, G3 = 2–10 km, G4 = ≤ 2 km). Odds ratios (ORs) and 95% confidence intervals (95%CI) were adjusted for sociodemographic and environmental covariates. Analysis of distance as a continuous variable indicated a decrease both in all types of cancer and lymphoid acute leukemia risk with greater distance (OR = 0.99; 95% CI 0.98–0.99), while as a categorical variable, it revealed a non-linear pattern. Specifically, the risk did not increase for those living within 2 km of the lagoon (OR = 0.87; 95% CI 0.52–1.37), whereas increased risks were observed in the 2–20 km range within Campo de Cartagena (G2; OR = 1.32; 95% CI 1.01–1.73 and G3; OR = 1.43; 95% CI 1.00–2.02). This suggests modulating factors near the lagoon may counterbalance risks from broader environmental contamination. These findings highlight the complexity of environmental health dynamics and the importance of detailed research to guide public health strategies and urban planning for environmental and child health protection.
Background Liver cancer is the sixth most prevalent cancer globally and the third leading cause of cancer-related mortality, with more than three-quarters of a million deaths. This has presented a significant challenge and imposed considerable strain on global public health systems. Therefore, evaluating the updated global burden of liver cancer and its recent trends in incidence and mortality is highly important, as it provides valuable insights for shaping public health policies and improving clinical practices. Methods The data in our article were obtained from the Global Burden of Disease Study 2021 (GBD 2021), which is available at https://vizhub.healthdata.org/gbd-results/ . In this study, liver cancer mortality and incidence were estimated via the cause of death ensemble (CODEm) model for every combination of sex, age, location, and year. The incidence was modelled with DisMod-MR 2.1, a Bayesian meta-regression tool. A linear regression model was employed to explore the temporal trend of these rates, formulated as y = α + βx + ε, where x represents the calendar year and y signifies the natural logarithm of the rate. For both incidence and mortality, the estimated annual percentage change (EAPC) was computed via the formula 100 × (e^β − 1), accompanied by a 95% confidence interval (CI). Results First, 529,000 cases were newly diagnosed, with an age-standardized incidence rate (ASIR) of 6.15 per 100,000 people. In terms of etiology, the incidence of liver cancer caused by metabolic factors has tended to increase. Additionally, the incidence of liver cancer was greater in males and older populations. Several specific regions presented liver cancer burdens that overwhelmingly surpassed the expected age-standardized rates (ASRs) each year from 1990 to 2021, regardless of their respective sociodemographic index (SDI) scores. Conclusion Our findings reveal that liver cancer continues to pose a significant public health challenge. These findings suggest that targeted interventions are needed to address both the infectious and non-infectious drivers of liver cancer in different socioeconomic settings. Hence, continued efforts in prevention through vaccination, antiviral therapies, and strategies to combat metabolic diseases are crucial for reducing the global burden of liver cancer in the coming decades.
Background Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Materials and methods Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Results Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24 weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5 weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3 months, P = 0.590) or PFS (9.8 vs. 7.5 months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Conclusion Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients .
Foundation models have shown promise in medical imaging but remain underexplored for three-dimensional imaging modalities. No foundation model currently exists for Digital Breast Tomosynthesis (DBT), despite its use for breast cancer screening.
To develop and evaluate a foundation model for DBT (DBT-DINO) across multiple clinical tasks and assess the impact of domain-specific pre-training.
Self-supervised pre-training was performed using the DINOv2 methodology on over 25 million 2D slices from 487,975 DBT volumes from 27,990 patients. Three downstream tasks were evaluated: (1) breast density classification using 5,000 screening exams; (2) 5-year risk of developing breast cancer using 106,417 screening exams; and (3) lesion detection using 393 annotated volumes.
For breast density classification, DBT-DINO achieved an accuracy of 0.79 (95\% CI: 0.76--0.81), outperforming both the MetaAI DINOv2 baseline (0.73, 95\% CI: 0.70--0.76, p<.001) and DenseNet-121 (0.74, 95\% CI: 0.71--0.76, p<.001). For 5-year breast cancer risk prediction, DBT-DINO achieved an AUROC of 0.78 (95\% CI: 0.76--0.80) compared to DINOv2's 0.76 (95\% CI: 0.74--0.78, p=.57). For lesion detection, DINOv2 achieved a higher average sensitivity of 0.67 (95\% CI: 0.60--0.74) compared to DBT-DINO with 0.62 (95\% CI: 0.53--0.71, p=.60). DBT-DINO demonstrated better performance on cancerous lesions specifically with a detection rate of 78.8\% compared to Dinov2's 77.3\%.
Using a dataset of unprecedented size, we developed DBT-DINO, the first foundation model for DBT. DBT-DINO demonstrated strong performance on breast density classification and cancer risk prediction. However, domain-specific pre-training showed variable benefits on the detection task, with ImageNet baseline outperforming DBT-DINO on general lesion detection, indicating that localized detection tasks require further methodological development.
Metaphors and metaphorical language (MLs) play an important role in healthcare communication between clinicians, patients, and patients' family members. In this work, we focus on Dutch language data from cancer patients. We extract metaphors used by patients using two data sources: (1) cancer patient storytelling interview data and (2) online forum data, including patients' posts, comments, and questions to professionals. We investigate how current state-of-the-art large language models (LLMs) perform on this task by exploring different prompting strategies such as chain of thought reasoning, few-shot learning, and self-prompting. With a human-in-the-loop setup, we verify the extracted metaphors and compile the outputs into a corpus named HealthQuote.NL. We believe the extracted metaphors can support better patient care, for example shared decision making, improved communication between patients and clinicians, and enhanced patient health literacy. They can also inform the design of personalized care pathways. We share prompts and related resources at https://github.com/4dpicture/HealthQuote.NL ;Ongoing project report, on behalf of 4D PICTURE https://4dpicture.eu/
The intersection of nutrition and health has received significant attention in recent years, with a particular emphasis on investigating the potential of edible mushrooms in preventing cancer. This chapter aims to provide a general scientific understanding regarding the connection between the consumption of edible mushrooms and their impact on cancer prevention. Researchers are investigating the potential anticancer effects of the complex bioactive compounds found in these mushrooms. These compounds include polysaccharides, beta-glucans, and a variety of secondary metabolites. In addition, the abstract delves into recent epidemiological studies and clinical trials that shed light on the potentially beneficial role that edible mushrooms play in reducing the risk of developing cancer. This article sheds light on the potential mechanisms by which these fungi exert their preventive effects. These mechanisms include immune modulation, anti-inflammatory properties, and antioxidant activities. Through the use of edible mushrooms as a dietary strategy for cancer prevention, the purpose of this chapter is to provide a comprehensive look into the emerging field of edible mushrooms. This highlights the importance of conducting additional research to unlock their therapeutic potential fully.
Background and objectives The aim of this study is to assess and examine the risk variables associated with pulmonary infections in non-small cell lung cancer (NSCLC) and to offer evidence-based recommendations for clinical prophylaxis. Methods Up to December 2023, database such as CNKI, Wanfang, VIP Chinese Science and Technology Journals, Chinese Biomedical, Pubmed, Web of science, and the Cochrane library were searched in order to find randomized controlled trials pertaining to non-small cell lung cancer complicated by pulmonary infection. The NOS scale was utilized to assess the quality of the included research, and the Q test findings were utilized to ascertain the degree of heterogeneity among the studies. Results After retrieving 957 studies in total, 10 literatures were ultimately included for additional analysis. Diabetes mellitus [OR, 2.89; 95% CI: 1.85–4.52; P < 0.00001)] hypoalbuminemia, radiotherapy [OR, 0.43; 95% CI: 1.89–4.07; P < 0.00001], and surgical duration exceeding 180 min [OR,1.10 (1.10 ~ 5.38); P = 0.03] were found to be risk factors for lung infection. Nevertheless, in NSCLC patients, pulmonary infection was not significantly correlated with factors such as age [OR, -0.16 (-0.96 ~ 0.64); P = 0.69], sex [OR, 1.08 (0.77 ~ 1.51); P = 0.66], smoking [OR, 1.10 (0.61 ~ 2.00); P = 0.75], adenocarcinoma [OR,1.10 (0.55 ~ 2.22); P = 0.79], OR, 1.08; 95% CI: 0.77–1.51; P = 0.66], TNMIII-IV stages [OR, 1.62; 95% CI: 0.96–2.75; P = 0.07], and hypertension [1.01(0.76 ~ 1.34); P = 0.94]. Conclusion Diabetes mellitus, radiation therapy, and longer than 180-minute surgeries are risk factors for lung infection in NSCLC patients. The incidence of lung infection can be reduced by quickly identifying these risk factors and putting preventive measures in place.
Histological grade holds great clinical significance in the management and prognosis of bladder cancer; therefore, timely and accurate prediction through non-invasive techniques such as MRI may improve health outcomes. Our objective was to create an MRI-based radiomics model that can predict the histological grade of cancer pre-operatively. In a prospective study, we gathered data from 45 bladder cancer patients who had an mpMRI scan from December 2018 to December 2022 prior to their operative procedure. Radiomics features were extracted from T2-weighted (T2W), diffusion-weighted imaging (DWI), and dynamic DCE-MRI-enhanced (DCE) MR images obtained from a 1.5 T MRI scanner. A standard 5-point VI-RADS scoring system was also assessed for each scan. The variable clustering algorithm was applied to these features, and all cluster features were univariably assessed using receiver operating characteristic (ROC) curves. Multiple predictive models were created and cross-validated based on multivariable analysis to minimize overfitting and predict the grade of the tumor. Among 45 eligible patients, 28 (62.2%) patients had high-grade tumors and the rest 17 (37.8%) were low grade. In the adjusted analysis, only DCE-MRI based (Gray Level Co-occurrence Matrix (Gray Level Co-occurrence Matrix (GLCM))-inverse variance (OR = 1.42, p = 0.028), Major Axis Length (OR = 1.04, p = 0.03)), and age (OR = 1.08, p = 0.039) were associated with the high-grade bladder cancer. Our radiomics models comprising DCE-MRI-based parameters, a T2W parameter, and age yielded the highest performance for predicting grades of bladder cancer (AUC = 0.91; 95% CI 0.82–1.00). These models demonstrated reasonably high predictive performance in bootstrap validation analysis as well. An mpMRI radiomics approach based on MRI has the potential to serve as a non-invasive imaging tool for preoperative grading of bladder cancer.
This perspective critically evaluates the global potential of drug repurposing strategies in oncology to advance health equity and sustainable innovation. Drug repurposing, especially with off-patent medications, offers significant advantages, including reduced costs, shortened timelines for clinical implementation, and enhanced approval success rates compared to new drug development. Herein, we advocate for leveraging of repurposing as a scientifically sound and ethically responsible strategy, while acknowledging the implementation barriers in low- and middle-income countries (LMICs) due to global systemic inequities. Fostering equitable investment in research and infrastructure worldwide is essential to realizing the full potential of this approach. We also identify specific barriers to drug repurposing, including limited funding for clinical trials, inadequate support for investigator-led trials, and the lack of commercial incentives due to non-patented drug utilization. To overcome these barriers, we propose enhanced funding mechanisms, robust advocacy, targeted education initiatives, and policy prioritization for repurposing studies. Case examples illustrate the clinical potential of drug repurposing in reducing metastatic progression and improving survival outcomes. Overall, this perspective underscores drug repurposing as a viable and impactful strategy to advance both innovation and the human right to health in cancer care for all populations. By fostering a collaborative interdisciplinary effort, the benefits of this approach can pave a way for a more equitable and sustainable future in cancer care.
Background The US National Health and Nutrition Examination Survey (NHANES) dataset does not include a specific question or laboratory test to confirm a history of cancer diagnosis. However, if straightforward variables for cancer history are introduced, US NHANES could be effectively utilized in future cancer epidemiology studies. To address this gap, the authors developed a cancer patient database from the US NHANES datasets by employing multiple R programming codes. Methods To illustrate the practical application of this methodology to a real-world problem, the authors extracted the R codes applied in an academic paper published in another journal on January 30th, 2024 ( https://doi.org/10.1016/j.heliyon.2024.e24337 ). This paper will focus on the construction of the database and analysis using R codes. Entire. Results In the first example, the urine concentration of monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate, and mono-2-hydroxy-iso-butyl phthalate (all ng/mL) were used as the independent variable, instead of the serum concentration of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), respectively. In the second example, the serum concentration of 2,3,3’,4,4’-Pentachlorobiphenyl (PCB105), 2,3,4,4´,5-Pentachlorobiphenyl (PCB114), 2,3’,4,4’,5-Pentachlorobiphenyl (PCB118), and 2,2’,3,4,4’,5’- and 2,3,3’,4,4’,6-Hexachlorobiphenyl (PCB138) were used as the independent variable, instead of the serum concentration of PFOA, PFOS, PFHxS, and PFNA, respectively. Discussion This research offers a comprehensive set of R codes aimed at creating a single, user-friendly variable that encapsulates the history of each type of cancer while also considering the age at which the diagnosis was made. The US NHANES provides a wealth of critical data on environmental toxicant exposures. By employing these R codes, researchers can potentially discover numerous new associations between environmental toxicant exposures and cancer diagnoses. Ultimately, these codes could significantly advance the field of cancer epidemiology in relation to environmental toxicant exposure.
Quiescence is a reversible cell cycle exit traditionally thought to be associated with a metabolically inactive state. Recent work in muscle cells indicates that metabolic reprogramming is associated with quiescence. Whether metabolic changes occur in cancer to drive quiescence is unclear. Using a multi-omics approach, we found that the metabolic enzyme ACSS2, which converts acetate into acetyl-CoA, is both highly upregulated in quiescent ovarian cancer cells and required for their survival. Indeed, quiescent ovarian cancer cells have increased levels of acetate-derived acetyl-CoA, confirming increased ACSS2 activity in these cells. Furthermore, either inducing ACSS2 expression or supplementing cells with acetate was sufficient to induce a reversible quiescent cell cycle exit. RNA-Seq of acetate treated cells confirmed negative enrichment in multiple cell cycle pathways as well as enrichment of genes in a published G0 gene signature. Finally, analysis of patient data showed that ACSS2 expression is upregulated in tumor cells from ascites, which are thought to be more quiescent, compared to matched primary tumors. Additionally, high ACSS2 expression is associated with platinum resistance and worse outcomes. Together, this study points to a previously unrecognized ACSS2-mediated metabolic reprogramming that drives quiescence in ovarian cancer. As chemotherapies to treat ovarian cancer, such as platinum, have increased efficacy in highly proliferative cells, our data give rise to the intriguing question that metabolically-driven quiescence may affect therapeutic response.
This paper addresses unsupervised diffusion-based single-channel speech enhancement (SE). Prior work in this direction combines a score-based diffusion model trained on clean speech with a Gaussian noise model whose covariance is structured by non-negative matrix factorization (NMF). This combination is used within an iterative expectation-maximization (EM) scheme, in which a diffusion-based posterior-sampling E-step estimates the clean speech. We first revisit this framework and propose to explicitly model both speech and acoustic noise as latent variables, jointly sampling them in the E-step instead of sampling speech alone as in previous approaches. We then introduce a new semi-supervised SE framework that replaces the NMF noise prior with a diffusion-based noise model, learned jointly with the speech prior in a single conditional score model. Within this framework, we derive two variants: one that implicitly accounts for noise and one that explicitly treats noise as a latent variable. Experiments on WSJ0-QUT and VoiceBank-DEMAND show that explicit noise modeling systematically improves SE performance for both NMF-based and diffusion-based noise priors. Under matched conditions, the diffusion-based noise model attains the best overall quality and intelligibility among unsupervised methods, while under mismatched conditions the proposed NMF-based explicit-noise framework is more robust and suffers less degradation than several supervised baselines. Code, demo, and supplementary materials are publicly available.
Couples therapy requires managing complex, evolving emotional dynamics between partners, but traditional training methods for therapists, like role-play, lack realism, consistency, and control. We present a multi-modal simulation that models therapy as a controlled, multi-agent dynamical system with structured interaction stages. Therapists practice with a pair of client-agents who go through six evolving stages that respond to therapist actions. This simulation enables practice with demand-withdraw conflict patterns in a closed-loop environment. The simulation uses a sense-plan-act architecture: it detects the therapist's input, updates agents' interaction states based on psychotherapy theory and transcript analysis, and generates realistic verbal and emotional responses. In an experiment with 21 licensed U.S. therapists, participants more accurately identified state transitions and rated the system as more realistic and responsive than a prompt-based baseline, demonstrating the value of stateful, interpretable simulation for therapist training.
Most numerical methods for time integration use real-valued time steps. Complex time steps, however, can provide an additional degree of freedom, as we can select the magnitude of the time step in both the real and imaginary directions. We show that specific paths in the complex time plane lead to expanded stability regions, providing clear computational advantages for complex-valued systems. In particular, we highlight the Schrödinger equation, for which complex time integrators can be uniquely optimal. Furthermore, we demonstrate that these benefits extend to certain classes of real-valued stiff systems by coupling complex time steps with the Projective Integration method.
We present a novel work-in-progress approach to the parsing of hypergraphs generated by context-free hyperedge replacement grammars. This method is based on a new LR parsing technique for positional grammars, which is also under active development. Central to our approach is a reduction from hyperedge replacement to positional grammars with additional structural constraints, enabling the use of permutation-based operations to determine the correct ordering of hyperedges on the right-hand side of productions. Preliminary results also reveal a distinction between ambiguity in graph generation and ambiguity in graph recognition. While the exact class of hyperedge replacement languages parsable under this method remains under investigation, the approach provides a promising foundation for future generalisations to more expressive grammar formalisms. Graph parsing remains a broadly relevant problem across numerous domains, and our contribution aims to advance both the theoretical and practical understanding of this challenge. ;In Proceedings GCM 2025, arXiv:2601.03249
Although Audio Large Language Models (ALLMs) have witnessed substantial advancements, their long audio understanding capabilities remain unexplored. A plethora of benchmarks have been proposed for general audio tasks, they predominantly focus on short-form clips, leaving without a consensus on evaluating ALLMs over extended durations. This paper proposes ChronosAudio, the first multi-task benchmark tailored for long-audio understanding in ALLMs. It encompasses six major task categories and comprises 36,000 test instances totaling over 200 hours audio, stratified into short, middle, and long-form categories to comprehensively evaluate length generalization. Extensive experiments on 16 state-of-the-art models using ChronosAudio yield three critical findings: 1.Precipitous Long-Context Collapse: ALLMs exhibit a severe inability to sustain performance, with the transition from short to long contexts triggering a staggering performance degradation of over 90% in specific tasks. 2.Structural Attention Dilution: Performance degradation stems from a fundamental failure in maintaining temporal locality; attention mechanisms suffer from significant diffusion in later sequences. 3.Restorative Ceiling of Mitigation: Current strategies only offer 50% recovery. These findings reveal significant challenges in long-audio, underscoring the urgent need for approaches to achieve robust, document-level audio reasoning.
The rapid evolution of text-to-image (T2I) models has enabled high-fidelity visual synthesis on a global scale. However, these advancements have introduced significant security risks, particularly regarding the generation of harmful content. Politically harmful content, such as fabricated depictions of public figures, poses severe threats when weaponized for fake news or propaganda. Despite its criticality, the robustness of current T2I safety filters against such politically motivated adversarial prompting remains underexplored. In response, we propose $PC^2$, the first black-box political jailbreaking framework for T2I models. It exploits a novel vulnerability where safety filters evaluate political sensitivity based on linguistic context. $PC^2$ operates through: (1) Identity-Preserving Descriptive Mapping to obfuscate sensitive keywords into neutral descriptions, and (2) Geopolitically Distal Translation to map these descriptions into fragmented, low-sensitivity languages. This strategy prevents filters from constructing toxic relationships between political entities within prompts, effectively bypassing detection. We construct a benchmark of 240 politically sensitive prompts involving 36 public figures. Evaluation on commercial T2I models, specifically the GPT series, shows that while all original prompts are blocked, $PC^2$ achieves attack success rates (ASRs) of up to 86% and outperforms state-of-the-art frameworks by a large margin. We further propose a ready-to-deploy multi-layered filtering mitigation against $PC^2$-style attacks, reducing ASR to approximately 10%. ;To appear in the 33rd ACM Conference on Computer and Communications Security (CCS 2026)
As contemporary microservice systems become increasingly popular and complex-often comprising hundreds or even thousands of fine-grained, interdependent subsystems-they are experiencing more frequent failures. Ensuring system reliability thus demands accurate root cause localization. While many traditional graph-based and deep learning approaches have been explored for this task, they often rely heavily on pre-defined schemas that struggle to adapt to evolving operational contexts. Consequently, a number of LLM-based methods have recently been proposed. However, these methods still face two major limitations: shallow, symptom-centric reasoning that undermines accuracy, and a lack of cross-alert reuse that leads to redundant reasoning and high latency. In this paper, we conduct a comprehensive study of how Site Reliability Engineers (SREs) localize the root causes of failures, drawing insights from professionals across multiple organizations. Our investigation reveals that expert root cause analysis exhibits three key characteristics: recursiveness, multi-dimensional expansion, and cross-modal reasoning. Motivated by these findings, we introduce AMER-RCL, an agentic memory enhanced recursive reasoning framework for root cause localization in microservices. AMER-RCL employs the Recursive Reasoning RCL engine, a multi-agent framework that performs recursive reasoning on each alert to progressively refine candidate causes, while Agentic Memory incrementally accumulates and reuses reasoning from prior alerts within a time window to reduce redundant exploration and lower inference latency. Experimental results demonstrate that AMER-RCL consistently outperforms state-of-the-art methods in both localization accuracy and inference efficiency. ;accepted by ICSE-SEIP'26
Self-supervised pretraining in remote sensing is mostly done using mid-spatial resolution (MR) image datasets due to their high availability. Given the release of high-resolution (HR) datasets, we ask how HR datasets can be included in self-supervised pretraining to enhance MR image representation learning and downstream segmentation performance on MR tasks. We design a spatial affinity component that can be added to existing self-supervised learning frameworks and that uses HR imagery to learn better representations of MR imagery. We test the spatial affinity component on two self-supervised learning frameworks and show that it outperforms models pretrained on HR or MR images alone.
We present a cost-effective two-step authentication system that integrates face identification and speaker verification using only a camera and microphone available on common devices. The pipeline first performs face recognition to identify a candidate user from a small enrolled group, then performs voice recognition only against the matched identity to reduce computation and improve robustness. For face recognition, a pruned VGG-16 based classifier is trained on an augmented dataset of 924 images from five subjects, with faces localized by MTCNN; it achieves 95.1% accuracy. For voice recognition, a CNN speaker-verification model trained on LibriSpeech (train-other-360) attains 98.9% accuracy and 3.456% EER on test-clean. Source code and trained models are available at https://github.com/NCUE-EE-AIAL/Two-step-Authentication-Multi-biometric-System. ;Accepted manuscript (author version, v2). The published version appears in IET Conference Proceedings; see DOI: 10.1049/icp.2024.4141. Code: https://github.com/NCUE-EE-AIAL/Two-step-Authentication-Multi-biometric-System
The security of scripting languages such as PowerShell is critical given their powerful automation and administration capabilities, often exercised with elevated privileges. Today, securing these languages still demands substantial human effort to craft and enforce rules, imposing heavy burdens on typical administrators and creating critical production risks (e.g., misoperations that shut down servers).Large language models (LLMs) have demonstrated strong capabilities in code generation, vulnerability detection, and automated repair for languages like Python and JavaScript. However, their ability to assist with generating secure scripting-language code remains largely underexplored. In this paper, we present SecGenEval-PS, a benchmark designed to systematically evaluate LLMs on secure scripting generation, security analysis, and automated repair. Our results show that both proprietary and open-source models fall short in these areas. For instance, over 60% of PowerShell scripts produced by GPT-4o and o3-mini are insecure without structured guidance.To bridge this gap, we propose PSSec, a framework that combines data synthesis with fine-tuning to enhance model security capabilities. We develop a self-debugging agent that integrates static analyzers with the reasoning abilities of advanced LLMs to synthesize large-scale structured triplets of insecure scripts, violation analyses, and corresponding repairs. We then fine-tune lightweight LLMs (as small as 1.7B parameters) using supervised fine-tuning (SFT) and reinforcement learning (RL), enabling security-aware reasoning and the generation of secure PowerShell code.Across multiple LLM families, including GPT and Qwen, \textit{PSSec}-trained models match or surpass general-purpose large models on PowerShell security tasks while reducing inference cost by more than an order of magnitude. ;19 pages,8 figures,conference
Human Activity Recognition (HAR) is a central problem for context-aware applications, especially for smart homes and assisted living. A few very recent studies have shown that Large Language Models (LLMs) can be used for HAR at home, reaching high performance and addressing key challenges. In this paper, we provide new experimental results regarding the use of LLMs for HAR, on two state-of-the-art datasets. More specifically, we show how recognition performance evolves depending on the size of the LLM used. Moreover, we experiment on the use of knowledge distillation techniques to fine-tune smaller LLMs with HAR reasoning examples generated by larger LLMs. We show that such fine-tuned models can perform almost as well as the largest LLMs, while having 50 times less parameters.
This paper presents finite-time and fixed-time stabilization results for inhomogeneous abstract evolution problems, extending existing theories. We prove well-posedness for strong and weak solutions, and estimate upper bounds for settling times for both homogeneous and inhomogeneous systems. We generalize finite-dimensional results to infinite-dimensional systems and demonstrate partial state stabilization with actuation on a subset of the domain. The interest of these results are illustrated through an application of a heat equation with memory term. ;The paper has some problems in the proofs
As AI agents increasingly operate in multi-agent environments, understanding their collective behavior becomes critical for predicting the dynamics of artificial societies. This study examines conformity, the tendency to align with group opinions under social pressure, in large multimodal language models functioning as AI agents. By adapting classic visual experiments from social psychology, we investigate how AI agents respond to group influence as social actors. Our experiments reveal that AI agents exhibit a systematic conformity bias, aligned with Social Impact Theory, showing sensitivity to group size, unanimity, task difficulty, and source characteristics. Critically, AI agents achieving near-perfect performance in isolation become highly susceptible to manipulation through social influence. This vulnerability persists across model scales: while larger models show reduced conformity on simple tasks due to improved capabilities, they remain vulnerable when operating at their competence boundary. These findings reveal fundamental security vulnerabilities in AI agent decision-making that could enable malicious manipulation, misinformation campaigns, and bias propagation in multi-agent systems, highlighting the urgent need for safeguards in collective AI deployments.
In the literature, it has been shown that the secrecy capacity of the additive white Gaussian noise (AWGN) wiretap channel with noise-free feedback equals the capacity of the same model without secrecy constraint, and the classical Schalkwijk-Kailath (SK) scheme achieves the secrecy capacity. In this paper, we show that in finite blocklength regime, the SK scheme is not optimal, and propose a modified SK scheme which may perform better than the classical one. Besides this, this paper establishes a finite blocklength converse for the AWGN wiretap channel with feedback, which can also be viewed as a converse for the same model without secrecy constraint. To the best of the authors' knowledge, this is the first paper to address such a problem, and the results of this paper are further explained via numerical examples.
Using large language models (LLMs) to predict relevance judgments has shown promising results. Most studies treat this task as a distinct research line, e.g., focusing on prompt design for predicting relevance labels given a query and passage. However, predicting relevance judgments is essentially a form of relevance prediction, a problem extensively studied in tasks such as re-ranking. Despite this potential overlap, little research has explored reusing or adapting established re-ranking methods to predict relevance judgments, leading to potential resource waste and redundant development. To bridge this gap, we reproduce re-rankers in a re-ranker-as-relevance-judge setup. We design two adaptation strategies: (i) using binary tokens (e.g., "true" and "false") generated by a re-ranker as direct judgments, and (ii) converting continuous re-ranking scores into binary labels via thresholding. We perform extensive experiments on TREC-DL 2019 to 2023 with 8 re-rankers from 3 families, ranging from 220M to 32B, and analyse the evaluation bias exhibited by re-ranker-based judges. Results show that re-ranker-based relevance judges, under both strategies, can outperform UMBRELA, a state-of-the-art LLM-based relevance judge, in around 40% to 50% of the cases; they also exhibit strong self-preference towards their own and same-family re-rankers, as well as cross-family bias.
Maize disease classification plays a vital role in mitigating yield losses and ensuring food security. However, the deployment of traditional disease detection models in resource-constrained environments, such as those using smartphones and drones, faces challenges due to high computational costs. To address these challenges, we propose LWMSCNN-SE, a lightweight convolutional neural network (CNN) that integrates multi-scale feature extraction, depthwise separable convolutions, and squeeze-and-Excitation (SE) attention mechanisms. This novel combination enables the model to achieve 96.63% classification accuracy with only 241,348 parameters and 0.666 GFLOPs, making it suitable for real-time deployment in field applications. Our approach addresses the accuracy--efficiency trade-off by delivering high accuracy while maintaining low computational costs, demonstrating its potential for efficient maize disease diagnosis on edge devices in precision farming systems.
Understanding narratives requires identifying which events are most salient for a story's progression. We present a contrastive learning framework for modeling narrative salience that learns story embeddings from narrative twins: stories that share the same plot but differ in surface form. Our model is trained to distinguish a story from both its narrative twin and a distractor with similar surface features but different plot. Using the resulting embeddings, we evaluate four narratologically motivated operations for inferring salience (deletion, shifting, disruption, and summarization). Experiments on short narratives from the ROCStories corpus and longer Wikipedia plot summaries show that contrastively learned story embeddings outperform a masked-language-model baseline, and that summarization is the most reliable operation for identifying salient sentences. If narrative twins are not available, random dropout can be used to generate the twins from a single story. Effective distractors can be obtained either by prompting LLMs or, in long-form narratives, by using different parts of the same story. ;EACL 2026
The primary objective of a diverse planning approach is to generate a set of plans that are distinct from one another. Such an approach is applied in a variety of real-world domains, including risk management, automated stream data analysis, and malware detection. More recently, a novel diverse planning paradigm, referred to as behaviour planning, has been proposed. This approach extends earlier methods by explicitly incorporating a diversity model into the planning process and supporting multiple planning categories. In this paper, we demonstrate the usefulness of behaviour planning in real-world settings by presenting three case studies. The first case study focuses on storytelling, the second addresses urban planning, and the third examines game evaluation.
This paper investigates reachability analysis for max-plus linear systems (MPLS), an important class of dynamical systems that model synchronization and delay phenomena in timed discrete-event systems. We specifically focus on backward reachability analysis, i.e., determining the set of states that can reach a given target set within a certain number of steps. Computing backward reachable sets presents significant challenges due to the non-convexity of max-plus dynamics and the complexity of set complement operations. To address these challenges, we propose a novel approximation framework that efficiently computes backward reachable sets by exploiting the structure of tropical polyhedra. Our approach reformulates the problem as a sequence of symbolic operations and approximates non-convex target sets through closure operations on unions of tropical polyhedra. We develop a systematic algorithm that constructs both outer (M-form) and inner (V-form) representations of the resulting sets, incorporating extremal filtering to reduce computational complexity. The proposed method offers a scalable alternative to traditional DBM-based approaches, enabling reliable approximate backward reachability analysis for general target regions in MPLS.
To achieve fast recovery from link failures, most modern communication networks feature fully decentralized fast re-routing mechanisms. These re-routing mechanisms rely on pre-installed static re-routing rules at the nodes (the routers), which depend only on local failure information, namely on the failed links incident to the node. Ideally, a network is perfectly resilient: the re-routing rules ensure that packets are always successfully routed to their destinations as long as the source and the destination are still physically connected in the underlying network after the failures. Unfortunately, there are examples where achieving perfect resilience is not possible. Surprisingly, only very little is known about the algorithmic aspect of when and how perfect resilience can be achieved.
We investigate the computational complexity of analyzing such local fast re-routing mechanisms. Our main result is a negative one: we show that even checking whether a given set of static re-routing rules ensures perfect resilience is coNP-complete. We also show coNP-completeness of the so-called ideal resilience, a weaker notion of resilience often considered in the literature. Additionally, we investigate other fundamental variations of the problem. In particular, we show that our coNP-completeness proof also applies to scenarios where the re-routing rules have specific patterns (known as skipping in the literature).
On the positive side, for scenarios where nodes do not have information about the link from which a packet arrived (the so-called in-port), we present linear-time algorithms for both the verification and synthesis problem for perfect resilience.
Optimizing LLM-based agentic workflows is challenging for scaling AI capabilities. Current methods rely on coarse, end-to-end evaluation signals and lack fine-grained signals on where to refine, often resulting in inefficient or low-impact modifications. To address these limitations, we propose JudgeFlow, an Evaluation-Judge-Optimization-Update pipeline. We incorporate reusable, configurable logic blocks into agentic workflows to capture fundamental forms of logic. On top of this abstraction, we design a dedicated Judge module that inspects execution traces particularly failed runs and assigns rank-based responsibility scores to problematic blocks. These fine-grained diagnostic signals are then leveraged by an LLM-based optimizer, which focuses modifications on the most problematic block in the workflow. Our approach improves sample efficiency, enhances interpretability through block-level diagnostics, and provides a scalable foundation for automating increasingly complex agentic workflows. We evaluate JudgeFlow on mathematical reasoning and code generation benchmarks, where JudgeFlow achieves superior performance and efficiency compared to existing methods.
For any positive integer $g \ge 2$, we derive general condition for the existence of a $2g$-cycle in the Tanner graph of two-dimensional ($2$-D) classical quasi-cyclic (QC) low-density parity-check (LDPC) codes. Depending on whether $p$ is an odd prime or a composite number, we construct two distinct families of $2$-D classical QC-LDPC codes with girth $>4$ by stacking $p \times p \times p$ tensors. Furthermore, using generalized Behrend sequences, we propose an additional family of $2$-D classical QC-LDPC codes with girth $>6$, constructed via a similar tensor-stacking approach. All the proposed $2\text{-D}$ classical QC-LDPC codes exhibit an erasure correction capability of at least $p \times p$. Based on the constructed $2\text{-D}$ classical QC-LDPC codes, we derive two families of $2\text{-D}$ entanglement-assisted (EA) quantum low-density parity-check (QLDPC) codes. The first family of $2\text{-D}$ EA-QLDPC codes is obtained from a pair of $2\text{-D}$ classical QC-LDPC codes and is designed such that the unassisted part of the Tanner graph of the resulting EA-QLDPC code is free of $4$-cycles, while requiring only a single ebit to be shared across the quantum transceiver. The second family is constructed from a single $2\text{-D}$ classical QC-LDPC code whose Tanner graph is free from $4$-cycles. Moreover, the constructed EA-QLDPC codes inherit an erasure correction capability of $p \times p$, as the underlying classical codes possess the same erasure correction property. ;10 pages, 4 figures
Cross-modal localization using text and point clouds enables robots to localize themselves via natural language descriptions, with applications in autonomous navigation and interaction between humans and robots. In this task, objects often recur across text and point clouds, making spatial relationships the most discriminative cues for localization. Given this characteristic, we present SpatiaLoc, a framework utilizing a coarse-to-fine strategy that emphasizes spatial relationships at both the instance and global levels. In the coarse stage, we introduce a Bezier Enhanced Object Spatial Encoder (BEOSE) that models spatial relationships at the instance level using quadratic Bezier curves. Additionally, a Frequency Aware Encoder (FAE) generates spatial representations in the frequency domain at the global level. In the fine stage, an Uncertainty Aware Gaussian Fine Localizer (UGFL) regresses 2D positions by modeling predictions as Gaussian distributions with a loss function aware of uncertainty. Extensive experiments on KITTI360Pose demonstrate that SpatiaLoc significantly outperforms existing state-of-the-art (SOTA) methods.
Diffusion models have emerged as a powerful class of generative models for molecular design, capable of capturing complex structural distributions and achieving high fidelity in 3D molecule generation. However, their widespread use remains constrained by long sampling trajectories, stochastic variance in the reverse process, and limited structural awareness in denoising dynamics. The Directly Denoising Diffusion Model (DDDM) mitigates these inefficiencies by replacing stochastic reverse MCMC updates with deterministic denoising step, substantially reducing inference time. Yet, the theoretical underpinnings of such deterministic updates have remained opaque. In this work, we provide a principled reinterpretation of DDDM through the lens of the Reverse Transition Kernel (RTK) framework by Huang et al. 2024, unifying deterministic and stochastic diffusion under a shared probabilistic formalism. By expressing the DDDM reverse process as an approximate kernel operator, we show that the direct denoising process implicitly optimizes a structured transport map between noisy and clean samples. This perspective elucidates why deterministic denoising achieves efficient inference. Beyond theoretical clarity, this reframing resolves several long-standing bottlenecks in molecular diffusion. The RTK view ensures numerical stability by enforcing well-conditioned reverse kernels, improves sample consistency by eliminating stochastic variance, and enables scalable and symmetry-preserving denoisers that respect SE(3) equivariance. Empirically, we demonstrate that RTK-guided deterministic denoising achieves faster convergence and higher structural fidelity than stochastic diffusion models, while preserving chemical validity across GEOM-DRUGS dataset. Code, models, and datasets are publicly available in our project repository.
Recent advancements in lightweight neural networks have significantly improved the efficiency of deploying deep learning models on edge hardware. However, most existing architectures still trade accuracy for latency, which limits their applicability on microcontroller and neural processing unit based devices. In this work, we introduce two new model families, STResNet for image classification and STYOLO for object detection, jointly optimized for accuracy, efficiency, and memory footprint on resource constrained platforms. The proposed STResNet series, ranging from Nano to Tiny variants, achieves competitive ImageNet 1K accuracy within a four million parameter budget. Specifically, STResNetMilli attains 70.0 percent Top 1 accuracy with only three million parameters, outperforming MobileNetV1 and ShuffleNetV2 at comparable computational complexity. For object detection, STYOLOMicro and STYOLOMilli achieve 30.5 percent and 33.6 percent mean average precision, respectively, on the MS COCO dataset, surpassing YOLOv5n and YOLOX Nano in both accuracy and efficiency. Furthermore, when STResNetMilli is used as a backbone with the Ultralytics training environment. ;9 pages, 1 figure
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.
Since the outbreak in Wuhan (China) at the end of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused instability at various levels of society. While most patients completely recover from their SARS-CoV-2 infection, 10–20% of infected persons and up to 60% of infected patients with cancer develop long COVID. Long COVID is defined as the continuation of symptoms, which cannot be explained by alternative causes, that last longer than four weeks after initial infection. Even though it is generally accepted that patients with cancer are at increased risk of developing severe COVID-19, it is still unclear how long COVID manifests and whether long COVID impacts quality of life in this cohort. Hence, this study observed that patients with cancer reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve. Introduction: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10–20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort. Methods: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection. Results: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes. Conclusion: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve.
Arid regions, the source of most airborne mineral dusts, comprise a third of the Earth’s land surface, where around two billion people are exposed daily to the fine particles raised by wind. Crossing political borders and traveling on air currents around the world, these particles affect the health of their local communities as well as distant populations—putting all at risk for cardiovascular and respiratory illnesses that are overlain with emerging health issues, including potential clinical misdiagnoses of tuberculosis, influenza, and SARS COVID that present similar initial symptoms. Risks of exposure are affected by local and regional weather characteristics and climatic conditions that are in a state of flux. Advances in science and technology promise to reduce the health problems, but windblown dusts and what travels with them can change the fundamental problem and appropriate response. This chapter uses examples of meningitis, asthma, and Valley fever to illustrate how risks may be lowered through an (environmental) dust-health early warning system. A half century of dedicated measurements of particulate air quality and of environmental science enhanced by Earth-orbiting satellites reveal the truth of airborne dust extent, and much of its variability in time and space. These truths have been essential in advancing numerical, dynamic models of the atmosphere which mimic and predict weather systems that loft and transport the airborne dusts that medical sciences and epidemiology prove harmful. The union of many scientific disciplines and services makes possible improved public health around the world.
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.
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.
Long COVID, previously known as Post-Acute Sequelae of SARS-CoV-2 (PASC), refers to prolonged symptoms or diagnosable conditions following COVID-19 infection. The neuropsychiatric profile of Long COVID patients remains ambiguous. This study aimed to assess neuropsychiatric symptoms in a retrospective cohort of Long COVID patients (N = 162) at a Rehabilitation Medicine clinic in South Texas. Clinical data from patient records were used to calculate a Symptom Score, and screening tools for stress/PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and quality of life (SWL) were employed to evaluate if Long COVID duration and severity could predict neuropsychiatric outcomes. The majority were female (71%) and Hispanics (53%) who presented for treatment of Long COVID symptoms during the study period, including fatigue (93%), coughing/shortness of breath (81%), fever (67%), anosmia (58%), ageusia (54%), and weight loss (56%). A minority of participants were hospitalized (N = 49) or required ventilator support (N = 5) during acute infection. There was a high burden of neuropsychiatric symptoms, including subjective cognitive impairment (79%), headache (74%), and insomnia (58%). Symptom Score (median = 9, IQR [8,11]) was significantly correlated with increased depression (PHQ-9; p < 0.05), anxiety (GAD-7; p < 0.05) and elevated stress/PTSD (PCL-5; p < 0.05) symptoms. Long COVID patients taking stimulants or mood stabilizers had higher GAD-7 (p < 0.031, p < 0.035) and PHQ-9 (p < 0.034, p < 0.009) scores but not PCL-5 scores. Importantly, duration of Long COVID symptomatology also did not predict PCL-5 scores. No patient factors (e.g., sex, age, BMI, ethnicity) mediated Symptom Score. Nonetheless, historically marginalized groups, such as women and Hispanics, have been disproportionately affected by COVID-19. This study is the first to utilize validated screening tools to determine the presence and severity of neuropsychiatric symptoms in Long COVID patients. These findings may guide clinical management and future research on Long COVID, especially in historically excluded populations. SCOPE STATEMENT: We enthusiastically submit our Original Research article, entitled “ Assessing Neuropsychiatric Symptoms in Long COVID: A Retrospective Cohort Study from a South Texas Long COVID Clinic ” for consideration for publication in the journal Frontiers in Neurology. We believe the scope of our article aligns well with the scope and aim of the journal’s Neurorehabilitation Section. Long COVID is a debilitating neurological disorder with prominent and enduring cognitive and psychological impact. This study sought to characterize Long COVID symptoms from a cohort of patients at a Rehabilitation Medicine/Long COVID clinic in Southwest Texas. We stratified symptoms using validated psychiatric evaluation tools (e.g., PCL-5, GAD-7, PHQ-9, SWL) to determine if and to what extent psychiatric comorbidity exacerbated Long COVID symptoms. Our findings suggest that a Long COVID patient’s depression, anxiety, and stress/post traumatic stress scores are highly correlated with other neurological symptoms. We advance the implementation of a Long COVID “Symptom Score”, as well as the use of validated screening instruments to identify psychiatric features of Long COVID with the goal of maximizing life satisfaction and function over the course of treatment.
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 People with long COVID report prolonged, multisystem involvement and significant disability. This study aimed to determine long COVID prevalence and factors associated with it among US adults using nationally representative data. Methods This cross-sectional analysis utilized data from 2022 Behavioral Risk Factor Surveillance System survey, a nationally representative telephone survey conducted among noninstitutionalized adults aged ≥ 18 years residing in the United States. Age-adjusted prevalence of long COVID was calculated using weighted survey analysis. Poisson regression was employed to assess adjusted prevalence ratios (aPRs) associated with long COVID across various demographic, socioeconomic and health-related characteristics. Results Among 390,233 participants, 120,178 reported COVID-19, with 25,582 experiencing long COVID. Age-adjusted prevalence of self-reported COVID-19 and long COVID were estimated at 34.1% (95% CI, 33.7–34.4%) and 7.2% (95% CI, 7.0–7.4%) as of 2022, respectively. Among adults reporting COVID-19, 20.9% (95% CI, 20.5–21.4%) had ever experienced long COVID. An inverted U-shaped association was observed between long COVID risk and age, with the highest prevalence (23.5%) in the 45–54 age group. Long COVID was more prevalent among women (aPR, 1.40 [95% CI, 1.34–1.47]), individuals without a spouse (aPR, 1.06 [95% CI, 1.00–1.13]), uninsured (aPR, 1.16 [95% CI, 1.06–1.27]), and those with a high school education (aPR, 1.17 [95% CI, 1.12–1.23]), cardiovascular disease (aPR, 1.17 [95% CI, 1.09–1.25]), depressive disorder (aPR, 1.41 [95% CI, 1.34–1.48]), chronic obstructive pulmonary disease (aPR, 1.33 [95% CI, 1.24–1.43]), asthma (aPR, 1.28 [95% CI, 1.21–1.35]), and kidney disease (aPR, 1.11 [95% CI, 1.01–1.21]). Long COVID was less prevalent among non-Hispanic Black (aPR, 0.87 [95% CI, 0.81–0.95]), students (aPR, 0.87 [95% CI, 0.76–0.99]) or retired individuals (aPR, 0.89 [95% CI, 0.82–0.98]), and those with household incomes ≥$100,000 (aPR, 0.85 [95% CI, 0.79–0.92]). Conclusions Long COVID affects 7.2% of US adults, with higher vulnerability among women, middle-aged individuals, White individuals, socioeconomically disadvantaged groups, and those with chronic conditions. These findings underscore the need for targeted public health strategies to address disparities in long COVID burden and support high-risk populations.
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.
PURPOSE: Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study’s objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae. DESIGN: Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed. RESULTS: Fourteen completed Immediate-CICT ( n =7) or TAU ( n =7); two withdrew from TAU before their second testing session. Completers were [ M (S D )]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance ( M =3.7 points, p<.001, d =2.6) and brain fog ( M =-4 points, p<.001, d =-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p =.048. CONCLUSIONS: CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group. IMPACT: Brain fog in adults with Long COVID is often associated with dysfunction in everyday activities and unemployment. Yet, there are no empirically supported treatments targeting cognition in this population. Findings from this small-scale, pilot randomized controlled trial (RCT) suggest that a novel intervention, i.e., Constraint-Induced Cognitive Therapy, is a feasible cognitive rehabilitation method in adults with Long COVID cognitive sequelae with promise of (a) improving performance of cognition-based tasks in daily life and (b) promoting return-to-work. Further studies with larger sample sizes are warranted. Speed of Processing Training (SOPT) has been shown to increase processing speed in older adults without neurological disorders but has not been applied to adults with brain fog due to Long COVID, in whom slowing of cognitive processing speed is common. The results of this pilot RCT suggest that SOPT, in conjunction with behavior change techniques, may increase cognitive processing speed in this brain-injured population.
The public confidence and trust in online healthcare information have been greatly dented following the COVID-19 pandemic, which triggered a significant rise in online health misinformation. Existing literature shows that different datasets have been created to aid with detecting false information associated with this COVID infodemic. However, most of these datasets contain mostly unimodal data, which comprise primarily textual cues, and not visual cues, like images, infographics, and other graphic data components. Prior works point to the fact that there are only a handful of multimodal datasets that support COVID misinformation identification, and they lack an organized, processed and analyzed repository of visual cues. The novel CoVCues dataset, which represents a varied set of image artifacts, addresses this gap and advocates for the use of visual cues towards detecting online health misinformation. As part of validating the contents and utility of our CoVCues dataset, we have conducted a preliminary user assessment study, where different participants have been surveyed through a set of questionnaires to determine how effectively these dataset images contribute to the user perceived information reliability. These survey responses helped provide early insights into how different stakeholder groups interpret visual cues in the context of online health information and communication. The findings from this novel user assessment study offer valuable feedback for refining our CoVCues dataset and for supporting our claim that visual cues are underutilized but useful in combating the COVID infodemic. To our knowledge, this user assessment research study, as described in this paper, is the first of its kind work, involving COVID visual cues, that demonstrates the important role that our CoVCues dataset can potentially play in aiding COVID infodemic related future research work. ;10 pages, To Be Published In Proceedings Of The 1st IEEE Workshop on Healthcare and Medical Device Security, Privacy, Resilience, and Trust (IEEE HMD-SPiRiT), Accepted & Presented At The 7th IEEE International Conference on Trust, Privacy & Security in Intelligent Systems, and Applications (IEEE TPS 2025) on Nov. 11, 2025 in Pittsburgh, PA, USA
Long COVID is a heterogeneous condition characterized by a wide range of symptoms that persist for 90 days or more following SARS-CoV-2 infection. Now more than five years out from the onset of the SARS-CoV-2 pandemic, the mechanisms driving Long COVID are just beginning to be elucidated. Adipose tissue has been proposed as a potential reservoir for viral persistence and tissue dysfunction contributing to symptomology seen in Long COVID. To test this hypothesis, we analyzed subcutaneous adipose tissue (SAT) from two cohorts: participants with subacute COVID-19 (28–89 days post-infection) compared to pre-pandemic controls, and participants with Long COVID compared to those with those classified as “indeterminate” based on the RECOVER-Adult Long COVID Research Index (12-47 months post-infection). We found no evidence of persistent SARS-CoV-2 RNA in adipose tissue in any participant. SAT from participants with subacute COVID-19 displayed significant transcriptional remodeling, including depleted immune activation pathways and upregulated Hox genes and integrin interactions, suggesting resident immune cell exhaustion and perturbations in tissue function. However, no consistent changes in gene expression were observed between Long COVID samples and samples from indeterminant participants. Thus, SAT may contribute to inflammatory dysregulation following COVID-19, but does not appear to play a clear role in Long COVID pathophysiology. Further research is needed to clarify the role of adipose tissue in COVID-19 recovery.
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.
Zang et al. use RECOVER EHR data to study Long COVID risk factors and apply mathematical modeling to predict the development of long COVID conditions. They find that severe acute SARS-CoV-2 infection, being underweight, and having baseline comorbidities are likely associated with increased risk of having Long COVID. Most people who develop COVID-19 make a full recovery, but some go on to develop post-acute sequelae of SARS-CoV-2 infection, commonly known as Long COVID. Up to now, we did not know why some people are affected by Long COVID whilst others are not. We conducted a study to identify risk factors for Long COVID and developed a mathematical modeling approach to predict those at risk. We find that Long COVID is associated with some factors such as experiencing severe acute COVID-19, being underweight, and having conditions including cancer or cirrhosis. Due to the wide variety of symptoms defined as Long COVID, it may be challenging to come up with a set of risk factors that can predict the whole spectrum of Long COVID. However, our approach could be used to predict a variety of Long COVID conditions. Background SARS-CoV-2-infected patients may develop new conditions in the period after the acute infection. These conditions, the post-acute sequelae of SARS-CoV-2 infection (PASC, or Long COVID), involve a diverse set of organ systems. Limited studies have investigated the predictability of Long COVID development and its associated risk factors. Methods In this retrospective cohort study, we used electronic healthcare records from two large-scale PCORnet clinical research networks, INSIGHT (~1.4 million patients from New York) and OneFlorida+ (~0.7 million patients from Florida), to identify factors associated with having Long COVID, and to develop machine learning-based models for predicting Long COVID development. Both SARS-CoV-2-infected and non-infected adults were analysed during the period of March 2020 to November 2021. Factors associated with Long COVID risk were identified by removing background associations and correcting for multiple tests. Results We observed complex association patterns between baseline factors and a variety of Long COVID conditions, and we highlight that severe acute SARS-CoV-2 infection, being underweight, and having baseline comorbidities (e.g., cancer and cirrhosis) are likely associated with increased risk of developing Long COVID. Several Long COVID conditions, e.g., dementia, malnutrition, chronic obstructive pulmonary disease, heart failure, PASC diagnosis U099, and acute kidney failure are well predicted (C-index > 0.8). Moderately predictable conditions include atelectasis, pulmonary embolism, diabetes, pulmonary fibrosis, and thromboembolic disease (C-index 0.7–0.8). Less predictable conditions include fatigue, anxiety, sleep disorders, and depression (C-index around 0.6). Conclusions This observational study suggests that association patterns between investigated factors and Long COVID are complex, and the predictability of different Long COVID conditions varies. However, machine learning-based predictive models can help in identifying patients who are at risk of developing a variety of Long COVID conditions.
Background The emergence of COVID-19 precipitated containment policies (e.g., lockdowns, school closures, etc.). These policies disrupted healthcare, potentially eroding gains for Sustainable Development Goals including for neonatal mortality. Our analysis aimed to evaluate indirect effects of COVID-19 containment policies on neonatal admissions and mortality in 67 neonatal units across Kenya, Malawi, Nigeria, and Tanzania between January 2019 and December 2021. Methods The Oxford Stringency Index was applied to quantify COVID-19 policy stringency over time for Kenya, Malawi, Nigeria, and Tanzania. Stringency increased markedly between March and April 2020 for these four countries (although less so in Tanzania), therefore defining the point of interruption. We used March as the primary interruption month, with April for sensitivity analysis. Additional sensitivity analysis excluded data for March and April 2020, modelled the index as a continuous exposure, and examined models for each country. To evaluate changes in neonatal admissions and mortality based on this interruption period, a mixed effects segmented regression was applied. The unit of analysis was the neonatal unit ( n = 67), with a total of 266,741 neonatal admissions (January 2019 to December 2021). Results Admission to neonatal units decreased by 15% overall from February to March 2020, with half of the 67 neonatal units showing a decline in admissions. Of the 34 neonatal units with a decline in admissions, 19 (28%) had a significant decrease of ≥ 20%. The month-to-month decrease in admissions was approximately 2% on average from March 2020 to December 2021. Despite the decline in admissions, we found no significant changes in overall inpatient neonatal mortality. The three sensitivity analyses provided consistent findings. Conclusion COVID-19 containment measures had an impact on neonatal admissions, but no significant change in overall inpatient neonatal mortality was detected. Additional qualitative research in these facilities has explored possible reasons. Strengthening healthcare systems to endure unexpected events, such as pandemics, is critical in continuing progress towards achieving Sustainable Development Goals, including reducing neonatal deaths to less than 12 per 1000 live births by 2030.
More than three years after the start of the COVID-19 pandemic, individuals are frequently reporting multiple COVID-19 infections. However, these reinfections remain poorly understood. Here, we investigate COVID-19 reinfections in a large electronic health record cohort of over 3 million patients. We use data summary techniques and statistical tests to characterize reinfections and their relationships with disease severity, biomarkers, and Long COVID. We find that individuals with severe initial infection are more likely to experience severe reinfection, that some protein levels are lower, leading to reinfection, and that a lower proportion of individuals are diagnosed with Long COVID following reinfection than initial infection. Our work highlights the prevalence and impact of reinfections and suggests the need for further research. Hadley et al. characterize COVID-19 re-infections utilizing electronic health record study cohort data of over 3 million patients. They find severe initial COVID-19 infection linked to severe reinfections and less frequent long COVID diagnosis after reinfection. Background Although the COVID-19 pandemic has persisted for over 3 years, reinfections with SARS-CoV-2 are not well understood. We aim to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection. Methods We use an electronic health record study cohort of over 3 million patients from the National COVID Cohort Collaborative as part of the NIH Researching COVID to Enhance Recovery Initiative. We calculate summary statistics, effect sizes, and Kaplan–Meier curves to better understand COVID-19 reinfections. Results Here we validate previous findings of reinfection incidence (6.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present findings that the proportion of Long COVID diagnoses is higher following initial infection than reinfection for infections in the same epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between initial infection and reinfection (chi-squared value: 25,697, p -value: <0.0001) with a medium effect size (Cramer’s V : 0.20, DoF = 3). Individuals who experienced severe initial and first reinfection were older in age and at a higher mortality risk than those who had mild initial infection and reinfection. Conclusions In a large patient cohort, we find that the severity of reinfection appears to be associated with the severity of initial infection and that Long COVID diagnoses appear to occur more often following initial infection than reinfection in the same epoch. Future research may build on these findings to better understand COVID-19 reinfections.
ABSTRACT IMPORTANCE: Over seven million U.S. adults experience "long COVID", or persistent health issues after COVID-19. Multiple guidelines recommend the inclusion of functional status in long COVID diagnostic criteria, but more evidence is needed to guide this recommendation. This study explores the adjusted odds of developing long COVID by pre-infection symptoms and functional status, and the feasibility of estimating functional status using health records data. DESIGN: Retrospective cohort study in a multicenter national longitudinal cohort of U.S. adults with history of COVID-19, using health records and survey responses through July 2022 (All of Us CDR 7.0). EXPOSURE(S): Pre-infection (-5 years) incidences of (a) at least one symptom common in long COVID, and (b) functional status, indicated by All of Us baseline survey responses and diagnostic/procedure/billing codes. Disease and demographic data covariates were included in the adjusted models. RESULTS: N = 65,464 met inclusion criteria (n=40,655 had post-infection occurrences of at least one symptom (long COVID group), while n=24,809 had none). Adjusted odds ratios within 99% confidence intervals [99% CI] of developing long COVID increased with lower pre-infection self-reported mental health ("Good" compared to "Excellent" AOR=1.14 [1.04,1.25], P>0.000), and more pre-infection symptoms (compared to the median of four, people with zero had much lower odds (AOR=0.15 [0.04,0.61], P=0.008). Adjusted odds were not significantly affected by any single pre-infection symptom, self-rated physical ability, or clinical documentation of functional impairment. CONCLUSIONS. Greater pre-illness symptom burden and lower self-rated mental health increased the odds of long COVID symptoms, after adjusting for demographics, variant, functional status, and individual symptoms. Long COVID represents a change from baseline functioning and health, even in people with pre-infection incident symptoms and functional impairments. This estimation of pre-infection functional status using harmonized electronic health records data demonstrated the feasibility of these data in developing the diagnostic utility of functional status changes in long COVID.
Nearly 7.5% U.S. adults have long COVID. Recent epidemiological studies indicated that long COVID, is significantly associated with subsequent brain structure changes. However, it remains unknown if long COVID is causally associated with brain structure change. Here we applied two Mendelian Randomization (MR) methods – Inverse Variance Weighting MR method (IVW) for correlated instrument variables and Component analysis-based Generalized Method of Moments (PC-GMM) – to examine the potential causal relationships from long COVID to brain structure changes. The MR study was based on an instrumental variable analysis of data from a recent long COVID genome-wide association study (GWAS) (3,018 cases and 994,582 controls), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) (Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). We found no significant causal relationship between long COVID and brain structure changes. As we gain more insights into long COVID and its long-term health outcomes, future works are necessary to validate our findings and understand the mechanisms underlying the observed associations, though not causal, of long COVID with subsequent brain structure changes.
Long COVID 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.
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)
The global pandemic due to emergence of COVID 19 has created the unrivaled
public health crisis. It has huge morbidity rate never comprehended in the
recent decades. Researchers have made many efforts to find the optimal solution
of this pandemic. Progressively, drug repurposing is an emergent and powerful
strategy with saving cost, time, and labor. Lacking of identified repurposed
drug candidates against COVID 19 demands more efforts to explore the potential
inhibitors for effective cure. In this study, we used the combination of
molecular docking and machine learning regression approaches to explore the
potential inhibitors for the treatment of COVID 19. We calculated the binding
affinities of these drugs to multitarget proteins using molecular docking
process. We perform the QSAR modeling by employing various machine learning
regression approaches to identify the potential inhibitors against COVID 19.
Our findings with best scores of R2 and RMSE demonstrated that our proposed
Decision Tree Regression (DTR) model is the most appropriate model to explore
the potential inhibitors. We proposed five novel promising inhibitors with
their respective Zinc IDs ZINC (3873365, 85432544, 8214470, 85536956, and
261494640) within the range of -19.7 kcal/mol to -12.6 kcal/mol. We further
analyzed the physiochemical and pharmacokinetic properties of these most potent
inhibitors to examine their behavior. The analysis of these properties is the
key factor to promote an effective cure for public health. Our work constructs
an efficient structure with which to probe the potential inhibitors against
COVID-19, creating the combination of molecular docking with machine learning
regression approaches.
;Comment: 22 pages
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
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.
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.
Viruses rely on host cellular machinery for replication. After entering the nucleus, the HIV genome accumulates in nuclear niches where it undergoes reverse transcription and integrates into neighboring chromatin, promoting high transcription rates and new virus progeny. Despite anti-retroviral treatment, viral genomes can persist in these nuclear niches and reactivate if treatment is interrupted, likely contributing to the formation of viral reservoirs. The post-nuclear entry dynamics of HIV remain unclear, and understanding these steps is critical for revealing how viral reservoirs are established. In this study, we elucidate the formation of HIV-induced CPSF6 puncta and the domains of CPSF6 essential for this process. We also explore the roles of nuclear speckle scaffold factors, SON and SRRM2, in the biogenesis of these puncta. Through genetic manipulation and depletion experiments, we demonstrate the key role of the intrinsically disordered region of SRRM2 in enlarging nuclear speckles in the presence of the HIV capsid. We identify the FG domain of CPSF6 as essential for both puncta formation and binding to the viral core, which serves as the scaffold for CPSF6 puncta. While the low-complexity regions (LCRs) modulate CPSF6 binding to the viral capsid, they do not contribute to puncta formation, nor do the disordered mixed charge domains (MCDs) of CPSF6. These results demonstrate how HIV evolved to hijack host nuclear factors, enabling its persistence in the host. Of note, this study provides new insights into the underlying interactions between host factors and viral components, advancing our understanding of HIV nuclear dynamics and offering potential therapeutic targets for preventing viral persistence. HIGHLIGHTS: The formation of HIV-induced CPSF6 puncta is critical for restoring HIV-1 nuclear reverse transcription (RT). CPSF6 protein lacking the FG peptide cannot bind to the viral core, thereby failing to form HIV-induced CPSF6 puncta. The FG peptide, rather than low-complexity regions (LCRs) or the mixed charge domains (MCDs) of the CPSF6 protein, drives the formation of HIV-induced CPSF6 puncta. HIV-induced CPSF6 puncta form individually and later fuse with nuclear speckles (NS) via the intrinsically disordered region (IDR) of SRRM2.
Background Chlamydia genital infections continue to be a serious health concern globally. Previous studies have reported that Chlamydia trachomatis infection alters the vaginal microbiota of infected women. This study investigated differences in the vaginal microbiome of South African pregnant women living with HIV with and without C. trachomatis infection. Methods This was a cross-sectional study among 385 pregnant women, recruited from the King Edward VIII Hospital in Durban, South Africa. C. trachomatis was detected using the Applied Biosystems™ TaqMan^® Assays. A total of 40 samples, 20 C. trachomatis positive and 20 C. trachomatis negative, were selected for sequencing. The sequencing of the vaginal microbiome was performed using the PacBio platform. Statistical analysis was performed on IBM SPSS version 26. Results The prevalence of C. trachomatis infection was 12.2% (47/385). The genus Gardnerella (32.14% vs. 24.02%) and species in the genus Gardnerella (31.97% vs. 24.03%) were more abundant in the C. trachomatis -infected group compared to the uninfected group. Lactobacillus iners were also more abundant in the C. trachomatis -infected women (28.30%) compared to the uninfected women. However, these observed patterns did not reach statistical significance. Discriminant analysis showed that the class Alpha-Proteobacteria ; order Bacillales ; family Enterococcaceae ; the genera Enhydrobacter , Enterococcus , and Parabacteroides ; Enterococcus spp.; and Pseudomonas stutzeri significantly contributed to a model separating C. trachomatis -infected women from the uninfected group ( p < 0.05). Conclusion The organisms and taxa that significantly contributed to separating the vaginal microbiota of C. trachomatis -infected women from the uninfected women in this study cohort have not been previously observed in association with C. trachomatis infection or the vaginal microbiota. Future studies in larger cohorts that will investigate the role of these microorganisms in C. trachomatis infection and the vaginal microbiota are required.
Cocaine use disorder (CUD) is highly comorbid with HIV infection and worsens HIV outcomes. Preclinical research on the outcomes of HIV infection may yield crucial information on neurobehavioral changes resulting from chronic drug exposure in people living with HIV (PLWH). Repeated exposure to cocaine alters behavioral responses to cocaine. This includes development of cocaine locomotor sensitization – or increased locomotor responses to the same doses of cocaine - which depends on nucleus accumbens (NAc) neural plasticity. NAc astrocytes are key regulators of neural activity and plasticity, and their function can be impaired by cocaine exposure and HIV infection, thus implicating them as potential regulators of HIV-induced changes in behavioral response to cocaine. To characterize the effects of HIV infection on cocaine locomotor sensitization, we employed the EcoHIV mouse model to assess changes in locomotor responses after repeated cocaine (10mg/kg) exposure and challenge. EcoHIV infection potentiated expression of cocaine sensitization. We also identified EcoHIV-induced increases in expression of the astrocytic nuclear marker Sox9 selectively in the NAc core. To investigate whether modulation of NAc astrocytes could reverse EcoHIV-induced deficits, we employed a chemogenetic approach. We found that chemogenetic activation of NAc astrocyte Gq signaling attenuated EcoHIV-enhanced cocaine sensitization. We propose that HIV infection contributes to cocaine behavioral sensitization and induces adaptations in NAc astrocytes, while promoting NAc astrocytic Gq-signaling can recover EcoHIV-induced behavioral changes. These findings identify potential cellular substrates of disordered cocaine-driven behavior in the context of HIV infection and point toward strategies to reduce cocaine-related behavior in PLWH.
This paper develops and analyzes a reaction-diffusion epidemic model to study the transmission dynamics of Human Immunodeficiency Virus (HIV). The model incorporates interactions among five distinct demographic groups to better capture the heterogeneity of disease spread. The primary objective is to investigate how spatial diffusion and treatment affect the long-term behavior of HIV transmission. Using the next-generation matrix approach, we derive the basic reproduction number $$\mathcal{R}_0$$ and examine the stability of both the disease-free and endemic equilibria. Existence of traveling wave solutions is analyzed within the framework of monotone dynamical systems. Numerical simulations are carried out using the Crank-Nicolson operator splitting method in both diffusive and non-diffusive settings. The results illustrate that diffusion plays a significant role in shaping spatial transmission patterns, and that effective treatment strategies can reduce $$\mathcal{R}_0$$ below unity, leading to eradication. These findings validate the theoretical analysis and highlight the importance of incorporating spatial effects when designing HIV control strategies.
Precise and scalable quantification of the genetically intact HIV reservoir is critical for advancing curative strategies. However, current HIV reservoir assays such as the intact proviral DNA assay (IPDA) are limited by quantification failures or misclassification of defective proviral genomes due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR assay that simultaneously targets four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. We benchmarked Q4ddPCR against 3,650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR using the same primer/probe sets. Q4ddPCR enabled intact reservoir quantification in 95% of samples from three independent cohorts and closely matched sequence-confirmed Q4PCR reservoir measurements. In addition, multi-probe readouts revealed clonal intact reservoir dynamics that are not detectable by IPDA. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reported lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays provide greater specificity and more accurately capture the dynamics of the intact HIV reservoir.
BACKGROUND: Differentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth. SETTING: Population-based household survey in east Zimbabwe. METHODS: HIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories. RESULTS: In total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months. CONCLUSION: The refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.
HIV is a lentivirus characterized by the formation of its mature core. Visualization and structural examination of HIV requires purification of virions to high concentrations. The yield and integrity of these virions are crucial for ensuring a uniform representation of all viral particles in subsequent analyses. In this study, we present a method for purification of HIV virions which minimizes forces applied to virions while maximizing the efficiency of collection. This method allows us to capture between 1,000 and 5,000 HIV virions released from individual HEK293 cells after transfection with the NL4.3 HIV backbone, a 10 fold advantage over other methods. We utilized this approach to investigate HIV core formation from several constructs: pNL4-3(RT:D (185) A&D (186) A) with an inactive reverse transcriptase, NL4.3(IN: V (165) A&R (166) A) with a type-II integrase mutation, and NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) featuring an edited Ѱ packaging signal. Notably, virions from NL4.3(Ѱ: Δ(105-278)&Δ(301-332)) displayed a mixed population, comprising immature virions, empty cores, and cores with detectable internal density. Conversely, virions derived from NL4.3(IN: V (165) A&R (166) A) exhibited a type II integrase mutant phenotype characterized by empty cores and RNP density localized around the cores, consistent with previous studies. In contrast, virions released from pNL4-3(RT:D (185) A&D (186) A) displayed mature cores containing detectable RNP density. We suggest that the purification methods developed in this study can significantly facilitate the characterization of enveloped viruses.
Background Antibiotics are globally overprescribed for the treatment of upper respiratory tract infections (URTI), especially in persons living with HIV. However, most URTIs are caused by viruses, and antibiotics are not indicated. De-implementation is perceived as an important area of research that can lead to reductions in unnecessary, wasteful, or harmful practices, such as excessive or inappropriate antibiotic use for URTI, through the employment of evidence-based interventions to reduce these practices. Research into strategies that lead to successful de-implementation of unnecessary antibiotic prescriptions within the primary health care setting is limited in Mozambique. In this study, we propose a protocol designed to evaluate the use of a clinical decision support algorithm (CDSA) for promoting the de-implementation of unnecessary antibiotic prescriptions for URTI among ambulatory HIV-infected adult patients in primary healthcare settings. Methods This study is a multicenter, two-arm, cluster randomized controlled trial, involving six primary health care facilities in Maputo and Matola municipalities in Mozambique, guided by an innovative implementation science framework, the Dynamic Adaption Process. In total, 380 HIV-infected patients with URTI symptoms will be enrolled, with 190 patients assigned to both the intervention and control arms. For intervention sites, the CDSAs will be posted on either the exam room wall or on the clinician´s exam room desk for ease of reference during clinical visits. Our sample size is powered to detect a reduction in antibiotic use by 15%. We will evaluate the effectiveness and implementation outcomes and examine the effect of multi-level (sites and patients) factors in promoting the de-implementation of unnecessary antibiotic prescriptions. The effectiveness and implementation of our antibiotic de-implementation strategy are the primary outcomes, whereas the clinical endpoints are the secondary outcomes. Discussion This research will provide evidence on the effectiveness of the use of the CDSA in promoting the de-implementation of unnecessary antibiotic prescribing in treating acute URTI, among ambulatory HIV-infected patients. Findings will bring evidence for the need to scale up strategies for the de-implementation of unnecessary antibiotic prescription practices in additional healthcare sites within the country. Trial registration ISRCTN, ISRCTN88272350. Registered 16 May 2024, https://www.isrctn.com/ISRCTN88272350
Background Mycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS). Case presentation A 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests. Conclusion MAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates Mtb infection outcomes in people living with HIV (PLWH). Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. Here, we investigated the immune responses elicited by BCG administered via intravenous (IV) or intradermal (ID) routes in Simian Immunodeficiency Virus (SIV)-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of Mtb challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic molecules, and key transcription factors. Our results showed that IV BCG induces a robust and sustained immune response, including tissue-resident memory T (T(RM)) cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of IV BCG-vaccinated MCM. Although IV BCG vaccination resulted in an influx of T(RM) cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>10(5) copies/mL) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on IV BCG-induced protection against Mtb.
