{"gname":"Stowers Institute for Medical Research","grp_id":"3","rels":[{"rel_title":"Integrative Genetic and Single-Cell Analysis Reveals Macrophages as Key Mediators Linking Aging and Osteoporosis","rel_doi":"10.64898\/2026.09.09.26362574","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362574","rel_abs":"Osteoporosis is a highly prevalent age-related disorder, and accumulating evidence suggests that it does not arise in isolation but is intrinsically linked to the aging process. Here, we employed integrative methods to systematically identify the relationship between aging and osteoporosis, and uncover the critical cell types and molecular regulators that mediate this association. Observational analysis of phenotypic data from UK Biobank and Mendelian Randomization analysis of summary-level statistics revealed that aging and osteoporosis are interrelated, acting as both causes and effects of each other. We identified macrophages as the key cell types mediating this association by integration of GWAS data with a comprehensively assembled single-cell transcriptomic atlas of bone remodeling. And the percentage of macrophages from bone marrow decreases with age. Additionally, shared genetic tools and weight co-expression network analysis were employed to uncover novel molecular regulators underlying this crosstalk. We identified TGFB1 and a novel gene, HNRNPUL1, as key regulators that influence macrophages differentiation and function. In conclusion, our study provides observational and genetic evidence for a bidirectional relationship between aging and osteoporosis and unveils a macrophage-centric mechanism regulated by TGFB1 and HNRNPUL1, offering new insights for age-related bone loss.","rel_num_authors":17,"rel_authors":[{"author_name":"Xin Li","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Meng-Yuan Yang","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Si-Rui Gai","author_inst":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University, Hangzhou 310030, China"},{"author_name":"Peng Wei","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Zeng-Hui Gu","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Ming-Yu Han","author_inst":"Institute for immunity, Transplantation and Infection, Stanford Medicine, Stanford University, 1215 Welch Road, Modular B Stanford, CA 94305, USA"},{"author_name":"Yue-Zhou Wu","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Jia-Sheng Yu","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Wang-Jun Chen","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Zhen-Rui Liao","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"},{"author_name":"Jia-Xuan Gu","author_inst":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University, Hangzhou 310030, China"},{"author_name":"Jia-Dong Zhong","author_inst":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study and Westlake University, Hangzhou 310030, China"},{"author_name":"Pian-Pian Zhao","author_inst":"School of Basic Medical Sciences, Suzhou Medical College of Soochow University Suzhou, Jiangsu, China"},{"author_name":"Ke Zhu","author_inst":"School of Basic Medical Sciences, Suzhou Medical College of Soochow University Suzhou, Jiangsu, China"},{"author_name":"Ching-Lung Cheung","author_inst":"The University of Hong Kong"},{"author_name":"David Karasik","author_inst":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel"},{"author_name":"Hou-Feng Zheng","author_inst":"Suzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Resolving the Genomic Context of Clinically Relevant Antibiotic Resistance Genes in Wastewater with Ligation-Mediated PCR","rel_doi":"10.64898\/2026.09.09.26361541","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26361541","rel_abs":"Abstract Antimicrobial resistance (AMR) is a pressing global public health challenge. AMR is driven in part by the spread of antibiotic resistance genes (ARGs) through bacterial communities via mobile genetic elements. Influent wastewater is a promising sample type for monitoring AMR because it pools biological inputs shed by individuals across a population. However, untargeted sequencing approaches, such as metagenomic sequencing, often miss low-abundance targets such as clinically important ARGs. In this work, we develop a ligation-mediated PCR (LM-PCR) enrichment strategy that can directionally capture the genomic context surrounding an ARG using long-read sequencing. We applied this method to study the natural genomic context diversity of four clinically relevant ARGs (blaCTX-M, blaKPC, and blaOXA-48-like, and qnrS) across 13 wastewater treatment plants in Washington state, each sampled at two timepoints. Across all timepoints, LM-PCR identified distinct genomic context cluster families associated with each ARG, including seven for blaKPC, 11 for blaCTX-M, 24 for qnrS, and one for blaOXA-48-like. Notably, 11 of the 24 qnrS containing clusters were putatively novel, with no matches to existing sequences in public databases. Genomic contexts associated with blaCTX-M and blaKPC were comparatively conserved across clusters, whereas qnrS was associated with a more diverse set of genetic sequences. Together, these results demonstrate that LM-PCR can resolve low-abundance, ARG-associated genomic variation in complex wastewater samples and provide a scalable framework for tracking the dissemination of clinically relevant AMR determinants.","rel_num_authors":15,"rel_authors":[{"author_name":"Megan E O'Brien","author_inst":"University of Washington"},{"author_name":"Bradie Ahern","author_inst":"Washington State Department of Health"},{"author_name":"Piper Brase","author_inst":"Washington State Department of Health"},{"author_name":"Sooyeol Kim","author_inst":"The University of Sydney"},{"author_name":"Caroline E.M. McCormack","author_inst":"University of California, Berkeley"},{"author_name":"Denise Garcia","author_inst":"University of California, Berkeley"},{"author_name":"Erika Keim","author_inst":"Washington State Department of Health"},{"author_name":"Erin Dahl","author_inst":"Washington State Department of Health"},{"author_name":"Matthew Feck","author_inst":"Washington State Department of Health"},{"author_name":"Kelly Kauber","author_inst":"Washington State Department of Health"},{"author_name":"Jorge A Marchand","author_inst":"University of Washington"},{"author_name":"Rose S Kantor","author_inst":"Lawerence Livermore National Lab"},{"author_name":"Amy J Pickering","author_inst":"University of California, Berkeley"},{"author_name":"Breanna McArdle","author_inst":"Washington State Department of Health"},{"author_name":"Erica R Fuhrmeister","author_inst":"University of Washington"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Resolving the Genomic Context of Clinically Relevant Antibiotic Resistance Genes in Wastewater with Ligation-Mediated PCR","rel_doi":"10.64898\/2026.09.09.26361541","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26361541","rel_abs":"Abstract Antimicrobial resistance (AMR) is a pressing global public health challenge. AMR is driven in part by the spread of antibiotic resistance genes (ARGs) through bacterial communities via mobile genetic elements. Influent wastewater is a promising sample type for monitoring AMR because it pools biological inputs shed by individuals across a population. However, untargeted sequencing approaches, such as metagenomic sequencing, often miss low-abundance targets such as clinically important ARGs. In this work, we develop a ligation-mediated PCR (LM-PCR) enrichment strategy that can directionally capture the genomic context surrounding an ARG using long-read sequencing. We applied this method to study the natural genomic context diversity of four clinically relevant ARGs (blaCTX-M, blaKPC, and blaOXA-48-like, and qnrS) across 13 wastewater treatment plants in Washington state, each sampled at two timepoints. Across all timepoints, LM-PCR identified distinct genomic context cluster families associated with each ARG, including seven for blaKPC, 11 for blaCTX-M, 24 for qnrS, and one for blaOXA-48-like. Notably, 11 of the 24 qnrS containing clusters were putatively novel, with no matches to existing sequences in public databases. Genomic contexts associated with blaCTX-M and blaKPC were comparatively conserved across clusters, whereas qnrS was associated with a more diverse set of genetic sequences. Together, these results demonstrate that LM-PCR can resolve low-abundance, ARG-associated genomic variation in complex wastewater samples and provide a scalable framework for tracking the dissemination of clinically relevant AMR determinants.","rel_num_authors":15,"rel_authors":[{"author_name":"Megan E O'Brien","author_inst":"University of Washington"},{"author_name":"Bradie Ahern","author_inst":"Washington State Department of Health"},{"author_name":"Piper Brase","author_inst":"Washington State Department of Health"},{"author_name":"Sooyeol Kim","author_inst":"The University of Sydney"},{"author_name":"Caroline E.M. McCormack","author_inst":"University of California, Berkeley"},{"author_name":"Denise Garcia","author_inst":"University of California, Berkeley"},{"author_name":"Erika Keim","author_inst":"Washington State Department of Health"},{"author_name":"Erin Dahl","author_inst":"Washington State Department of Health"},{"author_name":"Matthew Feck","author_inst":"Washington State Department of Health"},{"author_name":"Kelly Kauber","author_inst":"Washington State Department of Health"},{"author_name":"Jorge A Marchand","author_inst":"University of Washington"},{"author_name":"Rose S Kantor","author_inst":"Lawerence Livermore National Lab"},{"author_name":"Amy J Pickering","author_inst":"University of California, Berkeley"},{"author_name":"Breanna McArdle","author_inst":"Washington State Department of Health"},{"author_name":"Erica R Fuhrmeister","author_inst":"University of Washington"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Assessing and refining a metabolite-based distress score for use in different populations within three US cohorts","rel_doi":"10.64898\/2026.09.10.26362734","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362734","rel_abs":"Introduction: Psychological distress is associated with metabolic alterations that contribute to adverse cardiometabolic outcomes across diverse populations. We previously developed a metabolite-based distress score (MDS) in predominantly White women. Because men and Black individuals suffer high rates of cardiometabolic disease, we evaluated whether the MDS is similarly associated with depression in these populations, and derived a multi-ethnic MDS (MDS-ME) among Black individuals with replications in independent samples. Methods: Data were from three U.S. cohorts, the Multi-Ethnic Study of Atherosclerosis (MESA), Women's Health Initiative (WHI), and Nurses' Health Study (NHS), evaluated in 4 stages. Stages 1-3 included 2,477 White and 1,625 Black MESA participants with depression status data and plasma metabolomics assessed at baseline. Stage 1: We calculated the MDS and examined its association with depression status. Stage 2: We conducted an agnostic analysis among a 70% random subset of Black participants to identify additional relevant metabolites. Stage 3: We derived an MDS-ME in Black participants. Stage 4: We evaluated the MDS-ME using independent samples from all three cohorts. Results: The previously validated 20-metabolite MDS showed stronger associations with prevalent depression in White (OR: 1.93, 95% CI: 1.71, 2.19) versus Black (OR: 1.13, 95% CI: 0.97, 1.33) MESA participants. Associations were generally similar in men and women. The MDS-ME comprised 33 metabolites, and relative to the MDS was more strongly associated with depression in Black participants (OR: 1.45; 95% CI: 1.04, 2.03), with associations also evident in White participants (OR: 1.81; 95% CI: 1.60, 2.04). The MDS-ME was similarly associated with depression in Black women in WHI and NHS. Conclusion: Results suggest that incorporating metabolites identified in Black participants enhances the utility and generalizability of the MDS across more diverse populations.","rel_num_authors":21,"rel_authors":[{"author_name":"Tianyi Huang","author_inst":"Intramural Research Program, National Institute on Aging"},{"author_name":"Yiwen Zhu","author_inst":"Harvard University"},{"author_name":"Raji Balasubramanian","author_inst":"University of Massachusetts Amherst"},{"author_name":"Andrea Roberts","author_inst":"Harvard University"},{"author_name":"Clary B Clish","author_inst":"Broad Institute"},{"author_name":"Julian Avila Pacheco","author_inst":"The Broad Institute of MIT and Harvard"},{"author_name":"Jerome Rotter","author_inst":"The Lundquist Institute"},{"author_name":"Xiuqing Guo","author_inst":"The Lundquist Institute"},{"author_name":"Jie Yao","author_inst":"The Lundquist Institute for Biomedical Innovation"},{"author_name":"Yii-Der Ida Chen","author_inst":"The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center"},{"author_name":"Steve Rich","author_inst":"Virginia"},{"author_name":"Kent Taylor","author_inst":"The Lundquist Institute"},{"author_name":"Alexis Wood","author_inst":"Baylor College of Medicine"},{"author_name":"W. Craig Johnson","author_inst":"University of Washington"},{"author_name":"Katherine H. Shutta","author_inst":"Harvard T.H. Chan School of Public Health"},{"author_name":"Kathryn Rexrode","author_inst":"Brigham and Women's Hospital, Harvard Medical School"},{"author_name":"Aladdin H Shadyab","author_inst":"University of California, San Diego"},{"author_name":"Su Yon Jung","author_inst":"University of California Los Angeles"},{"author_name":"JoAnn E Manson","author_inst":"Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;"},{"author_name":"Susan E. Hankinson","author_inst":"University of Massachusetts Amherst"},{"author_name":"Laura D. Kubzansky","author_inst":"Harvard TH Chan School of Public Health"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Digital readiness for cardiovascular care in high-burden US communities with cardiology workforce constraints","rel_doi":"10.64898\/2026.09.11.26362838","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26362838","rel_abs":"Digital health may extend cardiovascular care in communities with limited specialist access, but its effectiveness depends on whether communities have the infrastructure, devices, affordability, and capacity needed to use digital services. We linked national data on cardiometabolic burden, cardiology workforce, and digital readiness across 82,999 US census tracts to identify communities where digital cardiovascular care could be deployed and those where enabling investment may be needed first. Among 49,948 tracts in 2,582 counties with no cardiologist or declining per-capita cardiologist supply, 26,517 had above-average cardiometabolic burden. Of these, 4,765 had digital readiness at or above the national median and were classified as deployment-priority tracts, whereas 21,752 had lower readiness and were classified as investment-priority tracts. Investment-priority tracts clustered in the rural Southwest, Deep South, Mississippi Delta, and Gulf and Florida metropolitan areas, whereas deployment-priority tracts were dispersed across urban counties nationwide. Contrasting classifications frequently occurred among neighboring census tracts within the same metropolitan area, highlighting geographic variation not captured by county-level targeting. Findings were broadly consistent across eight additional analyses varying measures of readiness, workforce access, and classification thresholds. We also developed public interactive dashboards that allow users to examine local patterns and modify classification thresholds. These findings provide a national framework for distinguishing communities where digital cardiovascular care may be deployed from those where infrastructure and adoption support may be needed to enable equitable implementation.","rel_num_authors":5,"rel_authors":[{"author_name":"Sudheesha Perera","author_inst":"Yale School of Medicine"},{"author_name":"Lovedeep Singh Dhingra","author_inst":"Yale School of Medicine"},{"author_name":"Bruno Batinica","author_inst":"Yale School of Medicine"},{"author_name":"Aline Pedroso","author_inst":"Yale School of Medicine"},{"author_name":"Rohan Khera","author_inst":"Yale School of Medicine"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Epigenetic Effects of HIV and Childhood Maltreatment in Women","rel_doi":"10.64898\/2026.09.11.26362833","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26362833","rel_abs":"Introduction: People with HIV have disproportionately higher rates of adverse childhood experiences compared to the general population. This, in turn, is linked to long-term physical and mental health consequences. DNA methylation - a heritable, reasonably stable and quantifiable epigenetic mechanism implicated in gene silencing - may offer a useful lens that helps understand how HIV and childhood trauma become biologically embedded and affect disease risk profiles. Methods: This study aimed to identify regional and network level methylomic signatures associated with HIV and childhood maltreatment scores in South African women who bear the highest dual burden. DNA methylation profiling using the Illumina Infinium EPIC V2 kit was performed on DNA