medRxiv : the preprint server for health sciences最新文献

{"title":"Endometriosis and Early-Onset Cardiovascular Disease Across Levels of Systemic Inflammation: A Cross-Sectional Study of NHANES 1999-2006.","authors":"Chidinma Oli, Natalie Chichetto","doi":"10.64898/2026.09.29.26364168","DOIUrl":"10.64898/2026.09.29.26364168","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis is a chronic gynecologic condition which has been linked with higher cardiovascular disease (CVD) risk. Although systemic inflammation is central to endometriosis and CVD pathophysiology, it remains unclear whether endometriosis is associated specifically with early-onset CVD and whether systemic inflammation modifies this association.</p><p><strong>Methods: </strong>This was a cross-sectional study of 5,345 women aged 20-54 years from the National Health and Nutrition Examination Survey (1999-2006). Endometriosis and early-onset CVD were self-reported. Early-onset CVD was defined as a composite measure of coronary heart disease, angina/angina pectoris, heart attack, congestive heart failure, or stroke. Systemic inflammation was measured using C-reactive protein [CRP; low/moderate (≤3 mg/L) and high (>3mg/L)] and the systemic immune-inflammation index (SII; tertiles). Survey-weighted logistic regression was used to assess associations and heterogeneity by systemic inflammation, with stabilized inverse probability weighting (IPW) to adjust for confounding.</p><p><strong>Results: </strong>Of the 5,435 women, 370 (6.9%) reported an endometriosis diagnosis and 162 (3.0%) early-onset CVD. After IPW adjustment for age, body mass index, smoking status, education, age at menarche, physical activity and race/ethnicity, endometriosis was associated with higher odds of early-onset CVD (prevalence odds ratio [POR] = 1.91, 95% CI: 1.23-2.97). This association was strongest among women with high CRP (POR= 2.33, 95% CI: 1.49-3.66), but not among those with low/moderate CRP levels (p-interaction= 0.086). Across SII strata, the strongest association was observed among women in the medium SII tertile (POR = 2.92, 95% CI: 1.47-5.78), with no associations in the low or high tertiles (p-interaction = 0.288).</p><p><strong>Conclusion: </strong>Endometriosis was associated with higher odds of early-onset CVD in this nationally representative sample of U.S. women. Although the strength of the association varied across CRP and SII strata, formal tests for interaction were not statistically significant. These findings should be understood as exploratory and require further investigation in prospective studies.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167589","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":"Evaluating Precision and Responsiveness of MRI-derived Brain Volumetric and Clinical Outcome Measures in CLN3 Disease.","authors":"Rakibul Hafiz, Cristan Farmer, Lisa Joseph, Ariane Soldatos, Amritha Nayak, Audrey E Thurm, An N Dang Do, Carlo Pierpaoli","doi":"10.64898/2026.09.29.26363931","DOIUrl":"10.64898/2026.09.29.26363931","url":null,"abstract":"<p><strong>Background and objective: </strong>For their acceptance as endpoints in clinical trials, biomarkers and clinical outcome assessment (COA) measures should show reliability by being reproducible (precise) and responsive to change. We evaluated precision and responsiveness of MRI-derived brain volume metrics and various COAs in ceroid-lipofuscinosis, neuronal-3 (CLN3) disease.</p><p><strong>Methods: </strong>This longitudinal observational study (NCT03307304) included 44 individuals with CLN3-related disease (ages 0.5-29.1 years, 48% female). Brain volumetric measures were computed using SynthSeg-v2.0 from T1-weighted 3D MPRAGE images acquired at 3T (Median [Q1, Q3] total MRI follow-up duration from baseline: 2.04 [0.00, 3.69] years). Compartmental tissue volumes were normalized to a model-adjusted total intracranial volume and scaled to the tissue-specific volume fraction expected in healthy adolescent brains to extract measures of brain atrophy. COAs included the Vineland Adaptive Behavior Scales, verbal IQ, and the Unified Batten Disease Rating Scale (UBDRS). Analysis of linear mixed-effects models included only CLN3 participants with syndromic presentation, having three or more visits per measurement to estimate slope, its relative standard error (RSE), and the minimum inter-visit interval (<i>T</i> _<i>min</i> ) for statistically significant progression for each participant. <i>T</i> _<i>min</i> to detect progression in 75% of the population (<i>T</i> _{<i>min,75%</i>} ) was computed for each metric.