Purpose of Review This review assessed the impact of climate change on HIV transmission and HIV care of children and adults in Eswatini, and what adaptation strategies can mitigate these impacts. Recent Findings The HIV crisis in Eswatini persists alongside the climate emergency, increasing poor health outcomes in individuals living with HIV. Although there is no clinical evidence of a direct influence of climate change on the biological effect of HIV, changing weather patterns have an effect on the livelihoods and sustenance of children, adults, and caregivers, which may consequently increase the likelihood of HIV transmission and disrupt HIV care. Summary Drought conditions—expected to increase with climate change—coupled with existing food insecurity and poverty are the main pathways linking HIV and climate change in Eswatini. Other climate-driven concerns for HIV treatment and care in Eswatini include heat waves, wildfires, floods, and storms.
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.
HIV is a retrovirus that attacks the human immune system and can lead to death without proper treatment. In collaboration with the WHO and the University of Witwatersrand, we study how to improve the efficiency of HIV testing with the goal of eventual deployment, directly supporting progress toward UN Sustainable Development Goal 3.3. While prior work has demonstrated the promise of intelligent algorithms for sequential, network-based HIV testing, existing approaches rely on assumptions that are impractical in our real-world implementations. Here, we study sequential testing on incrementally revealed disease networks and introduce Policy-Embedded Graph Expansion (PEGE), a novel framework that directly embeds a generative distribution over graph expansions into the decision-making policy rather than attempting explicit topological reconstruction. We further propose Dynamics-Driven Branching (DDB), a diffusion-based graph expansion model that supports decision making in PEGE and is designed for data-limited settings where forest structures arise naturally, as in our real-world referral process. Experiments on real HIV transmission networks show that the combined approach (PEGE + DDB) consistently outperforms baselines (e.g., 17.3% improvement in discounted reward and 15.4% more HIV detections with 25% of the population tested) and explore key tradeoffs that drive solution quality.
INTRODUCTION: Adolescents living with HIV are at an increased risk of experiencing mental health challenges, which may impact their overall well-being and adherence to treatment. Evidence-based interventions are crucial to addressing these issues; however, the effectiveness of these interventions remains unclear. This scoping review aimed to synthesize all interventions that tested either the prevention or improvement of mental health for adolescents living with HIV. METHODS: We used PubMed, PsycINFO, CINAHL, Embase, and Cochrane to identify RCTs evaluating mental health interventions for HIV-infected adolescents. RESULTS: A scoping review included 13 out of 1015 studies demonstrating the global relevance of addressing mental health in this population. Interventions were diverse and showed mixed effectiveness in improving mental health outcomes such as depression, anxiety, trauma, and behavioural symptoms. Factors contributing to mixed results included variations in intervention design, study characteristics, and contextual factors. Identified gaps in the literature encompassed the limited number of studies in some regions and the lack of research on specific subpopulations and long-term intervention effectiveness. CONCLUSION: A mixed result needs to be confirmed in future RCTs. This review provides valuable insights into improving the mental health of HIV-infected adolescents and can guide further research and practice in this area.
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
INTRODUCTION: Screening, Brief Interventions and Referral to Treatment (SBIRT) programs reduce unhealthy alcohol use among adolescents. However, self-report screening alone may lead to false negatives and low service use, especially in HIV care settings. This study explored the contextual implementation factors and strategies of an alcohol biomarker-augmented SBIRT program for HIV-affected adolescents in Zambia, where alcohol use and HIV prevalence are high. METHODS: We conducted key informant interviews (n=7) with mental health providers and policymakers and focus groups (n=16 groups; 10-11 participants each) with healthcare providers, adolescents, and caregivers, guided by a case vignette of the biomarker-augmented SBIRT program. Thematic analysis followed the implementation frameworks Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) and Practical, Robust Implementation and Sustainability Model (PRISM). RESULTS: Participants perceived the SBIRT program as appropriate for adolescent alcohol use. Key contextual factors included: lack of alcohol treatment programs, community stigma against HIV and alcohol use, and robust implementation infrastructure through HIV healthcare. Strategies to enhance acceptability included making alcohol screening universal to avoid labeling adolescents, privacy and confidentiality during biomarker sampling, and peer-led age-matched counseling at screening. To enhance reach, participants suggested designing the program with attention to gender-specific needs and integrating it into HIV healthcare and alcohol use hotspots (e.g. schools). CONCLUSIONS: Implementation strategies should be designed to reduce stigma, build trust, engage adolescents across genders, and reach youth through clinical and community channels. Future research should define how to select, train, and evaluate peer counselors and assess the effectiveness of alcohol biomarkers within SBIRT programs in motivating behavior change.
Background Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa. Methods We conducted a modelling study to simulate hypertension and CVD across 3000 scenarios representing a range of settings across eastern, southern, central, and western Africa. We evaluated two policies compared to current hypertension treatment: 1) expansion of HIV primary care clinics into chronic care clinics that provide hypertension treatment for all persons regardless of HIV status (chronic care clinic or CCC policy), and 2) CCC plus population-level hypertension screening of adults ≥40 years by community health workers (CHW policy). For our primary analysis, we used a cost-effectiveness threshold of US $500 per disability-adjusted life-year (DALY) averted, a 3% annual discount rate, and a 50-year time horizon. A strategy was considered cost-effective if it led to the lowest net DALYs, which is a measure of DALY burden that takes account of the DALY implications of the cost for a given cost-effectiveness threshold. Findings Among adults 45-64 years, CCC implementation would improve population-level hypertension control (the proportion of people with hypertension whose blood pressure is controlled) from mean 4% (90% range 1-7%) to 14% (6-26%); additional CHW screening would improve control to 44% (35-54%). Among all adults, CCC implementation would reduce ischemic heart disease (IHD) incidence by 10% (3-17%), strokes by 13% (5-23%), and CVD mortality by 9% (3-15%). CCC plus CHW screening would reduce IHD by 28% (19-36%), strokes by 36% (25-47%), and CVD mortality by 25% (17-34%). CHW screening was cost-effective in 62% of scenarios, CCC in 31%, and neither policy was cost-effective in 7% of scenarios. Pooling across setting-scenarios, incremental cost-effectiveness ratios were $69/DALY averted for CCC and $389/DALY averted adding CHW screening to CCC. Interpretation Leveraging existing healthcare infrastructure to implement population-level hypertension screening by CHWs and hypertension treatment through integrated chronic care clinics is expected to reduce CVD morbidity and mortality and is likely to be cost-effective in most settings across Africa.
INTRODUCTION: Key populations, including female sex workers (FSW), people who inject drugs (PWID), and people in serodiscordant partnerships, experience higher HIV incidence compared to the general population. Maternal HIV retesting, particularly during late pregnancy, helps detect new infections and prevent vertical HIV transmission, but optimal testing schedules among key populations are unknown. METHODS: We used a Markov model to estimate the health and economic impacts of maternal HIV retesting on vertical HIV transmission outcomes among FSW and PWID in Kenya, South Africa, and pre-war Ukraine as well as among pregnant people in serodiscordant partnerships in Kenya and South Africa. We calculated incremental cost-effectiveness ratios (ICERs) for seven maternal retesting scenarios that included HIV testing during early antenatal care (ANC) and retesting from late ANC through nine months postpartum. RESULTS: Retesting during late ANC was estimated to avert 16% (Kenya), 14% (South Africa), and 8% (Ukraine) of infant HIV infections among key populations. Retesting during late ANC was cost-saving or cost-effective among all populations included in our model in South Africa and Kenya. In Ukraine, HIV retesting during late ANC was cost-saving for PWID but not cost-effective for FSW. Postpartum retesting was not cost-effective in any population. CONCLUSIONS: Maternal HIV retesting during late ANC is cost-saving or cost-effective for vertical HIV transmission outcomes for pregnant key populations and serodiscordant couples in Kenya and South Africa and is cost-saving for PWID in Ukraine. FUNDING: USAID, Bill and Melinda Gates Foundation, and National Institutes of Health
Background Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies. Methods The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes. InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial. Discussion If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region. Trial registration ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1 .
Human Immunodeficiency Virus (HIV) stigma constitutes a major barrier to HIV prevention, testing, and treatment, and is associated with harmful consequences for people living with HIV such as discrimination, rejection from family and friends, and treatment nonadherence. This study aimed to understand the drivers, perpetuators, and outcomes of HIV-related stigma among young people living with HIV (YPLWH) in Lima, Peru. From November 2022 to June 2023, we conducted interviews and focus groups with a diverse group of 75 YPWLH, in addition to healthcare providers and HIV advocates, to discuss their experiences of HIV-related stigma. Audio recordings were transcribed verbatim and analyzed for emergent themes using framework analysis. Participants identified the drivers of HIV-related stigma as a lack of information about HIV and misinformation about HIV, and the key power groups who perpetuate this stigma, which included parents and older generations, educators, and healthcare providers. Participants reported outcomes of HIV-related stigma; these included feelings of fear, shame, and loneliness, and enacted behaviors such as treatment nonadherence, nondisclosure of HIV diagnosis, and social avoidance. Participants also reported health outcomes of sickness, death, and HIV transmission, and social outcomes including discrimination from employers, educators, and peers, and loss of social support. These findings are critical to understanding how HIV-related stigma manifests in the cultural context of Lima, Peru, and can be used to inform effective interventions to reduce and mitigate the impacts of HIV-related stigma.
Background In the US, 1.2 million people live with HIV (PWH). Despite having near-normal life expectancies due to antiretroviral therapy (ART), many PWH seek an HIV cure, even if it means risking their lives. This willingness to take risks for a cure raises questions about “affective forecasting biases,” where people tend to overestimate the positive impact of future events on their well-being. We conducted a study to test two interventions to mitigate affective forecasting in the decisions of PWH about taking HIV cure medication. Methods We recruited PWH to complete a 30-minute survey about their current quality of life (QoL) and the QoL they anticipate after being cured of HIV, and assigned them to either no additional intervention, to one of two interventions intended to reduce affective forecasting bias, or to both interventions: (1) a defocusing intervention designed to broaden the number of life domains people consider when imagining life changes associated with new circumstances (e.g. HIV cure); and (2) an adaptation intervention to help them gauge fading of strong emotions over time. The study design included a 2 × 2 design: defocusing (yes/no) x adaptation (yes/no) intervention. We assessed PWH’s willingness to take hypothetical HIV sterilizing cure medication using the Time Trade-Off (TTO) and their quality of life predictions with WHOQOL-HIV. Results 296 PWH participated. Counter to what we had hypothesized, neither intervention significantly reduced PWH’s willingness to trade time for a cure. Instead, the defocusing intervention increased their willingness to trade time (IRR 1.77, p = 0.03). Exploratory analysis revealed that PWH with lower current quality of life who received the defocusing intervention were more willing to trade time for a cure. Conclusion These negative findings suggest that either these biases are difficult to overcome in the settings of HIV curative medication or other factors beyond affective forecasting biases influence willingness to participate in HIV curative studies, such as respondents’ current quality of life.
Background Sexual and gender minorities (SGMs) are at higher risk of HIV incidence compared to their heterosexual cisgender counterparts. Despite the high HIV disease burden among SGMs, there was limited data on whether they are at higher risk of virologic failure, which may lead to potential disease progression and increased transmission risk. The All of Us (AoU) Research Program, a national community-engaged program aiming to improve health and facilitate health equity in the United States by partnering with one million participants, provides a promising resource for identifying a diverse and large volunteer TGD cohort. Leveraging various data sources available through AoU, the current study aims to explore the association between sexual orientation and gender identity (SOGI) and longitudinal virologic failure among adult people with HIV (PWH) in the US. Methods This retrospective cohort study used integrated electronic health records (EHR) and self-reported survey data from the All of Us (AoU) controlled tier data, version 7, which includes participants enrolled in the AoU research program from May 31, 2017, to July 1, 2022. Based on participants’ sexual orientation, gender identity, and sex assigned at birth, their SOGI were categorized into six groups, including cisgender heterosexual women, cisgender heterosexual men, cisgender sexual minority women, cisgender sexual minority men, gender minority people assigned female at birth of any sexual orientation, and gender minority people assigned male at birth of any sexual orientation. Yearly virologic failure was defined yearly after one’s first viral load testing, and individuals with at least one viral load test > 50 copies/mL during a year were defined as having virologic failure at that year. Generalized linear mixed-effects models were used to explore the association between SOGI and longitudinal virologic failure while adjusting for potential confounders, including age, race, ethnicity, education attainment, income, and insurance type. Results A total of 1,546 eligible PWH were extracted from the AoU database, among whom 1,196 (77.36%) had at least one viral failure and 773 (50.00%) belonged to SGMs. Compared to cisgender heterosexual women, cisgender sexual minority women (adjusted Odds Ratio [aOR] = 1.85, 95% CI: 1.05–3.27) were at higher risk of HIV virologic failure. Additionally, PWH who were Black vs. White (aOR = 2.15, 95% CI: 1.52–3.04) and whose insurance type was Medicaid vs. Private insurance (aOR = 2.07, 95% CI: 1.33–3.21) were more likely to experience virologic failure. Conclusions Maintaining frequent viral load monitoring among sexual minority women with HIV is warranted because it allows early detection of virologic failure, which could provide opportunities for interventions to strengthen treatment adherence and prevent HIV transmission. To understand the specific needs of subgroups of SGMs, future research needs to examine the mechanisms for SOGI-based disparities in virologic failure and the combined effects of multi-level psychosocial and health behavior characteristics.
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.
Large language models (LLMs) are emerging as valuable tools to support clinicians in routine decision-making. HIV management is a compelling use case due to its complexity, including diverse treatment options, comorbidities, and adherence challenges. However, integrating LLMs into clinical practice raises concerns about accuracy, potential harm, and clinician acceptance. Despite their promise, AI applications in HIV care remain underexplored, and LLM benchmarking studies are scarce. This study evaluates the current capabilities of LLMs in HIV management, highlighting their strengths and limitations. We introduce HIVMedQA, a benchmark designed to assess open-ended medical question answering in HIV care. The dataset consists of curated, clinically relevant questions developed with input from an infectious disease physician. We evaluated seven general-purpose and three medically specialized LLMs, applying prompt engineering to enhance performance. Our evaluation framework incorporates both lexical similarity and an LLM-as-a-judge approach, extended to better reflect clinical relevance. We assessed performance across key dimensions: question comprehension, reasoning, knowledge recall, bias, potential harm, and factual accuracy. Results show that Gemini 2.5 Pro consistently outperformed other models across most dimensions. Notably, two of the top three models were proprietary. Performance declined as question complexity increased. Medically fine-tuned models did not always outperform general-purpose ones, and larger model size was not a reliable predictor of performance. Reasoning and comprehension were more challenging than factual recall, and cognitive biases such as recency and status quo were observed. These findings underscore the need for targeted development and evaluation to ensure safe, effective LLM integration in clinical care.
Background Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV. Methods In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. We measured CD4 + T cells at baseline and followed the individuals longitudinally via chart review for 12 months. Fecal samples were assessed for parasitic infection, and standard 16S bacterial rRNA sequencing determined microbiome composition. We assessed alpha and beta diversity by clinical factors, e.g., ART duration, CD4 + T cells/µL, parasitic infection, and differential relative abundances via non-parametric tests and adjusted regression. We assessed the relationship between taxa and longitudinal change in CD4 + cells/µL via linear mixed models. Results This analysis of microbiome data among 175 participants found that alpha diversity was lower in participants with < 100 CD4 + T cells/µL versus their peers with higher CD4 + counts. Only the presence of Anaerococcus was inversely associated with CD4 + T cells/µL (Spearman correlation − 0.3207; p-value = 0.0000152). We observed no trends in beta diversity across clinical or demographic groups. Presence of Sutterella and Alcaligenaceae at baseline were associated with increasing CD4 + T cells/µL over time. Conclusions We identified three taxa associated with clinical parameters, and, importantly, that the fecal microbiome is less diverse at lower CD4 + T cells counts, which is concerning for relatively increased dysbiosis and worse outcomes. Given the large prevalence of HIV in Sub-Saharan Africa, key differences in factors that influence microbiome, and the apparent importance of the microbiome in health status, future microbiome research focused on diverse and rural African populations is warranted. Clinical trial Not applicable. This was not a clinical trial as no intervention was applied to the participant.
INTRODUCTION: Influenza virus infection is known to increase the risk of cardiovascular events, especially in populations with pre-existing cardiovascular disease (CVD). Considering that influenza is vaccine preventable, international guidelines recommend high-risk populations with CVD receive an influenza vaccine every year. However, there are various classifications of recommendations and levels of evidence. Previous systematic reviews concluded uncertain evidence on influenza vaccine efficacy for preventing cardiovascular events in the general population or in populations with pre-existing CVD. Limited safety data of influenza vaccines were reported for populations with pre-existing CVD. Randomised controlled trials with larger sample sizes relative to previous studies are emerging, the findings of these trials are likely to be highly influential on summary efficacy estimates. METHODS AND ANALYSIS: We aim to perform a living systematic review and a prospective meta-analysis to evaluate the efficacy and safety of influenza vaccines compared with no vaccines or placebo for preventing mortality or CVD events in the general population and in populations with pre-existing CVD. Any types of randomised controlled trial and observational study meeting the Population, Intervention, Comparator, Outcome and Study design criteria for the research question will be selected for inclusion. The living systematic review status will be maintained for 3 years with an update for every 6 months. Mainstream medical literature databases will be independently searched by two authors with predefined strategies. Two authors will perform the risk of bias assessment with consensus. Narrative synthesis and meta-analyses will be performed to summarise the results. ETHICS AND DISSEMINATION: Formal ethical review is not required as this study does not involve primary data collection. We will publish results of the living systematic review and prospective meta-analysis in a peer-reviewed journal. Findings will also be presented at relevant meetings. PROSPERO REGISTRATION NUMBER: CRD42021222519.
International audience;
Influenza A viruses still represent a major health issue, for both humans and animals. One of the main viral proteins of interest to target is the NS1 protein, which counters the host immune response and promotes viral replication. NS1 is a homodimer composed of a dimeric RNA-binding domain (RBD), which is structurally stable and conserved in sequence, and two effector domains that are tethered to the RBD by linker regions. This linker flexibility leads to NS1 polymorphism and can therefore exhibit different forms. Previously, we identified a putative drug-binding site, located in the RBD interface in a crystal structure of NS1. This pocket could be targeted to block RNA binding and inhibit NS1 activities. The objective of the present study is to confirm the presence of this druggable site, whatever the sequence variants, in order to develop a universal therapeutic compound that is insensitive to sequence variations and structural flexibility. Using a set of four NS1 full-length structures, we combined different bioinformatics approaches such as pocket tracking along molecular dynamics simulations, druggability prediction and classification. This protocol successfully confirmed a frequent large binding-site that is highly druggable and shared by different NS1 forms, which is promising for developing a robust NS1-targeted therapy.
Background Previous studies have shown inconsistent findings regarding the association of light to moderate alcohol consumption with cause-specific mortality. Therefore, this study sought to examine the prospective association of alcohol consumption with all-cause and cause-specific mortality in the US population. Methods This was a population-based cohort study of adults aged 18 years or older in the National Health Interview Survey (1997 to 2014) with linkage to the National Death Index records through December 31, 2019. Self-reported alcohol consumption was categorized into seven groups (lifetime abstainers; former infrequent or regular drinkers; and current infrequent, light, moderate, or heavy drinkers). The main outcome was all-cause and cause-specific mortality. Results During an average follow-up of 12.65 years, among the 918,529 participants (mean age 46.1 years; 48.0% male), 141,512 adults died from all causes, 43,979 from cardiovascular disease (CVD), 33,222 from cancer, 8246 from chronic lower respiratory tract diseases, 5572 from accidents (unintentional injuries), 4776 from Alzheimer’s disease, 4845 from diabetes mellitus, 2815 from influenza and pneumonia, and 2692 from nephritis, nephrotic syndrome, or nephrosis. Compared with lifetime abstainers, current infrequent, light, or moderate drinkers were at a lower risk of mortality from all causes [infrequent—hazard ratio: 0.87; 95% confidence interval: 0.84 to 0.90; light: 0.77; 0.75 to 0.79; moderate 0.82; 0.80 to 0.85], CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Also, light or moderate drinkers were associated with lower risk of mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. In contrast, heavy drinkers had a significantly higher risk of mortality from all causes, cancer, and accidents (unintentional injuries). Furthermore, binge drinking ≥ 1 day/week was associated with a higher risk of mortality from all causes (1.15; 1.09 to 1.22), cancer (1.22; 1.10 to 1.35), and accidents (unintentional injuries) (1.39; 1.11 to 1.74). Conclusions Infrequent, light, and moderate alcohol consumption were inversely associated with mortality from all causes, CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Light or moderate alcohol consumption might also have a beneficial effect on mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. However, heavy or binge had a higher risk of all-cause, cancer, and accidents (unintentional injuries) mortality.
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.
Huangqin Su (HQS) tablet is mainly composed of baicalein which has been evaluated for its ability to inhibit influenza. The present study aimed to investigate the effect of HQS and oseltamivir phosphate (OS) (single or combination therapy) on influenza-induced acute pneumonia in male and female ICR mice. The regulatory effect of HQS on gut microbiota was also studied by using 16 s rDNA sequencing, and the targets and mechanisms of HQS against influenza were comprehensively analyzed by network pharmacology. Pharmacodynamic results, including lung index and pathological changes, showed that HQS exhibited significant anti-influenza efficacy and could improve the efficacy of low-dose OS ( P < 0.05 and P < 0.01, respectively). The results of 16 s rDNA sequencing revealed that HQS modulated the gut microbiota and remarkably enriched the abundance of Lactobacillus . The findings of network pharmacology research suggested that the anti-influenza mechanism of HQS was related to TLRs, MAPK, and other signal transduction pathways. Taken together, this study identified the possibility of the combined use of HQS and OS and demonstrated the role of HQS in modulating the gut microbiota of mice against influenza. Network pharmacology studies also suggested that the anti-influenza effect of HQS was related to TLRs, MAPK, TNF, and other signaling pathways.
Background Early and accessible testing for influenza with point-of-care testing (POCT) can be a critical factor for deciding to begin antiviral treatment. More than 10,000 pharmacies across the USA offer Clinical Laboratory Improvement Amendments-waived POCT for infectious diseases, such as influenza A/B. Knowledge of barriers and facilitators to large-scale POCT implementation may be useful in scaling POCT for influenza test-and-treat services (Flu POCT). The objective of this study was to explore the experiences of pharmacists who were early adopters of Flu POCT and treatment under collaborative practice agreement in community pharmacy settings. Methods Qualitative research design with in-depth, semi-structured virtual video interviews of licensed US community pharmacists. Interview questions were derived from the Consolidated Framework for Implementation Research (CFIR). Interviewees were selected via a purposeful sampling of pharmacists who were enrolled in a nationwide clinical trial involving pharmacy-based influenza test-and-treat under a collaborative agreement. Interviews were recorded and transcribed. A deductive analytic approach was used via constructs from the CFIR. Results Six pharmacists were interviewed. Interviews ranged from 28 to 70 min, with an average length of 46 min. Four broad themes emerged from the data, and each had corresponding subthemes and supporting quotes: influence of the Flu POCT service characteristics on pharmacy implementation, influence of factors outside of the pharmacy setting in Flu POCT implementation, factors within the pharmacy setting influencing implementation, and process of implementing Flu POCT. A novel pharmacy-based Flu POCT implementation framework is presented. Conclusions Implementation of community pharmacy-based Flu POCT services is feasible; but, a thorough understanding of both barriers and facilitators to their implementation is needed to increase the spread and scale of these programs. Specifically, pharmacy stakeholders should focus efforts on increasing patient and provider awareness, pharmacist acceptance, leadership support, and support of health providers external to the pharmacy to improve implementation success.
Cold Spring Harbor LaboratoryJanuary 2024Influenza
Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), TLR7/8 adjuvant. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating the direct delivery of a RIG-I agonist to the cytosol. We have previously tested SDI and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated in a licensed vaccine setting (quadrivalent influenza vaccine or QIV) against H1N1 influenza virus, showing robust induction of antibody titres and T cell responses. Depending on the adjuvant combination and LNP lipid composition (K-Ac7-Dsa or S-Ac7-Dog lipids), humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with protection during viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was examined against challenge with the vaccine-matching strain of H1N1 influenza A virus. Groups that received either LNP formulated with SDI, IMDQ-PEG-Chol or both showed very low levels of viral replication in their lungs at five days post virus infection. LNP ionizable lipid composition as well as loading (empty versus SDI) also skewed host responses to infection, as reflected in the cytokine and chemokine levels in lungs of vaccinated animals upon infection. These studies show the potential of LNPs as adjuvant delivery vehicles for licensed vaccines and illustrate the importance of LNP composition for subsequent host responses to infection, an important point of consideration for vaccine safety.
Background Severe acute respiratory infection (SARI) is a leading cause of mortality globally, peaking during the COVID-19 pandemic. We analyzed SARI-associated deaths during the pre-and-pandemic periods in Bangladesh to identify the contributing factors. Methods We analyzed data from hospital-based influenza surveillance at nine tertiary-level hospitals in Bangladesh. We considered March 2018–February 2020 as the pre-pandemic period and March 2020–February 2022 as the pandemic period and included adult (≥ 18 years) participants in our study. Surveillance physicians identified WHO-SARI case definition meeting inpatients and collected demographics, clinical characteristics, and outcomes at hospital discharge and 30 days post-discharge. We performed rRT-PCR for influenza and SARS-CoV-2 viruses on collected nasopharyngeal and oropharyngeal swabs. We used multivariable Cox's regression models to calculate the hazard ratio (HR) for factors associated with SARI deaths in these adult patients. Results We enrolled 4392 SARI patients during the pre-pandemic and 3824 SARI patients during the pandemic period. Case fatality ratio was higher during the pandemic: 13.62% (521) [in-hospital: 6.45% (247); post-discharge: 7.17% (274)] compared to pre-pandemic, 6.01% (264) [in-hospital: 2.01% (89), post-discharge: 4% (175)] (p < 0.001). Pre-pandemic, influenza was detected in 14% (37/264) of SARI deaths. Influenza was detected during the pandemic in 2.3% (12/521), SARS-CoV-2 in 41.8% (218/521), and both viruses in only one SARI death. History of smoking and the presence of 1 or more co-morbid conditions independently attributed to SARI deaths in adults in the pre-pandemic period. SARI deaths in such patients were also associated with respiratory difficulties on admission in both pre-pandemic (aHR 2.36; 95% CI:1.65–3.36) and pandemic period (aHR 2.30; 95% CI: 1.57–3.35) after accounting for age, sex, smoking status, presence of 1 or more co-morbid conditions, and detection of influenza and SARS-CoV-2 viruses. Conclusions During the pandemic, SARI mortality increased; influenza-associated mortality declined, and SARS-CoV-2 caused over a third of SARI deaths. Post-discharge mortality was higher than in-hospital mortality during both periods. Limiting premature discharge and strengthening post-discharge monitoring and nursing services could reduce unexpected deaths. Formative research to better understand post-discharge mortality is essential to reduce SARI deaths.
Co-circulation of SARS-CoV-2 and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in co-infected patients. The initial lack of a readily available COVID-19 vaccine has reinforced the importance of influenza vaccine programmes during the COVID-19 pandemic. Live Attenuated Influenza Vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days pre- or post-SARS-CoV-2 infection. LAIV administration did not exacerbate SARS-CoV-2 disease course or lung pathology with either regimen. Additionally, LAIV administered prior to SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.
OBJECTIVE: To compare facility-level influenza vaccination rates in long-term care (LTC) homes from four countries and to identify factors associated with influenza vaccination among residents. DESIGN AND SETTING: Retrospective cross-sectional study of individuals residing in LTC homes in New Brunswick (Canada), New Zealand, Switzerland, and the Netherlands between 2017 and 2020. PARTICIPANTS: LTC home residents assessed with interRAI assessment system instruments as part of routine practice in New Brunswick (n=7006) and New Zealand (n=34 518), and national pilot studies in Switzerland (n=2760) and the Netherlands (n=1508). End-of-life residents were excluded from all country cohorts. OUTCOMES: Influenza vaccination within the past year. RESULTS: Influenza vaccination rates among LTC home residents were highest in New Brunswick (84.9%) and lowest in Switzerland (63.5%). For all jurisdictions where facility-level data were available, substantial interfacility variance was observed. There was approximately a fourfold difference in the coefficient of variation for facility-level vaccination rates with the highest in Switzerland at 37.8 and lowest in New Brunswick at 9.7. Resident-level factors associated with vaccine receipt included older age, severe cognitive impairment, medical instability, health conditions affecting a greater number of organ systems and social engagement. Residents who displayed aggressive behaviours and smoke tobacco were less likely to be vaccinated. CONCLUSION: There are opportunities to increase influenza vaccine uptake at both overall country and individual facility levels. Enhanced vaccine administration monitoring programmes in LTC homes that leverage interRAI assessment systems should be widely adopted.
Avian-origin H3N2 canine influenza virus (CIV) is one of the most prevalent influenza virus subtypes in dogs worldwide. Previous studies have shown that during the evolution of H3N2 CIV in dogs, its adaptability in mammals increased gradually, suggesting that dogs can serve as a potential intermediate host for cross-species transmission of the avian influenza virus. In this study, we report results from the surveillance and characterization of H3N2 CIVs isolated from animal hospitals and kennels in 2021 in China. We characterized the CIVs’ genetic and antigenic variation, receptor-binding specificity, and virulence in mice. The hemagglutinin (HA) phylogenetic result showed that these H3N2 CIVs belonged to Clade 5.1, a clade formed after 2019. Compared to the 2016–2019 strains in China, the 2021 H3N2 CIVs had similar antigenicity and receptor-binding specificity. The pathogenicity in mice was significantly reduced after infection with two 2021 strains, but the replication capacity was similar, suggesting that a virus-host balance might have been established. This report emphasizes the importance of close surveillance and monitoring of H3N2 CIVs in dogs to prevent the emergence of novel influenza viruses with public health threats.
Background Hospital-acquired influenza (HAI) is under-recognized despite its high morbidity and poor health outcomes. The early detection of HAI is crucial for curbing its transmission in hospital settings. Aim This study aimed to investigate factors related to HAI, develop predictive models, and subsequently compare them to identify the best performing machine learning algorithm for predicting the occurrence of HAI. Methods This retrospective observational study was conducted in 2022 and included 111 HAI and 73,748 non-HAI patients from the 2011–2012 and 2019–2020 influenza seasons. General characteristics, comorbidities, vital signs, laboratory and chest X-ray results, and room information within the electronic medical record were analysed. Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGB), and Artificial Neural Network (ANN) techniques were used to construct the predictive models. Employing randomized allocation, 80% of the dataset constituted the training set, and the remaining 20% comprised the test set. The performance of the developed models was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), the count of false negatives (FN), and the determination of feature importance. Results Patients with HAI demonstrated notable differences in general characteristics, comorbidities, vital signs, laboratory findings, chest X-ray result, and room status compared to non-HAI patients. Among the developed models, the RF model demonstrated the best performance taking into account both the AUC (83.3%) and the occurrence of FN (four). The most influential factors for prediction were staying in double rooms, followed by vital signs and laboratory results. Conclusion This study revealed the characteristics of patients with HAI and emphasized the role of ventilation in reducing influenza incidence. These findings can aid hospitals in devising infection prevention strategies, and the application of machine learning-based predictive models especially RF can enable early intervention to mitigate the spread of influenza in healthcare settings.
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 and objective
Seasonal influenza may cause serious illness, especially in high-risk populations such as older adults and individuals suffering from non-communicable diseases (NCD) and may be prevented by a vaccination. However, an assessment of the impact of the Swiss legal frameworks and number of health activities on influenza vaccination coverage of the population at the cantonal level is lacking.
Methods
Two participating healthcare insurers sent out 25,000 semi-structured questionnaires to their subscribers aged 60–85 in five Swiss cantons selected according to the number of health activities and legal framework regarding influenza vaccination and linguistic region. Influenza vaccination coverage of the participants was evaluated and stratified by disease status, age, canton, and linguistic region. Results were compared by cantonal activities, legal framework, and linguistic region.
Results
7,617 valid questionnaires were evaluated from the cantons Aargau, Jura, St. Gallen, Schwyz, and Vaud. 47.9 % stated to have an NCD, with the most frequent being muscle/ skeletal disease (36.7%). Before 2018, 48.6% were vaccinated against influenza, and 35.9% in 2019, with the highest in canton Vaud. In all cantons and in both survey periods, NCD patients and those aged 73–85 had a higher vaccination coverage than participants without NCD, and aged 60–72. There was no difference in the odds of getting an influenza shot based on legal framework. Although a comparison of the number of activities between the German-speaking cantons did not reveal any significant differences, the odds of the participants living in a French-speaking canton getting an influenza vaccination was more likely than those living in a German-speaking canton.
Conclusion
There was no association between the investigated cantonal frameworks and number of health activities and influenza vaccination coverage in NCD patients in the selected cantons. However, age, disease status and linguistic region appear to have an influence on vaccination uptake.
Cold Spring Harbor LaboratoryFebruary 2024Influenza
Influenza viruses cause a common respiratory disease known as influenza. In humans, seasonal influenza viruses can lead to epidemics, with avian influenza viruses of particular concern because they can infect multiple species and lead to unpredictable and severe disease. Therefore, there is an urgent need for a universal influenza vaccine that provides protection against seasonal and pre-pandemic influenza virus strains. The cyclic GMP-AMP (cGAMP) is a promising adjuvant for subunit vaccines that promotes type I interferons production through the stimulator of interferon genes (STING) pathway. The encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles (MPs) enhances its intracellular delivery. In this study, the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology was used to generate H1, H3, and H5 vaccine candidates. Monovalent and multivalent COBRA HA vaccines formulated with cGAMP Ace-DEX MPs were evaluated in a mouse model for antibody responses and protection against viral challenge. Serological analysis showed that cGAMP MPs adjuvanted monovalent and multivalent COBRA vaccines elicited robust antigen-specific antibody responses after a prime-boost vaccination and antibody titers were further enhanced after second boost. Compared to COBRA vaccine groups with no adjuvant or blank MPs, the cGAMP MPs enhanced HAI antibody responses against COBRA vaccination. The HAI antibody titers were not significantly different between cGAMP MPs adjuvanted monovalent and multivalent COBRA vaccine groups for most of the viruses tested in panels. The cGAMP MPs adjuvanted COBRA vaccines groups had higher antigen-specific IgG2a binding titers than the COBRA vaccine groups with no adjuvant or blank MPs. The COBRA vaccines formulated with cGAMP MPs mitigated disease caused by influenza viral challenge and decreased pulmonary viral titers in mice. Therefore, the formulation of COBRA vaccines plus cGAMP MPs is a promising universal influenza vaccine that elicits protective immune responses against human seasonal and pre-pandemic strains.
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Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal formulations incorporating conserved IAV epitopes, namely the long alpha helix (LAH) of the stalk domain of hemagglutinin and three tandem repeats of the ectodomain of the matrix protein 2 (3M2e), as universal mucosal anti-IAV vaccines in mice and chickens. The IAV epitopes were grafted to nanorings, a novel platform technology for mucosal vaccination formed by the nucleoprotein (N) of the respiratory syncytial virus, in fusion or not with the C-terminal end of the P97 protein (P97c), a recently identified Toll-like receptor 5 agonist. Fusion of LAH to nanorings boosted the generation of LAH-specific systemic and local antibody responses as well as cellular immunity in mice, whereas the carrier effect of nanorings was less pronounced towards 3M2e. Mice vaccinated with chimeric nanorings bearing IAV epitopes in fusion with P97c presented modest LAH- or M2e-specific IgG titers in serum and were unable to generate a mucosal humoral response. In contrast, N-3M2e or N-LAH nanorings admixed with Montanide™ gel (MG) triggered strong specific humoral responses, composed of serum type 1/type 2 IgG and mucosal IgG and IgA, as well as cellular responses dominated by type 1/type 17 cytokine profiles. All mice vaccinated with the [N-3M2e + N-LAH + MG] formulation survived an H1N1 challenge and the combination of both N-3M2e and N-LAH nanorings with MG enhanced the clinical and/or virological protective potential of the preparation in comparison to individual nanorings. Chickens vaccinated parenterally or mucosally with N-LAH and N-3M2e nanorings admixed with Montanide™ adjuvantsdeveloped a specific systemic humoral response, which nonetheless failed to confer protection against heterosubtypic challenge with a highly pathogenic H5N8 strain. Thus, while the combination of N-LAH and N-3M2e nanorings with Montanide™ adjuvants shows promise as a universal mucosal anti-IAV vaccine in the mouse model, further experiments have to be conducted to extend its efficacy to poultry.
CCSD;Oxford University Press (OUP)January 2022Influenza
International audience;
Abstract This paper uses a difference-in-differences (DID) framework to estimate the impact of non-pharmaceutical interventions (NPIs) used to fight the 1918 influenza pandemic and control the resultant mortality in 43 US cities. The results suggest that NPIs such as school closures and social distancing, as implemented in 1918, and when applied relatively intensively, might have reduced individual and herd immunity reducing the life expectancy of people with co morbidity, thereby leading to a significantly higher number of deaths in subsequent years. It would be difficult to draw any inference regarding the predicted impact of NPIs as implemented during the Covid-19 crisis as influenza and Covid-19 are two entirely different viruses and nowadays’ pharmaceutical technologies can limit these medium-term impacts.
BACKGROUND: Influenza spreads from schools to the rest of society. Thus, we conducted questionnaire surveys of influenza vaccination in elementary and middle schools in a district for 10 years to determine immunization rates and infection conditions among students who were potential sources of infection at home. METHODS: The questionnaire-based survey on influenza vaccine administration, influenza infection, and influenza types contracted, as well as influenza immunization history, was conducted in 10 seasons over a period of 10 years. RESULTS: In elementary schools, vaccination was associated with lower morbidity in most years, whereas in middle schools, morbidity increased among students who were vaccinated every year. Our study did not find consistent trends among faculty and staff. In addition, we found that morbidity was significantly higher among elementary (P < 0.001) and middle (P < 0.05) school students who had been vaccinated since infancy than among those who had not been vaccinated since infancy. CONCLUSIONS: The results of this study suggest that vaccinating infants for influenza may increase the risk of contracting influenza later in life. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-022-07898-y.
Background Novel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community. Methods PubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002–February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525). Results Twenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high ( n = 1) and unclear ( n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 ( P < 0.05), but risk of bias was high ( n = 7), unclear ( n = 5) or low ( n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent. Conclusions To our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.
Background The aim of this retrospective study was to examine the risk factors of positive lower respiratory tract cultures and to investigate whether nosocomial infections are common in patients with positive lower respiratory tract cultures. Methods We enrolled 86 patients diagnosed with influenza A-related critical illness who were treated at Fuzhou Pulmonary Hospital of Fujian in China between 1st October 2013 and 31st March 2019. The of admission were used to divide the enrolled patients into two groups. Sputum and bronchoalveolar lavage fluid specimens were collected within 48 h after admission for culture. All samples were cultured immediately after sampling. Nosocomial infections are defined as any symptom or sign of pulmonary infiltration, confirmed by X-ray, after 5 days of admission and positive results from one or more cultures. Results The average age of this cohort was (54.13 ± 16.52) years. Based on the culture results, Staphylococcus aureus and Candida albicans had the highest positive rates (3.40% (3/86) and 20.90% (18/86), respectively). In patients with positive lower respiratory tract cultures, the incidence of nosocomial infection was 73.30% (22/30) five days after admission. However, the incidence of nosocomial infection was lower (42.80%, 24/56) in patients with negative lower respiratory tract cultures. Hemoptysis, systolic pressure at admission, and blood urea nitrogen level at admission were all independent risk factors for positive lower respiratory tract cultures within 48 h of admission. Conclusion Our data showed that a significant proportion of patients with pneumonia exhibited co-infections with bacteria or fungi within five days of hospital admission. Hemoptysis, systolic pressure, and blood urea nitrogen levels at admission emerged as the key risk factors. These findings underscore the necessity of closely monitoring patients with influenza infection, particularly for positive bacterial or fungal cultures within the initial 48 h of admission.
The COVID-19 pandemic is frequently compared to historical influenza outbreaks, yet this analogy often obscures fundamental biological and epidemiological divergences. As the global health community confronts new threats like H5N1 avian influenza, a rigorous retrospective analysis is essential to distinguish the unique trajectory of SARS-CoV-2 from the influenza pandemics of 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1). This narrative review, adhering to best-practice guidance, synthesises literature published up to mid-2025. We performed targeted searches of PubMed, EMBASE, and WHO/CDC archives to compare SARS-CoV-2 critically and Influenza A across virological, clinical, and sociopolitical dimensions. Our analysis reveals that while both pathogens share respiratory transmission, they differ starkly in evolutionary mechanisms and systemic impact. Virologically, SARS-CoV-2 utilises convergent evolution and broad ACE2 tropism to cause multi-organ pathology and long-term sequelae (Long COVID), distinguishing it from the primarily respiratory effects and reassortment-driven shifts of influenza. Epidemiologically, SARS-CoV-2 exhibits a significantly higher basic reproduction number (R_0), rising from ~ 2.5 to > 9.5 in Omicron variants, and substantial asymptomatic transmission, necessitating non-pharmaceutical interventions of unprecedented scale compared to the modest measures of past flu pandemics. The public health response also highlighted a divergence in medical innovation: the development of mRNA vaccines within 11 months represented a “quantum leap” in vaccinology compared to the slower, egg-based timelines of 2009. In conclusion, COVID-19 represents a distinct biological and societal entity that defies the historical “flu template.” The transition to endemicity, marked by year-round waves of immune-evasive variants like JN.1, and the current emergence of mammalian H5N1 underscore the need for pathogen-agnostic preparedness. Future global health security depends on leveraging the genomic and technological assets developed during COVID-19 to counter threats that transcend historical expectations.
BACKGROUND: The European Medicines Agency (EMA) requires enhanced safety surveillance to be conducted for annual seasonal influenza vaccines with the aim of rapidly detecting any potential new safety concerns before the peak immunisation period of the vaccine in any given year. The aim of this study was to detect any clinically significant change in the frequency or severity of expected reactogenicity of the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunisation in Finland for the 2020/21 season. The primary objective was to investigate the frequency of suspected adverse drug reactions (ADRs) occurring within 7 days following vaccination. METHODS: Enhanced passive safety surveillance of individuals vaccinated with IIV4 was conducted from October 9, 2020 to November 30, 2020 across seven sites in Finland. The vaccinee reporting rate and ADR reporting rate were calculated and compared with known or expected safety data in order to identify any clinically significant changes. RESULTS: Data were collected from 1008 individuals with 29 vaccinees reporting 82 suspected ADRs. Of these, 28 people reported 79 suspected ADRs within 7 days following vaccination, corresponding to a vaccinee reporting rate of 2.78% (95% CI: 1.85, 3.99) (ADR reporting rate, 7.84% [95% CI: 6.25, 9.67%]). The most frequently reported ADRs were injection site reactions (vaccination site pain, vaccination site erythema and vaccination site swelling) (n = 46, 2.28%), myalgia (n = 9, 0.89%) and headache (n = 8, 0.79%). No serious suspected adverse events were reported at any point post-vaccination and ADR reporting rates were in general lower compared to those reported for IIV4 in the 2019/20 surveillance study. CONCLUSION: No clinically significant changes in what is known or expected for IIV4 were reported for the 2020/21 season which supports the safety profile of this vaccine and will help maintain public confidence in influenza vaccination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13898-z.
Understanding Influenza B virus infections is of critical importance in our efforts to control severe influenza and influenza-related disease. Until 2020, two genetic lineages of influenza B virus – Yamagata and Victoria – circulated in the population. These lineages are antigenically distinct but differences in virus replication or the induction of host cell responses after infection have not been carefully studied. Recent IBV clinical isolates of both lineages were obtained from influenza surveillance efforts of the Johns Hopkins Center of Excellence in Influenza Research and Response and characterized in vitro . B/Victoria and B/Yamagata clinical isolates were recognized less efficiently by serum from influenza-vaccinated individuals in comparison to the vaccine strains. B/Victoria lineages formed smaller plaques on MDCK cells compared to B/Yamagata, but infectious virus production in primary human nasal epithelial cell (hNEC) cultures showed no differences. While ciliated epithelial cells were the dominant cell type infected by both lineages, B/Victoria lineages had a slight preference for MUC5AC-positive cells, while B/Yamagata lineages infected more basal cells. Finally, while both lineages induced a strong interferon response 48 hours after infection of hNEC cultures, the B/Victoria lineages showed a much stronger induction of interferon related signaling pathways compared to B/Yamagata. This demonstrates that the two influenza B virus lineages differ not only in their antigenic structure but in their ability to induce host innate immune responses.
Epidemics of influenza are major public health concerns. Since influenza
prediction always relies on the weekly clinical or laboratory surveillance
data, typically the weekly Influenza-like illness (ILI) rate series, accurate
multi-step-ahead influenza predictions using ILI series is of great importance,
especially, to the potential coming influenza outbreaks. This study proposes
Comprehensive Learning Particle Swarm Optimization based Machine Learning
(CLPSO-ML) framework incorporating support vector regression (SVR) and
multilayer perceptron (MLP) for multi-step-ahead influenza prediction. A
comprehensive examination and comparison of the performance and potential of
three commonly used multi-step-ahead prediction modeling strategies, including
iterated strategy, direct strategy and multiple-input multiple-output (MIMO)
strategy, was conducted using the weekly ILI rate series from both the Southern
and Northern China. The results show that: (1) The MIMO strategy achieves the
best multi-step-ahead prediction, and is potentially more adaptive for longer
horizon; (2) The iterated strategy demonstrates special potentials for deriving
the least time difference between the occurrence of the predicted peak value
and the true peak value of an influenza outbreak; (3) For ILI in the Northern
China, SVR model implemented with MIMO strategy performs best, and SVR with
iterated strategy also shows remarkable performance especially during outbreak
periods; while for ILI in the Southern China, both SVR and MLP models with MIMO
strategy have competitive prediction performance
Influenza and other respiratory viral pathogens are leading causes of mortality and morbidity. We previously demonstrated that circadian rhythms confer temporal protection from influenza infection. Here, we investigated whether this protection requires rhythmic function after the initial infection by manipulating environmental cycles. We demonstrate that disrupting environmental lighting cues within a critical window of vulnerability abrogates time-of-day specific protection. This poor outcome is mediated by a dysregulated immune response, evidenced by the accumulation of inflammatory monocytes and CD8 (+) cells in the lungs and a transcriptomic profile indicative of an exaggerated immune response. Disruption of the light cycle does not affect outcomes in a clock mutant, indicating that it acts by compromising endogenous timekeeping. Importantly, rhythmic meal timing mitigates the adverse effects of disrupted light cycles, suggesting that external cycling cues, which act through different body clocks, can substitute for each other. Our findings highlight the crucial interplay between environmental factors and endogenous clocks in shaping influenza outcomes, offering significant translational potential for improving the care of critically ill patients with respiratory viral infections.
Abstract An investigation of freshwater fungi in Thailand resulted in the collection and isolation of a coelomycetous Seriascoma from submerged wood. The combined ITS and LSU sequence data placed the taxon within the sexual morphic Seriascoma acutisporum strains, ZHKUCC 22-0273 and ZHKUCC 22-0274, with high bootstrap support and confirmed the asexual morphic stage of the taxon. Seriascoma acutisporum MFLUCC 24-0091 shares the generic characteristics of having an immersed, eustromatic conidiomata and phialidic, cylindrical to ampulliform, hyaline, aseptate conidiogenous cells bearing hyaline conidia, but with smaller conidiomata and locules compared to other coelomycetous Seriascoma species.
Background Legionella pneumophila is a Gram-negative intracellular bacillus and is the causative agent of a severe form of pneumonia called Legionnaires’ disease which accounts for 2-9% of cases of community acquired pneumonia. It produces an extremely large protein belonging to the RTX ( R epeats in T o X in) family, called RtxA, and we previously reported that RtxA is transported by a dedicated type 1 secretion system (T1SS) to the cell surface. RTX proteins have been shown to participate in the virulence or biofilm formation of various bacteria, the most studied models being the pore forming hemolysin A (HlyA) of Escherichia coli and the biofilm associated protein LapA of P. fluorescens. LapA localization depends on the enzymatic release by LapD/LapG complex activity. This study aimed to elucidate the dual localization (cell surface associated or released state) of L. pneumophila RTX protein (RtxA) and whether this released versus sequestered state of RtxA plays a role in L. pneumophila virulence. Results The hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (position 108–109). Consistently, a strain lacking LapG protease maintains RtxA on the cell surface, whereas a strain lacking the c-di-GMP receptor LapD does not exhibit cell surface RtxA because of its continuous cleavage and release, as in the LapA-D-G model of Pseudomonas fluorescens . Interestingly, our data point out a key role of RtxA in enhancing the infection process of amoeba cells, regardless of its location (embedded or released); therefore, this may be the result of a secondary role of this surface protein. Conclusions This is the first experimental identification of the cleavage site within the RTX protein family. The primary role of RtxA in Legionella is still questionable as in many other bacterial species, hence it sounds reasonable to propose a major function in biofilm formation, promoting cell aggregation when RtxA is embedded in the outer membrane and facilitating biofilm dispersion in case of RtxA release. The role of RtxA in enhancing the infection process may be a result of its action on host cells (i.e., PDI interaction or pore-formation), and independently of its status (embedded or released).
A Special-purpose Committee on Fungal Names with the Same Epithet was established at the XIX International Botanical Congress (IBC) in Shenzhen, China in 2017, with a mandate to report to the 12th International Mycological Congress (IMC) with recommendations on a preferred course of action with respect to names of pleomorphic fungi sharing the same epithet under the International Code of Nomenclature for algae, fungi, and plants . This report provides a synthesis of the deliberations from the Special-purpose Committee. We discuss the arguments for and against the proposed solution to the problems that have arisen regarding the nomenclature of fungi described in multiple morphs using the same epithet. We also propose a gentler method of addressing the problem using existing procedures.
Abstract A model of a fragment of the Common Digital Space of Scientific Knowledge (CDSSK) is constructed. CDSSK contains virtual museum collections (VCs), which are structured sets of digital objects (images, texts, audio, video, 3D models) related by certain features and are an effective tool for popularizing science and culture. A special case of VCs is virtual exhibitions (VEs), some of which are presented on the platform of the electronic library “Scientific Heritage of Russia.” General information about VCs and VEs and their classification by types is provided. The construction of CDSSK elements characterizing the links of VC objects with objects of other classes—organizations, multimedia, encyclopedias, etc.—is described. The example of a virtual mycological collection was used to demonstrate the main stages of uploading of external VCs into the CDSSK using, among other things, the KAMIS Integrated Automated Museum Information System, which is most widely used in Russian museums, as well as the State Information System “Great Russian Encyclopedia.” The possibilities of navigation through the related elements of the generated model of the fragment of the CDSSK are shown.
Background Enterococcus faecium and Staphylococcus aureus are the Gram-positive pathogens of the ESKAPE group, known to represent a great threat to human health due to their high virulence and multiple resistances to antibiotics. Combined, enterococci and S. aureus account for 26% of healthcare-associated infections and are the most common organisms responsible for blood stream infections. We previously showed that the peptidyl-prolyl cis/trans isomerase (PPIase) PpiC of E. faecium elicits the production of specific, opsonic, and protective antibodies that are effective against several strains of E. faecium and E. faecalis . Due to the ubiquitous characteristics of PPIases and their essential function within Gram-positive cells, we hypothesized a potential cross-reactive effect of anti-PpiC antibodies. Results Opsonophagocytic assays combined with bioinformatics led to the identification of the foldase protein PrsA as a new potential vaccine antigen in S. aureus . We show that PrsA is a stable dimeric protein able to elicit opsonic antibodies against the S. aureus strain MW2, as well as cross-binding and cross-opsonic in several S. aureus , E. faecium and E. faecalis strains. Conclusions Given the multiple antibiotic resistances S. aureus and enterococci present, finding preventive strategies is essential to fight those two nosocomial pathogens. The study shows the potential of PrsA as an antigen to use in vaccine formulation against the two dangerous Gram-positive ESKAPE bacteria. Our findings support the idea that PPIases should be further investigated as vaccine targets in the frame of pan-vaccinomics strategy.
Background Extreme precipitation events often cause sudden drops in salinity, leading to disease outbreaks in shrimp aquaculture. Evidence suggests that environmental stress increases animal host susceptibility to pathogens. However, the mechanisms of how low salinity stress induces disease susceptibility remain poorly understood. Methods We investigated the acute response of shrimp gut microbiota exposed to pathogens under low salinity stress. For comparison, shrimp were exposed to Vibrio infection under two salinity conditions: optimal salinity (Control group) and low salinity stress (Stress group). High throughput 16S rRNA sequencing and real-time PCR were employed to characterize the shrimp gut microbiota and quantify the severity level of Vibrio infection. Results The results showed that low salinity stress increased Vibrio infection levels, reduced gut microbiota species richness, and perturbed microbial functions in the shrimp gut, leading to significant changes in lipopolysaccharide biosynthesis that promoted the growth of pathogens. Gut microbiota of the bacterial genera Candidatus Bacilliplasma, Cellvibrio , and Photobacterium were identified as biomarkers of the Stress group. The functions of the gut microbiota in the Stress group were primarily associated with cellular processes and the metabolism of lipid-related compounds. Conclusions Our findings reveal how environmental stress, particularly low salinity, increases shrimp susceptibility to Vibrio infection by affecting the gut microbiota. This highlights the importance of avoiding low salinity stress and promoting gut microbiota resilience to maintain the health of shrimp.
Fungal infections have emerged as a significant public health concern, especially with the increasing incidence of severe mycoses caused by pathogens such as Aspergillus fumigatus , Candida auris , Candida albicans , and Cryptococcus neoformans . These fungi, listed as critical priorities by the World Health Organization, pose a heightened risk due to rising antifungal resistance and their severe impact on immunocompromised individuals. This article, coordinated by the Portuguese Association of Medical Mycology, highlights the importance of adopting a One Health perspective to address fungal threats comprehensively. Drawing on interdisciplinary collaboration, the association aims to foster greater awareness, improve diagnostic capabilities, and stimulate research and public health policies in Portugal but also at global level. The paper outlines key strategies for surveillance, prevention, and innovation in fungal diagnostics and therapeutics. Moreover, it emphasizes the urgent need for national coordination and international cooperation in managing fungal infections, advocating for integrative approaches that link human, animal, and environmental health. By presenting a consolidated overview of current challenges and future priorities, this work seeks to enhance preparedness and response mechanisms in the face of escalating fungal threats.
Background 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.
Mushrooms, long recognized for their nutritional and medicinal value, are emerging as a critical resource in the development of next-generation immunomodulators and antiviral agents. This chapter synthesizes recent advances in understanding the bioactive potential of fungal metabolites, particularly β-glucans, terpenoids, and glycoproteins, which exhibit dual immunoenhancing and direct antiviral properties. These compounds orchestrate immune responses by activating macrophages, modulating cytokine networks, and enhancing natural killer (NK) cell cytotoxicity, while concurrently disrupting viral replication through mechanisms such as envelope protein inhibition and viral protease suppression. Notably, their efficacy against RNA viruses, including influenza, SARS-CoV-2, and HIV, highlights their relevance in combating pandemic threats and drug-resistant pathogens. Breakthroughs in biotechnological and nanotechnological approaches are revolutionizing the application of these compounds. Advances in nanoencapsulation (such as exosome-based delivery systems) address bioavailability challenges, enabling targeted immune cell engagement and sustained release of hydrophobic metabolites like ergosterol derivatives. Meanwhile, CRISPR-based metabolic engineering and fungal heterologous expression systems are overcoming barriers to the sustainable production of rare bioactives. This convergence of disciplines is accelerating the translation of mushroom-derived molecules into functional foods, adjuvants, and standalone therapeutics. Despite progress, challenges persist in standardization, pharmacokinetic optimization, and clinical validation. Future research must prioritize mechanistic elucidation of host–pathogen–bioactive interactions, coupled with robust clinical trials to establish efficacy and safety. By integrating mycological biodiversity with modern biotechnological tools, this field holds promise for delivering scalable, eco-conscious solutions to global health crises, bridging traditional medicine with twenty-first-century innovation.
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.
In the healthcare landscape, diseases such as cancer and HIV/AIDS have benefited from the patient's perspective. For fungal diseases, the patient voice remains absent in critical areas such as policy formulation, funding decisions, and research priorities. Patients affected by fungal disease, along with their caregivers and advocacy groups, possess invaluable insights into the challenges and unmet needs they face. By elevating their voices and experiences, policymakers, funding agencies, and researchers can gain a more comprehensive understanding of the multifaceted nature of fungal disease and the urgency of addressing them. This paper addresses the pressing need for a coordinated effort to elevate the patient voice in advocating for improved policies, increased funding, and enhanced research initiatives regarding fungal disease.
Background Chronic stress induces cognitive deficits. There is a well-established connection between the enteric and central nervous systems through the microbiota-gut-brain (MGB) axis. However, the effects of the gut microbiota on cognitive deficits remain unclear. The present study aimed to elucidate the microbiota composition in cognitive deficits and explore its potential in predicting chronic stress-induced cognitive deficits. Methods Mice were randomly divided into control and chronic restraint stress (CRS) groups. The mice subjected to CRS were further divided into cognitive deficit (CRS-CD) and non-cognitive deficit (CRS-NCD) groups using hierarchical cluster analysis of novel object recognition test results. The composition and diversity of the gut microbiota were analyzed. Results After being subjected to chronic restraint distress, the CRS-CD mice travelled shorter movement distances ( p = 0.034 vs. CRS-NCD; p < 0.001 vs. control) and had a lower recognition index than the CRS-NCD ( p < 0.0001 vs. CRS-NCD; p < 0.0001 vs. control) and control mice. The results revealed that 5 gut bacteria at genus levels were significantly different in the fecal samples of mice in the three groups. Further analyses demonstrated that Muricomes were not only significantly enriched in the CRS-CD group but also correlated with a decreased cognitive index. The area under the receiver operating curve of Muricomes for CRS-induced cognitive deficits was 0.96. Conclusions Our study indicates that the composition of the gut microbiota is involved in the development of cognitive deficits induced by chronic restraint stress. Further analysis revealed that Muricomes have the potential to predict the development of chronic stress-induced cognitive deficits in mice.
Brazil stands out in research, industrial development, and farmers' use of microbial inoculants, with an emphasis on getting benefits from the biological nitrogen fixation process with the soybean crop. Nowadays, about 140 million doses of inoculants are commercialized annually for the soybean in the country, and strain identification is achieved by rep-PCR, an effective but time-consuming method. Aiming to develop an easy, low-cost, and low-time-consuming method, we used a complete genome-based approach based on the unequivocal identification of unique genes present in the genomes of each of the four Bradyrhizobium strains used in commercial inoculants: Bradyrhizobium elkanii strains SEMIA 587 and SEMIA 5019, Bradyrhizobium japonicum SEMIA 5079, and Bradyrhizobium diazoefficiens SEMIA 5080. The unique pairs of primers able to amplify genomic regions of different sizes allowed the identification of the four strains in a simple multiplex polymerase chain reaction (PCR). Validation was confirmed by using single colonies, multiple cultures, and commercial inoculants. The number of labor hours of a technician was 3.08 times higher, and the final cost was 3.25 times higher in the rep-PCR than in the multiplex PCR. Most importantly, the results for multiplex PCR were obtained on the same day, in contrast with 15 days in the traditional methodology. The genomic approach developed can be easily applied to a variety of microbial inoculants worldwide, in addition to studies of ecology and evaluation of the competitiveness of the strains. Graphical Abstract
Background Superficial fungal infections (SFIs) are highly prevalent globally, affecting approximately 20–25% of the population. Their diverse and often non-specific clinical manifestations necessitate accurate and timely laboratory diagnosis. Traditional methods such as potassium hydroxide (KOH) microscopy and fluorescence staining, although widely used, are limited by operator dependency, variability in sensitivity, and time-consuming procedures. To improve diagnostic accuracy and efficiency, we evaluated the performance of a novel Artificial Intelligence (AI) -powered Fluorescence Microscopic Image Analyzer (FMIA) in the early detection of SFIs. Results Among 300 patients with suspected SFIs, 241 were confirmed using a comprehensive clinical and mycological reference standard. FMIA achieved the highest diagnostic sensitivity (96.27%), outperforming both fluorescence staining (92.95%) and KOH microscopy (75.52%). FMIA also demonstrated high specificity (96.61%) and an area under the ROC curve of 0.96. In spore-dominant infections such as Malassezia folliculitis, genital candidiasis, tinea capitis, and seborrheic dermatitis, where KOH microscopy showed lower detection rates ranging from 29 to 59%, FMIA achieved significantly higher sensitivities between 83% and 100%. Across various SFI subtypes, FMIA consistently exhibited excellent diagnostic performance, achieving 100% detection for tinea pedis, tinea manuum, tinea faciei, and pityriasis versicolor. The system provided results within three to five minutes at a low per-test cost, while automated focusing and frame validation effectively minimized false positives caused by artifacts. Conclusions The FMIA system offers a highly accurate, rapid, and cost-effective tool for diagnosing SFIs. By addressing the limitations of traditional microscopy and current AI-based image analysis methods, FMIA improves diagnostic precision and efficiency. Its fully automated workflow delivers significant clinical value for routine application in both high-throughput diagnostic laboratories and resource-limited healthcare settings.
Old cultural landscapes, such as old parks and gardens, can be expected to be rich lichen habitats, as they offer otherwise rare microstructures and a high habitat continuity. Yet, old parks are not well studied with regard to their lichen flora. In this study, we investigated three old castle parks in southwest Germany and recorded the epiphytic (bark-inhabiting) lichen flora on 205 native and non-native trees, belonging to 63 tree species. We surveyed lichens on tree stems and assessed tree diameter, bark furrow depth, bark type, and bark pH. We investigated species diversity patterns using a rarefaction/extrapolation approach and community composition using non-metric multidimensional scaling (NMDS). Then, we analysed patterns in species richness and community composition using generalized linear mixed effect models (GLMMs) and a permutation-based, multivariate ANOVA. Species richness was mainly affected by tree species identity and tree functional group, with highest species numbers recorded for Tilia spp., and deciduous trees hosting significantly more species than evergreen trees. Community composition was mainly affected by tree species identity and marginally by bark pH and bark furrow depth. Most lichen species were generally common epiphytes, with many species being indicative for eutrophication or high temperatures. In contrast to our expectation, rare or red-listed species were only rarely encountered. In summary, our results show that the epiphytic lichen communities in old parks are shaped by internal factors (i.e. tree species identity, tree microhabitats) and external factors (i.e. eutrophication, macroclimate). Based on our study results, we recommend maintaining a high (deciduous) tree species diversity, as different tree species hosted different lichen communities.
Background Owing to the widespread use of chemical pesticides to control agricultural pests, pesticide tolerance has become a serious problem. In recent years, it has been found that symbiotic bacteria are related to pesticides tolerance. To investigate the potential role of microorganisms in the pesticide tolerance of Chilo suppressalis , this study was conducted. Results The insect was fed with tetracycline and cefixime as the treatment group (TET and CFM, respectively), and did not add antibiotics in the control groups (CK). The 16S rDNA sequencing results showed that antibiotics reduced the diversity of C. suppressalis symbiotic microorganisms but did not affect their growth and development. In bioassays of the three C. suppressalis groups (TET, CFM, and CK), a 72 h LC_50 fitting curve was calculated to determine whether long-term antibiotic feeding leads to a decrease in pesticide resistance. The CK group of C. suppressalis was used to determine the direct effect of antibiotics on pesticide tolerance using a mixture of antibiotics and pesticides. Indirect evidence suggests that antibiotics themselves did not affect the pesticide tolerance of C. suppressalis . The results confirmed that feeding C. suppressalis cefixime led to a decrease in the expression of potential tolerance genes to chlorantraniliprole. Conclusions This study reveals the impact of antibiotic induced changes in symbiotic microorganisms on the pesticide tolerance of C. suppressalis , laying the foundation for studying the interaction between C. suppressalis and microorganisms, and also providing new ideas for the prevention and control of C. suppressalis and the creation of new pesticides.
Abstract Acinetobacter baumannii belongs to the ESKAPE group. It is classified as a critical priority group by the World Health Organization and a global concern on account of its capacity to acquire and develop resistance mechanisms to multiple antibiotics. Data from the United States indicates 500 deaths annually. Resistance mechanisms of this bacterium include enzymatic pathways such as ß-lactamases, carbapenemases, and aminoglycoside-modifying enzymes, decreased permeability, and overexpression of efflux pumps. A. baumannii has been demonstrated to possess efflux pumps, which are classified as members of the MATE family, RND and MFS superfamilies, and SMR transporters. The aim of our work was to assess the distribution of efflux pumps and their regulatory gene expression in clinical strains of A. baumannii isolated from burned patients. Methods From the Clinical Microbiology Laboratory at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra collection in Mexico, 199 strains were selected. Antibiotics susceptibilities were performed by broth microdilutions to determine minimal inhibitory concentrations. Phenotypic assays with efflux pump inhibitors were conducted using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and phenylalanine-arginine ß-naphthylamide (PAßN) in conjunction with amikacin, ceftazidime, imipenem, meropenem and levofloxacin. A search was conducted for structural genes that are linked to efflux pumps, and the relative expression of the adeR , adeS , and adeL genes was analyzed. Results Among a total of 199 strains, 186 exhibited multidrug resistance (MDR). Fluoroquinolones demonstrated the highest resistance rates, while minocycline and amikacin displayed comparatively reduced resistance rates (1.5 and 28.1, respectively). The efflux activity of fluorquinolones exhibited the highest phenotypic detection (from 85 to 100%), while IMP demonstrated the lowest activity of 27% with PAßN and 43.3% with CCCP. Overexpression was observed in adeS and adeL , with adeR exhibiting overexpression. Concluding that clinical strains of A. baumannii from our institution exhibited efflux pumps as one of the resistance mechanisms.
Background Endometrial hyperplasia (EH) is a precursor to endometrial cancer, and the role of the microbiome in its development is unclear. Results The present study investigated the uterine microbiome in patients with benign uterine conditions and endometrial hyperplasia. A significant structural shift in the uterine microbiome of patients with endometrial hyperplasia compared to those with benign conditions was found. Delftia , Serratia and Stenotrophomonas were significantly enriched in endometrial hyperplasia samples and associated with the presence of endometrial hyperplasia. Conclusions The novel finding suggested that increased abundance of Delftia , Serratia and Stenotrophomonas is associated with the presence of endometrial hyperplasia. Further investigation is needed to determine the value of these microbes as biomarkers for endometrial hyperplasia.
Background Taxol, derived from Taxus trees, is a valuable natural resource for the development of anticancer drugs. Endophytic fungi from Taxus trees are a promising alternative source of Taxol. However, the impact of plant-endophytic microbial interaction on the host’s Taxol biosynthesis is largely unknown. Results In the current study, the diversity of endophytic fungi in three different Taxus species was analyzed using Internal Transcribed Spacer sequencing. A total of 271 Operational Taxonomic Units (OTUs) were identified, grouping into 2 phyla, 8 classes, 16 orders, 19 families, and 19 genera. Alpha and beta diversity analysis indicated significant differences in endophytic fungal communities among the various Taxus trees. At the genus level, Alternaria and Davidiella were predominantly found in T. mairei and T. media , respectively. By utilizing a previously published dataset, a Pearson correlation analysis was conducted to predict the taxol biosynthesis-related fungal genera. Following screening, two isolates of Alternaria (L7 and M14) were obtained. Effect of inoculation with Alternaria isolates on the gene expression and metabolite accumulation of T. mairei was determined by transcriptomic and untargeted metabolomic studies. The co-inoculation assay suggests that the two Alternaria isolates may have a negative regulatory effect on taxol biosynthesis by influencing hormone signaling pathways. Conclusion Our findings will serve as a foundation for advancing the production and utilization of Taxus and will also aid in screening endophytic fungi related to taxol production.
Background More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC. Objective To analyze the characteristic microbes in AA. Methods Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and β diversity. α diversity included box diagram, and β diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed. Results The abundance of Prevotella sp900557255 , Alistipes putredinis , and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus , Felixounavirus , and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D , Prevotella sp900557255 , CAG-180 sp000432435 , Phocaeicola plebeiuA , Teseptimavirus , Svunavirus , Felixounavirus , and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively. Conclusion Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing. The bacteria (including Prevotella sp900557255 , Alistipes putredinis , Megamonas funiformis , etc. ) and viruses (including Lilyvirus , Felixounavirus , and Drulisvirus , etc.) existed differences in AA. And there were correlations between AA and basic information, lipid index and serological index. Prediction models based on bacteria and viruses were established to distinguish AA, and the accuracy reached 87.27% and 83.33%. A new typing method was established based on bacteria and viruses to divide gut microbes into 4 subtypes. Prediction models after typing had higher accuracy (100% in B1V1, 96.34% in B1V2, 100% in B2V1, 98.46% in B2V2).