extracted from blood samples of 238 women with or without HIV with varying levels of childhood maltreatment. Regional DNA methylation analyses, composed of correlation tests on specific CpG sites and on genetic regions, were conducted for each of HIV and childhood maltreatment scores. Thereafter, a weighted gene Co-Expression Network Analysis (WGCNA) was conducted on HIV and childhood maltreatment scores to determine co-expression modules associated with the variable of interest. Finally, causal mediation analysis of the most significant network module was conducted to clarify the direction of association. Results: Neither HIV status nor childhood maltreatment was associated with DNA methylation at site-specific or regional levels. Network methylation effects were, however, observed, with three out of four network modules that were differentially methylated in HIV, implicating genes involved in immune pathways. One network module, composed of an abundance of genes relating to neurotransmitter functioning, was associated with childhood maltreatment. Both causal analyses implied that HIV and childhood maltreatment preceded the epigenetic effects. Conclusions: The findings suggest that DNA methylation in immune pathways may partially explain the immune and neurologic effects of HIV. The link between childhood maltreatment and neuronal processes warrants further investigation.","rel_num_authors":6,"rel_authors":[{"author_name":"Aqeedah Abbas Roomaney","author_inst":"Stellenbosch University"},{"author_name":"Sian Megan Joanna Hemmings","author_inst":"Stellenbosch University"},{"author_name":"Georgina Spies","author_inst":"University of Cape Town"},{"author_name":"Scott Lee Letendre","author_inst":"University of California San Diego"},{"author_name":"Soraya Seedat","author_inst":"Stellenbosch University"},{"author_name":"Jacqueline Samantha Womersley","author_inst":"University of Cape Town"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Decision Analysis Modeling Favors Optimal Influenza Vaccination in Late November or Early December","rel_doi":"10.64898\/2026.09.11.26362843","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26362843","rel_abs":"Background: Waning vaccine protection and variable epidemic timing create a tradeoff between vaccinating before influenza circulation and preserving protection when disease burden is greatest. Existing guidance does not quantify the week that best balances this tradeoff. Objective: To estimate the optimal week for influenza vaccination while accounting for uncertainty in epidemic timing and vaccine protection. Design: Simulation-based probabilistic decision analysis. Setting: United States outpatient influenza surveillance from the 50 states and District of Columbia during the 2010\/11 through 2018\/19 and 2023\/24 through 2025\/26 seasons. Participants: People in the United States who would receive 1 influenza vaccine dose. Interventions: Vaccination during Morbidity and Mortality Weekly Report (MMWR) weeks 36 through 12. Measurements: We combined influenza-like illness (ILI) syndromic surveillance and influenza-specific data with uncertainty in epidemic timing, initial vaccine effectiveness, waning, and immune-response lag. For each candidate week, the model estimated direct protection against outpatient surveillance burden. Results: The primary model identified the optimal time to vaccinate as week 47, with weeks 47-48 being of similar utility. Our influenza-weighted outpatient analysis (ILI+) selected week 48. Compared with week 44, near the end of the current September-October guidance window, week 48 reduced modeled influenza-weighted outpatient burden by 50 visit equivalents per 10,000 weekly encounters. Limitations: The model assumed vaccination would occur, used outpatient surveillance burden rather than severe outcomes, and did not incorporate transmission effects. Conclusion: Under the primary waning model, these findings favor vaccinating during weeks 47-48, approximately late November through early December, for most one-dose recipients.","rel_num_authors":4,"rel_authors":[{"author_name":"Austin G Meyer","author_inst":"Baylor College of Medicine"},{"author_name":"Brittany N Rosales","author_inst":"University of Texas at Austin"},{"author_name":"Shihao Yang","author_inst":"Georgia Institute of Technology"},{"author_name":"Mauricio Santillana","author_inst":"Northeastern University"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Decision Analysis Modeling Favors Optimal Influenza Vaccination in Late November or Early December","rel_doi":"10.64898\/2026.09.11.26362843","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26362843","rel_abs":"Background: Waning vaccine protection and variable epidemic timing create a tradeoff between vaccinating before influenza circulation and preserving protection when disease burden is greatest. Existing guidance does not quantify the week that best balances this tradeoff. Objective: To estimate the optimal week for influenza vaccination while accounting for uncertainty in epidemic timing and vaccine protection. Design: Simulation-based probabilistic decision analysis. Setting: United States outpatient influenza surveillance from the 50 states and District of Columbia during the 2010\/11 through 2018\/19 and 2023\/24 through 2025\/26 seasons. Participants: People in the United States who would receive 1 influenza vaccine dose. Interventions: Vaccination during Morbidity and Mortality Weekly Report (MMWR) weeks 36 through 12. Measurements: We combined influenza-like illness (ILI) syndromic surveillance and influenza-specific data with uncertainty in epidemic timing, initial vaccine effectiveness, waning, and immune-response lag. For each candidate week, the model estimated direct protection against outpatient surveillance burden. Results: The primary model identified the optimal time to vaccinate as week 47, with weeks 47-48 being of similar utility. Our influenza-weighted outpatient analysis (ILI+) selected week 48. Compared with week 44, near the end of the current September-October guidance window, week 48 reduced modeled influenza-weighted outpatient burden by 50 visit equivalents per 10,000 weekly encounters. Limitations: The model assumed vaccination would occur, used outpatient surveillance burden rather than severe outcomes, and did not incorporate transmission effects. Conclusion: Under the primary waning model, these findings favor vaccinating during weeks 47-48, approximately late November through early December, for most one-dose recipients.","rel_num_authors":4,"rel_authors":[{"author_name":"Austin G Meyer","author_inst":"Baylor College of Medicine"},{"author_name":"Brittany N Rosales","author_inst":"University of Texas at Austin"},{"author_name":"Shihao Yang","author_inst":"Georgia Institute of Technology"},{"author_name":"Mauricio Santillana","author_inst":"Northeastern University"}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Trajectory of Hyper IgE complications","rel_doi":"10.64898\/2026.09.11.26362846","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26362846","rel_abs":"Abstract Objective Our objective was to define the natural history of hyper IgE syndrome. Well, there have been a number of large cross-sectional studies. It has been difficult to provide anticipatory care for the growing adult population. Methods The USIDNET registry was used to identify patients with hyper IgE syndrome. We evaluated all patients regardless of genetic etiology. Complications were extracted as text from the problem list or ICD codes, and each complication was date stamped, which allowed us to estimate the age at which the complication arose. Results Many of the complications previously identified were seen in this cohort. The most feared complications were uncommon, however, developmental delay and psychosis affected nearly a fifth of the cohort which has not been previously reported. Conclusions As the number of adults with hyper IgE syndrome increases our awareness of late onset complications is important. Aspergillus and pneumatoceles were less common than seen in some other cohorts. However, the significant rate of psychosis will represent a significant challenge for clinicians.","rel_num_authors":11,"rel_authors":[{"author_name":"Asteria Mao","author_inst":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"author_name":"Rui Xiao","author_inst":"Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"author_name":"Kathleen E Sullivan","author_inst":"Children's Hospital of Philadelphia"},{"author_name":"Ramsay Fuleihan","author_inst":"Northwestern University School of Medicine, Chicago, IL"},{"author_name":"Charlotte Cunningham-Rundles","author_inst":"Icahn School of Medicine at Mount Sinai New York, NY, USA"},{"author_name":"Jennifer Puck","author_inst":"UCSF Benihoff Children's Hospital, University of California San Francisco"},{"author_name":"Rebecca Marsh","author_inst":"University of Cincinnati College of Medicine"},{"author_name":"Roshini Abraham","author_inst":"Nationwide Children's Hospital"},{"author_name":"Luigi Daniele Notarangelo","author_inst":"National Institute of Allergy and Infectious Diseases, NIH"},{"author_name":"Vaibhavi Vichare","author_inst":"Children's Hospital of Philadelphia"},{"author_name":"- USIDNET Network members","author_inst":""}],"rel_date":"2026-09-13","rel_site":"medrxiv"},{"rel_title":"Longitudinal changes in control energy of brain networks in older adults at familial risk for Alzheimers disease","rel_doi":"10.64898\/2026.09.06.749740","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.06.749740","rel_abs":"The ability of structural brain networks to control neural dynamics is affected by healthy and pathological aging, including Alzheimers disease (AD). According to network control theory, transitions between functional brain states incur energetic costs. How these costs change longitudinally with aging remains unknown. Here, in 279 older adults at familial risk for AD, control energy increased longitudinally for state maintenance and transitions between sensorimotor and attentional networks, while decreasing for another sensorimotor--attentional transition. Changes in transition costs between higher-order networks were associated with cognitive performance: greater DorsAttn--Executive cost was associated with poorer immediate memory, while lower Executive--Def+Lim cost was associated with poorer attention. Higher plasma p-tau181 was associated with lower DorsAttn--Def+Lim transition cost. These findings reveal transition-specific alterations in the energetic landscape of aging and distinct relationships with cognition and AD pathology. Together, they highlight energetic constraints on brain network reconfiguration as a complementary perspective on neurocognitive aging.","rel_num_authors":11,"rel_authors":[{"author_name":"Paulina Skolasinska","author_inst":"McGill University"},{"author_name":"Alfie Wearn","author_inst":"McGill University"},{"author_name":"Daniel O'Sullivan","author_inst":"University of Ottawa"},{"author_name":"Isabella Stallworthy","author_inst":"University of Pennsylvania"},{"author_name":"Julia K Brynildsen","author_inst":"University of Pennsylvania"},{"author_name":"Ilana R Leppert","author_inst":"McGill University"},{"author_name":"Christine L Tardif","author_inst":"McGill University"},{"author_name":"Gary R Turner","author_inst":"York University"},{"author_name":"Dani S Bassett","author_inst":"University of Pennsylvania"},{"author_name":"R. Nathan Spreng","author_inst":"McGill University"},{"author_name":"- for the PREVENT-AD Research Group","author_inst":""}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Longitudinal changes in control energy of brain networks in older adults at familial risk for Alzheimers disease","rel_doi":"10.64898\/2026.09.06.749740","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.06.749740","rel_abs":"The ability of structural brain networks to control neural dynamics is affected by healthy and pathological aging, including Alzheimers disease (AD). According to network control theory, transitions between functional brain states incur energetic costs. How these costs change longitudinally with aging remains unknown. Here, in 279 older adults at familial risk for AD, control energy increased longitudinally for state maintenance and transitions between sensorimotor and attentional networks, while decreasing for another sensorimotor--attentional transition. Changes in transition costs between higher-order networks were associated with cognitive performance: greater DorsAttn--Executive cost was associated with poorer immediate memory, while lower Executive--Def+Lim cost was associated with poorer attention. Higher plasma p-tau181 was associated with lower DorsAttn--Def+Lim transition cost. These findings reveal transition-specific alterations in the energetic landscape of aging and distinct relationships with cognition and AD pathology. Together, they highlight energetic constraints on brain network reconfiguration as a complementary perspective on neurocognitive aging.","rel_num_authors":11,"rel_authors":[{"author_name":"Paulina Skolasinska","author_inst":"McGill University"},{"author_name":"Alfie Wearn","author_inst":"McGill University"},{"author_name":"Daniel O'Sullivan","author_inst":"University of Ottawa"},{"author_name":"Isabella Stallworthy","author_inst":"University of Pennsylvania"},{"author_name":"Julia K Brynildsen","author_inst":"University of Pennsylvania"},{"author_name":"Ilana R Leppert","author_inst":"McGill University"},{"author_name":"Christine L Tardif","author_inst":"McGill University"},{"author_name":"Gary R Turner","author_inst":"York University"},{"author_name":"Dani S Bassett","author_inst":"University of Pennsylvania"},{"author_name":"R. Nathan Spreng","author_inst":"McGill University"},{"author_name":"- for the PREVENT-AD Research Group","author_inst":""}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Clustering without clusters: the meta-criterion and centroid reliability mistake continuous dynamics for discrete states","rel_doi":"10.64898\/2026.09.06.749668","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.06.749668","rel_abs":"Microstate analysis starts with clustering and the meta-criterion is a heuristic to find an optimum cluster number. We address the following questions: (i) what number is found for non-cluster-forming dynamical systems, (ii) do centroids fall in random attractor regions, (iii) do EEG topographies form clusters or a single connected structure in sensor space? We find that (i) the meta-criterion suggests spurious optimal cluster numbers (4-8) with high confidence on different attractor geometries, (ii) cluster centroids reliably fall in the same attractor regions, (iii) topological analysis of dynamical systems and resting-state EEG suggests that all form a single connected structure in their respective phase space, not clusters. We conclude that the meta-criterion should be used with caution and its results should not be taken as representing a ground truth. Cluster numbers deviating from the meta-criterion should not be discarded. A more far-reaching implication is that evidence for the existence of clusters in resting-state EEG data is still lacking. Microstate clustering may correspond to the partitioning of a single connected structure.","rel_num_authors":2,"rel_authors":[{"author_name":"Frederic von Wegner","author_inst":"University of New South Wales"},{"author_name":"Gesine Hermann","author_inst":"Department of Neurology, Christian-Albrechts University, Arnold-Heller-Strasse 3, Kiel, 24105, Germany"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Large Language Models Predict Human Social Behavior via Interpretable Mechanisms","rel_doi":"10.64898\/2026.09.06.749667","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.06.749667","rel_abs":"The development of large language models (LLMs) offers promising opportunities for predicting human behavior across diverse contexts. However, most prior work has emphasized behavioral imitation, with limited attention to transparent or interpretable models of the cognitive mechanisms underlying human decisions. In this study, we introduce MindEvolve, an autonomous workflow designed to predict behavior in social interactions by generating interpretable symbolic models of cognition. We systematically evaluate the modeling capabilities of multiple LLMs across a battery of socioeconomic games covering four core domains of social cognition: economic preferences, social preferences, social reasoning (theory of mind), and recursive planning. The symbolic models proposed by the LLMs are assessed by expert human evaluators for interpretability and theoretical coherence. Our results show that while most LLMs robustly capture economic and social preferences in relatively simple strategic settings, and in some cases generate novel models that integrate broader knowledge than those proposed by human experts, their capacity to model more complex psychological processes remains limited. However, a subset of state-of-the-art models demonstrates promising performance in capturing higher-order reasoning processes such as theory of mind and recursive planning. Together, these findings highlight the emerging potential of LLMs not only to imitate behavior, but to generate