medRxiv : the preprint server for health sciences最新文献

{"title":"Polygenic Background and Penetrance of Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies.","authors":"Sarah A Abramowitz, Lily Hoffman-Andrews, David Zhang, Renae Judy, Thomas P Cappola, Sharlene M Day, Nosheen Reza, Anjali T Owens, Scott M Damrauer, Michael G Levin","doi":"10.1101/2025.06.20.25329138","DOIUrl":"10.1101/2025.06.20.25329138","url":null,"abstract":"<p><strong>Importance: </strong>Polygenic background modifies variant penetrance in hypertrophic (HCM) and dilated (DCM) cardiomyopathy, diseases with opposing morphologic characteristics and inversely related genetic pathways. Whether polygenic susceptibility for one disease protects against monogenic risk for the other remains unexplored.</p><p><strong>Objective: </strong>To characterize if polygenic background bidirectionally modifies pathogenicity of established rare variants associated with HCM and DCM.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Setting: </strong>The Penn Medicine BioBank (PMBB).</p><p><strong>Participants: </strong>Volunteers enrolled in PMBB with available electronic health record and genotyping data.</p><p><strong>Exposures: </strong>Normalized polygenic scores (PGS) for HCM and DCM, as well as carrier status of pathogenic variants in established HCM or DCM genes.</p><p><strong>Main outcomes: </strong>HCM and DCM defined using electronic health record diagnosis and procedure code, as well as echocardiogram measurements derived from medical records.</p><p><strong>Results: </strong>This study included 49,434 PMBB participants. An increased HCM PGS was associated with significantly increased left ventricular ejection fraction (LVEF), decreased left ventricular internal diameter at end-diastole (LVIDd), and increased interventricular septal thickness (IVS) (p<0.001). An increased DCM PGS was significantly (p<0.001) associated with decreased LVEF and increased LVIDd, but was not associated with IVS. A one standard deviation increase in HCM PGS was associated with increased risk of HCM (OR 1.8; 95% CI 1.6-2.0; p=9.6×10^-25) and decreased risk of DCM (OR 0.69; 95% CI 0.64-0.74; p=4.3×10^-22). A one standard deviation increase in DCM PGS was associated with an increased risk of DCM (OR 1.6; 95% CI 1.5-1.7; p=1.7×10^-40) and decreased risk of HCM (OR 0.69; 95% CI 0.63-0.76; p=3.0×10^Ȓ13). Monogenic and polygenic risk terms had significant, independent effects when combined in models of disease status and echocardiographic measurements; the additional inclusion of either an HCM or DCM PGS improved the discrimination of models of HCM and DCM that included age, sex, and monogenic variant status (>95% probability of difference in AUROC).</p><p><strong>Conclusions and relevance: </strong>HCM and DCM risk are markedly modified by polygenic background which exists on an overlapping spectrum. Consideration of polygenic background may offer clinical value through improving understanding and prediction of these inherited cardiomyopathies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532316","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":"Harmonization of cerebral blood flow measurements by multi-delay 3D gradient and spin echo, and single-delay 2D echo planar imaging.","authors":"Josiah B Lewis, Chunwei Ying, Michael M Binkley, Melanie E Fields, Igor Dedkov, Slim Fellah, Jingyi Zhang, Amy Mirro, Joshua S Shimony, Yasheng Chen, Jin-Moo Lee, Andria L Ford, Hongyu An, Kristin P Guilliams","doi":"10.1101/2025.06.20.25328792","DOIUrl":"10.1101/2025.06.20.25328792","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Cerebral blood flow (CBF) is commonly measured by pseudo-continuous arterial spin labeling (PCASL) in human research, but recent advancements in methodology have limited data reuse. The object of this work is to harmonize two distinct PCASL techniques within a cohort with a wide range of CBF values.