This study used berberine hydrochloride to treat the Asian paddle crab, Charybdis japonica infected with the Gram-negative bacterium Aeromonas hydrophila at concentrations of 0, 100, 200 and 300 mg/L. The effect of berberine hydrochloride on the survival rate and gut microbiota of C. japonica was investigated. Berberine hydrochloride improved the stability of the intestinal flora, with an increase in the abundance of probiotic species and a decrease in the abundance of both pathogenic bacteria after treatment with high concentrations of berberine hydrochloride. Berberine hydrochloride altered peroxidase activity (POD), malondialdehyde (MDA), and lipid peroxidation (LPO) in the intestinal tract compared to the control. Berberine hydrochloride could modulate the energy released from the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the intestinal tract of C. japonica infected with A. hydrophila. Zona occludens 1 (ZO-1), Zinc finger E-box binding homeobox 1 (ZEB1), occludin and signal transducer, and activator of transcription5b (STAT5b) expression were also increased, which improved intestinal barrier function. The results of this study provide new insights into the role of berberine hydrochloride in intestinal immune mechanisms and oxidative stress in crustaceans.
Background Alternaria alternata is the primary pathogen of potato leaf spot disease, resulting in significant potato yield losses globally. Endophytic microorganism-based biological control, especially using microorganisms from host plants, has emerged as a promising and eco-friendly approach for managing plant diseases. Therefore, this study aimed to isolate, identify and characterize the endophytic fungi from healthy potato leaves which had great antifungal activity to the potato leaf spot pathogen of A. alternata in vitro and in vivo. Results An endophytic fungal strain SD1-4 was isolated from healthy potato leaves and was identified as Talaromyces muroii through morphological and sequencing analysis. The strain SD1-4 exhibited potent antifungal activity against the potato leaf spot pathogen A. alternata Lill, with a hyphal inhibition rate of 69.19%. Microscopic and scanning electron microscope observations revealed that the strain SD1-4 grew parallel to, coiled around, shrunk and deformed the mycelia of A. alternata Lill. Additionally, the enzyme activities of chitinase and β-1, 3-glucanase significantly increased in the hyphae of A. alternata Lill when co-cultured with the strain SD1-4, indicating severe impairment of the cell wall function of A. alternata Lill. Furthermore, the mycelial growth and conidial germination of A. alternata Lill were significantly suppressed by the aseptic filtrate of the strain SD1-4, with inhibition rates of 79.00% and 80.67%, respectively. Decrease of leaf spot disease index from 78.36 to 37.03 was also observed in potato plants treated with the strain SD1-4, along with the significantly increased plant growth characters including plant height, root length, fresh weight, dry weight, chlorophyll content and photosynthetic rate of potato seedlings. Conclusion The endophyte fungus of T. muroii SD1-4 isolated from healthy potato leaves in the present study showed high biocontrol potential against potato leaf spot disease caused by A. alternata via direct parasitism or antifungal metabolites, and had positive roles in promoting potato plant growth.
Backgorund In recent years, there has been an increasing interest in the field of research into the isolation and characterization of probiotics in the prevention of diseases and the need to maintain the continuity of healthy microbiota. Therefore, the aim of this study is to isolate and identify bacteria found in maternal colostrum, breast milk, adult and infant feces, analyze possible probiotic potential, and reveal the developmental kinetics of selected strains. Results We isolated 40 bacterial species from 4 different sources and identified 19 bacteria in the form of bacilli through molecular biology and carried out studies with 11 of them. Five of the selected strains showed the better results considering bile salt resistance and ability to survive at different pH and antimicrobial effect. When the adhesion capacity in cell culture is examined, the better 2 strains are; Lactobacillus pontis ZZ6780 and Lactobacillus reuteri NBC2680 were selected and the growth kinetics of these strains were demonstrated at the 3 L bioreactor scale. Finally, the growth kinetics of selected strains were determined and the maximum specific growth rate of selected Lactobacillus pontis ZZ6780 and Lactobacillus reuteri NBC2680 was calculated as 0.412 h^− 1 and 0.481 h^− 1, respectively. In addition, the dry cell matter amounts were found to be and 4.45 g/L and 5.23 g/L, respectively. Conclusion This study established the groundwork for the selection of safety probiotics for the development and application of LAB. It is thought that the two strains obtained as a result of this study can be considered as potential probiotic strains in the food, pharmaceutical and cosmetic industries.
Background The emergence of fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae is a growing concern. To investigate the mechanisms behind this resistance, we studied a total of 215 K. pneumoniae isolates from hospitals in Bushehr province, Iran, collected between 2017 and 2019. Antimicrobial susceptibility test for fluoroquinolones was determined. The presence of plasmid mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining region (QRDR) of gyrA and parC genes in ciprofloxacin-resistant K. pneumoniae isolates were identified by PCR and sequencing. Results Out of 215 K. pneumoniae isolates, 40 were resistant to ciprofloxacin as determined by E-test method. PCR analysis revealed that among these ciprofloxacin-resistant isolates, 13 (32.5%), 7 (17.5%), 40 (100%), and 25 (62.5%) isolates harbored qnrB , qnrS , oqxA and aac(6’)-Ib-cr genes, respectively. Mutation analysis of gyrA and parC genes showed that 35 (87.5%) and 34 (85%) of the ciprofloxacin-resistant isolates had mutations in these genes, respectively. The most frequent mutations were observed in codon 83 of gyrA and codon 80 of parC gene. Single gyrA substitution, Ser83→ Ile and Asp87→Gly, and double substitutions, Ser83→Phe plus Asp87→Ala, Ser83→Tyr plus Asp87→Ala, Ser83→Ile plus Asp87→Tyr, Ser83→Phe plus Asp87→Asn and Ser83→Ile plus Asp87→Gly were detected. In addition, Ser80→Ile and Glu84→Lys single substitution were found in parC gene. Conclusions Our results indicated that 90% of isolates have at least one mutation in QRDR of gyrA or parC genes, thus the frequency of mutations was very significant and alarming in our region.
Background Staphylococcus aureus , a Gram-positive bacterium, poses a significant threat to public health and food safety due to its virulence and its ability to develop antimicrobial resistance (AMR). Moreover, S. aureus can form biofilms in food environments, making it difficult to eradicate and pose a major challenge in foodborne illness prevention. Methods The study aimed to investigate the biofilm-forming capabilities and AMR profiles of 107 S. aureus isolates derived from milk, chicken meat, and chicken eggs. Further, the study compared the biofilm formation tendencies between multi-drug resistant (MDR) and non-MDR S. aureus isolates. Additionally, the research explored the antibacterial and anti-biofilm properties of Lactobacillus rhamnosus and Lactobacillus casei , focusing on their aggregation and co-aggregation effects with S. aureus. Results Around 70.10% of S. aureus isolates were found to be resistant to at least three antibiotic classes. The biofilm assay revealed that 16.82% isolates were strong biofilm formers. The MDR isolates displayed a strong biofilm-forming ability (i.e., 18.67%) and a higher prevalence of biofilm-associated genes [i.e., ica A (53.33%) and ica D (44.0%)] compared to non-MDR isolates. The LAB strain, L. rhamnosus exhibited a 29.06 mm mean antibacterial inhibition zone, an average reduction of 48.19% in biofilm growth, 55.46% auto-aggregation, and 40.61% co-aggregation with S. aureus . Similarly, L. casei demonstrated a 21.80 mm mean antibacterial inhibition zone, an average reduction of 31.56% in biofilm growth, 45.23% auto-aggregation, and 36.81% co-aggregation with S. aureus isolates. Conclusion This study provides valuable insights into the biofilm formation of MDR S. aureus and underscores the potential of L. rhamnosus and L. casei as bio-control agents. These findings highlight the necessity for additional research into the mechanisms through which LAB strains inhibit pathogenic biofilms and their potential applications in enhancing food safety.
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.
The functional role of glutamatergic (vGluT2) neurons in the pedunculopontine nucleus (PPN) in modulating motor activity remains controversial. Here, we demonstrated that the activity of vGluT2 neurons in the rostral PPN is correlated with locomotion and ipsilateral head-turning. Beyond these motor functions, we found that these rostral PPN-vGluT2 neurons remarkably respond to salient stimuli. Furthermore, we systematically traced the upstream and downstream projections of these neurons and identified two downstream projections from these neurons to the caudal pontine reticular nucleus/anterior gigantocellular reticular nucleus (PnC/GiA) and the zona incerta (ZI). Our findings indicate that the projections to the PnC/GiA inhibit movement, consistent with ‘pause-and-play’ behavior, whereas those to the ZI promote locomotion, and others respond to a new ‘pause-switch-play’ pattern. Collectively, these findings elucidate the multifaceted influence of the PPN on motor functions and provide a robust theoretical framework for understanding its physiological and potential therapeutic implications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-024-01314-y.
During natural behavior, an action often needs to be suddenly stopped in response to an unexpected sensory input—referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multielectrode recordings in male rats performing a stop-signal task. In this task, rats have to initiate movement to a go-signal, and occasionally stop their movement to the go-signal side after a stop-signal, presented at various stop-signal delays. Both the OFC and STN show near-simultaneous field potential reductions in the beta frequency range (12–30 Hz) compared with the period preceding the go-signal and the movement period. These transient reductions (∼200 ms) only happen during reactive stopping, which is when the stop-signal was received after action initiation, and are well timed after stop-signal onset and before the estimated time of stopping. Phase synchronization analysis also showed a transient attenuation of synchronization between the OFC and STN in the beta range during reactive stopping. The present results provide the first direct quantification of local neural oscillatory activity in the OFC and STN and interareal synchronization specifically timed during reactive stopping.
The automatic copying of other people—automatic imitation—is one of the most widely studied topics in psychology. In this chapter, we review current evidence for the neurophysiological correlates of automatic imitation. To do so, we focus on one heavily used and influential paradigm that manipulates stimulus-response compatibility and is conducive to investigation using neuroscientific methods. We distinguish between two distinct mental processes that occur during imitation: action representation and action selection. Observed actions are perceived and represented and a particular action needs to be selected to be executed. Neuroscientific evidence concerning action representation appears relatively robust and engages a widespread and distributed network of visual and motor regions that span the ventral visual stream, as well as frontoparietal cortex. In contrast, the neurophysiological correlates of action selection during imitation are far from clear. The dominant view in the literature is that this particular task indexes processes relating to the control of automatic imitative tendencies, which rely on a self-other distinction mechanism that is uniquely tied to human social interaction and engages the theory-of-mind network. However, our analysis shows that this claim lacks essential evidence for four forms of validity (construct, internal, external, and statistical-conclusion validities). Instead, given current evidence, the best estimate is that this task engages domain-general forms of control that are underpinned by the multiple-demand network. For claims to be supported regarding socially specific forms of control when using this task, there is a burden of proof on researchers to show robust evidence for each of the four validities that we have outlined. Fortunately, with the emergence of the meta-science movement over the past 10 years, there are more resources than ever to help achieve this aim. More generally, even though we focus on one imitation task to provide a thorough test-case example, given the widespread and well-established lack of validity in psychology in general, we fully expect our analysis to be relevant across the full range of imitation tasks covered in this book, including imitation of speech, gestures, and emotions.
The human brain, while incredibly remarkable, is also fragile and susceptible to various issues, including brain tumors and neurological disorders. Fortunately, advanced techniques enable us to detect these anomalies. This research paper focuses on efficiently detecting and analyzing brain tumor types from magnetic resonance imaging (MRI) images. The approach involves creating a deep learning model using EfficientNet convolutional neural network and employing ImageNet for data augmentation. This combination performs exceptionally well on grayscale MRI images from computed tomography scans, achieving a 99.8% accuracy across diverse image data. The model is resilient, working on limited hardware resources, and the web application functions well in low-bandwidth conditions. Besides tumor detection, it provides treatment suggestions, offering a comprehensive solution to various challenges. This project aims to be a sustainable solution, aiding doctors with consistently high accuracy and precision.
Oxford University PressSeptember 2024Neurosciences
OBJECTIVE: This observational study examined the accuracy of simple reaction time (RT) measurements on various touchscreen tablet devices using the Automated Neuropsychological Assessment Metric (ANAM) UltraMobile test battery. The study investigated the implications of interpreting ANAM UltraMobile with laptop-based normative data by analyzing the magnitude and variability of RT accuracy across devices. METHOD: RT accuracy on 10 different tablets was assessed using a photodetector and robotic arm to respond to stimuli at predetermined response times. The recorded RT was compared with the true RT obtained from the robotic arm to calculate the RT error. RESULTS: ANAM UltraMobile recorded slower RTs than the laptop version. Additionally, RT error varied considerably among the 10 tablet models, suggesting psychometrically significant implications that could lead to interpretive errors when using laptop-based normative data. CONCLUSIONS: Relative to the RT error from the laptop-based version of ANAM, tablet data from ANAM UltraMobile are significantly slower and exhibit large variability between devices. These differences may have clinically significant implications for the comparability of the two versions. The findings suggest that further research with human participants is needed to assess the equivalence of ANAM UltraMobile with its predecessor.
OBJECTIVE: Cognitive dysfunction has been observed consistently in a subset of breast cancer survivors. Yet the precise neurophysiological origins of cancer-related cognitive decline remain unknown. The current study assessed neural noise (1/f activity in electroencephalogram [EEG]) in breast cancer survivors as a potential contributor to observed cognitive dysfunction from pre- to post-treatment. METHODS: We measured EEG in a longitudinal design during performance of the paired-click task and the revised Attention Network Test (ANT-R) to investigate pre- versus post-treatment effects of neural noise in breast cancer patients (n = 20 in paired click; n = 19 in ANT-R) compared with healthy controls (n = 32 in paired click; n = 29 in ANT-R). RESULTS: In both paradigms, one sensory (paired click) and one cognitive (ANT-R), we found that neural noise was significantly elevated after treatment in patients, remaining constant from pretest to posttest in controls. In the ANT-R, patients responded more slowly than controls on invalid cuing trials. Increased neural noise was associated with poorer alerting and poorer inhibitory control of attention (as measured by behavioral network scores), particularly for patients after treatment. CONCLUSIONS: The current study is the first to show a deleterious effect of breast cancer and/or cancer treatment on neural noise, pointing to alterations in the relative balance of excitatory and inhibitory synaptic inputs, while also suggesting promising approaches for cognitive rehabilitation.
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.
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.
Advancements in neuroscience and educational research have provided new opportunities to understand and explore dyscalculia, a specific learning disability that impairs students’ abilities in math and numerical operations. Neuroscientific studies have pinpointed critical brain regions, such as the intraparietal sulcus and left angular gyrus, as central to numerical magnitude processing—a fundamental skill for math competence. Furthermore, the frontal, temporal, and occipital lobes are implicated in math tasks, indicating a comprehensive neural network involved in math cognition. Neuroplasticity underscores the brain’s adaptive responses to new learning experiences, which holds significant implications for educational practices, particularly in the instruction of math. Despite expanding research on dyscalculia, there remains a scarcity of empirical data on the effectiveness of interventions and math support programs specifically for students who are English learners (ELs) in U.S. schools. Educational strategies, such as Dynamic Strategic Math (DSM), integrate culturally relevant materials, multisensory learning, scaffolding, and ample practice to enhance math achievement and retention. By synthesizing empirical studies and meta-analyses, this chapter aims to (a) provide an overview of educational neuroscience research on dyscalculia and (b) establish connections between educational neuroscience research and classroom interventions for ELs with dyscalculia.
An implicit tenet of the alcohol use disorder (AUD) research field is that knowledge of how alcohol interacts with the brain is critical to the development of an understanding of vulnerability to AUD and treatment approaches. Gaining this understanding requires the mapping of brain function critical to specific components of this heterogeneous disorder. Early approaches in humans and animal models focused on the determination of specific brain regions sensitive to alcohol action and their participation in AUD-relevant behaviors. Broadly speaking, this research has focused on three domains, Binge/Intoxication, Negative Affect/Withdrawal, and Preoccupation/Anticipation, with a number of regions identified as participating in each. With the generational advances in technologies that the field of neuroscience has undergone over the last two decades, this focus has shifted to a circuit-based analysis. A wealth of new data has sharpened the field’s focus on the specific roles of the interconnectivity of multiple brain regions in AUD and AUD-relevant behaviors, as well as demonstrating that the three major domains described above have much fuzzier edges than originally thought. In this chapter, we very briefly review brain regions previously implicated in aspects of AUD-relevant behavior from animal model research. Next, we move to a more in-depth overview of circuit-based approaches, and the utilization of these approaches in current AUD research.
The nucleus accumbens (NAc) is thought to contribute to motivated behavior by signaling the value of reward-predicting cues and the delivery of anticipated reward. The NAc is subdivided into core and shell, with each region containing different populations of neurons that increase or decrease firing to rewarding events. While there are numerous theories of functions pertaining to these subregions and cell types, most are in the context of reward processing, with fewer considering that the NAc might serve functions related to action selection more generally. We recorded from single neurons in the NAc as rats of both sexes performed a STOP–change task that is commonly used to study motor control and impulsivity. In this task, rats respond quickly to a spatial cue on 80% of trials (GO) and must stop and redirect planned movement on 20% of trials (STOP). We found that the activity of reward-excited neurons signaled accurate response direction on GO, but not STOP, trials and that these neurons exhibited higher precue firing after correct trials. In contrast, reward-inhibited neurons significantly represented response direction on STOP trials at the time of the instrumental response. Finally, the proportion of reward-excited to reward-inhibited neurons and the strength of precue firing decreased as the electrode traversed the NAc. We conclude that reward-excited cells (more common in core) promote proactive action selection, while reward-inhibited cells (more common in shell) contribute to accurate responding on STOP trials that require reactive suppression and redirection of behavior.
Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown. We hypothesized that dysregulated acetylcholine (ACh) release upon demyelination contributes to ligand-mediated activation hindering myelin repair. Following chronic cuprizone (CPZ)-induced demyelination (male and female mice), we observed a 2.5-fold increase in ACh concentration. This increase in ACh concentration could be attributed to increased ACh synthesis or decreased acetylcholinesterase-/butyrylcholinesterase (BChE)-mediated degradation. Using choline acetyltransferase (ChAT) reporter mice, we identified increased ChAT-GFP expression following both lysolecithin and CPZ demyelination. ChAT-GFP expression was upregulated in a subset of injured and uninjured axons following intraspinal lysolecithin-induced demyelination. In CPZ-demyelinated corpus callosum, ChAT-GFP was observed in Gfap(+) astrocytes and axons indicating the potential for neuronal and astrocytic ACh release. BChE expression was significantly decreased in the corpus callosum following CPZ demyelination. This decrease was due to the loss of myelinating oligodendrocytes which were the primary source of BChE. To determine the role of ligand-mediated muscarinic signaling following lysolecithin injection, we administered neostigmine, a cholinesterase inhibitor, to artificially raise ACh. We identified a dose-dependent decrease in mature oligodendrocyte density with no effect on OPC recruitment. Together, these results support a functional role of ligand-mediated activation of muscarinic receptors following demyelination and suggest that dysregulation of ACh homeostasis directly contributes to failure of remyelination in MS.
Chronic sleep disruption (CSD), from insufficient or fragmented sleep and is an important risk factor for Alzheimer's disease (AD). Underlying mechanisms are not understood. CSD in mice results in degeneration of locus ceruleus neurons (LCn) and CA1 hippocampal neurons and increases hippocampal amyloid-β(42) (Aβ(42)), entorhinal cortex (EC) tau phosphorylation (p-tau), and glial reactivity. LCn injury is increasingly implicated in AD pathogenesis. CSD increases NE turnover in LCn, and LCn norepinephrine (NE) metabolism activates asparagine endopeptidase (AEP), an enzyme known to cleave amyloid precursor protein (APP) and tau into neurotoxic fragments. We hypothesized that CSD would activate LCn AEP in an NE-dependent manner to induce LCn and hippocampal injury. Here, we studied LCn, hippocampal, and EC responses to CSD in mice deficient in NE [dopamine β-hydroxylase (Dbh)(−/−)] and control male and female mice, using a model of chronic fragmentation of sleep (CFS). Sleep was equally fragmented in Dbh(−/−) and control male and female mice, yet only Dbh(−/−) mice conferred resistance to CFS loss of LCn, LCn p-tau, and LCn AEP upregulation and activation as evidenced by an increase in AEP-cleaved APP and tau fragments. Absence of NE also prevented a CFS increase in hippocampal AEP-APP and Aβ(42) but did not prevent CFS-increased AEP-tau and p-tau in the EC. Collectively, this work demonstrates AEP activation by CFS, establishes key roles for NE in both CFS degeneration of LCn neurons and CFS promotion of forebrain Aβ accumulation, and, thereby, identifies a key molecular link between CSD and specific AD neural injuries.
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.
The implementation of low-dimensional movement control by the central nervous system has been debated for decades. In this study, we investigated the dimensionality of the control signals received by spinal motor neurons when controlling either the ankle or knee joint torque. We first identified the low-dimensional latent factors underlying motor unit activity during torque-matched isometric contractions in male participants. Subsequently, we evaluated the extent to which motor units could be independently controlled. To this aim, we used an online control paradigm in which participants received the corresponding motor unit firing rates as visual feedback. We identified two main latent factors, regardless of the muscle group (vastus lateralis-medialis and gastrocnemius lateralis-medialis). The motor units of the gastrocnemius lateralis could be controlled largely independently from those of the gastrocnemius medialis during ankle plantarflexion. This dissociation of motor unit activity imposed similar behavior to the motor units that were not displayed in the feedback. Conversely, it was not possible to dissociate the activity of the motor units between the vastus lateralis and medialis muscles during the knee extension tasks. These results demonstrate that the number of latent factors estimated from linear dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units. Overall, individual motor units were never controlled independently of all others but rather belonged to synergistic groups. Together, these findings provide evidence for a low-dimensional control of motor units constrained by common inputs, with notable differences between muscle groups.
We employ Reinforcement Learning (RL) models to unravel the mechanisms behind the learning behavior of two macaque monkeys engaged in a free-moving multi-target reaching task. The study was conducted using computer simulations reflecting the animal’s learning conditions, and compared with the actual arm movements recorded on two macaque monkeys on a Kinarm apparatus. Our paper thus provides important insights for the design of motor control learning systems, combining end-effector control design with the learning of motor chunks associations. Our research is of interest for the modeling and understanding of natural motor learning systems, but also heads toward the design of more “brain-inspired” adaptive robotic manipulators.
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.
Brain-based learning aligns educational strategies with the brain’s natural processes for absorbing, retaining, and applying knowledge. The purpose of this chapter is to explain the neurophysiology of learning and provide practical strategies that work with, rather than against, the brain’s natural learning mechanisms. When nursing students understand why certain approaches are more effective—like spaced repetition, chunking information, and active reflection—they are able to embrace these methods in their learning. The relationship between brain-based learning and critical thinking is explored through practical examples of how nursing students can apply these concepts in classroom, clinical, and simulation settings. Case studies demonstrate how understanding concepts like neurotransmitter function, memory formation, and the role of sleep in learning helps students optimize their study habits and learning techniques. Interactive learning activities and chapter synthesis exercises help students apply and integrate key concepts.
Migraine is a prevalent neurological disorder which encompasses severe headaches accompanied by various sensory sensitivities. When it becomes chronic, characterized by frequent attacks, it can be a very disabling disease with significant social and economic burdens. The typical treatment options for chronic migraine are pharmacological and non-pharmacological, with mixed and unsatisfying outcomes. Indeed, the effective management involves identifying triggers, modifying risk factors, and balancing pharmacological and non-pharmacological treatments to minimize medication overuse and address other possible associated factors, included mental health issues. In this chapter, we will analyze the topic of catastrophizing in migraine. Catastrophizing is a psychological characteristic of migraineurs. It consists of a disadaptive mindset made of irrational beliefs where negative events are exaggerated leading to heightened emotional distress and a belief in worst-case scenarios, while doubting one’s ability to cope. Catastrophic thinking can result in feelings of helplessness, depression, and anxiety, representing an extreme form of worrying that extends into pathological symptoms. Many literature studies documented catastrophizing in migraine, in both clinical and experimental settings, and some studies also revealed that some social variables, such as stigma for chronic illness, can mediate the relationship between migraine symptoms and catastrophizing. This negative mindset impacts not only adults but also children with migraines, with consequences on their overall quality of life, and parental catastrophizing can worsen their tendency toward catastrophic thoughts. Recently, also neuroscience investigated the relation between migraine and catastrophizing, finding changes in brain connectivity and central sensitization mechanisms as possible contributors. Nevertheless, the exact underlying mechanisms remain incompletely understood. To date, pharmacological treatments such as erenumab and OnabotulinumtoxinA and non-pharmacological treatments such as neurostimulation or behavioral approaches showed efficacy in relieving both migraine symptoms and catastrophizing, sometimes revealing some placebo effects. In this case as well, further studies delving into techniques such as mindfulness, psychoeducational interventions, and cognitive-behavioral therapy will be useful in determining the effectiveness of these treatments. To conclude, migraine is not the only chronic pain disease characterized by the catastrophic thinking. Indeed, many studies documented the presence of this cognitive feature in rheumatic diseases such as fibromyalgia, or in painful neuropathies. Also in this case, neuroimaging helped in revealing some cortical abnormalities which may contribute to the relation between catastrophizing and chronic pain symptoms. Further studies are needed to explore this relation while psychological intervention aimed at this cognitive schema would be helpful for patients in getting out from the negative loop of catastrophizing and awfulizing, possibly developing a more optimistic outlook, or at least acceptance, toward debilitating conditions such as those characterized by chronic pain.
This chapter offers a detailed examination of the neurophysiological mechanisms underlying neural activity, emphasizing the roles of neurotransmitters, neuroplasticity, and the effects of psychoactive substances. It starts with a discussion of fundamental neuronal functions, including action potentials and synaptic transmission. The chapter then explores long-term potentiation (LTP) and long-term depression (LTD) as critical mechanisms of synaptic plasticity. It further investigates the involvement of neurotransmission systems in various brain circuits related to inhibitory control, decision-making, and reward processing. The impact of psychoactive substances on these systems is analyzed, highlighting changes in neurotransmitter balance and subsequent neuroplastic adaptations. Particular attention is given to the mesocorticolimbic pathway and its modulation by drugs of abuse, as well as the roles of glutamate and GABAergic systems. The chapter concludes by examining the effects of substance use on brain function and behavior, particularly how these alterations persist during withdrawal and influence overall neuroadaptation.
The blood-brain barrier (BBB) is an essential physiological separator that controls substance movement into the central nervous system (CNS) and is crucial for CNS stability. However, the neuroprotective role of the BBB, especially in disease states, presents significant challenges for brain drug delivery. This is evident in conditions with overactive efflux transporters, which prevent drugs from reaching target brain tissues or achieving effective concentrations. These complexities have led to a rise in utilizing a variety of deep learning (DL) models, including the employment of neural network models and support vector machines to predict drug permeability across the BBB and develop personalized care for CNS disorders. Furthermore, the high specificity and accuracy of these models, along with their increased efficiency, make them more favorable than traditional models as well as machine learning. However, the complexity of DL models, data imbalances, and the opaque nature of these algorithms present ongoing challenges. Despite these challenges, DL models have the potential to truly innovate the sphere of personalized medicine, especially in terms of neurological therapies.
Tau pathologies are detected in the brains of some of the most common neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), chronic traumatic encephalopathy (CTE), and frontotemporal dementia (FTD). Tau proteins are expressed in six isoforms with either three or four microtubule-binding repeats (3R tau or 4R tau) due to alternative RNA splicing. AD, LBD, and CTE brains contain pathological deposits of both 3R and 4R tau. FTD patients can exhibit either 4R tau pathologies in most cases or 3R tau pathologies less commonly in Pick's disease, which is a subfamily of FTD. Here, we report the isoform-specific roles of tau in FTD. The P301L mutation, linked to familial 4R tau FTD, induces mislocalization of 4R tau to dendritic spines in primary hippocampal cultures that were prepared from neonatal rat pups of both sexes. Contrastingly, the G272V mutation, linked to familial Pick's disease, induces phosphorylation-dependent mislocalization of 3R tau but not 4R tau proteins to dendritic spines. The overexpression of G272V 3R tau but not 4R tau proteins leads to the reduction of dendritic spine density and suppression of mEPSCs in 5-week-old primary rat hippocampal cultures. The decrease in mEPSC amplitude caused by G272V 3R tau is dynamin-dependent whereas that caused by P301L 4R tau is dynamin-independent, indicating that the two tau isoforms activate different signaling pathways responsible for excitatory synaptic dysfunction. Our 3R and 4R tau studies here will shed new light on diverse mechanisms underlying FTD, AD, LBD, and CTE.
While the exertion of mental effort improves performance on cognitive tasks, the neural mechanisms by which motivational factors impact cognition remain unknown. Here, we used fMRI to test how changes in cognitive effort, induced by changes in task difficulty, impact neural representations of working memory (WM). Participants (both sexes) were precued whether WM difficulty would be hard or easy. We hypothesized that hard trials demanded more effort as a later decision required finer mnemonic precision. Behaviorally, pupil size was larger and response times were slower on hard compared with easy trials suggesting our manipulation of effort succeeded. Neurally, we observed robust persistent activity during delay periods in the prefrontal cortex (PFC), especially during hard trials. Yet, details of the memoranda could not be decoded from patterns in prefrontal activity. In the patterns of activity in the visual cortex, however, we found strong decoding of memorized targets, where accuracy was higher on hard trials. To potentially link these across-region effects, we hypothesized that effort, carried by persistent activity in the PFC, impacts the quality of WM representations encoded in the visual cortex. Indeed, we found that the amplitude of delay period activity in the frontal cortex predicted decoded accuracy in the visual cortex on a trial-wise basis. These results indicate that effort-related feedback signals sculpt population activity in the visual cortex, improving mnemonic fidelity.
Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HT(DRN) circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.
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There is a continued unmet need for treatments that can slow Parkinson's disease progression due to the lack of understanding behind the molecular mechanisms underlying neurodegeneration. Since its discovery, ferroptosis has been implicated in several diseases and represents a therapeutic target in Parkinson's disease. Here, we use two highly relevant human dopaminergic neuronal models to show that endogenous levels of α-synuclein can determine the sensitivity of dopaminergic neurons to ferroptosis. We show that reducing α-synuclein expression in dopaminergic neurons leads to ferroptosis evasion, while elevated α-synuclein expression in patients' small-molecule-derived neuronal precursor cells with SNCA triplication causes an increased vulnerability to lipid peroxidation and ferroptosis. Lipid profiling reveals that ferroptosis resistance is due to a reduction in ether-linked phospholipids, required for ferroptosis, in neurons depleted of α-synuclein (α-syn). These results provide a molecular mechanism linking α-syn levels to the sensitivity of dopaminergic neurons to ferroptosis, suggesting potential therapeutic relevance.
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Parkinson's disease is a neurodegenerative disease that affects more than 6.1 million people worldwide. In the clinical routine, the main tool to diagnose and monitor disease progression is based on motor impairments, such as postural instability, bradykinesia, tremor, among others. Besides, new biomarkers based on motion patterns have emerged to describe disease findings. Nonetheless, this motor characterization has low sensitivity, especially at early stages, and is largely expert-dependent, because protocols are mainly based on visual observations. However, most of these analyses require complex and some invasive systems that additionally only bring global information of complete recordings. This work introduces a multimodal approach that integrates gait and eye motion videos to quantify and predict patient stage on-the-fly. This method starts by computing dense apparent velocity maps that represent the local displacement of the person seen from the gait in a sagittal plane and as micro-movements during the fixation experiment. Then, each frame is described as a covariance descriptor of deep feature activation maps computed over the motion field at each video time. Then, the covariance video manifold is mapped to a recurrent LSTM network to learn higher non-local dependencies and quantify a motion descriptor. Also, an end-to-end scheme allows to lately fuse both modalities (gait and fixational eye) to obtain a more sensitive Parkinson disease descriptor. In a study with 25 subjects, the proposed approach reaches an average F1-score of 0.83 with an average recall of 0.78. In a temporal prediction analysis, the approach reports major correlations with the disease considering swing phase.
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.
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Acoustic realisation of the working vowel space has been widely studied in Parkinson's disease (PD). However, it has never been studied in atypical parkinsonian disorders (APD). The latter are neurodegenerative diseases which share similar clinical features with PD, rendering the differential diagnosis very challenging in early disease stages. This paper presents the first contribution in vowel space analysis in APD, by comparing corner vowel realisation in PD and the parkinsonian variant of Multiple System Atrophy (MSA-P). Our study has the particularity of focusing exclusively on early stage PD and MSA-P patients, as our main purpose was early differential diagnosis between these two diseases. We analysed the corner vowels, extracted from a spoken sentence, using traditional vowel space metrics. We found no statistical difference between the PD group and healthy controls (HC) while MSA-P exhibited significant differences with the PD and HC groups. We also found that some metrics conveyed complementary discriminative information. Consequently, we argue that restriction in the acoustic realisation of corner vowels cannot be a viable early marker of PD, as hypothesised by some studies, but it might be a candidate as an early hypokinetic marker of MSA-P (when the clinical target is discrimination between PD and MSA-P).
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People with Parkinson's disease (PwPD) exhibit various sexual difficulties (SDs) that may be due to motor and/or nonmotor symptoms or the use of antiparkinsonian medication. SDs are often underreported by PwPD and underexplored by physicians. This study aimed to explore the SDs experienced by PwPD and create a scale for assessing them. A corpus of items was generated from semistructured interviews to represent the experience of PwPD as closely as possible. The number of items was reduced according to the psychometric properties, and the scale's structure was subsequently examined. The final phase consisted of measuring the scale's validity and reliability. After assessment of the original corpus of 59 items by PwPD and clinicians, a 25-item version was obtained. The analysis of item properties led to the removal of fifteen items. An exploratory factor analysis of the first 10-item version with a first PwPD sample identified four components of the SDs among PwPD: "low sexual esteem," "sexual displeasure," "impact on sexual position" and "hypersexuality." With a second PwPD sample, a confirmatory factor analysis demonstrated a satisfactory fit between the model with four components and the data. The 10-item scale had good internal consistency and good temporal reliability. The Parkinson's Disease Sexual Difficulties Scale (PD-SDS) is a valid screening tool that facilitates the investigation of and communication about PD-related SDs. It is intended to improve the identification of vulnerable PwPD and to target the domain of sexual experience impacted by PD to better support PwPD.
Dementia in Parkinson's disease (PD) has become a major factor affecting the quality of life of patients with Parkinson's disease. Early detection and timely prevention can delay the progression of dementia, improve the quality of life of patients, and reduce the burden on society. This article is aimed at studying how to analyze the efficacy of moxibustion in the treatment of Parkinson's disease through meta-analysis on the basis of smart medicine. This article puts forward the related conceptual knowledge of smart medicine and meta-analysis and moxibustion treatment and proposes a deep learning method based on smart medicine to analyze the effects of moxibustion treatment on patients. The experiment in this article can be seen from the data in one of the figures that the highest curative effect of using a single moxibustion to treat Parkinson's disease is about 46%, while the curative effect of using a combination of moxibustion and Western medicine has reached 90%. It can be seen that a single moxibustion is not as effective as a combination of the two for Parkinson's disease. From the data in one of the tables, it can be seen that the proportion of Parkinson's disease in 2016 was 15%, showing an increase of 5%. By 2020, the proportion of Parkinson's disease was as high as 38%, and the growth rate reached 9%. It can be seen that the prevalence of this disease is getting higher and higher. Parkinson's disease has caused many undesirable effects on patients, such as slow movement, mental disorders, and a decline in mental state. Therefore, it is urgent to study the treatment of Parkinson's disease. Moxibustion can improve the patient's blood circulation and help the patient's local limbs to recover more easily and can help improve the patient's motor function.
Background Several non-motor symptoms are present in Parkinson's disease (PD), including increasing prevalence rates of cognitive impairment during disease progression. Due to its multifaceted nature, PD management involves pharmacotherapy and non-pharmacotherapies, ideally in a multidisciplinary manner. Evidence regarding the impact of multidisciplinary interventions on motor and non-motor symptoms, as well as its impact on quality of life and daily activities of living, is limited. Methods The aim of this real-life exploratory study was to investigate the effectiveness of a three-week clinical multidisciplinary Parkinson complex therapy (Parkinson-Komplexbehandlung, PKB), which is available as standard care for PD in the German health care system. Especially, the effect of neuropsychological attention training of 40 patients with PD was analyzed concerning their impact on motor abilities (UPDRS-III ON state), cognitive profiles and reported depressive symptoms and psychosocial function. Results Neuropsychological data showed an improvement in response inhibition after intervention ( z = − 2.611, p = 0.009). Additionally, improvements in verbal memory ( z = − 2.318, p = 0.020), motor functions (UPDRS-III-score; z = − 5.163, p < 0.001) and reduction in depression symptoms (BDI-II) ( z = − 2.944, p = 0.003) were also present. Conclusions Patients with PD benefited from this multidisciplinary Parkinson complex therapy in terms of improved cognitive functioning, including attention and verbal learning, motor symptoms and emotional well-being.
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Objective The purpose of this study was to simultaneously contrast prediagnostic clinical characteristics of individuals with a final diagnosis of dementia with Lewy Bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD) compared with controls without neurodegenerative disorders. Methods Using the longitudinal THIN database in the United Kingdom, we tested the association of each neurodegenerative disorder with a selected list of symptoms and broad families of treatments, and compared the associations between disorders to detect disease‐specific effects. We replicated the main findings in the UK Biobank. Results We used data of 28,222 patients with PD, 20,214 with AD, 4,682 with DLB, and 20,214 healthy controls. All neurodegenerative disorders were significantly associated with the presence of multiple clinical characteristics before their diagnosis, including sleep disorders, falls, psychiatric symptoms, and autonomic dysfunctions. When comparing patients with DLB with patients with PD and patients with AD patients, falls, psychiatric symptoms, and autonomic dysfunction were all more strongly associated with DLB in the 5 years preceding the first neurodegenerative diagnosis. The use of statins was lower in patients who developed PD and higher in patients who developed DLB compared to patients with AD. In patients with PD, the use of statins was associated with the development of dementia in the 5 years following PD diagnosis. Interpretation Prediagnostic presentations of falls, psychiatric symptoms, and autonomic dysfunctions were more strongly associated with DLB than PD and AD. This study also suggests that although several associations with medications are similar in neurodegenerative disorders, statin usage is negatively associated with PD but positively with DLB and AD as well as development of dementia in PD.
Cold Spring Harbor LaboratoryFebruary 2023Parkinson
Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson’s Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 (-5) ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.
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Background<p>Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later.</p></div> <div>Methods<p>We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these prodromal factors and the risk of receiving a diagnosis of AD, PD, or ALS.</p></div> <div>Findings<p>We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later.</p></div> <div>Interpretation<p>Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics are specific to ALS.</p></div> <div>Funding<p>EU Joint Programme -Neurodegenerative Disease Research.
Background In the daily life of individuals living with Parkinson's disease, their loved ones are crucial. Adapting family members to the patient's condition, support in providing care, and psychosocial adaptations is essential. Aim To explore family members' perception of everyday caregiving for a family member living with Parkinson's disease and to describe their role in the care and everyday life. Methods In a descriptive, qualitative thematic analysis study, semi-structured interviews were conducted with ten people between the ages of 20 and 70, the closest family members of people living with Parkinson's disease. The analysis of the collected data was carried out using thematic analysis. Results We generated the main theme: "Living with a family member with Parkinson’s disease", with associated secondary-level sub-themes: “Response”, “Change”, “Care”, and “Support”. Family members of individuals living with Parkinson's disease frequently encounter similar life situations. The most notable transformation in their daily lives primarily revolves around adapting to various activities. Conclusions Family members are the ones who most often take on the role of caregiver and provide help to their loved ones. Many of them accept the disease as a part of everyday life and learn to live with it. It is of fundamental importance that we offer family members the necessary support, knowledge, and involvement in holistic treatment and care.
My thesis is based on three axes: to develop a biophysical model, to propose a simulation tool, and exploit the model in simulation.We develop a biophysical model of the neuronal structure involved in Parkinson's disease, the basal ganglia. We simulate physiologically realistic neurons using the Hodgkin-Huxley formalism to incorporate specific ion channels present in different populations of GB neurons, including arkipallidal and proptotypic GPe, as well as dopaminergic D1 and D2 neurons in the striatum, whose cellular properties and connectivity appear to be prominent factors in the oscillatory behavior of the network. Our model is validated by experimental data in healthy conditions of the rat, collected by our biologist collaborators.We propose a simulation tool for impulse neural networks allowing realistic simulations on a large scale, > 1 million neurons, on a parallel machine i.e. Grid'5000, Explor, etc... SiReNe is a neural network simulator developed in the C language. This software is based on a hybrid simulation approach. It combines a numerical integration, Runge-Kutta 2, of the neuronal dynamics and an event-driven generation of the network connectivity during action potentials emissions. This approach, developed during the thesis, allows the simulation of large and very detailedneural networks of the Hodgkin-Huxley type.In the future, our model could be used in simulation to test some hypotheses on the pathological synchronization observed in Parkinson's disease. Like the role of GABAergic synaptic connections and the intrinsic neuronal properties of SK channels which control the precision of neuronal discharge. The simulation of large-scale models could be used to limit pathological synchronization and motor disorders through new neurostimulation methods, such as deep brain stimulation.
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Ma thèse s'articule autour de trois axes : développer un modèle biophysique, proposer un outil de simulation et exploiter le modèle en simulation. Développer un modèle biophysique de la structure neuronale impliquée dans la maladie de Parkinson, les ganglions de la base. Nous simulons des neurones physiologiquement réalistes à l'aide du formalisme d'Hodgkin-Huxley permettant d'intégrer des canaux ioniques spécifiques. Dans les différentes populations de neurones des GB, dont les arkipallidaux et les proptotypiques du GPe, ainsi que les neurones dopaminergiques D1 et D2 du striatum, les propriétés cellulaires et la connectivité semblent être des facteurs prépondérants dans le comportement oscillatoire du réseau. Notre modèle est validé par des données expérimentales en condition saine, recueillies par nos collaborateurs biologistes, chez le rat. Proposer un outil de simulation de réseaux de neurones impulsionnels permettant des simulations réalistes à grande échelle, > 1 million de neurones, sur machine parallèle i.e plateformes Grid'5000, Explor, etc... SiReNe est un simulateur de réseaux de neurones développé en langage C. Ce logiciel s'appuie sur une approche de simulation combinant une intégration numérique, Runge-Kutta 2, de la dynamique neuronale, et d'une génération événementielle de la connectivité du réseau lors des émissions des potentiels d'action. Cette approche hybride, développée pendant la thèse, permet de simuler des grands réseaux de neurones très détaillés du type Hodgkin-Huxley. Dans le futur, notre modèle pourra être exploité en simulation pour tester certaines hypothèses sur la synchronisation pathologique observée dans la maladie de Parkinson. Les hypothèses que nous envisageons d'étudier portent, principalement, sur le rôle des connexions synaptiques GABAergiques, et des propriétés neuronales, intrinsèques, des canaux SK qui contrôlent la précision de la décharge neuronale. La simulation de modèles à grande échelle pourra, notamment, être utilisée pour limiter la synchronisation pathologique, et les troubles moteurs, par le biais de nouvelles méthodes de neurostimulation, comme la stimulation cérébrale profonde.
PPINtonus is a system for the early detection of Parkinson's Disease (PD)
utilizing deep-learning tonal analysis, providing a cost-effective and
accessible alternative to traditional neurological examinations. Partnering
with the Parkinson's Voice Project (PVP), PPINtonus employs a semi-supervised
conditional generative adversarial network to generate synthetic data points,
enhancing the training dataset for a multi-layered deep neural network.
Combined with PRAAT phonetics software, this network accurately assesses
biomedical voice measurement values from a simple 120-second vocal test
performed with a standard microphone in typical household noise conditions. The
model's performance was validated using a confusion matrix, achieving an
impressive 92.5 \% accuracy with a low false negative rate. PPINtonus
demonstrated a precision of 92.7 \%, making it a reliable tool for early PD
detection. The non-intrusive and efficient methodology of PPINtonus can
significantly benefit developing countries by enabling early diagnosis and
improving the quality of life for millions of PD patients through timely
intervention and management.
Cortical cholinergic deficits contribute to cognitive decline and other deficits in Parkinson's disease. Cross-sectional imaging studies suggest a stereotyped pattern of posterior-to-anterior cortical cholinergic denervation accompanying disease progression in Parkinson's disease. We used serial acetylcholinesterase PET ligand imaging to characterize the trajectory of regional cholinergic synapse deficits in Parkinson's disease, testing the hypothesis of posterior-to-anterior progression of cortical cholinergic deficits. The 16 Parkinson's disease subjects (4 females/12 males; mean age: 64.4 ± 6.7 years; disease duration: 5.5 ± 4.2 years; Hoehn & Yahr stage: 2.3 ± 0.6 at entry) completed serial (11)C-methyl-4-piperidinyl propionate acetylcholinesterase PET scans over a 4–8 year period (median 5 years). Three-dimensional stereotactic cortical surface projections and volume-of-interest analyses were performed. Cholinergic synapse integrity was assessed by the magnitude, k(3), of acetylcholinesterase hydrolysis of (11)C-methyl-4-piperidinyl propionate. Based on normative data, we generated Z-score maps for both the k(3) and the k(1) parameters, the latter as a proxy for regional cerebral blood flow. Compared with control subjects, baseline scans showed predominantly posterior cortical k(3) deficits in Parkinson’s disease subjects. Interval change analyses showed evidence of posterior-to-anterior progression of cholinergic cortical deficits in the posterior cortices. In frontal cortices, an opposite gradient of anterior-to-posterior progression of cholinergic deficits was found. The topography of k(3) changes exhibited regionally specific disconnection from k(1) changes. Interval-change analysis based on k(3)/k(1) ratio images (k(3) adjustment for regional cerebral blood flow changes) showed interval reductions (up to 20%) in ventral frontal, anterior cingulate and Brodmann area 6 cortices. In contrast, interval k(3) reductions in the posterior cortices, especially Brodmann areas 17–19, were largely proportional to k(1) changes. Our results partially support the hypothesis of progressive posterior-to-cortical cholinergic denervation in Parkinson’s disease. This pattern appears characteristic of posterior cortices. In frontal cortices, an opposite pattern of anterior-to-posterior progression of cholinergic deficits was found. The progressive decline of posterior cortical acetylcholinesterase activity was largely proportional to declining regional cerebral blood flow, suggesting that posterior cortical cholinergic synapse deficits are part of a generalized loss of synapses. The disproportionate decline in regional frontal cortical acetylcholinesterase activity relative to regional cerebral blood flow suggests preferential loss or dysregulation of cholinergic synapses in these regions. Our observations suggest that cortical cholinergic synapse vulnerability in Parkinson's disease is mediated by both diffuse processes affecting cortical synapses and processes specific to subpopulations of cortical cholinergic afferents.
BACKGROUND: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. METHODS: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. FINDINGS: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of −9.1 points (95% CI, −11.8 to −6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR −26.0 to 0.0) in the EA group and 2.5 points (IQR: −11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. INTERPRETATION: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. FUNDING: Shanghai “Science and Technology Innovation Action Plan” Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).
Using speech samples as a biomarker is a promising avenue for detecting and monitoring the progression of Parkinson's disease (PD), but there is considerable disagreement in the literature about how best to collect and analyze such data. Early research in detecting PD from speech used a sustained vowel phonation (SVP) task, while some recent research has explored recordings of more cognitively demanding tasks. To assess the role of language in PD detection, we tested pretrained models with varying data types and pretraining objectives and found that (1) text-only models match the performance of vocal-feature models, (2) multilingual Whisper outperforms self-supervised models whereas monolingual Whisper does worse, and (3) AudioSet pretraining improves performance on SVP but not spontaneous speech. These findings together highlight the critical role of language for the early detection of Parkinson's disease. ;Accepted to IEEE Workshop on Machine Learning for Signal Processing (MLSP) 2025
Parkinson's disease (PD) is a neurodegenerative disease affecting about 1% of people over the age of 60, causing motor impairments that impede hand coordination activities such as writing and drawing. Many approaches have tried to support early detection of Parkinson's disease based on hand-drawn images; however, we identified two major limitations in the related works: (1) the lack of sufficient datasets, (2) the robustness when dealing with unseen patient data. In this paper, we propose a new approach to detect Parkinson's disease that consists of two stages: The first stage classifies based on their drawing type(circle, meander, spiral), and the second stage extracts the required features from the images and detects Parkinson's disease. We overcame the previous two limitations by applying a chunking strategy where we divide each image into 2x2 chunks. Each chunk is processed separately when extracting features and recognizing Parkinson's disease indicators. To make the final classification, an ensemble method is used to merge the decisions made from each chunk. Our evaluation shows that our proposed approach outperforms the top performing state-of-the-art approaches, in particular on unseen patients. On the NewHandPD dataset our approach, it achieved 97.08% accuracy for seen patients and 94.91% for unseen patients, our proposed approach maintained a gap of only 2.17 percentage points, compared to the 4.76-point drop observed in prior work. ;19 pages, 2 figures, 9 tables
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Neuropeptides are bioactive molecules, made up of small chains of amino acids, with many neuromodulatory properties. Several lines of evidence suggest that neuropeptides, mainly expressed in the central nervous system (CNS), play an important role in the onset of Parkinson's Disease (PD) pathology. The wide spread disruption of neuropeptides has been excessively demonstrated to be related to the pathophysiological symptoms in PD where impairment in motor function per example was correlated with neuropeptides dysregulation in the substantia niagra (SN). Moreover, the levels of different neuropeptides have been found modified in the cerebrospinal fluid and blood of PD patients, indicating their potential role in the manifestation of PD symptoms and dysfunctions. In this review, we outlined the neuroprotective effects of neuropeptides on dopaminergic neuronal loss, oxidative stress and neuroinflammation in several models and tissues of PD. Our main focus was to elaborate the role of orexin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), opioids, angiotensin, carnosine and many others in the protection and/or involvement in the neurodegeneration of striatal dopaminergic cells. Further studies are required to better assess the mode of action and cellular mechanisms of neuropeptides in order to shift the focus from the in vitro and in vivo testing to applicable clinical testing. This review, allows a support for future use of neuropeptides as therapeutic solution for PA pathophysiology.
Biomechanical analysis of gait initiation (GI) and steady state gait is necessary to understand motor dysfunctions associated with aging and neurological pathologies. This biomechanical analysis classically uses two types of system: force platforms (PF) and/or cameras with markers (CAM). However, both systems have their own specific constraints, e.g. spatial constraints for PFs, signal processing difficulties for PF and CAM, preparation time for experimental subjects, potential errors in segmental marker positioning for CAM, etc.). The markerless camera system represents an innovative solution to overcome all these constraints. The aim of this thesis is threefold: I) to validate the use of a markerless motion capture system for the biomechanical analysis of GI in a group of young healthy adults, a group of elderly healthy subjects and a group of subjects with Parkinson's disease (study 1 & 2); II) to assess the suitability of the Bootstrap statistical method coupled with principal component analysis to reliably differentiate on the basis of classical biomechanical variables of GI the three “target” populations of our study (study 3);III) to determine how many steps are required in GI to achieve steady state gait in these three populations (Study 4). The results of studies 1 & 2 validated the use of the markerless system to assess motor performance and postural stability during GI in our three populations, while highlighting the limitations of this system. The results of Study 3 highlighted the suitability of the Bootstrap method coupled with principal component analysis to discriminate Parkinsonian patients from healthy subjects with 98% accuracy. The results of Study 4 showed that two steps were necessary to reach a stationary state of postural stability and motor performance in a walking situation at spontaneous and maximum speed, in all three of our populations. However, the motor strategies used to achieve this stationary state differed between healthy subjects and Parkinson's patients. The overall results of this thesis should have potentially important repercussions in terms of movement analysis and clinical application, particularly in terms of Parkinson's disease detection and motor rehabilitation.
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L'analyse biomécanique de l'initiation de la marche (IM) et de la marche établie est nécessaire pour comprendre les dysfonctionnements moteurs liés au vieillissement et aux pathologies neurologiques. Cette analyse biomécanique implique classiquement deux types de système : plateformes de force (PF) et/ou caméras avec marqueurs (CAM). Ces deux systèmes présentent cependant des contraintes d'utilisation spécifiques, e.g. contraintes spatiales pour les PF, difficulté de traitement des signaux pour les PF et les CAM, durée de préparation des sujets expérimentaux, erreurs potentielles sur le positionnement des marqueurs segmentaires pour les CAM etc.). Le système de caméras sans marqueur constitue une solution innovante permettant de surmonter l'ensemble de ces contraintes. L'objectif de cette thèse est triple : I) valider l'utilisation d'un système de capture du mouvement sans marqueur pour l'analyse biomécanique de l'IM dans un groupe de jeunes adultes sains, un groupe de sujets âgés sains et un groupe de sujets atteints de la maladie de Parkinson (étude 1 & 2); II) évaluer la pertinence de la méthode statistique de Bootstrap couplée à l'analyse en composante principale pour différencier de façon fiable sur la base de variables biomécaniques classiques de l'IM les trois populations « cible » de notre étude (étude 3);III) déterminer combien de pas sont nécessaires à l'IM pour atteindre la marche établie dans ces trois populations (étude 4). Les résultats des études 1 & 2 ont permis de valider l'utilisation du système sans marqueurs pour évaluer la performance motrice et la stabilité posturale lors de l'IM dans nos trois populations, tout en soulignant les limitations de ce système. Les résultats de l'étude 3 ont mis en évidence la pertinence de la méthode de Bootstrap couplée à l'analyse en composante principale pour discriminer les patients parkinsoniens des sujets sains avec une précision de 98%. Les résultats de l'étude 4 ont mis en évidence que deux pas étaient nécessaires pour atteindre un état stationnaire de stabilité posturale et de performance motrice en situation de marche à vitesse spontanée et maximale, et ce, dans nos trois populations. Les stratégies motrices pour atteindre cet état stationnaire étaient cependant différentes entre les sujets sains et les patients parkinsoniens. L'ensemble des résultats de cette thèse devrait entraîner des répercussions potentiellement importantes en termes d'analyse du mouvement et d'application clinique, notamment en termes de détection de la maladie de Parkinson et de réhabilitation motrice.
Several epidemiological studies have identified associations between lifestyle exposures and Parkinson's disease (PD). However, given the long prodromal phase of PD, reverse causation bias may explain some of the associations previously reported. In addition, women are an understudied group in PD research since PD is more frequent in men than women.The aim of this thesis was to examine the relation of potentially modifiable health behaviours (physical activity, adiposity) and diabetes, with PD incidence in about 100,000 women from the French E3N cohort study over 29 years of follow-up, while accounting for the risk of reverse causation using appropriate statistical methods.We showed that higher levels of physical activity and adiposity were associated with a lower incidence of PD in women, while no association was found between diabetes and PD incidence. Analyses of trajectories suggest that reverse causation is unlikely to explain our results.This work underscores the importance of large cohort studies with long follow-ups to address the potential for reverse causation. Physical activity seems to be the most promising lifestyle intervention in terms of its potential to prevent PD. Further studies are needed to understand the mechanisms underlying the inverse association between obesity and PD and to confirm the lack of association between diabetes and PD.
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Plusieurs études épidémiologiques ont identifié des associations entre des expositions liées au mode de vie et la maladie de Parkinson (MP). Cependant, compte tenu de la longue phase prodromale de la MP, un biais de causalité inverse pourrait expliquer certaines des associations précédemment rapportées. De plus, les femmes constituent un groupe sous-étudié dans la recherche sur la MP, car la MP est plus fréquente chez les hommes que chez les femmes.L'objectif de cette thèse était d'examiner la relation entre des comportements de santé potentiellement modifiables (activité physique, adiposité) et le diabète avec l'incidence de la MP chez environ 100 000 femmes participant à l'étude de cohorte française E3N, au cours de 29 ans de suivi, tout en tenant compte du risque de causalité inverse grâce à des méthodes statistiques adaptées.Nos résultats ont montré que des niveaux plus élevés d'activité physique et d'adiposité étaient associés à une incidence plus faible de la MP chez les femmes, alors qu'aucune association n'a été retrouvée entre le diabète et l'incidence de la MP. Les analyses de trajectoires suggèrent que la causalité inverse n'explique vraisemblablement pas nos résultats.Ces travaux soulignent l'importance des études de cohortes de grande taille avec un long suivi pour prendre en compte le risque de causalité inverse dans l'étude des maladies neurodégénératives. L'activité physique nous semble être l'intervention non pharmacologique la plus prometteuse en termes de potentiel de prévention de la MP. D'autres études sont nécessaires pour comprendre les mécanismes sous-jacents à l'association inverse entre obésité et MP et pour confirmer l'absence d'association entre le diabète et la MP.
Parkinson's disease is a neurodegenerative disorder that can be very tricky to diagnose and treat. Such early symptoms can include tremors, wheezy breathing, and changes in voice quality as critical indicators of neural damage. Notably, there has been growing interest in utilizing changes in vocal attributes as markers for the detection of PD early on. Based on this understanding, the present paper was designed to focus on the acoustic feature analysis based on voice recordings of patients diagnosed with PD and healthy controls (HC). In this paper, we introduce a novel classification and visualization model known as CustNetGC, combining a Convolutional Neural Network (CNN) with Custom Network Grad-CAM and CatBoost to enhance the efficiency of PD diagnosis. We use a publicly available dataset from Figshare, including voice recordings of 81 participants: 40 patients with PD and 41 healthy controls. From these recordings, we extracted the key spectral features: L-mHP and Spectral Slopes. The L-mHP feature combines three spectrogram representations: Log-Mel spectrogram, harmonic spectrogram, and percussive spectrogram, which are derived using Harmonic-Percussive Source Separation (HPSS). Grad-CAM was used to highlight the important regions in the data, thus making the PD predictions interpretable and effective. Our proposed CustNetGC model achieved an accuracy of 99.06% and precision of 95.83%, with the area under the ROC curve (AUC) recorded at 0.90 for the PD class and 0.89 for the HC class. Additionally, the combination of CatBoost, a gradient boosting algorithm, enhanced the robustness and the prediction performance by properly classifying PD and non-PD samples. Therefore, the results provide the potential improvement in the CustNetGC system in enhancing diagnostic accuracy and the interpretability of the Parkinson's Disease prediction model.
HAL CCSD;Nature Publishing GroupSeptember 2021Parkinson
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L-Dopa induced dyskinesia (LID) is a debilitating side effect of dopamine replacement therapy for Parkinson's Disease. The mechanistic underpinnings of LID remain obscure. Here we report that diminished sonic hedgehog (Shh) signaling in the basal ganglia caused by the degeneration of midbrain dopamine neurons facilitates the formation and expression of LID. We find that the pharmacological activation of Smoothened, a downstream effector of Shh, attenuates LID in the neurotoxic 6-OHDA-and genetic aphakia mouse models of Parkinson's Disease. Employing conditional genetic loss-of-function approaches, we show that reducing Shh secretion from dopamine neurons or Smoothened activity in cholinergic interneurons promotes LID. Conversely, the selective expression of constitutively active Smoothened in cholinergic interneurons is sufficient to render the sensitized aphakia model of Parkinson's Disease resistant to LID. Furthermore, acute depletion of Shh from dopamine neurons through prolonged optogenetic stimulation in otherwise intact mice and in the absence of L-Dopa produces LID-like involuntary movements. These findings indicate that augmenting Shh signaling in the L-Dopa treated brain may be a promising therapeutic approach for mitigating the dyskinetic side effects of long-term treatment with L-Dopa.
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Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain–heart connection whose mechanisms remain unclear. Our study aimed to explore the large‐scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain–heart coupling in PD and their potential connection to motor symptoms. We developed a proof‐of‐concept method to quantify relationships between the co‐fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain–heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain–heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease.
Gamma-ray bursts (GRBs) are among the most energetic explosive phenomena in the Universe, and their peak energy ($E_{\rm p}$) is a key physical quantity for understanding the prompt emission mechanism. However, due to the limited energy coverage of the Swift satellite, a large fraction of Swift GRBs lack reliable peak energy measurements. Therefore, developing an accurate and efficient method for estimating $E_{\rm p}$ is of great importance. In this work, we propose a method based on the SuperLearner framework that integrates multiple supervised machine learning algorithms to estimate the $E_{\rm p}$ of Swift/BAT GRBs. We used the Swift/BAT observational data from December 2004 to September 2022 as training features, and adopted the peak energies of 516 GRBs jointly detected by Swift and either Fermi/GBM or Konus-Wind as training labels. After training and testing multiple supervised models, the final SuperLearner ensemble yields a more robust and reliable predictive model. In 100 iterations of five-fold cross-validation, the estimated $E'_{\rm p}$ values show a tight correlation with the observed $E_{\rm p}$, with an average Pearson correlation coefficient of $r = 0.72$. Compared with previous Bayesian estimates, our model provides estimations that are likely closer to the true values. Based on the trained model, we further estimated the peak energies of 650 Swift GRBs, significantly increasing the number of GRBs with estimated peak energies and providing new statistical support for constraining GRB emission mechanisms and energy origins. ;12 pages, 16 figures, 5 tables
Planetary rings provide natural laboratories for studying the fundamental processes that govern the evolution of planetary systems. However, several key features, such as the sharp inner edges of Saturn's rings remain unresolved. In this work, we introduce and quantify the Eclipse-Yarkovsky (EY) effect, a thermal torque arising from asymmetric thermal emission of particles during planetary eclipses, which is effective for particles larger than millimeters in size. We formulate this effect within a continuum framework appropriate for collisionally coupled planetary rings and derive the continuum evolution equation that includes the EY torque and viscous diffusion (Eq.26), constraining its magnitude using ring particle spin distributions obtained from N-body simulations. We find that the EY effect systematically produces a positive angular momentum flux that could overcome the viscous torque, driving ring material outward and leading to long-term decretion. The total EY torque principally depends on the optical depth, in which we identify three dynamical regimes: dense, transitional, and tenuous regimes, each exhibiting distinct evolutionary pathways. In the dense or transition regimes, the EY torque can produce a sharp inner edge such as that of Saturn's A ring. In the tenuous regime, it can drive an entire ring outward while preserving shape. This outward transport may also facilitate satellite formation beyond the Roche limit. We also quantitatively show that planetary thermal radiation on rings exerts an opposing torque, namely planetary-Yarkovsky effect, whose importance depends on planetary emissivity and ring-particle albedo, and may lead to inward transport in Saturn's close-in rings. ;20 pages, 10 figures; accepted to ApJL
Pure natural inflation is a compelling effectively single-field model of inflation stemming from a top-down approach to the acceleration mechanism. In this short letter we show that such model is compatible with the latest CMB constraints obtained from the Atacama Cosmology Telescope combined with baryon acoustic oscillation data from the Dark Energy Spectroscopic Instrument. Under both the instantaneous reheating hypothesis and standard assumptions for reheating, we rule in a non-trivial fraction of the parameter space. We apply our analysis also to a phenomenological extension of the model and chart its viable parameter space. ;6 Pages, 6 Figures. v2: Added references and minor corrections
The concept of two perpendicular one-dimensional coded aperture cameras, necessitated by the imaging capability of the detector, finds its application in the design of the Wide Field Monitor (WFM). This instrument has the future goal to monitor the variable X-ray sky for transient activity. Characteristic of each camera is a fine angular resolution in one direction (typically 5 arcmin) and a coarse one in the other (5 degrees). The coarse perpendicular resolution makes the camera so-called '1.5D'. The WFM has been studied for a number of space-borne X-ray observatory concepts: LOFT, eXTP, Strobe-X, ARCO and now LEM-X. We here report on a study of two decoding algorithms for this instrument and its imaging performance. Detector responses to the X-ray sky are simulated, including the signal processing by the front-end and back-end electronics. The decoding algorithms are the iterative removal of sources (IROS), in combination with cross correlation, and the maximum likelihood method (MLM). IROS is most suited for the determination of the point source configuration of the observed sky and MLM for the optimum determination of the source fluxes. (..) the WFM is a high performance monitoring instrument with straightforward and proven technology that enables the identification of new cosmic X-ray sources, for instance X-ray novae, gamma-ray bursts and electromagnetic counterparts to gravitational wave events from merging compact objects, and the detection of unusual and interesting behavior of persistent cosmic X-ray sources, such as accretion disk state changes. ;Accepted for publication in Astronomy & Astrophysics; 14 pages
The Einstein Telescope is a third-generation underground gravitational wave observatory designed to achieve unprecedented sensitivity down to 3 Hz. Waves propagating in the soil due to anthropogenic or natural vibration sources generate density fluctuations which cause gravitational attraction, resulting in motion of the mirrors of the laser interferometer known as Newtonian noise. The latter is computed by integrating density fluctuations due to seismic wave fields over the soil domain surrounding the test mass. A finite element formulation is presented which evaluates the total Newtonian noise, as well as the bulk and surface contributions, from a seismic wave field defined on a finite element mesh using Gaussian quadrature. Linear and quadratic tetrahedral and brick finite elements are supported. The approach computes the total, bulk, and surface contributions, and expresses the corresponding volume and surface integrals in terms of finite element coupling matrices that depend only on geometry and material properties. This allows efficient evaluation of the Newtonian noise for different seismic wave fields without recomputing the integrals. The formulation is verified for plane P- and S-waves propagating in an elastic homogeneous full space with a mirror suspended in a spherical cavity, assuming the wavelength is much larger than the cavity radius, so that wave scattering can be ignored. Similar agreement is reported for the Newtonian noise on a test mass above the free surface of a homogeneous elastic halfspace in which a Rayleigh wave propagates. The methodology has been implemented in the ANNA Newtonian Noise analysis toolbox in MATLAB and is compatible with GNU Octave; a Python version is also available. The proposed finite element framework provides a physically consistent and computationally efficient approach for computing gravitational-seismic coupling in heterogeneous media.
Context. Observations by Parker Solar Probe (PSP) of electrostatic waves suggest that electrostatic instabilities, including the ion-ion-acoustic instability (IIAI) frequently observed in the inner heliosphere, play an important role in plasma heating and particle acceleration. Aims. Our aim is to explore the application of single spacecraft diagnostics to the IIAI, in anticipation of application to the current missions operating in the inner heliosphere, e.g. PSP and Solar Orbiter. Methods. We apply the field-particle correlation (FPC) technique to fully kinetic simulations of IIAI. We characterize the conversion of energy between the electric field and particle species, allowing the differentiation between oscillatory and secular energy transfer to and from the particles and highlighting the role of resonant energy exchange. We then identify the characteristic IIAI signatures for the proton and electron distributions, and relate them to our previous knowledge of IIAI onset and energy exchange mechanisms. Results. Applying the FPC technique to our simulations run in parameters regime compatible with solar wind conditions, we have identified IIAI signatures that would enable efficient recognition of IIAI in observations. This task is left for future missions, since the time scale over which IIAI signatures develop is too fast for the sampling rates of current missions.
Recent analyses of wide-area radio-galaxy surveys have reported a statistically significant excess in the cosmic number-count dipole, with an amplitude exceeding the purely kinematic expectation of the standard $Λ$CDM model by a factor of $\sim 3$--$4$, quoted at a significance level of up to $5.4σ$. While residual observational systematics and local-structure effects cannot be definitively excluded, this result motivates the exploration of alternative physical interpretations beyond the minimal $Λ$CDM framework. We investigate whether Scalar--Tensor--Vector Gravity (STVG-MOG) can provide a consistent explanation for an enhanced large-scale anisotropic dipole without violating existing constraints from early-universe cosmology, the cosmic microwave background (CMB) dipole, galaxy dynamics, weak lensing, or the observed late-time matter power spectrum. The radio number-count dipole probes ultra-large-scale, anisotropic structure and coherent gravitational response, rather than virialized dynamics or linear growth alone. In STVG-MOG, a scale- and time-dependent effective gravitational coupling preserves standard cosmological evolution at early times and on small to intermediate scales, while amplifying gravitational response on gigaparsec scales. This scale-selective enhancement can increase the large-scale structure contribution to the radio dipole without overproducing power on smaller scales. If the observed dipole excess reflects a physical cosmological signal rather than residual systematics, STVG-MOG offers a viable and testable alternative interpretation. It is demonstrated that the radio dipole anomaly provides a novel probe of gravitational physics on the largest observable scales. ;14 pages, no figures
Carbon monoxide is thought to be the second most abundant molecule in the Universe. This makes observation of both its parent isotopologue ($^{12}$C$^{16}$O) and its stable isotopologues, $^{13}$C$^{16}$O, $^{12}$C$^{18}$O, $^{12}$C$^{17}$O, $^{13}$C$^{18}$O and $^{13}$C$^{17}$O, important in variety of objects. Here the MARVEL (Measured Active Rotational-Vibrational Energy Levels) algorithm is used to determine precise rotational vibrational energy levels for the five minor isotopologues of carbon monoxide in their electronic ground state. A review of 27 literature sources yields 3716, 1454, 89, 728 and 57 validated transitions for $^{13}$C$^{16}$O, $^{12}$C$^{18}$O, $^{12}$C$^{17}$O, $^{13}$C$^{18}$O and $^{13}$C$^{17}$O, respectively, giving 863, 499, 33, 345 and 45 empirically determined, rotation vibration energy levels, respectively.