interpretable, mechanistic accounts of human social decision-making. Our results provide a roadmap for advancing LLM-based cognitive modeling toward human-expert-level theory construction.","rel_num_authors":8,"rel_authors":[{"author_name":"Yingying Ye","author_inst":"East China Normal University"},{"author_name":"Youle Fang","author_inst":"Peking University"},{"author_name":"Xiaoxue Gao","author_inst":"East China Normal University"},{"author_name":"Vered Kurtz-David","author_inst":"Hebrew University of Jerusalem"},{"author_name":"Andreas Hula","author_inst":"Austrian Institute of Technology"},{"author_name":"Chun Fan","author_inst":"Peking University"},{"author_name":"Tingting Long","author_inst":"Peking University"},{"author_name":"Bo Shen","author_inst":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Structural Determinants of Synaptic Vesicle Protein 2C Ligand Selectivity and Their Impact on Dopamine Release","rel_doi":"10.64898\/2026.09.10.750697","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750697","rel_abs":"The synaptic vesicle protein 2 (SV2) family is a highly conserved group of transmembrane glycoproteins sharing approximately 70% sequence identity. SV2A and SV2B are broadly distributed throughout the brain, while SV2C, the evolutionarily oldest member of the family, is primarily found in dopaminergic brain regions in the basal ganglia. Genome-wide association studies have linked SV2C to Parkinson's disease, and SV2C appears to enhance dopamine storage in synaptic vesicles, but the basis for this effect is unknown. SV2s are the target of the racetam class of antiseizure medications, and SV2A-specific ligands are widely used to treat seizures. Recently several SV2C-specific ligands have been developed, but the structural basis for ligand specificity is unclear. A better understanding of SV2C structure, function, and pharmacology could lead to better targeted therapies for epilepsy, Parkinson's disease, and other dopamine-related conditions. Here we present cryo-EM structures of apo SV2C, SV2C bound to the high affinity non-selective SV2 ligand padsevonil, SV2C bound to the SV2C-selective ligand UCB-F, and SV2A bound to the SV2A-selective ligand plosaracetam (also known as ABBV-552\/SDI-118). We find that SV2C has a wider luminal opening than SV2A and SV2B, which allows for UCB-F to bind to the primary site and form favorable interactions that are not possible in the narrower primary binding site of SV2A and SV2B. We also demonstrate that UCB-F and padsevonil, but not plosaracetam, reduce dopamine release in striatal sections of mouse brain. Our biochemical experiments and structures provide insights into SV2 ligand specificity and offer a template for the rational development of therapeutics targeting SV2C.","rel_num_authors":13,"rel_authors":[{"author_name":"Matthew F Martin","author_inst":"University of Pittsburgh"},{"author_name":"Meghan L Bucher","author_inst":"Columbia University"},{"author_name":"Seejon Choi","author_inst":"Columbia University"},{"author_name":"Anshumali Mittal","author_inst":"University of Pittsburgh"},{"author_name":"Eugene Mosharov","author_inst":"Columbia University"},{"author_name":"Adrian Hall","author_inst":"UCB"},{"author_name":"Christian Wolff","author_inst":"UCB"},{"author_name":"Michel Gillard","author_inst":"UCB"},{"author_name":"Laurent Provins","author_inst":"UCB"},{"author_name":"Peter S Horanyi","author_inst":"UCB"},{"author_name":"David Sulzer","author_inst":"Columbia University"},{"author_name":"Gary W Miller","author_inst":"Columbia University"},{"author_name":"Jonathan Coleman","author_inst":"University of Pittsburgh"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"DDRKOL: A Focused CRISPR Library for Systematic Identification of DNA Damage Response Dependencies in Glioblastoma","rel_doi":"10.64898\/2026.09.11.750882","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.750882","rel_abs":"Background: DNA damage response (DDR) pathways are central regulators of genome maintenance and major determinants of cancer cell survival. The extensive genomic instability and high replicative stress that characterize glioblastoma render tumor cells highly dependent on DDR pathways to preserve genome integrity and sustain proliferation. This reliance creates potential therapeutic vulnerabilities, making the systematic identification of essential DDR genes a promising strategy for uncovering novel therapeutic targets. Methods: We developed DNA Damage Response KnockOut Library (DDRKOL), a custom CRISPR\/Cas9 sgRNA library targeting 819 DDR genes with approximately 10 sgRNAs per gene, together with positive (essential), negative (non-essential) and non-targeting controls. Parallel depletion screens were performed in Cas9-expressing U87-MG and A172 cells cultured for 15 population doublings. Hits were prioritized utilizing TCGA and DepMap databases and validated by viability, clonogenic, apoptosis and GFP competition assays. Clinically relevant patient-derived glioblastoma spheroids and an orthotopic xenograft model was employed to characterize the effects of hit genes. Results: Sequencing confirmed near-complete recovery of the designed sgRNAs from the plasmid pool, with uniform representation across the library and complexity preserved through transduction and selection. Essential-gene controls depleted strongly while non-targeting controls remained neutral, confirming screen performance in both cell lines. The screens identified DDR dependencies in each line and defined a shared core composed of 20 genes belonging to homologous recombination, nucleotide excision repair and ATM\/DSB signaling pathways. This shared dependency landscape highlighted four high-confidence candidate genes (TOP2A, CDK1, XRCC6, and RAD21), which were successfully validated across multiple orthogonal assays. These genes displayed grade-associated expression and their expressions were positively correlated with proliferation markers in TCGA. Individual knockouts reduced viability, colony formation and competitive fitness, induced apoptosis, and impaired growth of patient-derived glioblastoma spheroids. Both genetic depletion and pharmacological inhibition of TOP2A induced S\/G2-M cell cycle arrest. In orthotopic xenografts, TOP2A depletion prevented tumor progression, and led to significantly prolonged survival. Conclusion: DDRKOL represents a robust and versatile focused CRISPR platform for systematic functional interrogation of the DDR associated genes. Using glioblastoma, we demonstrate that the library reliably identifies biologically significant and clinically relevant genetic dependencies through multiple orthogonal validation approaches. As a reusable platform rather than a disease-specific tool, DDRKOL can be broadly applied across diverse biological contexts to discover context-dependent DDR vulnerabilities, therapeutic targets, and mechanisms of treatment resistance.","rel_num_authors":9,"rel_authors":[{"author_name":"Canan Bayraktar-Odabas","author_inst":"Koc University"},{"author_name":"Ipek Kok","author_inst":"Koc University"},{"author_name":"Altar Ozbiyik","author_inst":"Koc University"},{"author_name":"Alisan Kayabolen","author_inst":"Koc University"},{"author_name":"Ali Cenk Aksu","author_inst":"Koc University"},{"author_name":"Ayse Humeyra Dur Karasayar","author_inst":"Koc University"},{"author_name":"Ilknur Sur Erdem","author_inst":"Koc University"},{"author_name":"Ibrahim Kulac","author_inst":"Koc University"},{"author_name":"Tugba Bagci-Onder","author_inst":"Koc University"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Nonviral, ultrasound-triggered gene delivery platform via gas-core cationic nanobubbles","rel_doi":"10.64898\/2026.09.11.749060","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.749060","rel_abs":"Despite their promise, lipid nanoparticle gene delivery systems have repeatedly failed clinical trials and struggle to achieve efficient, localized transfection in target tissues. The majority of endocytosed nanoparticles are degraded before nucleic acid release, and an inability to track particle distribution in vivo prevents validation of successful delivery. Alternatively, nanobubbles (NBs) are lipid-shelled, gas-core preclinical ultrasound contrast agents and stimuli-responsive drug delivery vehicles. Under varying acoustic pressures, NBs expand, contract, and burst, releasing cargo in an externally controlled, site-specific manner while scattering unique echoes for simultaneous ultrasound visualization. Here, we introduce a cationic nanobubble (CNB) formulation with a +42.3 mV zeta potential, 265 nm diameter, and 2.43x1011 NBs\/mL concentration. CNBs produce stable ultrasound contrast, electrostatically load plasmid DNA onto their surface, and internalize into >99% of human prostate cancer cells within 15 minutes in vitro. CNBs remain brightly echogenic intracellularly and induce sonication-dependent expression of green fluorescent protein (GFP). In vivo, CNBs generate contrast in mouse livers for 50 minutes after intravenous administration. Therapeutic ultrasound stimulation over the liver causes a sharp reduction in ultrasound contrast, visualizing localized cavitation in the target organ and inducing a 2.5-fold increase in anti-GFP mean fluorescence intensity relative to the untransfected control. Importantly, no GFP expression is observed without ultrasound stimulation, supporting a mechanism for selective and site-specific gene delivery. This study presents a highly stable CNB capable of efficient DNA loading and ultrasound-dependent gene expression. These results provide a foundation for the future development of CNB platforms to advance image-guided, ultrasound-triggered gene therapy.","rel_num_authors":18,"rel_authors":[{"author_name":"Laura E. Chen","author_inst":"Case Western Reserve University"},{"author_name":"Pinunta Nittayacharn","author_inst":"Mahidol University"},{"author_name":"Aayushi Laliwala","author_inst":"Case Western Reserve University"},{"author_name":"Marcus Vincent Bella Jaro","author_inst":"Case Western Reserve University"},{"author_name":"Salima El Yakhlifi","author_inst":"Case Western Reserve University"},{"author_name":"Jean F. Eastman","author_inst":"Case Western Reserve University"},{"author_name":"Xu Han","author_inst":"Case Western Reserve University"},{"author_name":"Aaqib H. Khan","author_inst":"Case Western Reserve University"},{"author_name":"Kathryn HartMoore","author_inst":"University of Colorado Anschutz Medical Campus"},{"author_name":"Fatma Dogan","author_inst":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School"},{"author_name":"Valentina F. Giai","author_inst":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School"},{"author_name":"Timothy Brauns","author_inst":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School"},{"author_name":"Mark C. Poznansky","author_inst":"Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School"},{"author_name":"Richard K.P. Benninger","author_inst":"University of Colorado Anschutz Medical Campus"},{"author_name":"Marvin T. Nieman","author_inst":"Case Western Reserve University"},{"author_name":"Ilya Bederman","author_inst":"Case Western Reserve University"},{"author_name":"Mitchell L. Drumm","author_inst":"Case Western Reserve University"},{"author_name":"Agata A. Exner","author_inst":"Case Western Reserve University"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"A genetically encoded redox bottleneck constrains human developmental rate","rel_doi":"10.64898\/2026.09.10.750701","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750701","rel_abs":"The intrinsically slow pace of human development poses challenges for regenerative medicine and disease modeling. This trait is attributed to low metabolic rates, yet the endogenous mechanisms determining species-specific metabolic flux remain unknown. Here, we identify coupling between glycolytic NADH production and mitochondrial oxidation through the glycerol-3-phosphate (G3P) shuttle as a genetic bottleneck constraining human developmental tempo. Using stem cell-derived models of the segmentation clock, an oscillator whose period reflects developmental rate, we show that low expression of the G3P shuttle enzyme GPD1L limits NADH oxidation in human progenitors compared to mouse. Overexpressing GPD1L boosts metabolic flux, accelerating the segmentation clock, cell cycle, and differentiation across germ layers. G3P-mediated redox coupling is thus a genetically encoded, rate-limiting mechanism that sets the tempo of human development.","rel_num_authors":15,"rel_authors":[{"author_name":"Gabriel E. Valdebenito","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Jack P. Madden","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Carolina Mendez","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Leslie M. Azurdia","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Xintao Zhu","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; D"},{"author_name":"Siyu Chen","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Diana Atlas","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Katherine Introcaso","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"},{"author_name":"Hao Zhang","author_inst":"Center of Mass Spectrometry & Metabolic Tracing, Washington University in St. Louis, St. Louis, MO, USA; Department of Chemistry, Washington University in St. L"},{"author_name":"Yahui Wang","author_inst":"Center of Mass Spectrometry & Metabolic Tracing, Washington University in St. Louis, St. Louis, MO, USA; Department of Chemistry, Washington University in St. L"},{"author_name":"Fangcong Dong","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Boston, MA, USA; Department of Systems "},{"author_name":"Rohit Sharma","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Boston, MA, USA; Department of Systems "},{"author_name":"Vamsi K. Mootha","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Boston, MA, USA; Department of Systems "},{"author_name":"Gary J. Patti","author_inst":"Center of Mass Spectrometry & Metabolic Tracing, Washington University in St. Louis, St. Louis, MO, USA; Department of Chemistry, Washington University in St. L"},{"author_name":"Margarete Diaz-Cuadros","author_inst":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"A transitional senescence program drives inflammatory monocyte state expansion in aging humans","rel_doi":"10.64898\/2026.09.09.750459","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750459","rel_abs":"Dysfunctional monocyte states contribute to age-related pathologies and systemic inflammation. However, the gene regulatory networks governing the transition to these states remain unknown. Here we used bulk and single-cell multidimensional integrative profiling to reveal previously uncharacterized monocyte state transitions during human aging. We show that a transient senescent-like population arising from classical CD14++ CD16- monocytes drives the accumulation of an inflammatory monocyte state in aging humans. This senescence-associated transition is orchestrated by the master senescence regulator AP-1, which acts on a pre-established chromatin landscape to rewire the monocyte transcription factor (TF) network and activate both senescence- and age-associated inflammatory transcriptional programs. Through integration with clinical transcriptomic datasets, we demonstrate that senescent-like and aged monocytes are transcriptionally primed toward sepsis-associated states. Overall, our study provides the core gene-regulatory principles underlying a senescent-like transitional state in monocytes and identifies AP-1 as an attractive target to modulate systemic inflammation in age and disease.","rel_num_authors":8,"rel_authors":[{"author_name":"Themistoklis Vasilopoulos","author_inst":"Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, USA."},{"author_name":"Paolo S Turano","author_inst":"Rutgers-New Jersey Medical School, Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, 205 South Orange Avenue, Newark, "},{"author_name":"Luis Garza-Martinez","author_inst":"Rutgers-New Jersey Medical School, Department of Pathology, Immunology, and Laboratory Medicine, 185 South Orange Avenue, Newark, NJ, USA"},{"author_name":"Elizabeth Akbulut","author_inst":"Rutgers-New Jersey Medical School, Department of Pathology, Immunology, and Laboratory Medicine, 185 South Orange Avenue, Newark, NJ, USA"},{"author_name":"Mounika Konda","author_inst":"Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, USA."},{"author_name":"Utz Herbig","author_inst":"Rutgers-New Jersey Medical School, Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, 205 South Orange Avenue, Newark, "},{"author_name":"Patricia Fitzgerald-Bocarsly","author_inst":"Rutgers-New Jersey Medical School, Department of Pathology, Immunology, and Laboratory Medicine, 185 South Orange Avenue, Newark, NJ, USA"},{"author_name":"Ricardo Ivan Martinez Zamudio","author_inst":"Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, USA."