medRxiv : the preprint server for health sciences最新文献

{"title":"Association of Body Composition With Tumor Proteomics and Survival in Patients With Clear Cell Renal Cell Carcinoma.","authors":"Cuthbert Mario Mahenge, Rand Talal Akasheh, Xuan Nguyen, Ting-Yuan David Cheng","doi":"10.1101/2025.09.19.25336108","DOIUrl":"https://doi.org/10.1101/2025.09.19.25336108","url":null,"abstract":"<p><strong>Background: </strong>Prognoses for patients with clear cell renal cell carcinoma (ccRCC) are associated with complex interactions between tumor and patient characteristics. This study investigated associations between body composition and tumor proteomics and their interaction with survival among patients with ccRCC.</p><p><strong>Methods: </strong>Data from 178 patients in the TCGA-KIRC project were analyzed to assess adipose and skeletal muscle tissue areas at the third lumbar vertebra of diagnostic computed tomography scan images. Patients were classified into four body composition types: high muscle with low adiposity; high muscle with high adiposity; low muscle with low adiposity; and low muscle with high adiposity. Proteins with differential expression were screened for interactions with body composition type on survival. Linear regression was used to assess associations, and Cox regression models-adjusted for age, tumor stage, sex, race, and ethnicity-were utilized for survival analysis.</p><p><strong>Results: </strong>Patients having low muscle with low adiposity exhibited worse survival than those having high muscle with high adiposity (hazard ratio, 3.74 [95% CI, 1.69-8.27]). Low muscle with low adiposity was also associated with increased expression of P-cadherin and decreased expression of DIRAS3 (P<0.05; false discovery rate-corrected P<0.1), both associated with poor survival in the entire KIRC cohort. Among patients having low muscle with high adiposity, high (vs. low) PREX1 expression was associated with 15.8-fold (95% CI, 3.08-80.78) increased mortality.</p><p><strong>Conclusion: </strong>Body composition is associated with differential expression of proteins and survival in ccRCC. <b>Impact:</b> Body composition and tumor proteomics may be prognostic biomarkers and therapeutic targets in ccRCC.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152625","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":"The Potential Effect of Ending CDC Funding for HIV Tests: A Modeling Study in 18 States.","authors":"Ruchita Balasubramanian, Melissa Schnure, Ryan Forster, William P Hanage, D Scott Batey, Keri N Althoff, Kelly A Gebo, David W Dowdy, Maunank Shah, Parastu Kasaie, Anthony T Fojo","doi":"10.1101/2025.09.19.25336182","DOIUrl":"10.1101/2025.09.19.25336182","url":null,"abstract":"<p><strong>Background: </strong>Timely HIV diagnosis and treatment is critical to preventing transmission. The US Centers for Disease Control and Prevention (CDC) provides funding for HIV testing to local health departments and community organizations. We sought to estimate the number of additional HIV infections that would result from ending or interrupting CDC funding for HIV tests in US states.</p><p><strong>Methods: </strong>We used a validated model of HIV transmission to simulate HIV epidemics in 18 US states. We projected incidence forward under three scenarios where all CDC-funded HIV testing ends in October 2025 and (1) never resumes, (2) returns to previous levels between January and December 2027, and (3) returns from January to December 2029. We calculated the excess incident HIV infections compared to a scenario where CDC-funded testing continues uninterrupted.</p><p><strong>Results: </strong>If CDC funding for HIV tests were to end on October 1, 2025, we project 12,719 additional HIV infections across 18 states by 2030 (95% Credible Interval 4,547 to 21,896) - an increase of 10%. The projected effects varied by state, ranging from a 2.7% increase in Washington (1.0 to 4.7%) to a 29.9 increase in Louisiana (9.4 to 59.9%). States that perform more CDC-funded tests and states with more rural HIV epidemics were projected to see greater rises in incidence.</p><p><strong>Conclusions: </strong>Disruptions to CDC-funded HIV testing would substantially increase new infections, particularly in states with more rural epidemics. These findings demonstrate the value of the CDC's HIV testing activities in curbing the spread of HIV in the US.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152651","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":"Optimal cutoff, cognitive impairment diagnostic performance, reliability and concurrent validity of the Ascertaining Dementia 8 (AD8) questionnaire among Latinos.","authors":"Jaime Perales-Puchalt, Adam Parks, Tina Lewandowski, Jeffrey M Burns, Eric D Vidoni","doi":"10.1101/2025.09.19.25336192","DOIUrl":"10.1101/2025.09.19.25336192","url":null,"abstract":"<p><p>The Ascertaining Dementia 8 (AD8) is a brief informant- or self-administered questionnaire designed to screen for cognitive impairment, offering several advantages over performance-based screening tests. We analyzed cross-sectional data from a non-probabilistic sample of English- and Spanish-speaking Latinos who were either cognitively unimpaired or had a research diagnosis of mild cognitive impairment or dementia. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis, and the Youden Index was used to determine the optimal cutoff score. Internal consistency was tested with the Kuder-Richardson Formula 20, and concurrent validity with correlations to the Clinical Dementia Rating scale, Mini-Mental State Exam, and Montreal Cognitive Assessment scores. Among 46 participants, the optimal cutoff was 3 or higher for the total sample and in both language groups. At this threshold, the AD8 showed a sensitivity of 73.7% and specificity of 85.2%, with an area under the curve of 0.843. The AD8 achieved good internal consistency of 0.872 and demonstrated correlations in the expected directions with the cognitive impairment measures. The Spanish version generally outperformed the English version. The AD8 questionnaire has adequate psychometric properties and diagnostic performance among US Latinos. To our knowledge, this is the first manuscript to validate the AD8 among US Latinos. These findings support its use in healthcare settings and its applicability for multiple research purposes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152503","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":"Impact of the COVID-19 Pandemic on Adult Asthma-Related Healthcare Utilization.","authors":"Lizbeth F Gómez, Kimberly D Lactaoen, Patrick K Gleeson, Alana Schreibman, Jason D Christie, Andrea J Apter, Rebecca A Hubbard, Gary E Weissman, Blanca E Himes","doi":"10.1101/2025.09.19.25336168","DOIUrl":"10.1101/2025.09.19.25336168","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic prompted unprecedented changes to chronic disease self-management and healthcare systems worldwide, including shifts in access to services and medications. While children with asthma had decreased exacerbations and healthcare encounters during 2020, the impact of lockdowns on adults with asthma, who faced different challenges during the pandemic than children, are less understood.</p><p><strong>Objective: </strong>We sought to characterize changes in adult asthma-related healthcare utilization during the COVID-19 pandemic in 2020 versus prior (2017-2019) and subsequent (2021-2024) years by leveraging electronic health record (EHR) data from a large, multi-hospital health system in a major US city.</p><p><strong>Methods: </strong>We conducted a retrospective EHR database study of 42,242 adults with asthma who received care at Penn Medicine from 2017 to 2024. We analyzed weekly encounter counts across five encounter types (refill, telemedicine, telephone/audio, outpatient, emergency encounters) and prescriptions for short-acting beta agonists (SABA), inhaled corticosteroids (ICS), and oral corticosteroids (OCS). Generalized linear models assessed changes in asthma-related encounter rate in pandemic (2020) and post-pandemic (2021-2024) periods relative to pre-pandemic (2017-2019). We stratified on weekly intervals that captured transitional timepoints in healthcare utilization in 2020 (Weeks 1-8, 9-18, and 19-52).</p><p><strong>Results: </strong>In 2017-2019, there were on average 397 weekly visits for asthma at Penn Medicine; in 2020, the weekly average increased to 481. This change was driven primarily by a surge during the lockdown weeks in refill and telemedicine encounters by 123% and 36,445%, respectively and by a decrease in outpatient visits by 65%. During the lockdown weeks in 2020, asthma related prescriptions of SABA and ICS prescriptions increased 73% and 43%, respectively, compared to pre-pandemic years, while OCS prescriptions decreased by 5%. White patients showed earlier healthcare-seeking responses than other racial groups. Changes persisted in post-pandemic years as the average of weekly asthma-related visits was 445 in 2021-2024. Telemedicine remained 38-76 times higher than pre-pandemic baseline, refills doubled compared to 2017-2019 levels, and outpatient visits remained 35-43% below pre-pandemic levels.</p><p><strong>Conclusion: </strong>COVID-19 transformed adult asthma care delivery and led to sustained increases in virtual care and medication refills potentially due to virtual care compensating for reductions in traditional outpatient encounters.