</p><p><strong>Results: </strong>Among brain volumetric measures, brain parenchyma volume (BPV) and gray matter volume (GMV) were the most precise and responsive metrics. BPV showed an overall <i>intra</i>-individual decline with age of -1.32%/year (95% CI: -1.64% to -0.99%), low RSE of 12.5%, and short <i>T</i> _{<i>min,75%</i>} of 0.85 years (95% CI: 0.47-1.24). Amongst COAs, the UBDRS Clinical Global Impression (CGI) score was the most precise and responsive with an overall <i>intra</i>-individual increase of 1.26 units/year (95% CI: 1.03-1.49), RSE of 24.10%, and <i>T</i> _{<i>min,75%</i>} of 2.56 years (95% CI: 1.73-3.46), though with lower precision (RSE higher) and lower responsiveness (<i>T</i> _{<i>min,75%</i>} longer) than BPV.</p><p><strong>Discussion: </strong>MRI-derived metrics, in particular BPV and GMV, detected change in brain atrophy with high precision and responsiveness suggesting that they would be informative for evaluating potential neuroprotective therapies in CLN3 disease. These findings support incorporating MRI-derived volumetric measurements alongside clinical assessments in future clinical trials in CLN3.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168839","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":"Preindex Social Context and Cardiovascular Events Across Blood Pressure, LDL Cholesterol, and A1c Cohorts.","authors":"Sana Mirza, Joshua Moen","doi":"10.64898/2026.09.28.26364240","DOIUrl":"10.64898/2026.09.28.26364240","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular prevention is organized around target metrics. Blood pressure, LDL cholesterol, and A1c define treatment targets, quality metrics, and, implicitly, who is considered safe. Yet a value below a cutoff is a correlative measurement, not an outcome. We tested whether social context recorded before the measurement separated subsequent cardiovascular events among people whose numbers already met the cutoff.</p><p><strong>Methods: </strong>In this retrospective cohort study, we analyzed All of Us participants without recorded cardiovascular disease and with low comorbidity in three separately indexed cohorts: systolic blood pressure (SBP), LDL cholesterol, and A1c. A preindex score combined household income, education, food security, physical activity, and ZIP-linked deprivation, standardized against a fixed pooled reference of 325,652 eligible people. Cox models adjusted for the measured biomarker value, its square, a score-by-biomarker term, medication exposure, and clinical covariates. The outcome was first myocardial infarction, ischemic stroke, or heart failure. A sensitivity analysis indexed participants at the first measurement after the score became computable and counted only events recorded in inpatient or emergency settings.</p><p><strong>Results: </strong>The SBP, LDL, and A1c cohorts included 19,525, 16,578, and 18,539 participants with 144, 129, and 191 events. Each one-SD more favorable score was associated with lower hazard: HR 0.611 (95% CI 0.498-0.749), 0.631 (0.512-0.778), and 0.544 (0.457-0.648), respectively. Below each study cutoff (SBP <140 mmHg, LDL <100 mg/dL, A1c <8%), less favorable context had event rates of 3.39 versus 1.68, 7.16 versus 2.05, and 8.67 versus 2.34 per 1,000 person-years. In a one-year analysis restricted to 2019-2023 index dates, the corresponding adjusted HRs were 0.530, 0.336, and 0.365. In the sensitivity cohorts (54,338, 41,451, and 33,607 participants; 493, 288, and 316 events), HRs were 0.732 (0.657-0.815), 0.660 (0.573-0.761), and 0.631 (0.552-0.722).</p><p><strong>Conclusions: </strong>A biomarker below the study cutoff did not identify a uniform, low-risk population. Social context recorded before the measurement separated cardiovascular events after adjustment for the measured value and clinical factors. Risk assessment that stops at the number misses this variation.