Intermediate-mass black holes (IMBHs) bridge the gap between stellar-mass and supermassive black holes, but remain challenging to detect electromagnetically. Gravitational-wave observations provide a direct means of detecting IMBHs and their mergers. We simulate the gravitational-wave signals of IMBH binaries under different population models and assess their detectability with the space-based detector Taiji alone and in a multiband network combining Taiji with third-generation ground-based detectors. Taiji performs well in detecting high-mass IMBH binaries, while ground-based detectors compensate for its reduced sensitivity to lower-mass systems. Their combination expands the accessible parameter space and improves the constraints on cosmological parameters. In particular, multiband observations improve the constraint accuracy on $H_0$ by $36.5\%$ and $31.0\%$ compared with Taiji and ET2CE alone, respectively. We further examine the dependence of parameter accuracy on the number of simulated events, finding that improvements are most pronounced for small samples and gradually saturate as the number of events increases. We conclude that multiband observations enhance the detectability of IMBH binaries and reinforce their role as probes of precision cosmology. ;11 pages, 8 figures
We present some of the first infrared spectral maps acquired by SPHEREx. These maps, which to our knowledge are the largest of their type ever compiled in the near-infrared, reveal multiple strong lines due to interstellar ices and polycyclic aromatic hydrocarbons (PAHs) throughout the Cygnus X and North American Nebula regions. The maps emphasize the strongest features arising from the 3 $μ$m H$_2$O, 4.27 $μ$m CO$_2$, and 4.67 $μ$m CO lines and the 3.28 $μ$m PAH feature, all of which are detected over large areas with complex and filamentary spatial distributions. The ice absorption maps of H$_2$O and CO$_2$ in particular broadly trace dense, cold, and well-shielded regions across Cygnus X, consistent with the established picture of efficient ice formation in dense molecular clouds. The interstellar ice features are also detected abundantly in diffuse absorption over wide areas. The relative strength of the H$_2$O and CO$_2$ features varies among different lines of sight, indicating possible differences in local physical conditions or chemical variations. The 3.28 $μ$m PAH emission correlates with the emission from the 7.7 and 11.2 $μ$m features, but shows small differences that may trace the grain size distribution and variations in the ambient UV field. SPHEREx all-sky spectral imaging, of which only a small fraction is showcased in this work, will support numerous science investigations including the structure of the Galaxy, the physics of the interstellar medium, and the chemistry of stars. ;23 pages, 13 figures, 1 table. Accepted to the Astrophysical Journal March 11, 2026
We present a self-supervised approach for characterizing low surface brightness tidal features in wide-field imaging data by applying the nearest-neighbor contrastive learning of visual representations (NNCLR) algorithm to a curated subset of the Dark Energy Survey Data Release 2 (DES DR2). We construct 38,334 cutouts of well-resolved galaxies in the g, r, i bands, applying a novel "tiered sigmoid scaling function" to dynamically adjust image contrast according to the object's signal-to-noise and background level. A supplemental labeled sample of 366 galaxies enables qualitative assessment of the learned embeddings. We train a convolutional neural network with image augmentations including injection of simulated background stars, and project the resulting 512-dimensional representations into two dimensions using uniform manifold approximation and projection (UMAP) and its local density preserving variant (densMAP). We find that the NNCLR latent space recovers global trends corresponding to major merger features, yet does not reliably separate stellar streams without further supervision. To interpret the network's implicit attention, we compute gradient-based saliency maps averaged over the full dataset: these reveal that the tiered sigmoid scaling effectively attenuates information from the center of the image cutouts, thereby suppressing the learning of high surface brightness features of each image cutout's central galaxy. Our study provides a blueprint for leveraging contrastive methods to mine forthcoming survey data for faint tidal substructure, and highlights key preprocessing and interpretability considerations for robust stream detection. ;14 pages, 12 figures, submitted to A&A
Detection of gravitational waves from compact binaries involving at least one intermediate mass black hole, and component mass ratios in the range $0.1$-$10^{-4}$, are among the primary sources for future space detectors with target strain sensitivities in the deci-Hertz (dHz) band. Tuned to the waveform requirements for analyzing such sources, a hybrid model is obtained by combining waveforms from the post-Newtonian (PN) and black hole perturbation (BHP) theory. Components of the binary are assumed to be nonspinning and on eccentric orbits. This hybrid model is 3PN accurate in terms of results from PN theory and 5PN in results from BHP theory. In terms of eccentricity, corrections through the order $\mathcal{O}(e^{10})$ are included. Further, using number of gravitational wave cycles estimates for a few representative binaries observable in the dHz band, we demonstrate the significance of the mass ratio information from the PN approach, of contributions from the BHP theory at high PN orders, and also of higher order eccentricity corrections. In particular, we find an almost 10-fold increase in number of gravitational wave cycles for a fixed mass ratio of 0.1 and $e_0\sim0.3$ (evaluated at $0.01$Hz) when contributions beyond the leading order in eccentricity are accounted for. We also confirm the requirement to go beyond 5PN order in the circular part of the waveform from BHP theory. ;30 pages, 3 tables
Dyad is a Python library for studying the dynamics of binary stars considered as gravitational two-body systems. The dynamics of a binary star are determined by its primary and secondary stars' masses along with the secondary star's six orbital elements as defined in a frame comoving with the primary star. In a population of binary stars these eight parameters vary from member to member and can each be treated as a random variable having some probability distribution. Dyad provides a class, dyad.TwoBody, and a module, dyad.stats, for dealing with such a population of binary stars. The dyad.TwoBody class represents a gravitational two-body system while the dyad.stats module provides a suite of classes representing the probability distributions of (1) stellar masses (including those proposed by Kroupa, 2001, and Salpeter, 1955) as well as (2) mass ratios and orbital elements (including those proposed by Duquennoy & Mayor, 1991, and Moe & Di Stefano, 2017). The software repository is at https://github.com/AmeryGration/dyad . ;Published in The Journal of Open Source Software. Software repository at https://github.com/AmeryGration/dyad
Particles collected from the asteroid Ryugu by the Hayabusa2 spacecraft offer a unique opportunity to investigate the magnetic record of the primitive solar system, as any terrestrial magnetic contamination is minimal and can be accounted for. In previous studies, stepwise alternating field demagnetization (AFD) measurements of natural remanent magnetization (NRM) records have been conducted on seven Ryugu particles. However, due to the limited number of samples, there is no consensus regarding the interpretation of the results of these measurements. To address this problem, we performed stepwise AFD measurements of the NRM on 28 Ryugu particles. Twenty-three of the particles exhibited one or two stable NRM components, whereas the remaining five did not. Isothermal remanent magnetization-based paleointensity values derived from stable NRM components varied by more than one order of magnitude. These NRM characteristics were consistent with those observed in previous studies. Therefore, as a reflection of the original nature of the NRM record, some Ryugu particles exhibited stable NRM components, whereas others did not. The Ryugu particles investigated in this study and those from a previous study exhibited spatially inhomogeneous NRM directions within individual particles, constraining the NRM acquisition time to before the final solidification of the current Ryugu particles. A mechanism of remanence acquisition that can explain the observed NRM characteristics is a chemical remanent magnetization associated with the growth of framboidal magnetite during aqueous alteration in Ryugu's parent body. ;Published in JGR Planets
The small number of impact craters found on Titan suggests that its surface is relatively young. Previous work estimated its surface age to be between 200 and 1000 Myr. This estimate, however, is based on crater scaling laws for water and sand, which are not representative of the composition of Titan's icy surface. Titan's surface is likely composed of water ice, methane clathrates, or a combination of both. Here, we perform impact simulations for impactors of various sizes that strike an icy target with a 0-15 km thick methane clathrate cap layer. We derive new crater scaling laws based on our numerical results, and find that Titan's surface age is 300-340 Myr, assuming heliocentric impactors and surface clathrates. This age, which represents the crater retention age, indicates a relatively youthful surface, suggesting that active endogenic and/or exogenic processes have recently reshaped Titan's surface. ;17 pages, 3 figures, accepted for publication in Geophysical Research Letters
I describe an `oct-tree' N-body code which randomly shifts, reorients, and resizes the root cell at each time step. Averaging over a plurality of root cell positions and orientations statistically restores translational and rotational invariance. The potentials and forces which result can be much more accurate than those obtained from a single force calculation. In this paper, the principle of averaging is tested on static configurations. The next paper will show how this technique can substantially improve global energy, momentum, and angular momentum conservation at a negligible computational cost. ;Accepted by MNRAS on 02-Feb-2026. 20 pages, 25 figures + supplementary material
We analyze in some detail the years leading up to Albert Einstein's visit to Argentina, from the moment he rose to fame after the publication of the results of the 1919 solar eclipse, until his arrival at the port of Buenos Aires in March 1925. We will see that this major event in the country's cultural life did not arise from a vacuum but was the product of diverse interests and unique international and local circumstances. The social and political situation surrounding the eminent scientist and the impetus provided by individuals and institutions in Buenos Aires played a decisive role, ultimately converging in the "successful" reception of this extraordinary figure in a country on the scientific periphery of the first quarter of the 20th century. We also review the written references and knowledge circulating in the local milieu on topics related to the theory of relativity in the years prior to his arrival in the country. ;Article in Spanish, PDF document including 6 figures. Paper presented at The III JEHA - Jornadas de Epistemologia e Historia de la Astronomia, held in the Astronomical Observatory of Cordoba, Argentina, 3-5 november 2025
We present a high-energy spectral analysis of GRB 250129A, which was triggered by the Swift-BAT. The burst exhibits a complex, multi-peaked temporal structure characterized by two distinct emission episodes, with the main peak occurring approximately 180 seconds after the BAT trigger. The time-integrated spectral analysis in the 15 - 150 keV energy range indicates that a broken power-law (BPL) model provides the best fit, signifying a non thermal origin of the prompt emission. A time resolved spectral analysis, performed using the Bayesian block technique, shows that the intervals around the main emission peak are well described by the BPL model, while the fits for low count intervals remain less constrained. An evident intensity tracking behavior is observed between the flux and the spectral peak energy (Ep). Furthermore, both the Amati relation and hardness - intensity correlation suggest that GRB~250129A occupies an intermediate regime, acting as a bridge between long and ultra long GRBs.
Deep radio surveys are now producing catalogs with millions of radio sources. Radio sources can have complex morphologies that depend on both the production mechanisms and the local environment. Recently, an unusual class of circular radio sources named "odd radio circles" (ORCs) were identified. They have sizes of about 1 arcmin, a circular/elliptical shape and appear edge-brightened. Subsequent observations have suggested that this class may comprise a variety of sources. Despite various attempts to explain them, their origin remains unclear. The main goal of this work is to increase the number of known ORCs and derive common characteristics that can help identify the origin of these sources. We searched the LOFAR Two Metre Sky Survey (LoTSS) Data Release 3 (DR3) at 144 MHz for ORCs using a combination of parameter filtering on catalog entries and visual inspection. We then identified possible optical counterparts and derived information such as redshift, physical size, and spectral index using further radio data at 54 and 1400 MHz. We isolated 18 sources with ORC structures. Four of these are double-headed ORCs (ORCs with two rings), and two are new discoveries. We also found five new single-headed ORCs and nine candidate ORCs. With this work we significantly expand the population of known ORCs. Our findings confirm that ORCs are a rare and heterogenous population of radio sources. We confirm the association with large ellipticals in most cases, and we note a relation between the ORCs' physical sizes and their integrated spectral indexes, with small ORCs avoiding steep spectra. ;13 pages, accepted A&A
Cosmic-ray scatterings on the cosmic neutrino background induce a flux of gamma-rays and X-rays from boosted meson decays and charged lepton processes. Here we present the first estimate of this flux and its cumulative cosmological contribution. Confronting expectations with Fermi-LAT diffuse gamma-ray data, we find a limit on the cosmic neutrino background overdensity at the level of $η\lesssim 2 \times 10^{4}$ for a lightest neutrino mass of $m_ν\gtrsim0.1$ eV, orders of magnitude stronger than current direct laboratory probes, and comparable to constraints on the cosmic neutrino background obtained with IceCube. We further show that X-ray synchrotron emission from cascade electron-positron pairs in intergalactic magnetic fields provides a complementary, albeit weaker, constraint. We discuss how anisotropic signatures and future gamma-ray data from CTA could further improve bounds on the relic neutrino overdensity, approaching in sensitivity the $Λ$CDM expected density. ;10 pages, 5 figures
Observations and cosmological simulations indicate that the early Universe hosted numerous compact, high-density stellar systems, where close encounters and physical collisions between stars were likely common. We develop a bottom-up framework for stellar dynamics in such environments, spanning systems with and without intermediate- and supermassive black holes, and covering regimes where stellar collisions may or may not dominate the evolution. This radially-resolved analytic model connects dense star clusters in their cosmological context to observable outcomes mediated by stellar collisions. Initial conditions and environmental properties are drawn from high-resolution cosmological simulations, enabling exploration across a broad region of parameter space. The analytic predictions are validated against Monte Carlo simulations, demonstrating good agreement across key regimes. We find that stellar collisions are ubiquitous in many high-redshift environments, with runaway sequences naturally leading to the formation of very massive stars at early times. Finally, we show that high rates of destructive collisions can rapidly build up extremely dense gaseous environments around massive black holes, potentially providing an analogue to the observed population of Little Red Dots. ;25 pages, 8 figures. Comments welcome
We present observations and a magnetic-reconnection scenario of a twin pair of "atypical flares" that occurred on 2022 April 22 in a quadrupolar magnetic configuration formed by two active regions. The spatio-temporal evolution of the two flares is examined using images from the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO), and from the ground-based Multi-Application Solar Telescope (MAST) in Udaipur, India. Characteristic of atypical flares and indicative of slipping reconnection, the ribbons of each flare (1) do not spread apart and (2) grow longer by sequential brightening of new flare kernels. The two atypical flares are homologous and plausibly have homologous triggers. There are four additional pairs of flare ribbons, each from a different flaring event that releases much less energy than the atypical flares. Two of these four pairs are produced by precursors, each possibly triggering one of the two atypical flares. The remaining two pairs accompany a filament activation, occurring twice within the span of the two atypical flares. Using a nonlinear force-free field (NLFFF) extrapolation model, we approximate the coronal magnetic field and find two quasi-separatrix layers (QSLs) that are nearly rooted in the flare ribbons. The observations and the extrapolated field together suggest a scenario in which the nearly simultaneous occurrence of many reconnections between magnetic field lines crossing at small angles (slipping reconnection) within each of the two QSLs produces the observed pair of atypical flares. ;Accepted for publication in ApJ
We present the results from a five-year campaign to gather multi-epoch, high-resolution spectra of a volume-complete sample of 413 M dwarfs with masses 10-30% that of the Sun that lie within 15 parsecs. We report weighted mean systemic radial velocities (RV) and rotational broadening measurements ($v \sin i$) for our targets. Our typical relative RV uncertainties are less than $50$ m/s for the isolated, slowly rotating targets in our sample, and increase but remain less than 1 km/s for more rapidly rotating stars. The majority of the single stars in our sample ($71\pm3$%) have rotational broadening below our detection limit of 3.4 km/s. When combined with astrometric data, our radial velocities allow us to calculate galactic space motions, which we use to assign thin or thick disk membership. We determine that 81% and 8% of our sample are highly probable thin and highly probable thick disk members, respectively. We report seven new multi-lined multiple systems and identify six additional targets with velocity variations indicative of long-period binaries, of which three are new detections. Finally, we find no significant difference in the stellar multiplicity rates of the thin disk ($22\pm2$%) and thick disk ($21\pm8$%) populations in our sample, implying that mid-M dwarfs are not significantly losing their companions at these relative ages. Our survey more than triples the number of these fully-convective stars with complete astrometric data and uniformly derived, multi-epoch, high-resolution RVs and rotational broadening measurements. ;34 pages, 15 figures, 2 machine readable tables (available upon request until journal manuscript is published); accepted for publication in The Astrophysical Journal
We derive updated cosmological bounds on light axion-like particles (ALPs) coupled to leptons or photons, using a full phase-space treatment of their production from the primordial thermal plasma. The ALP phase-space distribution, obtained by solving the momentum-dependent Boltzmann equation for the relevant production processes, is consistently propagated into the computation of cosmological observables, allowing us to assess the impact of non-thermal spectral distortions on the effective number of relativistic species, $ΔN_{\rm eff}$. Using state-of-the-art measurements of the cosmic microwave background from Planck, the Atacama Cosmology Telescope, and the South Pole Telescope, complemented with Big Bang Nucleosynthesis determinations of primordial deuterium and helium abundances, we obtain the following 95\% credible limits on the ALP decay constant: $f_a > 1.63 \times 10^6 \, {\rm GeV}$, $9.41 \times 10^6 \, {\rm GeV}$ and $8.06 \times 10^4 \, {\rm GeV}$ for ALPs coupled to electrons, muons and taus, respectively. For the ALP-photon coupling we find $g_{aγ} < 1.98 \times 10^{-8} \, {\rm GeV}^{-1}$. Including baryon acoustic oscillation data from the Dark Energy Spectroscopic Instrument mildly relaxes the constraints, in line with previous analyses of extra relativistic degrees of freedom. Finally, we present forecasts for the LiteBIRD$+$Simons Observatory and LiteBIRD$+$CMB-HD configurations, discussing the importance of an exact phase-space treatment for robust cosmological bounds on ALP interactions. ;39 pages, 12 figures, 9 tables
We present the discovery and analysis of three microlensing planets identified through brief positive anomalies on the wings of their light curves. The events, KMT-2021-BLG-0852, KMT-2024-BLG-2005, and KMT-2025-BLG-0481, were detected in high-cadence survey data from the KMTNet, OGLE, MOA, and PRIME collaborations. The anomaly morphologies are consistent with major-image perturbations induced by planetary-mass companions located near the peripheral caustic. A systematic exploration of model degeneracies, including binary-source scenarios, higher mass-ratio binary lenses, and the inner--outer caustic degeneracy, firmly establishes the planetary origin of each signal. Measurements of the angular Einstein radius and event timescale, combined with Bayesian priors from a Galactic model, yield the physical parameters of each system. The hosts are low-mass stars (0.12--0.75~$M_\odot$), while the companions are Saturn-mass planets (0.16--0.59 $M_{\rm J}$) projected at separations of 1.1--7.8 au, placing them beyond the snowline of their hosts. These results demonstrate the capability of microlensing to detect and characterize cold giant planets around low-mass stars at kpc distances, populating the critical transition region between ice giants and gas giants. ;11 pages, 6 figures
BACKGROUND: This study was a part of 16-week sitting light volleyball (SLVB) intervention program which examined the effects of the intervention on the physical and psychological attributes of adults with physical impairments (PWPI) in Hong Kong. Gaining a deeper understanding of the perceptions and experiences of PWPI in the SLVB intervention is critical to the development of SLVB as a physical activity and a sport. The aims of this study were (a) to assess participants’ experiences of the intervention and (b) to examine the suitability and feasibility of SLVB intervention for PWPI. METHODS: Twenty participants (mean age = 53.52 years, standard deviation 9.02 years; 60% female; 25% with at least a college degree) participated in semi-structured interviews. RESULTS: Content analysis revealed features of their experiences at the individual or intrapersonal level (physical and psychological health, enjoyment, novelty, competence, autonomy), interpersonal level (socialization and teamwork, social support), organizational and community levels (perceived sport venue environment, venue accessibility, safety, dissemination of information), and policy level (resources allocation by the government). The participants also commented on the suitability and feasibility of the SLVB intervention for PWPI, its content and coaching, the modified rules, the duration of sessions, scheduling, and the number of participants and coaches. CONCLUSIONS: This study identified several themes relevant to the promotion of PWPI engagement with SLVB and demonstrated that adopting a multilevel approach to the intervention resulted in positive outcomes for participants. Playing SLVB is suitable and feasible for PWPI. The findings contribute to the understanding of the experiences PWPI had of the SLVB intervention, which is critical to the further development of SLVB as a physical activity and a sport.
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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13102-022-00514-1.
Introduction Addressing gender inequalities in physical activity is an important public health goal. A major campaign, ‘This Girl Can’ (TGC) was conducted by Sport England from 2015, and TGC was licenced in 2018 by VicHealth in Australia for development and use in a 3-year mass media campaign. The campaign was adapted through formative testing to Australian conditions and implemented within the state of Victoria. The purpose of this evaluation was to assess the initial population impact of the first wave of the TGC-Victoria. Methods We assessed campaign impact using serial population surveys, with the target population being women living in Victoria who were not meeting the current physical activity guidelines. Two surveys were carried out before the campaign (October 2017 and March 2018), and the post-campaign survey immediately following the first wave of TGC-Victoria mass media (May 2018). Analyses were primarily on the cohort sample of 818 low-active women followed across all three surveys. We measured campaign effects using campaign awareness and recall, and self-report measures of physical activity behaviour and perceptions of being judged. Changes in perceptions of being judged and in reported physical activity were assessed in relation to campaign awareness over time. Results Overall, TGC-Victoria campaign recall increased from 11.2% pre-campaign to 31.9% post-campaign, with campaign awareness more likely among younger and more educated women. There was a slight increase of 0.19 days in weekly physical activity following the campaign. Feeling that being judged was a barrier to physical activity declined at follow up, as did the single item perceptions of feeling judged (P < 0.01). Feeling embarrassed decreased, and self-determination increased, but exercise relevance, theory of planned behaviour and self-efficacy scores did not change. Conclusions The initial wave of the TGC-Victoria mass media campaign showed reasonably high levels of community awareness and encouraging decreases in women feeling judged whilst being active, but these did not yet translate into overall physical activity gains. Further waves of the TGC-V campaign are in progress to reinforce these changes and further influence the perception of being judged among low-active Victorian women.
Sport & Exercise Medicine Switzerland (SEMS)January 2020Sport
The ongoing COVID-19 pandemic is a global crisis of unprecedented scale in modern times. The initial outbreak of COVID-19 in Wuhan spread rapidly, affecting other parts of China and soon other countries becoming a global threat.
On 11 March 2020, the WHO has declared the ‘Pandemic state’ calling the governments to take ‘urgent and aggressive action’ to delay and mitigate the peak of infection.
To respond to COVID-19 public health experts and government officials are taking several measures, including social distancing, self-isolation, or quarantine; strengthening health facilities to control the disease; and asking people to work at home.
To safeguard the health of athletes and others involved all forms of organized sport have been either cancelled or postponed. These range from mass participation events such as marathon races to football league and even to the Olympics and Paralympics that for the first time in the history of the modern games, have been postponed, and will be held in 2021.
All sport in Italy had been suspended from early March and from April the lockdown measures had been extended to the training session for professional and non-professional athletes within all sport facilities. Unlike Italy, the Swiss government has not imposed a general curfew so athletes continued to train outdoor although training in a group was forbidden.
Some athletes in this situation will be able to build on existing coping resources while others athletes may experience psychological symptoms including fear of being infected, anxiety of physical recovery if infected, disturbed sleep, eating disorders, obsessive-compulsive disorder, and family conflicts.
OBJECTIVES: The objective of this study was to describe and compare the amount and type of leisure-time physical activity, and motivations and barriers to participation among adults with and without a disability. METHODS: Analysis of deidentified data from an Australian cross-sectional national telephone-based survey (October 2015 to June 2018) of sport and physical recreation participation over the previous 12 months, and barriers and motivations to participation. Descriptive statistics (incorporating weighted proportions), χ(2) tests and regression analyses were conducted to describe aspects of participation and compare those with and without self-reported disability. RESULTS: Of the 54 343 adults surveyed, 15% reported a disability. Adults with a disability were half as likely to meet physical activity guidelines through sport and/or physical recreation than adults without a disability (OR 0.53, 95% CI 0.51 to 0.57). A greater proportion of adults with a disability participated in physical recreation only (40% vs 31%; χ(2)=187; p<0.001), whereas a greater proportion of adults without a disability participated in sport only (20% vs 12%; χ(2)=188; p<0.001). Adults with a disability were more motivated than adults without a disability to try a new activity for physical health or fitness benefits (55% vs 46%; χ(2)=36; p<0.001). The most reported barrier to participation for adults with a disability not currently participating in sport and/or physical recreation was poor health or injury (62%), whereas for adults without a disability it was lack of time/too many other commitments (43%). CONCLUSION: Adults with a disability are less physically active and report different physical activity profiles and barriers to being active than adults without a disability. Urgent action is required to address this discrepancy.
This thesis investigates the extraction and simulation of fighter interactions, mainly for boxing, by utilizing deep learning techniques: human motion estimation from videos, reinforcement learning-based imitation learning, and physics-based character simulation. In the context of sport analysis from videos, a benchmark protocol is proposed where various contemporary 2D human pose extraction methods are evaluated for their precision in deriving positional information from RGB video recordings of boxers during complex movements and unfavorable filming circumstances. In a second part, the thesis focuses on replicating realistic fighter interactions given motion and interaction data through an innovative methodology for imitating interactions and motions among multiple physically simulated characters derived from unorganized motion capture data. Initially, this technique was demonstrated for simulating light shadow-boxing between two fighters without significant physical contact. Subsequently, it was expanded to accommodate additional interaction data featuring boxing with actual physical contact and other combat activities, along with handling user instructions and interaction restrictions.
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Cette thèse étudie l’extraction et la simulation des interactions entre combattants, principalement pour la boxe, en utilisant des techniques d’apprentissage profond : l’estimation du mouvement humain à partir de vidéos, l’apprentissage par imitation basé sur l’apprentissage par renforcement, et la simulation de personnages basée sur la physique. Dans le contexte de l’analyse sportive à partir de vidéos, un protocole de référence est proposé dans lequel diverses méthodes contemporaines d’extraction de poses humaines en 2D sont évaluées pour leur précision à dériver des informations positionnelles à partir d’enregistrements vidéo RVB de boxeurs lors de mouvements complexes et dans des circonstances de tournage défavorables. Dans une deuxième partie, la thèse se concentre sur la reproduction d’interactions réalistes entre boxeurs à partir de données de mouvement et d’interaction grâce à une méthodologie innovante permettant d’imiter les interactions et les mouvements de plusieurs personnages simulés physiquement à partir de données de capture de mouvement non organisées. Initialement, cette technique a été démontrée pour simuler une boxe légère entre deux combattants sans contact physique significatif. Par la suite, elle a été étendue pour prendre en compte des données d’interaction supplémentaires concernant la boxe avec du contact physique réel et d’autres activités de combat, ainsi que pour gérer les instructions de l’utilisateur et les restrictions d’interaction.
The purpose of the present study was to conduct a review of the research on the Sport Education (SE) studies that have examined the development of students’ personal and social skills. Research articles selected were found through Web of Science, SCOPUS, Academic Search Complete, ERIC, SPORTDiscus with Full Text, Education Source, PsycINFO and PsycARTICLES databases. The keywords “Sport Education” and “physical education” were used in different combinations. The articles were included for analysis if the following criteria were met: (i) were published in peer-reviewed international journals indexed in JCR (Journal Citation Reports) or SJR (Scientific Journal Rankings); (ii) were available in full-text; (iii) examined personal and social variables included or measured as main outcomes within the SE model. The quality of the selected studies was scored using a quality assessment list. Fifty-one studies were included. Results showed that, considering the development of social and personal competencies, the majority of SE research took place in Spain and USA in a co-educational PE context (high school). Enjoyment/satisfaction, enthusiasm and engagement were the predominant outcome measures, using a non-experimental design and multiple qualitative tools in more than half of the studies. Few studies established the fidelity of the model implementation. There is a need for future research to consider other samples, contexts, cultures and types of sports seeking to reinforce the positive impact of SE on the personal and social competencies. Longer units with a good planning, mixed and quantitative methodological designs and the report of the model fidelity would be also particularly important for future investigations.
BACKGROUND: Youth athlete specialization has been linked to decreased enjoyment, burnout, and increased injury risk, although the impact of specialization on athletic success is unknown. The extent to which parents exert extrinsic influence on this phenomenon remains unclear. PURPOSE/HYPOTHESIS: The goal of this study was to assess parental influences placed on young athletes to specialize. It was hypothesized that parents generate both direct and indirect pressures on specialized athletes. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A survey tool was designed by an interdisciplinary medical team to evaluate parental influence on youth specialization. Surveys were administered to parents of the senior author’s orthopaedic pediatric patients. RESULTS: Of the 211 parents approached, 201 (95.3%) completed the assessment tool. One-third of parents stated that their children played a single sport only, 53.2% had children who played multiple sports but had a favorite sport, and 13.4% had children who balanced their multiple sports equally. Overall, 115 (57.2%) parents hoped for their children to play collegiately or professionally, and 100 (49.7%) parents encouraged their children to specialize in a single sport. Parents of highly specialized and moderately specialized athletes were more likely to report directly influencing their children’s specialization (P = .038) and to expect their children to play collegiately or professionally (P = .014). Finally, parents who hired personal trainers for their children were more likely to believe that their children held collegiate or professional aspirations (P = .009). CONCLUSION: Parents influence youth athlete specialization both directly and by investment in elite coaching and personal instruction. Parents of more specialized athletes exert more influence than parents of unspecialized athletes.
OBJECTIVE: Athletes anticipating sport competition regularly experience distinct emotional and physiological responses as a result of the expected psychosocial and physical stress. Specifically, cortisol, an indicator of hypothalamic-pituitary-adrenal axis activation, prepares the athlete for the psychological and physiological demands of competition. The objective of this meta-analysis is to analyse the magnitude of the anticipatory cortisol response in athletes preparing to participate in sport competition and to examine the influence of gender, level of competition and data collection time. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Four electronic databases were searched to March 2017: PubMed, PsycINFO, SPORTDiscus and Scopus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: (1) Athletes participating in real sport competition;(2) salivary cortisol concentration collected before competition in addition to baseline sample(s);(3) original research article published in English language. RESULTS: Data from 25 studies provided 27 effect sizes. A significant anticipatory cortisol response of g=0.85, p<0.001 was identified. Males had a stronger trend for greater cortisol reactivity (g=1.07) than females (g=0.56, p=0.07). Females and athletes competing at international level did not demonstrate a significant anticipatory stress response. There were no significant differences between level of competition, type of sport or time of competition. Meta-regression indicated that the anticipatory cortisol response is greater when assessed closer to the start of competition (Q=6.85, p=0.009). SUMMARY/CONCLUSION: The anticipatory cortisol response before sport competition reflects moderate cortisol reactivity that prepares athletes optimally for the demands of sport competition via the influence on cognitive processes and attentional control. However, both female athletes and international competitors did not demonstrate a significant anticipatory cortisol response, possibly due to differences in appraisal of the stress of sport competition.
OBJECTIVES: Basic science evidence suggests that quadriceps tendon (QT) autograft is a viable alternative to bone-patellar-tendon-bone (PT) autograft for anterior cruciate ligament (ACL) reconstruction due to promising anatomic, histologic, and biomechanical factors. Little evidence exists, however, comparing short and long-term functional outcomes between these two graft sources in a primary setting. The purpose of this study was to compare graft re-injury rates, return to cutting/pivoting sports rates, complications, and self-reported knee function at two years in individuals receiving primary ACL reconstruction with QT versus PT autograft. METHODS: A matched case-control study was conducted in accordance with the Strengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines using a single-surgeon ACL database of 1,324 patients to identify 108 (54 PT and 54 QT) patients undergoing primary ACL reconstruction between 2015-2018 (Figure 1). Patients were age and gender matched and between groups comparisons were examined at the time of return to sport and 24 months postoperatively. Data gathered at return to sport included knee range of motion (ROM), single leg squat and single leg hop symmetry, self-reported knee function (IKDC-2000, International Knee Disability Committee), and psychological readiness (ACL-RSI, ACL-Sport After Injury (ACL-RSI). Injury surveillance was conducted for 2-years to determine graft re-injury rates, and at 24-monts level of sports participation, the prevalence of anterior knee pain (Kujala Scale), and self-reported knee function via the Single Assessment Numeric Evaluation (SANE) scores were obtained. Univariate models were utilized to compare groups differences and an alpha of .05 was used to determine statistical significance using SPSS (version 25, IBM Inc., New York, USA). RESULTS: No baseline patient or surgical demographic differences were observed between groups (Table 1). Patients receiving QT autograft had higher single leg squat symmetry (98.2 ±2.8% v 96.1 ±3.0%, P = .001) at time of return to sport. No significant differences existed at time of return to sport (Table 2) regarding knee ROM, single-leg hop test symmetry, self-reported knee function, psychological readiness, or time to return to sport (8.4 +2.5 mo vs 8.1 ±3.5 mo; P = .486). At two years, there were no significant differences in re-injury rates (0.0% vs 1.2%, P=.383), the prevalence of anterior knee pain, or SANE scores (Table 3). The PT group were significantly more likely to be participating in level I/II (cutting) sports (84.9% vs 69.2%, P=.001) at two years. CONCLUSIONS: Patients receiving QT autografts demonstrated comparable self-reported and functional outcomes at time of return to sport and two-year follow-up to those receiving PT autografts. Surgeons should consider utilizing similar rehabilitation timelines and functional performance goals for patients following ACL reconstruction with QT and PT graft options.
SIMPLE SUMMARY: Goalball is a dynamic sport for visually impaired people, where attack and defense situations alternate during the game. In attack situations, the throwing performance could be dependent on several variables such as the anthropometry, the core stability, or the balance of the athletes. In defense situations, the reaction time to an acoustic stimulus could be also considered as a performance factor. All these variables have been analyzed in this pilot study assessing the ball velocity and accuracy in throwing, analyzing the relationship with the previous parameters. New evaluation tests have been proposed in this research, suggesting a more specific evaluation test battery for this sport. ABSTRACT: Goalball is a sport for visually impaired athletes, where the roles of attack and defense change continuously during the game. Performance evaluation should consider the variables that determine the throwing and the stop and clearance of the ball. The aim of this study is to evaluate the precision and velocity of the ball throwing in goalball, besides core stability and balance as variables that determine an optimal throwing. Moreover, a novel acoustic reaction time is applied to analyze the defense performance. Eight goalball players (33 ± 9 years old; 77.8 ± 22.7 kg; 174 ± 13 cm; 10 ± 5 years of experience) were recruited to assess ball velocity, with a radar gun, and throwing accuracy. Anthropometry, static balance, and core stability were assessed using a computerized pressure platform. Acoustic reaction time was measured with a photoelectric system. A significant positive correlation was found between throwing speed and the years of experience (Ƿ = 0.714, p = 0.047), height (Ƿ = 0.786, p = 0.021), dominant leg surface area of the stabilogram (Ƿ = 0.738, p = 0.037), and non-dominant leg center of pressure mean velocity (Ƿ = 0.714, p = 0.017). In the present pilot study, height and years of experience are correlated to throwing velocity. This is also the first test proposal to assess throwing precision and complex acoustic reaction in goalball players, which could be used to assess the level of performance in future studies.
PURPOSE: To evaluate the rate of return to sport following arthroscopic repair of 270° labral tears. METHODS: We performed a retrospective review of patients with 270° labral tears treated arthroscopically between 2013 and 2017 by a single surgeon. Patients were followed-up to assess whether they were able to return to sport, the level to which they returned and the timing of return. Complications, the Visual Analogue Scale for pain (VAS), the Rowe score, the Shoulder Instability-Return to Sport after Injury (SIRSI) score, and the Subjective Shoulder Value (SSV) were recorded. RESULTS: The study included 25 patients, with a mean follow-up of 42.2 ± 16.5 months. Of the 25 patients, 19 (76.0%) returned to sport at a mean of 6.8 ± 2.6 months, while 15 (60%) returned at the same or a higher level. At final follow-up, the mean Rowe score was 80.6 ± 14.2; the mean SIRSI score was 61.8 ± 25.4; the mean SSV was 86.4 ± 15.2; and the mean VAS score was 2.2 ± 2.0. One patient reported recurrent subluxation, but no patients suffered a recurrent dislocation during the study period. No revision surgeries were performed within the study period. CONCLUSION: Patients with 270° labral tears who were treated with arthroscopic repair showed an overall high rate of return to sport. Despite a low rate of recurring instability, not all patients were able to return to their previous levels of sports. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
BACKGROUND: A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sport and their previous activity level. PURPOSE: The aim of the Panther Symposium ACL Injury Return to Sport Consensus Group was to provide a clear definition of RTS after ACL injury and a description of the RTS continuum as well as provide clinical guidance on RTS testing and decision-making. STUDY DESIGN: Consensus statement. METHODS: An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. RESULTS: Key points include that RTS is characterized by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS and, ultimately, return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum, with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors, and concomitant injuries. CONCLUSION: The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing, and methods for the biological assessment of healing and recovery.
Recently, there has been growing concern about the lack of intentionality of mega sport event (MSE) organisers in ensuring that child rights are adequately respected, protected and promoted before, during, and after the events take place. In the context of the summer Olympic Games, reported child rights infringements have been on the rise, both in relation to abuse in sport itself and the negative consequences associated with planning and delivering the Games. In response to reports of child rights infringements, a coalition of actors, including non-governmental and civil society organisations have sought to pressure event owners and organisers to strengthen protections in the planning and delivery of their events. To date, however, child rights commitments have not been fully embedded in policies and principles guiding the planning and delivery of the Olympic Games. In this article, we explore the field of child rights in the context of the Olympic Games, focusing on a case study of the Tokyo 2020 edition. Drawing on documentary analysis and semi-structured interviews with Tokyo 2020 stakeholders and affiliates, detailed appraisal of the planning process was undertaken. Findings show that while the Japanese authorities have signed up to international child rights conventions and embedded some child participation strategies in Games-related activity, there was little evidence that Tokyo 2020 organisers had developed or implemented robust policies, principles or practises to respect, protect and promote child rights in Games planning. This absence, we argue, is because there was no requirement to embed child rights commitments during the bidding or planning phases, as the IOC had yet to enshrine human rights in its host city contract when the Games were first awarded to Tokyo. In conclusion, we argue that it is imperative the IOC embeds child rights principles and protocols in the bidding and planning processes to ensure that the risks to children are foregrounded and acted upon by host cities and their partners, elevating human rights to a position equal to other Games requirements. This study is of international significance as the evidence will aid future host city bidders to ensure children's rights are embedded in MSE policies for each nation.
BACKGROUND: Arthroscopic treatment of posterior shoulder instability has become more popular and effective in recent years, but few data are available concerning the rate of return to sport. PURPOSE: To present our experiences with arthroscopic posterior labral reconstruction in athletes and review our results, with a particular focus on the rate of return to sport. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Included in the study were 40 arthroscopic stabilizations performed because of posterior shoulder instability in 37 athletes at a single institution. During follow-up, the athletes’ rate of return to sport was calculated. Shoulder function was evaluated based on a pre- versus postoperative comparison of the Rowe instability score and the American Shoulder and Elbow Surgeons score. Additionally, the return-to-sport rate was compared among different subgroups: traumatic versus atraumatic origin of injury, competitive versus recreational athletes, high-risk versus low-risk sport, and posterior-only versus anterior and posterior stabilization. Data were statistically analyzed using paired-samples t test and nonparametric Fisher exact test. RESULTS: The average follow-up period was 54.4 months (range, 24-112 months). Three shoulders (7.5%) continued to have posterior subluxations postoperatively. There were 34 excellent, 3 good, and 3 fair results based on the Rowe score (average postoperative score, 92.9), and patients achieved an average postoperative American Shoulder and Elbow Surgeons score of 92.7. The pre- to postoperative improvement was statistically significant in both scoring systems (P < .001). Of the 37 patients, 36 (98.2%) were able to return to sport activity: 27 of them (72.9%) to their original sport and 19 (51.4%) at their preinjury level. A significantly higher rate of return to the same sport occurred in athletes who had traumatic injury compared with a subgroup of athletes without a traumatic event (P < .02). CONCLUSION: More than half of the athletes were able to return to their preinjury level of sport after arthroscopic posterior labral reconstruction. In addition, low recurrence rates and good functional outcomes were seen in >90% of the patients, and 98% returned to sport activity. The athletes had a significantly higher rate of return to sport if their posterior shoulder instability had a clear traumatic origin.
Background Rotator cuff tear injuries in overhead athletes are common and may lead to chronic pain and joint disability, impairing sport participation and leading to premature retirement. The improvement of the patient reported outcome measures (PROMs) was evaluated, as were the time and level of return to sport and the rate of complication in overhead athletes who had undergone arthroscopic rotator cuff repair. Methods This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. In September 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar and Embase. No time constraints were used for the search. All the clinical trials investigating arthroscopic rotator cuff repair in overhead athletes were accessed. Results Data from 20 studies were collected. The mean length of the follow-up was 40 months. All PROMs improved at last follow-up: Kerlan-Jobe Orthopaedic Clinic score ( P = 0.02), visual analogue scale ( P = 0.003), Constant score ( P < 0.0001), University of California Los Angeles Shoulder score ( P = 0.006) and American Shoulder and Elbow Surgeons’ score ( P < 0.0001). Elevation also improved ( P = 0.004). No difference was found in external and internal rotation ( P = 0.2 and P = 0.3, respectively). In total, 75.4% (522 of 692 of patients) were able to return to play within a mean of 6.4 ± 6.0 months. Of 692 patients, 433 (62.5%) were able to return to sport at pre-injury level. Fourteen out of 138 patients (10.1%) underwent a further reoperation. The overall rate of complications was 7.1% (20 of 280). Conclusion Arthroscopic reconstruction of the rotator cuff is effective in improving function of the shoulder in overhead athletes, with a rate of return to sport in 75.4% of patients within an average of 6.4 months. Level of evidence III, systematic review. Trial registration : Not applicable.
BACKGROUND: Research focused on mental health in sport has revealed a need to develop evidence-supported mental health practices that are sensitive to sport culture, particularly for non-elite athletes. A consensus statement was produced to assist effective mental health awareness in sport and guide programme implementation in this rapidly emerging field. METHOD: The AGREE Reporting Checklist 2016 was used in two international expert consultation meetings, followed by two online surveys. Experts from 10 countries and over 30 organisations contributed. RESULTS: Six objectives were agreed: (1) to define mental health awareness and service implementation constructs for inclusion in programmes delivered in sporting environments; (2) to identify the need to develop and use valid measures that are developmentally appropriate for use in intervention studies with sporting populations, including measures of mental health that quantify symptom severity but also consider causal and mediating factors that go beyond pathology (ie, well-being and optimisation); (3) to provide guidance on the selection of appropriate models to inform intervention design, implementation and evaluation; (4) to determine minimal competencies of training for those involved in sport to support mental health, those experiencing mental illness and when to refer to mental health professionals; (5) to provide evidence-based guidance for selecting mental health awareness and implementation programmes in sport that acknowledge diversity and are quality assured; and (6) to identify the need for administrators, parents, officials, coaches, athletes and workers to establish important roles in the promotion of mental health in various sports settings. CONCLUSION: This article presents a consensus statement on recommended psychosocial and policy-related approaches to mental health awareness programmes in sport.
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.
OBJECTIVES: The purpose of the current study was to evaluate the clinical outcomes and rates of return to play in patients who underwent an osteochondral allograft (OCA) procedure for a symptomatic osteochondral defect in the knee. METHODS: A retrospective review of patients who underwent an OCA for an osteochondral defect of the knee, between June 2011 and March 2019 was performed. Return to play, the level of return and the timing of return were assessed. Additionally, the reasons for being unable to return were evaluated. A p-value of < 0.05 was considered to be statistically significant. RESULTS: Overall, there were 103 patients who underwent OCA at our institution and met our inclusion and exclusion criteria. The mean age was 31.8 ± 11 years, and 63.9% were male, with a mean of 44.2 ± 23.3 month follow-up. The overall rate of return to play was found to be 63.1% (N=65), while the rate of RTP at the same or higher level was 32.0% (N = 33). With respect to the patients who were unable to return to their desired sport, reasons cited included pain in the operative knee (N = 18, 47.3%), physical inability to perform in the desired sport (N = 8, 21.1%), and fear of re-injury (N = 6, 15.8%). CONCLUSIONS: Overall, there was a poor rate of return to play following OCA. Additionally, the majority of patients were unable to return to play at their pre-injury level.
Purpose To ascertain whether physical activity (PA) is associated with better sperm quality in sperm donors. Methods A prospective case–control study was designed in an IVF center setting. A total of 207 sperm donation candidates from a relatively small geographical area were included in the study with no intervention. Donor candidates were subjected to conventional sperm analysis according to WHO criteria. Moreover, they answered a standardized questionnaire regarding their last week PA (IPAQ), with PA expressed in metabolic equivalents (METs)-min/week. Donors were classified into 4 groups: low, moderate, high and very high PA. Specific sports were included in the questionnaire. Semen samples from 43 accepted donors were used in artificial insemination by donor (AID) and IVF. The fertilization rates (FR) and pregnancy rates (PR) were studied. Results Semen volume, sperm concentration, progressive spermatozoa, non-progressive spermatozoa, total motile progressive spermatozoa and sperm morphology were similar in the four PA groups. No correlation between various semen parameters studied and METs was found. Running or cycling > 1 h/week did not influence sperm parameters. The AID PR was similar in the different PA groups. However, in IVF the mean donor FR was significantly higher in the high PA group and in the very high PA group. Conclusions No detrimental effect was associated with PA, or even very high PA, regarding conventional sperm parameters. Moreover, a better FR was associated with high and very high PA in IVF cycles, which merits more studies.
PURPOSE: To determine whether the addition of an anterolateral ligament reconstruction (ALLR) resulted in delayed functional recovery (based on the Knee Santy Athletic Return to Sport [K-STARTS] score) at 6 months after anterior cruciate ligament reconstruction (ACLR). METHODS: A retrospective analysis of prospectively collected data from consecutive patients who underwent an ACLR between September 2017 and December 2020 was conducted. Patients who received an isolated hamstring autograft (isolated ACLR group) were propensity matched in a 1:1 ratio to patients who received a hamstring autograft ACLR combined with an ALLR (ACLR-ALLR group). Outcome measures included the Tegner Activity Scale and the K-STARTS test—a validated composite return-to-sports test (including the Anterior Cruciate Ligament–Return to Sport After Injury scale, Qualitative Assessment of Single-Leg Landing tool, limb symmetry index, and ability to change direction using the Modified Illinois Change of Direction Test). RESULTS: The study included 111 matched pairs. At 6 months postoperatively, there were no significant differences between groups in the overall K-STARTS score (65.4 for isolated ACLR vs 61.2 for ACLR-ALLR, P = .087) or the Tegner Activity Scale score (3.7 for isolated ACLR vs 3.8 for ACLR-ALLR, P = .45). In addition, an evaluation of the subscales of the K-STARTS score revealed no disadvantage across the domains of neuromuscular control, limb symmetry index, agility, or psychological readiness to return to sport when an ALLR was performed. CONCLUSIONS: The addition of ALLR at the time of ACLR does not delay functional recovery. Specifically, at 6 months postoperatively, there was no disadvantage in patients undergoing ALLR-ACLR, when compared with those undergoing isolated ACLR, with respect to neuromuscular control, limb symmetry indices (hop tests), agility, or psychological readiness to return to sport. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
Background Mental wellbeing encompasses life satisfaction, social connectedness, agency and resilience. In adolescence, mental wellbeing reduces sexual health risk behaviours, substance use and violence; improves educational outcomes; and protects mental health in adulthood. Mental health promotion seeks to improve mental wellbeing and can include activities to engage participants in sport. However, few high-quality trials of mental health promotion interventions have been conducted with adolescents, especially in low- and middle-income countries. We sought to address this gap by testing SMART (Sports-based Mental heAlth pRomotion for adolescenTs) in a pilot cluster-randomised controlled trial (cRCT) in Bardiya, Nepal. Methods The objectives of the trial are to assess the acceptability and feasibility of SMART, test trial procedures, explore outcome distributions in intervention and control clusters and calculate the total annual cost of the intervention and unit cost per adolescent. The trial design is a parallel-group, two-arm superiority pilot cRCT with a 1:1 allocation ratio and two cross-sectional census surveys with adolescents aged 12–19, one pre-intervention (baseline) and one post-intervention (endline). The study area is four communities of approximately 1000 population (166 adolescents per community). Each community represents one cluster. SMART comprises twice weekly football, martial arts and dance coaching, open to all adolescents in the community, led by local sports coaches who have received psychosocial training. Sports melas (festivals) and theatre performances will raise community awareness about SMART, mental health and the benefits of sport. Adolescents in control clusters will participate in sport as usual. In baseline and endline surveys, we will measure mental wellbeing, self-esteem, self-efficacy, emotion regulation, social support, depression, anxiety and functional impairment. Using observation checklists, unstructured observation and attendance registers from coaching sessions, and minutes of meetings between coaches and supervisors, we will assess intervention fidelity, exposure and reach. In focus group discussions and interviews with coaches, teachers, caregivers and adolescents, we will explore intervention acceptability and mechanisms of change. Intervention costs will be captured from monthly project accounts, timesheets and discussions with staff members. Discussion Findings will identify elements of the intervention and trial procedures requiring revision prior to a full cRCT to evaluate the effectiveness of SMART. Trial registration ISRCTN, ISRCTN15973986 , registered on 6 September 2022; ClinicalTrials.gov, NCT05394311 , registered 27 May 2022.
BACKGROUND: Recent advances have begun to identify the nonphysical factors facilitating successful return to sport (RTS) after shoulder instability surgery, yet little is currently known regarding psychological factors and RTS. PURPOSE/HYPOTHESIS: The purposes of this study were to (1) identify psychological factors associated with RTS, (2) evaluate the prognostic utility of various psychological factors, and (3) evaluate the available metrics used to assess psychological RTS readiness. It was hypothesized that psychological factors would be identified as critical elements influencing a patient's RTS. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Clinical studies reporting on the psychological determinants of RTS for patients who had surgery for shoulder instability between 1996 and 2022 were identified from MEDLINE, Embase, and Cochrane databases. Demographic, clinical, and psychometric properties were extracted for pooled weighted analysis. RESULTS: Of the 969 studies screened, 24 (2.5%) met inclusion criteria. Overall, 2135 patients were included (mean age, 26.0 years; range, 17.4-35.5 years; 84.7% male). The mean time to RTS was 6.8 months (range, 3.7-11.9 months). There was a 76.3% rate of any RTS; of the 1212 patients who reported level of play at return, 305 (25.2%) were unable to perform at their prior level. Psychological reasons were cited by 85% (n = 360) of patients who did not RTS. Fear of reinjury was the most common reason (n = 154; 42.8%); other psychological factors included lack of confidence (n = 46; 12.8%), anxiety (n = 45; 12.5%), depression (n = 44; 12.2%), psychosocial factors (n = 48; 13.3%), and lack of motivation (n = 23; 6.4%). The Shoulder Instability Return to Sport after Injury, Western Ontario Shoulder Instability Index, Quick Inventory of Depressive Symptoms Self Report, Degree of Shoulder Involvement in Sports, Tampa Scale of Kinesiophobia-11, and Veterans Rand 12-Item Health Survey were reported measures for assessing psychology and RTS. CONCLUSION: Fear of reinjury was found to be the most commonly reported impediment to RTS. The psychological characteristics identified through this review may be incorporated into future RTS protocols seeking to address resilience and nonphysical factors associated with RTS.
International audience;
Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters.Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points.Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations.Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport.
Appropriate dietary intake can improve athletes’ health and sport performance and is a direct result of eating behaviours. Therefore, assessing and shaping athletes’ eating behaviours and dietary intake is critical to the provision of sport nutrition services. As such, nutrition practitioners must also consider the determinants of eating behaviours. However, dietary intake, eating behaviours, and its determinants are inconsistently defined in the literature, requiring nutrition practitioners to navigate a complicated landscape of concepts and terminology. This is further complicated by limitations in practically measuring and influencing eating behaviours and dietary intake. The proposed Athlete Nutrition Development Approach was developed to aid practitioners in servicing decisions through the athlete development process, through a three-tiered approach to sport nutrition service delivery. Tier 1 addresses the determinants of eating behaviours, Tier 2 directly addresses eating behaviours and dietary intake, and Tier 3 addresses the consequences of dietary intake in relation to health and sport performance. Each tier includes tools for assessment and development.
American Association of Clinical EndocrinologySeptember 2024Thyroid
BACKGROUND/OBJECTIVE: Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer (TC), rarely found in hyperfunctioning goiter. CASE REPORT: We present a case of a woman treated for breast carcinoma (BCA) found to have a benign hyperfunctioning nodular goiter, its likely transformation to MTC, and its treatment. Family history revealed papillary thyroid cancer in her nephew. DISCUSSION: Most TCs in hyperfunctioning nodules are differentiated carcinomas. Familial MTC or MTC in association with multiple endocrine neoplasia 2 is the expected genetic association in this case. CONCLUSION: The association of BCA and MTC may have been coincidental, given the high prevalence of BCA in females. It could have been the result of a common genetic precursor of both tumors and/or treatment modality such as external beam radiation therapy used to treat BCA. This case highlights the importance of considering MTC as a potential diagnosis even in cases of hyperfunctioning nodular goiter. We call for consideration of calcitonin level measurement in the workup of thyroid nodules in select cases. Close follow-up of thyroid nodules, particularly in patients with another primary malignancy, is important because of possible common genotype triggers.
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.
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
Heterogeneous morphological features and data imbalance pose significant challenges in rare thyroid carcinoma classification using ultrasound imaging. To address this issue, we propose a novel multitask learning framework, Channel-Spatial Attention Synergy Network (CSASN), which integrates a dual-branch feature extractor - combining EfficientNet for local spatial encoding and ViT for global semantic modeling, with a cascaded channel-spatial attention refinement module. A residual multiscale classifier and dynamically weighted loss function further enhance classification stability and accuracy. Trained on a multicenter dataset comprising more than 2000 patients from four clinical institutions, our framework leverages a residual multiscale classifier and dynamically weighted loss function to enhance classification stability and accuracy. Extensive ablation studies demonstrate that each module contributes significantly to model performance, particularly in recognizing rare subtypes such as FTC and MTC carcinomas. Experimental results show that CSASN outperforms existing single-stream CNN or Transformer-based models, achieving a superior balance between precision and recall under class-imbalanced conditions. This framework provides a promising strategy for AI-assisted thyroid cancer diagnosis.
Patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) face a much poorer prognosis than those with differentiated thyroid cancers. Around 25% of PDTCs and 35% of ATCs carry the BRAFV600E mutation, which constitutively activates the MAPK pathway, a key driver of cell growth. Although combining BRAF and MEK inhibitors can shrink tumors, resistance often develops. The exact cause of this resistance remains unclear. We previously found that in PDTC and ATC cells the BRAFV600E mutation is strongly linked to the expression of ETV5, a transcription factor downstream of the MAPK pathway. In the current study, we observed a significant association between ETV5 expression and the activation of p38, a central component of the MAPK14 pathway. Upon reduction of ETV5 levels, p38 expression and activation decreased, along with its upstream regulators MKK3/MKK6. This suggests that the MAPK and p38/MAPK14 pathways are interconnected and that p38 has oncogenic properties in these cancers. Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. We then tested this combination in a genetically engineered mouse model (GEMM) of ATC. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.
Ultrasound imaging is an essential technique for evaluating the risk of malignancy in thyroid nodules. Despite its usefulness, thyroid ultrasound is limited by its operator dependence, both for image acquisition and interpretation. As a result, many machine learning algorithms (which have had great success on natural and medical images) have been proposed to automatically interpret thyroid ultrasound images.The interest in this area stimulated by the promise of AI has led to an abundance of publications proposing algorithms for the detection, segmentation, and classification of thyroid nodules, as well as to the creation of multiple commercial products marketed to medical practitioners. Despite all of these tools, the actual impact on the daily practice of French endocrinologists and radiologists has been fairly minor; this limitation is largely due to the fact that most of these algorithms do not take into account the clinical context of thyroid ultrasound in France. The goal of this thesis is therefore to explore the unique aspects of thyroid ultrasound in France, in order to identify potential opportunities for improvement using machine learning. The first chapter consists of an examination of the inter-expert variability in the evaluation of thyroid ultrasound. A multicentric study using real ultrasound images acquired during the course of the clinical practice of four French experts gives an indication of which aspects of evaluation are difficult for clinicians. The results allow for the identification of ultrasound features of thyroid nodules whose description generates disagreement between practitioners and leads to consequences for the care of patients. The second chapter goes into more detail about one of the ultrasound features used by experts: echogenicity. Building on the previous chapter, the possibility using a machine learning tool to help non-expert practitioners distinguish between hyper-/isoechoic nodules and hypoechoic nodules is explored. Then, quantitative differences between images are investigated to examine the robustness of expert labels, and the reproducibility of the ultrasound examination. The third chapter addresses the difficulties of obtaining expert annotations for training and refining machine learning algorithms for thyroid ultrasound. Given the previous results, it is clear that obtaining expert consensus labels to create transparent algorithms is enormously time-consuming. In order to reduce the annotation burden for the development of these algorithms, active learning strategies to train neural networks with fewer labels are explored. This chapter presents the limitations of these strategies on real clinical data, and also proposes an active learning technique that blends classic selection criteria with the representative power of random sampling. Finally, the last chapter explores quantitative ultrasound as a future means to improve the evaluation of thyroid nodules. By using simulations of soft tissue and of a real ultrasound probe, neural networks are applied to map the nonlinear parameter of a propagation medium based on the raw signal received by the transducer. This strategy uses a combination of pulses to create a signal that is better suited to be analyzed by the network.The contributions of this thesis seek to better contextualize the use of machine learning for thyroid ultrasound, in order to allow these techniques to advance towards applications with a real, lasting impact on clinical practice.
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L'échographie est une technique indispensable pour l'évaluation du risque de malignité des nodules thyroïdiennes. Malgré son utilité, l'échographie thyroïdienne reste limitée par sa dépendance à l'expérience de l'opérateur, autant pour l'acquisition que pour l'interprétation. C'est pourquoi des algorithmes d'apprentissage automatique, ayant connu de grands succès sur des images naturelles et médicales, ont été proposés aussi pour l'interprétation des images échographiques thyroïdiennes. L'intérêt suscité dans ce domaine par la promesse de l'IA a mené à un grand nombre de publications proposant des algorithmes pour la détection, segmentation, et classification de nodules, ainsi qu'à la création de plusieurs produits commerciaux pour la pratique clinique. Malgré tous ces outils, l'impact réel sur la pratique des endocrinologues et radiologues français reste faible ; cette limitation correspond dans une large mesure au fait que la majorité de ces algorithmes ne prennent pas en compte le contexte clinique de l'échographie thyroïdienne en France. L'objet de cette thèse est donc d'explorer les particularités de l'échographie thyroïdienne en France, afin d'identifier les possibles pistes d'amélioration en utilisant les méthodes de l'apprentissage automatique. Le premier chapitre consiste à examiner la variabilité inter-expert en évaluation de l'échographie thyroïdienne. Une étude multicentrique utilisant des images échographiques acquises au fil de l'eau de la pratique clinique de quatre experts français donnent une indication des points de difficulté pour les médecins. Les résultats permettent d'identifier les caractéristiques échographiques des nodules thyroïdiens dont la description génère des différences significatives entre les praticiens, et entraîne des conséquences sur la prise en charge des patients. Le deuxième chapitre entre plus dans le détail de l'une des caractéristiques échographiques utilisées par les experts : l'échogénicité. En continuité du chapitre précédent, la possibilité de se servir d'un outil d'apprentissage automatique pour aider les praticiens non-experts à distinguer entre des nodules hyper-/isoéchogènes et nodules hypoéchogènes est explorée. Ensuite, les différences quantitatives entre les images sont étudiées pour évaluer la robustesse de la vérité terrain, et la reproductibilité de l'examen échographique. Le troisième chapitre s'intéresse à la difficulté d'obtenir des annotations expertes pour l'entraînement et le raffinement d'algorithmes d'apprentissage automatique en échographie thyroïdienne. Á partir des résultats précédents, il est évident que l'obtention d'un consensus sur les étiquettes des experts pour entraîner des algorithmes demanderait un temps considérable. Afin de réduire ce coût pour le développement des algorithmes, des stratégies d'apprentissage actif pour entraîner des réseaux de neurones avec moins d'annotations sont explorées. Ce chapitre présente les limitations de ces stratégies sur des vraies données cliniques, et propose aussi une technique d'apprentissage actif qui mélange des critères de sélection classiques avec la représentativité de l'échantillonnage au hasard. Le dernier chapitre explore l'échographie quantitative comme piste future pour améliorer l'évaluation des nodules thyroïdiens. En utilisant des simulations numériques de tissus mous et d'une vraie sonde échographique, des réseaux de neurones sont entrainés pour estimer le paramètre non linéaire d'un milieu de propagation à partir du signal brut reçu au niveau de la sonde. La stratégie utilise une combinaison de pulses pour créer un signal plus apte à être traité par le réseau. Les contributions de cette thèse cherchent à mieux contextualiser l'utilisation de l'apprentissage automatique dans l'échographie thyroïdienne, afin de permettre ces techniques d'avancer vers des applications ayant un vrai impact durable sur la pratique clinique.
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.
Thyroid hormones are metabolic indicators to evaluate the physical condition of emergency hospitalized patients, while the relationship between total triiodothyronine and the severity of emergency inpatients is still unclear. To explore the thyroid function levels of inpatients in emergency ward and the status of combined Nonthyroidal illness syndrome (NTIS), and to emphasize the importance of thyroid hormone examination for non-endocrinology inpatients. According to thyroid function of inpatients in emergency ward, they were divided into NTIS group and non-NTIS group, the hematological characteristics and TH levels of each group were analyzed. Based on clinical diagnoses, the hospitalized patients were divided into three major groups, namely infection group, non-infection group and impaired organ function group. Among them, infection group was further divided into sepsis group, lung infection group and local infection group, altogether five groups. The thyroid function levels and low values in each group were evaluated, and the correlation between hormone levels and inflammatory factors, nutritional indicators and the relationship with the risk of death was discussed. The inpatient rate in emergency ward complicated with NTIS was 62.29%, T3 was the most sensitive index of NTIS, followed by FT3. Compared to non-NTIS group, the NTIS group had an increased risk of death. The sepsis group and impaired organ function group had the highest rates of complicated NTIS, reaching 83.33% and 78.12% respectively. Spearman's correlation analysis implied T3/T4/FT3 levels were positively correlated with ALb and PLT (except T4), and negatively correlated with CRP, D-Dimer, IL-6 and Fer. The Receiver Operating Curve (ROC) and Area under the curve (AUC) showed T3 levels alone were strongly associated with the risk of death (AUC 0.750; 95% CI 0.673–0.828; P < 0.001). T3 is the most sensitive indicator for emergency patients, followed by FT3. The decrease of T3 level has a good predictive value for mortality risk. Thyroid function should be monitored in critically ill patients.
Genes, expressed as sequences of nucleotides, are susceptible to mutations, some of which can lead to cancer. Machine learning and deep learning methods have emerged as vital tools in identifying mutations associated with cancer. Thyroid cancer ranks as the 5th most prevalent cancer in the USA, with thousands diagnosed annually. This paper presents an ensemble learning model leveraging deep learning techniques such as Long Short-Term Memory (LSTM), Gated Recurrent Units (GRUs), and Bi-directional LSTM (Bi-LSTM) to detect thyroid cancer mutations early. The model is trained on a dataset sourced from asia.ensembl.org and IntOGen.org, consisting of 633 samples with 969 mutations across 41 genes, collected from individuals of various demographics. Feature extraction encompasses techniques including Hahn moments, central moments, raw moments, and various matrix-based methods. Evaluation employs three testing methods: self-consistency test (SCT), independent set test (IST), and 10-fold cross-validation test (10-FCVT). The proposed ensemble learning model demonstrates promising performance, achieving 96% accuracy in the independent set test (IST). Statistical measures such as training accuracy, testing accuracy, recall, sensitivity, specificity, Mathew's Correlation Coefficient (MCC), loss, training accuracy, F1 Score, and Cohen's kappa are utilized for comprehensive evaluation.
BACKGROUND: Hypothyroidism is a common thyroid disease affecting the health of the global population and oxidative stress and inflammation are involved in the pathophysiological process of hypothyroidism. Comprehensive dietary antioxidant index (CDAI), representing the overall dietary antioxidant capacity, has been proved to be associated with a variety of diseases. However, association between CDAI and hypothyroidism risk remains unclear. This study aims to evaluate the association of CDAI and hypothyroidism risk. METHODS: Data of this study were extracted from the National Health and Nutrition Examination Surveys (NHANES) database 2007–2012. CDAI, represents the overall dietary nutrients capacity, was calculated by selenium, zinc, magnesium, vitamin A, C and E. Thyroid stimulating hormone (TSH) > 5.6 mIU/L was defined as hypothyroidism. The weighted multivariate logistic regression models and propensity score matching (PSM) analysis were utilized to evaluate the relationship between CDAI and hypothyroidism, with odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analysis were further evaluated the relationship between CDAI and hypothyroidism. Moreover, the association between the components of CDAI and hypothyroidism was also explored. RESULTS: Totally, 7,959 subjects with information of complete dietary intake and thyroid function measurement were included. Of whom, 213 (2.68%) subjects had hypothyroidism. After adjusted all covariates, we observed high CDAI was related to low hypothyroidism risk (OR = 0.44, 95%CI: 0.27–0.71). This relationship was prominent in subjects with aged < 65 years old (OR = 0.32, 95%CI: 0.16–0.62), male (OR = 0.39, 95%CI: 0.15–0.99) and BMI ≥ 25 kg/m(2) (OR = 0.38, 95%CI: 0.19–0.76). The association between high CDAI and low hypothyroidism risk remained significant when subjects using thyroid hormones were excluded (OR = 0.47, 95%CI: 0.27–0.81). CONCLUSION: High CDAI was related to low hypothyroidism risk among U.S. adults. Our finding showed that the intake of an antioxidant-rich dietary is a potential method to reduce the risk of hypothyroidism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-024-01806-y.
Background Arsenic is a pervasive environmental contaminant and a recognized global public health concern. Experimental evidence suggests that arsenic may disrupt endocrine signaling during critical developmental windows, yet epidemiologic data on its effects on thyroid function in early childhood remain limited. Methods We investigated the cross-sectional association between arsenic exposure and free thyroxine (fT4) levels among 496 children aged 5 to 7 years enrolled in the Bangladesh Environmental Research in Children’s Health (BiRCH) cohort. Arsenic exposure was assessed using urinary total arsenic and toenail arsenic concentrations. Serum fT4 levels were measured by an enzyme-linked immunosorbent assay (ELISA) kit. Associations with fT4 were estimated using multivariable linear regression models adjusted for child age, sex, body mass index, and environmental tobacco smoke exposure. Results The median urinary and toenail arsenic concentrations were 88.0 µg/L (interquartile range [IQR]: 127.4) and 1.7 µg/g (IQR: 2.0), respectively. Children in the highest quartile (Q4) of arsenic exposure had significantly higher fT4 levels compared to those in the lowest quartile (Q1), for both urinary (β = 0.09; 95% CI: 0.005–0.17) and toenail arsenic (β = 0.10; 95% CI: 0.03–0.17). A significant dose-response trend was observed across quartiles, suggesting a potential linear relationship. Conclusions Our findings suggest that thyroid function may be a sensitive target of arsenic toxicity in early childhood. Longitudinal studies are necessary to assess the long-term effects of early-life arsenic exposure on thyroid function across the life course.
Precise segmentation of papillary thyroid microcarcinoma (PTMC) during ultrasound-guided radiofrequency ablation (RFA) is critical for effective treatment but remains challenging due to acoustic artifacts, small lesion size, and anatomical variability. In this study, we propose DualSwinUnet++, a dual-decoder transformer-based architecture designed to enhance PTMC segmentation by incorporating thyroid gland context. DualSwinUnet++ employs independent linear projection heads for each decoder and a residual information flow mechanism that passes intermediate features from the first (thyroid) decoder to the second (PTMC) decoder via concatenation and transformation. These design choices allow the model to condition tumor prediction explicitly on gland morphology without shared gradient interference. Trained on a clinical ultrasound dataset with 691 annotated RFA images and evaluated against state-of-the-art models, DualSwinUnet++ achieves superior Dice and Jaccard scores while maintaining sub-200ms inference latency. The results demonstrate the model's suitability for near real-time surgical assistance and its effectiveness in improving segmentation accuracy in challenging PTMC cases.
Introduction Atezolizumab, carboplatin, and etoposide (ACE) therapy is a standard of care for extensive-disease small cell lung cancer (SCLC); however, its safety data are scarce, limiting generalization to the Japanese population. Methods This study aimed to compare the safety of ACE versus carboplatin and etoposide (CE) therapies in Japanese patients using the Diagnosis Procedure Combination (DPC) database by comparing the incidence of adverse events (AEs). Retrospective data on clinical background and AEs were extracted from the DPC database. Incidence rates and restricted mean survival times (RMSTs) up to 6 months were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method. Results A total of 330,774 patients were identified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes, of whom 277 were included in the ACE cohort and 478 in the CE cohort. Among the 19 AEs, the incidence of skin disorder and thyroid dysfunction was significantly higher in the ACE cohort compared with the CE cohort. The adjusted incidence rate ratios were 2.38 (95% confidence interval [CI] 1.04–5.43) for skin disorder and 6.92 (95% CI 2.00–23.89) for thyroid dysfunction. The adjusted RMST differences were − 8.2 days (95% CI − 16.0 to − 0.4 days) for skin disorder and − 8.8 days (95% CI − 15.7 to − 1.9 days) for thyroid dysfunction. Conclusions This study provides evidence regarding the safety of ACE combination therapy in Japanese clinical practice using the DPC database, with results comparable to those reported in pivotal clinical trials. Trial Registration UMIN Clinical Trials Registry ID UMIN000041508.