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152609","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":"Complex Genetics and Regulatory Drivers of Hypermobile Ehlers-Danlos Syndrome: Insights from Genome-Wide Association Study Meta-analysis.","authors":"Taylor Petrucci-Nelson, Sacha Guilhaumou, Takiy E Berrandou, Cortney Gensemer, Adrien Georges, Matthew Huff, Margaux-Alison Fustier, Asraa Esmael, Josephine Henry, Olivia Jaye, Ranan Phookan, Sarah Dooley, Kathryn Byerly, Brian Loizzi, Roman Fenner, Emma Mach, Amy Weintraub, Victoria Daylor, Julianna Weninger, Natalie Koren, Erika Bistran, Charlotte Griggs, Molly Griggs, Sydney Severance, Rebecca Byrd, Sunil Patel, Steven A Kautz, Anne Maitland, Nabila Bouatia-Naji, Russell A Norris","doi":"10.1101/2025.09.19.25336146","DOIUrl":"10.1101/2025.09.19.25336146","url":null,"abstract":"<p><strong>Background: </strong>Hypermobile Ehlers-Danlos syndrome (hEDS) is the most common subtype of EDS, a group of heritable connective tissue disorders. Clinically, hEDS is defined by generalized joint hypermobility and chronic musculoskeletal pain, but its impact extends beyond the musculoskeletal system. Affected individuals frequently experience autonomic, gastrointestinal, immune, and neuropsychiatric involvement, highlighting both the multisystemic nature of the condition and challenges of diagnosis. In contrast to other EDS subtypes with defined genetic causes, the molecular basis of hEDS has remained elusive.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) of hEDS across three case controls studies, including 1,815 cases and 5,008 ancestry-matched controls. Fixed-effects meta-analysis of 6.2 million variants was complemented with LDAK gene-based association testing, transcriptome-wide association studies, and integrative annotation across multiple tissues and cell types including eQTLs, enhancer marks and open chromatin accessibility profiles, supported by luciferase assays on one candidate variant. LD-score genetic correlations were assessed between hEDS and 19 frequently reported comorbid conditions.</p><p><strong>Results: </strong>Two loci reached genome-wide significance, including a regulatory region near the atypical chemokine receptor 3 gene (<i>ACKR3</i>) on chromosome 2. Functional annotation supports <i>ACKR3</i> risk alleles colocalize with eQTLs in tibial nerve, alter enhancer activity, and generate a <i>de novo</i> AHR transcription factor regulatory site, implicating neuroimmune and pain signaling pathways. Gene-based and transcriptome-wide analyses identified common variants in a locus containing multiple candidates, including <i>SLC39A13,</i> a zinc transporter critical for connective tissue development previously implicated in a rare form of EDS, and <i>PSMC3</i>, a gene involved in central nervous system development. LD-score regression revealed significant genetic correlations between hEDS and joint hypermobility, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, depression, anxiety, autism spectrum disorder, migraine, and gastrointestinal diseases.</p><p><strong>Conclusions: </strong>These results establish the first evidence of common variant contributions to hEDS, supporting a complex, multisystem model involving neuroimmune-stromal dysregulation. Our findings add novel indications to hEDS pathogenesis and provide solid foundations for future molecular definition and therapeutic discovery.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152448","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":"Cross-sectional associations between lifecourse dementia risk factors, plasma neurodegenerative biomarkers, and cognition in older adults in India.","authors":"Sarah Gao, Alden L Gross, Leon M Aksman, Masroor Anwar, Eileen M Crimmins, Sharmistha Dey, Abhishek Gupta, Bharat Thyagarajan, Jinkook Lee, Emma Nichols","doi":"10.1101/2025.09.19.25336183","DOIUrl":"10.1101/2025.09.19.25336183","url":null,"abstract":"<p><strong>Background: </strong>Plasma neurodegenerative biomarkers are a potential low-cost tool for studying Alzheimer's disease and dementia in population-based research, especially in low- and middle-income countries (LMIC). However, their associations with modifiable risk factors and utility as an outcome in epidemiologic studies remain unclear.</p><p><strong>Objective: </strong>Our objective was to estimate the cross-sectional association between modifiable lifecourse risk factors for dementia and plasma-based neurodegenerative biomarkers, and to compare those with the associations between lifecourse risk factors and cognition in a population-representative Indian sample.</p><p><strong>Methods: </strong>Using nationally representative data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N=1625, average age 68.2 years), we estimated linear regressions to compare cross-sectional associations between lifecourse risk factors and both neurodegenerative biomarkers (β-amyloid 42/40, total-tau, phosphorylated Tau181, GFAP, NfL) and cognitive outcomes (general cognition, memory).</p><p><strong>Results: </strong>Despite significant associations between seven of thirteen risk factors and cognitive outcomes, associations between risk factors and neurodegenerative biomarkers were largely null with some exceptions; for example, hypertension (β=0.17SD; 95% CI:0.08,0.26) and diabetes (β=0.21SD; 95% CI:0.09, 0.32) were associated with higher NfL.