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172271","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 Clinical-Genomic Reanalysis Identifies Diagnostic Gaps and Candidate Genes in a Pediatric Rare Disease Cohort.","authors":"Hyunjung Gu, Aniko Sabo, Sharayu V Jangam, Hirokazu Hashimoto, Christina Y Miyake, Bo Yuan, Charul Gijavanekar, Eric Venner, Viktoriya Korchina, Sarah H Elsea, Donna M Muzny, Elizabeth Mizerik, Blake Vuocolo, Poyyapakkam Srivaths, Lisa F Satter, Sebastian Ochoa, Stephanie Sisley, Polle B Mihindou, Oguz Kanca, Shinya Yamamoto, Zhandong Liu, Michael F Wangler, Richard A Gibbs, Hugo J Bellen, Katherine Y King","doi":"10.64898/2026.09.24.26363679","DOIUrl":"https://doi.org/10.64898/2026.09.24.26363679","url":null,"abstract":"<p><strong>Purpose: </strong>Children with suspected rare genetic disorders often remain undiagnosed after exome, gene panel, or chromosomal microarray testing. We sought to define recurrent missed-diagnosis mechanisms and evaluate an integrated clinical-genomic reanalysis framework.</p><p><strong>Methods: </strong>We studied 75 participants with rare or striking pediatric-onset phenotypes who remained undiagnosed after prior genetic testing. Trio genome sequencing evaluated SNVs, indels and copy-number variants. RNA sequencing was performed in 63 participants to assess aberrant expression and splicing, with targeted follow-up assays used selectively for prioritized variants. Clinician-genome scientist review integrated longitudinal phenotyping, physician input, and inheritance. Unresolved cases underwent research-level candidate prioritization.</p><p><strong>Results: </strong>Clinically reportable findings were returned in 9, including two with multilocus findings: 5 explained the primary phenotype and 4, while not fully explanatory, were clinically relevant and informing surveillance, management, or family follow-up. Previously missed findings reflected technical limitations, including deep intronic splice-altering variants supported by transcriptome analysis and a genomic deletion, and interpretive limitations related to incomplete phenotype integration or narrowly scoped prior testing. Research-level analysis prioritized six candidate genes, including biallelic <i>ACHE</i> variants with reduced enzymatic activity.</p><p><strong>Conclusion: </strong>Integrated clinical-genomic reanalysis framework identified diagnostic gaps, recovered care-informing findings, and prioritized candidate genes for rare disease discovery.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169017","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":"Inflammatory Burden, Structural Exposure, and Racial Disparities in Incident Heart Failure: Evidence from the Multi-Ethnic Study of Atherosclerosis.","authors":"Félix E Rivera-Mariani, Tashoy Campbell, Emily Solomon","doi":"10.64898/2026.09.28.26364238","DOIUrl":"https://doi.org/10.64898/2026.09.28.26364238","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Racial disparities in incident heart failure (HF) are well documented, yet the extent to which systemic inflammatory burden-shaped by structural determinants of environmental exposure-accounts for these disparities remains unquantified in multi-ethnic prospective cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Among 6785 participants in the Multi-Ethnic Study of Atherosclerosis (enrolled 2000-2002; 4 racial/ethnic groups) followed for approximately 16 years, we estimated associations of 4 prespecified baseline inflammatory and hemostatic biomarkers (interleukin-6 [IL-6], C-reactive protein [CRP], fibrinogen, and D-dimer; per 1-SD increment) with incident HF (485 events) using Cox proportional hazards models. A composite inflammatory burden index was derived by principal components analysis. Race × biomarker multiplicative interactions were tested with Holm correction. Sequential biomarker adjustment quantified the percentage of the Black-White log-hazard difference explained relative to a clinical-only model. Robustness to ambient air pollution (PM &lt;sub&gt;2.5&lt;/sub&gt; , NO &lt;sub&gt;2&lt;/sub&gt; ) was assessed in a geocoded subcohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All 4 biomarkers were independently associated with incident HF (IL-6: hazard ratio [HR], 1.20 [95% CI, 1.08-1.34]; D-dimer: 1.18 [1.06-1.30]; CRP: 1.14 [1.02-1.27]; fibrinogen: 1.13 [1.02-1.24]). The composite index (first principal component, 53.7% of variance explained) yielded an HR of 1.25 (1.12-1.39) per 1-SD increase. No multiplicative race × biomarker interaction was detected (all Holm-corrected P=1.0), indicating that the per-SD inflammatory hazard was directionally consistent across groups. Sequential biomarker adjustment reduced the Black-White log-hazard difference by 57.5%, a pattern consistent with-but not sufficient to prove-attenuation by inflammatory pathways. Associations were robust to PM &lt;sub&gt;2.5&lt;/sub&gt; /NO &lt;sub&gt;2&lt;/sub&gt; co-adjustment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Inflammatory and hemostatic burden partially explains the Black-White disparity in incident HF. The null multiplicative interaction pattern indicates that per-unit biological risk is equitable across groups, consistent with differential structural exposure-rather than differential susceptibility-as a primary driver of disparity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical perspective: &lt;/strong&gt;&lt;b&gt;What Is New?