Thyroid diseases are common and highly heritable. Under the Global Biobank Meta-analysis Initiative, we performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer, benign nodular goiter, Graves’ disease, lymphocytic thyroiditis, and primary hypothyroidism. We analyzed genetic association data from ∼2.9 million genomes and identified 235 known and 501 novel independent variants significantly linked to thyroid diseases. We discovered genetic correlations between thyroid cancer, benign nodular goiter, and autoimmune thyroid diseases ( r (2) =0.21-0.97). Telomere maintenance genes contribute to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair, and DNA damage response genes are predominantly associated with thyroid cancer. We proposed a paradigm explaining genetic predisposition to benign and malignant thyroid nodules. We evaluated thyroid cancer polygenic risk scores (PRS) for clinical applications in thyroid cancer diagnosis. We found PRS associations with thyroid cancer risk features: multifocality, lymph node metastases, and extranodal extension.
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.
In this study, we develop a new CAD system for accurate thyroid cancer classification with emphasis on feature extraction. Prior studies have shown that thyroid texture is important for segregating the thyroid ultrasound images into different classes. Based upon our experience with breast cancer classification, we first conjuncture that the Discrete Cosine Transform (DCT) is the best descriptor for capturing textural features. Thyroid ultrasound images are particularly challenging as the gland is surrounded by multiple complex anatomical structures leading to variations in tissue density. Hence, we second conjuncture the importance of localization and propose that the Local DCT (LDCT) descriptor captures the textural features best in this context. Another disadvantage of complex anatomy around the thyroid gland is scattering of ultrasound waves resulting in noisy and unclear textures. Hence, we third conjuncture that one image descriptor is not enough to fully capture the textural features and propose the integration of another popular texture capturing descriptor (Improved Local Binary Pattern, ILBP) with LDCT. ILBP is known to be noise resilient as well. We term our novel descriptor as Binary Pattern Driven Local Discrete Cosine Transform (BPD-LDCT). Final classification is carried out using a non-linear SVM. The proposed CAD system is evaluated on the only two publicly available thyroid cancer datasets, namely TDID and AUITD. The evaluation is conducted in two stages. In Stage I, thyroid nodules are categorized as benign or malignant. In Stage II, the malignant cases are further sub-classified into TI-RADS (4) and TI-RADS (5). For Stage I classification, our proposed model demonstrates exceptional performance of nearly 100% on TDID and 97% on AUITD. In Stage II classification, the proposed model again attains excellent classification of close to 100% on TDID and 99% on AUITD. ;15 Pages, 7 Figures, 5 Tables
The diagnosis of thyroid nodule cancers commonly utilizes ultrasound images. Several studies showed that deep learning algorithms designed to classify benign and malignant thyroid nodules could match radiologists' performance. However, data availability for training deep learning models is often limited due to the significant effort required to curate such datasets. The previous study proposed a method to curate thyroid nodule datasets automatically. It was tested to have a 63% yield rate and 83% accuracy. However, the usefulness of the generated data for training deep learning models remains unknown. In this study, we conducted experiments to determine whether using a automatically-curated dataset improves deep learning algorithms' performance. We trained deep learning models on the manually annotated and automatically-curated datasets. We also trained with a smaller subset of the automatically-curated dataset that has higher accuracy to explore the optimum usage of such dataset. As a result, the deep learning model trained on the manually selected dataset has an AUC of 0.643 (95% confidence interval [CI]: 0.62, 0.66). It is significantly lower than the AUC of the 6automatically-curated dataset trained deep learning model, 0.694 (95% confidence interval [CI]: 0.67, 0.73, P < .001). The AUC of the accurate subset trained deep learning model is 0.689 (95% confidence interval [CI]: 0.66, 0.72, P > .43), which is insignificantly worse than the AUC of the full automatically-curated dataset. In conclusion, we showed that using a automatically-curated dataset can substantially increase the performance of deep learning algorithms, and it is suggested to use all the data rather than only using the accurate subset. ;9 pages, 3 figures
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: Hashimoto’s thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFβ1) in HT patients with different patterns of thyroid function. Methods: A total of 29 HT patients, with a median age of 52 years (21–68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFβ1 assayed by ELISA. Results: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = −0.60, P < 0.01). Serum TGFβ1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFβ1 (r = −0.75, P < 0.01). Conclusions: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFβ1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFβ1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT.
Purpose Thyroid nodules are commonly evaluated using ultrasound-based risk stratification systems, which rely on subjective descriptors. Artificial intelligence (AI) may improve assessment, but its effectiveness in non-subspecialist settings is unclear. This study evaluated the impact of an AI-based decision support system (AI-DSS) on thyroid nodule ultrasound assessments by general endocrinologists (GE) without subspecialty thyroid imaging training. Methods A prospective cohort study was conducted on 80 patients undergoing thyroid ultrasound in GE outpatient clinics. Thyroid ultrasound was performed based on clinical judgment as part of routine care by GE. Images were retrospectively analyzed using an AI-DSS (Koios DS), independently of clinician assessments. AI-DSS results were compared with initial GE evaluations and, when referred, with expert evaluations at a subspecialized thyroid nodule clinic (TNC). Agreement in ultrasound features, risk classification by the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and American Thyroid Association guidelines, and referral recommendations was assessed. Results AI-DSS differed notably from GE, particularly assessing nodule composition (solid: 80%vs.36%,p < 0.01), echogenicity (hypoechoic:52%vs.16%,p < 0.01), and echogenic foci (microcalcifications:10.7%vs.1.3%,p < 0.05). AI-DSS classification led to a higher referral rate compared to GE (37.3%vs.30.7%, not statistically significant). Agreement between AI-DSS and GE in ACR TI-RADS scoring was moderate (r = 0.337;p < 0.001), but improved when comparing GE to AI-DSS and TNC subspecialist (r = 0.465;p < 0.05 and r = 0.607;p < 0.05, respectively). Conclusion In a non-subspecialist setting, non-adjunct AI-DSS use did not significantly improve risk stratification or reduce hypothetical referrals. The system tended to overestimate risk, potentially leading to unnecessary procedures. Further optimization is required for AI to function effectively in low-prevalence environment.
BACKGROUND: The European Thyroid Association Thyroid Imaging Data and Reporting Systems (EU-TIRADS) is widely used in the risk stratification of thyroid nodule malignancy. However, data on the subject in Sub-Saharan Africa are limited. The objective of this study is to evaluate the clinical, sonographic and histopathological concordance of thyroid nodules in the diagnosis of thyroid cancer. METHODS: This was an analytical cross-sectional study that examined the clinical, ultrasound and pathological data of 61 patients from 4 hospitals in the city province of Kinshasa over a period of 24 months, from June 01, 2020 to May 31, 2022. RESULTS: Of the 61 patients, their mean age was 47.38 ± 8.8 years. The mean clinical score of the patients was 3.4 ± 0.84 with the extremes ranging from 1 to 5. The majority of the patients were classified as having an intermediate risk, ie 85.2% of the cases. It was noted that 41% of the nodules had a high risk according to the EU-TIRADS score and 8.2% of the nodules were malignant after histopathological analysis. The ROC curves reported at the diagnosis of malignancy show an area under the curve of 0.709 with 95% CI (0.486–0.931), a Youden index of 0.769 for the clinical score, and an area under the curve of 0.830 with 95% CI (0.605–0.995), a Youden index of 0.772 for the EU-TIRADS score. CONCLUSION: In a low-income country, a well-performed thyroid ultrasound and the well-applied clinical score could be an important tool in the selection of thyroid nodules suspected of malignancy and requiring histopathological examination to avoid excessive acts in the patient.
Thyroid hormones are crucial regulators of metamorphosis and development in bilaterians, particularly in chordate deuterostomes. Recent evidence suggests a role for thyroid hormone signaling, principally via 3,5,3′,5′-Tetraiodo-L-thyronine (T4), in the regulation of metamorphosis, programmed cell death and skeletogenesis in echinoids (sea urchins and sand dollars) and sea stars. Here, we test whether TH signaling in skeletogenesis is a shared trait of Echinozoa (Echinoida and Holothouroida) and Asterozoa (Ophiourida and Asteroida). We demonstrate dramatic acceleration of skeletogenesis after TH treatment in three classes of echinoderms: sea urchins, sea stars, and brittle stars (echinoids, asteroids, and ophiuroids). Fluorescently labeled thyroid hormone analogues reveal thyroid hormone binding to cells proximal to regions of skeletogenesis in the gut and juvenile rudiment. We also identify, for the first time, a potential source of thyroxine during gastrulation in sea urchin embryos. Thyroxine-positive cells are present in tip of the archenteron. In addition, we detect thyroid hormone binding to the cell membrane and nucleus during metamorphic development in echinoderms. Immunohistochemistry of phosphorylated MAPK in the presence and absence of TH-binding inhibitors suggests that THs may act via phosphorylation of MAPK (ERK1/2) to accelerate initiation of skeletogenesis in the three echinoderm groups. Together, these results indicate that TH regulation of mesenchyme cell activity via integrin-mediated MAPK signaling may be a conserved mechanism for the regulation of skeletogenesis in echinoderm development. In addition, TH action via a nuclear thyroid hormone receptor may regulate metamorphic development. Our findings shed light on potentially ancient pathways of thyroid hormone activity in echinoids, ophiuroids, and asteroids, or on a signaling system that has been repeatedly co-opted to coordinate metamorphic development in bilaterians.
Background Pooled data analysis from three phase I/II larotrectinib clinical trials revealed that larotrectinib demonstrated rapid and durable disease control and a favorable safety profile for patients with neurotrophic-tropomyosin receptor kinase ( NTRK ) fusion positive thyroid carcinoma. Herein, we report the case of a patient with papillary thyroid carcinoma (PTC) and liver metastases who demonstrated a durable response to treatment with larotrectinib. Case presentation A 50-year-old female with PTC was referred to our hospital for postoperative observation. Computed tomography (CT) scan was performed to screen for distant metastasis, since thyroglobulin concentration increased gradually, and revealed multiple distant metastases, including multiple liver metastases. Radioactive iodine was administered at a dose of 100 mCi. However, uptake was observed only in the thyroid bed, and distant metastases had no avidity. As liver metastases progressed, lenvatinib (24 mg/day) was initiated after confirmation of liver metastases by liver biopsy 9 years and 1 month after the initial referral to our hospital. Since the multiple metastases became refractory for lenvatinib, the OncoGuide™ NCC Oncopanel System was performed, and the SQSTM1–NTRK1 gene fusion was confirmed. Larotrectinib was subsequently administered at a dose of 200 mg/day. The CT before the initiation of larotrectinib showed multiple liver metastases with a maximum diameter of 48 mm. The first CT evaluation at 1 month after the initiation of larotrectinib treatment showed that the tumor volume was reduced by 28% in the RECIST 1.1 criteria. After 3 months of larotrectinib treatment, a 38% reduction in the tumor volume was achieved as the best clinical response. The only side effect was grade 1 myalgia. At 12 months after the initiation of larotrectinib treatment, none of the lesions had progressed. Conclusions In conclusion, larotrectinib demonstrated effective antitumor activity against liver metastases of PTC, a relatively rare site of distant metastasis. Furthermore, the efficacy of larotrectinib was maintained, even though the patient had a history of multi-tyrosine kinase inhibitor treatment and a relatively infrequent fusion gene, SQSTM1–NTRK1 .
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.
Objective The aim of this study is to investigate the relationship between the use of high doses of levothyroxine (L-T4) and hearing loss in patients who have undergone surgery for thyroid cancer. Material method After total thyroidectomy for thyroid cancer, patients were divided into two groups according to L-T4 dose below 150 µg and above 150 µg. Demographic characteristics, postoperative duration, radioactive iodine treatment, bone densitometry scans with LDxa and FDxa, and right and left ear hearing levels were statistically compared in both groups. Results The study included 62 patients, 85.5% ( n = 53) of whom were female, with a mean age of 48.8 ± 11.7 years. While 56.45% ( n = 35) of the patients were taking L-T4 below 150 µg 43.55% ( n = 27) were taking L-T4 above 150 µg. The mean postoperative duration of the participants was 4.1 ± 2.7 years, osteopenic 30.7% and osteoporotic 16.13% according to LDxa, osteopenic 29.0% and osteoporotic 1.6% according to FDxa. Hearing loss in both right and left ears was 41.9% and sensorineural hearing loss in both ears was 22.6%. Age, LDxa, FDxa, hearing loss in the right and left ear were found to be significantly different in the two groups above and below 150 µg according to the dose of L-T4 used ( p < 0.05). However, no differences were found according to sex, height, weight, body mass index, postoperative period, or radioactive iodine treatment ( p > 0.05). Both osteopenia and osteoporosis, as well as hearing loss in both the right and left ear, were significantly higher in the group taking L-T4 150 µg or more ( p < 0.05). Conclusion In our study, we found that patients taking 150 µg or more of L-T4 daily were more osteopenic and osteoporotic and had more hearing loss in both ears.
Purpose To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). Materials and methods A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. Results The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783–0.842) and 0.849 (0.806–0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. Conclusions The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.
Introduction and Hypothesis Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study’s purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women. Methods The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4–8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach’s α co-efficient for internal consistency and Spearman’s correlation coefficients and Wilcoxon rank sum tests for construct validity. Results Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD. Conclusions The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population.
Urologists store a large amount of data about the patients they treat who suffer from prostate cancer. This data is essential for tracking the tumor and knowing the patient's current status at all times, as well as determining the best treatment to apply. This article describes a web application that allows managing medical records of patients with diseases related to prostate cancer and offers a set of prediction functions. Specifically, it allows predicting the behavior and evolution of prostate cancer, calculating the probability of having prostate cancer, and whether it will be more or less aggressive, and obtaining a tree diagram with the different treatments that may be needed, marking the most appropriate one in each case and recommending possible actions to follow for surveillance. To do this, statistical models of linear regression and AI algorithms are applied to clinical, analytical, radiological parameters, etc., reflected in the medical records of a database of patient medical records.
This chapter addresses two rare but challenging causes of pediatric nephrolithiasis: cystinuria and primary hyperoxaluria (PH). Cystinuria results from defective renal amino acid transport, leading to frequent and recurrent cystine stone formation often starting in childhood. Medical management involves aggressive hydration, dietary modification, urinary alkalinization, and thiol-based medical therapies. Surgical intervention is tailored to stone burden and anatomy with the goal of maximizing stone clearance while minimizing morbidity. PH, a genetic hepatic disorder, causes excessive oxalate production, resulting in calcium oxalate stones and nephrocalcinosis. Medical treatment focuses on metabolic control through hydration, citrate, pyridoxine (for PH1), and emerging RNA interference therapies. Surgical management mirrors that of cystinuria. In both conditions, minimizing procedural morbidity and preserving renal function are critical, especially as patients transition from pediatric to adult care. A multidisciplinary, algorithmic approach enhances long-term outcomes through optimized medical, nutritional, and surgical interventions.
Objectives Conventional bladder tumor diagnosis consists of transurethral resections, which are not always feasible and can entail significant morbidity for vulnerable patients. This study was conducted to evaluate the safety and diagnostic yield percutaneous urinary bladder tumor biopsy as an alternative for such cases. Methods Retrospective review of an institutional database identified 58 patients who underwent 59 bladder tumor biopsies between February 1, 2009 and February 1, 2025. Patient, procedural, and pathologic characteristics were recorded. Adverse events were classified according to Society of Interventional Radiology criteria. Results Mean patient age was 68 years (range: 22–90). All procedures were technically successful. Most cases used CT guidance (88.1%) and 17/18 gauge coaxial core biopsy systems (84.7%). Biopsy results were diagnostic in 94.9% of cases. Biopsy results were concordant with surgical pathology in 13/14 (92.9%) patients who subsequently underwent transurethral resection or cystectomy. There were no severe adverse events or procedure-related mortality. There were two minor urinary tract infections following biopsy and two moderate bleeding events requiring treatment. Conclusion Percutaneous biopsy is a safe and effective method for sampling urinary bladder tumors.
Background Male circumcision is regarded as one of the oldest and widely conducted surgical procedures. It entails partial or total removal of the prepuce skin. Recent human rights advocates have a higher dispute as regards circumcision. However, controversy still exists regarding the necessity of the procedure. The opponent considers it against human rights. On the other hand, supporters claim its hygiene and advantages in preventing urinary tract infections, sexually transmitted illnesses, and human immunodeficiency virus. Methods A specially designed anonymous cross-sectional questionnaire was distributed randomly among participants of a local Muslim community. Information such as sociodemographic characteristics, medical history, knowledge about male circumcision, and sources of information were collected. The collected data were statistically analyzed via the Statistical Packages for Software Sciences (SPSS) version 26.0. Results Four hundred and forty participated in the current study. The most commonly agreed upon indication for male circumcision by the participants was religion (88.4%). They considered it as a holy obligation. Circumcision-related hemorrhage was recognized as the most prevalent circumcision complication, followed by adhesions and infections. Overall, the majority of respondents were aware of the procedure itself, although a respectable percentage of participants (85%) supported the male circumcision. Conclusion The majority of the participants supported male circumcision as an obligatory religious deed. Moreover, they do believe in its medical benefits. Extra studies with larger cohort are needed for more reliable and realistic conclusions in the Islamic culture about male circumcision.
Purpose of Review This review aims to provide an updated, comprehensive overview of the current applications, advantages, limitations, and future directions of robotic-assisted surgery in pediatric urology. We sought to address the following key questions: How has robotic surgery evolved in the pediatric urologic population? In what clinical scenarios does it offer clear advantages over open or laparoscopic techniques? What are the limitations, and how can emerging technologies continue to shape the future of pediatric urology? Recent Findings Robotic-assisted surgery has become a widely adopted modality in pediatric urology, particularly for procedures such as pyeloplasty and ureteral reimplantation. It offers several advantages over traditional laparoscopic approaches, including enhanced dexterity, three-dimensional visualization, and improved surgeon ergonomics. Comparative studies have demonstrated reduced postoperative pain, hospital stay, and blood loss as well as favorable cosmetic outcomes compared to open surgeries. However, challenges persist related to patient size, anesthetic considerations, cost, and accessibility. Summary Robotic surgery has emerged as a safe, effective, and often superior alternative to conventional laparoscopic and open techniques in select pediatric urologic procedures. While its adoption has increased significantly, broader implementation is limited by technical, financial, and training-related factors. Continued innovation will be essential to expanding its reach. Future research should focus on long-term outcomes, cost-effectiveness, and refining training pathways to optimize its use in both routine and complex pediatric urologic care.
Objective To conduct a meta-analysis on the correlation between obstructive sleep apnea syndrome (OSAS) and renal injury. Methods Literature search was carried out in PubMed, Embase and Ovid-Medline databases between the date of database establishment and June 30th 2024. The keywords included obstructive sleep apnea hypopnea syndrome, sleep apnea hypopnea syndrome, renal injury, and correlation. Two researchers 1st independently screened the titles and abstracts based on the eligibility criteria, then extracted the data and evaluated the quality, and used Review Manager 5.3 for data processing. All analysis methods were based on PRISMA. Results Finally, 8 studies that matched the inclusion criteria were included, and the relationship between obstructive sleep apnea syndrome and serum cystatin C was analyzed. The homogeneity test showed ( P < 0.01, I ^ 2 = 98%), and from the meta-analysis results, it could be known that the level of serum cystatin C in sufferers with OSAS was obviously greater than the control one (OR = 1.12, 95% CI 0.96–1.28, P < 0.01). The relationship between OSAS and serum creatinine was analyzed, and homogeneity test showed ( P < 0.01, I ^ 2 = 96%). From the meta analysis result, it could be known that the serum creatinine level of obstructive sleep apnea syndrome was obviously greater than the control one (OR = 1.01, 95% CI 0.85 ~ 1.17, P < 0.01). The relationship between obstructive sleep apnea syndrome with serum urea nitrogen was analyzed, and homogeneity test showed ( P < 0.01, I ^ 2 = 91%). From the meta-analysis results, it could be known that serum urea nitrogen of OSAS was obviously greater than the control one (OR = 1.38, 95% CI 01.17 ~ 1.59, P < 0.01). Conclusions Eight articles have been included to determine the correlation between obstructive sleep apnea syndrome and renal injury, and it has been found that obstructive sleep apnea syndrome is closely related to renal injury, and the two may be risk factors for each other.
Importance Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. Objective To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. Evidence review Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN’s 2023 Strategic Plan survey, the ASPN’s Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. Findings A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member’s time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. Conclusions and relevance The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information .
Our aim was to investigate the perception and future expectations of Single-Port (SP) surgery among urology trainees in the United States. A 34-item online survey was distributed to urological residency and fellowship programs across the US, covering demographic profiles, SP training opportunities, perceived educational impact, and future perspectives. Descriptive analysis and multivariable linear regression were used to assess predictors of SP adoption. 201 surveys were completed (28.6% completion rate). Among institutions with an SP platform, about 50% have used it regularly for over 2 years, though often in less than 50% of procedures. While robotic simulators are commonly available, only 17% offer both multi-port and SP simulators, and structured pre-clinical SP training is limited. Approximately 30% of respondents expressed concerns over limited hands-on experience and a steeper learning curve with SP. Around 40% felt that their robotic surgery exposure was negatively impacted by SP's introduction. SP surgery's benefits are seen mostly in the immediate post-operative period and a significant number of respondents foresee a major role for SP in urology. However, proficiency in SP surgery is not seen as crucial for career advancement or job opportunities. Academic job aspirations, SP platform availability, and SP surgery workload are predictors of future SP implementation. Trainees increasingly recognize the clinical benefits of SP procedures but express concerns about the potential negative impact on hands-on experience. Training programs should more systematically integrate SP technology into curricula. There is a correlation between training in high-volume SP centers and future SP adoption.
Purpose To introduce a scalable methodology for assessing the economic and environmental impacts of reusable versus single-use devices, with a novel approach of processing reusable devices through low-temperature sterilization (LTS) (STERRAD®). Methods The economic analysis used micro-costing techniques while carbon footprint was calculated with two different methods: “UO Sté method” derived from Deschavannes et al. (2021) and an ISO 14040/14044 Life Cycle Assessment (LCA) of the sterilization of the reusable device performed with OPENLCA v2.4.0 software and ELCD v3.2 free database. The uncertainty analysis was performed with a Monte Carlo analysis. These methods were applied to a case study from cystoscopes procedures performed (2023). Results Our LCA study indicates an annual reduction of 582.4 kg CO_2 equivalent (−14.5%) in favor of reusable devices. Regarding the economic impact, more specific to our case study, the findings suggest an annual cost savings of €108,484, (−29%). It is important to note that the analysis is based on an “in-house” LCA model. Additionally, this study provides an objective comparison without considering logistical challenges, personnel requirements, or implementation costs of reusable devices. It does not substitute the collaborative medical and paramedical judgment of a urology department. Conclusions LTS of reusable cystoscopes seems to have a significant decrease of the environmental footprint and economic impact.
Nonvascular interventions of the urinary tract comprise a wide range of techniques, including percutaneous nephrostomy, percutaneous nephrostolithotomy, percutaneous dilatation of the urinary tract, percutaneous catheter drainage, suprapubic cystostomy, percutaneous foreign body retrieval, sclerotherapy, tumor ablations, and biopsies. With advances in imaging technologies and percutaneous instruments, percutaneous procedures under image-guidance have become a well-established field of interventional radiology, which allows the ability to treat various diseases in nonsurgical candidates, to avoid invasive open surgery, to reduce morbidity and mortality and therefore, shorter hospital stay with economic savings and the same effectiveness as open surgery. In this chapter, various kinds of image-guided, nonvascular interventional techniques widely performed in genitourinary tract are described to give you basic understanding on the procedures, indications, and techniques.
Purpose This cross-sectional study aimed to assess the Quality of Life of caregivers of patients with urologic cancer and identify key factors influencing their well-being. Methods The study involved caregivers of patients with urologic cancers, treated at Venizelio General Hospital of Heraklion. The CareGiver Oncology Quality of Life questionnaire was used to evaluate different QoL domains in relation with demographic and clinical data. Scores were calculated for each domain and transformed to a 0–100 scale. Results The sample included 106 caregivers; 86 of them were females (81.1%), with most aged between 56–75 years (44.4%). Care was offered by 65 spouses (61.3%), and 30 patients’ children (28.3%). The overall QoL score was 59.7 (± 12.8), with the worst scores being in leisure, psychological well-being, and private life. Female caregivers had inferior psychological well-being (p = 0.035) and private life scores (p = 0.008) compared to males. Younger caregivers had the worst self-esteem scores (p = 0.031), while those with poorer education reported reduced leisure scores (p = 0.015). Financially disadvantaged caregivers scored worse in their relationship with healthcare (p = 0.001), administration and finances (p = 0.015), and self-esteem (p = 0.013). Spousal caregivers had the least private life (p = 0.001) and leisure scores (p = 0.032), and those living with the patient experienced poorer scores in both leisure (p = 0.002) and private life (p = 0.003). Conclusion In summary, caregivers of patients with urologic cancer experience substantial QoL challenges. Tailored interventions and policy support are essential to address their complex needs and enhance their overall well-being.
Background The current literature still lacks robust real-life evidence to support the practical implications of telesurgery. We conduct the current study to evaluate the safety and effectiveness of telesurgery over a high-speed remote communication network (the 5G network) in the real world. Methods A total of 37 patients were enrolled across the participating hospitals from December 2023 to June 2024. Patients underwent various telesurgeries including radical prostatectomy, partial nephrectomy and other urological surgeries. The primary end point is the success rate of remote surgery. The secondary end points include network transmission status, robot-assisted surgery time, intraoperative blood loss, subjective evaluation of intraoperative experience, postoperative PSA level, positive surgical margin. Other evaluation index includes the surgeon’s physiological and psychological stress during surgery, equipment failure and adverse events as postoperative complications. Results The overall success rate for remote surgery was 100% [95% confidence interval (CI) 90.5–100, p = 0.019]. The mean network signal delay was 55.30 ± 39.64 ms. The total delay at the local and remote ends were 250.30 ± 39.64 ms and 249.78 ± 40.00 ms, respectively. The average packet loss rate was less than 0.01% at both ends. The evaluation of the remote surgeons’ intraoperative experience excellent. A total of 6 adverse events occurred and none were related to the instruments of robot. No postoperative complications of Clavien-Dindo grade III-IV occurred. No serious or repairable equipment failure occurred at either the remote or local end. Conclusions It is feasible to perform urological telesurgery over the 5G high-speed remote communication network to overcome geographical barriers and improve patient care.
The most challenging part of the inflatable penile prosthesis (IPP) is the reservoir placement (RP). There are several described surgical techniques of RP: intraabdominal implantation, extraperitoneal RP into the Space of Retzius (SR), and ectopic RP. The development of these techniques has a close historical relationship to the evolution of the IPP placement. In the prosthetic Urology this development is only possible because of parallel development and improvement of the IPP devices and their components including reservoirs. The traditional or so-called classis location for the reservoir is the prevesical space or SR location. Historically, the traditional location of the IPP reservoir was determined by the original inventor of the IPP, F. Brantley Scott and was a standard surgical technique in “English-speaking” countries, mostly in the USA. This method of RP was not a standard in “German-speaking” countries. This has less surgical but mostly historical background. As German German-certified urologist I primarily learned so-called “Prof. Schreiter way im RP”, who promoted a pelvic intraperitoneal location for the reservoir in the 1990s requiring a second suprainguinal incision. This method of RP is still widely spread in Germany, Austria, and Switzerland because of the similar surgical school in this region of Europe. In general, change a strategy or search for alternative surgical methods predestined by complications or bad outcome. The recent patient’s preference of minimally invasive robot-assisted surgery has led to increasing numbers of robotic-assisted prostatectomies, cystectomies, or rectum resections. Because the peritoneal veil is not restored after robotic surgery scar formation and adhesions in the space of Retzius hinder SR reservoir placement. Today, most high-volume implanters are using non-traditional reservoir location on a regular basis, and some have switched to it exclusively.
Purpose of Review Supporting struggling urology residents is an important yet challenging task. We describe strategies to assess resident performance, challenges in the clinical learning environment that contribute to resident remediation, and support mechanisms. This review highlights existing resources for positive outcomes in remediation and promotes exploration of innovative strategies to support future urology residents. Recent Findings Burnout is associated with poor resident performance. Factors that promote burnout include unsatisfactory work-life balance, education or financial debt, access to mental health care, and identifying as a member of an underrepresented group. Competency-based assessment and tailored educational interventions can effectively address the needs of a struggling learner. Efforts to create standardized language, specialty-specific remediation programs, and robust mentorship infrastructure have been successful in other specialties. Summary Study of interventions and outcomes for struggling urology residents is somewhat limited; deeper understanding of prevailing remediations practices and individual needs of struggling residents will be critical to develop more robust support for trainees.
Purpose of Review To provide a primer for how augmented reality (AR)-guided surgical technology works at a fundamental level and discuss recent advances and limitations in a rapidly advancing field, including studies aiming to reduce current issues limiting wider adoption. Recent Findings Among the studies published within the last five years, AR-guided technologies have advanced from pre-operative planning to intraoperative use in procedures including robot-assisted radical prostatectomy, percutaneous nephrolithotomy, and renal transplantation. Artificial intelligence (AI) and deep learning techniques have allowed for development of automatic registration to address challenges with soft tissue deformation. Subspecialities which may benefit from further AR/MR adoption include reconstructive and andrology, which were underrepresented in our review. Summary Augmented reality refers to the process of superimposing digital information (e.g., preoperative imaging) on top of the physical world. Along with its interactive counterpart, mixed reality (MR), AR has become an area of sustained research interest in the urological surgery space. This technology has significant implications for surgical accuracy, efficiency, and medical education. As a result, it is critical for clinicians to both be aware of advancements in the field and understand the basics of this technology. We discuss articles published from March 2021 to February 2025, across a range of urologic procedures and applications, and discuss how recent trends point to a shift towards higher-powered, prospective studies incorporating intraoperative usage of AR/MR.
Purpose Technological evolution is radically changing medical learning models. We evaluated the learning outcomes of urological concepts using ChatGPT, traditional lecture and combined approach. Methods We conducted a randomized triple-blind study on 121 medical students with no previous formal curriculum in urology. Students were randomly divided into three study classes with different learning methods: ChatGPT, Lecture and ChatGPT + Lecture. The “adrenal glands” were randomly extracted as the subject of the lessons. Students were evaluated using a thirty-question test. Results The evaluation test median score was higher for students who underwent ChatGPT + Lecture compared with those who had only ChatGPT (10 vs. 12, p = 0.007). Such differences remained statistically significant also in multivariable models adjusting according to year of course, gender and previous ChatGPT experience (estimate: 2.6, p-value = 0.002). For most of the questions (about 70%), the proportion of students correctly answering was higher in the ChatGPT + Lecture learning groups than in the other groups. Conclusion ChatGPT loses its potential if used without a previous background. The limits of scientific reliability persist and a teacher-guided method is still essential. ChatGPT + traditional lecture gives more effective results than the single traditional lecture also allowing a better use of the chatbot.
Background Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). However, the relationship between HCQ blood concentration and the therapeutic effect for IgAN has not yet been defined. This study investigates the optimal and efficacious range of HCQ blood concentrations in Chinese patients with IgAN. Methods Seventy-three patients with biopsy-proven IgAN who were at risk of progression were included in this study. Thirty-eight patients with IgAN were treated with HCQ plus an optimized renin–angiotensin–aldosterone system inhibitor (RAASi), and thirty-five patients received only RAASi. Blood HCQ concentration and 24-h proteinuria were examined at three and six months after treatment. Results The baseline proteinuria levels were comparable between the RAASi and HCQ groups. The HCQ group had lower 24-h proteinuria than the RAASi group three months after treatment, though the difference was not significant ( p = 0.38). After six months, the median proteinuria level was significantly lower in the HCQ group than in the RAASi group ( p < 0.05). The percentage reduction in 24-h proteinuria in the HCQ group was greater than that in the RAASi group at three ( p < 0.05) and six months ( p < 0.05). Hydroxychlorquine blood concentration and efficacy were positively correlated at three months ( r = 0.428, p < 0.05) and six months ( r = 0.48, p < 0.05). Moreover, the optimal blood concentration of HCQ for three-month efficacy was 418.96 ng/mL and that for six-month efficacy was 582.48 ng/mL. No serious adverse events were reported during HCQ treatment. Conclusions Hydroxyhloroquine safely reduces proteinuria in Chinese patients with IgAN. The efficacy of HCQ is positively correlated with its blood concentration. Graphical abstract
Despite total knee arthroplasty (TKA) being the gold standard for end-stage knee osteoarthritis, 20% of patients remain dissatisfied. Robotic-assisted arthroplasty promises unparalleled control of the accuracy of bone cuts, implant positioning, control of gap balance, and resultant hip–knee–ankle (HKA) axis. Patients underwent clinical and radiological assessments, including knee CT scans and patient-reported outcome measures (PROMs), preoperatively. Follow-up assessments were conducted at 2 weeks, 6 weeks, and 3 months post-operatively, with imaging repeated at 6 weeks. A total of 155 patients underwent robotic-assisted TKA and have completed 3 months of follow-up. Mean pre-operative HKA axis was 7.39 ± 5.52 degrees varus, improving to 1.34 ± 2.22 degrees varus post-operatively. Restoration of HKA axis was 0.76 ± 1.9 degrees from intra-operative planning ( p < 0.0005). Implant placement accuracy in the coronal plane was 0.08 ± 1.36 degrees ( p = 0.458) for the femoral component and 0.71 ± 1.3 degrees ( p < 0.0005) for the tibial component. Rotational alignment mean deviation was 0.39 ± 1.49 degrees ( p = 0.001). Most patients (98.1%) had ≤ 2 mm difference in extension–flexion gaps. PROM scores showed improvement and exceeded pre-operative scores by 6 weeks post-surgery. Robotic-assisted knee arthroplasty provides precise control over traditionally subjective factors, demonstrating excellent early post-operative outcomes. Level of evidence Prospective observational study—II.
The function of the lower urinary tract, to store and periodically eliminate urine, is very simple but its neuronal control is complex and reflects the high prevalence of dysfunction in patients with neurological diseases. The aims of the neuro-urological management are the preservation of upper urinary tract function, enhancing of quality of life, control of urinary tract infection, and maintenance of a low-pressure bladder that is both continent and capable of emptying completely. An appropriate neuro-urological work-up is essential to achieve these goals including (as appropriate) medical history, validated questionnaires, bladder diary, physical examination, urethro-cystoscopy with bladder washing cytology, renal function assessment, and non-invasive / invasive urodynamics. In the neuro-urological patient, meticulous lower urinary tract function assessment is crucial. It is the prerequisite for clinical decision making and for tailoring treatment to the individual patient.
We beschrijven een casus van een 22-jarige patiënt die door gebruik van desmopressine in combinatie met alcohol in comateuze toestand is opgenomen op de intensive care. Er was sprake van hersenoedeem door een diepe hyponatriëmie van 117 mmol/l. We gaan in op de verschillende oorzaken die hiertoe hebben geleid en op welke manier een dergelijk ernstig incident voorkomen kan worden. We describe a case of a 22-year old patient who went in a coma and was admitted to the Intensive Care unit after consuming alcohol in combination with desmopressin. Cerebral edema was diagnosed, blood tests revealed a sodium level of 117 mmol/L. The reasons leading to these events are discussed, as well as preventive measures.
Robot-assisted surgery (RAS) has now become widely adopted in the clinical field, and there is one platform, the da Vinci system, which has captured the lion’s share of the world market. The size, acquisition, and upkeep expenses of this incumbent device, however, have limited its use in resource-constrained areas. The MP1000 robotic surgical system is an independently developed surgical robot that has been introduced into the clinical setting in recent years. This study was designed to evaluate and compare the perioperative outcomes of the MP1000 with the da Vinci platform across major urologic oncologic procedures. A systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library was performed to identify clinical studies directly comparing the MP1000-assisted platform with the da Vinci system in urologic surgery. Outcomes examined included total operative time, estimated blood loss, docking time, console time, positive surgical margins (PSM), and overall complications. Procedure-specific subgroup analyses were conducted for robot-assisted radical prostatectomy (RARP), robot-assisted partial nephrectomy (RAPN), and robot-assisted radical cystectomy (RARC). Six articles provided seven datasets comprising 510 patients (203 MP1000, 307 da Vinci). Procedure-specific analyses revealed differential findings. For RAR P, MP1000 was associated with significantly longer operative time (MD 20.12 min, 95% CI 2.43–37. 81, p < 0.05) and higher complication rates (OR 3.65, 95% CI 1.08–12.31, p < 0.05), but no significant differences in blood loss or PSM. For RAPN, no significant differences were observed for operative time, blood loss, complications, or PSM; however, patients in the MP1000 arm had lower RENAL nephrometry scores (less complex tumors), representing selection bias favoring the novel system. For RARC, limited data (single study) showed higher blood loss with MP1000 attributable to a single case with severe adhesions. Across procedures, docking time (WMD = 1. 58 min, 95% CI: 1.29 to 1.87, p < 0.05) and console time (WMD = 20. 44 min, 95% CI: 8.57 to 32.31, p < 0.05) were significantly longer with MP1000. The absence of PSM events in RAPN and RARC cohorts reflected small sample sizes rather than definitive oncologic equivalence. Preliminary findings suggest that the MP1000 platform demonstrates perioperative outcomes that did not differ significantly from the da Vinci system for several endpoints in select urologic oncologic procedures. Due to the relative inexperience of the operative team with this new technology, however, longer docking and console times were needed with the MP1000. Importantly, the absence of statistically significant differences should not be interpreted as evidence of equivalence or noninferiority. Large-scale multicenter randomized controlled trials—adequately powered and conducted after overcoming the learning curve—are required to validate these preliminary findings and provide evidence-based support for expanding surgical options in clinical practice.
Robotics have been at the forefront of technological applications in healthcare Over the past 20 years, this technology has undergone significant expansion, resulting in enhanced precision, improved accuracy, and the groundbreaking ability to perform teleoperations. These advancements, however, would not have been possible without the support of robust telecommunication and network infrastructures. These supporting technologies ensure seamless connectivity and reliability during remote procedures. Despite its widespread implementation in some Asian and western countries, this industry remains at its infancy in developing countries. This article explores the use of surgical robotics in the context of developing countries, with a particular focus on Morocco. It examines the current state of the technology, potential applications, and presents a groundbreaking pilot case where a telesurgery was successfully performed in Morocco by a surgical team based in China. Finally, the article outlines a roadmap for future implementations of robotics in the surgical field in Morocco.
Introduction High cord radical orchidectomy (HRCO) is accepted as the standard surgical approach in testicular cancer, however low cord orchidectomy (LCRO) can reduce the morbidity of operation without worsening the oncological outcomes. Methods We retrospectively re-examined the specimens of men to determine the level of spermatic cord invasion (SCI). Men who had proximal SCI with negative surgical margins after HRCO were assumed to have de-novo residual tumour if LCRO was performed. Others were assumed as oncologically similar. We examined the relation between pre-operative variables and SCI and proximal SCI to determine whether prediction of proximal SCI is possible. Results 196 patients were included. 22 (11%) had SCI and ten (5%) had proximal SCI. Four patients with proximal SCI had positive surgical margins even after HRCO and didn’t require additional local treatment. Six patients were assumed to have de-novo residual tumour if LCRO was performed. All six patients were metastatic and had systemic chemotherapy. High platelet count, tumour size, N stage, S stage and M stage were all significantly related with both SCI and proximal SCI (p < 0.05). Conclusion Due to low probability of SCI, we think LCRO can safely be performed to reduce morbidity in Stage 1 patients. Although there is a risk for residual tumour in Stage 2–3 patients, currently there is no data that residual tumour would impair the success of systemic chemotherapy. Therefore we can not assume that these patients would be negatively affected. Pre-operative data can be useful to predict the presence of proximal SCI and select appropriate patients for LCRO.
Urban sludge contains pharmaceutical residues and various biocides, which are partly treated in wastewater treatment plants. Liquid manure contains also veterinary pharmaceuticals and biocides used to clean livestock installations. Both sludge and manure are spread as agricultural fertilisers. Traces of human and veterinary pharmaceutical residues, as well as biocides, are also present in many rivers and aquifers, and in agricultural soils in France and around the world. The thesis is devoted to the evaluation of transfers of and processes (degradation, infiltration, adsorption, etc.) related to pharmaceutical residues and biocides from both urban sludge and liquid manure spread on fields as fertilizer for agriculture. It is part of the Telesphore project carried out on the SIPIBEL observatory. The main objective is to evaluate the possible contamination of soil and groundwater by pharmaceuticals and biocides due to organic waste products (OWPs) spread for fertilizing. The experimental part is based on three scales experiments: (i) controlled microcosm assays to characterise sorption onto soils and soil/OWP mixtures (ii) lab soil column assays under controlled conditions on soil columns to assess vertical transport and (iii) \textit{in situ} spreading campaigns on lysimeters, under both actual and augmented conditions of OWPs spreading. The sorption parameters obtained from the microcosm assays were used for HYDRUS-1D modelling of reactive transport in the soil columns. The contrasting behaviour of pharmaceutical and biocides residues at the different scales highlights the complexity of the processes involved in the fate of pharmaceutical and biocidal residues after spreading of OWPs. Overall, the results show that manure and sludge spread at agronomic rates do not lead to the accumulation of pharmaceutical and biocidal residues in the soil, and that the flux of compounds retained in the soil or transported to groundwater represent a small fraction of what is spread with the OWPs.
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Les boues urbaines contiennent des résidus pharmaceutiques et des biocides divers, partiellement traités dans les stations d’épuration. Le lisier contient des pharmaceutiques vétérinaires et des biocides utilisés pour le nettoyage des installations d’élevage. Les boues comme les lisiers sont épandus comme fertilisant pour l’agriculture. Des traces de résidus pharmaceutiques humains et vétérinaires, ainsi que des biocides sont ainsi présents dans de nombreuses rivières et aquifères, et dans les sols agricoles en France et dans le monde entier. La thèse est consacrée à l'évaluation des transferts et des processus associés (dégradation, infiltration, adsorption, etc.) liés aux résidus pharmaceutiques et aux biocides provenant à la fois des boues des stations d'épuration urbaines et des lisiers épandus sur les champs comme engrais pour l'agriculture. Elle fait partie du projet Telesphore réalisé sur l'observatoire SIPIBEL. L'objectif principal est d'évaluer la contamination possible par les produits pharmaceutiques et les biocides des sols et des eaux souterraines due à l'épandage de produits résiduaires organiques (PRO) comme fertilisants. La partie expérimentale est bâtie sur trois échelles d’étude (i) des essais en microcosme pour caractériser la sorption à des sols et des mélanges sol/PRO (ii) des essais en conditions contrôlées sur colonnes de sol pour évaluer les transferts verticaux et (iii) des campagnes in situ sur des lysimètres (Fig. 1) soit en condition réelle d’épandage, soit en taux d’application élevé de PRO. Les paramètres de sorption obtenus par les essais en microcosme sont utilisés pour la modélisation sur HYDRUS 1D du transfert réactif des essais sur colonnes de sol.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people globally since its first detection in late 2019. Besides humans, cats and, to some extent, dogs were shown to be susceptible to SARS-CoV-2, highlighting the need for surveillance in a One Health context. Seven veterinary clinics from regions with high incidences of coronavirus disease (COVID-19) were recruited during the early pandemic (March to July 2020) for the screening of patients. A total of 2257 oropharyngeal and nasal swab specimen from 877 dogs and 260 cats (including 18 animals from COVID-19-affected households and 92 animals with signs of respiratory disease) were analyzed for the presence of SARS-CoV-2 RNA using reverse transcriptase real-time polymerase chain reaction (RT-qPCR) targeting the viral envelope (E) and RNA dependent RNA polymerase (RdRp) genes. One oropharyngeal swab from an Italian cat, living in a COVID-19-affected household in Piedmont, tested positive in RT-qPCR (1/260; 0.38%, 95% CI: 0.01-2.1%), and SARS-CoV-2 infection of the animal was serologically confirmed six months later. One oropharyngeal swab from a dog was potentially positive (1/877; 0.1%, 95% CI: 0.002-0.63%), but the result was not confirmed in a reference laboratory. Analyses of convenience sera from 118 animals identified one dog (1/94; 1.1%; 95% CI: 0.02-5.7%) from Lombardy, but no cats (0/24), as positive for anti-SARS-CoV-2 receptor binding domain (RBD) antibodies and neutralizing activity. These findings support the hypothesis that the prevalence of SARS-CoV-2 infection in pet cat and dog populations, and hence, the risk of zoonotic transmission to veterinary staff, was low during the first wave of the pandemic, even in hotspot areas.
Background The veterinary care of cats and dogs is increasingly embracing innovations first applied to human health, including an increased emphasis on preventative care and precision medicine. Large scale human population biobanks have advanced research in these areas; however, few have been established in veterinary medicine. The MARS PETCARE BIOBANK™ (MPB) is a prospective study that aims to build a longitudinal bank of biological samples, with paired medical and lifestyle data, from 20,000 initially healthy cats and dogs (10,000 / species), recruited through veterinary hospitals over a ten-year period. Here, we describe the MPB protocol and discuss its potential as a platform to increase understanding of why and how diseases develop and how to advance personalised veterinary healthcare. Methods At regular intervals, extensive diet, health and lifestyle information, electronic medical records, clinicopathology and activity data are collected, genotypes, whole genome sequences and faecal metagenomes analysed, and blood, plasma, serum, and faecal samples stored for future research. Discussion Proposed areas for research include the early detection and progression of age-related disease, risk factors for common conditions, the influence of the microbiome on health and disease and, through genome wide association studies, the identification of candidate loci for disease associated genetic variants. Genomic data will be open access and research proposals for access to data and samples will be considered. Over the coming years, the MPB will provide the longitudinal data and systematically collected biological samples required to generate important insights into companion animal health, identifying biomarkers of disease, supporting earlier identification of risk, and enabling individually tailored interventions to manage disease.
The indiscriminate usage and overuse of antimicrobials in pets or companion animals are underlying causes of antimicrobial resistance (AMR). Despite the multi-faceted global challenge presented by antimicrobial resistance, very few studies have appraised pet practitioners’ factors, such as written policy on antimicrobials, dose rate prescribed, use of critically important antimicrobials, and antimicrobial prescription in clean surgical procedures, which can contribute to AMR. In the present study, an online cross-sectional survey among randomly selected pet practitioners (n = 104) of various Indian provinces and union territories was conducted using a questionnaire comprising 33 closed-ended questions on different parameters, viz., the dosage regimen and level of compliance towards guidelines of the World Health Organization (WHO), other relevant veterinary associations, and their opinion while prescribing antimicrobials. Almost every practitioner of the 104 respondents had revealed the difficulties with owner compliance; i.e., incomplete course of the antibiotics, inappropriate follow-ups, and improper care of the sick animals. The majority of practitioners (95%) reported self-prescription of antimicrobials by the owner before presenting the pet(s) to the veterinary clinic, whereas more than half of the respondents (64%) revealed unavailability of antibiogram facilities. Furthermore, a large number (76%) of practitioners stated empirical treatment based on their experience as the main criteria for antimicrobial choice in the absence of timely results from the laboratory. Although non-necessitated use of antimicrobials in clean surgical procedures has been claimed, surprisingly, the majority of pet practitioners (97%) reported their use to reduce the post-operative complications. The use of the highest priority, critically important antimicrobials (HPCIA) listed by the WHO for humans, particularly quinolones and third-generation cephalosporin, also has been reported for different infections. The treatment durations were nearly as per the recommended guidelines issued by the Danish Small Animal Veterinary Association (DSAVA) for different ailments. Analysis using chi-square tests exhibited a significant correlation between less experienced veterinarians (less than 5 years) and prescription of antimicrobials restricted for critically important infections in human medicine. However, there seems to be no association between the experience of the practitioner and the further studied parameters, namely, antimicrobial regimen prescription, weighing the animals before prescription, dose rate calculation, and antimicrobial selection and use after clean surgical operations. The findings suggest periodic awareness campaigns among practitioners regarding the implementation of the official guidelines, the need for systematic surveillance of AMR, awareness among pet owners about antimicrobial resistance, and the importance of rational use of antimicrobials on their pets.
Background The Shar Pei is a common dog breed with a distinctive appearance caused by hyaluronosis that has been linked with several health conditions. Anonymised primary-care veterinary clinical records were explored to extract data on the demography, common disorders and mortality of Shar Pei in the UK in 2013. Results The study population of 455,557 dogs included 1913 (0.42%) Shar Pei. The mean adult bodyweight was 22.26 kg. The most prevalent fine-level precision disorders were entropion (prevalence 17.88%, 95% CI: 16.16-19.59), otitis externa (16.36%, 95% CI: 14.70-18.02), ear disorders (6.69%, 95% CI: 5.57-7.81), aggression (5.23%, 95% CI: 4.23-6.22), and pyoderma (4.29%, 95% CI: 3.38-5.19). The most prevalent disorder groups were ophthalmologic (prevalence = 22.27%, 95% CI: 20.40-24.13), dermatological (21.01%, 95% CI: 19.19-22.84), aural (18.66%, 95% CI: 16.92-20.41), traumatic injury (7.53%, 95% CI: 6.35-8.71) and behavioural (7.21%, 95% CI: 6.05-8.37). The median longevity of 190 Shar Pei that died during the study period was 7.28 years (IQR 5.04-10.05, range 0.04-15.04). Of 184 deaths with a recorded method of death, 157 (85.33%) deaths involved euthanasia and 27 (14.67%) deaths were unassisted. Among 136 (71.58%) deaths with a recorded biomedical cause of death, the most common causes of death at group level precision were neoplasia (15.44%, 95% CI: 9.37-21.51), renal disorders (13.24%, 95% CI: 7.54-18.93), and behavioural disorders (11.03%, 95% CI: 5.76-16.29). Conclusions Almost one fifth of Shar Pei receive veterinary care each year for entropion, a condition linked strongly with the extreme conformation of thickened and folded skin and bristly hair that characterises the Shar Pei breed. Several other common disorders are also linked to hyaluronosis. Current UK legislation can help support efforts to avoid breeding or acquiring animals with extreme conformations and to promote adequate veterinary care for already-owned animals with extreme conformations. The Shar Pei dog breed is instantly recognisable by their copious loose folded skin and bristly coat, with Shar Pei translating from Chinese as ‘sand paper skin’. Although originally a fighting, hunting and guarding dog in China, the Shar Pei breed was re-invented in the US as a companion animal in the late 1970s where a more wrinkled and heavy-set American ‘meat mouth’ variety replaced the traditional ‘bone mouth’ variety originally popular in China. However, the underlying disease of hyaluronosis that causes the characteristic extreme appearance of the Shar Pei has also been linked with several other health problems in the breed such as in-turned eyelids (entropion) and ear disease. Using anonymised veterinary clinical records collected within the VetCompass Programme at the Royal Veterinary College (RVC), Shar Pei made up 0.4% of all dogs in the UK in 2013 and had an average adult bodyweight of 22 kg. The most common specific disorders diagnosed in Shar Pei were in-turned eyelids (17.88%), ear infection (16.36%), ear problems (6.69%), aggression (5.23%), and skin infection (4.29%). Among the 30 most common specific disorders, females were more likely to show in-turned eyelids and conjunctivitis, while males were more likely to show aggression and infected paws. Once the disorders were grouped, the most common disorder groups were eye disorders (22.27%), skin (21.01%), ear (18.66%), traumatic injury (7.53%), and behavioural (7.21%). The average lifespan of Shar Pei was 7.28 years. The most common causes of death were cancer (15.44%,), kidney disorders (13.24%), and behavioural disorders (11.03%). This study highlights that almost one fifth of the breed receive veterinary care each year for in-turned eyelids that can lead to extreme pain and are linked to the thickened and folded skin that humans find so appealing in this breed. Current UK legislation can help support concerted efforts from all animal welfare stakeholders to avoid breeding or acquiring animals with these and other extreme conformations and to promote adequate veterinary care for already-owned animals with extreme conformations.
Background The UK Canine Diabetes Register and Archive (UKCDRA), established in 1999, is a valuable resource of clinical data and blood samples from diabetic dogs. This study aimed to provide updated information about the epidemiology and clinical management of canine diabetes mellitus (DM) in UK veterinary practices. Method Data from samples submitted to UKCDRA between December 2005 and December 2019 were divided into three groups according to DM aetiology: juvenile-onset, adult-onset non-dioestrus and adult-onset female entire. Epidemiological and clinical factors were analysed across groups. Breeds with more than 5 UKCDRA DM cases and/or ≥ 5000 dogs in the non-diabetic VetCompass denominator population were compared to those in the wider UK VetCompass™ population to explore breed DM risk. Results Ninety-nine breeds were represented in the study, with 25 breeds having 5 or more diabetic cases. Samoyeds and Tibetan terriers demonstrated the highest odds of DM in both of the adult-onset DM groups. Age of adult-onset DM onset co-varied with breed, with the Standard Doberman Pinscher and Rottweiler demonstrating youngest onset age. Twice daily Caninsulin (40 iu/ml porcine insulin) was the most commonly reported treatment. Twice-daily rather than once-daily insulin therapy in canine DM has become more prevalent since the archive was founded. Limitations UKCDRA does not capture detailed information on concurrent diseases or DM environmental risk factors. Conclusion This study provides an update to an earlier UKCDRA report and demonstrates shared breed-associated risk factors for adult-onset non-dioestrus and female entire DM.
Background Advanced diagnostic imaging is an essential part of preoperative planning for oral and maxillofacial surgery in veterinary patients. 3-dimensional (3D) printed models and surgical guides generated from diagnostic imaging can provide a deeper understanding of the complex maxillofacial anatomy, including relevant spatial relationships. Additionally, patient-specific 3D printed models allow surgeons and trainees to better examine anatomical features through tactile and visuospatial feedback allowing for improved preoperative planning, intraoperative guidance, and enhanced trainee education. Furthermore, these models facilitate discussions with pet owners, allowing for improved owner understanding of pathology, and educated decision-making regarding treatment. Case presentation Our case series consists of three 3D printed models segmented from computed tomography (CT) and cone beam CT (CBCT) and fabricated via desktop vat polymerization for preoperative planning and intraoperative guidance for resection of maxillary osteosarcoma, mandibular reconstruction after mandibulectomy, and gap arthroplasty for temporomandibular joint ankylosis in dogs. Conclusions We illustrate multiple benefits and indications for 3D printing in veterinary oral and maxillofacial surgery. 3D printed models facilitate the understanding of complex surgical anatomy, creating an opportunity to assess the spatial relationship of the relevant structures. It facilitates individualized surgical planning by allowing surgeons to tailor and augment the surgical plan by examining patient-specific anatomy and pathology. Surgical steps may also be simulated in advance, including planning of osteotomy lines, and pre-contouring of titanium plates for reconstruction. Additionally, a 3D printed model and surgical guide also serve as invaluable intraoperative reference and guidance. Furthermore, 3D printed models have the potential to improve veterinary resident and student training as well as pet owner understanding and communication regarding the condition of their pets, treatment plan and intended outcomes.
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.
SIMPLE SUMMARY: Inappropriate use of regular anthelmintic drugs has led to the development of anthelmintic resistance in sheep gastrointestinal nematodes (GINs) and consequently caused huge economic losses. Therefore, researchers worldwide are making efforts in finding novel strategies to control these parasites, which are mostly based on the rational use of synthetic drugs and the use of various alternatives, such as botanical anthelmintics. The aim of this study was to evaluate the anthelmintic efficacy of the essential oil (EO) of oregano (Origanum vulgare (L.)) against sheep GINs and to demonstrate the possibility of its use in veterinary practice. For obtaining clear results, both in vitro (egg hatch test) and in vivo efficacy tests (fecal egg count reduction test), as well as toxicity studies, on the hosts (clinical examination, blood count, and liver or kidney function test) were performed. The egg hatch test demonstrated the anthelmintic potential of the tested EO with an efficacy of 71.3%–93.7%, which was also demonstrated in the fecal egg count reduction test with an efficacy of 60.1% in total (on the second farm, 78.26%) shown on day 14 after treatment. Moreover, no negative or side effects of the applied EO formulation to the sheep were noticed in toxicity studies. The obtained results indicate the high potential of the O. vulgare EO for use in veterinary practice to control sheep GINs, as a part of an integrated strategy aimed to reduce the use of conventional anthelmintics. Therefore, these results may be significant for the future management of these infections. ABSTRACT: The development of anthelmintic resistance in sheep gastrointestinal nematodes (GINs) requires novel strategies for the sustainable control of these parasites. This study aimed to evaluate the anthelmintic efficacy of the Origanum vulgare (L.) essential oil (EO) against sheep GINs and to evaluate the possibility of its use in control practice. The in vitro egg hatch test was conducted at eight different concentrations (50, 12.5, 3.125, 0.781, 0.195, 0.049, 0.025, and 0.0125 mg/mL) of the tested EO. For the in vivo fecal egg count reduction test, the EO of O. vulgare was administrated orally at a mean single dose of 150 mg/kg to sheep from two farms in Southern Italy, whereby potential toxic effects to the hosts were also evaluated. In the egg hatch test, the inhibition of egg hatchability varied from 71.3% to 93.7%, depending on the concentration used. The high anthelmintic potential was confirmed in the fecal egg count reduction test with an average reduction of nematode eggs in feces of 43.2% and 60.1% on days 7 and 14 after treatment, respectively. In addition, no toxic effects were noticed during the clinical examination of sheep or by observing blood count and liver or kidney function test results. The obtained results suggest the strong activity of the O. vulgare EO against sheep GINs, probably due to a high percentage of carvacrol (76.21%), whereby it can be considered safe for sheep at the dose tested in vivo. Therefore, it is suitable for use in veterinary practice as a part of an integrated strategy for the control of sheep GINs.
Animal welfare monitoring is a vital part of veterinary medicine and can be challenging due to a range of factors that contribute to the perception of welfare. Tools can be used, however; there are few validated and objective methods available for veterinary and animal welfare professionals to assess and monitor the welfare of dogs over their lifetime. This study aimed to adapt a framework previously validated for other species, The Animal Welfare Assessment Grid (AWAG), for dogs and to host the tool on an accessible, easy to use online platform. Development of the AWAG for dogs involved using the scientific literature to decide which factors were relevant to score welfare in dogs and to also write the factor descriptors. The primary tool was trialed with veterinary professionals to refine and improve the AWAG. Content validity was assessed by subject matter experts by rating the validity of the factors for assessing dog welfare using the item-level content validity index (I-CVI) and scale-level content validity index based on the average method (S-CVI/Ave). Construct validity was evaluated by users of the tool scoring healthy and sick dogs, as well as healthy dogs undergoing neutering procedures. Mann Whitney tests demonstrate that the tool can differentiate between healthy and sick dogs, and healthy and healthy dogs post elective surgery. Test re-test reliability was tested by users conducting multiple assessments on individual dogs under non-changing conditions. Inter-rater reliability was assessed by two users scoring an individual dog at the same time in veterinary referral practice. Repeated measures ANOVA for test re-test and inter-rater reliability both show no statistical difference between scores and that the scores are highly correlated. This study provides evidence that the AWAG for dogs has good content and construct validity, alongside good test re-test and inter-rater reliability.
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.
SIMPLE SUMMARY: This report describes how to apply the combination of 3D scanning, computer-aided design (CAD), and 3D printing to make a protective device for rescuing wild animals. In recent years, although 3D tools have become relatively low-cost and reachable, veterinary medical applications based on this technology are quite limited. The present article successfully extricates a wild freshwater turtle from an extensive shell defect within a short period. Integration of multiple sciences to 3D technology can provide a facile model for veterinary medical applications. ABSTRACT: Numerous cases and a shortage of resources usually limit wild animal rescue. New technology might save these severely injured wild animals from euthanasia by easing the requirement of intensive medication. Three-dimensional (3D) technologies provide precise and accurate results that improve the quality of medical applications. These 3D tools have become relatively low-cost and accessible in recent years. In the medical field of exotic animals, turtle shell defects are highly challenging because of inevitable water immersion. This report is the first attempt to apply the combination of 3D scanning, computer-aided design (CAD), and 3D printing to make a device that protects the wound from exposure to water or infection sources. The presented techniques successfully extricate a wild freshwater turtle from an extensive shell defect within a short period. Integration of multiple sciences to 3D technology can provide a facile model for veterinary medical applications.
Pugs have become phenomenally popular in the UK over recent decades. The breed has a flat-faced look (brachycephalic) that many humans find highly attractive and ‘cute’ but this flat face is also linked to several serious health problems. Consequently, there is growing concern about the welfare issues associated with the popularity and health issues of Pugs. To get a better overall perspective on the health of Pugs, this study aimed to compare the risks of common disorders between Pugs and all remaining dogs. The study collected clinical information from first opinion veterinary practices in the UK that were participating in VetCompass. Dogs were grouped as either Pugs or non-Pugs. Information was gathered from the clinical records on all disorders diagnosed in each group during 2016 and a list of the most common disorders in each group was generated. From 905,544 dogs in the overall study, there were 16,218 (1.79%) Pugs and 889,326 (98.21%) non-Pugs. Pugs (2.36 years, interquartile range [IQR] 1.16–4.53) were generally younger than non-Pugs (4.44 years, IQR 1.90–8.12). Pugs (8.95 kg, IQR 7.80–10.17) were also generally lower in bodyweight than non-Pugs (14.07 kg, IQR 8.15–25.20). From a combined list of 40 common disorders among both groups of dogs, Pugs had increased risk for 23 (57.5%) but had reduced risk for 7 (17.5%) disorders compared to non-Pugs. The disorders with the highest relative risk in Pugs included brachycephalic obstructive airway syndrome (BOAS) (× 53.92 risk), narrowed nostrils (× 51.25), eye ulceration (× 13.01), and skin fold infection (× 10.98). Disorders with the lowest relative risk in Pugs included heart murmur (× 0.23), fatty lump (× 0.24), aggression (× 0.31), and wounds (× 0.53). The study provides a broad evidence base on the positive and negative aspects of the health of Pugs. Disease predispositions were more common than disease protections, confirming the hypothesis that there are many critical health-related welfare challenges to overcome for Pugs. The widely differing health profiles between Pugs and other dogs in the UK suggest that the Pug has now diverged to such an extent from mainstream dog breeds that it can no longer be considered as a typical dog from a health perspective. Background Pugs are a brachycephalic dog breed that has become phenomenally popular over recent decades. However, there is growing concern about serious health and welfare issues in the breed. To augment the evidence-base on the comparative health of Pugs, this study aimed to compare the odds of common disorders between Pugs and all remaining dogs under primary veterinary care in the UK during 2016. A cross-sectional study design of VetCompass clinical records was used to estimate the one-year (2016) period prevalence for the disorders most commonly diagnosed in Pugs and non-Pugs. Risk factor analysis applied multivariable logistic regression modelling methods to compare the odds of 40 common disorders between Pugs and non-Pugs. Results From a study population of 905,544 dogs, the analysis included random samples of 4308 Pugs and 21,835 non-Pugs. Pugs were younger (2.36 years, range 0.07–16.24 vs 4.44 years, range 0.01–20.46, p < 0.001) and lighter (8.95 kg, range 5.00–13.60 vs. 14.07 kg, range 1.41–85.00, p < 0.001) than non-Pugs. Pugs had 1.86 (95% confidence interval [CI] 1.72 to 2.01) times the adjusted odds of diagnosis with ≥1 disorder than non-Pugs. Pugs had significantly increased adjusted odds for 23/40 (57.5%) common disorders. These included: brachycephalic obstructive airway syndrome (odds ratio [OR] 53.92; 95% CI 36.22 to 80.28), stenotic nares (OR 51.25; 95% CI 24.93 to 105.37) and corneal ulceration (OR 13.01; 95% CI 10.50 to 16.11). Conversely, Pugs had significantly reduced adjusted odds of 7/40 (17.5%) common disorders compared to non-Pugs. These included: heart murmur (OR 0.23; 95% 0.13 to 0.14), lipoma (OR 0.24; 95% CI 0.11 to 0.55) and aggression (OR 0.31; 95% CI 0.21 to 0.47). Conclusions The current study highlights that predispositions outnumber protections between Pugs and non-Pugs for common disorders, suggesting some critical health welfare challenges to overcome for Pugs. Highly differing heath profiles between Pugs and other dogs in the UK suggest that the Pug has diverged substantially from mainstream dog breeds and can no longer be considered as a typical dog from a health perspective.
International audience;
Background:Access to veterinary drugs for livestock has become a major issue over the last decade. Analysis has tended to focus on the demand for these products, while studies looking at the drivers behind their use generally focus on farmer behavior and interactions between veterinarians and farmers. However, the use of drugs also depends on structural factors that determine the functioning of the drug supply chain and farmers' access to the drugs. This article presents an overview of the factors that limit access to veterinary drugs in sub-Saharan Africa (SSA) as well as the international policy tools and arrangements that claim to improve it. Methods:We have conducted a scoping review of the scientific and grey literature as well as the publicly-available data from both the animal health industry and international organizations. We aimed to gather information on the veterinary drugs market in SSA as well as on the international norms, recommendations, guidelines, and initiatives that impact SSA farmers' access to these drugs. Findings:We highlight numerous barriers to veterinary drug access in SSA. The SSA market is highly dependent on imports, yet the region attracts little attention from the international companies capable of exporting to it. It suffers from a high level of fragmentation and weak distribution infrastructures and services, and is driven by the multiplication of private non-professional actors playing a growing role in the veterinary drug supply chain. The distribution system is increasingly dualized, with on the one hand the public sector (supported by development organizations) supplying small scale farmers in rural areas, but with limited and irregular means; and on the other side a private sector largely unregulated which supplies commercial and industrial farming systems. Different innovations have been developed at the international and regional levels to try to reduce barriers, such as homogenizing national legislations, donations, and vaccine banks. Alongside decades-old inter-state cooperation, many new forms of public-private partnerships and other hybrid forums continue to emerge, signaling the private sector's increasing influence in global governance. Conclusions:Policies on animal health would be bolstered by a better understanding of the drivers behind and the components of access to veterinary drugs in different regional and national contexts. Inequalities in drug access need to be addressed and a market-driven approach adopted in order to strengthen our understanding of what determines veterinary drug use at the farm level. Policies should balance the interests of the various stakeholders, being careful not to reinforce bias toward certain diseases deemed “interesting” and neglect others that could prove to be highly important for veterinary public health.
BACKGROUND: In dogs, antimicrobial drugs are widely prescribed for aspiration pneumonia (AP) despite poor documentation of bacterial infection in AP (b‐AP) using bronchoalveolar lavage fluid (BALF) analysis. Interpretating discordant cytology and culture results is challenging, contributing to lack of a criterion standard, and highlighting differences between veterinary and human medical criteria for b‐AP. OBJECTIVES: Determine how many dogs with AP had BALF collection and differences in diagnosis of b‐AP using veterinary vs human medical criteria. Report findings of noninvasive markers (e.g. fever, band neutrophilia, radiographic severity score) in dogs with and without b‐AP. ANIMALS: Retrospective cohort study of client‐owned dogs (n = 429) with AP at 2 university veterinary hospitals. Twenty‐four dogs met enrollment criteria. METHODS: Inclusion criteria were radiographic diagnosis of AP, ≥1 risk factor, CBC findings, and BALF cytology and culture results. Veterinary medical b‐AP criteria were cytology findings compatible with sepsis with or without positive culture, or cytology findings not consistent with sepsis and positive culture (≥1.7 × 10(3) cfu/mL). Human medical b‐AP criteria required culture with ≥10(4) cfu/mL or > 7% cells with intracellular bacteria on cytology. RESULTS: Only 24/429 dogs met all enrollment criteria; 379/429 dogs lacked BALF collection. Diagnosis of b‐AP differed using veterinary (79%) vs human (29%) medical criteria. Fever, band neutrophils and high radiographic scores were noted in dogs with and without b‐AP. CONCLUSIONS AND CLINICAL IMPORTANCE: Lack of routine BALF collection hampers definitive recognition of bacterial infection in AP. Differences in dogs meeting veterinary vs human medical definitions for b‐AP and usefulness of noninvasive markers warrant further study to improve understanding of the role of bacteria in AP.
BACKGROUND: Retractions are a key proxy for recognizing errors in research and publication and for reconciling misconduct in the scientific literature. The underlying factors associated with retractions can provide insight and guide policy for journal editors and authors within a discipline. The goal of this study was to systematically review and analyze retracted articles in veterinary medicine and animal health. A database search for retractions of articles with a veterinary/animal health topic, in a veterinary journal, or by veterinary institution-affiliated authors was conducted from first available records through February 2019 in MEDLINE/PubMed, Web of Science, Scopus, Retraction Watch, and Google Scholar. Annual frequency of retractions, journal and article characteristics, author affiliation and country, reasons for retraction, and retraction outcomes were recorded. RESULTS: Two-hundred-forty-two articles retracted between 1993 and 2019 were included in the study. Over this period, the estimated rate of retraction increased from 0.03/1000 to 1.07/1000 veterinary articles. Median time from publication to retraction was 478 days (range 0-3653 days). Retracted articles were published in 30 (12.3%) veterinary journals and 132 (81.5%) nonveterinary journals. Veterinary journals had disproportionately more retractions than nonveterinary journals (P = .0155). Authors/groups with ≥2 retractions accounted for 37.2% of retractions. Authors from Iran and China published 19.4 and 18.2% of retracted articles respectively. Authors were affiliated with a faculty of veterinary medicine in 59.1% of retracted articles. Of 242 retractions, 204 (84.3%) were research articles, of which 6.4% were veterinary clinical research. Publication misconduct (plagiarism, duplicate publication, compromised peer review) accounted for 75.6% of retractions, compared with errors (20.6%) and research misconduct (18.2%). Journals published by societies/institutions were less likely than those from commercial publishers to indicate a reason for retraction. Thirty-one percent of HTML articles and 14% of PDFs were available online but not marked as retracted. CONCLUSIONS: The rate of retraction in the field of veterinary and animal health has increased by ~ 10-fold per 1000 articles since 1993, resulting primarily from increased publication misconduct, often by repeat offenders. Veterinary journals and society/institutional journals could benefit from improvement in the quality of retraction notices. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-022-03167-x.