</p><p><strong>Conclusions: </strong>While we found expected associations between lifecourse risk factors for dementia and cognition, there was not strong evidence of cross-sectional associations between risk factors for dementia and plasma-based biomarkers.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152437","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":"<i>APOE4</i> genotype and <i>MAPT</i> haplotype modify repetitive head impact biomarkers in retired professional fighters.","authors":"Xiaowei Zhuang, Dietmar Cordes, Lynn Bekris, Edwin C Oh, Charles Bernick","doi":"10.1101/2025.09.19.25335803","DOIUrl":"https://doi.org/10.1101/2025.09.19.25335803","url":null,"abstract":"<p><p>Long-term vulnerability to brain injury after repetitive head impacts (RHI) is poorly predicted <i>in vivo.</i> The wide heterogeneity of outcomes suggests that common genetic variants may act as modifiers of RHI-related neurodegeneration. Here, we tested whether <i>APOE</i> ε4 and <i>MAPT</i> H1/H2 haplotypes function as genetic modifiers of biomarker trajectories in 111 retired professional fighters from the Professional Athletes Brain Health Study (PABHS), the largest systematically characterized living cohort of fighters. RHI exposure was indexed by lifetime number of professional bouts. Primary outcomes included plasma GFAP (astroglial activation), NfL (axonal injury), and hippocampal volumes, measured cross-sectionally and longitudinally. Pre-specified linear models tested exposure × genotype interactions with false-discovery-rate correction. Across genotypes, greater fight exposure was associated with higher GFAP and smaller hippocampal volume. <i>APOE</i> ε4 modified longitudinal GFAP responses, with carriers showing stronger exposure-related increases than noncarriers, consistent with heightened astroglial reactivity. Conversely, the <i>MAPT</i> H2 haplotype mitigated associations between exposure, NfL, and hippocampal atrophy, suggesting partial protection against neuroaxonal injury and structural decline. Exploratory analyses showed <i>MAPT</i> H1/H1 enrichment among fighters meeting traumatic encephalopathy syndrome (TES) criteria (OR=3.33). Plasma p-tau231 was unrelated to exposure, indicating these effects are unlikely to reflect concurrent Alzheimer-type tau pathology. Together, these findings provide <i>in vivo</i> evidence that <i>APOE</i> and <i>MAPT</i> act as genetic modifiers of RHI-related brain injury, complementing postmortem evidence linking <i>MAPT</i> to chronic traumatic encephalopathy and highlighting the potential of genotype-informed monitoring in contact-sport populations.</p><p><strong>Significance statement: </strong>Repetitive head impacts (RHI) can lead to lasting brain damage, but not everyone exposed to RHI experiences the same outcomes. In retired fighters, we show that common genetic variants influence whether individuals are more vulnerable or resilient to brain inflammation and injury after repeated trauma. Specifically, APOE4 increased susceptibility, while a MAPT H2 variant appeared protective. These results provide the first in vivo evidence that inherited genetic differences modify long-term brain responses to RHIs. Incorporating genetic risk into studies of brain injury could enable earlier identification of at-risk individuals and support more personalized strategies for monitoring, prevention, and intervention.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152535","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":"Prevalence of Biochemically-Verified Substance Use in Healthy Adolescents Across the United States: Hair Toxicology Results in the ABCD Study.","authors":"Natasha E Wade, Yajuan Si, Susan F Tapert, Janosch Linkersdörfer, Krista M Lisdahl, Hailley R Moore, Laila Tally, Biplabendu Das, Marilyn A Huestis, Alexander L Wallace, Ryan M Sullivan, Veronica Szpak, Le Zhang, Laura R Ziemer, Wesley K Thompson","doi":"10.1101/2025.09.19.25336190","DOIUrl":"10.1101/2025.09.19.25336190","url":null,"abstract":"<p><strong>Objective: </strong>To determine correspondence between self-reported substance use and biochemical verification through hair samples and to estimate U.S. prevalence of adolescent substance use.</p><p><strong>Methods: </strong>Data came from the nationwide Adolescent Brain Cognitive Development Study (n=11,868; age 9-10 at Baseline, age 15-16 at Wave 6). Past-3-month substance use was measured annually from 2016 to 2024. Hair samples objectively detected moderate+ substance use in a subsample of participants (n_samples=11,865; n=6,133 unique participants). Multi-step weighting methods estimated national prevalence trends of cannabis, alcohol, and nicotine use over time, adjusting for discrepancies in sample representation due to recruitment demography, missed visits, and hair samples testing.