&lt;/b&gt; Baseline interleukin-6, C-reactive protein, fibrinogen, and D-dimer were each independently associated with incident heart failure in the Multi-Ethnic Study of Atherosclerosis, and a principal-components composite of the 4 markers outperformed any single marker.The per-SD hazard associated with inflammatory and hemostatic burden was consistent across the 4 racial and ethnic groups, whereas baseline burden was systematically higher among Black and Hispanic participants.Sequential adjustment for the 4-marker panel reduced the Black-White log-hazard difference for incident heart failure by 57.5%. &lt;b&gt;What ","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170627","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":"Delayed Coal Plant Retirements in the Era of Data Centers Carry a Measurable Mortality Cost.","authors":"Suhwan Bong, Gianluca Guidi, Michael Cork, Lucas Henneman, Francesca Dominici","doi":"10.64898/2026.09.29.26364336","DOIUrl":"10.64898/2026.09.29.26364336","url":null,"abstract":"<p><p>Coal-fired power plants remain a major source of fine particulate matter (PM_2.5) exposure and mortality in the United States. Announced retirement dates mark when those burdens are expected to end, but rising electricity demand, partly from data centers supporting cloud computing and artificial intelligence, has led utilities and regulators to revisit them. Of 50 coal plants scheduled in January 2024 to retire before 2035, 20 had later or removed dates by January 2026. Projecting coal PM_2.5 and mortality among Medicare beneficiaries from the 20 plants for 2026-2035, we estimate the revised schedule would result in 1,256 additional deaths (1,136 to 1,376), raising mortality to 3.1 times the original burden. Eighteen plants operate in balancing authorities with hyperscale data-center demand, and federal orders and utility filings supporting several plants' operation cited data-center growth. Retirement schedules are revised faster than health consequences are assessed, and those delays carry a measurable mortality cost.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172220","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":"Predicting Rates of Cognitive Decline in Older Adults with Brain- and Cardiac-Imputed Transcripts.","authors":"Ali Razavi, Nathan R Tucker, Auyon J Ghosh, Stephen V Faraone, Stephen J Glatt, Jonathan L Hess","doi":"10.64898/2026.09.29.26364189","DOIUrl":"10.64898/2026.09.29.26364189","url":null,"abstract":"<p><p>Severe cognitive decline due to dementia is an important clinical indicator signaling neurodegeneration. Predicting cognitive decline rates can be useful in establishing prognosis and modifying treatment regimens. The rate of decline is highly variable across patients with dementia and may be determined by an interplay of many factors. This variability poses challenges to existing tools for predicting disease progression. Changes in heart and brain tissue have been associated with cognitive decline, yet tissue-specific molecular data are difficult to obtain. In this study, we sought to estimate cognitive decline-related transcripts in the brain and heart of people actively living with and without dementia. We reconstructed transcriptomic profiles in brain and heart with the transcriptome-imputation algorithms <i>BrainGENIE</i> and <i>HeartGENIE,</i> and identified several hundreds of transcripts associated with cognitive decline over a two-year assessment window, with the cerebellar hemisphere, left ventricle of the heart, and atrial appendage showing the largest number of cognitive-related transcripts. Pathway analysis revealed an enrichment among cognition-related transcripts of gene sets involved in synaptic, proteostasis/autophagy, immunologic, and mitochondrial respiratory chain functioning. Hundreds of perturbagens show significant concordance with cognitive decline-related transcriptomic