}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Demography and selection shape gene loss in freshwater sticklebacks - A pangenomic perspective","rel_doi":"10.64898\/2026.09.08.750278","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750278","rel_abs":"The extent of within-species variation in genome assembly size, and the relative contributions of neutral vs. adaptive processes to it, remains poorly understood. We assembled the pangenome for the nine-spined stickleback (Pungitius pungitius) from whole-genome resequencing data obtained from range-wide sampling of 1,478 individuals across 47 populations. Our analysis recovered approximately 234.15 Mb of novel sequence and identified 11,151 protein-coding genes annotated in non-reference-represented regions, which accounted for 28.8% of all annotated pangenomic genes, corresponding to a 40.6% expansion relative to the 27,450 protein-coding genes annotated in the updated v8 reference genome. The identified presence\/absence variation (PAV) genes exhibited a higher incidence of deleterious and non-synonymous mutations than core genes. Freshwater populations with smaller effective population sizes had lost more genes and had smaller assembly sizes relative to larger marine populations. Larger genome sizes of marine populations were primarily associated with higher transposable element content. Across gene categories, patterns of molecular variation were consistent with weaker purifying selection in freshwater populations than in marine populations, while recurrent freshwater-biased loss of a subset of PAV genes suggested that gene loss is not entirely random. Together, these results indicate that demographic history explains the overall pattern of gene loss, whereas negative natural selection may contribute to repeated loss of a subset of genes.","rel_num_authors":5,"rel_authors":[{"author_name":"Hongbo Wang","author_inst":"The University of Hong Kong"},{"author_name":"Chaowei Zhang","author_inst":"The University of Hong Kong, Area of Ecology & Biodiversity, School of Biological Sciences"},{"author_name":"Dandan Wang","author_inst":"The University of Hong Kong, Area of Ecology & Biodiversity, School of Biological Sciences"},{"author_name":"Kerry Reid","author_inst":"The University of Hong Kong"},{"author_name":"Juha Merila","author_inst":"The University of Hong Kong"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Multigenerational machine learning-based genomic prediction for dermo resistance in eastern oyster Crassostrea virginica","rel_doi":"10.64898\/2026.09.08.750100","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750100","rel_abs":"Dermo disease caused by the protist Perkinsus marinus poses a major threat to Eastern oyster aquaculture. We previously conducted genomic selection for dermo resistance and found increased effectiveness over phenotypic selection. Here, we report improved genomic predictions using combined data from three successive generations. We evaluated nine different genomic selection models, including three supervised machine learning architectures: gradient boosting, logistic regression, and random forest. Combining data across multiple generations did not, by itself, substantially improve the accuracy of most models, but the increased sample size provided genotyping confidence of loci with rare alleles. Correlation accuracy of all models significantly increased with the inclusion of low-frequency variants and strong-effect markers identified through a genome-wide association study. Gradient boosting machine learning models outperformed other genomic selection models across all training scenarios, suggesting enhanced capacity to learn generalizable genomic signals associated with dermo resistance. The best gradient boosting model achieved a peak correlation accuracy of 0.410, a substantial improvement over the previous peak accuracy of 0.274 from traditional models. Together, our results highlight the potential of machine learning for genomic selection and the significance of rare variants in determining dermo resistance.","rel_num_authors":10,"rel_authors":[{"author_name":"Henry Sun","author_inst":"Duke University"},{"author_name":"Paul Coyne","author_inst":"Rutgers University"},{"author_name":"Zhenwei Wang","author_inst":"Rutgers University"},{"author_name":"Sandra Casas","author_inst":"Louisiana State University"},{"author_name":"Jerome La Peyre","author_inst":"Louisiana State University"},{"author_name":"Mason L Williams","author_inst":"Auburn University"},{"author_name":"Scott Rikard","author_inst":"Auburn University"},{"author_name":"David Bushek","author_inst":"Rutgers University"},{"author_name":"Juliet Wong","author_inst":"Duke University"},{"author_name":"Ximing Guo","author_inst":"Rutgers University"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Delta rhythm and voice familiarity organize neural entrainment in the infant brain","rel_doi":"10.64898\/2026.09.10.750698","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750698","rel_abs":"The delta frequency band (~0.5-3.5 Hz) represents a phylogenetically conserved tempo of biological communication, and neural entrainment to this timescale would be a key mechanism through which the brain might generate temporal predictions. While entrainment at different levels has been characterized in adults, the mechanisms of auditory temporal prediction remain poorly studied across developmental trajectories, particularly regarding the roles of stimulus rhythmicity, frequency specificity, and voice familiarity. Using high-density EEG, we examined neural entrainment in thirty 6-month-old infants exposed to vocally rhythmic syllables produced by their mother or a stranger at delta (2 Hz) or theta (4 Hz) rates, as well as a non-rhythmic control. Auditory temporal regularity elicited a broad frontotemporal entrainment response. Critically, delta-band entrainment was frequency-specific across frontal and temporal clusters, with right-frontal selectivity progressively strengthening throughout the entrainment period as expected if this region actively refines a temporal model of the input rather than passively resonating to it; no significant theta-band specificity was observed. Entrainment was further shaped by voice familiarity: the left temporal cortex entrained selectively to the mother's voice, whereas the right frontal cluster responded selectively to the stranger's voice. This is consistent with an implementation in which familiarity-based processing within mid-temporal language-related regions interfaces with novelty-sensitive frontal mechanisms, and reflects the ongoing updating of internal predictive models rather than passive sensory registration. The co-occurrence of frequency-specific delta entrainment and experience-dependent hemispheric asymmetries reveals a neural functional network for hierarchical temporal predictions, shaped by early auditory experience and already in place at 6 months.","rel_num_authors":7,"rel_authors":[{"author_name":"Isabelle Rambosson","author_inst":"University of Geneva"},{"author_name":"Damien Benis","author_inst":"University of Geneva"},{"author_name":"Francisca Barcos-Munoz","author_inst":"University Hospitals of Geneva"},{"author_name":"Claire Kabdebon","author_inst":"CNRS"},{"author_name":"Leonardo Ceravolo","author_inst":"Universoty of Geneva"},{"author_name":"Didier Grandjean","author_inst":"University of Geneva"},{"author_name":"Manuela Filippa","author_inst":"University of Geneva"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Neural tracking of surprisal and semantic distance in naturalistic movie viewing","rel_doi":"10.64898\/2026.09.09.749230","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.749230","rel_abs":"Understanding speech requires listeners to integrate incoming input with prior linguistic and thematic knowledge to access meaning, a task greatly aided by prediction. Surprisal and related phenomena (e.g., next word prediction) tend to be associated with broad activation of language regions during listening. A major challenge for interpreting the neural correlates of surprisal is that lexical expectancies are constrained both by syntactic and semantic information. In contrast, semantic distance yields more of a pure metric of relatedness between one language constituent (e.g., word, phrase, n-gram) and another within a high-dimensional semantic space. We contrasted surprisal and semantic distance in running discourse during naturalistic audiovisual language comprehension. We analyzed fMRI scans from 20 English-speaking adults who viewed the full-length film 500 Days of Summer. Our focus was on brain sensitivity to either surprisal or semantic distance as language unfolded word-by-word. To this end, we implemented a series of hierarchical voxelwise encoding models. After accounting for low-level auditory and visual features, the addition of either surprisal or semantic distance improved prediction in bilateral superior temporal gyrus (STG), left inferior frontal gyrus, and right cerebellum. Critically, both semantic distance and surprisal explained unique variation in bilateral temporal cortex after accounting for the other. These results support the notion that the brain tracks both broad probabilistic prediction as well as semantic integration. More generally, these findings extend previous work on auditory-only speech by demonstrating that surprisal and semantic distance predict meaningful neural variation even within a rich audiovisual context.","rel_num_authors":5,"rel_authors":[{"author_name":"Ryan M. O'Leary","author_inst":"Northeastern"},{"author_name":"Hailey C. Smith","author_inst":"Northeastern University"},{"author_name":"Emily B. Myers","author_inst":"University of Connecticut"},{"author_name":"Jamie Reilly","author_inst":"Temple"},{"author_name":"Jonathan E Peelle","author_inst":"Northeastern University"}],"rel_date":"2026-09-13","rel_site":"biorxiv"},{"rel_title":"Speech Intelligibility Index (SII) as a Potential Referral Metric for Adult Cochlear Implant Candidacy Evaluation","rel_doi":"10.64898\/2026.09.10.26362790","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362790","rel_abs":"Objectives: The purpose of this pilot study was to investigate (1) if the Speech Intelligibility Index (SII) could be used to identify ears that meet cochlear implant (CI) candidacy beyond the \"60\/60\" referral guidelines and (2) investigate the relationship between SII from patients' own hearing aids (HAs) and SII from optimally fit clinic-stock HAs such that a patient's own HAs can act as a proxy for an optimally fit HA and thus as a referral metric. Design: Prospective study of 23 participants ([&ge;] 18 years) with bilateral moderate to profound sensorineural hearing loss who were CI candidates in at least one ear. SII-Clinic (SII-C) values were recorded with probe-microphone measures using a Verifit II device (NAL-N2 targets) with speech stimuli presented at 60 dB A during patient CI evaluation in either their own HAs or clinic-stock HAs. SII values from participants' own HAs were recorded as part of a larger research protocol, thus SII-Personal (SII-P), with probe-microphone measures using a Verifit I device (NAL-RP targets) with pink noise stimuli presented at 65 dB A. Participants that did not wear HAs did not have SII-P calculated. Data was collapsed across ears. Correlation analysis between SII and best-aided consonant-nucleus-consonant (CNC) was conducted. Benchmark SII values were extrapolated using a best-fit line and CI candidacy rates reflecting various aided CNC scores that could be applied across CI centers. Nested logistic regression models were used to determine if the SII-C could improve model fit beyond the revised ear-specific 60\/60 referral guideline. The relationship between SII-C and SII-P was assessed with Wilcoxon signed-rank test and Spearman correlation. Results: Correlation between SII-C and aided CNC score was r = 0.82 (p < 0.001), and the correlation between SII-P and aided CNC was r = 0.46 (p = 0.014). Extrapolated benchmarks of SII were calculated based on different CNC candidacy cutoffs, and benchmarks were able to capture at least 83% of the ears that met CNC candidacy cutoffs. SII was also found to improve model fit with word recognition score (WRS) and pure tone average (PTA) for 60% CNC candidacy cutoff ({chi}2 = 9.7; p = 0.002) and increased discrimination (AUC = 0.89 to AUC = 0.99). There was no significant difference between SII-C and SII-P using the Wilcoxon signed-rank test (p = 0.559). Conclusions: A larger study is needed that includes more ears that do not qualify for a CI; however, the results of this study demonstrate that (1) SII has the potential to be used in conjunction with the 60\/60 referral guideline for CI candidacy evaluations and (2) SII can be used as a marker of audibility across different devices, including patients' own HAs, making SII an accessible metric during HA fittings and fine tunings.","rel_num_authors":4,"rel_authors":[{"author_name":"Jennifer A Kong","author_inst":"Vanderbilt University School of Medicine"},{"author_name":"Terrin N Tamati","author_inst":"The Ohio State University"},{"author_name":"Aaron C Moberly","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Jonathan D Neukam","author_inst":"Vanderbilt University Medical Center"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"AI detects a distributed blood metabolomic Systemotype associated with early stage ovarian cancer","rel_doi":"10.64898\/2026.09.10.26362758","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362758","rel_abs":"Early detection of ovarian cancer remains a clinical challenge because available blood biomarkers lack the sensitivity and specificity required for population screening. We tested whether early-stage ovarian cancer is associated with a distributed physiological state in the circulating metabolome. We analyzed untargeted metabolomic profiles from two independent retrospective cohorts: 91 serum samples (59 ovarian cancer, 32 healthy controls) and 83 plasma samples (63 ovarian cancer, 20 healthy controls). Assay-specific boosted decision trees were trained and evaluated independently within each cohort using five-fold cross-validation repeated over 50 randomized rounds. At selected operating points, mean cross-validated sensitivity and specificity were 99.0% and 99.8% in serum and 97.7% and 99.7% in plasma. Restricting inputs to strongly dysregulated features did not improve the overall sensitivity false positive rate trade off, and smaller panels reduced sensitivity. The cohorts shared 239 concordantly altered annotated features spanning lipid, amino-acid, steroid, central-carbon, and redox metabolism. These findings are consistent with a distributed metabolic response involving tumor and host, although tissue contributions were not measured. We propose that the classifier recognizes a metabolomic Systemotype, an integrated physiological state reflected in circulating metabolites. The results support further investigation of this framework.","rel_num_authors":4,"rel_authors":[{"author_name":"Hongyi Zhou","author_inst":"Georgia Institute of Technology"},{"author_name":"Jean-Luc Chaubard","author_inst":"OmicsIQ LLC"},{"author_name":"Benedict Benigno","author_inst":"Ovarian Cancer Institute"},{"author_name":"Jeffrey Skolnick","author_inst":"Georgia Tech"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Polygenic Risk and Genetic Predisposition in Post-Traumatic Epilepsy: A Framework for Risk Estimation","rel_doi":"10.64898\/2026.09.10.26362755","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362755","rel_abs":"Background Post-traumatic epilepsy (PTE) can be a lifelong complication of traumatic brain injury (TBI). We hypothesize that PTE develops according to a Two-Hit Hypothesis, in which the first hit is a genetic predisposition and the second hit is the TBI. Using two independent datasets, we provide the first evidence that PTE is a polygenic disorder, and we propose a whole-exome sequencing (WES) based framework to estimate the risk of developing PTE. Methods From a pool of thousands of screened veterans, we recruited a cohort of PTE subjects (n=28) and a control cohort of TBI subjects without PTE (n=22) and then performed WES. Approximately 375000 variants identified in each subject were compared to approximately 15000 verified epilepsy-associated variants from ClinVar. Fisher's exact test was used to identify variants associated with PTE, which were subsequently classified as either PTE-prone or PTE-protective. Odds ratios (ORs) were calculated at both the variant and subject levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive model. A second dataset was used to validate the model, and logistic calibration was performed to estimate the probability of developing PTE. Results Thirty PTE-prone and 56 PTE-protective variants were identified, with corresponding large-effect ORs. ROC analysis demonstrated excellent discrimination (AUC=0.97). Polygenic variant patterns differed between cohorts, with a predominance of PTE-prone variants in affected individuals and PTE-protective variants in controls. Conclusion Our findings support a polygenic framework consistent with the Two-Hit Hypothesis. In addition, we developed a framework to estimate individual polygenic risk for PTE.","rel_num_authors":6,"rel_authors":[{"author_name":"James WY Chen","author_inst":"VAGLAHS"},{"author_name":"Cindy Le","author_inst":"VAGLAHS"},{"author_name":"Kathleen Cui","author_inst":"VAGLAHS"},{"author_name":"Olga M Alexeeva","author_inst":"VAGLAHS"},{"author_name":"Janice Joo","author_inst":"VAGLAHS"},{"author_name":"Julia