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Participants had two PCASL sequences collected within a single session: a single post-label delay sequence with a 2D echo-planar imaging (EPI) readout, \" &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;1&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; \", and a five post-label delay sequence with gradient and spin echo (GRASE) 3D readout, \" &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;5&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; \". Linear regression modeling to impute &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;5&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; from &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;1&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; , hemoglobin, and age were assessed within gray matter (GM) and white matter (WM) using leave-one-out cross-validation for prediction errors and confidence intervals. Within-subject coefficient of variation (wsCV) and inter-class correlation coefficient (ICC) were calculated using &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;5&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; imputed vs. measured as pseudo test-retest pairs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fifty participants, ages 8-45 (median 25) years, had usable &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;5&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; and &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;1&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; , including 17 participants with sickle cell disease (SCD), who were matched by age ( &lt;math&gt;&lt;mi&gt;p&lt;/mi&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;0.90&lt;/mn&gt;&lt;/math&gt; ) and sex ( &lt;math&gt;&lt;mi&gt;p&lt;/mi&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;0.16&lt;/mn&gt;&lt;/math&gt; ) to those without SCD. A multiple linear regression model including hemoglobin and age fit GM CBF ( &lt;math&gt; &lt;msub&gt; &lt;mrow&gt; &lt;msup&gt;&lt;mrow&gt;&lt;mtext&gt;R&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msup&gt; &lt;/mrow&gt; &lt;mrow&gt;&lt;mtext&gt;adj.&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;0.82&lt;/mn&gt;&lt;/math&gt; ; for WM CBF &lt;math&gt; &lt;msub&gt; &lt;mrow&gt; &lt;msup&gt;&lt;mrow&gt;&lt;mtext&gt;R&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msup&gt; &lt;/mrow&gt; &lt;mrow&gt;&lt;mtext&gt;adj.&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;0.78&lt;/mn&gt;&lt;/math&gt; ). The wsCV for &lt;math&gt; &lt;msub&gt;&lt;mrow&gt;&lt;mtext&gt;CBF&lt;/mtext&gt;&lt;/mrow&gt; &lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt; &lt;mtext&gt;D&lt;/mtext&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;5&lt;/mn&gt; &lt;mtext&gt;PLD&lt;/mtext&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/math&gt; was 9.1% for GM, 11.3% for WM. ICC was 0.89 for GM and 0.87 for WM. Models without age or hemoglobin fit slight","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532274","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":"Utilizing virus genomic surveillance to predict vaccine effectiveness.","authors":"Jiye Kwon, Ke Li, Joshua L Warren, Sameer Pandya, Anne M Hahn, Virginia E Pitzer, Daniel E Weinberger, Nathan D Grubaugh","doi":"10.1101/2025.06.20.25329795","DOIUrl":"https://doi.org/10.1101/2025.06.20.25329795","url":null,"abstract":"<p><p>As new vaccines are being developed for fast-evolving viruses, determining when and how to update them, and what data should inform these decisions, remains a significant challenge. We developed a model to inform these vaccine updates in near real-time and applied it to SARS-CoV-2 by quantifying the relationship between vaccine effectiveness (VE) and genetic distance from mRNA vaccine formulation sequences using 10,156 genomes from Connecticut (April 2021-July 2024) and data from over one million controls, employing a two-stage statistical approach. We showed a strong inverse correlation between spike gene amino acid distance and VE; every 10 amino acid substitutions away from the vaccine sequences resulted in a 15.4% (95% credible intervals (CrI): -2.0%, 34.6%) reduction in VE. Notably, this framework allows us to quantify the anticipated impact of emerging variants on VE, as demonstrated by the predicted 43.4% (95% CrI: -5.7%, 90.1%) drop in VE for the 2023/24 vaccine following the emergence of JN.1 variants based on sequence data alone. By linking amino acid substitutions to VE, this approach leverages genomic surveillance to monitor population-level protection and inform timely vaccine updates.