Drug resistance threatening humans may be linked with antimicrobial and anthelmintic resistance in other species, especially among farm animals and, more in general, in the entire environment. From this perspective, Green Veterinary Pharmacology was proven successful for the control of parasites in small ruminants and for the control of other pests such as varroa in bee farming. As in anthelmintic resistance, antimicrobial resistance (AMR) represents one of the major challenges against the successful treatment of infectious diseases, and antimicrobials use in agriculture contributes to the spread of more AMR bacterial phenotypes, genes, and proteins. With this systematic review, we list Italian plants with documented antimicrobial activity against possible pathogenic microbes. Methods: The literature search included all the manuscripts published since 1990 in PubMed, Web of Science, and Scopus using the keywords (i) “antimicrobial, plants, Italy”; (ii) “antibacterial, plant, Italy”; (iii) “essential oil, antibacterial, Italy”; (iv) “essential oil, antimicrobial, Italy”; (v) “methanol extract, antibacterial, Italy”; (vi) “methanol extract, antimicrobial, Italy”. Results: In total, 105 manuscripts that documented the inhibitory effect of plants growing in Italy against bacteria were included. One hundred thirty-five plants were recorded as effective against Gram+ bacteria, and 88 against Gram−. This will provide a ready-to-use comprehensive tool to be further tested against the indicated list of pathogens and will suggest new alternative strategies against bacterial pathogens to be employed in Green Veterinary Pharmacology applications.
Despite the important role of antimicrobial use in companion animals in the global challenge presented by antimicrobial resistance (AMR), very few studies have quantified pet owner factors that can contribute to suboptimal veterinary antimicrobial use. We conducted an online survey of pet owners, asking about their experiences with veterinarians, their opinions on antibiotic use and knowledge of antibiotics, and their communication preferences regarding judicious prescribing. Just over half (54%) of the 558 pet owners had received antibiotics for their pet at their last non-routine veterinary consultation and most owners were happy (83%) with the antibiotic prescribing decision of their veterinarian. A quarter (25%) indicated that they had been surprised, disappointed or frustrated when a veterinarian had not given their pet antibiotics; 15% had explicitly requested them. Owners placed a higher priority on their pet receiving the most effective treatment than on treatment being cheap or convenient. Most respondents recognized the limitations of antibiotic therapy and the risks associated with antibiotic use, but 50% believed the risks were confined to the treated animal; only a minority was aware of inter-species transfer of bacteria. Pet owners indicated that they would find judicious prescribing messages focused on the direct risks of antibiotics to their pet more compelling than those about public health. Our findings suggest that veterinary communications about responsible antibiotic use should focus on pet owners’ priorities and address or bypass their gaps in understanding regarding antibiotic resistance.
Recently, with increasing interest in pet healthcare, the demand for
computer-aided diagnosis (CAD) systems in veterinary medicine has increased.
The development of veterinary CAD has stagnated due to a lack of sufficient
radiology data. To overcome the challenge, we propose a generative active
learning framework based on a variational autoencoder. This approach aims to
alleviate the scarcity of reliable data for CAD systems in veterinary medicine.
This study utilizes datasets comprising cardiomegaly radiograph data. After
removing annotations and standardizing images, we employed a framework for data
augmentation, which consists of a data generation phase and a query phase for
filtering the generated data. The experimental results revealed that as the
data generated through this framework was added to the training data of the
generative model, the frechet inception distance consistently decreased from
84.14 to 50.75 on the radiograph. Subsequently, when the generated data were
incorporated into the training of the classification model, the false positive
of the confusion matrix also improved from 0.16 to 0.66 on the radiograph. The
proposed framework has the potential to address the challenges of data scarcity
in medical CAD, contributing to its advancement.
SIMPLE SUMMARY: Formal tools are available to aid veterinary assessment of canine quality of life. However, they are rarely applied in practice, and previous research suggests a veterinary perception of owner resistance to their use. Through an online questionnaire, we found that almost all UK dog owners (95.8%) were comfortable discussing their dogs’ quality of life with their vets, yet only a third of owners (32%) reported this topic to have been raised by their vets. Furthermore, the majority of owners (70.8%) were interested in accessing tools to assess their dog’s quality of life, but very few had experienced any form of formal health or well-being assessment tool (4.4%) with their vets. A subset of owners was interviewed about their experiences with such tools, and three main themes were generated from their feedback: ‘Use of assessment tools supports client-vet relationship and empowers owners’, ‘owners want to talk about holistic dog care’, and ‘owner feelings on the wider application of assessment tools’. Overarching findings suggest that owners want to discuss QOL and are interested in using formal assessment tools. Indeed, the uptake of tools appears to be valuable in improving the vet-client relationship and owner confidence in the treatment of their dogs. ABSTRACT: Few veterinary professionals use formal quality of life (QOL) assessment tools despite their recommendation from veterinary governing bodies to enable holistic welfare assessments and target welfare improvement strategies. Perceived barriers include resistance from owners, and this study aimed to elucidate understanding of dog owner engagement with conversations and tools relating to QOL. An online survey that investigated owner experience, comfort, and opinions about vet-client discussions on topics connected to canine health and well-being, including QOL, was completed by 410 owners. Almost all owners (95.8%) were reportedly comfortable discussing QOL, yet only 32% reported their vets had addressed it. A high proportion of owners (70.8%) expressed interest in assessment tools, but only 4.4% had experienced one, none of which were QOL tools per se. Semi-structured interviews of a sub-set of four owners provided a more in-depth examination of their experience of a health and well-being assessment tool. Thematic analysis generated three themes: ‘Use of assessment tools supports client-vet relationship and empowers owners’, ‘Owners want to talk about holistic dog care’, and ‘Owner feelings on the wider application of assessment tools’. Overall, our findings suggest that owners want to broaden the veterinary consultation conversation to discuss QOL and are interested in using tools, and therefore veterinary perceptions of owner-related barriers to tool application appear unfounded. Indeed, tool uptake appears to improve the vet-client relationship and boost owner confidence.
Mary Ann Liebert, Inc., publishersFebruary 2023Veterinary
High-quality, well-annotated, healthy tissue specimens are crucial to the success of basic and translational research, but often difficult to procure. Postmortem (PM) tissue collections provide the opportunity to collect these healthy biospecimens. PM procurement programs led by biobanks can further contribute by providing researchers with rare biospecimens collected with short postmortem intervals (PMI) in controlled environments. To support biomedical and translational research, the Cornell Veterinary Biobank (CVB), an ISO 20387 accredited core resource at the Cornell University College of Veterinary Medicine, has performed PM tissue collections from research and privately owned animals since 2013. The CVB PM collection team, consisting of a board-certified veterinary pathologist, a licensed veterinary technician collection specialist, and a data capture specialist, performs rapid tissue collections during controlled warm necropsies, with an accepted PMI of ≤2 hours and a target PMI of ≤1 hour. A retrospective analysis of PM collections between 2013 and 2020 was completed, consisting of 4077 aliquots of 1582 biospecimens from 69 donors (48 canine, 16 feline, and 5 equine). An average of 22.93 biospecimens per donor were collected (range: 1–49). The average PMI for standard collections was 43.48 ± 2.30 minutes, starting on average 20.81 ± 1.61 minutes after time of death. Thus far, the CVB has a favorable utilization rate, with 414 aliquots (10.15%) from 350 specimens (20.12%) and 45 animals (65.22%) distributed to researchers. The success of the CVB PM tissue biobanking program, collecting high-quality biospecimens with short PMIs, was due to support from veterinary pathologists, the competence of CVB personnel, and the continuous evolution of methods within a quality management system. Improvement of PM tissue collection programs in biobanks, with standardized practices for all processes and specialized personnel, can enhance the quality and increase utilization of its biospecimens and associated data.
Mesenchymal stem cell (MSC) therapy is a promising approach for treating orthopaedic conditions in veterinary clinical patients. MSCs exhibit remarkable regenerative properties, including multilineage differentiation, immunomodulation, and tissue repair, making them an attractive alternative to conventional therapies. This comprehensive review explores the clinical potential of MSCs in managing a range of canine orthopaedic disorders, including fractures, degenerative joint diseases, and tendon injuries. Evidence from canine clinical studies highlights the ability of MSCs to enhance tissue healing, reduce pain, and restore function, offering valuable insights into their therapeutic utility. Optimizing delivery methods, such as intra-articular injections and scaffold-based approaches, is critical for maximizing therapeutic efficacy. Clinical trials in dogs have shown significant improvements in mobility and recovery, underscoring the relevance of MSC therapy for specific orthopaedic applications. Despite its potential, MSC therapy faces several challenges. One major hurdle is study heterogeneity, which complicates evidence synthesis. Differences in cell sourcing, dosage, and injection frequency make it difficult to establish a consensus on optimal treatment protocols. Future advancements should focus on expanding cell-free approaches utilizing MSC-derived bioactive molecules and extracellular vesicles. Furthermore, collaborative efforts between veterinarians, researchers, and industry partners will be critical in translating preclinical findings into viable commercial veterinary stem cell products. Large-scale, randomized clinical trials with standardized methodologies are necessary to validate the efficacy of MSC therapy across different orthopaedic conditions. Graphical abstract
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.
SIMPLE SUMMARY: Parasitic infections are a significant problem in veterinary medicine, and their management requires an in-depth understanding of the parasite life cycle, host-parasite interactions, and the appropriate use of antiparasitic drugs. In this study, we aimed to investigate the knowledge, approaches, and practices of veterinarians in Türkiye regarding parasitic infections and antiparasitic drugs usage. Our study surveyed a diverse group of veterinarians working in various fields of veterinary medicine, including small animal, large animal, and mixed animal practices. The results of our study revealed that while veterinarians in Türkiye generally have a good understanding of parasitic infections and antiparasitic drugs, there are still gaps in their practice, particularly regarding testing anthelmintic resistance, using parasitic diagnostic methods, and attending conferences, symposia, and workshops. Overall, our study provides valuable insights into the current state of parasitic infections and anthelmintic resistance management in veterinary medicine in Türkiye. We believe that the findings of our study will help inform the development of more effective strategies for the prevention and treatment of parasitic infections in animals and contribute to the ongoing efforts to improve animal health and welfare in the region. Our results are also expected to raise awareness about anthelminthic resistance and parasite infections among veterinarians in Türkiye. ABSTRACT: Despite a global background of increasing anthelmintic resistance in parasites, little is known about the current parasite control strategies adopted within the livestock industry in Türkiye. The aim of this survey is to identify the parasitic diseases encountered by veterinarians, the methods and drugs used for the diagnosis and treatment of these diseases, parasite control practices, and other related factors. This survey was conducted online between October 2018 and March 2019 with the participation of 607 veterinarians working in different areas from seven different geographical regions of Türkiye. A total of 29 questions were posed to the veterinarians in the online survey. As a result of this survey, it was determined that veterinarians should utilize laboratory methods more frequently for the detection and diagnosis of parasitic diseases and anthelmintic resistance. It was concluded that to effectively implement diagnosis, prevention, and control measures for parasitic diseases, field veterinarians need to establish closer relationships within academia and increase their participation in national and international conferences, symposia, and workshops where knowledge sharing and exchange take place. In conclusion, antiparasitic drug resistance has become increasingly important recently, and therefore measures taken to prevent the development of resistance should be increased.
Background The success of workplace clinical training (WCT) is important given that veterinary students are licensed to work independently upon graduation. Considering this, it is perhaps surprising that there is limited published work describing what it means to be prepared for this educational experience, particularly given that the transition to WCT can be stressful for students. This paper reports the results of a qualitative study aiming to generate a rich understanding of veterinary student preparedness for WCT using emic, or insider, perspectives of key stakeholders. Methods From a constructivist standpoint, homogenous online group interviews were held with final year veterinary students, recent student alumni, clinical supervisors, faculty, and academic educationalists to discuss what it means to be prepared for WCT. The data was analysed using a template analysis approach. Results A three-tier taxonomy to describe preparedness for WCT was constructed from the data. At the topmost level, there were seven themes to illuminate different aspects of preparedness: students should be prepared 1) for the transition to learning and working in a clinical and professional environment, 2) for self-directed and experiential learning whilst working, 3) with a growth mindset, 4) with intrinsic motivation and enthusiasm for learning and working, 5) for communication, consultation and clinical reasoning, 6) with the knowledge for work, and 7) with the practical competence and confidence for work. Conclusions This study provides a deeper understanding of the tools we can provide, and the attributes we can nurture in, senior veterinary students to facilitate their learning and working during WCT. This improved understanding is a necessary precursor to refining pedagogical support and curriculum design within veterinary schools.
Respiratory Medicine, Immuno-allergology, and Dermatology
25 recent scientific publications in the field of Respiratory Medicine, Immuno-allergology, and Dermatology
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Advances in Dermatology a...
Wróblewska, Agnieszka
Termedia Publishing HouseNovember 2023Respiratory Medicine, Immuno-allergology, and Dermatology
Morphea en coup de sabre and progressive hemifacial atrophy are extremely rare connective tissue disorders causing facial deformity. In extreme cases, morphological disorders are accompanied by symptoms of a clear impairment of the stomatognathic system. The aetiology of the above-mentioned diseases is still unknown. Properly planned therapy in the field of maxillofacial orthopaedics makes it possible to correct the asymmetric pattern of hard tissue growth and thus enable rehabilitation. The task of augmentation techniques is the volumetric supplementation of tissue defects resulting from atrophic processes. The degree of destruction and the extent of changes determine the method of correction. Mild and moderate defects are treated mainly with biomaterials and autologous adipose tissue. The severe course of hemifacial atrophy and morphea en coup de sabre and the associated significant tissue atrophy necessitate the search for more complex methods of treatment. In this paper, we summarize the disturbances of the stomatognathic system in patients with craniofacial morphea, together with an analysis of current treatment options.
OceanSide Publications, Inc.September 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Patients with severe uncontrolled asthma (SUA) overwhelmingly contribute to the economic burden of asthma and may require biologic therapy. However, the impact of the CoronaVirus Disease of 2019 (COVID-19) on asthma costs and biologic use has yet to be evaluated. OBJECTIVE: The objective was to test the hypothesis that SUA costs and biologic use decreased during the pandemic. METHODS: We analyzed medical costs and biologic use in patients with SUV from January 2017 to December 2021, by using claims data from a large managed care organization and electronic health record data from Robert Wood Johnson Barnabas Health, according to provider specialty. RESULTS: Of the 3817 managed care organization enrollees within Robert Wood Johnson Barnabas Health with a primary diagnosis of asthma, 348 were identified as having SUA. A nested sample of 151 patients revealed that 50% were managed by primary care physicians (PCP) and specialists, 43% by PCPs only, and 4% by specialists only. The total costs of the claims were $10.8 million over 5 years ($2.2 million per year), with 60% generated from patients seeing PCPs and specialists, 27% from PCPs only, and 15% from specialists only. During the pandemic, total average costs decreased for all care groups (34% PCP-only patients and 45% for both specialist-only and PCP and specialist patients). Inpatient and outpatient costs also decreased and were lowest for patients who saw specialists and highest for patients who saw PCPs and specialists. In contrast, prescription costs increased during the pandemic. Biologic use was steadily increasing until a twofold decrease was observed during the pandemic. Thirteen patients were on biologics: two were managed by PCPs, four by specialists, and seven by both. CONCLUSION: Inpatient and outpatient costs decreased during the COVID-19 pandemic, but prescription costs increased. Biologic use was increasing among patients with SUA before the pandemic but then drastically decreased and remained lower during the observational interval.
World Allergy OrganizationOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Basic management for food allergy (FA) is eliminating causative food from the diet, which can impact normal growth. This study examined the association between food avoidance and growth failure among children with FA aged 0–3 years using the Japan Environment and Children's Study (JECS) data. METHODS: Data on height, weight, and FA history registered were collected using self-administered questionnaires at age 1, 1.5, 2, and 3 years. A general linear model was used to examine whether dietary restriction affected body size. Height, weight, and body mass index (BMI) were adjusted for age in months using standard deviation (SD) scores for each age group by month of measurement. Presence of FA or dietary restriction was used as a binary variable. RESULTS: Of the 38 477 participants included in this analysis, 4070 with FAs had significantly lower SD scores for height and weight at age 3 years. With milk avoidance, significantly lower SD scores for height (male: β = −0.097 [95%CI: 0.175, −0.019], female: β = −0.103 [95%CI: 0.204, −0.002]), a significantly lower SD score for weight (male: β = −0.115[95%CI: 0.187, −0.043], female β = −0.114[95%CI: 0.203, −0.026]) were observed. Soy avoidance in males marked a lower SD score for height (β = −0.307 [95%CI: 0.474, −0.140]). Continued food avoidance until age 3 resulted in significantly lower SD score for height and weight regardless of gender. CONCLUSION: Growth impairment was observed with food avoidance at age 3 years. Growth impairment were more obvious in males than in females. With regards food items, the impact of milk and soy was more significant.
BioMed CentralFebruary 2024Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Mepolizumab, the first widely available anti-interleukin 5 biologic, targets eosinophilic inflammation and has been shown in clinical trials to reduce exacerbations, oral corticosteroid dependence, and healthcare utilization in patients with severe asthma. The impact of mepolizumab in a real-world, publicly funded healthcare setting is unknown. The objective of this study was to describe the demographics and clinical characteristics of real-world patients receiving mepolizumab, and to compare asthma-related outcomes and associated asthma-related costs before and during mepolizumab use. METHODS: This retrospective, observational study in Ontario, Canada, included patients initiating mepolizumab between February 2016 and March 2019. Patients were identified using the mepolizumab patient support program and linked to the Institute for Clinical Evaluative Sciences database of publicly accessed healthcare. Patient outcomes were obtained for 12 months pre- and post-mepolizumab initiation and compared. RESULTS: A total of 275 patients were enrolled in the overall patient support program cohort (mean [standard deviation] age 57.6 [13.5] years, mean [standard deviation] of the median per-patient eosinophil count 540.4 [491.9] cells/μL). Mepolizumab was associated with reductions in asthma exacerbations (46.1%, P < 0.001) and in the number of asthma-related visits to general practitioners (40.2%, P < 0.001), specialists (27.2%, P < 0.001), and emergency departments (52.1%, P < 0.001). Associated costs were significantly lower post- versus pre-mepolizumab for asthma-related general practitioner and specialist visits, and for all-cause emergency department visits and hospital admissions. CONCLUSIONS: In a real-world population of Canadian patients with severe asthma with an eosinophilic phenotype, the use of mepolizumab within a patient support program reduced asthma exacerbations and decreased asthma-related healthcare resource utilization and associated costs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00863-7.
BioMed CentralAugust 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Interleukin (IL)-36 family cytokines have received increasing attention, especially in the fields of inflammation and immunity research. However, whether IL-36 family cytokine levels are correlated with the results of the assessment of allergic rhinitis (AR) and affect the severity of AR remains unknown. Therefore, this study aimed to investigate the correlations between IL-36 family cytokine levels and subjective and objective assessment results and to further analyze the possible mechanisms of IL-36 family cytokines in the development of AR. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of the IL-36 family cytokines IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 in the peripheral blood of patients with AR. The condition of patients with AR was assessed by 22-item sino-nasal outcome test (SNOT-22) score, visual analogue scale (VAS) scores for disease severity, and serum inhalant allergen immunoglobulin E (IgE) detection. Correlations between IL-36 family cytokine levels and subjective and objective assessment results in patients with AR were analyzed. RESULTS: The concentration of IL-36α in the peripheral blood of patients with AR was the highest, and the concentration of IL-36β was the lowest. The concentration of IL-36α was higher in juvenile patients than in adult patients, and there was a difference in the IL-36Ra level between the perennial allergen group and the seasonal allergen group. There was a positive correlation between IL-36α level and IL-36γ level, IL-36γ level and IL-36Ra level, and IL-36Ra level and IL-38 level, and IL-36β level was positively correlated with IL-36Ra and IL-38 levels, respectively. IL-36α level was positively correlated with VAS score for nasal congestion symptom. IL-36β level was positively correlated with the total VAS score for ocular symptoms and VAS scores for ocular itching and eye pain symptoms. However, there was no correlation between the levels of all cytokines in IL-36 family and SNOT-22 score, the number of positive inhaled allergens, or the highest positive intensity of allergen specific immunoglobulin E (sIgE). CONCLUSION: Peripheral blood IL-36 family cytokines play an important role in AR, and the concentrations of IL-36α and IL-36β were related to the severity of symptoms in patients with AR.
World Allergy OrganizationOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
This study aimed to evaluate the prevalence and risk factors of mental disorders in patients with chronic urticaria (CU) in a cohort of adult outpatients. Mental disorders occurred in almost one-sixth of the patients with CU, depression (9.7%), and anxiety (5.0%) being the most prevalent conditions. Furthermore, a significant difference in impairment of quality of life was seen between patients with mental disorders compared to patients without. Although, the prevalence of mental disorders in patients with CU is high, larger clinical studies are needed to investigate and understand the association and risk factors of mental disorders in patients with CU.
John Wiley and Sons Inc.March 2024Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: The incidence of atopic dermatitis (AD) in children is increasing. Early exposure to stress factors may be associated with the AD development. This study aimed to summarize studies that reported an association between stress exposure and AD development in later life. METHODS AND FINDINGS: A comprehensive literature search was performed using online databases (PubMed, EMBASE, PsycINFO, and Web of Science) for articles published up to May 1, 2023. Eligible studies were screened and selected based on the inclusion criteria. We incorporated cohort or case‐control studies published in English which explored the relationship between stress experienced by parents or children and AD. The pooled odds ratio (OR) was calculated according to the type of stress using a random‐effects model. Twenty‐two studies were included. AD was related to maternal distress (OR 1.29, 95% Confidence Interval [CI]: 1.13–1.47), maternal anxiety (OR 1.31, 95% CI: 1.18–1.46), and negative life events (OR 2.00, 95% CI: 1.46–2.76). Maternal depression during pregnancy was associated with AD (OR 1.21, 95% CI: 1.09–1.33), whereas no significant association was found for postpartum depression. Research on stress experienced by paternal or children is scare. CONCLUSIONS: Early maternal stress may potentially elevate the risk of AD in their offspring. Importantly, rigorously designed studies are required to corroborate the link between maternal stress and AD in children. These studies should aim to gather insights about the impact of stress during specific trimesters of pregnancy, postnatal stress, and paternal stress, and to identify potential prevention strategies.
Termedia Publishing HouseFebruary 2024Respiratory Medicine, Immuno-allergology, and Dermatology
INTRODUCTION: Melasma is an acquired hypermelanosis and occurs in areas exposed to sunlight. AIM: To investigate the effectiveness of Danggui Shaoyao powder (DSP) as a complementary drug in the treatment of melasma. MATERIAL AND METHODS: A total of 40 melasma patients over the age of 18 who met the inclusion criteria entered the study randomly in two DSP + Hydroquinone (DSP + H) and Hydroquinone (H) groups. RESULTS: At the beginning of the study, the average MASI score of the two groups of patients had no statistical difference (DSP + H: 15.79 ±1.01 vs. H: 15.37 ±1.17, p = 0.23). But from the eighth week of treatment, the MASI score of the patients decreased significantly and in the DSP + H group it decreased statistically significantly compared to the H group (DSP + H: 5.83 ±0.97 vs. H: 8.29 ±2.23, p < 0.001 for the eighth week and DSP + H: 3.60 ±0.58 vs. H: 5.52 ±1.73, p < 0.001 for the twelfth week of the treatment). It means after 12 weeks of treatment, the average MASI score of patients in the DSP + H group decreased by 77.26 ±2.70%, but in the grroup H, it decreased by 64.31 ±9.68% (p < 0.001). Dynamic PGA showed that excellent treatment occurred in 65% of the + H group H, but only 20% of the H group (p = 0.01). CONCLUSIONS: Oral DSP for 12 weeks along with hydroquinone cream can significantly reduce the MASI score of melasma patients and increase the patients’ recovery and satisfaction.
DoveSeptember 2023Respiratory Medicine, Immuno-allergology, and Dermatology
Asthma continues to be a disease for which there is no cure, even if it can be very well controlled with the appropriate therapies, which take into account the specific phenotype. The paradox of asthma is that asthma can heal spontaneously, albeit in a small percentage of cases. This observation is highly relevant, since understanding the mechanisms of spontaneous healing can pave the way for new strategies for treating asthma. It is likely that the lack of cure for asthma is due to the fact that current therapies target downstream mediators of the inflammatory response. Asthma can be considered a response of maladaptation of the airway epithelium to the environment, through the orientation of the innate immunity towards an inflammatory response. The important effect of the environment on asthma progress comes from interventions which help children who live in disadvantaged urban neighborhoods move to higher resourced neighborhoods. It is quite interesting that the magnitude of decrease of exacerbations associated with moving was larger than the effect of inhaled corticosteroids and similar to that observed for the effect of biologic agents. Alpine altitude climate treatment is a natural treatment that targets biological pathway, improving various outcomes such as asthma control and quality of life, exacerbation rate and hospitalizations. If as researchers we want to set ourselves the goal of achieving complete remission of asthma, without the need for ongoing maintenance treatment, we need to change the approach to finding new asthma treatment strategies. The One Health approach, an interdisciplinary strategy with focal point on human, animal, and environmental health interconnections, appears to be the right tool for researching asthma prevention and treatment.
DoveOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
INTRODUCTION: To date, the role of standard asthma care in reducing asthma-related health services use (HSU) during the COVID-19 pandemic remains unclear. This study examined the impact of guideline-based asthma treatment on the use of asthma-related emergency department (ED) visits, polyclinic visits (total visits and urgent visits characterized by nebuliser use) before and during the pandemic. METHODS: Data from April 2017 to October 2020 was obtained from the National University Health System, one of the three healthcare clusters in Singapore. Using generalized linear models, we estimated the joint effects of the ratio of preventer to reliever dispensations (PRR) and COVID-19 on asthma-related ED visits per hospital per month, total asthma-related polyclinic visits and asthma-related urgent polyclinic visits per clinic per month. RESULTS: Findings show that before the onset of COVID-19, for every 0.5 unit increase in PRR, the number of asthma-related ED visits and urgent polyclinic visits decreased by 12.9% (95% CI: −13.0% to −12.9%) and 6.8% (95% CI: −6.9% to –6.7%), respectively, whereas total asthma-related polyclinic visits increased by 1.0% (95% CI: 0.9% to 1.0%). During the pandemic, a 0.5 unit increase of PRR decreased the number of asthma-related ED visits, urgent and total polyclinic visits by 16.9% (95% CI: −17.0% to – 16.9%), 9.3% (95% CI: −9.5% to −9.2%) and 0.7% (95% CI: −0.8% to −0.7%), respectively. DISCUSSION: These findings suggest that regardless of the COVID-19 pandemic, an increase in PRR consistently reduced the frequency of asthma-related urgent and emergent care, although it barely influenced routine asthma follow-up visits.
Termedia Publishing HouseJuly 2023Respiratory Medicine, Immuno-allergology, and Dermatology
INTRODUCTION: Chronic wounds are an increasing problem for health care all over the world. New treatment options for this illness are desired, especially antimicrobial agents. Silver nanoparticles (AgNPs) can be a potential substance that may be used in treatment of chronic wounds due to the growing antibiotic resistance. AIM: To synthetize silver nanoparticles that are stable, pure and effective against bacteria. MATERIAL AND METHODS: The synthesis was conducted with chemical methods using different coating factors. The antistaphylococcal properties were analysed with the microdilution method to determine minimal inhibition concentrations (MIC) value. AgNPs were purified by dialysis. Moreover, keratinocyte cytotoxic properties of AgNPs were also assessed. RESULTS: A method of synthesizing stable and efficient AgNPs has been developed. The type of the coating substance has a significant effect on AgNPs antimicrobial properties. Most of the silver nanoparticles, synthesized based on literature data, turned out to be durable during a few hours. This study has proven that depending on the coating factor, AgNPs stability ranges from 4 weeks to even 12 months. Unfortunately, the type of the stabilizer used also affects the cytotoxicity of AgNPs. It has been shown that dialysis is a substance purification method that is cheap, simple and easy to apply when dealing with high volume solutions. CONCLUSIONS: AgNPs could be an alternative to widely used antibiotics and disinfectants. Nevertheless, the introduction of those substances to health care requires detailed long-term research not only in the field of safe use, yet also durability and purity of AgNPs solutions used.
Lippincott Williams & WilkinsOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by atopic dermatitis, recurrent skin and lung infections, and significantly elevated serum immunoglobulin E levels. Autosomal dominant and loss-of-function pathogenic variants in the STAT3 gene are the most common causes of the disease and studies have shown that the presence of IL-4 receptor (IL-4R) is upregulated in patients with dominant-negative mutations in the STAT3 gene expression. Dupilumab is a monoclonal antibody that targets the IL-4α receptor and improves the symptoms of atopic dermatitis by inhibiting IL-4 and IL-13. We used dupilumab to treat severe dermatitis in a patient with STAT3-HIES and achieved satisfactory results.
Termedia Publishing HouseFebruary 2024Respiratory Medicine, Immuno-allergology, and Dermatology
INTRODUCTION: Secukinumab (SEC) has been shown to be highly effective and safe in the treatment of moderate to severe plaque psoriasis (PsO), but data on SEC’s long-term drug survival are limited. AIM: To analyse the survival rate of SEC and its predictive factors of survival, together with the drug safety and efficacy. MATERIAL AND METHODS: Data of 268 patients who received SEC between May 2018 and April 2022 with moderate to severe psoriasis and/or psoriatic arthritis were analysed retrospectively. Psoriasis Area Severity Index (PASI) was used to define effectiveness. Drug survival was examined using the Kaplan-Meier analysis and Cox regression analysis was used to analyse predictive factors. RESULTS: PASI 75/90/100 responses achieved at week 16 (89.5%, 78%, and 16.2%, respectively) were well maintained at week 52 (96.3%, 90.7%, and 15.4%, respectively). The drug survival probability rates for SEC were 94.4% at 12 months, 88.4% at 24 months, 78.6% after 3 years, 52.7% after 4 years. Concomitant treatments, dose escalation and family history of psoriasis were associated with a higher risk for SEC withdrawal. CONCLUSIONS: Close monitoring may improve SEC survival in psoriasis patients who require dose escalation and concomitant drugs.
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory DiseaseOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
PURPOSE: Suppression of tumorigenicity 2 (ST2) has been proposed as the receptor contributing to neutrophilic inflammation in patients with type 2-low asthma. However, the exact role of ST2 in neutrophil activation remains poorly understood. METHODS: A total of 105 asthmatic patients (classified into 3 groups according to control status: the controlled asthma [CA], partly-controlled asthma [PA], and uncontrolled asthma [UA] groups), and 104 healthy controls were enrolled to compare serum levels of soluble ST2 (sST2) and interleukin (IL)-33. Moreover, the functions of ST2 in neutrophils and macrophages (Mφ) were evaluated ex vivo and in vivo. RESULTS: Serum sST2 levels were significantly higher in the UA group than in the CA or PA groups (P < 0.05 for all) with a negative correlation between serum sST2 and forced expiratory volume in 1 second % (r = −0.203, P = 0.038). Significantly higher expression of ST2 receptors on peripheral neutrophils was noted in the UA group than in the PA or CA groups. IL-33 exerted its effects on the production of reactive oxygen species, the formation of extracellular traps from neutrophils, and Mφ polarization/activation. In neutrophilic asthmatic mice, treatment with anti-ST2 antibody significantly suppressed proinflammatory cytokines (tumor necrosis factor-alpha and IL-17A) as well as the numbers of immune cells (neutrophils, Mφ, and group 3 innate lymphoid cells) in the lungs. CONCLUSIONS: These results suggest that IL-33 induces the activation of neutrophils and Mφ via ST2 receptors, leading to neutrophilic airway inflammation and poor control status of asthma. ST2 could be a therapeutic target for neutrophilic airway inflammation in patients with UA.
BioMed CentralNovember 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders. METHODS: Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented. RESULTS: One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2–4 foods after 3, 6, and 12 months of the food ladder compared to baseline. CONCLUSION: The Canadian food ladders are safe tools for children with cow’s milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00847-7.
BioMed CentralMarch 2024Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications. OBJECTIVE: Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma. METHODS: This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models. RESULTS: SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort. CONCLUSION: SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-024-00882-y.
BioMed CentralOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
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.
Lippincott Williams & WilkinsApril 2024Respiratory Medicine, Immuno-allergology, and Dermatology
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. An expert panel of specialists from the Asian-Pacific region and Russia was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations from this panel to provide guidance for clinicians in these areas. Etiology and pathogenetic mechanisms in CRSwNP are heterogeneous and complex. In many patients, CRSwNP is primarily driven by type 2 inflammation, although this may be less important in Asian populations. Frequent comorbidities include asthma and other inflammatory diseases such as non-steroidal anti-inflammatory drug (NSAID)/aspirin-exacerbated respiratory disease or atopic dermatitis. Clinical management of CRSwNP is challenging, and a multidisciplinary approach to evaluation and treatment is recommended. While many patients respond to medical treatment (topical irrigation and intranasal corticosteroids, and adjunctive short-term use of systemic corticosteroids), those with more severe/uncontrolled disease usually require endoscopic sinus surgery (ESS), although outcomes can be unsatisfactory, requiring revision surgery. Biological therapies targeting underlying type 2 inflammation offer additional, effective treatment options in uncontrolled disease, either as an alternative to ESS or for those patients with persistent symptoms despite ESS.
BioMed CentralNovember 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: The diagnosis of Alpha-gal Syndrome (AGS) is based on the presence of symptoms after being exposed to potential sources of alpha-gal together with values of specific IgE (sIgE) to alpha-gal ≥ 0.1 kUA/L or ≥ 0.35 kUA/L. The aim of this study was to evaluate the diagnostic validity of sIgE levels to alpha-gal ≥ 0.1 kUA/L for identifying AGS. METHODS: This was a cross-sectional analysis of adult patients with available data on sIgE levels to alpha-gal, classified into two groups according to the presence (Group 1) or absence (Group 2) of symptoms after being exposed to potential sources of alpha-gal. Values of sIgE to alpha-gal ≥ 0.1 kUA/l were considered a positive result. A descriptive analysis of internal and external validity parameters was performed in the entire population and adjusted by sex. RESULTS: The study included 33 individuals in Group 1 and 65 in Group 2, with a mean age of around 47 years. The analysis of internal validity parameters revealed a high sensitivity, specificity, and positive probability ratio, with higher sensitivity in men and higher specificity in women. The analysis of external validity parameters showed a high negative predictive value and global value in all populations and both sexes. However, the positive predictive value was relatively high in men, but low in women. CONCLUSIONS: Our results suggest that sIgE levels ≥ 0.1 kUA/L may be a useful tool for the diagnosis of AGS, although other factors and diagnostic techniques should also be considered.
World Allergy OrganizationJanuary 2024Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Emerging observational studies showed an association between atopic dermatitis (AD) and gastrointestinal cancers. However, it remains unclear whether this association is causal, particularly in the case of cancers like esophageal cancer, which exhibit ancestral genetic traits. METHODS: To assess the potential causal relationship between AD and esophageal cancer across diverse ancestral backgrounds, we conducted a 2-sample Mendelian randomization study. Independent genetic instruments for AD from the FinnGen consortium (N case = 7024 and N control = 198 740), BioBank Japan (N case = 2385 and N control = 209 651) and Early Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium (N case = 18 900 and N control = 84 166, without the 23andMe study) were used to investigate the association with esophageal cancer in the UK Biobank study (N case = 740 and N control = 372 016) and BioBank Japan esophageal cancer sample (N case = 1300 and N control = 197 045). RESULTS: When esophageal cancer extracted from East Asian ancestry was used as a outcome factor, AD data extracted from BioBank Japan (OR = 0.90, 95% CI: 0.83–0.98), FinnGen consortium (OR = 0.86, 95% CI: 0.77–0.96), and EAGLE consortium (OR = 0.92, 95% CI: 0.81–1.06) were negatively associated with esophageal cancer susceptibility. However, AD as a whole did not show an association with esophageal cancer from European ancestry. CONCLUSION: This study provides support for a causal relationship between AD and esophageal cancer in East Asian populations but not between AD and esophageal cancer from European ancestry. The specific associations between esophageal cancer and AD appear to exhibit significant disparities between the East Asian and European regions.
DoveOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
PURPOSE: Earlier coronavirus-19 (COVID-19) pandemic reports did not implicate increased disease burden in asthmatics while subsequent findings have been inconsistent. To date, the impact of COVID-19 on childhood asthma remains undetermined and is further complicated with ongoing emergence of new variants. This study aimed to investigate association between asthma and COVID-19 for children in New South Wales (NSW), Australia and compare its differences across four major outbreaks from alpha, delta and omicron variants/subvariants. METHODS: This is a retrospective cross-sectional study of all children aged ≤17 years old who sought care for COVID-19 at Sydney Children’s Hospitals Network (SCHN) between 1 January 2020 and 31 May 2022. RESULTS: Of the 18,932 children with polymerase chain reaction (PCR) confirmed COVID-19 who attended SCHN, 60% received their care during delta wave, and 5.41% (n = 913) had prior diagnosis of asthma. Among children with COVID-19, the odds of having asthma were lower during alpha (aOR = 0.43; 95% CI, 0.19–0.83) and delta wave (aOR = 0.84; 95% CI, 0.73–0.96), but were higher during omicron wave (aOR = 1.56; 95% CI, 1.23–1.95). Length of hospital stay (LOS) for asthmatic children were increased by 0.55 days and 1.17 days during delta and the second omicron wave, respectively. Intensive care and mechanical ventilation requirements were not significantly different between asthmatic and non-asthmatic children. Eleven deaths were reported but none had asthma. CONCLUSION: Although children with asthma were more susceptible to COVID-19 infections during omicron waves compared to that of alpha or delta waves, they were not at greater risk of COVID-19 severity at any stage of the outbreak regardless of the predominant SARS-CoV-2 variants/subvariants.
World Allergy OrganizationJanuary 2024Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: In previous studies, several asthma phenotypes were identified using clinical and demographic parameters. Transcriptional phenotypes were mainly identified using sputum and bronchial cells. OBJECTIVE: We aimed to investigate asthma phenotypes via clustering analysis using clinical variables and compare the transcription levels among clusters using gene expression profiling of the blood. METHODS: Clustering analysis was performed using 6 parameters: age of asthma onset, body mass index, pack-years of smoking, forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, and blood eosinophil counts. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and RNA was extracted from selected PBMCs. Transcriptional profiles were generated (Illumina NovaSeq 6000) and analyzed using the reference genome and gene annotation files (hg19.refGene.gft). Pathway enrichment analysis was conducted using GO, KEGG, and REACTOME databases. RESULTS: In total, 355 patients with asthma were included in the analysis, of whom 72 (20.3%) had severe asthma. Clustering of the 6 parameters revealed 4 distinct subtypes. Cluster 1 (n = 63) had lower predicted FEV1 % and higher pack-years of smoking and neutrophils in sputum. Cluster 2 (n = 43) had a higher proportion and number of eosinophils in sputum and blood, and severe airflow limitation. Cluster 3 (n = 110) consisted of younger subjects with atopic features. Cluster 4 (n = 139) included features of late-onset mild asthma. Differentially expressed genes between clusters 1 and 2 were related to inflammatory responses and cell activation. Th17 cell differentiation and interferon gamma-mediated signaling pathways were related to neutrophilic inflammation in asthma. CONCLUSION: Four clinical clusters were differentiated based on clinical parameters and blood eosinophils in adult patients with asthma form the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) cohort. Gene expression profiling and molecular pathways are novel means of classifying asthma phenotypes.
BioMed CentralSeptember 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps. METHODS: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023. RESULTS: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment. CONCLUSION: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13223-023-00841-z.
Lippincott Williams & WilkinsOctober 2023Respiratory Medicine, Immuno-allergology, and Dermatology
BACKGROUND: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. OBJECTIVES: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. METHODS: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. RESULTS: The clinical pathway was piloted employing a “hub-and-spoke” approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist’s care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. CONCLUSIONS: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.
Lippincott Williams & WilkinsJune 2025Respiratory Medicine, Immuno-allergology, and Dermatology
Allergen immunotherapy (AIT) is an evidence-based therapy for allergic rhinitis and allergic asthma. AIT is largely recognized as the only causal treatment of allergic diseases that targets the underlying pathophysiology and may have a disease-modifying effect in addition to the antisymptomatic effect. Carbamylated monomeric allergoids (CMAs) are chemically modified allergens with reduced IgE-binding activity (reduced allergenicity) but full immunogenicity. The carbamylation process allows them to be much smaller than other modified allergens, making them ideal for sublingual immunotherapy (SLIT), and reduced allergenicity makes them safe and well tolerated. CMAs have several advantages over other SLIT products: smaller size for easier absorption through mucosa, greater resistance to proteolytic degradation, greater bioavailability, and reduced allergenicity with full immunogenicity. The tablet form allows for accurate dosing and compliance is easy to monitor. Safety is an especially important consideration when treating conditions in pediatric populations, as is patient compliance. This review focused on the efficacy, safety, and clinical application of monomeric allergoid SLIT for allergic disease in children and its suitability as an alternative to subcutaneous immunotherapy.
X-ray quasi-periodic eruptions (QPEs) are a novel mode of variability in
nearby galactic nuclei whose origin remains unknown. Their multi-wavelength
properties are poorly constrained, as studies have focused almost entirely on
the X-ray band. Here we report on time-resolved, coordinated Hubble Space
Telescope far ultraviolet and XMM-Newton X-ray observations of the shortest
period X-ray QPE source currently known, eRO-QPE2. We detect a bright UV point
source ($L_{\rm FUV} \approx {\rm few} \times 10^{41}$ erg s$^{-1}$) that does
not show statistically significant variability between the X-ray eruption and
quiescent phases. This emission is unlikely to be powered by a young stellar
population in a nuclear stellar cluster. The X-ray-to-UV spectral energy
distribution can be described by a compact accretion disk ($R_{\rm out} =
343^{+202}_{-138} \ R_{\rm g}$). Such compact disks are incompatible with
typical disks in active galactic nuclei, but form naturally following the tidal
disruption of a star. Our results rule out models (for eRO-QPE2) invoking i) a
classic AGN accretion disk and ii) no accretion disk at all. For orbiter
models, the expected radius derived from the timing properties would naturally
lead to disk-orbiter interactions for both quasi-spherical and eccentric
trajectories. We infer a black hole mass of log$_{10}(M_{\rm BH}) = 5.9 \pm
0.3$ M$_{\odot}$ and Eddington ratio of 0.13$^{+0.18}_{-0.07}$; in combination
with the compact outer radius this is inconsistent with existing disk
instability models. After accounting for the quiescent disk emission, we
constrain the ratio of X-ray to FUV luminosity of the eruption component to be
$L_{\rm X} / L_{\rm FUV} > 16-85$ (depending on the intrinsic extinction).
;Comment: 11 pages and 4 figures; accepted for publication in ApJ Letters
International audience;
Monitoring volcanoes is of the most importance in volcano risk mitigation to safeguard lives and economies. Thanks to recent technological advances, both on-ground and in space, our understanding of volcanic processes has improved significantly. Though there is no one-system-fits-all, optimizing infrastructure for efficient monitoring stands as key objective. The impacts of volcanic hazards can span from local to global scales, affecting us both in the short and long term. This highlights the worldwide significance of improving volcano monitoring. Previously reliant on local ground-based instruments, today's monitoring approach is enhanced by remote and space-based techniques such as satellite remote sensing, scanning-Differential Optical Absorption Spectroscopy (DOAS), and infrasound. Designing an effective monitoring infrastructure for volcano observatories involves careful consideration of various factors such as network coverage, type of sensors, data transmission, and power supply to ensure that the targeted parameters meet the specific needs of each volcano (e.g., type of activities, early warning systems). Additionally, fostering collaboration and information sharing within the global scientific community is essential for addressing the current challenges in volcanology. In line with this, we've established the Global Volcano Monitoring Infrastructure Database (GVMID) to compile data from volcano monitoring across the globe. Global Volcano Monitoring Infrastructure Database serves as an integral component of WOVOdat, the global volcano unrest database, aiming to enhance our understanding of eruptive processes and improve eruption forecasts. The database incorporates monitoring metadata comprising networks, stations, and instruments, all standardized and managed using a MySQL relational database management system. Accessed through a web-based interface (https://wovodat.org/gvmid/home.php), GVMID offers an informative snapshot and foundational overview of the techniques and instruments in place at diverse volcanoes. This interactive platform allows for queries, visualizations, and downloads, serving as a valuable resource for the volcano community. GVMID can assist observatories in various ways, by: (a) Facilitating the setup or enhancement of monitoring systems for specific volcanoes. (b) Providing insights into the latest monitoring technologies and instrumentation. (c) Identifying existing monitoring gaps that could be addressed through remote sensing infrastructure and future instrument deployments. We extend an invitation to the global volcano community to actively participate in the development and enrichment of GVMID. Our aim is for it to become a continually updated and indispensable resource that caters to diverse needs within the volcanology community.
The Cenozoic magmatism of the Central Tethyan orogenic belt, which links the tectonic zones of Iran, the South Armenian Block (lesser Caucasus), and Turkey, remains a topic of debate. This research focuses on the thick geological succession of high-K calc-alkaline shoshonitic volcanic rocks exposed in the Talysh Massif, part of the Alborz magmatic belt, northwestern Iran. The aim of this study is to investigate the relatively unstudied volcanic rocks of the Talysh Massif to better constrain the geodynamic setting of magmatism during regional convergence. A comprehensive study including new field data, mineral chemistry, bulk-rock major and trace element geochemistry, isotope composition (Sr, Nd, Pb, Hf), geochronology 40Ar-39Ar, and zircon U-Pb. We classify them as olivine, clinopyroxene-phyric basalts, clinopyroxene-phyric basalts, amphibole-phyric basalts, tephrites, trachy-andesites, and pyroclastic rocks. They contain multiple crystal populations, including phenocrysts, antecrysts, and xenocrysts: olivine, clinopyroxene, amphibole, and re-equilibrium phlogopite, along with complex oscillatory and reverse zoning, sieve textures, and resorption textures, which suggests that the magmas stalled and differentiated in the crust prior to eruption. Olivine-clinopyroxene-phyric samples in the southern part of the study area exhibit olivine phenocrysts chemically balanced with their host rock, with a slight zoning from high-Mg# cores (Mg# = 90) to rims (Mg# = 80). Furthermore, the amphiboles, biotite 40Ar-39Ar ages of basalts, and zircon U-Pb ages of pyroclastic rocks indicate that volcanic activity took place for ~ 10 Myr (between 49 and 38 Myr). Enrichment in LILE and depletion in Nb, Ta, and Ti are characteristics of the Talysh lavas, which exhibit arc geochemical features. They have isotopic compositions that vary, for 87Sr/86Sr (i) from 0.7045 to 0.7066, for ɛNd(i) from ~-2.2 to +1.7, and ɛHf(i) from -2.5 to +3.6. The rocks have radiogenic lead 206Pb/204Pb ratios from 18.51 to 19.04, 207Pb/204Pb from 15.59 to 15.63, and 208Pb/204Pb from 38.67 to 39.15. The major elements of most primitive samples (MgO > 5 wt%) are comparable to those of melts obtained from low-degree (4–9%) partial melting of a spinel-garnet lherzolite with garnet:spinel ratios of 40:60 to 20:80. The results obtained from clinopyroxene-liquid geothermobarometry indicate a variety of magma reservoirs, ranging from deep levels (79–60 km) to shallower levels (2 km). The isotopic ratios of Sr, Nd, Pb, and Hf, as well as the similar chondrite-normalized REE and primitive-mantle-normalized incompatible trace element patterns along thermobarometry estimates on olivine, clinopyroxene, and amphibole crystals, suggests that the mantle source is an enriched asthenospheric source, and that continental crust was mixed in during the differentiation process. The data are consistent with the partial melting of a garnet-bearing subduction-modified subcontinental mantle and interactions with a spinel-bearing mantle during magmatic ascent. This magmatic flare-up could have been triggered by an asthenosphere upwelling related to the onset of south-dipping subduction of the Transcaucasus basin. Asthenosphere flow and magmatic ascent were likely facilitated by trans-lithospheric strike-slip faults and block rotations highlighted by paleomagnetic data. A transition from calc-alkaline towards a more alkaline magmatic component with time, from south to north of the Talysh massif, suggests a slab steepening in response to roll-back in the Late Eocene. After this period, volcanism stopped in the South Talysh and significantly decreased in the North Talysh massif, where it evolved into an adakitic-type magmatism during the Late Miocene and Quaternary.
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Le magmatisme cénozoïque de la ceinture orogénique qui relie les zones tectoniques de l'Iran, du bloc arménien méridional (petit Caucase) et de la Turquie, reste un sujet de débat. Cette recherche se concentre sur l'épaisse succession géologique de roches volcaniques shoshonitiques calco-alcalines riches en K exposées dans le massif de Talysh, qui fait partie de la ceinture magmatique de l'Alborz, dans le nord-ouest de l'Iran. L'objectif de cette étude est d'étudier les roches volcaniques relativement peu étudiées du massif de Talysh afin de mieux contraindre le cadre géodynamique du magmatisme pendant la convergence régionale. Une étude complète incluant de nouvelles données de terrain, la chimie minérale, la géochimie des éléments majeurs et traces des roches totales, la composition isotopique (Sr, Nd, Pb, Hf), la géochronologie 40Ar-39Ar, et le zircon U-Pb. Cette montre une série magmatique de basaltes riches en olivine, basaltes à clinopyroxène-phyrique, basaltes à clinopyroxène-phyrique, basaltes à amphibole-phyrique, téphrites, trachy-andésites et roches pyroclastiques. Ils contiennent de multiples populations de cristaux : olivine, clinopyroxène, amphibole et phlogopite, avec des textures de rééquilibrage ainsi qu'une zonation oscillatoire et inverse complexe, des textures criblées et des textures de résorption, ce qui suggère que les magmas ont été stockés dans et différenciés dans des chambres magmatiques avec des réinjections successives avant l'éruption. En outre, les âges 40Ar-39Ar de la biotite et des amphiboles des basaltes et les âges U-Pb du zircon des roches pyroclastiques indiquent que l'activité volcanique s'est déroulée pendant ~ 10 Myr (49-38 Myr). L'enrichissement en LILE et l'appauvrissement en Nb, Ta et Ti sont des caractéristiques des laves de Talysh, qui présentent des caractéristiques géochimiques d'arc. Leurs compositions isotopiques varient : 87Sr/86Sr (i) de 0,7045 à 0,7066, ɛNd(i) de ~-2,2 à +1,7, et ɛHf(i) de -2,5 à +3,6. Les roches ont des compositions radiogéniques en plomb (206Pb/204Pb de 18,51 à 19,04, 207Pb/204Pb de 15,59 à 15,63, et 208Pb/204Pb de 38,67 à 39,15). Les éléments majeurs de la plupart des échantillons primitifs (MgO > 5 % en poids) sont comparables à ceux des fusions partielles à faible degré (4-9%) d'une lherzolite à grenat et spinelle avec des rapports grenat:spinelle de 40:60 à 20:80. Les résultats obtenus par géothermobarométrie clinopyroxène-liquide indiquent une variété de réservoirs magmatiques, allant de niveaux profonds (79-60 km) à des niveaux moins profonds (2 km). Les rapports isotopiques de Sr, Nd, Pb et Hf, ainsi que les profils similaires d'éléments traces incompatibles normalisés par la chondrite et par le manteau primitif, ainsi que les estimations thermobarométriques sur les cristaux d'olivine, de clinopyroxène et d'amphibole, suggèrent que la source mantellique est une source asthénosphérique enrichie et que de la croûte continentale a été mélangée au cours du processus de différenciation. Les données sont cohérentes avec la fusion partielle d'un manteau sous-continental à grenat modifié par subduction et les interactions avec un manteau à spinelle pendant l'ascension magmatique. La phase magmatique éocène pourrait avoir été déclenchée par une remontée de l'Asthénosphère liée au début de la subduction à pendage sud du bassin transcaucasien. L'ascension magmatique a probablement été facilitée par des failles décrochantes trans-lithosphériques mises en évidence par les données paléomagnétiques. Le passage d'une composante magmatique calco-alcaline à une composante magmatique plus alcaline avec le temps, du sud au nord du massif de Talysh, suggère un raidissement de la plaque en réponse à un retournement à l'Éocène supérieur. Après cette période, le volcanisme s'est arrêté dans le Talysh Sud et a considérablement diminué dans le massif du Talysh Nord, où il a évolué vers un magmatisme de type adakitique au cours du Miocène supérieur et du Quaternaire.
HAL CCSD;Académie des sciences (Paris)January 2022Volcanology
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A multichannel seismic reflection profile acquired during the SISMAORE cruise (2021) provides the first in-depth image of the submarine volcanic edifice, named Fani Maore, that formed 50 km east of Mayotte Island (Comoros Archipelago) in 2018–2019. This new edifice sits on a »140 m thick sedimentary layer, which is above a major, volcanic layer up to »1 km thick and extends over 120 km along the profile. This volcanic unit is made of several distinct seismic facies that indicate successive volcanic phases. We interpret this volcanic layer as witnessing the main phase of construction of the Mayotte Island volcanic edifice. A »2.2–2.5 km thick sedimentary unit is present between this volcanic layer and the top of the crust. A complex magmatic feeder system is observed within this unit, composed of saucer-shape sills and seal bypass systems. The deepest tip of this volcanic layer lies below the top-Oligocene seismic horizon, indicating that the volcanism of Mayotte Island likely began around 26.5Ma, earlier than previously assumed.
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Un profil de sismique réflexion multitrace acquis lors de la campagne océanographique SISMAORE (2021) apporte la première image en profondeur du volcan sous-marin Fani Maore, qui s’est formé à 50 km à l’est de l’île de Mayotte (archipel des Comores) en 2018–2019. Ce nouvel édifice repose sur une première couche sédimentaire d’environ 140 m d’épaisseur au-dessus d’une couche volcanique majeure épaisse de 1 km et qui s’étend sur 120 km le long du profil. Cette dernière unité volcanique est constituée de plusieurs faciès sismiques distincts qui indiquent des phases volcaniques successives. Nous interprétons cette couche volcanique comme le témoin de la phase principale de construction de l’édifice volcanique de l’île de Mayotte. Une couverture sédimentaire de »2.2–2.5 km d’épaisseur est présente entre cette couche volcanique et le toit de la croûte. On y observe de nombreux sills en forme de soucoupe ainsi que des zones à faciès de remontées de fluides, dessinant un système d’alimentation magmatique complexe sous la principale couche volcanique. L’extrémité la plus profonde de cette couche volcanique se place en dessous de l’horizon sismique de l’Oligocène supérieur et indique que le volcanisme de l’île de Mayotte a probablement commencé vers 26.5 Ma, plus tôt que ce qui était supposé auparavant.
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Fixed drug eruption is characterized by recurrent, well-circumscribed, erythematous patches that arise at the same site as a result of systemic drug exposure. Since the first report in 1996, some cases were published related to food, beverage with quinine-based drinks or plant intake and called ‘fixed food eruption’ (FFE). We report a case of FFE to Moringa oleifera with positive rechallenge.
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Volcanic domes are inherently unstable structures that form when lava is too viscous to flow away from the vent. Dome collapse poses a hazard via volcanic landslides and debris avalanches that can threaten nearby communities. Dome collapse can be promoted by hydrothermal alteration, which can weaken volcanic rock and is commonly concentrated in regions with high fluid flow, such as fractures and areas of high permeability within the dome. Here, we focus on understanding how alteration affects dome stability, collapse volumes and runout distances, using the case study of La Soufrière de Guadeloupe, in the Eastern Caribbean. We present new 3D models that combine geophysical and mechanical data to investigate different post-emplacement dome stability scenarios that incorporate hydrothermal alteration. Our results demonstrate that increased alteration-induced weakening (i.e., to 50% or 10% of the original rock strength) leads to greater displacements and causes dome destabilisation. Additionally, we show displacement and finite shear strain as a result of varying the spatial extent (the thickness and location) of the alteration zones. We also show that incorporating mechanical heterogeneity is crucial for accurate hazard modelling. We introduce a novel method using the La Soufrière de Guadeloupe dome to offer a comprehensive understanding of the alteration process from initiation to deposit. Our results indicate that hydrothermal alteration significantly increases collapse volumes and thus runout distances, which are critical for understanding the potential impact of dome collapse and a critical motivation for our 3D modelling approach. By capturing the full process from internal weakening to hazard potential, this method enhances our ability to anticipate future dome collapse events, and thus, mitigate their effects.
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Abstract Volcanoes produce a variety of seismic signals and, therefore, continuous seismograms provide crucial information for monitoring the state of a volcano. According to their source mechanism and signal properties, seismo‐volcanic signals can be categorized into distinct classes, which works particularly well for short transients. Applying classification approaches to long‐duration continuous signals containing volcanic tremors, characterized by varying signal characteristics, proves challenging due to the complex nature of these signals. That makes it difficult to attribute them to a single volcanic process and questions the feasibility of classification. In the present study, we consider the whole seismic time series as valuable information about the plumbing system (the combination of plumbing structure and activity distribution). The considered data are year‐long seismograms recorded at individual stations near the Klyuchevskoy Volcanic Group (Kamchatka, Russia). With a scattering network and a Uniform Manifold Approximation and Projection (UMAP), we transform the continuous data into a two‐dimensional representation (a seismogram atlas), which helps us to identify sudden and continuous changes in the signal properties. We observe an ever‐changing seismic wavefield that we relate to a continuously evolving plumbing system. Through additional data, we can relate signal variations to various state changes of the volcano including transitions from deep to shallow activity, deep reactivation, weak signals during quiet times, and eruptive activity. The atlases serve as a visual tool for analyzing extensive seismic time series, allowing us to associate specific atlas areas, indicative of similar signal characteristics, with distinct volcanic activities and variations in the volcanic plumbing system.
Frequencies of volcanic eruptions in the past 270 years are compared with
variations of solar activity and summary curve of principal components of the
solar background magnetic field (SBMF).Frequency analysis with Morlet wavelet
reveals the most pronounced period of volcanic eruptions of 22 years. There is
a strong correlation (0.84) between volcanic frequencies and the summary curve
of SBMF for 11 cycles after 1868. The maxima of volcanic eruptions are shown to
occur during solar activity cycles with the southern magnetic polarity. The
next anticipated maximum of volcanic eruptions is expected to occur during
cycle 26, when SBMF have a southern magnetic polarity.
;Comment: 9 pages, 6 figures
CCSD;AGU and the Geochemical SocietyApril 2024Volcanology
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Abstract The Lucky Strike volcano is the central edifice of the Lucky Strike segment on the slow spreading Mid‐Atlantic Ridge. The volcano summit hosts one of the largest known deep‐sea hydrothermal fields, and overlies an axial magma chamber (AMC) whose summit reflector lies 3–3.8 km beneath the seafloor. We present a 12‐year microearthquake catalog beneath the volcano, which we constructed using data collected from 2007 to 2019 as part of the EMSO‐Azores observatory. The catalog reveals continuous low magnitude seismicity (85% with M L < 0), focused mainly north‐northwest of the hydrothermal field and 0–2 km above the AMC reflector. Focal mechanisms estimated only from the 2010–2011 deployment show a mixture of thrust, normal and strike/slip faulting mechanisms. We propose that the observed microearthquake activity is due to thermal cracking, tectonic cracking, and possible small dike injections occurring at the base of hydrothermal downflow zones. We document a ∼800 m eastward shift of the seismicity sometime during a catalog gap from June 2013 to April 2015, accompanied by a change in the seismicity pattern from a patch just above the AMC to a more vertically aligned structure. We also identify several higher seismicity periods, often including relatively large magnitude events ( M L > 0.8). We interpret the spatio‐temporal variations in seismicity patterns and the correlation between larger magnitude events and higher seismicity periods to indicate that the hydrothermal domain is a dynamic interface, where the variations are caused by changes in permeability and/or temperature induced by tectonic and small episodic melt injections.
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The thermal properties of volcanic materials are required for modelling and for understanding volcanic surface heat fluxes and timescales for cooling magma. However, compared to volcanic rocks, there are relatively few thermal property data for unlithified granular volcanic materials. Here, we measured the thermal properties of a suite of hydrothermally altered powders from La Soufrière de Guadeloupe (Eastern Caribbean) as a function of water saturation degree. Our data show, under dry conditions, that thermal conductivity and thermal diffusivity decrease, and that specific heat capacity does not change systematically, as a function of the degree of alteration of the unlithified granular material. For example, thermal conductivity decreases from ~0.3 to ~0.2 W·m−1·K−1 as the quantity of alteration minerals in the samples increases from ~10 to ~70 wt%. We interpret the decrease in thermal conductivity with increasing alteration as the result of the lower thermal conductivity of the alteration mineral assemblage relative to the unaltered assemblage. Our data also show that thermal conductivity increases from ~0.2–0.3 to ~0.8–1.1 W·m−1·K−1 as saturation degree increases from dry to at, or close to, complete saturation, due to the higher thermal conductivity of water compared to air. We show that an empirical model for variably saturated granular media is in general agreement with our data and provides a framework to predict the thermal conductivity of unlithified granular volcanic materials as a function of saturation degree. The data and modelling provided herein can help improve heat flux calculations designed to inform on volcanic and geothermal processes.
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Risk mitigation in long-dormant volcanic provinces is a challenge due to the absence of collective memory of past disasters as well as the scarcity, and subtlety, of unrest signals that can be monitored. In this study, the impact of a potential limnic eruption is assessed at the 92-m-deep lake Pavin (French Massif Central). The lake is hosted in a maar crater formed during the last eruptive event in metropolitan France (~7 ka) and contains dissolved CO2 in the deepest water layer, below 60 m. Carbon dioxide (CO2) emissions measured at the lake surface (0.44 km 2) reach up to 10.1 tons/day during the winter. Beyond this (limited) continuous degassing of the lake, the current CO2 budget in the monimolimnion layer (at a depth of 60 m to 92 m) was estimated at 1750 tons, of which about 450 tons are available for release in case of overturn of the lake. Scenarios for CO2 dispersion in the lower atmosphere were simulated with the DISGAS and TWODEE-2 models by varying (i) meteorological conditions, (ii) the amount of CO2 released, (iii) and the mechanisms of degassing during a potential limnic eruption. The simulations allowed identification and delimitation of areas potentially impacted by hazardous CO2 levels in the air down-valley from the lake and directly around the lake. The spatio-temporal evolution of the potential CO2 cloud raises issues regarding the impacts of such a hypothetical event in the close vicinity of the lake and, given the area is populated and highly visited, needs to be considered in future risk mitigation strategies.
We aim to investigate the blowout jet-like prominence eruption, which occurred on October 6$^{th}$, 2023, with the help of imaging and spectroscopic observations. Firstly, the prominence rises slowly with a speed of 33 km/s, followed by a fast rise (i.e., 338 km/s). Later, the northern leg breaks completely, and the eruption forms the blowout jet. The jet consists of different plasma threads, which show a range of upflow (i.e., 125 to 593 km/s) and downflow velocities (i.e., 43 to 158 km/s). The jet plasma column exhibits transverse oscillations, and this motion (untwisting motion) propagate at the speed of 267 km/s, are consistent with being Alfev{é}n waves. The transverse motion has the time period, amplitude, and transverse velocity of 1332 s, 26.19 Mm, and 126.18$\pm$7.27 km/s, respectively, and this transverse oscillation decays over time. Interestingly, the different plasma threads within the jet's body exhibit decayless transverse oscillations, and these decayless oscillations are related to the main decaying transverse oscillation. The transverse velocity of these decayless oscillations ranges from 66 to 30 km/s, the amplitudes from 8.52 to 2.74 Mm, and periods from 811 to 406 s. In addition, the spectroscopic analysis reveals Si~{\sc iv} lines are forming in the optically thick conditions in high electron density regions (i.e., near the base of the blowout jet). Lastly, we mention that two weak C-class flares occurred during this event, and further, one CME also occurred, which propagated with the speed of $\sim$250 km/s. ;22 Pages, 12 Figures, Accepted for Publication in ApJ
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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.
Seventeen representative samples of volcanic origin were collected from
Ecuador (Pichincha Volcano), Iceland (Eyjafjallaj\"okull Volcano), India
(Deccan Traps), Hawaii, Kilimanjaro, Mt. Etna, Rwanda (Virunga Mountains), and
Uganda (Virunga Mountains). Neutron activation analysis (NAA) was performed to
determine the concentration of 33 chemical elements, including 21 trace
elements, 20 heavy metals, and 9 rare earth elements: Al, As, Ba, Ca, Ce, Cl,
Co, Cr, Cs, Dy, Eu, Fe, Hf, K, La, Lu, Mg, Mn, Na, Nd, Rb, Sb, Sc, Sm, Sr, Ta,
Tb, Th, Ti, U, Yb, Zn, and Zr.
Correlation analysis of the abundance of samples from different islands in
the Hawaii archipelago (Kauai, Kilauea, Mauna Loa, and Haleakala) confirmed
that the islands were likely formed by two different lava sources.
Additionally, the upper limit of iridium was determined in 11 of these samples
using Bayesian analysis, which does not support the hypothesis that volcanic
activity caused the extinction of the dinosaurs.
We also discuss how the abundance of thorium and uranium in lava from
different geological formations and depths can contribute to building a better
map of natural radioisotope occurrences on Earth, which is important for
geoneutrino experiments. A high abundance of rare elements was reported in some
of the analyzed locations, indicating potential commercial interest and the
possibility of exploring volcanoes as sources of chemical elements used in
electronic devices.
The Vaca Muerta Formation (Neuquén Basin, Argentina) is a late Jurassic-early Cretaceous source rock that has received renewed interest since 2010 when it was shown that hydrocarbons could be extracted from it non-conventionally. Since then, this formation has been studied thanks to its beautiful outcrops and abundant sedimentary cores.The study carried out in this thesis is based on a coupled sedimentological, mineralogical and geochemical approach of surface and subsurface mudstone and volcanic ash samples at different degrees of maturity. The objective is to describe and study the diagenetic transformations that affected the Vaca Muerta rocks, as well as the burial conditions that led to these transformations. The study of the petrographic and mineralogical characterization of the facies of the Vaca Muerta formation revealed that these mudstones, or shales, were dominated by an association of three dominant lithologies: carbonate, mixed carbonate-silica and mixed silica, depending on the variable proportion of calcite (~15-45%), quartz (~20-40%), albite (~8-20%) and clay minerals (~15-25%). The mixed siliceous lithologies are the richest in organic matter (2-8 wt%). Petrographic observations of paragenesis, coupled with geochemistry, have allowed the determination of a diagenetic sequence for the Vaca Muerta mudstones. Early diagenesis includes the precipitation of pyrite, calcite, apatite, quartz, kaolinite, and the early stages of illitisation of smectites. Late diagenetic processes (>70°C) include illitisation of I/S interlayers, albitisation of plagioclase feldspars, precipitation of calcite, dolomite, quartz, pyrite and chlorite. The observation and characterization of the volcanic ash present in the Vaca Muerta have made it possible to describe two distinct facies: the CRAB (Clay Rich Ash Beds) and the CCAB (Calcite Cemented Ash Beds). These facies result from andesitic-rhyodacitic calc-alkaline volcanism and are characterized by distinct mineral paragenesis and diagenetic evolution, probably related to textural differences and distinct volcanic glass and microphenocrystals content. The main distinction between the CRAB and CCAB is the early carbonate cementation, pre-compaction, which preserved the primary textures of the glass chips in the CCAB.
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La Formation Vaca Muerta (bassin de Neuquén, Argentine) est une roche mère de la fin du Jurassique et début Crétacé qui a connu un regain d'intérêt depuis 2010 ou l'on a montré que l'on pouvait y extraire des hydrocarbures de façon non conventionnelle. Depuis, cette formation est étudiée grâce à ses beaux affleurements, et aux abondantes carottes sédimentaires. L'étude réalisée dans cette thèse est basée sur une approche couplée sédimentologique, minéralogique et géochimique d'échantillons de mudstones et de cendres volcaniques de surface et de subsurface à différents degrés de maturité. L'objectif est de décrire et d'étudier les transformations diagénétiques qui ont affectées les roches de Vaca Muerta, ainsi que les conditions d'enfouissement qui ont conduit à ces transformations. L'étude de la caractérisation pétrographique et minéralogique des faciès de la formation Vaca Muerta a révélé que ces mudstones, ou shales en anglais, étaient dominés par une association de trois lithologies dominantes : carbonaté, mixte carbonate siliceux et mixte siliceux, en fonction de la proportion variable de calcite (~15-45%), de quartz (~20-40%), d'albite (~8-20%) et de minéraux argileux (~15-25 %). Les lithologies mixtes siliceuses sont les plus riches en matière organique (2-8 % en poids). Les observations pétrographiques de la paragenèse, couplées à la géochimie, ont permis de déterminer une séquence diagénétique pour les mudstones de Vaca Muerta. La diagenèse précoce comprend la précipitation de pyrite, de calcite, d'apatite, de quartz, de kaolinite, ainsi que les premiers stades de l'illitisation des smectites. Les processus diagénétiques tardifs (> 70°C) comprennent l'illitisation des interstratifiés I/S, l'albitisation des feldspaths plagioclases, la précipitation de calcite, de dolomite, de quartz, de pyrite et de chlorite.L'observation et la caractérisation des cendres volcaniques présentes dans la Vaca Muerta ont permis de décrire deux faciès distincts : les CRAB (Clay Rich Ash Beds, riches en minéraux argileux) et les CCAB (Calcite Cemented Ash Beds, riches en calcite). Ces faciès résultent d'un volcanisme calco-alcalin andésitique-rhyodacitique et sont caractérisés par une paragenèse minérale et une évolution diagénétique distinctes, probablement liées aux différences texturales et au contenu distinct en verre volcanique et en microphénocristaux. La principale distinction entre les CRAB et les CCAB est la cimentation carbonatée précoce, pré-compaction, qui a préservé les textures primaires des éclats de verre dans les CCAB.