Bailey","author_inst":"VAGLAHS"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Caregiver-Rated Inappropriate Speech and Post-cTBS Motor Cortical Facilitation in Autism: A Pilot Biomarker Study","rel_doi":"10.64898\/2026.09.10.26362749","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362749","rel_abs":"Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items (\"Talks excessively\" and \"Talks to self loudly\") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.","rel_num_authors":12,"rel_authors":[{"author_name":"Joshua Ryan Smith","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Maria Bonnee","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Sarah Marler","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Rowan Atwood","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Brianna Lewis","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Seri Lim","author_inst":"Widener University, Institute of Graduate Clinical Psychology"},{"author_name":"Isaac Baldwin","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Hao Wu","author_inst":"Vanderbilt University"},{"author_name":"Jinyuan Liu","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Carissa Cascio","author_inst":"University of Kansas"},{"author_name":"Gagan Joshi","author_inst":"Massachusetts General Hospital"},{"author_name":"Paul Ryan Croarkin","author_inst":"Mayo Clinic Rochester"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Caregiver-Rated Inappropriate Speech and Post-cTBS Motor Cortical Facilitation in Autism: A Pilot Biomarker Study","rel_doi":"10.64898\/2026.09.10.26362749","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362749","rel_abs":"Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items (\"Talks excessively\" and \"Talks to self loudly\") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.","rel_num_authors":12,"rel_authors":[{"author_name":"Joshua Ryan Smith","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Maria Bonnee","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Sarah Marler","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Rowan Atwood","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Brianna Lewis","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Seri Lim","author_inst":"Widener University, Institute of Graduate Clinical Psychology"},{"author_name":"Isaac Baldwin","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Hao Wu","author_inst":"Vanderbilt University"},{"author_name":"Jinyuan Liu","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Carissa Cascio","author_inst":"University of Kansas"},{"author_name":"Gagan Joshi","author_inst":"Massachusetts General Hospital"},{"author_name":"Paul Ryan Croarkin","author_inst":"Mayo Clinic Rochester"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Atrial Cardiomyopathy Refines Cardiovascular Mortality Risk Across Cardiometabolic Risk Factor Burden","rel_doi":"10.64898\/2026.09.09.26362666","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362666","rel_abs":"Background: Electrocardiographic markers of atrial cardiomyopathy (AtCM) are associated with adverse cardiovascular outcomes. Whether AtCM further refines cardiovascular disease (CVD) mortality risk across increasing cardiometabolic risk factor (CMRF) burden is unclear. Methods: We analyzed 7,083 adults free of baseline CVD. AtCM was defined by the presence of [&ge;]1 ECG marker: prolonged P-wave duration [&ge;]120 ms in lead II, abnormal P-wave axis outside 0-75, or deep terminal negativity of the P wave in V1 <-100 V. CMRF burden was defined as the presence of 0, 1, or [&ge;]2 of hypertension, diabetes, and obesity. CVD mortality was ascertained through December 31, 2006. Results: Among 7,083 participants (mean age 58 years and 48% men), CVD mortality rates increased progressively across the six combined exposure groups. In a multivariable adjusted Cox proportional hazard analysis, AtCM identified higher-risk subgroups within each CMRF burden category, with risk increasing progressively across combined exposure groups and highest among participants with [&ge;]2 risk factors and AtCM (HR 2.25, 95% CI 1.75-2.87). In secondary analyses, a similar pattern was observed for individual CMRFs, with the combination of AtCM and hypertension, diabetes, or obesity conferring the highest risk compared with participants with neither condition (HR (95% CI): 1.58 (1.31-1.89); 2.08 (1.62-2.68); and 1.47 (1.19-1.82), respectively). Conclusions: ECG-defined AtCM refined CVD mortality risk across increasing CMRF burden. Individuals with both AtCM and multiple CMRFs had the highest risk. These findings support the potential role of ECG-based AtCM assessment as a scalable approach to improve cardiovascular risk stratification among individuals with CMRFs.","rel_num_authors":9,"rel_authors":[{"author_name":"Asem M Mohsen","author_inst":"Epidemiological Cardiology Research Center (EPICARE), Department of Cardiovascular Medicine, Wake Forest University School of Medicine"},{"author_name":"Moustafa Elnewishy","author_inst":"Epidemiological Cardiology Research Center (EPICARE), Department of Cardiovascular Medicine, Wake Forest University School of Medicine"},{"author_name":"Tarek Zaho","author_inst":"Cardiology department, Wake Forest School of Medicine"},{"author_name":"Patrick Cheon","author_inst":"Wake Forest School of Medicine"},{"author_name":"Brian C. Boursiquot","author_inst":"Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center"},{"author_name":"Parag A. Chevli","author_inst":"Department of Cardiovascular Medicine, Wake Forest University School of Medicine"},{"author_name":"Richard Kazibwe","author_inst":"Department of Internal Medicine, Wake Forest University School of Medicine"},{"author_name":"Prashant D. Bhave","author_inst":"Department of Cardiovascular Medicine, Wake Forest University School of Medicine"},{"author_name":"Elsayed Z. Soliman","author_inst":"Epidemiological Cardiology Research Center (EPICARE), Department of Cardiovascular Medicine, Wake Forest University School of Medicine"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Factors associated with a willingness to accept latent tuberculosis infection treatment among non-U.S.-born individuals: a situational choice experiment","rel_doi":"10.64898\/2026.09.09.26362665","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362665","rel_abs":"Introduction Despite efforts to eliminate tuberculosis (TB) in the United States (U.S.), many individuals diagnosed with latent TB infection (LTBI) who are at increased risk of progressing to TB disease do not initiate TB preventive treatment. Methods Among adults receiving primary care in a federally qualified community health center in the San Francisco Bay Area, California, we conducted a cross-sectional online survey using a situational choice experiment to assess the circumstances in which individuals at risk for TB based on nativity would accept LTBI treatment. In 10 randomized choice tasks, participants answered whether or not they would accept LTBI treatment. In situations where LTBI treatment was accepted, participants were asked a follow-up question about whether they would change their response knowing that reinfection is still possible with LTBI treatment. Attributes assessed included risk level of progression to TB, side effects, changes to co-medication, cost, number of clinic visits, blood draws, and reinfection risk. We conducted a mixed-effects logistic regression to estimate factors associated with treatment acceptance and predicted acceptance across scenarios. Results Of 852 individuals who consented, 458 (53.8%) had complete responses and were included in the analysis. LTBI treatment was accepted in 69.4% of choice scenarios (3180\/4580); among scenarios where treatment was initially accepted, 91.5% of scenarios (2911\/3180) remained accepted when reinfection possibility was introduced. Compared to situations with low risk of TB progression, high TB progression risk increased the acceptance of LTBI treatment (adjusted odds ratio aOR 2.55, 95% Confidence Interval (CI) = 2.03-3.19). Compared with fatigue as a referent, risk of any liver injury\/inflammation (aOR 0.29, 95% CI = 0.22-0.38), gastrointestinal side effects (aOR 0.53, 95% CI 0.41-0.69), rash (aOR 0.62, 95% CI 0.48-0.80) and out-of-pocket cost of $100 (aOR 0.32, 95% CI = 0.26-0.41 compared to $0) were associated with lower acceptance of LTBI treatment. Conclusions The decision to accept LTBI treatment was sensitive to treatment characteristics, suggesting that shared decision-making should be broadly promoted among individuals diagnosed with or at risk of LTBI, particularly in diverse primary care settings serving individuals born in high TB burden countries, with attention to individual concerns such as cost and side effects to improve LTBI treatment uptake.","rel_num_authors":15,"rel_authors":[{"author_name":"Sutina Chou","author_inst":"University of California, San Francisco"},{"author_name":"H\u00e9l\u00e8ne E Aschmann","author_inst":"University of California, San Francisco"},{"author_name":"Amy Tang","author_inst":"North East Medical Services"},{"author_name":"Meagan Lee","author_inst":"North East Medical Services"},{"author_name":"Zinnia Dong","author_inst":"North East Medical Services"},{"author_name":"Kit Lui","author_inst":"North East Medical Services"},{"author_name":"Yuqian Ouyang","author_inst":"North East Medical Services"},{"author_name":"Gina Chen","author_inst":"North East Medical Services"},{"author_name":"Katya L Salcedo","author_inst":"California Department of Public Health"},{"author_name":"Matthew T Murrill","author_inst":"University of California, San Francisco"},{"author_name":"Mehabuba Rahman","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Jennifer Flood","author_inst":"California Department of Public Health"},{"author_name":"Andrew Kerkhoff","author_inst":"University of California, San Francisco"},{"author_name":"Priya B Shete","author_inst":"University of California San Franciso"},{"author_name":"Tracy K Lin","author_inst":"University of California, San Francisco"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Co-Designing Pay-It-Forward Strategies to Improve Retention in Cervical Cancer Care in Kenya: A Formative Participatory Study","rel_doi":"10.64898\/2026.09.10.26362751","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362751","rel_abs":"Background: Retention is the bridge between diagnosis and survival in low and middle-income countries, including Kenya, where the cost of cervical cancer treatment can amount to several years of an average woman's earnings. Pay-it-forward (PIF), a prosocial approach in which an individual receives a gift and then considers supporting another person, offers a community-driven strategy to reduce barriers and improve engagement and retention in cancer care. This study explored opportunities to integrate PIF strategies into cervical cancer care through a human-centered design (HCD) workshop. Methods: We conducted a two-day HCD workshop in Kenya, informed by the WHO\/UNICEF normative guide on co-creation with women with cervical cancer (on treatment or survivors), community representatives, and oncology care providers. Experience diagramming mapped the patient journey and identified barriers to retention. A designer-led team then developed the initial PIF prototypes, which were iteratively co-designed and refined with participants to align with their needs and preferences. Audio recordings and photographs of the co-design activities were transcribed and analyzed using rapid, team-based qualitative synthesis. Results: Among 25 participants, 52% (n=13) were women with cervical cancer and 48% (n=12) were health care providers or community representatives. Participants identified costs, extenuating circumstances, treatment side effects, health system challenges, discrimination, fear, and anxiety as barriers to retention. These barriers informed the co-design of six PIF component strategies: peer navigation, transport voucher fund, integrated service gift, a message board in clinic waiting areas, health insurance support fund, and a basket of kindness at checkout. Three of these (peer navigation, transport voucher fund, and health insurance support) have been effectively implemented in Kenya before for other health services. Participants noted that including both monetary and non-monetary nudges was essential but emphasized the need for transparency and oversight in monetary approaches. Conclusion: The Kenyan context provided rich opportunities for PIF component strategies to explore and enhance retention in cancer care. We hypothesize that PIF may improve retention by activating social capital through reciprocity, empathy, and a sense of belonging. Future work should pilot these PIF strategies to assess feasibility, acceptability, and appropriateness, and determine whether reciprocal giving can be sustained. Keywords: Pay-it-forward, cervical cancer, retention, engagement, and co-design Contributions to Literature We propose a hypothesized mechanism through which pay-it-forward may improve engagement and retention in care by activating social capital through reciprocity, empathy, trust, commitment, and belonging. We provide a menu of monetary and non-monetary pay-it-forward strategies that can be adapted and tested across different health care settings, offering practical options for addressing financial and psychosocial barriers to retention. We extend the pay-it-forward literature beyond one-time, low-cost preventive services by applying the approach to long-term, high-cost cancer care, where sustained engagement presents distinct implementation challenges.","rel_num_authors":17,"rel_authors":[{"author_name":"Harriet  Fridah Adhiambo","author_inst":"Kenya Medical Research Institute, Washington University in St. Louis"},{"author_name":"Anne Trolard","author_inst":"Washington University In St Louis: Washington University in St Louis"},{"author_name":"Dorothy  Imbuka Mangale","author_inst":"Washington University in St Louis"},{"author_name":"Eric Thuo","author_inst":"Washington University in St. Louis"},{"author_name":"Philippa Kadama Makanga","author_inst":"Infectious Diseases Institute"},{"author_name":"Lucy Akoo","author_inst":"Jaramogi Oginga Odinga Teaching and Referral Hospital"},{"author_name":"Jerome Katumba","author_inst":"Maseno University, School of Medicine"},{"author_name":"Phiona Adagi","author_inst":"Jaramogi Oginga Odinga Teaching and Referral Hospital"},{"author_name":"Betsy Abente","author_inst":"Washington University in St. Louis"},{"author_name":"Beryne Odeny","author_inst":"Washington University in St. Louis"},{"author_name":"Elizabeth Bukusi","author_inst":"Kenya Medical Research Institute"},{"author_name":"Byron Powell","author_inst":"Washington University in St. Louis"},{"author_name":"Bettina Drake","author_inst":"Washington University in St. Louis"},{"author_name":"Dickens Onyango","author_inst":"County Department of Health, Kisumu County Government"},{"author_name":"Elvin Geng","author_inst":"Washington University in St. Louis"},{"author_name":"Joseph D. Tucker","author_inst":"University of North Carolina, Chapel Hill"},{"author_name":"Thomas Odeny","author_inst":"Washington University in St. Louis"}],"rel_date":"2026-09-12","rel_site":"medrxiv"},{"rel_title":"Evidence of Chemical Wave-Electric Field Interaction in Bacterial Cells","rel_doi":"10.64898\/2026.09.05.749092","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.05.749092","rel_abs":"Charge neutrality is widely assumed in living cells, yet this approximation breaks down in micron-scale bacteria where charge imbalance and spatial confinement are significant. Using Poisson-Nernst-Planck modeling, we show that unequal cation-anion effectiveness and bounded geometry generate extended intracellular diffuse layers and steady electric fields. We demonstrate that such fields couple directly to intracellular chemical waves, focusing on the Min-protein oscillator of Escherichia coli. Electric-field-driven transport skews the dispersion-mode structure, induces mode crossings, and selectively amplifies Turing and Hopf-Turing instabilities over intermediate length scales, constraining the permitted {omega}-k spectrum and setting optimal wavelengths and modal growth-rate velocities. Experiments in wild-type, anucleate, and antibiotic-treated cells, together with simulations of nucleoid-dependent charge density and field strength, quantitatively validate these predictions and explain observed pattern asymmetries and frequency modulations. Crucially, asymmetric wave-field coupling promotes quasi-periodicity through controlled mode competition, enhancing robustness to noise, cell-size variation, and growth. These findings identify intracellular electric fields as active regulators of biochemical patterning and suggest a general role for wave-field interactions in cellular self-organization.","rel_num_authors":2,"rel_authors":[{"author_name":"Jie-Pan Shen","author_inst":"Academia Sinica"},{"author_name":"Chia-Fu Chou","author_inst":"Academia Sinica"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Mapping tsetse fly connectivity in Uganda with machine learning landscape genetics","rel_doi":"10.64898\/2026.09.11.750686","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.750686","rel_abs":"Introduction - Tsetse flies (genus Glossina) are biting insects that transmit human and animal trypanosomiases across sub-Saharan Africa, and sustainable vector control depends on understanding dispersal barriers and reinvasion routes. Despite major progress toward elimination, Uganda remains at risk for both human forms of the disease (Trypanosoma brucei gambiense and T. b. rhodesiense) and planners still lack reliable maps of tsetse movement and reinvasion risk. Methods and Results - We address this gap with machine-learning landscape genetics and species distribution models, integrating estimates of population genetic distance and geospatial environmental data to predict and map Glossina fuscipes fuscipes connectivity across Uganda and western Kenya. Inputs included microsatellite genotypes from 11 loci genotyped in 2,736 flies sampled from 87 localities and remotely sensed environmental predictors summarized along least-cost paths. Random forest models predicted patterns of genetic differentiation better than distance-only models, supporting the use of a machine-learning framework for connectivity inference across complex heterogeneous landscapes, and identified variables related to temperature and water availability as the strongest predictors of genetic connectivity. Conclusions - Combining landscape genetics predictions of connectivity with a species distribution model revealed regions with high habitat suitability but low connectivity that represent priority zones for area-wide integrated pest management strategies, including established riverine control tools such as tiny targets and other targeted interventions aimed at reducing reinvasion risk. These results provide biologically interpretable maps and quantitative uncertainty metrics that can guide targeted tsetse control, while providing a transferable analytical pipeline for modeling and mapping genetic connectivity across other species and landscapes.","rel_num_authors":15,"rel_authors":[{"author_name":"Norah P. Saarman","author_inst":"Utah State University"},{"author_name":"Ryan Griffiths","author_inst":"Utah State University; Purdue University"},{"author_name":"Anusha Bishop","author_inst":"University of California, Davis"},{"author_name":"Camilla Moses","author_inst":"Utah State University"},{"author_name":"Emily Calhoun","author_inst":"Utah State University"},{"author_name":"Ethan Meredith","author_inst":"Utah State University"},{"author_name":"Rosemary Bateta","author_inst":"Kenya Agricultural and Livestock Research Organization"},{"author_name":"Winnie A. Okeyo","author_inst":"Kenya Agricultural and Livestock Research Organization; Maseno University"},{"author_name":"Paul O. Mireji","author_inst":"Kenya Agricultural and Livestock Research Organization; Kenya Medical Research Institute"},{"author_name":"Grace Murilla","author_inst":"Kenya Agricultural and Livestock Research Organization"},{"author_name":"Sylvance Okoth","author_inst":"Kenya Agricultural and Livestock Research Organization"},{"author_name":"Robert Opiro","author_inst":"Gulu University"},{"author_name":"Richard Echodu","author_inst":"Gulu University"},{"author_name":"Serap Aksoy","author_inst":"Yale School of Public Health"},{"author_name":"Adalgisa Caccone","author_inst":"Yale University"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Genomic characterization reveals high clonal redundancy in two Acropora cervicornis nurseries in the Dominican Republic","rel_doi":"10.64898\/2026.09.11.750210","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.750210","rel_abs":"Acropora cervicornis is often propagated through fragmentation (i.e., clonal propagation), a common practice implemented by restoration projects. Known as asexual propagation, this strategy may rapidly increase coral cover but reduces genetic variation. We used 2b-RAD sequencing to characterize multilocus genotypic variation among 45 A. cervicornis colonies maintained in two in-situ nurseries (Cap Cana, Acuario) in Punta Cana, Dominican Republic. After reference-based SNP discovery and filtering, 2,515 high-quality SNPs were retained in the dataset. Principal coordinate analysis (PCoA), hierarchical clustering, identity-by-state (IBS) distances, and relatedness estimates identified only three multilocus genets among the 45 colonies (AC1, AC2, and AC3). Of these, AC2 was the most abundant (n = 23; 51.1%), followed by AC3 (n = 14; 31.1%) and lastly AC1 (n = 8; 17.8%). Within-genet IBS distances (0.153-0.227) did not overlap with between-genet distances (0.406-0.497). AC1 and AC2 were detected in both nurseries, whereas AC3 was limited to Acuario. These results reveal substantial clonal redundancy among sampled nursery colonies that determines local reef conservation efforts. These data highlight the value of incorporating genotype identification in nursery-based coral restoration projects.","rel_num_authors":6,"rel_authors":[{"author_name":"Shamwari Anseeuw Carrasco","author_inst":"Rutgers University"},{"author_name":"Kasey H Walsh","author_inst":"Rutgers University"},{"author_name":"Rebecca Garcia-Camps","author_inst":"Fundacion Punta Cana"},{"author_name":"Ainhoa L Zubillaga","author_inst":"Fundacion Puntacana"},{"author_name":"Aldo Croquer","author_inst":"The Nature Conservancy"},{"author_name":"Debashish Bhattacharya","author_inst":"Rutgers University"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"The caddisfly gut microbiome contributes to the consumption of riparian leaf litter within rivers","rel_doi":"10.64898\/2026.09.10.749941","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.749941","rel_abs":"Ecosystem functions can be regulated by biodiversity ranging from broad to narrow scales, including variation within a species. For most multicellular life, intraspecific variation is determined not only by an organism's phenotype and genotype, but also variation imparted by their microbiome. Here, we investigate how leaf decomposition in rivers is affected by phenotypic variation in plant secondary metabolites (PSMs) and antibiotic-induced variation within the gut microbiomes of aquatic macroinvertebrate decomposers. We found that consumption by Dicosmoecus caddisflies was inhibited by the presence of dietary PSMs from riparian Alnus rubra trees, irrespective of the state of their gut microbiome. We further compared consumption of diets prepared from 20 different local and non-local A. rubra trees. We found that antibiotic-treated and control caddisflies consumed similar amounts of diets containing local A. rubra PSMs. However, compared to caddisflies with an intact gut microbiome, antibiotic-treated caddisflies consumed less of non-local A. rubra diets. Thus, decomposition by caddisflies could be regulated by both host adaptation to local resources and bacterial-mediated digestion of non-local resources. Overall, our study suggests that gut microbiomes can facilitate adjustment of macroinvertebrate decomposers to novel plant phenotypes, which may arise from shifting spatial distributions of plants in response to global change.","rel_num_authors":5,"rel_authors":[{"author_name":"Jonathan R Dickey","author_inst":"University of California San Diego, Department of Ecology, Behavior and Evolution, La Jolla, California, USA, 93093"},{"author_name":"Dahlia A Loomis","author_inst":"University of California San Diego, Department of Ecology, Behavior and Evolution, La Jolla, California, USA, 93093"},{"author_name":"Andres Mauricio Caraballo Rodriguez","author_inst":"University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, California, 92093, USA"},{"author_name":"Pieter Dorrestein","author_inst":"University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, California, 92093, USA"},{"author_name":"Sara L Jackrel","author_inst":"University of California San Diego, Department of Ecology, Behavior and Evolution, La Jolla, California, USA, 93093"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Improved two-stage GWAS identifies rare genetic variants associated with dermo susceptibility in the eastern oyster","rel_doi":"10.64898\/2026.09.08.750289","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750289","rel_abs":"Perkinsus marinus is a protist that causes the wasting disease dermo in the Eastern oyster, Crassostrea virginica. The disease causes high mortality of both wild and cultured oysters, impacting ecosystem health and aquaculture. Despite decades of research, the genetic mechanisms of dermo resistance remain poorly understood. Traditional selective breeding based on phenotypes has yielded improvements in dermo resistance, but progress has been slow, likely due to the trait's complex genetic architecture. Understanding the genetic mechanisms underlying dermo resistance may facilitate advanced breeding to accelerate improvement. This study conducted genome-wide association studies (GWAS) of dermo resistance, leveraging a multi-generational dataset comprising 2,423 oysters phenotyped for survival following a dermo challenge and genotyped using a high-density 66K SNP array. A two-stage GWAS with more inclusive quality control identified 48 dermo-resistance markers, including many associated with genes for innate immune response and energy metabolism. Most dermo-resistance markers showed rare minor alleles occurring at higher frequencies in oysters that died after challenge, suggesting that these rare alleles are deleterious and associated with dermo susceptibility. The strongest association was with a polymorphism in the mucin-5AC-like gene, explaining 8.1% of phenotypic variation and suggesting that mucus production plays a crucial role in dermo resistance. The inclusion of these markers has improved genomic prediction accuracy, and their identification provides new insights into genomic variation and the architecture of dermo resistance, informing future strategies for genetic improvement.","rel_num_authors":9,"rel_authors":[{"author_name":"Paul Coyne","author_inst":"Rutgers University"},{"author_name":"Henry Sun","author_inst":"Duke University"},{"author_name":"Zhenwei Wang","author_inst":"Rutgers University"},{"author_name":"Sandra Casa","author_inst":"Louisiana State University"},{"author_name":"Jerome La Peyre","author_inst":"Louisiana State University"},{"author_name":"Mason Williams","author_inst":"Auburn University"},{"author_name":"Scott Rikard","author_inst":"Auburn University"},{"author_name":"David Bushek","author_inst":"Rutgers University"},{"author_name":"Ximing Guo","author_inst":"Rutgers University"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Environment-Aware DNA Language Model for Stress-Responsive Genomic Prioritization in Maize","rel_doi":"10.64898\/2026.09.11.749989","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.749989","rel_abs":"Abiotic stresses such as heat and drought severely reduce maize productivity, yet identifying genomic regions that confer stress resilience remains a challenge. Inspired by advances in Large Language Models (LLMs), Genomic Foundation Models (GFMs) have recently emerged as a promising approach for capturing regulatory patterns through large-scale pre-training on DNA sequences. However, their application to plant stress-response analysis remains unexplored. This study presents an environment-aware DNA-LLM that adapts AgroNT, a transformer-based GFM pre-trained on diverse plant genomes, by incorporating stress-specific prompt tokens. Through parameter-efficient fine-tuning, the model learns stress-conditioned sequence representations that form distinct clusters in the embedding space across environmental contexts. By combining stress-induced shifts in these sequence representations relative to control conditions with transformer attention patterns, we prioritized putative heat- and drought-responsive genomic regions associated with grain yield in the Genomes-to-Fields (G2F) panel. Prioritized regions were supported by spatiotemporal differential gene-expression evidence and overlap with stress-associated quantitative trait loci. They were further characterized through transcription-factor family analysis and regulatory motif enrichment. Attention-guided analysis additionally identified stress-associated motifs enriched within model-emphasized sequence regions. Overall, the prioritized loci were proximal to genes involved in transcriptional regulation, signaling, and metabolic pathways relevant to abiotic-stress adaptation, demonstrating the potential of stress-conditioned transformer-based sequence modeling for environment-aware genome-to-phenome analysis.","rel_num_authors":6,"rel_authors":[{"author_name":"Debasmita Pal","author_inst":"Michigan State University"},{"author_name":"Aaron Odell","author_inst":"University of North Carolina Chapel Hill"},{"author_name":"Anuradha Singh","author_inst":"Michigan State University"},{"author_name":"Addie M. Thompson","author_inst":"Michigan State University"},{"author_name":"Arun Ross","author_inst":"Michigan State University"},{"author_name":"Anne Thessen","author_inst":"University of North Carolina Chapel Hill"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Microevolutionary cophylogeny reflects host-symbiont population dynamics and human mitonuclear interactions","rel_doi":"10.64898\/2026.09.11.751054","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.751054","rel_abs":"Cophylogeny, the study of phylogenetic similarity between interacting organisms, provides insights into the specificity and shared evolutionary history of symbiosis. While the ecological drivers of cophylogeny have been investigated at the macroevolutionary scale, the influence of these processes on microevolution remains unclear. This is due, in part, to the fact that the ancestral relations between individuals within a sexually reproducing eukaryotic host species cannot be well represented with a single phylogenetic tree, since genetic distances between individuals change substantially across the genome due to meiotic recombination. This heterogeneity can be captured and utilized through the inference of an ancestral recombination graph (ARG) built from the genomic data of the host. Here, we propose to measure microevolutionary cophylogeny by comparing a symbiont evolutionary tree to a host ARG. This approach simultaneously measures genome-wide cophylogeny, as well as locus-specific signals. Through simulations, we investigate the effects of transmission mode, population structure, admixture, and allelic incompatibility on microevolutionary cophylogeny. In contrast to macroevolutionary patterns, we find a limited relationship between cophylogeny and vertical transmission, with vertically transmitted host-symbiont systems displaying no cophylogeny in large panmictic populations. We apply our approach to mitochondrial and nuclear genomes within the 1000 Genomes Project--a host-symbiont system with strict maternal transmission--and observe substantial variation in mitochondrial-nuclear (mitonuclear) cophylogeny across human populations. Finally, we investigate locus-specific signals of cophylogeny and observe limited evidence of mitonuclear incompatibility.","rel_num_authors":2,"rel_authors":[{"author_name":"Rowan Hart","author_inst":"University of Chicago, Dept. of Ecology & Evolution"},{"author_name":"Matthias Steinruecken","author_inst":"University of Chicago, Dept. of Ecology & Evolution"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"High ammonium suppresses nitrate transporter expression and constrains thermal plasticity in the green macroalga Codium cylindricum","rel_doi":"10.64898\/2026.09.10.750591","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750591","rel_abs":"Nitrogen source and availability can modulate thermal stress responses in marine macroalgae, yet the transcriptional mechanisms underpinning these effects in green seaweeds remain poorly understood. We tested how three N sources (ammonium, nitrate, urea) at low (5 M) and high (100 M) concentrations influence the thermal physiology and gene expression of Codium cylindricum. Thermal performance curves were constructed for growth, photosynthesis, and pigment content across a 5-29 {degrees}C gradient, coupled with transcriptomic analysis at three key temperatures. At high concentrations, ammonium reduced maximum growth rate by 25% and lowered the thermal optimum relative to nitrate and urea, while nitrate supported the broadest thermal performance. Urea constrained thermal breadth regardless of concentration. These responses were linked to differential expression of Nitrogen assimilation genes. Ammonium suppressed nitrate transporter genes (NRT) and nitrite transporter (FNT), and drove pigment accumulation with rising temperature despite reduced growth, suggesting resource reallocation from growth to photoprotection. In contrast, nitrate upregulated photosystem and phosphorylation-related genes. Our findings demonstrate that Nitrogen source and concentration jointly determine the thermal threshold of C. cylindricum, with high ammonium reducing both maximum growth and the temperature at which it is achieved. This highlights how shifting coastal nutrient regimes may alter macroalgal resilience under ocean warming.","rel_num_authors":4,"rel_authors":[{"author_name":"Kai-Le Zhong","author_inst":"The University of Hong Kong"},{"author_name":"Pamela A. FERNANDEZ","author_inst":"Universidad de Los Lagos"},{"author_name":"Bayden