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532352","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":"SmokeBERT: A BERT-based Model for Quantitative Smoking History Extraction from Clinical Narratives to Improve Lung Cancer Screening.","authors":"Yiming Xue, Yunzheng Zhu, Luoting Zhuang, YongKyung Oh, Ricky Taira, Denise R Aberle, Ashley E Prosper, William Hsu, Yannan Lin","doi":"10.1101/2025.06.18.25329870","DOIUrl":"10.1101/2025.06.18.25329870","url":null,"abstract":"<p><p>Tobacco use is a critical risk factor for diseases such as cancer and cardiovascular disorders. While electronic health records can capture categorical smoking statuses accurately, granular quantitative details, such as pack years and years since quitting, are often embedded in clinical narratives. This information is crucial for assessing disease risk and determining eligibility for lung cancer screening (LCS). Existing natural language processing (NLP) tools excelled at identifying smoking statuses but struggled with extracting detailed quantitative data. To address this, we developed SmokeBERT, a fine-tuned BERT-based model optimized for extracting detailed smoking histories. Evaluations against a state-of-the-art rule-based NLP model demonstrated its superior performance on F1 scores (0.97 vs. 0.88 on the hold-out test set) and identification of LCS-eligible patients (e.g., 98% vs. 60% for ≥20 pack years). Future work includes creating a multilingual, language-agnostic version of SmokeBERT by incorporating datasets in multiple languages, exploring ensemble methods, and testing on larger datasets.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532256","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":"Integrated treatment-decision algorithms for childhood TB: modelling diagnostic performance and costs.","authors":"Mary Gaeddert, Devan Jaganath, Abdulkadir Civan, Hoa Nguyen, Maryline Bonnet, Eric Wobudeya, Olivier Marcy, Manuela De Allegri, Claudia M Denkinger","doi":"10.1101/2025.06.20.25329945","DOIUrl":"10.1101/2025.06.20.25329945","url":null,"abstract":"<p><strong>Background: </strong>To improve childhood tuberculosis (TB) diagnosis, treatment-decision algorithms (TDAs) with and without chest X-ray (CXR) were developed for children under age 10. We aimed to model diagnostic performance and costs of implementing TDAs in primary healthcare (PHC) and district hospital (DH) settings in Uganda.</p><p><strong>Methods: </strong>We developed decision-tree models following the TDA pathway from evaluation to treatment-decision. We compared six scenarios with combinations of diagnostic testing (stool and respiratory Xpert, urine lipoarabinomannan, and/or CXR) at PHCs and DHs. Outcomes were diagnostic accuracy and cost per correct treatment-decision for a cohort of 10,000 children with presumptive TB using a Monte Carlo simulation from a health system perspective. Costs were reported in 2024 International dollars.</p><p><strong>Results: </strong>In all scenarios, TDA's had high sensitivity (80.8-91.9%) but low specificity (51.2-60.9%). Total diagnostic and treatment costs for the cohort were I$1,768,958-2,458,790; largely driven by overtreatment of false-positive cases. Diagnostic costs were mostly offset by reducing overtreatment. The cost per treatment-decision was lowest using mobile CXR at PHC (I$287.40) and highest with DH referral (I$445.84).</p><p><strong>Conclusion: </strong>The TDAs have high sensitivity and can be implemented at PHCs with lower costs than DHs. Improving specificity and reducing treatment costs would enable affordable, large-scale implementation.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532230","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":"Chronic Disease and Risk Factor Prevalence in Multiracial Subgroups: California, 2014-2023.","authors":"Tracy Lam-Hine, Michelle C Odden, Aliya Saperstein, Tainayah W Thomas, David H Rehkopf","doi":"10.1101/2025.06.19.25329941","DOIUrl":"10.1101/2025.06.19.25329941","url":null,"abstract":"<p><strong>Background: </strong>Multiracial adults represent a growing U.S. population but are often grouped together or reassigned to single-race categories in public health data. Aggregation can obscure important variation across subgroups, limiting opportunities for targeted prevention.