medRxiv : the preprint server for health sciences最新文献

{"title":"A head-to-head comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials.","authors":"Matthew D Zammit, Julie C Price, Bradley T Christian, Michael S Rafii","doi":"10.1101/2025.03.18.25324200","DOIUrl":"https://doi.org/10.1101/2025.03.18.25324200","url":null,"abstract":"<p><p>Adults with Down syndrome carry high risk of developing Alzheimer's disease and efforts to include this population in clinical trials remain limited. A barrier to recruitment for anti-amyloid trials includes the availability of the same amyloid PET radiotracer to multiple treatment centers. 237 adults with Down syndrome from the Trial-Ready Cohort - Down syndrome and Alzheimer Biomarker Consortium - Down syndrome studies were imaged using T1-w MRI and using PET images of PiB, Florbetapir (FBP), NAV4694 (NAV) or Flutemetamol (FMM) to screen for amyloid plaque (Aβ) burden. PiB displayed the largest effect size to measure amyloid change while FBP had a small effect size. NAV and PiB, which are structurally similar compounds, displayed similar sensitivity to measure longitudinal amyloid increase. The estimated age at amyloid onset showed no significant difference between PiB, FBP, NAV or FMM. The findings suggest that different amyloid PET radiotracers provide consistent estimates of amyloid onset age for adults with Down syndrome. Multicenter studies of Alzheimer's disease therapeutics can utilize multiple amyloid PET radiotracers to facilitate recruitment, however, PiB and NAV displayed the greatest sensitivity to detect longitudinal change.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Aortic Regurgitation Detection and Quantification: A Deep Learning Approach Using Multi-View Echocardiography.","authors":"Christina Binder, Yuki Sahashi, Hirotaka Ieki, Milos Vukadinovic, Victoria Yuan, Meenal Rawlani, Paul Cheng, David Ouyang, Robert J Siegel","doi":"10.1101/2025.03.18.25323918","DOIUrl":"https://doi.org/10.1101/2025.03.18.25323918","url":null,"abstract":"<p><strong>Background: </strong>Accurate evaluation of aortic regurgitation (AR) severity is necessary for early detection and chronic disease management. AR is most commonly assessed by Doppler echocardiography, however limitations remain given variable image quality and need to integrate information from multiple views. This study developed and validated a deep learning model for automated AR severity assessment from multi-view color Doppler videos.</p><p><strong>Methods: </strong>We developed a video-based convolutional neural network (R2+1D) to classify AR severity using color Doppler echocardiography videos from five standard views: parasternal long-axis (PLAX), PLAX-aortic valve focus, apical three-chamber (A3C), A3C-aortic valve focus, and apical five-chamber (A5C). The model was trained on 47,638 videos from 32,396 studies (23,240 unique patients) from Cedars-Sinai Medical Center (CSMC) and externally validated on 3369 videos from 1504 studies (1493 unique patients) from Stanford Healthcare Center (SHC).</p><p><strong>Results: </strong>Combining assessments from multiple views, the EchoNet-AR model achieved excellent identification of both at least moderate AR (AUC 0.95, [95% CI 0.94-0.96]) and severe AR (AUC 0.97, [95% CI 0.96 - 0.98]). This performance was consistent in the external SHC validation cohort for both at least moderate AR (AUC 0.92, [95% CI 0.88-0.96]) and severe AR (AUC 0.94, [95% CI 0.89-0.98]). Subgroup analysis showed robust model performance across varying image quality, valve morphologies, and patient demographics. Saliency map visualizations demonstrated that the model focused on the proximal flow convergence zone and vena contracta, appropriately narrowing on hemodynamically significant regions.</p><p><strong>Conclusion: </strong>The EchoNet-AR model accurately classifies AR severity and synthesizes information across multiple echocardiographic views with robust generalizability in an external cohort. The model shows potential as an automated clinical decision support tool for AR assessment, however clinical interpretation remains essential, particularly in complex cases with multiple valve pathologies or altered hemodynamics.