signatures in brain and heart, pointing to potentially druggable targets. Top brain- and heart-specific cognition-associated transcripts were incorporated into LASSO regression models predicting future cognitive decline and were compared to two models, one utilizing age, sex and educational attainment, and a hybrid model incorporating both data types. Our models were able to achieve statistically significant correlations in the test set, yet had weak overall. Together, these findings demonstrate that brain and heart transcriptomes capture distinct aspects of biology related to cognitive decline, providing more nuanced insights into normal and aberrant brain aging that may inform drug-repurposing and risk-prediction efforts.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172341","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":"Associations of Outdoor Air Pollution With Cause-specific Mortality in Metastatic Prostate Cancer: A cohort study.","authors":"Andrea Cosenza, David-Dan Nguyen, Zhiyu Qian, Vincenzo Striano, Leonard Appleman, Francesco Montorsi, Alberto Briganti, Giorgio Gandaglia, Benjamin J Davies, Bruce L Jacobs, Quoc-Dien Trinh, Hari S Iyer","doi":"10.64898/2026.09.29.26364034","DOIUrl":"https://doi.org/10.64898/2026.09.29.26364034","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease is an important competing cause of death in men with metastatic prostate cancer, and ambient air pollution may increase cardiovascular vulnerability. We evaluated associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with all-cause, cardiovascular, and prostate cancer-specific mortality, including joint associations with androgen deprivation therapy (ADT).</p><p><strong>Methods: </strong>We analyzed 33,384 men from 11 US state registries diagnosed with metastatic prostate cancer during 2000-2015 and followed through 2018. Residential PM2.5 and NO2 concentrations at diagnosis were assigned using 1-km exposure models. Multivariable Cox models estimated all-cause mortality, and inverse-probability-weighted Cox models assessed cause-specific mortality.</p><p><strong>Results: </strong>Each interquartile-range increase in PM2.5 was associated with higher cardiovascular mortality (HR 1.04, 95% CI 1.02-1.07; p-trend=0.008). Cardiovascular mortality was also higher in the fourth and fifth PM2.5 quintiles versus the first (HR 1.18 and 1.21, respectively). Higher NO2 was associated with prostate cancer-specific mortality in the highest quintile (HR 1.07, 95% CI 1.01-1.13). In joint analyses, ADT-treated men with high versus low PM2.5 exposure had higher cardiovascular mortality (HR 1.19, 95% CI 1.05-1.34), without clear evidence of effect modification (p-interaction=0.051).</p><p><strong>Conclusions: </strong>In men with metastatic prostate cancer, higher PM2.5 exposure was associated with cardiovascular mortality, particularly among ADT-treated patients, supporting further study of environmental exposures and systemic therapy in cardiooncology.</p><p><strong>What this study adds: </strong>Men with metastatic prostate cancer receiving androgen deprivation therapy may be particularly vulnerable to cardiovascular complications. In this large population-based cohort, higher residential PM2.5 exposure was associated with increased cardiovascular mortality, including among men receiving ADT. Although we found no clear evidence that ADT modified the effect of PM2.5, the joint exposure pattern suggests that environmental air pollution may contribute to cardiovascular vulnerability in patients already exposed to cardiometabolic effects of systemic therapy. These findings extend environmental epidemiology to a clinically high-risk cancer population.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170313","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":"Disorder-specific and shared genetic architecture underlying schizophrenia and bipolar disorder.","authors":"Upasana Bhattacharyya, Jibin John, Michael Preuss, Max Lam, Todd Lencz","doi":"10.64898/2026.07.07.26357436","DOIUrl":"10.64898/2026.07.07.26357436","url":null,"abstract":"<p><p>Schizophrenia (SCZ) and bipolar disorder (BIP) share substantial genetic liability, yet exhibit heterogeneity in cognition, illness course and cardiometabolic health. Conventional disorder-level genome-wide association studies (GWASs) aggregate genetic liability obscuring this heterogeneity. We applied zero-phase component analysis whitening and common factor