</p><p><strong>Results: </strong>Correspondence between self-report and toxicological data improved with age (ages 11-12=<1%; ages 15-16=45%). Weighted estimates of biochemically verified substance use indicated 7.1% of 15-16 year olds engaged in moderate-to-heavy cannabis use, 0.3% heavily used alcohol, and 4.7% heavily used nicotine.</p><p><strong>Conclusions: </strong>Youth reported substance use patterns demonstrated improved biochemical verification with age. Biochemical verification reflects substantive cannabis and nicotine use by ages 15-16, supporting combining toxicological and self-report data to improve identification of substance use in youth.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152578","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":"Cannabis and Tobacco Co-Use Predicts Psychosis in Clinical High Risk Cohorts.","authors":"Daniel Bello, Sophia H Blyth, Rachel A Rabin, Jean Addington, Carrie E Bearden, Kristin Cadenhead, Tyrone D Cannon, Ricardo E Carrión, Barbara Cornblatt, Matcheri Keshavan, Daniel H Mathalon, Diana O Perkins, Larry Seidman, William S Stone, Ming T Tsuang, Elaine F Walker, Scott Woods, Roscoe O Brady, Heather Burrell Ward","doi":"10.1101/2025.09.19.25336202","DOIUrl":"10.1101/2025.09.19.25336202","url":null,"abstract":"<p><p>Cannabis and tobacco use are highly prevalent among people with psychosis and are associated with medical comorbidities and poor prognosis. Concurrent use of cannabis and tobacco (\"co-use\") is rising in the general population but has not been studied in psychosis. Given the devastating consequences of cannabis and tobacco use, it is critical to understand how their co-use affects psychiatric symptoms and the development of psychosis. We used the North American Prodrome Longitudinal Study 2, a multi-site prospective study of individuals at clinical high risk for psychosis (CHR) and healthy controls, to examine baseline differences in psychiatric symptoms and conversion to psychosis across substance groups: 1) CHR tobacco use, 2) CHR cannabis use, 3) CHR co-use, 4) CHR non-tobacco or cannabis substance use, 5) CHR without substance use, and 6) healthy controls. Among 1,014 participants (734 CHR, 280 controls), more frequent cannabis and tobacco use was linked to greater psychiatric symptom severity, including psychosis, anxiety, and depression. In survival analyses, co-use (HR <i>=</i> 2.53, 95% CI [1.44-4.45], <i>p</i> = .001), especially heavy co-use (HR = 3.63, 95% CI: 1.53-8.63, <i>p</i> = 0.003), was associated with increased risk of conversion to psychosis. Co-use of tobacco and cannabis was not associated with psychiatric symptom severity but did predict higher risk of conversion to psychosis. The combination of cannabis and tobacco use may exert a synergistic effect, amplifying conversion risk more than either substance alone, or may be a marker of an elevated underlying psychosis risk. These results highlight the need for early intervention strategies that address co-use in CHR populations to mitigate potential long-term psychiatric consequences.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152586","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":"Combining blood transcriptomic signatures improves the prediction of progression to tuberculosis among household contacts in Brazil.","authors":"Sarah Lundell, Vaishnavi Kaipilyawar, W Evan Johnson, Reynaldo Dietze, Jerrold J Ellner, Rodrigo Ribeiro-Rodrigues, Padmini Salgame","doi":"10.1101/2025.09.19.25336212","DOIUrl":"https://doi.org/10.1101/2025.09.19.25336212","url":null,"abstract":"<p><p>Tuberculosis remains a major health threat, infecting nearly a third of the world's population. Of those infected, 5-10% progress from latent infection to active tuberculosis (TB) disease and biomarkers to identify which individuals will progress are needed to allow targeted prophylactic treatment. Several risk biomarkers have been developed to predict progression but have not been tested head-to-head on the same platform. Here, we used the NanoString platform and compared the performance of 15 published gene signatures in predicting progression at baseline in a household contact cohort. Expression of gene signatures was profiled in RNA extracted from whole blood and scored using GSVA and PLAGE. We found that specificity is enhanced by combining signatures and report that the performance of a combined signature that includes a newly derived parsimonious signature through machine learning and a published signature met WHO TPP levels for a triage test. The combined signature had a 90.9% sensitivity and 88% specificity with a PPV of 0.24 and NPV of 1. This combined signature has potential clinical utility in identifying high-risk individuals for targeted prophylaxis to prevent TB morbidity and mortality.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152297","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}