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress induced liver damage in dengue is exacerbated in those with obesity.","authors":"Heshan Kuruppu, Maneshka Karunananda, Chandima Jeewandara, Laksiri Gomes, D M C B Dissanayake, Chathura Ranatunga, Padukkage Harshani Chathurangika, Nushara Senatilleke, Navanjana Warnakulasuriya, Rivindu H Wickramanayake, Ananda Wijewickrama, Damayanthi Idampitiya, Graham S Ogg, Gathsaurie Neelika Malavige","doi":"10.1101/2025.03.18.25324170","DOIUrl":"https://doi.org/10.1101/2025.03.18.25324170","url":null,"abstract":"<p><strong>Background: </strong>Obesity and diabetes are risk factors for severe dengue. As there are limited data on the association of obesity with liver dysfunction and oxidative stress in patients with acute dengue, we investigated liver dysfunction associated with obesity, oxidative stress and inflammatory markers, in a large cohort of patients with varying severity of acute dengue.</p><p><strong>Methods: </strong>577 adults dengue patients with acute disease, presenting with a duration of illness ≤ 4 days, were enrolled and followed up from admission to discharge, with clinical and laboratory features recorded. Aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein, ferritin, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) levels were measured, along with the height, weight and waist circumference.</p><p><strong>Results: </strong>AST, ALT, CRP and ferritin levels were significantly higher in patients with central obesity (waist circumference of ≥80cm in women or ≥90cm in men) compared to leaner individuals. ALT and CRP levels were also significantly higher in patients with a BMI of ≥ 23.9 kg/m ² . 4-HNE levels significantly increased with the rise in AST levels and with ALT levels although not significant. In contrast, MDA levels gradually decreased with the rise in AST levels and ALT levels. There were no differences in 4-HNE and MDA levels in relation to clinical disease severity. However, MDA levels were significantly higher in younger individuals, and leaner individuals with a normal BMI. Furthermore, MDA levels inversely correlated with serum ferritin levels, while AST, ALT and CRP levels significantly correlated ferritin levels.</p><p><strong>Conclusions: </strong>4-HNE and MDA which are markers of lipid peroxidation, appear to play different roles in the pathogenesis of dengue, which should be further investigated for identification of therapeutic targets for treatment of dengue.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.","authors":"Nathaniel G Harnett, Soumyaa Joshi, Poornima Kumar, Courtney Russell, Daniel G Dillon, Justin T Baker, Diego A Pizzagalli, Milissa L Kaufman, Lisa N Nickerson, Neda Jahanshad, Lauren E Salminen, Sophia I Thomopoulos, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam van Zuiden, Ye Zhu, Gen Li, Jonathan Ipser, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Delin Sun, Ahmed Hussain, Ashley A Huggins, Tanja Jovanovic, Sanne J H van Rooij, Negar Fani, Anna R Hudson, Anika Sierk, Antje Manthey, Henrik Walter, Nic J A van der Wee, Steven J A van der Werff, Robert R J M Vermeiren, Pavel Říha, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Israel Liberzon, Mike Angstadt, Seth G Disner, Scott R Sponheim, Sheri-Michelle Koopowitz, David Hofmann, Rongfeng Qi, Adi Maron-Katz, Austin Kunch, Hong Xie, Wissam El-Hage, Hannah Berg, Steven E Bruce, Katie A McLaughlin, Matthew Peverill, Kelly Sambrook, Marisa Ross, Ryan J Herringa, Jack B Nitschke, Richard J Davidson, Terri A deRoon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Steven M Nelson, Evan M Gordon, Maria Densmore, Jean Théberge, Richard W J Neufeld, Miranda Olff, Li Wang, Dan J Stein, Yuval Neria, Jennifer S Stevens, Sven C Mueller, Judith K Daniels, Ivan Rektor, Anthony King, Nicholas D Davenport, Thomas Straube, Guangming Lu, Amit Etkin, Xin Wang, Yann Quidé, Shmuel Lissek, Josh Cisler, Daniel W Grupe, Christine Larson, Brandee Feola, Geoffrey May, Chadi G Abdallah, Ruth Lanius, Paul M Thompson, Rajendra A Morey, Kerry Ressler","doi":"10.1101/2025.03.18.25324188","DOIUrl":"https://doi.org/10.1101/2025.03.18.25324188","url":null,"abstract":"<p><strong>Background: </strong>Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust - and potentially a pretrauma - marker of vulnerability.