</p><p><strong>Methods: </strong>We analyzed 2014-2023 California Behavioral Risk Factor Surveillance System data (n=100,177) to estimate prevalence of 28 health indicators across racial and ethnic groups, including disaggregated Multiracial subgroups. We categorized participants based on all self-identified races and aggregated subgroups with N<50. We standardized prevalence by age and sex using 2020 California census data, calculated relative standard errors, and used survey-weighted methods to compare prevalence and subgroup differences.</p><p><strong>Results: </strong>Among 100,177 participants, Multiracial subgroups had the highest prevalence for 24 of 28 outcomes. American Indian or Alaska Native-Black and Hispanic-Black-White adults had the highest prevalence of chronic conditions, poor general health, and disability. In contrast, Asian Multiracial subgroups (e.g., Asian-Black, Asian-Pacific Islander) more often had the lowest prevalence, though Asian-White adults were not consistently the healthiest subgroup. Differences across Multiracial subgroups exceeded 20 percentage points for nearly half of all outcomes.</p><p><strong>Discussion: </strong>Wide health variation among Multiracial adults is masked by common aggregation practices. Subgroups with the highest burden may be overlooked if data are not routinely disaggregated. Public health surveillance systems should expand capacity to collect and report disaggregated race and ethnicity data to better inform prevention strategies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532271","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":"West Nile morbidity and mortality in a Mid-Atlantic healthcare system, 2013-2024.","authors":"Seth D Judson, Paul Auwaerter, David Dowdy","doi":"10.1101/2025.06.18.25329873","DOIUrl":"10.1101/2025.06.18.25329873","url":null,"abstract":"<p><p>We investigated West Nile cases in a Mid-Atlantic healthcare system, finding significant morbidity and mortality from neuroinvasive disease, notably among immunocompromised patients. Encephalitis was the most common complication and was associated with increased age, alcohol use disorder, immunocompromised status, and a higher Charlson Comorbidity Index.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532354","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":"Anisotropy boosting improves ODF-Fingerprinting tractography in edematous brain.","authors":"Patryk Filipiak, Kamri Clarke, Timothy M Shepherd, Mary Bruno, Dimitris G Placantonakis, Steven H Baete","doi":"10.1101/2025.06.18.25329353","DOIUrl":"https://doi.org/10.1101/2025.06.18.25329353","url":null,"abstract":"<p><p>Peritumoral vasogenic edema of the brain is a major confounding factor for diffusion MRI tractography. Excessive fluids accumulated in edematous white matter decrease anisotropy of water self-diffusion which affects tracking algorithms. We address this hurdle with ODF-Fingerprinting (ODF-FP) - a dictionary-based fiber reconstruction algorithm that accommodates variability of neural tissue. By adding a regularization term to the ODF-FP matching formula, we boost diffusion anisotropy to improve white matter fiber identification in edematous regions.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532241","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":"Association of Pulmonary Artery Compliance and Adverse Cardiac Events.","authors":"Louisa A Mounsey, Sophie M Nemeth, Leah B Kosyakovsky, Jenna N McNeill, Michael H Picard, Eugene V Pomerantsev, Juhi K Parekh, Noah Schoenberg, David Furfaro, Cyrus Kholdani, Jennifer E Ho","doi":"10.1101/2025.06.19.25329923","DOIUrl":"https://doi.org/10.1101/2025.06.19.25329923","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary artery compliance (PAC), the ratio of stroke volume to pulmonary artery pulse pressure, reflects the pulsatile component of right ventricular afterload. While lower PAC is associated with right heart failure (HF) and death in patients with pulmonary arterial hypertension, the association of PAC with clinical outcomes among individuals with a broader range of cardiopulmonary comorbidities is unclear.