HAL CCSD;Geological Society of LondonJanuary 2022Volcanology
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Transform marginal plateaus (TMPs) are large and flat structures commonly found in deep oceanic domains, but their origin and relationship to adjacent oceanic lithosphere remain poorly understood. This paper focuses on two conjugate TMPs, the Demerara Plateau off Suriname and French Guiana and the Guinea Plateau, located at the junction of the Jurassic Central Atlantic and the Cretaceous Equatorial Atlantic oceans. The study helps to understand (1) the tectonic history of both Demerara and Guinea plateaus and (2) the relationship between the Demerara Plateau and the adjacent oceanic domains, and finally, (3) throws light on the formation of TMPs. We analyse two existing wide-angle seismic-derived velocity models from the MARGATS seismic experiment (Demerara Plateau), and adjacent composite industrial seismic lines covering the Demerara and Guinea plateaus. The Demerara Plateau displays a 30 km thick crust, subdivided into three layers, including a high-velocity lower crust. The velocities and velocity gradients do not fit the values of typical continental crust but instead correspond to volcanic margin-or large igneous province-type crusts. We propose that the, possibly continental, lower crust is intruded by magmatic material and that the upper crustal layer is made from extrusive volcanic rocks of the same magmatic origin, forming thick seaward (westward)-dipping reflectors (SDRs) sequences. This SDR complex extends to the Guinea Plateau as well and was emplaced during hotspot (Sierra Leone)-related volcanic rifting preceding the Jurassic opening of the Central Atlantic and forming the western margin of the plateau. North-south composite lines linking the Demerara and Guinea plateaus reveal the spatial extent of the SDR complex but also a pre-existing basement ridge separating the two plateaus. The entire Demerara-Guinea margin would therefore be an inherited Jurassic volcanic margin bordering the Central Atlantic Ocean to the east, with a possible conjugate being the Bahamas Plateau on the other side of the ocean. This margin was then reworked during a non-coaxial Cretaceous second phase of rifting potentially accompanied by a magmatic event. Opening of the northern margin occurred in a transform mode splitting the
Cette thèse est sous embargo jusqu’au 04/02/2025.;
Landscape evolution on volcanic islands is driven by complex interactions between volcano growth and destruction by a variety of processes (explosive eruptions, landslides, riverine erosion, weathering). Major climate changes, may impact the dynamics of degradation processes at different spatial and temporal scales. For example, extreme rain can produce an immediate hydrological response causing important destruction. Changes in weathering rates, sensitive to precipitation and temperature, can trigger changes in soil fertility but also modify global carbon cycling.The Azores volcanic islands provide an ideal setting to study these interactions, with both scientific and societal significance, especially in the context of ongoing global warming. Located in the Central North Atlantic, they are under the influence of major climatic drivers. Most of them had pulses of volcanic activity over the past 1 Myr, a period characterized by high-amplitude glacial-interglacial transitions with major climatic changes. While global climatic variations have been relatively well-studied for this period, reconstructing the atmospheric paleoclimate and its effects at local/regional scales remains challenging. Paleosols (PSs) are fossil soils formed by weathering at surface, and later incorporated into the geological record. Their geochemistry provides valuable insights into past environmental conditions, while the geochronology of volcanic products “bracketing” PSs allows their temporal constraint.In this work, we reconstructed mean annual precipitations (MAP) and air temperature (MAAT) over the last 1 Myr in the Azores region through a combined geochemical-geochronological study of PSs. Two proxies based on PSs’ major element were used: the weathering index (CIA-K) and the Clayeyness, both validated in other volcanic settings. The precise dating of volcanic units by either unspiked K-Ar on lava flow groundmass separates or ⁴⁰Ar/³⁹Ar on single K-feldspar of trachytic fallout evidence “pulses” of soil-formation within only a few kyr. This occurred especially after glacial terminations (MIS 21, 19, 11, 9e, 5e and 1), under wet and warm conditions. Fast paleoenvironmental changes were recorded in PSs’ geochemistry, and MAAT reconstructions (12-28 ᵒC) agree with previously published Sea Surface Temperatures, pointing to a tight ocean-atmosphere teleconnection. Those “pulses” suggest sustained weakening phases for the Azores High, allowing humid air currents (Westerlies) to reach further to the south.Our data also show contrasted rates of vertical soil development (3-180 mm/kyr). Weathering was favored by the structure and texture of parental materials, as PSs formed under lower MAP in pyroclastic deposits than in lava flows (~500 and ~800 mm/yr thresholds). This highlights the influence of fragmentation on weathering’s kinetics due to higher specific surface area. Enhanced weathering at surface and along geological discontinuities may have promoted mechanical weakening, favoring erosion and landslides. Notably, high MAPs (up to 1500 mm/yr) obtained around the Eemian interglacial stage are coincident in time with the initiation of a large slide complex on the southern flank of Pico. Intense precipitation may have led to increased water infiltration favoring enhanced hydromagmatic interactions. Drastic increase in pore pressure may then have triggered the initiation of the flank movement along listric faults that are still active. Current conditions in the Azores are wetter and slightly warmer than during the last Myr. Increased infiltration along faults could partly control subsequent movement and yield to detachment of the outer flank of Pico, with potentially dramatic consequences.More generally, present temperature and humidity increase on volcanic islands points to intense weathering, resulting in fast landscape evolution, increased lixiviation and elementary export and high atmospheric CO₂ uptaking, with local, regional and global impacts.
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L'évolution des îles volcaniques résulte d'interactions complexes entre croissance des volcans et processus de destruction (éruptions explosives, glissements de terrain, érosion fluviale, altération). Les changements climatiques peuvent influencer ces processus sur des échelles variées. A l’échelle événementielle, des précipitations intenses peuvent engendrer des épisodes érosifs extrêmes. Sur le long-terme, des variations des taux d'altération, sensibles aux précipitations et à la température, peuvent impacter la fertilité des sols et le cycle global du carbone.Les îles volcaniques des Açores offrent un cadre idéal pour étudier ces interactions, avec une grande importance scientifique et sociétal, en particulier dans le contexte actuel du réchauffement climatique. Au centre de l'Atlantique Nord, elles sont influencées par des facteurs climatiques majeurs. Ces îles ont eu des pulses d'activité volcanique au cours du dernier million d'années (Ma), une période marquée par d’importants changements climatiques liés aux cycles glaciaires-interglaciaires. Si les variations des conditions globales ont été bien documentées sur cette période, la reconstruction paléoclimatique aux échelles locales/régionales reste un défi. Les paléosols (PSs) sont des anciens sols inclus dans le registre géologique. Leur géochimie fournit des informations précieuses sur les conditions paléo-environnementales, et la géochronologie des produits volcaniques les encadrant permet leur contrainte temporelle.Dans ce travail, nous avons reconstruit les conditions moyennes annuelles de précipitation (MAP) et de température de l’air (MAAT) aux Açores au cours du dernier Ma. Deux proxies basés sur la composition en éléments majeurs des PSs ont été utilisés : l’indice d'altération CIA-K et l’argilosité, tous deux validés dans d'autres milieux volcaniques. La datation précise des unités volcaniques par K-Ar sur mésostase séparée (laves) et par ⁴⁰Ar/³⁹Ar sur monocristaux de feldspath potassique (dépôts pyroclastiques), révèle des «pulses» d‘altération sur quelques milliers d’années, notamment après les terminaisons glaciaires (MIS 21, 19, 11, 9e, 5e et 1). La géochimie des PSs montre des changements environnementaux rapides et des MAATs (12-28 ᵒC) en accord avec les données de température marine de surface établies à partir d’archives océaniques. Cette concordance indique une étroite relation océan-atmosphère. Ces «pulses» suggèrent en outre des phases d'affaiblissement de l'anticyclone des Açores, permettant aux courants d'air humides d'atteindre des secteurs plus au sud.Les taux moyens de formation des sols (3-180 mm/kyr) ont été influencés par la structure et la texture du substrat rocheux. Des PSs se sont formés lors de MAPs plus faibles dans les dépôts pyroclastiques que dans les coulées de lave (seuils de ~500 et ~800 mm/an). Cette différence supporte une cinétique favorisée par la fragmentation et une surface spécifique élevée. L’altération accrue en surface et le long des discontinuités géologiques de sub-surface peut avoir favorisé l'érosion par glissements de terrain. Des MAPs élevées (jusqu'à 1500 mm/an) sont notamment obtenues autour du stade interglaciaire de l’Eemien, qui coïncide avec l’initiation d’un glissement complexe sur le flanc Sud de Pico. Des MAPs intenses ont pu accélérer l’infiltration des eaux et favoriser les interactions hydromagmatiques. L’augmentation associée de pression interstitielle a ainsi pu déclencher la mise en mouvement du flanc le long de failles listriques toujours actives. Les conditions actuelles aux Açores sont plus humides et légèrement plus chaudes qu’au cours du dernier Ma, ce que pourrait favoriser le détachement du flanc externe de Pico, avec des conséquences potentiellement drastiques.Plus généralement, l’altération accrue favorise l’évolution rapide du paysage sur de telles îles et engendre des flux élémentaires et une absorption de CO₂ atmosphérique croissantes, ce qui a impacts locaux, régionaux et globaux.
On 8 November 2013 a halo-type coronal mass ejection (CME) was observed,
together with flares and type II radio bursts, but the association between the
flares, radio bursts, and the CME was not clear. Our aim is to identify the
origin of the CME and its direction of propagation, and to exclude features
that were not connected to it. On the Earth-facing side, a GOES C5.7 class
flare occurred close to the estimated CME launch time, followed by an X1.1
class flare. The latter flare was associated with an EUV wave and metric type
II bursts. On the far side of the Sun, a filament eruption, EUV dimmings, and
ejected CME loops were observed by imaging instruments onboard the Solar
TErrestrial RElations Observatory (STEREO) spacecraft that were viewing the
backside of the Sun. The STEREO radio instruments observed an interplanetary
(IP) type II radio burst at decameter-hectometric wavelengths, which was not
observed by the radio instrument onboard the Wind spacecraft located at L1 near
Earth. We show that the halo CME originated from the eruption on the far side
of the Sun, and that the IP type II burst was created by a shock wave ahead of
the halo CME. The radio burst remained unobserved from the earthside, even at
heliocentric source heights larger than 9 solar radii. During the CME
propagation, the X-class flare eruption caused a small plasmoid ejection
earthward, the material of which was superposed on the earlier CME structures
observed in projection. The estimated heights of the metric type II burst match
well with the EUV wave launched by the X-class flare. As this radio emission
did not continue to lower frequencies, we conclude that the shock wave did not
propagate any further. Either the shock driver died out, as a blast wave, or
the driver speed no longer exceeded the local Alfven speed.
International audience;
The Djibouti area is located in the Afar depression which corresponds to the core of a major hot spot at the junction of three rifts: The Red Sea oceanic rift, the Gulf of Aden oceanic rift and the East African continental rift. In the extension of the Gulf of Aden, the opening of the Gulf of Tadjourah in the last 30 million years was followed by the establishment of parallel NW-SE oriented depressions (Gobaad, Hanle, Gaggade, Assal-Ghoubbet). This region is characterised by high heat flow, complex volcanic and tectonic activity, and a dense network of faults favorable to the development of hydrothermal activities. A field survey was conducted to study the gas composition and origin in thermal springs and fumaroles along a transect running from the Lake Abbhé to Djibouti. Hydrogen traces were detected at fumaroles and hot springs associated with hydrothermal systems at the edges of the Gobaad, Hanlé, Gaggade, Assal-Ghoubbet and Arta area. The processes governing to the origin of H2 and its consumption at different levels of the magmatic-hydrothermal systems are discussed. H2 is interpreted as related to several processes including, chemical equilibrium in magmatic gases, alteration of FeII-rich rocks, and oxidation of volcanic H2S. Methane associated with the hydrogen has mostly an abiotic origin and could result from the reaction of hydrogen with carbon oxides. Also, helium emanations have been observed notably on the sides of the Lake Abbhé in boiling hot springs. Gas samples have shown R/RA isotopic ratios of helium up to 10, which is are characteristic values for helium of mantle origin characterized an 3He enrichment with respect to air values.
Introduction Evaluation of the eruption of mandibular third molars in orthopantomograms (OPGs) is a method of forensic age assessment. The objective of our study was to provide valid reference data for this trait within a population of black South Africans. The study was guided by the criteria for reference studies in age assessment. Materials and methods A study population from Pretoria, South Africa comprising 670 OPGs obtained from 338 black females and 332 black males aged between 15.00 and 25.97 years was analysed. All OPGs were performed for medical indication during the period from 2011 to 2022 and were retrospectively evaluated. From the 670 OPGs, a total of 1021 mandibular third molars were evaluated. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two experienced dentists evaluated the OPGs independently of each other. If the two examiners diverged in their assessments, a consensus stage was assigned. Results As expected, the mean, median and minimal age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.79 years in females and 16.62 years in males. Conclusion As it is the case for previous reference studies in other countries, placing exclusive reliance on the evaluation of mandibular third molar eruption is inadequate for ascertaining the age of majority among Black South Africans. Future studies need to examine if our results are transferable to other countries in Sub-Saharan Africa.
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The new submarine volcano Fani Maoré offshore Mayotte (Comoros archipelago) discovered in 2019 has raised the awareness of a possible future eruption in Petite-Terre island, located on the same 60 km-long volcanic chain. In this context of a renewal of the volcanic activity, we present here the first volcanic hazard assessment in Mayotte, focusing on the potential reactivation of the Petite-Terre eruptive centers. Using the 2-D tephra dispersal model HAZMAP and the 1979 - 2021 meteorological ERA-5 database, we first identify single eruptive scenarios of various impacts for the population of Mayotte. Even when considering the least impacting scenario, we show that ~ 30,000 people could be threatened by a future explosive eruption in the highly densely populated island of Petite-Terre. We then use a Monte Carlo approach to sample a series of eruptive scenarios and produce a probabilistic map allowing a long-term vision of the tephra fallout hazard in Mayotte. Finally, we discuss the probability of the different eruptive scenarios based on new field data and show that both Mamoudzou (Grande-Terre) and Petite-Terre could be impacted by at least 5 to 40 cm of tephra. These crucial results will be included in Mayotte’s first volcano emergency plan.
Coastal erosion is a phenomenon with many scientific and social implications. However, the factors controlling this erosion over the long term are still poorly understood, due to the difficulty of quantifying a phenomenon whose cycles can extend over several thousand years. In order to address these issues, we propose in this PhD thesis two new methods to quantify coastal erosion on the scale of a thousand to a hundred thousand years. The first method consists in reconstructing the initial shape of volcanic islands with high radial symmetry in order to calculate the total retreat of coastal cliffs and the total volume eroded by the sea since the maximum extension of the island. The second method uses the measurement of cosmogenic isotope abundance in coastal cliff colluvium to infer coastal erosion rates. The application of our two methods on various coasts shows that they provide realistic results whose spatial variations are consistent with the geomorphological context of the coastal cliffs. The comparative application of our two methods on the same object, the island of Fogo (Cape Verde), shows that they offer results with similar and coherent spatial variations, although the erosion rate values obtained have different orders of magnitude. Due to different integration times for our two methods, these differences may reflect a change in coastal erosion rate over the long term, thus overcoming the integrative nature of the measurement. By applying our first method on six different islands, we were able to build the CoastErV2I database from our results. The analysis of this database shows a general decrease of coastal erosion rates over time, controlled by the morphological evolution of the rocky coast, and a strong control of waves on the spatial variations of coastal erosion, except when the coast is undergoing important vertical dynamics. Expanding the database to other islands and other observable factors will confirm these initial observations.
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L'érosion côtière est un phénomène revêtant de nombreux enjeux scientifiques et sociaux. Les facteurs contrôlant cette érosion sur le long-terme sont cependant encore mal connus, du fait de la difficulté de quantifier un phénomène dont les cycles peuvent s'étaler sur plusieurs milliers d'années. Afin de répondre à ces enjeux, nous proposons dans cette thèse deux nouvelles méthodes permettant de quantifier l'érosion côtière sur l'échelle du millier à la centaine de milliers d'années. La première méthode consiste à reconstruire la forme initiale d'îles volcaniques présentant une forte symétrie radiale afin de calculer le recul total des falaises côtières et le volume total érodé par la mer depuis l'extension maximale de l'île. La seconde méthode utilise la mesure de l'abondance en isotopes cosmogéniques dans les colluvions falaises côtières pour en déduire des taux d'érosion côtière. L'application de nos deux méthodes sur divers côtes montre qu'elles offrent des résultats réalistes dont les variations spatiales sont cohérentes avec le contexte géomorphologique des falaises côtières. L'application comparée de nos deux méthodes sur un même objet, l'île de Fogo (Cap Vert), montre qu'elles offrent des résultats aux variations spatiales similaires et cohérentes, bien que les valeurs de taux d'érosion obtenues aient des ordres de grandeur différents. Du fait de temps d'intégration différents pour nos deux méthodes, ces différences peuvent témoigner d'un changement de vitesse de l'érosion côtière sur le long terme, outrepassant ainsi le caractère intégratif de la mesure. En appliquant notre première méthode sur six îles différentes, nous avons pu constituer la base de données CoastErV2I à partir de nos résultats. L'analyse de cette base de données montre notamment une diminution générale des taux d'érosion côtière au court du temps, contrôlée par l'évolution morphologique de la côte rocheuse, et un contrôle fort des vagues sur les variations spatiales de l'érosion côtière, sauf lorsque la côte subit une importante dynamique verticale. Élargir la base de données à d'autres îles et d'autres facteurs observables permettra de confirmer ces premières observations.
CCSD;AGU and the Geochemical SocietyApril 2026Volcanology
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Abstract Many intraplate volcanic chains are explained as hotspot trails formed by plate motion over mantle plumes, yet some deviate from this model. The Rodrigues Ridge, a volcanic lineament extending eastward from the Réunion hotspot track toward the Central Indian Ridge (CIR), is one such case. To assess its origin, we integrated field studies with zircon U‐Pb and (U‐Th)/He geo‐/thermochronology, groundmass K‐Ar dating, and major and trace element analyses of volcanic rocks from Rodrigues Island. Our results reveal that Rodrigues Island experienced a prolonged subaerial volcanic history from 4.1 to 1.1 Ma, 2.7 million years longer than previously thought. This history shows two episodes of volcanic construction: (a) a circular volcano construction between 4.1 and 2.5 Ma, followed by erosion, subsidence, and coral reef development and (b) fissural volcanism from 2.3 to 1.1 Ma, which shaped the island's elongated morphology. Subaerial lavas are more alkalic and enriched in incompatible elements than older submarine ridge lavas. This geochemical evolution suggests an eastward migration of partial melting, with oceanic accretion driving magmatism along the Rodrigues Ridge. Combined with magnetic anomalies of the oceanic lithosphere, the chronology points to at least two propagation episodes toward the CIR (≥9.9–7.9 Ma and 4.1–0.4 Ma). We conclude that the Rodrigues Ridge originated as a fracture in the oceanic lithosphere, driven by plume‐related buoyancy forces and asthenospheric flow beneath the CIR, without any direct contribution from the Réunion plume to the partial melting degree. These findings emphasize the role of lithospheric stresses and oceanic accretion in shaping off‐axis volcanic chains.
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The physical processes that operate within, and beneath, a volcano control the frequency, duration, location and size of volcanic eruptions. Volcanotectonics focuses on such processes, combining techniques, data, and ideas from structural geology, tectonics, volcano deformation, physical volcanology, seismology, petrology, rock and fracture mechanics and classical physics. A central aim of volcanotectonics is to provide sufficient understanding of the internal processes in volcanoes so that, when combined with monitoring data, reliable forecasting of eruptions, vertical (caldera) and lateral (landslide) collapses and related events becomes possible. To gain such an understanding requires knowledge of the material properties of the magma and the crustal rocks, as well as the associated stress fields, and their evolution. The local stress field depends on the properties of the layers that constitute the volcano and, in particular, the geometric development of its shallow magma chamber. During this decade an increasing use of data from InSAR, pixel offset and structure-from-motion, as well as dense, portable seismic networks will provide further details on the mechanisms of volcanic unrest, magma-chamber rupture, the propagation of magma-filled fractures (dikes, inclined sheets and sills) and lateral and vertical collapse. Additionally, more use will be made of accurate quantitative data from fossil and active volcanoes, combined with realistic numerical, analytical and machine-learning studies, so as to provide reliable models on volcano behaviour and eruption forecasting.
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Volcano geodesy often involves the use of models to explain observed surface deformation. A variety of forward models are used, from analytical point sources to numerical simulations that consider complex magma system geometries, topography, and material properties. Various inversion methods can then be used to relate observed volcano data to models. Ideally, forward models should be verified through intercomparison, to check for implementation errors and quantify the error induced by any approximations used. Additionally, forward models and inversion methods should be validated through tests with synthetic and/or real data, to determine their ability to match data and estimate parameter values within uncertainty. However, to date there have not been comprehensive verification and validation efforts in volcano geodesy. Here, we report on the first phase of the Drivers of Volcano Deformation (DVD) exercises, which were designed to build community involvement through web-based exercises involving calculations of static elastic displacement around pressurized magma reservoirs. The forward model exercises begin with a spherical reservoir in a homogeneous half space, then introduce topography, heterogeneous elastic properties, and spheroidal geometries. The inversion exercises provide synthetic noisy surface displacement data for a spherical reservoir in a homogeneous half space and assess consistency in estimates of reservoir location and volume/pressure change. There is variability in the results from both forward modeling and inversions, which highlights the strengths and limitations of different forward models, as well as the importance of inversion method choice and uncertainty quantification. This first phase of the DVD exercises serves as a community resource and will facilitate further efforts to develop standards of reproducibility.
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The solar carbo-thermal and methano-thermal reduction of both MgO and ZnO were performed in a flexible solar reactor operated at low pressure through both batch and continuous operations. The pyro-metallurgical process is an attractive sustainable pathway to convert and store concentrated solar energy into high-value metal commodities and fuels. Substituting fossil fuel combustion with solar energy when providing high-temperature process heat is a relevant option for green extractive metallurgy. In this study, a thermodynamic equilibrium analysis was first performed to compare the thermochemical reduction of MgO and ZnO with solid carbon or gaseous methane, and to determine the product distribution as a function of the operating conditions. The carbo-thermal and methano-thermal reduction of the MgO and ZnO volatile oxides was then experimentally assessed and compared using a directly irradiated cavity-type solar reactor under different operating conditions, varying the type of carbon-based reducing agent (either solid carbon or methane), temperature (in the range 765–1167 °C for ZnO and 991–1550 °C for MgO), total pressure (including both reduced 0.10–0.15 bar and atmospheric ~0.90 bar pressures), and processing mode (batch and continuous operations). The carbo-thermal and methano-thermal reduction reactions yielded gaseous metal species (Mg and Zn) which were recovered at the reactor outlet as fine and reactive metal powders. Reducing the total pressure favored the conversion of both MgO and ZnO and increased the yields of Mg and Zn. However, a decrease in the total pressure also promoted CO2 production because of a shortened gas residence time, especially in the case of ZnO reduction, whereas CO2 formation was negligible in the case of MgO reduction, whatever the conditions. Continuous reactant co-feeding (corresponding to the mixture of metal oxide and carbon or methane) was also performed during the solar reactor operation, revealing an increase in both gas production yields and reaction extent while increasing the reactant feeding rate. The type of carbon reducer influenced the reaction extent, since a higher conversion of both MgO and ZnO was reached when using carbon with a highly available specific surface area for the reactions. The continuous solar process yielded high-purity magnesium and zinc content in the solar-produced metallic powders, thus confirming the reliability, flexibility, and robustness of the solar reactor and demonstrating a promising solar metallurgical process for the clean conversion of both metal oxides and concentrated solar light to value-added chemicals.
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Hot droughts are expected to increase in Europe and disturb forest ecosystem functioning. Wood formation of trees has the potential to adapt to those events by compensatory mechanisms between the rates and durations of tracheid differentiation to form the typical pattern of vital wood anatomical structures. We monitored xylogenesis and measured wood anatomy of mature silver fir ( Abies alba Mill.) and Scots pine ( Pinus sylvestris L.) trees along an elevational gradient in the Black Forest during the hot drought year of 2018. We assessed the kinetics of tracheid differentiation and the final tracheid dimensions and quantified the relationship between rates and durations of cell differentiation over the growing season. Cell differentiation kinetics were decoupled, and temperature and water availability signals were imprinted in the tree ring structure. The sudden decline in woody biomass production provided evidence for a disruption in carbon sequestration processes due to heat and drought stress. Growth processes of Scots pine (pioneer species) were mainly affected by the spring drought, whereas silver fir (climax species) growth processes were more disturbed by the summer drought. Our study provides novel insights on the plasticity of wood formation and carbon allocation in temperate conifer tree species in response to extreme climatic events.
HAL CCSD;Institute of Electrical and Electronics EngineersAugust 2021Climate Science
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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 performance of surface temperature is very similar across all considered MISTIGRI spectral configurations, with RMSE variation within 0.2 K.
This thesis is focused on the study of the carbon dioxide hydrogenation reaction towards gaseous and liquid hydrocarbons over a supported K-Fe/Al2O3 catalyst. The subject is part of the framework of the Power-to-X technologies that aim at storing surplus electric power derived from renewable energy into the form of gaseous and liquid chemical compounds. In particular, the electricity is used to perform the water electrolysis to produce hydrogen, then the obtained hydrogen is used to convert carbon dioxide into hydrocarbons. These hydrocarbons can have applications as feedstock in the chemical industry or as fuels in the transport field. The carbon dioxide hydrogenation is a catalytic reaction, generally performed over Fe-based catalysts, consisting in two steps: first, carbon dioxide is converted into carbon monoxide via the reverse water-gas shift reaction (RWGS), and then it is further transformed into hydrocarbons via the Fischer-Tropsch synthesis (FT). One of the main constraints of this reaction is its low selectivity, as a variety of hydrocarbons can be obtained. For an eventual application of this process at the industrial scale, it is necessary to deeper understand and better describe the selectivity of the reaction to optimize the productivity of the desired products. In this work, we have carried out an experimental study of the reaction in a lab-scale fixed bed reactor and developed an analytic protocol that allows the quantification of all the products obtained. Moreover, we have developed a macro-kinetic model that describes with a semi-empirical approach the formation of all the products considered; and a micro-kinetic model, that contributes to give insights about the reaction mechanism. Finally, we have modelled a scaled-up reactor with a heterogeneous and a pseudo-homogeneous approach and we have simulated the global process to estimate its carbon and energy efficiencies.
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Cette thèse porte sur l'étude de la réaction d'hydrogénation du dioxyde de carbone vers des hydrocarbures gazeux et liquides sur un catalyseur supporté K-Fe/Al2O3. Le sujet s'inscrit dans le cadre des technologies Power-to-X qui visent à stocker les excès d’énergie électrique issue des énergies renouvelables sous forme de composés chimiques gazeux et liquides. En particulier, l'électricité est utilisée pour produire de l'hydrogène via l’électrolyse de l'eau, puis l'hydrogène obtenu est utilisé pour convertir le dioxyde de carbone en hydrocarbures. Ces hydrocarbures peuvent avoir des applications comme matière première dans l'industrie chimique ou comme carburants dans le domaine des transports. L'hydrogénation du dioxyde de carbone est une réaction catalytique, généralement réalisée sur des catalyseurs à base de fer, et s’effectue en deux étapes : d'abord, le dioxyde de carbone est converti en monoxyde de carbone via la réaction inverse de conversion eau-gaz (RWGS), puis le monoxyde de carbone est transformé en hydrocarbures via la synthèse Fischer-Tropsch (FT). L'une des principales contraintes de cette réaction est sa faible sélectivité, car une grande variété d'hydrocarbures peut être obtenue. Pour une éventuelle application de ce procédé à l'échelle industrielle, il est nécessaire de comprendre comment la sélectivité de la réaction pourrait être orientée vers la formation des produits visés. Dans ce travail, une étude expérimentale à l'échelle du laboratoire a été réalisée dans un lit fixe continu et un protocole analytique qui permet la quantification de tous les produits obtenus a été développé. De plus, nous avons développé un modèle macro-cinétique qui décrit avec une approche semi-empirique la formation de tous les produits considérés ; et un modèle micro-cinétique, qui contribue à apporter un éclairage sur les mécanismes de réaction possibles. Enfin, nous avons modélisé un réacteur à plus grande échelle avec des approches hétérogène et pseudo-homogène et nous avons simulé le procédé global pour estimer son bilan carbone et son efficacité énergétique.
Abstract. Oceanic particulate organic carbon (POC) is a relatively small (~4 Pg C) but dynamic component of the global carbon cycle with fast mean turnover rates compared to other oceanic, continental and atmospheric carbon stocks. Biogeochemical models historically focused on reproducing the sinking flux of POC driven by large fast-sinking particles (bPOC). However, suspended and slow-sinking particles (sPOC) typically represent 80–90 % of the POC stock, and can make important seasonal contributions to vertical fluxes through the mesopelagic layer (200–1000 m). Recent developments in the parameterization of POC reactivity in the PISCES model (PISCESv2_RC) have greatly improved its ability to capture sPOC dynamics. Here we evaluated this model by matching 3D and 1D simulations with BGC-Argo and satellite observations in globally representative ocean biomes, building on a refined scheme for converting particulate backscattering profiles measured by BGC-Argo floats to POC. We show that PISCES captures the major features of sPOC and bPOC as seen by BGC-Argo floats across a range of spatiotemporal scales, from highly resolved profile time series to biome-aggregated climatological profiles. Our results also illustrate how the comparison between the model and observations is hampered by (1) the uncertainties in empirical POC estimation, (2) the imperfect correspondence between modelled and observed variables, and (3) the bias between modelled and observed physics. Despite these limitations, we identified characteristic patterns of model-observations misfits in the mesopelagic layer of subpolar and subtropical gyres. These misfits likely result from both suboptimal model parameters and model equations themselves, pointing to the need to improve the model representation of processes with a critical influence on POC dynamics, such as sinking, remineralization, (dis)aggregation and zooplankton activity. Beyond model evaluation results, our analysis identified inconsistencies between current estimates of POC from satellite and BGC-Argo data, as well as POC partitioning into phytoplankton, heterotrophs and detritus deduced from in situ bio-optical data. Our approach can help constrain POC stocks, and ultimately budgets, in the epipelagic and mesopelagic ocean.
John Wiley and Sons Inc.December 2022Climate Science
Stable carbon isotopes in plants can help evaluate and improve the representation of carbon and water cycles in land‐surface models, increasing confidence in projections of vegetation response to climate change. Here, we evaluated the predictive skills of the Joint UK Land Environmental Simulator (JULES) to capture spatio‐temporal variations in carbon isotope discrimination (Δ(13)C) reconstructed by tree rings at 12 sites in the United Kingdom over the period 1979–2016. Modeled and measured Δ(13)C time series were compared at each site and their relationships with local climate investigated. Modeled Δ(13)C time series were significantly correlated (p < 0.05) with tree‐ring Δ(13)C at eight sites, but JULES underestimated mean Δ(13)C values at all sites, by up to 2.6‰. Differences in mean Δ(13)C may result from post‐photosynthetic isotopic fractionations that were not considered in JULES. Inter‐annual variability in Δ(13)C was also underestimated by JULES at all sites. While modeled Δ(13)C typically increased over time across the UK, tree‐ring Δ(13)C values increased only at five sites located in the northern regions but decreased at the southern‐most sites. Considering all sites together, JULES captured the overall influence of environmental drivers on Δ(13)C but failed to capture the direction of change in Δ(13)C caused by air temperature, atmospheric CO(2) and vapor pressure deficit at some sites. Results indicate that the representation of carbon‐water coupling in JULES could be improved to reproduce both the trend and magnitude of interannual variability in isotopic records, the influence of local climate on Δ(13)C, and to reduce uncertainties in predicting vegetation‐environment interactions.
[Image: see text] Enhanced weathering is a carbon dioxide (CO(2)) mitigation strategy that promises large scale atmospheric CO(2) removal. The main challenge associated with enhanced weathering is monitoring, reporting, and verifying (MRV) the amount of carbon removed as a result of enhanced weathering reactions. Here, we study a CO(2) mineralization site in Consett, Co. Durham, UK, where steel slags have been weathered in a landscaped deposit for over 40 years. We provide new radiocarbon, δ(13)C, (87)Sr/(86)Sr, and major element data in waters, calcite precipitates, and soils to quantify the rate of carbon removal. We demonstrate that measuring the radiocarbon activity of CaCO(3) deposited in waters draining the slag deposit provides a robust constraint on the carbon source being sequestered (80% from the atmosphere, 2σ = 8%) and use downstream alkalinity measurements to determine the proportion of carbon exported to the ocean. The main phases dissolving in the slag are hydroxide minerals (e.g., portlandite) with minor contributions (<3%) from silicate minerals. We propose a novel method for quantifying carbon removal rates at enhanced weathering sites, which is a function of the radiocarbon-apportioned sources of carbon being sequestered, and the proportion of carbon being exported from the catchment to the oceans.
Composting organic matter can lower the global warming potential of food and agricultural waste and provide a nutrient-rich soil amendment. Compost applications generally increase net primary production (NPP) and soil water-holding capacity and may stimulate soil carbon (C) sequestration. Questions remain regarding the effects of compost nitrogen (N) concentrations and application rates on soil C and greenhouse gas dynamics. In this study, we explored the effects of compost with different initial N quality (food waste versus green waste compost) on soil greenhouse gas fluxes, aboveground biomass, and soil C and N pools in a fire-impacted annual grassland ecosystem. Composts were applied annually once, twice, or three times prior to the onset of the winter rainy season. A low-intensity fire event after the first growing season also allowed us to explore how compost-amended grasslands respond to burning events, which are expected to increase with climate change. After four growing seasons, all compost treatments significantly increased soil C pools from 9.5 ± 0.9 to 30.2 ± 0.7 Mg C ha^−1 (0–40 cm) and 19.5 ± 0.9 to 40.1 ± 0.7 Mg C ha^−1 (0–40 cm) relative to burned and unburned controls, respectively. Gains exceeded the compost-C applied, representing newly fixed C. The higher N food waste compost treatments yielded more cumulative soil C (5.2–10.9 Mg C ha^−1) and aboveground biomass (0.19–0.66 Mg C ha^−1) than the lower N green waste compost treatments, suggesting greater N inputs further increased soil stocks. The three-time green waste application increased soil C and N stocks relative to a single application of either compost. There was minimal impact on net ecosystem greenhouse gas emissions. Aboveground biomass accumulation was higher in all compost treatments relative to controls, likely due to increased water-holding capacity and N availability. Results show that higher N compost resulted in larger C gains with little offset from greenhouse gas emissions and that compost amendments may help mediate effects of low-intensity fire by increasing fertility and water-holding capacity.
Climate change is known to simultaneously increase berry sugars but decrease anthocyanins, leading to an imbalance between sugars and anthocyanins in grape berries. To restore the balance of sugars and anthocyanins, carbon limitation by leaf removal and exogenous abscisic acid (ABA) were separately or simultaneously applied to Vitis vinifera cv. Cabernet Sauvignon fruit cuttings to decipher their effects on berry quality with metabolite and whole-genome transcriptome analyses. Carbon limitation decreased the hexose concentration and fully blocked the accumulation of anthocyanins. However, exogenous ABA increased the anthocyanin concentration under both carbon limitation and sufficient conditions. Carbon limitation and exogenous ABA induced the profound remodeling of the whole-genome transcriptome and altered the anthocyanin concentration by regulating the transcription levels of genes involved in the anthocyanin biosynthesis pathways as well as in the genes involved in various types of hormone signaling. Moreover, two pertinent candidate genes were identified based on the co-expression network analysis between the berry metabolite and transcriptome results, including a transcriptional factor, ERF2, and a calcineurin B-like protein-interacting protein kinase gene, CIPK25. In summary, simultaneously modifying the carbon supply by leaf removal and spraying exogenous ABA could re-establish the balance between sugars and anthocyanins to improve the qualities of grape berries via whole-genome transcriptome remodeling.
Greenhouse effects are a natural phenomenon that plays a high role in shaping the climate system. In this research, MEA solution was used for CO(2) capture in presence of activated carbon particles from waste walnut shells as a biosorbent. The process parameters including temperature, pressure, MEA concentration, and activated carbon were used in the central composite design (CCD) model. The absorption experiments were carried out in a laboratory setup at operational conditions including temperature in range of 20–60 °C, pressure in range of 3.5–9.5 bar, MEA concentration in range of 2.5–8.5 wt%, and active carbon amount in range of 0.3–0.9 g/L. The process responses including CO(2) loading, the amounts of CO(2) absorption, and absorption percentage were obtained in the range of 0.444–0.720 mol(CO2)/mol(MEA), 0.294–0.687 mol/L, and 19.32–52.25%, respectively. The optimal value of CO(2) loading was obtained at temperature of 30 °C, pressure of 5.19 bar, activated carbon of 0.75 g, and MEA concentration of 7.00 wt%. The optimum values of responses were obtained 0.531, 0.609 mol/L and 50.04% for maximum loading, absorption amount, and absorption percentage, respectively. From the results, carbon dioxide loading in MEA solution increases in presence of activated carbon particles.
The ocean plays a critical role in sustainable development, particularly in climate change mitigation. Among marine ecosystems, blue carbon ecosystems are recognized as important natural carbon sinks. In this context, this paper addresses precise seaweed classification for blue carbon quantification in Ocean Digital Twin initiatives. Conventional methods, including supervised learning (limited by data scarcity and domain gaps) and self-supervised learning (unable to assign class labels), struggle with underwater complexities and diverse seaweed species. To overcome this, we propose a novel two-stage seaweed segmentation technique. This technique first utilizes Supervised and Self-supervised Learning Model Propagation (SSL.Prop.), which leverages supervised learning for initial class information and approximate locations, guiding self-supervised learning for detailed, accurate segmentation. Subsequently, MaskFusion (MF) refines these results by merging instance-level masks for highly accurate segmentation. This integrated approach allows automatic class label assignment and mitigates domain gap effects. Specifically, instance segmentation estimates sparse point locations which then guide self-supervised learning for detailed region segmentation. Evaluated with underwater images from Yamaguchi Prefecture, our full proposed method (SSL.Prop.+MF) achieved a 0.082 mIoU improvement over USIS-SAM, demonstrating significant accuracy gains, particularly for small seaweed. This approach demonstrates strong potential for improving blue carbon quantification and marine ecosystem monitoring. ;Accepted to ASME OMAE 2026
Anthropogenic greenhouse gases (GHGs) emissions are causing irreversible climate change. To address this issue, the European Union (EU) committed to strong decreases in GHGs emissions. However, to reach carbon (C) neutrality by 2050 it will also be necessary to implement atmospheric C removals by natural sinks, such as soils. To partially compensate for CO2 emissions, the 4 per 1000 initiative of 2015 proposed an annual 4‰ soil organic carbon (SOC) stock increase in the first 30-40 cm depth of the soil. Yet, the feasibility of such an ambitious target is still under debate because it may require substantial and rapid changes in agricultural practices that would be hard to achieve. The most efficient way to increase SOC stocks is to increase the C input to the soil. Pro-cess-based biogeochemical models can simulate the dynamics of SOC and are increasingly used to support decision-makers on SOC mitigation policies. Despite the numerous models available to describe the SOC dynamics, simulations are still somewhat unreliable. This is because uncertainties not only derive from the mechanistic structure of the models and the processes included, but also from the input data and the parameter values used.The objective of this thesis is to estimate the C input required to yearly increase SOC stocks by 4‰ in European croplands. To solve this problem, we build an inverse modeling approach and apply it to a multi-model ensemble to assess the uncertainties of the estimations according to different representations of the SOC dynamics. Then, to improve the simulation of SOC stocks, we test a new, statistically derived, parametrization technique.As a first attempt to provide insights for policymakers, we generate maps of the C input required to reach the 4‰ target in the whole European cropland area, under two scenarios of climate change. Our study demonstrates that there are substantial uncertainties around the C input required to reach a 4‰ target. However, a general pattern emerges at the European cropland scale, where the 4‰ target seems feasible under future scenarios of climate change, only assuming drastic increases of C input to the soil. In particular, higher C input is required in Northern Europe, while higher uncertainties are associated with the European South. The high variability of the simulated C input requirements highlights the advantage of using multi-model ensembles, in order to consider the range of uncertainty linked to their different mechanistic structures. Yet, multi-model ensembles still tend to underestimate the C input required to increase SOC stocks. Major efforts should be made to improve model simulations, especially to capture the effect of additional C input on the accumulation of SOC. At a local scale, the calibration of model parameters was necessary to fit observed SOC stock variations. When long-term SOC stock monitoring is not available, the necessity for improved parametrization techniques emerges. The calibration that we proposed at the European scale improved the simulation of first-year SOC stocks. However, it increased the divergence of predicted SOC stocks across models. Future work should focus on the reduction of model uncertainties in order to provide reliable predictions of future SOC stock variations and their related processes.
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Les émissions anthropiques de gaz à effet de serre (GES) provoquent un changement climatique irréversible. L'Union Européenne (UE) s'est engagée à diminuer fortement ses émissions de GES. Cependant, pour atteindre la neutralité carbone (C) d'ici 2050, elle devra également séquestrer du C atmosphérique dans des puits naturels, tels que les sols. Pour compenser partiellement les émissions de CO2, l'initiative 4 pour 1000 a proposé en 2015 un objectif d'augmentation annuelle de 4‰ des stocks de carbone organique du sol (COS) dans les 30-40 premiers cm de profondeur du sol. Pourtant, la faisabilité d'une telle augmentation fait l'objet de débats car elle pourrait nécessiter des changements substantiels et rapides dans les pratiques agricoles qui seraient difficiles à mettre en œuvre. Le moyen le plus efficace pour accroître les stocks de COS est d'augmenter l'apport de C dans le sol. Les modèles basés sur les processus biogéochimiques peuvent simuler la dynamique du COS et sont de plus en plus utilisés pour aider les décideurs dans leurs politiques d'atténuation du COS. Cependant, malgré les nombreux modèles disponibles pour décrire la dynamique du COS, les simulations sont encore peu fiables. En effet, les incertitudes ne proviennent pas seulement de la structure mécaniste des modèles et des processus qu’ils prennent en compte, mais aussi des données utilisées en entrée et des valeurs des paramètres.L'objectif de cette thèse est d'estimer l'apport de C nécessaire pour augmenter annuellement les stocks de COS de 4‰ dans les terres cultivées européennes. Pour cela, nous avons construit une modélisation inverse et l'avons appliquée à un ensemble multi-modèle. Nous avons ainsi évalué les incertitudes dans les estimations des entrées de C selon différentes représentations de la dynamique du COS. Ensuite, pour améliorer la simulation des stocks de COS, nous avons testé une nouvelle paramétrisation issue de dérivée statistiques.Afin de fournir un premier aperçu aux décideurs politiques, nous avons généré des cartes de l'apport de C nécessaire pour atteindre l'objectif de 4‰ dans l'ensemble des terres cultivées européennes, et ce, pour deux scénarios de changement climatique.Notre étude a démontré qu'il existe des incertitudes substantielles autour de l'apport de C nécessaire. Cependant, un profil général émerge, où atteindre un objectif d'augmentation de 4‰ du stock de COS à l'échelle des terres cultivées européennes semble réalisable pour les scénarios futurs de changement climatique seulement via des augmentations drastiques de d'apport de C. En particulier, un apport de C plus élevé est nécessaire en Europe du Nord, tandis qu’en Europe du Sud les incertitudes sont plus élevées. La grande variabilité dans les simulations d'apport de C nécessaires à l’objectif 4‰ souligne l'avantage d'utiliser des ensembles multi-modèles, afin de prendre en compte la gamme d'incertitudes liées à leurs différentes structures mécanistiques. Cependant, les ensembles multi-modèles ont encore tendance à sous-estimer l'apport de C nécessaire pour augmenter les stocks de COS. Des progrès importants doivent donc encore être faits pour améliorer les simulations des modèles, en particulier pour saisir l'effet d'un apport supplémentaire de C sur l'accumulation de COS. A l'échelle locale, la calibration des paramètres des modèles a été nécessaire pour simuler les variations observées des stocks de COS. Lorsque le suivi à long terme du stock de COS n'est pas disponible, il est nécessaire d'améliorer les techniques de paramétrisation. La calibration que nous avons proposée à l'échelle européenne a amélioré la simulation des stocks de COS de la première année mais a augmenté la divergence des stocks de COS prédits par les modèles. De futurs travaux se concentrant sur la réduction des incertitudes des modèles afin de fournir des prédictions fiables des variations futures des stocks de COS et des processus associés sont donc essentiels.
Oceanic carbon storage is one of the main sinks for atmospheric CO2, and thought to be the major contributing factor for CO2 drawdown during past glacial periods. Both physical and biogeochemical processes control the capacity of carbon storage in the ocean. During glacial periods of the Pleistocene the larger volume of deep-water masses of Southern Hemisphere origin in the Atlantic has been shown to promote carbon storage in the Southern Ocean. However, the latitudinal extension of this water mass in the Indian Ocean has been scarcely studied. In this study, we combine foraminiferal εNd and benthic δ13C of two sediment cores in the southwest Indian Ocean (MD96–2077, 33°S, 3781 m water depth; MD96–2052, 19°S, 2627 m water depth), to reconstruct the spatial and temporal evolution of glacial carbon-rich deep waters in the SW Indian over the last 630 kyr. The combined use of foraminiferal εNd and benthic δ13C allows to distinguish δ13C changes related to water mass mixing and from respired carbon accumulation within the water masses. Nutrient-rich deep waters, which cannot be explained by the enhanced proportion of southern-sourced waters, were present at core sites deeper than 2700 m during glacial periods and extended at least until 33°S into the SW Indian Ocean. From Marine Isotope Stage (MIS) 14 to MIS 10, glacial carbon storage increased gradually until reaching its highest capacity during the extreme glacial periods MIS 12 and 10. Orbital forcing (100-kyr eccentricity, 41-kyr obliquity), restricted air-sea exchange and enhanced ocean stratification, fostered higher carbon storage during periods of relatively lower eccentricity and obliquity. Furthermore, after MIS 10, a progressive transition was observed from 100-kyr eccentricity to 41-kyr obliquity cycles in benthic δ13C and δ18O records of core MD96–2077 and sea-ice cover changes derived from ice-rafted debris of the Agulhas Plateau composite core site.
Mesospheric CO2 clouds are one of two types of carbon dioxide clouds known on
Mars. We present observations of mesospheric CO2 clouds made by Atmospheric
Chemistry Suit (ACS) onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter (TGO).
We analyzed 1663 solar occultation sessions of Thermal InfraRed (TIRVIM) and
Middle InfraRed (MIR) channels of ACS covering more than two Martian years that
contain spectra of 2.7 {\mu}m carbon dioxide ice absorption band. That allowed
us to unambiguously discriminate carbon dioxide ice aerosols from mineral dust
and water ice aerosols, not relying on the information of atmospheric thermal
conditions. CO2 clouds were detected in eleven solar occultation observations
at altitudes from 39 km to 90 km. In five cases, there were two or three layers
of CO2 clouds that were vertically separated by 5-15 km gaps. Effective radius
of CO2 aerosol particles is in the range of 0.1-2.2 {\mu}m. Spectra produced by
the smallest particles indicate a need for a better resolved CO2 ice refractive
index. Nadir optical depth of CO2 clouds is in the range 5*10^{-4}-4*10^{-2} at
both 2.7 {\mu}m and 0.8 {\mu}m. Asymmetrical diurnal distribution of detections
observed by ACS is potentially due to local time variations of temperature
induced by thermal tides. Two out of five cases of carbon dioxide cloud
detections made by the TIRVIM instrument reveal the simultaneous presence of
CO2 ice and H2O ice aerosols. Temperature profiles measured by the Near
InfraRed (NIR) channel of ACS are used to calculate CO2 saturation ratio S at
locations of carbon dioxide clouds. Supersaturation S > 1 is detected in only 5
out of 19 cases of CO2 cloud layers; extremely low values of S < 0.1 are found
in 9 out of 19 cases.
;Comment: 29 pages, 10 figures. Submitted to Icarus
The carbon-capturing process with the aid of CO2 removal technology (CDRT)
has been recognised as an alternative and a prominent approach to deep
decarbonisation. However, the main hindrance is the enormous energy demand and
the economic implication of CDRT if not effectively managed. Hence, a novel
deep reinforcement learning agent (DRL), integrated with an automated
hyperparameter selection feature, is proposed in this study for the real-time
scheduling of a multi-energy system coupled with CDRT. Post-carbon capture
systems (PCCS) and direct-air capture systems (DACS) are considered CDRT.
Various possible configurations are evaluated using real-time multi-energy data
of a district in Arizona and CDRT parameters from manufacturers' catalogues and
pilot project documentation. The simulation results validate that an optimised
soft-actor critic (SAC) algorithm outperformed the TD3 algorithm due to its
maximum entropy feature. We then trained four (4) SAC agents, equivalent to the
number of considered case studies, using optimised hyperparameter values and
deployed them in real time for evaluation. The results show that the proposed
DRL agent can meet the prosumers' multi-energy demand and schedule the CDRT
energy demand economically without specified constraints violation. Also, the
proposed DRL agent outperformed rule-based scheduling by 23.65%. However, the
configuration with PCCS and solid-sorbent DACS is considered the most suitable
configuration with a high CO2 captured-released ratio of 38.54, low CO2
released indicator value of 2.53, and a 36.5% reduction in CDR cost due to
waste heat utilisation and high absorption capacity of the selected sorbent.
However, the adoption of CDRT is not economically viable at the current carbon
price. Finally, we showed that CDRT would be attractive at a carbon price of
400-450USD/ton with the provision of tax incentives by the policymakers.
;Comment: 39 pages; postprint
International audience;
This paper deals with the carbon footprint of distributed maintenance operations. It concerns the maintenance scheduling of a set of geographically distributed production sites where pieces of equipment are subject to failure. Their health state is monitored by a central maintenance workshop (CMW), which plans the corresponding preventive maintenance (PM) tasks and repairs defective equipment. A mobile maintenance workshop (MMW) transports all the resources necessary to maintain each piece of equipment, following the predefined schedule. This study aims to propose an approach to reducing CO2 emissions of the MMW routing. The model allows choosing the optimal position of the CMW and the capacity of vehicles, both satisfying a low cost and a low carbon footprint. We conduct several experiments from a real-world case study and European Union (EU) regulation. The results show a trade-off between operational profitability and strategic sustainability.
John Wiley and Sons Inc.November 2023Climate Science
Microbial metabolism offers a wide variety of opportunities to produce chemicals from renewable resources. Employing such processes of industrial biotechnology provides valuable means to fight climate change by replacing fossil feedstocks by renewable substrate to reduce or even revert carbon emission. Several yeast species are well suited chassis organisms for this purpose, illustrated by the fact that the still largest microbial production of a chemical, namely bioethanol is based on yeast. Although production of ethanol and some other chemicals is highly efficient, this is not the case for many desired bulk chemicals. One reason for low efficiency is carbon loss, which decreases the product yield and increases the share of total production costs that is taken by substrate costs. Here we discuss the causes for carbon loss in metabolic processes, approaches to avoid carbon loss, as well as opportunities to incorporate carbon from CO(2), based on the electron balance of pathways. These aspects of carbon efficiency are illustrated for the production of succinic acid from a diversity of substrates using different pathways.
International audience;
Building on near-real-time and spatially explicit estimates of daily carbon dioxide (CO 2) emissions, here we present and analyze a new city-level dataset of fossil fuel and cement emissions, Carbon Monitor Cities, which provides daily estimates of emissions from January 2019 through December 2021 for 1500 cities in 46 countries, and disaggregates five sectors: power generation, residential (buildings), industry, ground transportation, and aviation. The goal of this dataset is to improve the timeliness and temporal resolution of city-level emission inventories and includes estimates for both functional urban areas and city administrative areas that are consistent with global and regional totals. Comparisons with other datasets (i.e. CEADs, MEIC, Vulcan, and CDP-ICLEI Track) were performed, and we estimate the overall annual uncertainty range to be ±21.7%. Carbon Monitor Cities is a near-real-time, city-level emission dataset that includes cities around the world, including the first estimates for many cities in low-income countries.
Decoding from large language models (LLMs) typically relies on fixed sampling hyperparameters (e.g., temperature, top-p), despite substantial variation in task difficulty and uncertainty across prompts and individual decoding steps. We propose to learn adaptive decoding policies that dynamically select sampling strategies at inference time, conditioned on available compute resources. Rather than fine-tuning the language model itself, we introduce lightweight decoding adapters trained with reinforcement learning and verifiable terminal rewards (e.g. correctness on math and coding tasks). At the sequence level, we frame decoding as a contextual bandit problem: a policy selects a decoding strategy (e.g. greedy, top-k, min-p) for each prompt, conditioned on the prompt embedding and a parallel sampling budget. At the token level, we model decoding as a partially observable Markov decision process (POMDP), where a policy selects sampling actions at each token step based on internal model features and the remaining token budget. Experiments on the MATH and CodeContests benchmarks show that the learned adapters improve the accuracy-budget tradeoff: on MATH, the token-level adapter improves Pass@1 accuracy by up to 10.2% over the best static baseline under a fixed token budget, while the sequence-level adapter yields 2-3% gains under fixed parallel sampling. Ablation analyses support the contribution of both sequence- and token-level adaptation.
International audience;
Context As a widespread species, sessile oak ( Quercus petraea ) populations occupy a wide range of ecological conditions, with large gradients of soil water availability. Drought acclimation involves a plastic increase in water-use efficiency (WUE), a trait that is easily measured using the carbon isotope composition (δ 13 C). However, the question remains whether WUE is an adaptive trait that impacts the fitness of trees in natural environments. Objectives and Methods To investigate whether WUE was a drought-adaptive trait, we studied a sample of 600 trees originating from 16 provenances, grown for 21 years in a common garden. Intrinsic WUE (WUE i ), estimated from tree ring δ 13 C, was compared among and within populations for three climatically contrasted years. The adaptive character of WUE i was evaluated by relating population mean WUE i , as well as its plasticity to drought, to the pedoclimatic conditions of their provenance sites. The contribution of WUE i to tree and population fitness was finally assessed from the relationship between WUE i and tree radial growth (GI). Results Significant differences in WUE i were found among populations but a much larger variability was observed within than among populations. The population WUE i of the juvenile oak trees growing in the relatively mesic conditions of the common garden showed no relationship with a modeled water deficit index for the provenance sites. However, a higher population WUE i plasticity to severe drought was related to a higher proportion of silt and carbon and a lower proportion of sand in the soil of the provenance sites. In response to severe drought, populations with a higher increase in WUE i showed a lower decrease in GI. Populations with lower GI reduction were from sites with higher vapor pressure deficit in May–July (VPD). For the wet year only, populations with a higher WUE i also had a higher GI. Conclusion The correlations observed at the common garden site between (i) population means of WUE i plasticity to drought and soil texture of the provenance sites, and (ii) GI plasticity to drought and VPD, suggested a local adaptation of sessile oak.
International audience;
Peatlands at high latitudes have accumulated >400 Pg carbon (C) because saturated soil and cold temperatures suppress C decomposition. This substantial amount of C in Arctic and Boreal peatlands is potentially subject to increased decomposition if the water table (WT) decreases due to climate change, including permafrost thaw-related drying. Here, we optimize a version of the Organizing Carbon and Hydrology In Dynamic Ecosystems model (ORCHIDEE-PCH4) using site-specific observations to investigate changes in CO2 and CH4 fluxes as well as C stock responses to an experimentally manipulated decrease of WT at six northern peatlands. The unmanipulated control peatlands, with the WT <20 cm on average (seasonal max up to 45 cm) below the surface, currently act as C sinks in most years (58 ± 34 g C m−2 year−1; including 6 ± 7 g C–CH4 m−2 year−1 emission). We found, however, that lowering the WT by 10 cm reduced the CO2 sink by 13 ± 15 g C m−2 year−1 and decreased CH4 emission by 4 ± 4 g CH4 m−2 year−1, thus accumulating less C over 100 years (0.2 ± 0.2 kg C m−2). Yet, the reduced emission of CH4, which has a larger greenhouse warming potential, resulted in a net decrease in greenhouse gas balance by 310 ± 360 g CO2-eq m−2 year−1. Peatlands with the initial WT close to the soil surface were more vulnerable to C loss: Non-permafrost peatlands lost >2 kg C m−2 over 100 years when WT is lowered by 50 cm, while permafrost peatlands temporally switched from C sinks to sources. These results highlight that reductions in C storage capacity in response to drying of northern peatlands are offset in part by reduced CH4 emissions, thus slightly reducing the positive carbon climate feedbacks of peatlands under a warmer and drier
The fungi in Glomeromycota are mutualistic symbionts of plant roots and produce a special glycoprotein called “glomalin” on their spores and mycelium cell wall. The glomalin enters adjacent soil after cell wall death and decomposition. It contains 3–5% nitrogen and 36–59% carbon with considerable amounts of iron (0.8–8%). Glomalin is considered a recalcitrant source of carbon. The half-life of glycoprotein is approximately 50 years, so it has a relatively long persistence in soil. Therefore, it could contribute to the sequestration of carbon in land-based ecosystems. The rate of carbon flow from the plant to the underground parts and then to the fungal symbionts affects the amount of glomalin synthesis by the fungi. The impact of different environmental factors such as nutrient availability, tillage, atmospheric CO_2 level, drought, salinity, and heavy metal toxicity stresses on carbon allocation to the fungi and its consequence on the amount of glomalin production are addressed here. Also, the contribution of glomalin in carbon sequestration in soils is discussed.
My research investigates the structure and spatio-temporal variability of phytoplankton communities, which are central to marine food webs and the regulation of the oceanic biological carbon pump. I use a combination of satellite ocean color data and in situ measurements from research vessels and BioGeoChemical-Argo (BGC-Argo) profiling floats to study how these communities respond to environmental variability and how they, in turn, influence carbon fluxes in both the global ocean and region-specific regimes, such as the Mediterranean Sea and the Southern Ocean. Over the past years, my work has addressed several key questions: How do bio-optical properties vary across oceanic regimes, and how do these variations affect the interpretation of autonomous observations? How can we infer phytoplankton diversity from bio-optical observations to better understand the temporal and vertical dynamics of phytoplankton communities? What are the patterns and biogeochemical significance of deep chlorophyll maxima in stratified oligotrophic systems? Finally, how can we integrate satellite and in situ observations to produce 3D global fields of phytoplankton community biomass and composition? Building on previous work, my research project focuses on the Southern Ocean, a climatically critical region exhibiting diverse biogeochemical regimes. This project aims to understand how environmental forcing affects phytoplankton bloom phenology, community structure, and the cascading impacts on trophic interactions and carbon fluxes. It combines novel observations from a new generation of BGC-Argo floats, ship-based data, and machine learning–derived biogeochemical products. This interdisciplinary approach will contribute to reducing uncertainties in predicting the Southern Ocean's response to climate change.
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Mes recherches portent sur la variabilité spatio-temporelle des communautés de phytoplancton – en termes de biomasse et de composition – qui jouent un rôle majeur dans les réseaux trophiques et la régulation de la pompe biologique à carbone dans l’océan. Plus spécifiquement, je cherche à comprendre comment les communautés phytoplanctoniques répondent à la variabilité environnementale et influencent en retour les flux de carbone et la structuration des écosystèmes, tant à l’échelle globale que dans des régimes régionaux comme la Mer Méditerranée et l’Océan Austral. Pour ce faire, je m’appuie sur le couplage de données optiques et biogéochimiques acquises par des moyens d’observation complémentaires en termes de variables et de couverture spatio-temporelle, i.e. les navires de recherche, les flotteurs profileurs du réseau BioGeoChemical-Argo (BGC-Argo) et les satellites d’observation de la couleur de l’océan. Ces dernières années, mes travaux ont abordé plusieurs questions clés: Comment les propriétés bio-optiques varient-elles selon les régimes océaniques et comment ces variations influencent-elles l’interprétation des observations autonomes, satellitaires ou in situ ? Est-il possible d’estimer la diversité des communautés de phytoplancton à partir des observations bio-optiques autonomes, afin de mieux comprendre leur dynamique temporelle et verticale ? Quels sont les mécanismes de formation, ainsi que l’importance biogéochimique des maxima profonds de chlorophylle dans les régimes stratifiés oligotrophes ? Enfin, comment combiner les observations satellitaires et in situ pour produire des champs tridimensionnels (3D) globaux de la biomasse et de la composition des communautés phytoplanctoniques nécessaires notamment à l’élaboration de bilans biogéochimiques et la validation des modèles globaux ? Prolongeant ces travaux, mon projet de recherche actuel se concentre sur l’Océan Austral, une région climatiquement critique, caractérisée par une grande diversité de régimes biogéochimiques. Ce projet vise à comprendre comment les forçages environnementaux influencent la dynamique saisonnière des efflorescences phytoplanctoniques, la structure des communautés, ainsi que les effets en cascade sur les interactions trophiques et les flux de carbone. Il s’appuie notamment sur les observations issues d’une nouvelle génération de flotteurs profileurs BGC-Argo, de données collectées à bord des navires océanographiques, ainsi que de produits biogéochimiques 3D dérivés par apprentissage automatique. Cette approche interdisciplinaire contribuera à mieux comprendre et prédire la réponse de l’Océan Austral au changement climatique.
Background The carbon metabolism pathway is of paramount importance for the growth and development of plants, exerting a pivotal regulatory role in stress responses. The exacerbation of drought impacts on the plant carbon cycle due to global warming necessitates comprehensive investigation into the response mechanisms of Masson Pine ( Pinus massoniana Lamb.), an exemplary pioneer drought-tolerant tree, thereby establishing a foundation for predicting future forest ecosystem responses to climate change. Results The seedlings of Masson Pine were utilized as experimental materials in this study, and the transcriptome, metabolome, and photosynthesis were assessed under varying temperatures and drought intensities. The findings demonstrated that the impact of high temperature and drought on the photosynthetic rate and transpiration rate of Masson Pine seedlings was more pronounced compared to individual stressors. The analysis of transcriptome data revealed that the carbon metabolic pathways of Masson Pine seedlings were significantly influenced by high temperature and drought co-stress, with a particular impact on genes involved in starch and sucrose metabolism. The metabolome analysis revealed that only trehalose and Galactose 1-phosphate were specifically associated with the starch and sucrose metabolic pathways. Furthermore, the trehalose metabolic heat map was constructed by integrating metabolome and transcriptome data, revealing a significant increase in trehalose levels across all three comparison groups. Additionally, the PmTPS1, PmTPS5, and PmTPPD genes were identified as key regulatory genes governing trehalose accumulation. Conclusions The combined effects of high temperature and drought on photosynthetic rate, transpiration rate, transcriptome, and metabolome were more pronounced than those induced by either high temperature or drought alone. Starch and sucrose metabolism emerged as the pivotal carbon metabolic pathways in response to high temperature and drought stress in Masson pine. Trehalose along with PmTPS1, PmTPS5, and PmTPPD genes played crucial roles as metabolites and key regulators within the starch and sucrose metabolism.
Carbon sequestration and storage in biomass is one of the most important measures to mitigate climate change. Mediterranean woody crops can sequestrate carbon in the biomass of their permanent structures for decades; however, very few studies have focused on an assessment of biomass and carbon sequestration in these types of crops. This study is the first to estimate above- and belowground biomass carbon stock in Mediterranean woody crops through a bottom-up approach in the NE Iberian Peninsula in 2013. Moreover, this is the first time that an assessment of the annual changes in carbon stock in the study area over a six-year period is presented. For this purpose, eight crop- and site-specific equations relating biomass or biometric variables to crop age were calculated. Most of the data were our own measurements, but unpublished data supplied from other authors as well as data from literature were also considered. Census of Agriculture data was used to scale results from individual data up to the municipality level at the regional scale. Results show that in woody cropland in NE Spain the total biomass carbon stock in 2013 was 5.48 Tg C, with an average value of 16.44 ± 0.18 Mg C ha^−1. Between 2013 and 2019, although there was a 2.8% mean annual decrease in the area covered by woody crops, the carbon stock in the biomass of these crops increased annually by 3.8% due to the growth of the remaining woody cropland. This new estimation of carbon stocks may contribute to better understand carbon balances and serve as a baseline to global inventories. It may also serve to assess and manage carbon storage as an ecosystem service provided by Mediterranean woody cropland for mitigating climate change and, in combination with adaptive strategies, for supporting a productive and resilient agro-food system.
Background and Objective Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic antimicrobial prescribing in Australian residential aged-care facilities and thereby provide insight into antimicrobial stewardship strategies that might be required. Methods Annual point prevalence data submitted by participating residential aged-care facilities as part of the Aged Care National Antimicrobial Prescribing Survey between 2016 and 2020 were extracted. All antimicrobials except anti-virals were counted; methenamine hippurate was classified as an antibacterial agent. Results The overall prevalence of residents prescribed one or more prophylactic antimicrobial on the survey day was 3.7% ( n = 4643, 95% confidence interval 3.6–3.8). Of all prescribed antimicrobials ( n = 15,831), 27.1% ( n = 4871) were for prophylactic use. Of these prophylactic antimicrobials, 87.8% were anti-bacterials and 11.4% antifungals; most frequently, cefalexin (28.7%), methenamine hippurate (20.1%) and clotrimazole (8.8%). When compared with prescribing of all antimicrobial agents, prophylactic antimicrobials were less commonly prescribed for pro re nata administration (7.0% vs 20.3%) and more commonly prescribed greater than 6 months (52.9% vs 34.1%). The indication and review or stop date was less frequently documented (67.5% vs 73.8% and 20.9% vs 40.7%, respectively). The most common body system for which a prophylactic antimicrobial was prescribed was the urinary tract (54.3%). Of all urinary tract indications ( n = 2575), about two thirds ( n = 1681, 65.3%) were for cystitis and 10.6% were for asymptomatic bacteriuria. Conclusions Our results clearly identified immediate antimicrobial stewardship strategies that aim to improve prophylactic antimicrobial prescribing in Australian residential-aged care facilities are required.
Ring-like communication graphs appear in UAV formations, cyclic patrols, perimeter monitoring, and other multi-agent tasks in which agents exchange information mainly with neighboring vehicles along a closed route. When measurement and actuation noise are persistent, a useful augmentation should improve both the convergence rate of consensus and the steady-state disagreement level. This paper studies the addition of a single weighted chord to a connected weighted cycle. The central observation is that a chord is not just a generic rank-one edge update: it splits the cycle into two complementary resistance arcs, and this resistance split governs both the algebraic-connectivity gain and the Kirchhoff-index reduction. We first derive exact chord-induced effective-resistance and Kirchhoff-index update formulas, giving a closed-form coherence objective. We then prove that, under bounded conductances and small resistance discrepancy, near-antipodal resistance-balanced chords are near-optimal for algebraic-connectivity improvement; an i.i.d. bounded-conductance model yields the same conclusion with high probability. Finally, because the best convergence-rate chord and the best coherence chord need not coincide, we formulate the design as a finite Pareto problem and introduce RBAPS and AW-RBAPS, two resistance-balanced screening rules that retain only linear or near-linear candidate sets. Numerical experiments show that AW-RBAPS remains effective beyond the formal moderate-heterogeneity regime and approximates the exhaustive Pareto front with mean hypervolume ratio $0.9987$ while evaluating about $10.1\%$ of admissible chords.
Cold Spring Harbor LaboratoryApril 2023Antimicrobial resistance
Antibiotic prophylaxis sets the stage for an intestinal bloom of Candida albicans , which can progress to invasive candidiasis in patients with hematologic malignancies. Commensal bacteria can reestablish microbiota-mediated colonization resistance after completion of antibiotic therapy, but they cannot engraft during antibiotic prophylaxis. Here we use a mouse model to provide a proof of concept for an alternative approach, which replaces commensal bacteria functionally with drugs to restore colonization resistance against C. albicans . Streptomycin treatment, which depletes Clostridia from the gut microbiota, disrupted colonization resistance against C. albicans and increased epithelial oxygenation in the large intestine. Inoculating mice with a defined community of commensal Clostridia species reestablished colonization resistance and restored epithelial hypoxia. Notably, these functions of commensal Clostridia species could be replaced functionally with the drug 5-aminosalicylic acid (5-ASA), which activates mitochondrial oxygen consumption in the epithelium of the large intestine. When streptomycin-treated mice received 5-ASA, the drug reestablished colonization resistance against C. albicans and restored physiological hypoxia in the epithelium of the large intestine. We conclude that 5-ASA treatment is a non-biotic intervention that restores colonization resistance against C. albicans without requiring the administration of live bacteria.