</p><p><strong>Methods: </strong>We analyzed data from the ENIGMA-PTSD dataset (n = 2,814) and the Human Connectome Project - Young Adult (HCP-YA) dataset (n = 890) to investigate whether structural covariance of early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress.</p><p><strong>Results: </strong>Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms and no association was observed between loadings and perceived stress measures in the HCP-YA dataset.</p><p><strong>Conclusion: </strong>Structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of GGC Repeat Expansions in <i>ZFHX3</i> Among Chilean Movement Disorder Patients.","authors":"Paula Saffie-Awad, Abraham Moller, Kensuke Daida, Pilar Alvarez Jerez, Zhongbo Chen, Zachary B Anderson, Mariam Isayan, Kimberly Paquette, Sophia B Gibson, Madison Fulcher, Abigail Miano-Burkhardt, Laksh Malik, Breeana Baker, Paige Jarreau, Henry Houlden, Mina Ryten, Bida Gu, Mark Jp Chaisson, Danny E Miller, Pedro Chaná-Cuevas, Cornelis Blauwendraat, Andrew B Singleton, Kimberley J Billingsley","doi":"10.1101/2025.03.17.25323863","DOIUrl":"https://doi.org/10.1101/2025.03.17.25323863","url":null,"abstract":"<p><strong>Background: </strong>Hereditary ataxias are genetically diverse, yet up to 75% remain undiagnosed due to technological and financial barriers. A pathogenic <i>ZFHX3</i> GGC repeat expansion was recently linked to spinocerebellar ataxia type 4 (SCA4), characterized by progressive ataxia and sensory neuropathy, with all reported cases in individuals of Northern European ancestry.</p><p><strong>Methods: </strong>We performed Oxford Nanopore Technologies (ONT) genome long-read sequencing (>115 GB per sample) on a total of 15 individuals from Chile; 14 patients with suspected hereditary movement disorders and one unrelated family member. Variants were identified using PEPPER-Margin-DeepVariant 0.8 (SNVs), Sniffles 2.4 (SVs), and Vamos 2.1.3 (STRs). Ancestry was inferred using GenoTools with reference data from the 1000 Genomes Project, Human Genome Diversity Project, and an Ashkenazi Jewish panel. Haplotype analysis was conducted by phasing SNVs within <i>ZFHX3</i> , and methylation profiling was performed with modbamtools.</p><p><strong>Results: </strong>We identified <i>ZFHX3</i> GGC repeat expansions (47-55 repeats) in four individuals with progressive ataxia, polyneuropathy, and vermis atrophy. One case presented parkinsonism-ataxia, expanding the phenotype. Longer expansions correlated with earlier onset and greater severity. Hypermethylation was detected on the expanded allele, and haplotype analysis linked ultra-rare <i>ZFHX3</i> variants to distant Swedish ancestry.</p><p><strong>Conclusion: </strong>This is the first report of SCA4 outside Northern Europe, confirming a shared founder haplotype and expansion instability. The presence of parkinsonism broadens the clinical spectrum. Comprehensive genetic testing across diverse populations is crucial, and long-read sequencing enhances diagnostic yield by detecting repeat expansions and SNVs in a single assay.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Self-reported and Device-Derived Sleep Quality in a Sample of Older Adults with Chronic Musculoskeletal Pain.","authors":"Soamy Montesino-Goicolea, Pedro Antonio Valdes-Hernandez, Olga Nin, Cameron Smith, Eric C Porges, Yenisel Cruz-Almeida","doi":"10.1101/2025.03.17.25324131","DOIUrl":"https://doi.org/10.1101/2025.03.17.25324131","url":null,"abstract":"<p><strong>Objectives: </strong>Our primary aim was to evaluate the agreement between subjective and objective methods of measuring sleep quality in a musculoskeletal pain sample. Secondly, we aimed to explore the relationship between subjective and objective sleep quality-and its impact on function-and clinical and experimental pain.