GWAS to SCZ and BIP summary statistics, deriving a shared component (PSY_shared) and two mutually orthogonal, disorder-predominant components (SCZ_~BIP and BIP_~SCZ). We then examined whether the three profiles differed in locus architecture, pathway enrichment, developmental expression and intermediate-phenotype associations. The decomposition identified 261 loci, of which 201 (77%) were component-specific and 16 loci were not reported in any previous larger SCZ and BIP GWASs or multivariate psychosis GWASs. PSY_shared was enriched for synaptic architecture, nuclear organisation and protein trafficking, with developmental signals spanning early- and late-mid-prenatal stages, late infancy and young adulthood. SCZ_~BIP implicated cortical neuronal differentiation, DNA/RNA regulation and protein turnover, with developmental associations in late infancy and young adulthood. BIP_~SCZ showed synaptic release and transport signals, alongside exploratory associations with gene/protein regulation and mitochondrial translation (nominal P < 0.001), with significant developmental enrichment in late infancy. Correlations of SCZ and BIP with intermediate traits were asymmetric, whereas SCZ_~BIP and BIP_~SCZ diverged in opposite directions across cognitive performance, educational attainment, metabolic syndrome, and systemic inflammatory markers. In contrast, both orthogonal components correlated positively with risk taking, with a larger estimate for BIP_~SCZ; PSY_shared showed the largest estimate among the derived components. Steiger tests showed that the components differed significantly across all six phenotypes. Component contrasts were 1.63-2.07-fold greater than corresponding SCZ-BIP contrasts with the increase reaching significance for cognitive performance and metabolic syndrome. These findings support a multidimensional representation of SCZ-BIP liability and provide a framework for testing whether relative component burdens account for variation in cognition, cardiometabolic and inflammatory burden, illness course, and treatment response beyond diagnosis.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475103","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":"Declining Adherence to Dietary Approaches to Stop Hypertension (DASH) Diet Among US Adults with Hypertension: NHANES 2003-2018.","authors":"Vijaya Parameswaran, Anjali Phalke, Christopher Gardner, David J Maron","doi":"10.64898/2026.09.28.26364241","DOIUrl":"https://doi.org/10.64898/2026.09.28.26364241","url":null,"abstract":"<p><strong>Background: </strong>Data from National Health and Nutrition Examination Survey (NHANES) cycles 1988-1994 and 1999-2004 show a declining trend in the adherence to Dietary Approaches to Stop Hypertension (DASH) among adults. Since then, DASH evidence, dietary guidelines, and public-facing dietary resources have advanced, but whether national DASH adherence has improved is uncertain.</p><p><strong>Methods: </strong>We extended the Mellen et al. NHANES analysis among 14,163 adults with self-reported hypertension (N=6,914, 2003-2010, N=7,249, 2011-2018). DASH score included 9 nutrient components: total fat, saturated fat, protein, cholesterol, fiber, calcium, magnesium, potassium, and sodium, with adherence defined as a score ≥4.5. Survey-weighted multivariable models compared DASH score, adherence, and nutrient-threshold attainment across periods.</p><p><strong>Results: </strong>In 2011-2018, U.S. adults with self-reported hypertension represented 76.2 million individuals (33.8%). Multivariable-adjusted DASH adherence declined from 22.1% in 2003-2010 to 18.6% in 2011-2018 (p=0.003), and mean DASH score declined from 2.98 to 2.85 (p=0.007). Adjusted odds of adherence were lower in 2011-2018 compared with 2003-2010 (OR, 0.78; 95% CI, 0.67-0.91; p=0.002). Adherence was lower among non-Hispanic Black adults (OR, 0.70; 95% CI, 0.59-0.84), adults with BMI ≥30 kg/m² (OR, 0.61; 95% CI, 0.51- 0.73), and adults with prior stroke (OR, 0.71; 95% CI, 0.56-0.89). Total fat and sodium threshold attainment declined from 20.9% to 18.7% and 13.8% to 11.8%, respectively.</p><p><strong>Conclusions: </strong>DASH adherence among U.S. adults with self-reported hypertension declined from 2003-2011 to 2011-2018. Implementation strategies should identify barriers to adoption and address the full DASH dietary pattern.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171768","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}