Background The genus Corynebacterium comprises well-known animal and human pathogens as well as commensals of skin and mucous membranes. Species formerly regarded as contaminants are increasingly being recognized as opportunistic pathogens. Corynebacterium oculi has recently been described as a human ocular pathogen but has so far not been reported in dogs. Case presentation Here we present two cases of infection with a novel Corynebacterium sp. , a corneal ulcer and a case of bacteriuria. The two bacterial isolates could not be identified by MALDI-TOF MS. While 16 S rRNA gene (99.3% similarity) and rpoB (96.6% identity) sequencing led to the preliminary identification of the isolates as Corynebacterium ( C. ) oculi , whole genome sequencing revealed the strains to be closely related to, but in a separate cluster from C. oculi . Antimicrobial susceptibility testing showed high minimal inhibitory concentrations of lincosamides, macrolides, tetracycline, and fluoroquinolones for one of the isolates, which also contained an erm (X) and tet -carrying plasmid as well as a nonsynonymous mutation leading to an S84I substitution in the quinolone resistance determining region of GyrA. Conclusions While the clinical signs of both dogs were alleviated by antimicrobial treatment, the clinical significance of these isolates remains to be proven. However, considering its close relation with C. oculi , a known pathogen in humans, pathogenic potential of this species is not unlikely. Furthermore, these bacteria may act as reservoir for antimicrobial resistance genes also in a One Health context since one strain carried a multidrug resistance plasmid related to pNG3 of C. diphtheriae .
Continuous Fibre Reinforced Polymer Composites are increasingly used in structural applications, particularly in the fields of aeronautics and space. These materials indeed have several advantages such as good corrosion resistance, low density, and good mechanical properties. However, certain properties remain to be improved, such as resistance to delamination, particularly critical for impact resistance. The PhD work is carried out within the framework of the collaborative project FUI ATIHS aimed at the improvement of the resistance of satellite structures to hypervelocity impacts from space debris. It concerns the incorporation of VACNTs (Vertically Aligned Carbon Nanotubes) mats within an organic matrix composite with long carbon fibers with the aim of developing a new composite material with improved mechanical properties for static and impact loads. A first part of the work is devoted to the development and implementation of the process for the manufacture of a new laminated composite material by placing mats of nanotubes at the inter-plies. The first step is to control the transfer of the VACNTs mats onto M55J-M18 prepreg, by regulating through time, temperature and pressure control the capillary rise of the resin and then separating the VACNTs from its growth substrate. The second step is to consolidate the laminated composite while maintaining the initial morphology of the VACNTs and avoiding the formation of porosity. Through observations from the microscopic to the macroscopic scales, the work has enabled the identification of process parameters meeting these objectives and a better understanding of the mechanisms involved. After a development stage carried out at small scale, the process for developing the new composite has been validated on a larger scale allowing structural applications to be considered. A second part of the work consists in the study of the mechanical behavior of the new composite material under different types of static tests, in particular those stressing the plies interfaces. The approach is based on a comparison with the unreinforced reference material. It combines analyzes of mechanical test results and microstructural observations at different scales. It again permitted a better understanding of the damage mechanisms at the inter-plies of laminated composites. Shifts in damage zones have been observed due to the introduction of VACNTs to the inter-folds, which opens up prospects for the further development of carbon nanotube-reinforced composites with improved performances.
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Les matériaux composites à matrice organique et à fibres longues occupent une place grandissante dans des applications structurales, notamment dans les domaines de l’aéronautique et du spatial. Ces matériaux présentent en effet un ensemble d’atouts tels qu’une bonne résistance à la corrosion, une faible masse volumique et de bonnes propriétés mécaniques. Néanmoins, certaines propriétés restent à améliorer comme la résistance au délaminage, notamment critique pour des sollicitations d’impact. Le travail de thèse est réalisé dans le cadre du projet collaboratif FUI ATIHS (Amélioration de la Tenue des structures satellites aux Impacts Hypervitesse de débris Spatiaux). Il porte sur l’incorporation de tapis de nanotubes de carbone verticalement alignés, ou tapis de VACNTs (Vertically Aligned Carbon Nanotubes) dans un composite à matrice organique à fibres longues de carbone dans l’objectif de développer un nouveau matériau composite aux propriétés mécaniques améliorées pour des sollicitations statiques et à l’impact. Une première partie du travail de thèse est consacrée au développement et à la mise en œuvre du procédé d’élaboration d’un nouveau matériau composite stratifié en plaçant des tapis de nanotubes aux interplis. Il s’agit en premier lieu de maîtriser le transfert des tapis de VACNTs sur un pré-imprégné M55J-M18, par montée capillaire partielle de la résine puis séparation du substrat de croissance des VACNTs. Dans un deuxième temps, il s’agit de consolider le composite stratifié en conservant la morphologie initiale des VACNTs et en évitant la formation de porosité. Par des observations de l’échelle microscopique à l’échelle macroscopique, le travail a permis une identification de paramètres procédé répondant à ces objectifs et une meilleure compréhension des mécanismes mis en jeu. Après une étape de mise au point réalisée à petite échelle, le procédé d’élaboration du nouveau composite a été validé à une échelle permettant d’envisager des applications structurales. Une deuxième partie du travail concerne l’étude du comportement mécanique du nouveau matériau composite sous différents types d’essais statiques, notamment ceux sollicitant les interfaces. La démarche est basée sur une comparaison avec le matériau de référence non renforcé. Elle couple des analyses des résultats d’essais mécaniques et d’observations microstructurales à différentes échelles. Elle permet à nouveau une meilleure compréhension des mécanismes d’endommagement. Des déplacements des zones d’endommagement ont été constatés du fait de l’introduction des VACNTs aux interplis, ce qui permet de dégager des perspectives pour la poursuite du développement de composites renforcés de nanotubes de carbone.
Extracellular vesicles (EVs) constitute a vital component of intercellular communication, exerting significant influence on metastasis formation and drug resistance mechanisms. Malignant melanoma (MM) is one of the deadliest forms of skin cancers, because of its high metastatic potential and often acquired resistance to oncotherapies. The prevalence of BRAF mutations in MM underscores the importance of BRAF-targeted therapies, such as vemurafenib and dabrafenib, alone or in combination with the MEK inhibitor, trametinib. This study aimed to elucidate the involvement of EVs in MM progression and ascertain whether EV-mediated metastasis promotion persists during single agent BRAF (vemurafenib, dabrafenib), or MEK (trametinib) and combined BRAF/MEK (dabrafenib/trametinib) inhibition. Using five pairs of syngeneic melanoma cell lines, we assessed the impact of EVs – isolated from their respective supernatants – on melanoma cell proliferation and migration. Cell viability and spheroid growth assays were employed to evaluate proliferation, while migration was analyzed through mean squared displacement (MSD) and total traveled distance (TTD) measurements derived from video microscopy and single-cell tracking. Our results indicate that while EV treatments had remarkable promoting effect on cell migration, they exerted only a modest effect on cell proliferation and spheroid growth. Notably, EVs demonstrated the ability to mitigate the inhibitory effects of BRAF inhibitors, albeit they were ineffective against a MEK inhibitor and the combination of BRAF/MEK inhibitors. In summary, our findings contribute to the understanding of the intricate role played by EVs in tumor progression, metastasis, and drug resistance in MM.
American Chemical SocietyMarch 2024Antimicrobial resistance
[Image: see text] This study presents an in-depth investigation into the wear characteristics of ultrahigh-molecular-weight polyethylene (UHMWPE) composites reinforced with microsized MoS(2) and nanosized graphite particles. The objective is to enhance the wear resistance of the UHMWPE by examining the effects of various parameters and optimizing the wear performance. To achieve this goal, wet wear tests were conducted under controlled conditions, and the results were compared between composites with micro MoS(2) and nano graphite reinforcements. The Taguchi method was employed to design the experiments (DOE) using an L9 orthogonal array. Four key parameters, namely, reinforcement percentage, load, speed, and track radius, were varied systematically to analyze their impact on wear characteristics, including wear rate, frictional forces, and the coefficient of friction (COF). The data obtained from the experiments were subjected to analysis of variance (ANOVA) to identify the significant factors affecting wear behavior. Subsequently, the optimal wear parameters were determined through regression analysis, allowing for the prediction of wear characteristics under the optimum conditions. This research not only provides insights into the comparative performance of micro MoS(2) and nano graphite reinforcements in UHMWPE composites but also offers a comprehensive approach to optimizing wear resistance by employing advanced statistical and experimental techniques. The findings contribute to the development of more durable and wear-resistant materials with potential applications in various industries, such as those investigated in the study, which are commonly employed, such as automotive, aerospace, medical devices, or manufacturing.
American Chemical SocietyMarch 2023Antimicrobial resistance
[Image: see text] The contact resistance of the transition metal dichalcogenide (TMD) devices is not comparable to that of their silicon counterparts, probably due to a lack of clarity in their interface chemistry. Looking beyond the conventional Schottky–Mott rule, the metal chalcogen orbital overlaps, tunnel barrier, and metal-induced gap states (MIGSs) are crucial factors determining different metals’ contact properties with TMDs. Exploring their properties helps TMDs’ contact resistance engineering, driven mainly by their orbital overlaps and perturbing parameters. This work presents the interface chemistry of TMDs (MoS(2), MoSe(2), WS(2), and WSe(2)) with different metals (Au, Cr, Ni, and Pd) in detail using density functional theory computations. Additionally, the work discusses the role of the chalcogen vacancy and interstitial defects in the metal–TMD interactions and corresponding MIGS features. The investigations reveal that Au does not show any significant MIGS due to its weak interactions with all the TMDs. However, other investigated metals have a strong affinity with TMDs, making significant MIGS contributions. All the metals offer n-type doping characteristics to TMDs due to valence charge transfer from the metals toward TMDs. The chalcogen vacancy boosts the orbital overlaps of the TMDs with all the metals. The vacancy reduces metal–TMD interfacial distance, which can be a promising technique to reduce the tunnel barrier and contact resistance. The MIGS and defect-induced gap states (DIGSs) reflect the possibility of Fermi-level pinning in the TMDs’ contacts with Cr, Ni, and Pd. Besides, the work discloses that the chalcogen vacancy converts an n-type Pd–TMD interface into p-type due to reverse charge transfer after the vacancy. Chalcogen interstitial impurity also helps with contact resistance engineering for some metal–TMD systems by reducing the bond distance of the metal TMDs. Our study highlights the possibility of defect-assisted and MIGS-based contact engineering at the metal–TMD interfaces.
Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.
Cold Spring Harbor LaboratoryJune 2025Antimicrobial resistance
Individual cells within a given population exhibit striking variability in viral susceptibility, but it remains unknown whether this heterogeneity reflects memories encoded into the cellular lineage or true probabilistic variability. We used multi-color lineage tracing in a human primary organotypic skin model to reveal that viral resistance is encoded within specific cellular lineages. These lineages create distinct boundaries that block viral spread. Our lineage analyses in vitro confirmed that viral susceptibility exhibits strong heritability across cell generations, with siblings and cousins displaying remarkably similar infection outcomes. ATAC and proteomics profiling of resistant and susceptible clones revealed distinct epigenomic and proteomic states, with the transcription factor AP-1 emerging as a potential central regulator of lineage-encoded viral resistance. Inducing AP-1 activity with PMA rendered cells resistant to viral infection, suggesting a causative role in mediating resistance memory. Our findings demonstrate that antiviral resistance in human skin cells is encoded within cellular lineages and preserved through cell divisions, revealing how cell memory may shape infection dynamics and viral containment in tissues.
Objective The World Health Organization (WHO) has declared antimicrobial resistance (AMR) as one of the top threats to global public health. While AMR surveillance of human clinical isolates is well-established in many countries, the increasing threat of AMR has intensified efforts to detect antibiotic resistance genes (ARGs) accurately and sensitively in environmental samples, wastewater, animals, and food. Using five ARGs and the 16S rRNA gene, we compared quantitative PCR (qPCR) and metagenomic sequencing (MGS), two commonly used methods to uncover the wastewater resistome. We compared both methods by evaluating ARG detection through a municipal wastewater treatment chain. Results Our results demonstrate that qPCR was more sensitive than MGS, particularly in diluted samples with low ARG concentrations such as oxidation pond water. However, MGS was potentially more specific and has less risk of off-target binding in concentrated samples such as raw sewage. MGS analysis revealed multiple subtypes of each gene which could not be distinguished by qPCR; these subtypes varied across different sample types. Our findings affect the conclusions that can be drawn when comparing different sample types, particularly in terms of inferring removal rates or origins of genes. We conclude that both methods appear suitable to profile the resistome of wastewater and other environmental samples, depending on the research question and type of sample.
Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of Pulsatilla chinensis ( P. chinensis ), to inhibit the polarization of M2 macrophages induced by IL-4. Our results showed that 23-HBA reduced the expression of M2 specific marker CD206, while downregulating the mRNA levels of M2 related genes (CD206, Arg1, IL-10, and CCL2). Additionally, 23-HBA effectively attenuated the inhibitory effects of the conditioned medium from M2 macrophages on apoptosis in colorectal cancer SW480 cells. Mechanistically, 23-HBA prevented the phosphorylation and nuclear translocation of the STAT6 protein, resulting in the inhibition of IL-10 release in M2 macrophages. Moreover, it interfered with the activation of the IL-10/STAT3/Bcl-2 signaling pathway in SW480 cells, ultimately reducing M2 macrophage-induced resistance to 5-FU. Importantly, depleting STAT6 expression in macrophages abolished the suppressive effect of 23-HBA on M2 macrophage polarization, while also eliminating its ability to decrease M2 macrophage-induced 5-FU resistance in cancer cells. Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer.
John Wiley and Sons Inc.October 2021Antimicrobial resistance
BACKGROUND: Despite multiple treatment advances for castration‐resistant prostate cancer (CRPC), there are currently no curative therapies and patients ultimately to succumb to the disease. Docetaxel (DTX) is the standard first‐line chemotherapy for patients with metastatic CRPC; however, drug resistance is inevitable and often develops rapidly, leading to disease progression in nearly all patients. In contrast, when DTX is deployed with androgen deprivation therapy in castration‐sensitive disease, more durable responses and improved outcomes are observed, suggesting that aberrant androgen receptor (AR) signaling accelerates DTX resistance in CRPC. In this study, we demonstrate that AR dysregulates the mitotic checkpoint, a critical pathway involved in the anticancer action of DTX. METHODS: Androgen‐dependent and independent cell lines were used to evaluate the role of AR in DTX resistance. Impact of drug treatment on cell viability, survival, and cell‐cycle distribution were determined by plate‐based viability assay, clonogenic assay, and cell‐cycle analysis by flow cytometry, respectively. Mitotic checkpoint kinase signal transduction and apoptosis activation was evaluated by Western blotting. Pathway gene expression analysis was evaluated by RT‐PCR. A Bliss independence model was used to calculate synergy scores for drug combination studies. RESULTS: Activation of AR in hormone‐sensitive cells induces a rescue phenotype by increasing cell viability and survival and attenuating G2/M arrest in response to DTX. Analysis of mitotic checkpoint signaling shows that AR negatively regulates spindle checkpoint signaling, resulting in premature mitotic progression and evasion of apoptosis. This phenotype is characteristic of mitotic slippage and is also observed in CRPC cell lines where we demonstrate involvement of AR splice variant AR‐v7 in dysregulation of checkpoint signaling. Our findings suggest that DTX resistance is mediated through mechanisms that drive premature mitotic exit. Using pharmacologic inhibitors of anaphase‐promoting complex/cyclosome and polo‐like kinase 1, we show that blocking mitotic exit induces mitotic arrest, apoptosis, and synergistically inhibits cell survival in combination with DTX. CONCLUSION: Our results suggest that targeting the mechanisms of dysregulated mitotic checkpoint signaling in AR‐reactivated tumors has significant clinical potential to extend treatment benefit with DTX and improve outcomes in patients with lethal prostate cancer.
BACKGROUND: Aphanomyces euteiches is a soil-borne oomycete that causes root rot in pea and other legume species. Symptoms of Aphanomyces root rot (ARR) include root discoloration and wilting, leading to significant yield losses in pea production. Resistance to ARR is known to be polygenic but the roles of single genes in the pea immune response are still poorly understood. This study uses transcriptomics to elucidate the immune response of two pea genotypes varying in their levels of resistance to A. euteiches. RESULTS: In this study, we inoculated roots of the pea (P. sativum L.) genotypes ‘Linnea’ (susceptible) and ‘PI180693’ (resistant) with two different A. euteiches strains varying in levels of virulence. The roots were harvested at 6 h post-inoculation (hpi), 20 hpi and 48 hpi, followed by differential gene expression analysis. Our results showed a time- and genotype-dependent immune response towards A. euteiches infection, involving several WRKY and MYB-like transcription factors, along with genes associated with jasmonic acid (JA) and abscisic acid (ABA) signaling. By cross-referencing with genes segregating with partial resistance to ARR, we identified 39 candidate disease resistance genes at the later stage of infection. Among the genes solely upregulated in the resistant genotype ‘PI180693’, Psat7g091800.1 was polymorphic between the pea genotypes and encoded a Leucine-rich repeat receptor-like kinase reminiscent of the Arabidopsis thaliana FLAGELLIN-SENSITIVE 2 receptor. CONCLUSIONS: This study provides new insights into the gene expression dynamics controlling the immune response of resistant and susceptible pea genotypes to A. euteiches infection. We present a set of 39 candidate disease resistance genes for ARR in pea, including the putative immune receptor Psat7g091800.1, for future functional validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-024-04817-y.
Much is known about estrogen action in experimental animal models and in human physiology. This article reviews the mechanisms of estrogen activity in animals and humans and the role of its two receptors α and β in terms of structure and mechanisms of action in various tissues in health and in relationship with human pathologies (e.g., osteoporosis). Recently, the spectrum of clinical pictures of estrogen resistance caused by estrogen receptors gene variants has been widened by our description of a woman with β-receptor defect, which could be added to the already known descriptions of α-receptor defect in women and men and β-receptor defect in men. The essential role of the β-receptor in the development of the gonad stands out. We summarize the clinical pictures due to estrogen resistance in men and women and focus on long-term follow-up of two women, one with α- and the other with β-receptor resistance. Some open questions remain on the complex interactions between the two receptors on bone metabolism and hypothalamus-pituitary-gonadal axis, which need further deepening and research.
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Introduction: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant isolates. However, while growing prevalence has been reported around the world, data on the prevalence of carbapenem resistance in developing countries are fairly limited. In this study, we investigated and determined the resistance rate to carbapenems among multidrug-resistant Gram-negative bacteria (MDR-GNB) isolated in Djibouti and characterized their resistance mechanisms. Results: Of the 256 isolates, 235 (91.8%) were identified as Gram-negative bacteria (GNB). Of these GNBs, 225 (95.7%) isolates exhibited a multidrug resistance phenotype, and 20 (8.5%) isolates were resistant to carbapenems, including 13 Escherichia coli, 4 Acinetobacter baumannii, 2 Klebsiella pneumoniae and 1 Proteus mirabilis. The most predominant GNB in this hospital setting were E. coli and K. pneumoniae species. Carbapenemase genes such as blaOXA-48 and blaNDM-5 were identified, respectively, in six and four E. coli isolates, whereas the carbapenemase blaNDM-1 was identified in three E. coli, two K. pneumoniae, one P. mirabilis and one A. baumannii. Moreover, three A. baumannii isolates co-hosted blaOXA-23 and blaNDM-1. Materials and Methods: A total of 256 clinical strains collected between 2019 and 2020 were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Antibiotic susceptibility testing was performed using disk diffusion and E-test methods. Real-time polymerase chain reaction (RT-PCR), standard PCR and sequencing were used to investigate genes encoding for extended-spectrum-β-lactamases, carbapenemases and colistin resistance genes. Conclusions: We report, for the first time, the presence of MDR-GNB clinical isolates and the emergence of carbapenem-resistant isolates in Djibouti. In addition to performing antimicrobial susceptibility testing, we recommend phenotypic and molecular screening to track the spread of carbapenemase genes among clinical GNB isolates.
American Society for MicrobiologyJune 2022Antimicrobial resistance
Oral antibiotic treatment is often applied in animal studies in order to allow establishment of an introduced antibiotic-resistant bacterium in the gut. Here, we compared the application of streptomycin dosed orally in microcontainers to dosage through drinking water. The selective effect on a resistant bacterial strain, as well as the effects on fecal, luminal, and mucosal microbiota composition, were investigated. Three groups of rats (n = 10 per group) were orally dosed with microcontainers daily for 3 days. One of these groups (STR-M) received streptomycin-loaded microcontainers designed for release in the distal ileum, while the other two groups (controls [CTR] and STR-W) received empty microcontainers. The STR-W group was additionally dosed with streptomycin through the drinking water. A streptomycin-resistant Escherichia coli strain was orally inoculated into all animals. Three days after inoculation, the resistant E. coli was found only in the cecum and colon of animals receiving streptomycin in microcontainers but in all intestinal compartments of animals receiving streptomycin in the drinking water. 16S rRNA amplicon sequencing revealed significant changes in the fecal microbiota of both groups of streptomycin-treated animals. Investigation of the inner colonic mucus layer by confocal laser scanning microscopy and laser capture microdissection revealed no significant effect of streptomycin treatment on the mucus-inhabiting microbiota or on E. coli encroachment into the inner mucus. Streptomycin-loaded microcontainers thus enhanced proliferation of an introduced streptomycin-resistant E. coli in the cecum and colon without affecting the small intestine environment. While improvements of the drug delivery system are needed to facilitate optimal local concentration and release of streptomycin, the application of microcontainers provides new prospects for antibiotic treatment. IMPORTANCE Delivery of antibiotics in microcontainer devices designed for release at specific sites of the gut represents a novel approach which might reduce the amount of antibiotic needed to obtain a local selective effect. We propose that the application of microcontainers may have the potential to open novel opportunities for antibiotic treatment of humans and animals with fewer side effects on nontarget bacterial populations. In the current study, we therefore elucidated the effects of streptomycin, delivered in microcontainers coated with pH-sensitive lids, on the selective effect on a resistant bacterium, as well as on the surrounding intestinal microbiota in rats.
Cordyline fruticosa , also known to Indonesians as andong, is one of the simplest plants to grow. This plant is commonly used as an ornamental plant in yards, gardens, cemeteries, as well as a road barrier. Although it is primarily grown for ornamental purposes, the leaves of this plant empirically have been used to treat diarrhea and dysentery. The goal of this study was to determine what chemicals are present in andong leaves, as well as to see if an extract derived from the leaves has any activity against microbes that cause diarrhea, such as Shigella dysenteriae and Candida albicans . Andong leaves were extracted using two different methods, namely maceration with 96% ethanol as a solvent and infusion with distilled water heated to 90 ℃. Phytochemicals screening test was conducted qualitatively using the color-change reaction method. While antimicrobial activity test was performed using the disk diffusion method and continued with the Minimum Inhibitory Concentration (MIC) test using the solid dilution method. Phytochemicals screening revealed that the ethanol extract and infusion of andong leaves contained flavonoids, tannins, saponins, and phenols. The antimicrobial activity results showed that the ethanol extract and infusion of andong leaves inhibited the growth of S. dysenteriae but had no effect on C. albicans . These findings suggest that andong leaves have the potential to treat diarrhea caused by S. dysentriae , but not by C. albicans .
Background Antibiotic-resistant Klebsiella pneumoniae has emerged as a critical public health threat worldwide. Understanding the antimicrobial resistance mechanisms of multidrug-resistant K. pneumoniae (MDR-Kp) and its prevalence in time and space would provide clinical significance for managing pathogen infection. Methods Eighteen clinical MDR-Kp strains were analyzed by whole genome sequencing (WGS), and the antimicrobial resistance genes and associated resistance mechanisms were compared with results obtained from the conventional microbiological test (CMT). The sequence homology across strains in our study and those previously collected over time from a wide geographical region was assessed by phylogenetic analysis. Results MDR-Kp strains were collected from eighteen patients who had received empirical treatment before strain collection, with sputum (83.3%, 15/18) being the primary source of clinical samples. The commonly received treatments include β-lactamase inhibitors (55.6%, 10/18) and carbapenems (50%, 9/18). Using CMT, we found that all 18 strains were resistant to aztreonam and ciprofloxacin, while 14 (77.8%) showed resistance to carbapenem. Polymyxin B and tigecycline were the only antibiotics to which MDR-Kp strains were sensitive. A total of 42 antimicrobial resistance mechanisms were identified by WGS, surpassing the 40 detected by the conventional method, with 25 mechanisms shared between the two techniques. Despite a 100% accuracy rate of WGS in detecting penicillin-resistant strains, the accuracy in detecting cephalosporin-resistant strains was only at 60%. Among all resistance genes identified by WGS, Klebsiella pneumoniae carbapenemase-2 ( KPC-2 ) was present in all 14 carbapenem-resistant strains. Phenotypic analysis indicated that sequence type (ST) 11 isolates were the primary cause of these MDR-Kp infections. Additionally, phylogenic clustering analysis, encompassing both the clinical and MDR-Kp strains previously reported in China, revealed four distinct subgroups. No significant difference was observed in the sequence homology between K. pneumoniae strains in our study and those previously collected in East China over time. Conclusion The application of WGS in identifying potential antimicrobial-resistant genes of MDR-Kp has demonstrated promising clinical significance. Comprehensive genomic information revealed by WGS holds the promise of guiding treatment decisions, enabling surveillance, and serving as a crucial asset in understanding antibiotic resistance.
Background Wheat is one of the important grain crops in the world. The formation of lesion spots related to cell death is involved in disease resistance, whereas the regulatory pathway of lesion spot production and resistance mechanism to pathogens in wheat is largely unknown. Results In this study, a pair of NILs (NIL- Lm5 ^W and NIL- Lm5 ^M) was constructed from the BC_1F_4 population by the wheat lesion mimic mutant MC21 and its wild genotype Chuannong 16. The formation of lesion spots in NIL- Lm5 ^M significantly increased its resistance to stripe rust, and NIL- Lm5 ^M showed superiour agronomic traits than NIL- Lm5 ^W under stripe rust infection.Whereafter, the NILs were subjected to transcriptomic (stage N: no spots; stage S, only a few spots; and stage M, numerous spots), metabolomic (stage N and S), and hormone analysis (stage S), with samples taken from normal plants in the field. Transcriptomic analysis showed that the differentially expressed genes were enriched in plant-pathogen interaction, and defense-related genes were significantly upregulated following the formation of lesion spots. Metabolomic analysis showed that the differentially accumulated metabolites were enriched in energy metabolism, including amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Correlation network diagrams of transcriptomic and metabolomic showed that they were both enriched in energy metabolism. Additionally, the contents of gibberellin A7, cis-Zeatin, and abscisic acid were decreased in leaves upon lesion spot formation, whereas the lesion spots in NIL- Lm5 ^M leaves were restrained by spaying GA and cytokinin (CTK, trans-zeatin) in the field. Conclusion The formation of lesion spots can result in cell death and enhance strip rust resistance by protein degradation pathway and defense-related genes overexpression in wheat. Besides, the formation of lesion spots was significantly affected by GA and CTK. Altogether, these results may contribute to the understanding of lesion spot formation in wheat and laid a foundation for regulating the resistance mechanism to stripe rust.
Background The Mesenchymal epithelial transition factor ( MET ) gene encodes a receptor tyrosine kinase with pleiotropic functions in cancer. MET exon 14 skipping alterations and high-level MET amplification are oncogenic and targetable genetic changes in patients with non-small-cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitors (TKIs) has been a major challenge for targeted therapies that impairs their clinical efficacies. Methods Eighty-six NSCLC patients were categorized into three cohorts based on the time of detecting MET tyrosine kinase domain (TKD) mutations (cohort 1: at baseline; cohort 2: after MET-TKI treatment; cohort 3: after EGFR-TKI treatment). Baseline and paired TKI treatment samples were analyzed by targeted next-generation sequencing. Results MET TKD mutations were highly prevalent in METex14 -positive NSCLC patients after MET-TKI treatment, including L1195V, D1228N/H/Y/E, Y1230C/H/N/S, and a double-mutant within codons D1228 and M1229. Missense mutations in MET TKD were also identified at baseline and in post-EGFR-TKI treatment samples, which showed different distribution patterns than those in post-MET-TKI treatment samples. Remarkably, H1094Y and L1195F, absent from MET-TKI-treated patients, were the predominant type of MET TKD mutations in patients after EGFR-TKI treatment. D1228H, which was not found in treatment-naïve patients, also accounted for 14.3% of all MET TKD mutations in EGFR-TKI-treated samples. Two patients with baseline EGFR -sensitizing mutations who acquired MET -V1092I or MET -H1094Y after first-line EGFR-TKI treatment experienced an overall improvement in their clinical symptoms, followed by targeted therapy with MET-TKIs. Conclusions MET TKD mutations were identified in both baseline and patients treated with TKIs. MET -H1094Y might play an oncogenic role in NSCLC and may confer acquired resistance to EGFR-TKIs. Preliminary data indicates that EGFR -mutated NSCLC patients who acquired MET -V1092I or MET -H1094Y may benefit from combinatorial therapy with EGFR-TKI and MET-TKI, providing insights into personalized medical treatment.
HAL CCSD;FrontiersJanuary 2022Antimicrobial resistance
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Vitis vinifera is the most widely cultivated grapevine species. It is highly susceptible to Plasmopara viticola and Erysiphe necator , the causal agents of downy mildew (DM) and powdery mildew (PM), respectively. Current strategies to control DM and PM mainly rely on agrochemical applications that are potentially harmful to humans and the environment. Breeding for resistance to DM and PM in wine grape cultivars by introgressing resistance loci from wild Vitis spp. is a complementary and more sustainable solution to manage these two diseases. During the last two decades, 33 loci of resistance to P. viticola ( Rpv ) and 15 loci of resistance to E. necator ( Ren and Run ) have been identified. Phenotyping is salient for QTL characterization and understanding the genetic basis of resistant traits. However, phenotyping remains a major bottleneck for research on Rpv and Ren/Run loci and disease resistance evaluation. A thorough analysis of the literature on phenotyping methods used for DM and PM resistance evaluation highlighted phenotyping performed in the vineyard, greenhouse or laboratory with major sources of variation, such as environmental conditions, plant material (organ physiology and age), pathogen inoculum (genetic and origin), pathogen inoculation (natural or controlled), and disease assessment method (date, frequency, and method of scoring). All these factors affect resistance assessment and the quality of phenotyping data. We argue that the use of new technologies for disease symptom assessment, and the production and adoption of standardized experimental guidelines should enhance the accuracy and reliability of phenotyping data. This should contribute to a better replicability of resistance evaluation outputs, facilitate QTL identification, and contribute to streamline disease resistance breeding programs.
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Hepatokines (liver secreted proteins with possible distant action) are emerging potential players in insulin resistance in type 2 diabetic patients. Here, we explored the effect of a high-fat diet on the expression of fetuin-A, one of those candidate liver proteins, and its relationship with liver macrophage activation. Mice were fed a normal diet or a high-fat diet for 3 days, known to initiate steatosis and liver insulin resistance. A preventive liver macrophage depletion was obtained by intravenous injection of clodronate-loaded liposomes. The mRNA and protein expression of fetuin-A was evaluated by qPCR, Western blot and immunofluorescence on different insulin-sensitive tissues (liver, adipose tissue, and muscle). Short-term high-fat diet-induced steatosis, liver macrophage activation, and hepatic insulin resistance together with a significantly increased expression of liver AHSG (α2-HS glycoprotein/fetuin-A) mRNA and serum fetuin-A concentration. On immunofluorescence, fetuin-A was mostly expressed in centrilobular hepatocytes. This increase in fetuin-A under high-fat diet was not evidenced in other peripheral insulin-sensitive tissues (skeletal muscle and adipose tissue). The mRNA expression of α2-HS glycoprotein was 800 times higher within the liver compared with the adipose tissue or the muscle. Liver macrophage depletion that significantly ameliorated insulin sensitivity was associated with a significant decrease in α2-HS glycoprotein mRNA expression. In conclusion, this study demonstrated liver fetuin-A overexpression at the initiation of high-fat diet feeding, concurrent with hepatic steatosis and insulin resistance. Targeting liver macrophages in this setting reduced liver α2-HS glycoprotein expression suggesting that fetuin-A acts as an hepatokine with proinsulin resistance effects.
Root-knot nematodes (RKN), genus Meloidogyne, are microscopic plant parasitic worms which infect roots of more than 5 000 cultivated plant species and cause massive crop yield losses worldwide. Within host root, RKN induce the formation of root galls by inducing the dedifferentiation of root vascular cells into giant and multinucleated feeding cells. The formation of feeding cells can be split into two phases: successive nuclear divisions during the first ten days post infection (dpi), then from 10 to 21 dpi feeding cells nuclei undergo extensive endoreduplication and plant growth. These feeding cells supply water and nutrients essential for nematode development. The formation of these feeding cells is the result of an extensive reprogramming of gene expression in targeted root cells as shown by transcriptome analyses. However, few data are available on the regulation of gene expression in these structures. The objective of my PhD thesis was to study small non-coding RNAs, microRNAs, that are key regulators of gene expression. microRNAs act at the post-transcriptional level by inducing the degradation or inhibition of the translation of targeted messenger RNAs (mRNAs). During my PhD thesis, sequencing of small RNAs from tomato (Solanum lycopersicum) galls induced by Meloidogyne incognita RKN and uninfected roots identified 174 microRNAs that are differentially expressed in galls at 7 and/or 14 dpi. mRNAs targeted by microRNAs in tomato galls were then identified by integrating microRNA sequencing data with data from transcriptome analysis and from a specific sequencing of cleaved mRNAs named degradome approach. This integrative analysis built a microRNA-gene regulatory network acting during the formation of galls and feeding cells in tomato roots. Three microRNAs families, miR167, miR398 and miR408, were selected for functional analyses. MiR167 family targets the auxin-response factors ARF8A and ARF8B. These ARFs belong to auxin signaling pathway, a key hormone in plant-RKN interaction. Using tomato lines expressing the two ARF8 promoters fused to GUS reporter gene, I showed a strong activity of both ARF8 promoters in galls at 7 and 14 dpi, confirming the transcriptomic analyzes. Moreover, we analyzed the effect of a CRISPR deletion within ARF8A and ARF8B coding sequences on the infection by M. incognita. Both CRISPR lines showed a significantly increased resistance to nematode infection correlated with defects in feeding cell formation. Altogether, these result showed that ARF8A and ARF8B expression is required for successful tomato-RKN interaction. The two conserved microRNA families, miR398 and miR408, are upregulated in tomato and Arabidopsis thaliana galls. miR398 and miR408 and their targets have been previously described to be involved in the copper signaling pathway. MIR398 and MIR408 expression is activated in response to copper starvation by the SPL7 transcription factor and mature miR398 and miR408 repress expression of genes encoding copper binding proteins non-essential for plant development. By using Arabidopsis lines expressing transcriptional fusion with GUS reporter gene, I showed that both MIR408 and SPL7 were expressed within nematode induced feeding cells. Moreover, infection assays with mir408 and spl7 mutants or lines expressing mutated targets resistant for miR398 cleavage showed an increased resistance of these lines to nematode infection. Finally, watering plants with copper sulfate, at concentration below toxic concentrations for the plants or for the nematodes, induced a strong resistance to nematode infection. Altogether, these results demonstrate the role of the copper signaling through activation of miR398 and miR408 by SPL7 in the formation of giant feeding cells. To conclude, the work presented in this thesis demonstrates the important role of three microRNAs families and their targets in the formation of nematode-induced feeding cells.
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Les nématodes à galles, du genre Meloidogyne, sont des vers microscopiques parasites des plantes qui infectent les racines de plus de 5 000 espèces de plantes et causent des pertes de rendement massives. Ces nématodes induisent la formation de galles en induisant la dédifférenciation de cellules racinaires en cellules nourricières géantes. La formation des cellules nourricières peut être divisée en deux phases : des mitoses successives sans cytokinèse au cours des dix premiers jours après infection (jai) puis de 10 à 21 jai, une phase d’endoreduplication et de forte croissance cellulaire. La formation de ces cellules est le résultat d'une reprogrammation massive de l'expression génique dans les cellules racinaires ciblées, comme le montrent les analyses transcriptomiques de galles. L’objectif de ma thèse était d’étudier des petits ARN non codants, les microARN, qui sont des régulateurs clés de l'expression génique chez les eucaryotes. Ces microARN agissent en induisant la dégradation ou l'inhibition de la traduction des ARN messagers (ARNm) ciblés. Au cours de ma thèse, le séquençage des petits ARN de galles de tomate induites par le nématode Meloidogyne incognita et de racines non infectés a permis d’identifier 174 microARN qui sont différentiellement exprimés dans les galles à 7 et/ou 14 jai. Les ARNm ciblés par les microARN dans ces galles ont été identifiés en intégrant les données de séquençage des microARN avec les données de transcriptome et d'un séquençage spécifique des ARNm clivés appelé dégradome. Cette analyse intégrative a permis la construction d’un réseau de régulation de l’expression génique agissant lors de la formation des cellules nourricières chez la tomate. Trois familles de microARN, miR167, miR398 et miR408, ont été sélectionnées pour les analyses fonctionnelles. La famille miR167 ciblent les transcrits d’ARF8A et ARF8B, codant des facteurs de réponse à l'auxine appartiennent à la voie de signalisation de l'auxine, un régulateur majeur dans l'interaction plante-nématode. En utilisant des lignées de tomates exprimant les deux promoteurs ARF8 fusionnés au gène rapporteur GUS, nous avons montré une forte activité des deux promoteurs dans les galles à 7 et 14 jai, confirmant les analyses transcriptomiques. Nous avons analysé l'effet d'une délétion CRISPR au sein des séquences codantes ARF8A et ARF8B sur l'infection par M. incognita. Ces deux lignées présentent une résistance accrue à l'infection en raison de défauts de formation des cellules nourricières. L'ensemble des résultats a montré que l'expression d'ARF8A et d’ARF8B est nécessaire pour la formation des cellules nourricières. Les familles de microARN conservées, miR398 et miR408, sont surexprimées dans les galles de tomate et d'Arabidopsis thaliana. Ces microARN et leurs cibles sont impliqués dans la signalisation du cuivre. Lors de carence en cuivre, l'expression des gènes MiR398 et MIR408 est activée par le facteur de transcription SPL7, réprimant alors l'expression de gènes codant des protéines liant le cuivre non essentiel au développement des plantes. En utilisant des lignées d’A. thaliana exprimant une fusion transcriptionnelle avec le gène GUS, nous avons montré que MIR408 et SPL7 étaient exprimés dans des cellules nourricières. Des tests d'infection réalisés avec des mutants mir408 et spl7, ou des lignées exprimant des cibles mutées résistantes au clivage par miR398 ont montré une résistance accrue de ces lignées aux nématodes. L'apport de sulfate de cuivre, à une concentration inférieure aux concentrations toxiques, a induit une forte résistance à l'infection. L’ensemble de ces résultats montrent le rôle de l’homéostasie du cuivre dans la formation de cellules géantes via le module SPL7, miR408 et miR398. Pour conclure, les travaux présentés dans ce travail de thèse démontrent le rôle de ces trois familles de microARN et de leurs cibles dans la formation de cellules nourricières géantes induites par les nématodes.
Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.
Distributed systems in general and cloud systems in particular, are
susceptible to failures that can lead to substantial economic and data losses,
security breaches, and even potential threats to human safety. Software ageing
is an example of one such vulnerability. It emerges due to routine re-usage of
computational systems units which induce fatigue within the components,
resulting in an increased failure rate and potential system breakdown. Due to
its stochastic nature, ageing cannot be directly measured, instead ageing
indicators as proxies are used. While there are dozens of studies on different
ageing indicators, their comprehensive comparison in different settings remains
underexplored. In this paper, we compare two ageing indicators in OpenStack as
a use case. Specifically, our evaluation compares memory usage (including swap
memory) and request response time, as readily available indicators. By
executing multiple OpenStack deployments with varying configurations, we
conduct a series of experiments and analyze the ageing indicators. Comparative
analysis through statistical tests provides valuable insights into the
strengths and weaknesses of the utilised ageing indicators. Finally, through an
in-depth analysis of other OpenStack failures, we identify underlying failure
patterns and their impact on the studied ageing indicators.
Cold Spring Harbor LaboratoryApril 2025Longevity & aging
Nicotinamide adenine dinucleotide (NAD (+) ) is an essential redox cofactor and signaling molecule linked to age-dependent metabolic decline, with its compartmentalization regulated by the mitochondrial carrier SLC25A51. The mechanisms contributing to declining NAD (+) levels during aging and the consequences of altered NAD (+) homeostasis across tissues are poorly understood. Here, we show that SLC25A51 is upregulated in aging and aging-associated conditions, particularly in senescent cells. In a mouse model of beta-cell senescence, upregulated SLC25A51 was associated with beta-cell identity loss, senescence progression, and a reduced NAD (+) /NADH ratio. SLC25A51 was elevated following p16 (INK4a) -, replicative-, irradiation-, and H (2) O (2) -induced senescence, with NRF2 implicated as a potential transcriptional regulator. Overexpression of SLC25A51, but not a transport-dead mutant, induced senescence factors, while its deletion prevented this effect. Beta-cell-specific deletion of SLC25A51 lowered p16 (INK4a) levels in pancreatic islets, circulating insulin, and glucose levels, improving insulin sensitivity and indicating its role in cellular senescence and the metabolic control of beta-cell function.
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Glycation reactions play a key role in the senescence process and are involved in numerous age-related pathologies, such as diabetes complications or Alzheimer’s disease. As a result, past studies on glycation have mostly focused on human and laboratory animal models for medical purposes. Very little is known about glycation and its link to senescence in wild animal species. Yet, despite feeding on high-sugar diets, several bat and bird species are long-lived and seem to escape the toxic effects of high glycaemia. The study of these models could open new avenues both for understanding the mechanisms that coevolved with glycation resistance and for treating the damaging effects of glycations in humans. Our understanding of glycaemia’s correlation to proxies of animals’ pace of life is emerging in few wild species; however, virtually nothing is known about their resistance to glycation, nor on the relationship between glycation, species’ life-history traits and individual fitness. Our review summarizes the scarce current knowledge on the links between glycation and life-history traits in non-conventional animal models, highlighting the predominance of avian research. We also investigate some key molecular and physiological parameters involved in glycation regulation, which hold promise for future research on fitness and senescence of individuals.
BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults. METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value <0.05. FINDINGS: Higher PRS for insomnia was associated with lower global cognitive function and higher risk of mild cognitive impairment (MCI) (OR = 1.20, 95% CI [1.06, 1.36]). Higher PRS for daytime sleepiness was also associated with increased MCI risk (OR = 1.14, 95% CI [1.02, 1.28]). Sleep duration PRS was associated with reduced MCI risk among short and normal sleepers, while among long sleepers it was associated with reduced global cognitive function and with increased MCI risk (OR = 1.40, 95% CI [1.10, 1.78]). Furthermore, adjustment of analyses for the measured sleep phenotypes and APOE- [Formula: see text] allele had minor effects on the PRS associations with the cognitive outcomes. INTERPRETATION: Genetic measures underlying insomnia, daytime sleepiness, and sleep duration are associated with MCI risk. Genetic and self-reported sleep duration interact in their effect on MCI. FUNDING: Described in Acknowledgments.
Background Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. Methods Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin–p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. Results The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin–p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. Conclusion Oxidative stress-triggered premature senescence via nuclear progerin–p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.
Down syndrome (DS) induces a variable phenotype including intellectual disabilities and early development of Alzheimer’s disease (AD). Moreover, individuals with DS display accelerated aging that affects diverse organs, among them the brain. The Ts65Dn mouse is the most widely used model to study DS. Progressive loss of cholinergic neurons is one of the hallmarks of AD present in DS and in the Ts65Dn model. In this study, we quantify the number of cholinergic neurons in control and Ts65Dn mice, observing a general reduction in their number with age but in particular, a greater loss in old Ts65Dn mice. Increased expression of the m1 muscarinic receptor in the hippocampus counteracts this loss. Cholinergic neurons in the Ts65Dn mice display overexpression of the early expression gene c-fos and an increase in the expression of β-galactosidase, a marker of senescence. A possible mechanism for senescence induction could be phosphorylation of the transcription factor FOXO1 and its retention in the cytoplasm, which we are able to confirm in the Ts65Dn model. In our study, using Ts65Dn mice, we observe increased cholinergic activity, which induces a process of early senescence that culminates in the loss of these neurons.
ABSTRACT Senescence is an irreversible proliferation withdrawal that can be initiated after DNA damage-induced cell cycle arrest in G2 phase to prevent genomic instability. Senescence onset in G2 is not well understood; it requires p53 and RB family tumour suppressors, but how they are regulated to convert a temporary cell cycle arrest into a permanent one remains unknown. Here, we show that a previously unrecognised balance between the CDK inhibitor p21 and Chk1 controls D-type cyclin-CDK activity during G2 arrest. In non-transformed cells, p21 activates RB in G2 by inhibiting Cyclin D1-CDK2/CDK4. The resulting G2 exit, which precedes appearance of senescence markers, is associated with a mitotic bypass, Chk1 inhibition and DNA damage foci reduction. In p53/RB-proficient cancer cells, compromised G2 exit correlates with sustained Chk1 activity, delayed p21 induction, untimely Cyclin E1 re-expression and genome reduplication. Chk1 depletion promotes cell cycle exit by inducing p21 binding to Cyclin D1 and Cyclin E1-CDK complexes and down-regulating CDK6, whereas Chk2 knockdown promotes RB phosphorylation and delays G2 exit. In conclusion, p21 and Chk2 oppose Chk1 to maintain RB activity, thus controlling DNA damage-induced senescence onset in G2.
Mitochondria play a pivotal role in energy generation and cellular physiological processes. These organelles are highly dynamic, constantly changing their morphology, cellular location, and distribution in response to cellular stress. In recent years, the phenomenon of mitochondrial transfer has attracted significant attention and interest from biologists and medical investigators. Intercellular mitochondrial transfer occurs in different ways, including tunnelling nanotubes (TNTs), extracellular vesicles (EVs), and gap junction channels (GJCs). According to research on intercellular mitochondrial transfer in physiological and pathological environments, mitochondrial transfer hold great potential for maintaining body homeostasis and regulating pathological processes. Multiple research groups have developed artificial mitochondrial transfer/transplantation (AMT/T) methods that transfer healthy mitochondria into damaged cells and recover cellular function. This paper reviews intercellular spontaneous mitochondrial transfer modes, mechanisms, and the latest methods of AMT/T. Furthermore, potential application value and mechanism of AMT/T in disease treatment are also discussed.
BACKGROUND: Healthy ageing (HA) has been defined using multiple approaches. We aim to produce a comprehensive overview and analysis of the theoretical models underpinning this concept and its associated normative terms and definitions. METHODS: We conducted a systematic review of peer-reviewed HA models in Embase.com, Medline (Ovid), Cochrane CENTRAL, CINAHL, PsycINFO, and Web of Science until August 2022. Original theoretical papers, concept analyses, and reviews that proposed new models were included. Operational models/definitions, development psychology theories and mechanisms of ageing were excluded. We followed an iterative approach to extract the models’ characteristics and thematically analyze them based on the approach of Walker and Avant. The protocol was registered in PROSPERO (CRD42021238796). FINDINGS: Out of 10,741 records, we included 59 papers comprising 65 models/definitions, published in English (1960–2022) from 16 countries in Europe, Asia, and America. Human ageing was described using 12 normative terms, mainly (models (%)): successful (34 (52%)), healthy (eight (12%)), well (five (8%)), and active (four (6%)). We identified intrinsic/extrinsic factors interacting throughout the life course, adaptive processes as attributes, and outcomes describing ageing patterns across objective and subjective dimensions (number of models/definitions): cognitive (62), psychological (53), physical (49), social (49), environmental (19), spiritual (16), economic (13), cultural (eight), political (six), and demographic (four) dimensions. Three types of models emerged: health-state outcomes (three), adaptations across the life course (31), or a combination of both (31). Two additional sub-classifications emphasized person-environment congruence and health promotion. INTERPRETATION: HA conceptualizations highlight its multidimensionality and complexity that renders a monistic model/definition challenging. It has become evident that life long person-environment interactions, adaptations, environments, and health promotion/empowerment are essential for HA. Our model classification provides a basis for harmonizing terms and dimensions that can guide research and comparisons of empirical findings, and inform social and health policies enabling HA for various populations and contexts. FUNDING: MM, ZMRD, and OI are supported by the European Union’s Horizon 2020 Marie Skłodowska-Curie grant No 801076, and MM is also supported by the Swiss National Foundation grant No 189235.
Background There is a complete lack of studies focusing on the association between care degree (reflecting the long-term care need) and loneliness or social isolation in Germany. Aims To investigate the association between care degree and loneliness as well as perceived social isolation during the COVID-19 pandemic. Methods We used data from the nationally representative German Ageing Survey, which covers community-dwelling middle-aged and older individuals aged 40 years or over. We used wave 8 of the German Ageing Survey (analytical sample: n = 4334 individuals, mean age was 68.9 years, SD: 10.2 years; range 46–100 years). To assess loneliness, the De Jong Gierveld instrument was used. To assess perceived social isolation, the Bude and Lantermann instrument was used. Moreover, the level of care was used as a key independent variable (absence of care degree (0); care degree 1–5). Results After adjusting for various covariates, regressions showed that there were no significant differences between individuals without a care degree and individuals with a care degree of 1 or 2 in terms of loneliness and perceived social isolation. In contrast, individuals with a care degree of 3 or 4 had higher loneliness ( β = 0.23, p = 0.034) and higher perceived social isolation scores ( β = 0.38, p < 0.01) compared to individuals without a care degree. Discussion/conclusions Care degrees of 3 or 4 are associated with higher levels of both loneliness and perceived social isolation. Longitudinal studies are required to confirm this association.
Background Being overweight or obese may be associated with lower physical and cognitive function, but in late-adulthood (≥ 65 years) evidence is mixed. This study aimed to investigate how being overweight or obese affected interactions between muscle strength, function and cognition in Australians aged ≥ 50 years, and whether interactions varied according to age (i.e. ≥ 50–65 vs > 65 years). Methods This study included 2368 adults [mean (standard deviation) age: 63 (7) years; 56% female] from the 2011/2012 Australian Diabetes, Obesity and Lifestyle (AusDiab) follow-up. Physical function was assessed via timed up-and-go (TUG) and muscle strength from knee extensor strength (KES). Cognition was assessed using Mini-Mental-State Exam (MMSE), Spot-the-Word (STW), California Verbal Learning Test (CVLT) and Symbol–Digit-Modalities Test (SDMT). Beta binomial regression was used to evaluate how being overweight or obese influenced strength, physical and cognitive function associations. Results Being overweight or obese did not affect strength-cognition associations regardless of sex or age. With slower physical function; obese females showed better STW (odds ratio [OR] 95% CI]: 1.070 [1.016, 1.127], P = 0.011); obese men better MMSE (OR [95% CI]: 1.157 [1.012, 1.322], P = 0.033); and obese men aged > 65 better CVLT (OR [95% CI]: 1.122 [1.035, 1.217], P = 0.019) and MMSE (OR [95% CI]: 1.233 [1.049, 1.449], P = 0.017) compared to normal weight participants. Conclusion Slower physical function was associated with better performance in some cognitive domains in obese, but not in non-obese adults aged ≥ 50 years. These findings suggest some benefits of obesity to aspects of cognition when physical function is slower, but longitudinal follow-up studies are needed.
The study aims to investigate associations between cardiovascular health (CVH) metrics and retinal ageing indexed by retinal age gap. A total of 26,354 participants from the UK Biobank study with available CVH metrics and qualified retinal imaging were included in the present analysis. CVH included 7 metrics (smoking, physical activity, diet, body mass index [BMI], total cholesterol, blood pressure [BP], blood glucose). These were summarized to classify the overall CVH as poor (0–7), intermediate (8–10) or ideal (11–14). Retinal age gap was defined as the difference between biological age predicted by fundus images and chronological age. Accelerated and non-accelerated retinal ageing was defined if retinal age gap was in the upper or lower 50% quantiles of the study population, respectively. Linear and logistic regression models estimated the association of overall CVH and each metric of CVH with retinal age gap respectively. Our results showed that in the fully adjusted model, each one-unit score increase in overall CVH was negatively associated with retinal age gap (odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.87-0.92, P < 0.001). Compared with poor overall CVH, people with intermediate and ideal overall CVH had significantly lower retinal age gap (OR = 0.76, 95%CI: 0.67–0.85, P < 0.001; OR = 0.58, 95%CI: 0.50–0.67, P < 0.001). Similar associations were found between overall CVH and accelerated retinal ageing. CVH metrics including smoking, BMI, BP, and blood glucose were also significantly associated with higher retinal age gap. Taken together, we found a significant and inverse dose-response association between CVH metrics and retinal age gap, indicating that maintaining healthy metrics especially smoking, BMI, BP, and blood glucose may be crucial to slow down biological ageing.
Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8^+ T-lymphocytes (CD8^+ T_EMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8^+ T-lymphocytes which were CD8^+ T_EMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8^+ T_EMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/μl (95% CI: 117–452 cells/ μ l, p < 0.004), driven by significant increases from baseline in CD3^+, CD4^+, and CD8^+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8^+ T_EMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.
Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated ( r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
Hippocampal blood–brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood–brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as K _ i values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus ( p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores ( p < 0.01). Regional BBB differences revealed higher K _ i values in the hippocampus and white matter than in the thalamus ( p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter ( p = 0.015) and thalamus ( p = 0.016), which was associated with a higher Fazekas score ( p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability.
The stress response – a suite of physiological and behavioural adjustments – allows organisms to support heightened energy requirements associated with unpredictable environmental challenges (i.e. stressors). The stress response involves the activation of different physiological systems, among which the most studied is the hypothalamic-pituitary-adrenal axis leading to the enhanced production of glucocorticoids (GCs). At baseline levels, the primary role of GCs is energy mobilisation and regulation. These hormones act as mediators of allostasis, the active process of reaching differential homeostatic states according to physiological demands. Following exposure to a short-term, temporary stressor (i.e. acute stress), increased GC levels favour energy allocation towards functions promoting immediate survival at the expense of other non-immediately essential functions (e.g. growth, reproduction), and is therefore adaptive. On the other hand, individuals repeatedly exposed to stressors, or exposed to stressors that last for longer (i.e. days-weeks) can have elevated baseline GC levels. They enter into states of chronic stress during which resources are deviated from physiological functions such as growth, reproduction or immunity on the long-term, with expected adverse consequences on fitness. Measuring states of chronic stress in the wild is challenging and associations between GCs and fitness-related traits are equivocal due to the influence of life-history and environmental contexts on such relationships. Throughout my Ph.D., I aimed at evaluating the relationships between baseline GC levels and fitness-related traits reflecting individual health (i.e. body mass, physiological condition, immunity), and their senescence patterns in a long-lived mammal. This work was conducted in two roe deer (Capreolus capreolus) populations experiencing markedly contrasted environmental conditions, and which have been longitudinally followed at the individual-based level. I evidenced that GCs related to health parameters on the short-term (i.e. when measured at the same sampling event), but that GCs did not have carry-over effects on the senescence of those traits. In a first chapter, I showed that GCs were negatively associated to body mass in adults, but not juveniles, of both populations and both sexes, supporting the idea that is is essential to take into account the life-history stage when evaluating relationships between GCs and life-history traits. I also found that the Neutrophil:Lymphocyte (N:L) ratio – another biomarker increasingly used as a proxy of the stress response – related negatively to body mass on the medium term (i.e. change in individual body mass between two consecutive years) during the late growth phase. This suggests that GCs and N:L ratios describe different components of the stress response and are not interchangeable. In a second part, I showed that GCs positively related to creatinine levels (i.e. a proxy of muscle mass and renal efficacy) on the short-term, suggesting an increased catabolic state in individuals with elevated GCs. I also found a sex-specific association between GCs and albumin, the main blood protein, suggesting that sex hormones can modulate GC-life-history trait relationships. In a third chapter, I found that GCs measured during early-life did not modulate patterns of immunosenescence but were only positively associated to the abundance of lung parasites in adults. In a last chapter, I discuss the relevance of the present work for the field of ecophysiology. I have investigated of the associations between GCs and various fitness-related traits at different temporal scales, using longitudinal data on a free-ranging mammal. This allowed to account for much of the sources of variations identified in the literature. I then explore and develop future research perspectives, both for the roe deer program, and for research in general.
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En réponse à des fluctuations environnementales imprévisibles (i.e. stresseurs), les organismes ont développé une série de réponses physiologiques et comportementales, i.e. la réponse au stress, qui leur permettent de répondre aux exigences physiologiques accrues associées à ces fluctuations. La réponse au stress se traduit par l'activation de systèmes physiologiques, parmi lesquels le plus étudié est l'axe hypothalamo-pituitaire-surrénalien, qui entraîne une production accrue de glucocorticoïdes (GCs). Les GCs sont des hormones présentes à des niveaux basaux et dont le rôle principal est la mobilisation et la régulation de l'énergie. Ils agissent comme médiateurs de l'allostasie, le processus actif permettant l’établissement et la réalisation d’états homéostatiques fonction des exigences physiologiques. Suite à une exposition à un stresseur temporaire et de courte durée (i.e. stress aigu), l’augmentation des niveaux de GCs contribue à mettre à disposition des ressources énergétiques pour des fonctions favorisant la survie immédiate, ce qui est adaptatif, au détriment d'autres fonctions non immédiatement essentielles (comme la croissance ou la reproduction). En revanche, les individus exposés de manière répétée à des stresseurs ou exposés à des stresseurs de longue durée (i.e. jours-semaines) peuvent présenter des niveaux basaux de GCs élevés et entrer dans des états de stress chronique, au cours desquels les ressources sont détournées des fonctions physiologiques telles que la croissance, la reproduction ou l'immunité sur le long terme, avec des conséquences préjudiciables attendues sur les traits liés à l'histoire de vie et la valeur sélective. Mesurer les états de stress chronique dans la nature pose un problème complexe, et les associations entre les GCs et les traits liés à l'histoire de vie ou à la valeur sélectives sont équivoques, notamment en raison de l'influence des contextes liés à l'histoire de vie et de l'environnement sur de telles relations. Dans ce contexte, j'ai cherché à évaluer les relations entre une mesure intégrée des niveaux de GCs basaux et la performance et sénescence de différents traits liés à l'histoire de vie et à la valeur sélective, reflétant l'état de santé d'un individu (i.e. masse corporelle, condition physiologique, immunité), chez un mammifère sauvage longévif. Ce travail a été mené dans deux populations de chevreuils (Capreolus capreolus) présentant des conditions environnementales nettement contrastées, et qui ont été suivies longitudinalement au niveau individuel, avec des informations individuelles et environnementales disponibles. Ce travail a permis de montrer que les GCs étaient liés aux paramètres de santé à court terme (c'est-à-dire mesurés lors de la même prise d'échantillon), mais que les GCs n'avaient pas d’effets durables sur la sénescence de ces traits.
PURPOSE: The Norwegian Survey of Health and Ageing (NORSE) was set up to provide internationally comparable data on ageing in Norway, which includes measured intrinsic capacity and cognitive function. PARTICIPANTS: NORSE is a population-based health examination study of seniors aged 60+ from the 1921–1958 birth cohorts in the former Norwegian county of Oppland, interviewed and examined during 2017–19 (N = 957, 16% response rate). NORSE is to some extent based on the SHARE-questionnaire (share-project.org), which includes work-related information, self-assessed and retrospective health, and expectations on longevity, quality of life, volunteering activities, consumption, and financial arrangements. In addition, several objective measures of intrinsic and cognitive capacity are included in NORSE. FINDINGS TO DATE: A shorter preferred life expectancy (PLE) was found to be associated with the prospects of a life with dementia and chronic pain. Motivation for retirement was found to be related to work-life experience and health. Social media was mostly used in the younger age groups and there was a tendency towards more use in the higher educational groups. NORSE incorporates questions on religion, and older women tend to have a higher degree of religiosity (proxied as self-assessed religiosity) than men in their 80s, but more similar (and lower levels) among those in their 60s. FUTURE PLANS: NORSE participants have allowed their data to be linked to National registry data and midlife health examination studies and thereby provide a longitudinal design as well as information on disability status, socioeconomic status, household and marital status, support to/from children and parents, and pension status. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-021-12294-3.
Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production and antioxidant defenses, oxidative stress occurs. Persistent oxidative stress leads to cellular senescence, an important hallmark of aging, and is involved in several age-related conditions and illnesses. This study aims to investigate whether Weo electrolyzed water (WEW) could modulate the phenotype of senescent cells. We compared normal human lung fibroblasts (BJ) and breast cancer cells (T47D) treated with hydrogen peroxide (H(2)O(2)) to induce senescence. We assessed the molecular impact of WEW on markers of cellular senescence, senescence-associated secretory phenotype (SASP) factors, and stress response genes. Treatment with WEW modulated markers of cellular senescence, such as the senescence-associated β-galactosidase (SA-β-gal) activity, EdU incorporation and p21 expression, similarly in both cell types. However, WEW modulated the expression of SASP factors and stress response genes in a cell type-dependent and opposite fashion, significantly decreasing them in BJ cells, while stimulating their expression in T47D cells. Reduction in the expression of SASP factors and stress-related genes in BJ cells suggests that WEW acts as a protective factor, thereby reducing oxidative stress in normal cells, while making cancer cells more sensitive to the effects of cellular stress, thus increasing their elimination and consequently reducing their deleterious effects. These findings suggest that, due to its differential effects as a senomorphic factor, WEW could have a positive impact on longevity and age-related diseases.
The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. The efficacy of disease-modifying therapies (DMTs) for RMS declines with age. Also, older persons with MS may be more susceptible to infections, hospitalisations and malignancy. Aging people with MS have higher rates of comorbidities versus aged-matched controls, increasing the individual risk of disability. We review the therapeutic properties of cladribine tablets (CladT) in ageing people with RMS, with regard to their utility for allowing these individuals to cease continuous administration of a DMT (i.e. to act as an “exit therapy”). CladT is thought to be an immune reconstitution therapy, in that two short courses of oral treatment 1 year apart provide suppression of MS disease activity in responders that far outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. Post hoc analyses, long-term follow-up of populations with RMS in randomised trials, and real-world evidence suggest that the efficacy of CladT is probably independent of age, although more data in the elderly are still needed. No clear adverse signals for lymphopenia or other adverse safety signals have emerged with increasing age, although immunosenescence in the setting of age-related “inflammaging” may predispose elderly patients to a higher risk of infections. Updating vaccination status is recommended, especially against pneumococci and herpes zoster for older patients, to minimise the risk of these infections. CladT may be a useful alternative treatment for ageing people with MS who often bear a burden of multiple comorbidities and polypharmacy and who are more exposed to the adverse effects of continuous immunosuppressive therapy.
Background Understanding health and developing trends among the older population is essential for countries to tackle the challenges of an ageing population and formulate relevant policies. Facilitating healthy ageing is an essential strategy to address the issues arising among the aged. The concept of healthy ageing is defined as “the process of developing and maintaining the functional ability that enables wellbeing in old age (WHO),“ where “functional ability comprises the health-related attributes that enable people to be and to do what they have reason to value.“ People have different ageing pathways depending on their genetic profile and different life course health risk exposures. Therefore, ageing, more specifically healthy ageing, largely depends on individual lifestyle choices. This study examines the association between lifestyle behaviours and healthy ageing among older adults in India. Methods Based on the first round of LASI in 2017-18, we conceptualized healthy ageing within the WHO functional ability framework. We developed a Healthy Ageing Index (HAI), which incorporates physiological health, functional health, cognitive functions, psychological well-being, and social engagement. We used principal component analysis to generate a composite score for HAI. We then used multiple linear regression to demonstrate the association between lifestyle behaviours and HAI. Result The mean HAI was 82.8%, indicating that the study population is healthier. The study findings show that smoking and drinking are more prevalent among males, rural residents, illiterate individuals, those currently employed, and those belonging to the poorest wealth quintile. Engaging in physical activity is associated with better health outcomes (β = 2.36; 95% CI: 2.16–2.56). Conclusion This study emphasizes the importance of adopting a healthier lifestyle to achieve healthy ageing. Health behaviours are modifiable, so our results highlight the need for policy interventions to promote a healthier lifestyle from an early age.
John Wiley and Sons Inc.August 2024Longevity & aging
The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24(−/−) mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans. Nevertheless, inhibition of the inflammasomes would be a beneficial therapy for progeria. Here, we show that OLT1177 (dapansutrile), other NLRP3 inhibitor, improved cellular and animal phenotypes using progeroid fibroblasts and a Lmna(G609G/G609G) mouse model. In both cases dapansutrile reduced progerin accumulation, NLRP3‐inflammasome activation and secretory phenotype of senescence, extended the lifespan of progeroid animals, preserved bodyweight, and reduced kyphosis, inflammation, and senescence. Interestingly, dapansutrile further improved the effect of lonafarnib, the only FDA‐approved drug for the progeria. The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co‐adjuvant treatment with lonafarnid in HGPS.
Summary Exogenous melatonin inhibited the senescence of preosteoblast cells in type 1 diabetic (T1D) mice and those cultured in high glucose (HG) by multiple regulations. Exogenous melatonin had a protective effect on diabetic osteoporosis, which may depend on the inhibition of senescence. Introduction Senescence is thought to play an important role in the pathophysiological mechanisms underlying diabetic bone loss. Increasing evidence has shown that melatonin exerts anti-senescence effects. In this study, we investigated whether melatonin can inhibit senescence and prevent diabetic bone loss. Methods C57BL/6 mice received a single intraperitoneal injection of 160 mg/kg streptozotocin, followed by the oral administration of melatonin or vehicle for 2 months. Then, tissues were harvested and subsequently examined. MC3T3-E1 cells were cultured under HG conditions for 7 days and then treated with melatonin or not for 24 h. Sirt1-specific siRNAs and MT1- or MT2-specific shRNA plasmids were transfected into MC3T3-E1 cells for mechanistic study. Results The total protein extracted from mouse femurs revealed that melatonin prevented senescence in T1D mice. The micro-CT results indicated that melatonin prevented bone loss in T1D mice. Cellular experiments indicated that melatonin administration prevented HG-induced senescence, whereas knockdown of the melatonin receptors MT1 or MT2 abolished these effects. Sirt1 expression was upregulated by melatonin administration but significantly reduced after MT1 or MT2 was knocked down. Knockdown of Sirt1 blocked the anti-senescence effects of melatonin. Additionally, melatonin promoted the expression of CDK2, CDK4, and CyclinD1, while knockdown of MT1 or MT2 abolished these effects. Furthermore, melatonin increased the expression of the polycomb repressive complex (PRC), but knockdown of MT1 or MT2 abolished these effects. Furthermore, melatonin increased the protein levels of Sirt1, PRC1/2 complex–, and cell cycle–related proteins. Conclusion This work shows that melatonin protects against T1D-induced bone loss, probably by inhibiting senescence. Targeting senescence in the investigation of diabetic osteoporosis may lead to novel discoveries.
Cognitive dysfunction in aging is a major biomedical challenge without medical therapies. Here, Castner et al. show that longevity factor klotho enhances cognition in aged nonhuman primates, increasing its relevance for a therapeutic path to humans. Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.
Background Tinnitus affects 10 to 15% of the population, but its underlying causes are not yet fully understood. Hearing loss has been established as the most important risk factor. Ageing is also known to accompany increased prevalence; however, the risk is normally seen in context with (age-related) hearing loss. Whether ageing per se is a risk factor has not yet been established. We specifically focused on the effect of ageing and the relationship between age, hearing loss, and tinnitus. Methods We used two samples for our analyses. The first, exploratory analyses comprised 2249 Austrian individuals. The second included data from 16,008 people, drawn from a publicly available dataset (NHANES). We used logistic regressions to investigate the effect of age on tinnitus. Results In both samples, ageing per se was found to be a significant predictor of tinnitus. In the more decisive NHANES sample, there was an additional interaction effect between age and hearing loss. Odds ratio analyses show that per unit increase of hearing loss, the odds of reporting tinnitus is higher in older people (1.06 vs 1.03). Conclusions Expanding previous findings of hearing loss as the main risk factor for tinnitus, we established ageing as a risk factor in its own right. Underlying mechanisms remain unclear, and this work calls for urgent research efforts to link biological ageing processes, hearing loss, and tinnitus. We therefore suggest a novel working hypothesis that integrates these aspects from an ageing brain viewpoint.
Late life insomnia may increase risk for accelerated biological aging. Intervening to treat insomnia may provide protection from biological aging by reducing the prevalence of senescent cells in the immune system, as indicated by gene expression of a marker of cellular senescence, p16^INK4a. In the present study, we determine whether treatment of insomnia in older adults with cognitive behavioral therapy for insomnia (CBT-I) would reduce p16^INK4a gene expression in peripheral blood mononuclear cells (PBMC), compared to a sleep education therapy (SET), an active comparator condition. Secondly, we investigate the relationship between sustained insomnia remission and reduced expression of p16^INK4a. Participants 60 + years old with insomnia were enrolled in a randomized controlled trial and assigned to CBT-I or SET. Analyses of 231 older adults (CBT-I = 119; SET = 112) examine baseline, post (2 months), and 24 months gene expression of p16^INK4a. Compared to baseline, expression of p16^INK4a increased in the SET group over 24 months ( P = 0.03), but showed no change in the CBT-I group. Those who received CBT-I and experienced sustained remission of insomnia had a significant decline in p16^INK4a expression by 24 months compared to baseline ( P = 0.02). Individuals not sustaining remission of insomnia exhibited overall increase expression of p16^INK4a by 24 months ( P = 0.03). In older adults with insomnia, p16^INK4a increases over 24 months, while CBT-I treatment of insomnia mitigates the increase in p16^INK4a. Further, sustained remission of insomnia using CBT-I leads to a decrease in p16^INK4a. These results suggest that behavioral interventions that are effective at treating insomnia might reduce the population of senescent cells in circulating blood.
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