</p><p><strong>Methods: </strong>We assessed subjective sleep using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep using the Oura ring-a wearable characterizing sleep stages. Participants had musculoskeletal pain (intensity>4/10 most days in past 3 months) and poor sleep (PSQI total>5). To enable direct comparisons, via correlations, between subjective and objective sleep (primary aim), we emulated the equivalent of PSQI's answers and components by averaging the appropriate Oura data over the month covered by the PSQI. We used partial correlations to assess sleep-pain relationships (second aim)-controlling for age and sex.</p><p><strong>Results: </strong>Answers to PSQI questions about total bedtime and sleep duration, and the PSQI duration component, correlated with their Oura equivalents, whereas PSQI failed to capture Oura's Sleep Latency, Efficiency, and Disturbances. On the other hand, PSQI total score and its sleep latency component correlated with WOMAC-pain score, MPQ scores (total, neuropathic, continuous, and intermittent) and GCPS-pain intensity, while Oura's Sleep Latency correlated with conditioned pain modulation. No significant association between Oura measures and pain was found.</p><p><strong>Conclusions: </strong>The findings highlight the complementary roles of subjective and objective measures and the need for integrated approaches to refine sleep assessments in musculoskeletal pain. Future studies should investigate the causes of these discrepancies to enhance understanding of sleep-related health outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome-wide association studies at cell state level using single-cell eQTL data.","authors":"Guanghao Qi, Eardi Lila, Zhicheng Ji, Ali Shojaie, Alexis Battle, Wei Sun","doi":"10.1101/2025.03.17.25324128","DOIUrl":"https://doi.org/10.1101/2025.03.17.25324128","url":null,"abstract":"<p><p>Transcriptome-wide association studies (TWAS) have been widely used to prioritize relevant genes for diseases. Current methods for TWAS test gene-disease associations at bulk tissue or cell-type-specific pseudobulk level, which do not account for the heterogeneity within cell types. We present TWiST, a statistical method for TWAS analysis at cell state resolution using single-cell expression quantitative trait loci (eQTL) data. Our method uses pseudotime to represent cell states and models the effect of gene expression on trait as a continuous pseudotemporal curve. Therefore, it allows flexible hypothesis testing of global, dynamic, and nonlinear effects. Through simulation studies and real data analysis, we demonstrated that TWiST leads to significantly improved power compared to pseudobulk methods that ignores heterogeneity due to cell states. Application to the OneK1K study identified hundreds of genes with dynamic effects on autoimmune diseases along the trajectory of immune cell differentiation. TWiST presents great promise to understand disease genetics using single-cell eQTL studies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Structural Cardiovascular Disease, HIV, and Tuberculosis in East Africa (ASANTE): Cross-sectional study protocol for a multimodal cardiac imaging study in Nairobi, Kenya.","authors":"Saate S Shakil, Sidney Korir, Geoffrey Omondi, Boni Maxime Ale, Bernard Gitura, Marian Morris Tofeles, John Kinuthia, Bhavna Chohan, Norrisa Haynes, Carey Farquhar, Priscilla Y Hsue, Chris T Longenecker, Alfred O Osoti","doi":"10.1101/2025.03.16.25323832","DOIUrl":"https://doi.org/10.1101/2025.03.16.25323832","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Persons living with HIV (PLWH) have an augmented risk of cardiovascular disease, including atherosclerosis and myocardial dysfunction, despite effective viral suppression with antiretroviral therapy (ART). Despite the majority of PLWH residing in sub-Saharan Africa, there are limited reports from the region on structural cardiovascular changes due to this residual risk.Methods and analysisThe Early Structural Cardiovascular Disease, HIV, and Tuberculosis (ASANTE) cross-sectional study will be conducted in a public hospital in Nairobi, Kenya. It will enroll 400 participants (50% female, 50% PLWH) to undergo comprehensive cardiovascular phenotyping using multimodal imaging (coronary CT angiography [CCTA], echocardiography) and banking of biological samples (whole