</p><p><strong>Methods: </strong>We examined consecutive ambulatory and hospitalized patients undergoing clinically indicated right heart catheterization at a single center between 2005 and 2016. Multivariable Cox models were used to investigate the association of PAC with clinical outcomes including HF hospitalization and mortality. Analyses were stratified by presence and absence of pulmonary hypertension (PH) and by PH hemodynamic subtype.</p><p><strong>Results: </strong>Among 7966 patients (mean age 63 years, 39% women), median PAC was 3.29 (IQR 2.19, 4.70) mL/mmHg. PAC was significantly inversely associated with mortality (HR 0.59 per 1-SD higher PAC, 95% CI 0.56, 0.63) and HF hospitalization (HR 0.56, 95% CI 0.52, 0.59) across the whole sample and among those with PH (mortality: HR 0.69, 95% CI 0.64, 0.74, HF: HR 0.65, 95% CI 0.61, 0.70) and without PH (mortality: HR 0.74, 95% CI 0.66, 0.84, HF: HR 0.72, 95% CI 0.61, 0.85). Similarly, PAC was associated with mortality across all PH subtypes: precapillary PH (HR 0.56, 95% CI 0.48, 0.65), combined PH (HR 0.75, 95% CI 0.66, 0.86) and isolated post-capillary PH (HR 0.88, 95% CI 0.79, 0.98).</p><p><strong>Conclusions: </strong>Among patients undergoing clinically indicated right heart catheterization, lower PAC is associated with adverse outcomes irrespective of presence or absence of PH. Our findings support potential clinical utility of PAC in risk stratification across a broad spectrum of cardiopulmonary disease.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532244","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":"Rapidly Progressing Glaucoma: Clinical, Structural, and Socioeconomic Drivers of Treatment Escalation.","authors":"Lok Hin Lee, Yangyiran Xie, Chris Bradley, Jithin Yohannan","doi":"10.1101/2025.05.18.25327880","DOIUrl":"https://doi.org/10.1101/2025.05.18.25327880","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate clinical and sociodemographic factors associated with selecting treatments in glaucoma patients with rapid visual field (VF) progression.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Participants: </strong>2,782 eyes from 1,812 adults with 5 or more 24-2 visual fields over five years and at least one optical coherence tomography (OCT) scan.</p><p><strong>Methods: </strong>Rapid progressors were defined by mean deviation (MD) slopes worse than -1 dB/year. Demographic (age, gender, race), clinical (intraocular pressure (IOP), VF metrics, OCT measures), and socioeconomic (social vulnerability index, or SVI) variables were collected. Patients were categorized based on the most intensive treatment received in the first seven years: medical management, minimally invasive procedures (e.g., minimally invasive glaucoma surgery or laser), or aggressive procedures (e.g., filtering surgery or external ciliodestruction). Logistic regression was performed to identify demographic, clinical, and socioeconomic factors associated with treatment intensity.</p><p><strong>Main outcome measures: </strong>Odds of treatment selection based on rapid VF progression.</p><p><strong>Results: </strong>Rapid progressors had significantly higher odds of receiving aggressive procedures (odds ratio [OR] 3.83, 95% confidence interval [CI] 2.56-5.74, p < 0.001) and any procedure (OR 3.15, 95% CI 2.28-4.35, p < 0.001), yet only 23% of rapid progressors underwent aggressive procedures in the first seven years. Among rapid progressors, worse MD and smaller rim area predicted aggressive procedures and higher IOP predicted any procedure. Higher SVI was associated with a reduced likelihood of receiving minimally invasive procedures among rapid progressors (OR 0.05, 95% CI 0.00-0.76, p = 0.031).</p><p><strong>Conclusion: </strong>Although rapid progression was a strong predictor of aggressive procedures, fewer than one in four underwent aggressive IOP-lowering interventions. Baseline IOP and structural severity appeared to supersede VF progression in clinical decisions. Patients in areas of higher socioeconomic vulnerability were also less likely to receive less invasive procedures. Better integrating rates of functional decline and addressing socioeconomic barriers may help optimize care for rapidly progressing glaucoma patients.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532326","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}