Russell","author_inst":"The University of Hong Kong"},{"author_name":"Juan Diego Gaitan Espitia","author_inst":"The University of Hong Kong"}],"rel_date":"2026-09-12","rel_site":"biorxiv"},{"rel_title":"Impact of Australias 60-Day Dispensing Policy on Medicine Use: An Interrupted Time Series of the Stage 1 Roll-out","rel_doi":"10.64898\/2026.09.09.26362679","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362679","rel_abs":"Objective: To evaluate the real-world impact of Stage 1 of Australias 60-day dispensing policy on medicine utilisation and contextualise changes in dispensing with medicine shortages. Methods: We conducted an interrupted time series analysis of aggregated national monthly dispensing data from the Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme for the 247 medicines included in Stage 1 of the 60-day dispensing policy. Data from January 2020 to October 2025 were analysed, with September 2023 defined as policy implementation. Linear regression assessed changes in monthly dispensing trends before and after implementation, accounting for autocorrelation and seasonal variation. A relative change of at least 5% in the post-intervention dispensing slope compared with the pre-intervention slope was prespecified as a potentially clinically meaningful change. Therapeutic Goods Administration shortage reports were used to contextualise observed changes. Results: Of 247 medicines, 131 (53%) had increasing and 116 (47%) had decreasing post-intervention dispensing trends; of which 86 (66%) and 71 (61%), were statistically significant, respectively. However, only 8 medicines (3%) demonstrated at least 5% relative change in dispensing slope, six of which had reported shortages. Medicine-specific changes coincided with shortages, product deletions and therapeutic substitution, complicated attribution of changes to the 60-day dispensing policy. Conclusion: Stage 1 of Australias 60-day dispensing policy was not associated with widespread changes in dispensing for most included medicines. Limited changes were plausibly influenced by concurrent shortages and other supply-related events. These findings provide reassurance that extended dispensing did not result in major increases in medicine utilisation at the population level, although continued monitoring is warranted as policy uptake expands.","rel_num_authors":6,"rel_authors":[{"author_name":"Jack Janetzki","author_inst":"Adelaide University"},{"author_name":"Nicole Pratt","author_inst":"Adelaide University"},{"author_name":"Lachlan Dalli","author_inst":"Monash University"},{"author_name":"Pilar Cataldo Miranda","author_inst":"Monash University"},{"author_name":"Sallie-Anne Pearson","author_inst":"University of New South Wales"},{"author_name":"Lisa Kalisch Ellett","author_inst":"Adelaide University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Out-of-pocket costs and productivity losses associated with influenza illness and caregiving in a household study in the United States, 2024-2025","rel_doi":"10.64898\/2026.09.10.26362662","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362662","rel_abs":"Background: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [&ge;]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([&ge;]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.","rel_num_authors":18,"rel_authors":[{"author_name":"Elizabeth B White","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Jamison Pike","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Celibell Y Vargas","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Yuwei Zhu","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Caroline A O'Neil","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Jessica E Biddle","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Lydia Bristol","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Emily McNair","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Son H McLaren","author_inst":"Columbia University Irving Medical Cetner"},{"author_name":"Ellen Sano","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Theresa A Scott","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Rachel Presti","author_inst":"Washington University School of Medicine"},{"author_name":"Stephanie A Fritz","author_inst":"Washington University School of Medicine"},{"author_name":"Lisa A Prosser","author_inst":"University of Michigan"},{"author_name":"Melissa S Stockwell","author_inst":"Columbia University Vagelos College of Physicians and Surgeons"},{"author_name":"Carlos G Grijalva","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Jennie H Kwon","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Alexandra Mellis","author_inst":"Centers for Disease Control and Prevention"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Out-of-pocket costs and productivity losses associated with influenza illness and caregiving in a household study in the United States, 2024-2025","rel_doi":"10.64898\/2026.09.10.26362662","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362662","rel_abs":"Background: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [&ge;]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([&ge;]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.","rel_num_authors":18,"rel_authors":[{"author_name":"Elizabeth B White","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Jamison Pike","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Celibell Y Vargas","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Yuwei Zhu","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Caroline A O'Neil","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Jessica E Biddle","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Lydia Bristol","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Emily McNair","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Son H McLaren","author_inst":"Columbia University Irving Medical Cetner"},{"author_name":"Ellen Sano","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Theresa A Scott","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Rachel Presti","author_inst":"Washington University School of Medicine"},{"author_name":"Stephanie A Fritz","author_inst":"Washington University School of Medicine"},{"author_name":"Lisa A Prosser","author_inst":"University of Michigan"},{"author_name":"Melissa S Stockwell","author_inst":"Columbia University Vagelos College of Physicians and Surgeons"},{"author_name":"Carlos G Grijalva","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Jennie H Kwon","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Alexandra Mellis","author_inst":"Centers for Disease Control and Prevention"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Out-of-pocket costs and productivity losses associated with influenza illness and caregiving in a household study in the United States, 2024-2025","rel_doi":"10.64898\/2026.09.10.26362662","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362662","rel_abs":"Background: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [&ge;]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([&ge;]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.","rel_num_authors":18,"rel_authors":[{"author_name":"Elizabeth B White","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Jamison Pike","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Celibell Y Vargas","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Yuwei Zhu","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Caroline A O'Neil","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Jessica E Biddle","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Lydia Bristol","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Emily McNair","author_inst":"Centers for Disease Control and Prevention"},{"author_name":"Son H McLaren","author_inst":"Columbia University Irving Medical Cetner"},{"author_name":"Ellen Sano","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Theresa A Scott","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Rachel Presti","author_inst":"Washington University School of Medicine"},{"author_name":"Stephanie A Fritz","author_inst":"Washington University School of Medicine"},{"author_name":"Lisa A Prosser","author_inst":"University of Michigan"},{"author_name":"Melissa S Stockwell","author_inst":"Columbia University Vagelos College of Physicians and Surgeons"},{"author_name":"Carlos G Grijalva","author_inst":"Vanderbilt University Medical Center"},{"author_name":"Jennie H Kwon","author_inst":"Northwestern University Feinberg School of Medicine"},{"author_name":"Alexandra Mellis","author_inst":"Centers for Disease Control and Prevention"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Estrogen interactions with breast cancer risk variants in regulatory DNA","rel_doi":"10.64898\/2026.09.09.26362309","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362309","rel_abs":"Insight into population-level gene-environment (GxE) interactions is a major goal in understanding polygenic diseases, such as breast cancer. We integrated massively parallel reporter assays (MPRA), chromatin profiling, and network analysis to identify estrogen-responsive breast cancer variants. Screening 1,604 GWAS-identified breast cancer variants identified 73 estrogen-modulated SNVs (emSNVs). Chromatin accessibility modeling validated allele-specific effects, identifying variants that disrupt pioneer factor binding to chromatin and others that modulate transcription factor (TF) recruitment to pre-accessible enhancers. emSNV targets converged on pathways including mitochondrial metabolism, NF-{kappa}B signaling, and chromatin regulation. Aggregating emSNVs into a polygenic risk score (PRSE2) revealed interactions with reproductive risk factors in 13,026 post-menopausal BRCA cases and 108,265 controls, including age at first birth (p=0.0052); a control PRS lacking estrogen-responsive variants showed no interactions. This framework bridges molecular and epidemiological GxE studies to uncover variants whose disease associations depend on environmental context, with implications for understanding polygenic disease risk.","rel_num_authors":20,"rel_authors":[{"author_name":"Ibtihal M Elfaki","author_inst":"Stanford University"},{"author_name":"Laura Kellman","author_inst":"Stanford University"},{"author_name":"Robin Meyers","author_inst":"Stanford University"},{"author_name":"Luca Ducoli","author_inst":"Stanford University"},{"author_name":"Martina Fu","author_inst":"Stanford University"},{"author_name":"Kamal Obbad","author_inst":"Stanford University"},{"author_name":"Smarajit Mondal","author_inst":"Stanford University"},{"author_name":"Xue Yang","author_inst":"Stanford University"},{"author_name":"Douglas F Porter","author_inst":"Stanford University"},{"author_name":"David Reynolds","author_inst":"Stanford University"},{"author_name":"Suhas Srinivasan","author_inst":"Stanford University"},{"author_name":"Taishi Nakase","author_inst":"Stanford University"},{"author_name":"Mineto Ota","author_inst":"The University of Tokyo"},{"author_name":"Tania Fabo","author_inst":"Stanford University"},{"author_name":"Jordan Meyers","author_inst":"Stanford University"},{"author_name":"Lu Yang","author_inst":"Stanford University"},{"author_name":"Nasa Sinnot-Armstrong","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Kenneth Westerman","author_inst":"Massachusetts General Hospital"},{"author_name":"Linda Kachuri","author_inst":"Stanford University"},{"author_name":"Paul Khavari","author_inst":"Stanford University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Lived experiences and occupational pressures among Vietnamese nail salon workers in Maryland","rel_doi":"10.64898\/2026.09.10.26362742","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362742","rel_abs":"Individuals of Vietnamese descent comprise a majority of the United States nail salon workforce. Whereas prior research has centered on chemical exposures, thematic analysis of interviews with Vietnamese nail salon workers around Baltimore, Maryland examined the lived experiences of nail salon workers. Six themes were identified: (1) nail work as a familial livelihood and a sacrifice-oriented pathway towards intergenerational mobility; (2) perceived flexibility within the workplace with low control; (3) professional pride grounded in artistry, detail, and customer care; (4) cumulative occupational risks; (5) emotional labor as an expected and core component of nail salon work; and (6) limited perceived capacity to change working conditions. These findings suggest that the occupational pressures in nail salon work cannot be solely framed as a lack of worker knowledge or motivation towards adopting safer practices. Intervention success depends on a holistic view of workers' lives, whose choices are shaped by family obligations, customer demands, and conditions largely outside their control. Therefore, efforts to improve nail salon health may benefit from shifting the burden of risk management away from individual workers and engaging the wider community.","rel_num_authors":2,"rel_authors":[{"author_name":"Kevin K. Nguyen","author_inst":"The Johns Hopkins University"},{"author_name":"Emily M. Agree","author_inst":"The Johns Hopkins University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"The Impact of Opioid, Opioid Agonist Therapy, and Cannabis Exposure on Fetal Growth: A Population-Based Cohort Study","rel_doi":"10.64898\/2026.09.10.26362743","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362743","rel_abs":"Objectives. The primary objective is to determine the extent to which fetal growth profiles in opioid and opioid agonist (OAT) exposed pregnancies are influenced by cannabis exposure. Secondary objectives are to examine differences in fetal and neonatal morbidity and mortality. Design. Population-based cohort study. Setting. Ontario, Canada, in a public healthcare system. Participants. All live\/stillborn births between April 1st, 2013, and March 31st, 2021. Exposures. Substance exposure in pregnancy, including opioids, opioid agonist therapy, cannabis, and nicotine. Main Outcome Measures. Primary outcome measures included incidence of small for gestational age (<3rd and <10th percentile for sex) and intrauterine growth restriction. Secondary outcome measures included incidence of stillbirth, severe neonatal morbidity (SNM), neonatal mortality, and neonatal abstinence syndrome (NAS). Results. 959,731 births are included with exposures classified as 864,508 (88.0%) no substance, 73,815 (7.7%) nicotine, 23,003 (2.4%) cannabis, 7,694 (0.8%) opioid, and 5,353 (0.6%) OAT. Cannabis co-exposure was reported in 1 out of every 6 opioid and\/or OAT exposed births. The observed proportions of SGA and IUGR were approximately doubled across substance-exposed groups compared with the no substance exposure group. In adjusted analyses, cannabis exposure alone was associated with an 84% increased risk of IUGR, compared with 14% for opioid exposure alone and 60% for OAT exposure alone. SNM was observed in 7.2% of no substance exposure neonates, compared to 13.9% and 14.2% of opioid and OAT exposed neonates, respectively. NAS was diagnosed in 70.6% of all OAT exposed neonates, compared to 34.3% of all opioid exposed neonates. Risks for all outcomes across all cannabis co-exposure groups were significantly elevated relative to the no substance exposure group, with estimates ranging from 43% to 107% increased risk. Conclusions. Prenatal co-exposure to opioid and\/or OAT along with cannabis appears to place infants at the highest risk. Isolated cannabis use has similar, if not more significant, impacts on fetal growth as opioid and\/or OAT use. This information may serve as an important starting point in the design of effective harm reduction strategies in this patient population.","rel_num_authors":6,"rel_authors":[{"author_name":"Jessica Pudwell","author_inst":"Queen's University"},{"author_name":"Kira King","author_inst":"Queen's University"},{"author_name":"Wenbin Li","author_inst":"Queen's University"},{"author_name":"Maria P. Velez","author_inst":"McGill University"},{"author_name":"Shannon Bainbridge","author_inst":"University of Ottawa"},{"author_name":"Laura Gaudet","author_inst":"Queen's University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"The Impact of Opioid, Opioid Agonist Therapy, and Cannabis Exposure on Fetal Growth: A Population-Based Cohort Study","rel_doi":"10.64898\/2026.09.10.26362743","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362743","rel_abs":"Objectives. The primary objective is to determine the extent to which fetal growth profiles in opioid and opioid agonist (OAT) exposed pregnancies are influenced by cannabis exposure. Secondary objectives are to examine differences in fetal and neonatal morbidity and mortality. Design. Population-based cohort study. Setting. Ontario, Canada, in a public healthcare system. Participants. All live\/stillborn births between April 1st, 2013, and March 31st, 2021. Exposures. Substance exposure in pregnancy, including opioids, opioid agonist therapy, cannabis, and nicotine. Main Outcome Measures. Primary outcome measures included incidence of small for gestational age (<3rd and <10th percentile for sex) and intrauterine growth restriction. Secondary outcome measures included incidence of stillbirth, severe neonatal morbidity (SNM), neonatal mortality, and neonatal abstinence syndrome (NAS). Results. 