blood, peripheral blood mononuclear cells, serum, and urine). We will define the prevalence of subclinical coronary atherosclerosis by coronary CT angiography (CCTA) and subclinical myocardial dysfunction by transthoracic echocardiography, and evaluate both traditional and non-traditional risk factors, including endemic infections such as latent tuberculosis. This study will contribute important data on phenotypes of and risk factors for HIV-associated cardiovascular disease in this under-studied region.Ethics and disseminationEthical approval for the ASANTE study was granted by the University of Nairobi-Kenyatta National Hospital Ethical Review Committee, Nairobi, Kenya. Results will be submitted for publication in peer-reviewed journals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/strong&gt;&lt;b&gt;What is already known on this topic:&lt;/b&gt; In studies from high-income countries, HIV infection is an independent risk factor for structural cardiovascular abnormalities (atherosclerosis, myocardial remodeling) and corresponding incident cardiovascular events.Emerging data from sub-Saharan Africa suggest there may be a unique epidemiological profile, in which HIV and traditional cardiometabolic risk factors (e.g., hypertension, diabetes, overweight/obesity, smoking) are not associated with coronary atherosclerosis.Unique endemic risk factors for cardiovascular disease in HIV have yet to be defined in sub-Saharan Africa.&lt;b&gt;What this study adds:&lt;/b&gt; We will define the prevalence of and risk factors for subclinical coronary atherosclerosis and myocardial disease in a cohort of Kenyan adults with and without HIV who have been enriched for cardiometabolic risk factors using multimodal imaging (coronary CT angiography, speckle tracking echocardiography).We will assess the contribution of latent tuberculosis infection as a potential endemic risk factor for subclinical cardiovascular abnormalities identified on multimodal imaging.&lt;b&gt;How this study might affect research, practice, or policy:&lt;/b&gt; Delineating the burden, phenotypes, and unique risk factors for early cardiovascular disease in this setting will facilitate tailored interventions for screening, monitoring, and management among pers","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression Risk and Work Hours in Training Physicians Before and During the COVID-19 Pandemic.","authors":"Jennifer L Cleary, Karina Pereira-Lima, Xianda Ma, Lihong Chen, Margit Burmeister, Lisa M Meeks, Zhuo Zhao, Jun Ye, Yu Fang, Zhenke Wu, Elena Frank, Ruyuan Zhang, Suhua Zeng, Qian Zhao, Douglas A Mata, Amy Bohnert, Weidong Li, Srijan Sen","doi":"10.1101/2025.03.09.25323517","DOIUrl":"https://doi.org/10.1101/2025.03.09.25323517","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;In the general population, depression increased with the onset of the COVID-19 pandemic. In addition to the general pandemic impact, training physicians faced many sudden and dramatic changes in their training environment. However, the effects of these changes on the mental health of training physicians remains unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To identify change in depression risk among training physicians with the onset of the COVID-19 pandemic and factors associated with risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Prospective cohort study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;University- and community-based health care institutions in the United States and Shanghai, China.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;First-year resident physicians (interns) serving during the 2018-19 (n=1844), 2019-20 (n=1201), and 2020-21 (n=2448) academic years (U.S. sample); interns serving during the 2021-22 academic year (n=471) (Shanghai sample).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measurements: &lt;/strong&gt;Depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) and work hours were assessed quarterly for all U.S. cohorts. The 2019-20 cohort completed supplemental surveys of these measures in April and May 2020. Shanghai sample interns were assessed for depressive symptoms (PHQ-9) and work hours quarterly before, during, and after the 2022 lockdown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Within the 2019-20 U.S. cohort, depressive symptom scores decreased from the pre-pandemic (September, December) to the pandemic period (April, May, June) (5.5 [3.9] vs. 4.9 [4.3], &lt;i&gt;p&lt;/i&gt; &lt;0.001). In causal mediation analysis, 62% of this change was mediated through work hours (0.62, 95% CI [0.44-1.00]). Descriptive comparisons of this cohort with cohorts training immediately before (2018-19) and after (2020-21) the pandemic onset demonstrated that both work hours and depressive symptoms were significantly lower in spring 2020, but returned to pre-pandemic levels by fall 2020. In the parallel Shanghai cohort serving during the April 2022 lockdown, we found a similar magnitude drop in depressive symptoms (5.6 [3.3] vs. 4.9 [4.8], p=0.005), with 64% of the effect mediated through work hours (0.64, 95% CI [0.24-1.84]).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Interns experienced a 11% decrease in depressive symptoms with the onset of the pandemic, which was primarily driven by reduced work hours. The identified associations between work hours and depressive symptoms early in the pandemic may inform strategies to support physician wellness moving forward.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;&lt;b&gt;Question:&lt;/b&gt; How did depressive symptoms in training physicians change during the COVID-19 pandemic?&lt;b&gt;Findings:&lt;/b&gt; In a prospective cohort study including 1201 U.S. first-year residents during the 2019-2020 academic year, we found an 11% decrease in depressive symptoms with the pandemic onset. Causal mediation analysis identified that work hours mediated 62% of t","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Parkinson's Disease Genetic Risk Factors Within and Across European Populations.","authors":"Hampton L Leonard","doi":"10.1101/2025.03.14.24319455","DOIUrl":"https://doi.org/10.1101/2025.03.14.24319455","url":null,"abstract":"<p><strong>Introduction: </strong>We conducted a meta-analysis of Parkinson's disease genome-wide association study summary statistics, stratified by source (clinically-recruited case-control cohorts versus population biobanks) and by general European versus European isolate ancestries. This study included 63,555 cases, 17,700 proxy cases with a family history of Parkinson's disease, and 1,746,386 controls, making it the largest investigation of Parkinson's disease genetic risk to date.</p><p><strong>Methods: </strong>Meta-analyses were performed using standard fixed and random effect models for the European sub-populations, the case-control studies, and the population biobanks separately. Finally, all of the European ancestries for all study types as well as proxy cases were combined in our final cross-European meta-analysis. We estimated heritable risk across ancestry groups, investigated tissue and cell-type enrichment, and prioritized risk genes using public data to facilitate functional follow-up efforts.</p><p><strong>Results: </strong>The final combined cross-European meta-analysis identified 134 risk loci (59 novel), with a total of 157 independent signals, significantly expanding our understanding of Parkinson's disease risk. Multi-omic data integration revealed that expression of the nominated risk genes are highly enriched in brain tissues, particularly in neuronal and astrocyte cell types. Additionally, we prioritized 33 high-confidence genes across these 134 loci for future follow-up studies.</p><p><strong>Conclusions: </strong>By integrating diverse European populations and leveraging harmonized data from the Global Parkinson's Genetics Program (GP2), we reveal new insight into the genetic architecture of Parkinson's disease. We identified a total of 134 risk loci, expanding the number of known loci associated with PD by approximately 24%. We also provided an initial layer of biological context to these results through follow-up analyses in an effort to facilitate follow-up studies and precision medicine efforts with the goal of advancing Parkinson's disease research.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}