959,731 births are included with exposures classified as 864,508 (88.0%) no substance, 73,815 (7.7%) nicotine, 23,003 (2.4%) cannabis, 7,694 (0.8%) opioid, and 5,353 (0.6%) OAT. Cannabis co-exposure was reported in 1 out of every 6 opioid and\/or OAT exposed births. The observed proportions of SGA and IUGR were approximately doubled across substance-exposed groups compared with the no substance exposure group. In adjusted analyses, cannabis exposure alone was associated with an 84% increased risk of IUGR, compared with 14% for opioid exposure alone and 60% for OAT exposure alone. SNM was observed in 7.2% of no substance exposure neonates, compared to 13.9% and 14.2% of opioid and OAT exposed neonates, respectively. NAS was diagnosed in 70.6% of all OAT exposed neonates, compared to 34.3% of all opioid exposed neonates. Risks for all outcomes across all cannabis co-exposure groups were significantly elevated relative to the no substance exposure group, with estimates ranging from 43% to 107% increased risk. Conclusions. Prenatal co-exposure to opioid and\/or OAT along with cannabis appears to place infants at the highest risk. Isolated cannabis use has similar, if not more significant, impacts on fetal growth as opioid and\/or OAT use. This information may serve as an important starting point in the design of effective harm reduction strategies in this patient population.","rel_num_authors":6,"rel_authors":[{"author_name":"Jessica Pudwell","author_inst":"Queen's University"},{"author_name":"Kira King","author_inst":"Queen's University"},{"author_name":"Wenbin Li","author_inst":"Queen's University"},{"author_name":"Maria P. Velez","author_inst":"McGill University"},{"author_name":"Shannon Bainbridge","author_inst":"University of Ottawa"},{"author_name":"Laura Gaudet","author_inst":"Queen's University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Immune Profiling after treatment with an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Treatment-Refractory Progressive Multiple Sclerosis","rel_doi":"10.64898\/2026.09.11.26361992","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.11.26361992","rel_abs":"Treatment targeting progressive multiple sclerosis (MS) have limited efficacy, as central nervous system (CNS) resident B cells are resistant to peripheral B cell depletion by antiCD20 monoclonal antibodies. CD19 targeted chimeric antigen receptor (CAR)T cells offer the promise to deplete B cells more extensively in both the peripheral and CNS compartments. Two adult participants with treatment-refractory progressive MS were treated with 0.33e8 autologous anti CD19 CAR T cells (mivocabtagene autoleucel, miv-cel) intravenously after a preconditioning regimen. Participant 1 (50's year old female, EDSS 6) had no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Participant 2 (60's year old female, EDSS 4.5) had grade 1 CRS and no ICANS. Expansion of CAR T cells in the cerebrospinal fluid (CSF) at Day 14 was noted in both participants, remarkably with sustained disappearance of disease-associated oligoclonal band (OCB) or normalization of IgG index despite peripheral naive B cell reconstitution. MRI and clinical outcomes showed sustained stability at Week 48. Serologic studies showed a decline in anti-Epstein Barr Virus seropositivity. Single cell myeloid and proteomic signatures showed a decline in proinflammatory profiles. In the 2 subjects with progressive MS reported here, low dose anti CD19 CAR T cell therapy (miv-cel) was safe, penetrated the CSF effectively, reduced intrathecal humoral activity, modulated peripheral immune tone, and appeared to stabilize EDSS scores. Overall, these results support the continued investigation of CAR T cell therapy in MS.","rel_num_authors":25,"rel_authors":[{"author_name":"Sasha Gupta","author_inst":"University of California, San Fransisco"},{"author_name":"Madhav R Seshadri","author_inst":"University of California, San Fransisco"},{"author_name":"Ravi Dandekar","author_inst":"University of California, San Fransisco"},{"author_name":"Leonie Mueller-Jensen","author_inst":"University of California, San Fransisco"},{"author_name":"Krista McCutcheon","author_inst":"University of California, San Fransisco"},{"author_name":"Leslie A Scarffe","author_inst":"University of California, San Fransisco"},{"author_name":"ShiLu Vanasupa","author_inst":"University of California, San Fransisco"},{"author_name":"Megumi Sunahara","author_inst":"University of California, San Fransisco"},{"author_name":"Fumie Hayashi","author_inst":"University of California, San Fransisco"},{"author_name":"Colette Caspar","author_inst":"University of California, San Fransisco"},{"author_name":"Robin Lincoln","author_inst":"University of California, San Fransisco"},{"author_name":"Naomi Okinishi","author_inst":"University of California, San Fransisco"},{"author_name":"Nancy Thomas","author_inst":"University of California, San Fransisco"},{"author_name":"Samantha Shenoy","author_inst":"University of California, San Fransisco"},{"author_name":"Samantha Zylberman","author_inst":"University of California, San Fransisco"},{"author_name":"Camille Fouassier","author_inst":"University of California, San Fransisco"},{"author_name":"Ebtesam Hassan","author_inst":"University of California, San Fransisco"},{"author_name":"Sam Klauer","author_inst":"University of California, San Fransisco"},{"author_name":"Jenai Wilmoth","author_inst":"University of California, San Fransisco"},{"author_name":"Joseph J Sabatino Jr.","author_inst":"University of California, San Fransisco"},{"author_name":"Aaron Bodansky","author_inst":"University of California, San Fransisco"},{"author_name":"Ahmed Abdelhak","author_inst":"University of California, San Francisco"},{"author_name":"Stephen L Hauser","author_inst":"University of California, San Fransisco"},{"author_name":"Michael R Wilson","author_inst":"University of California, San Fransisco"},{"author_name":"Bruce A.C. Cree","author_inst":"University of California, San Fransisco"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Evaluation of Urinary Circulating Tumor DNA to Detect Minimal Residual Disease in Patients with High-Risk Non-Muscle Invasive Bladder Cancer","rel_doi":"10.64898\/2026.09.09.26362655","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362655","rel_abs":"Purpose Restaging transurethral resection of bladder tumor (reTURBT) is the standard-of-care for some patients with high-risk non-muscle invasive bladder cancer (NMIBC). However, it may lead to complications and biomarkers to avoid unnecessary reTURBT are needed. Materials and Methods Patients with high-risk NMIBC undergoing reTURBT were prospectively enrolled. Whole-exome sequencing along with low-pass whole-genome sequencing were performed on index TURBT samples to generate mutational profiles and copy number variation. Up to 50 personalized mutations and a fixed panel of 500 hotspot mutations were used for detecting variants from urine samples collected prior to reTURBT. Using a prespecified algorithm, tumor fraction (TF) and copy number burden (CNB) score were used to measure minimal residual disease and correlated with reTURBT pathology. Results Overall, 72\/76 urine samples collected from patients with high-risk NMIBC prior to reTURBT passed quality check. From the indext TURBT specimens, a median of 39 personalized variants from the index TURBT were used for disease tracking. Overall, median TF was 0.206 vs. 0.001 in patients with and without residual tumor, respectively (p<0.001). Similarly, CNB score was elevated (7.34 vs. 4.02, p<0.001). utDNA achieved sensitivity of 97.8% and specificity of 69.2%, with area under the curve (AUC) of 0.932 in predicting disease found on reTURBT. Analyses of the index and reTURBT tissue and urine mutational profiles provided evidence for underdiagnosis of subclinical disease at the time of reTURBT. Conclusion Paired personalized and panel utDNA can be used to accurately detect residual disease in patients with high-risk NMIBC with potentially wide-ranging clinical applications.","rel_num_authors":24,"rel_authors":[{"author_name":"Roger Li","author_inst":"Moffitt"},{"author_name":"Josh Linscott","author_inst":"Moffitt"},{"author_name":"Prithvi Murthy","author_inst":"Moffitt"},{"author_name":"Kyle Rose","author_inst":"Moffitt"},{"author_name":"Young Pak","author_inst":"Moffitt"},{"author_name":"Frank Zhang","author_inst":"Predicine"},{"author_name":"Yong Huang","author_inst":"Predicine"},{"author_name":"G Daniel Grass","author_inst":"Moffitt"},{"author_name":"Jon Chatzkel","author_inst":"Moffitt"},{"author_name":"Noah Hahn","author_inst":"Johns Hopkins"},{"author_name":"David McConkey","author_inst":"Rochester"},{"author_name":"Josh Meeks","author_inst":"Northwestern"},{"author_name":"Siamak Daneshmand","author_inst":"USC"},{"author_name":"Tom Flaig","author_inst":"Colorado"},{"author_name":"Seth Lerner","author_inst":"Baylor"},{"author_name":"Logan Zemp","author_inst":"Moffitt"},{"author_name":"Michael Poch","author_inst":"Moffitt"},{"author_name":"Philippe Spiess","author_inst":"Moffitt"},{"author_name":"Wade Sexton","author_inst":"Moffitt"},{"author_name":"Scott Gilbert","author_inst":"Moffitt"},{"author_name":"Hongzhi Xu","author_inst":"Moffitt"},{"author_name":"Pan Du","author_inst":"Predicine"},{"author_name":"Shidong Jia","author_inst":"Predicine"},{"author_name":"Xuefeng Wang","author_inst":"Moffitt"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"A Systems Biology Model Linking Peripheral NIMETOX Biomarkers to Multilevel Brain Structural and Functional Alterations Across Major Depression and Schizophrenia","rel_doi":"10.64898\/2026.09.09.26362608","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362608","rel_abs":"Peripheral lipid and antioxidant-related biomarkers may help contextualize brain abnormalities across psychiatric disorders, but their relationships with brain structure, intrinsic activity, and dimensional symptoms remain incompletely characterized. In this cross-sectional study, 93 adults were recruited: 38 with major depressive disorder, 29 with schizophrenia, and 26 healthy controls. Eighty-seven participants met resting-state functional MRI quality-control criteria. Assessments included structural and functional MRI, serum lipids, albumin, apolipoprotein A-I, childhood maltreatment, psychological resilience, and clinical symptoms. Exploratory analyses combined regional imaging measures, within-network connectivity, statistical mediation, and partial least squares structural equation modeling. Group-related functional abnormalities involved parietal, sensorimotor, cingulate, insular, and temporal regions. Peripheral lipid and antioxidant-related measures were associated with regional gray matter measures and intrinsic activity. Childhood maltreatment and resilience were associated with mood-related symptom burden, whereas lower connectivity and nodal strength within the selected 11-region network were associated with psychosis-related and overall illness severity. Exploratory structural equation models accounted for 66.4% of the variance in the mood-related composite and 25.3% of the variance in local intrinsic activity. These findings describe cross-sectional relationships among peripheral biological measures, regional brain characteristics, developmental adversity, and psychopathology. They provide a framework for further investigation rather than evidence of a causal blood-to-brain sequence. Independent replication with prospectively defined measures and longitudinal assessments is needed.","rel_num_authors":17,"rel_authors":[{"author_name":"Hongzhou Wu","author_inst":"University of Electronic Science and Technology of China"},{"author_name":"Chenghui Yang","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Ying He","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Xianfeng Qu","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Abbas F. Almulla","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Yingqiang Zhang","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Jinming Xiao","author_inst":"Sichuan Normal University"},{"author_name":"Chengxiao Yang","author_inst":"University of Electronic Science and Technology of China"},{"author_name":"Drozdstoj Stoyanov","author_inst":"Medical University of Plovdiv"},{"author_name":"Bharat B Biswal","author_inst":"University of Electronic Science and Technology of China"},{"author_name":"Benjamin Klugah-Brown","author_inst":"University of electronic science and technology of China"},{"author_name":"Andre F. Carvalho","author_inst":"Deakin University"},{"author_name":"Licia Pacheco Luna","author_inst":"Johns Hopkins Hospital"},{"author_name":"Stefania Ferraro","author_inst":"University of Electronic Science and Technology"},{"author_name":"Yuting Wang","author_inst":"Sichuan Provincial People's Hospital"},{"author_name":"Elijah Agoalikum","author_inst":"University of Electronic Science and Technology of China"},{"author_name":"Michael Maes","author_inst":"University of Electronic Science and Technology of China"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Validation of Algorithms to Identify Small or Large for Gestational Age in the Korean Nationwide Healthcare Database","rel_doi":"10.64898\/2026.09.09.26362678","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362678","rel_abs":"Objective: Small for gestational age (SGA) and large for gestational age (LGA) are critical endpoints in perinatal pharmacoepidemiology, yet gestational age is frequently missing in administrative databases. This study validated algorithms for identifying SGA and LGA in the Korean National Health Information Database (NHID). Methods: We linked the NHID with national vaccination and infant health screening registries (2018-2021) to create a validation cohort of 94,159 pregnancies with reference standard gestational age and birth weight; infants with birth weights below the 10th or above the 90th percentile were considered SGA or LGA, respectively. We evaluated four algorithms: ICD-10 diagnosis codes from infant claims (Method A), maternal claims (Method B), either infant or maternal claims (Method C), and birth weight combined with estimated gestational age (Method D). Results: ICD-10-based algorithms consistently underestimated prevalence, showing high specificity but low sensitivity (<17%). In contrast, Method D demonstrated superior performance: for SGA, sensitivity was 89.3%, specificity 96.8%, and positive predictive value (PPV) 71.6%; for LGA, sensitivity was 77.5%, specificity 98.3%, and PPV 84.7%. Conclusion: SGA and LGA can be identified with reasonable accuracy in the NHID using birth weight and estimated gestational age, whereas diagnosis codes alone can underestimate prevalence.","rel_num_authors":5,"rel_authors":[{"author_name":"Yongtai Cho","author_inst":"Department of Pharmacy, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea"},{"author_name":"HyunJoo Lim","author_inst":"Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea."},{"author_name":"Bohyun Suh","author_inst":"Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea."},{"author_name":"Yubin Lee","author_inst":"Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea."},{"author_name":"Ju-Young Shin","author_inst":"College of Pharmacy, Seoul National University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Effectiveness and safety of a New Standardised TrEatment Protocol based on initial\/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants","rel_doi":"10.64898\/2026.09.10.26362712","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362712","rel_abs":"Background Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. Objective To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. Methods The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness of the intervention. Results Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. Conclusions The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies.","rel_num_authors":23,"rel_authors":[{"author_name":"Rupasvi Dhurjati","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Rashmi Pant","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Amit Kumar","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Anshika Mittal","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Krishnaiah Chappidi","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Gautam Satheesh","author_inst":"University of Sydney"},{"author_name":"Parul Puri","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Sasi Kumar Tiruttani","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Shwetha Rajaram","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Aneesh Basheer","author_inst":"1.\tDepartment of Medicine, SRM Medical College Hospital and Research Centre, SRMIST, Kattankulathur, Chengalpet, Chennai, India"},{"author_name":"Prabhdeep kaur","author_inst":"IISc, Bengaluru, India"},{"author_name":"Andrew Moran","author_inst":"Resolve to Save Lives, New York, NY; Division of General Medicine, Columbia University Medical Center, New York, NY"},{"author_name":"Andres Rosende","author_inst":"Department of Noncommunicable Diseases and Mental Health, Pan American Health Organization, Washington, D.C., United States of America"},{"author_name":"Poongothai Subramani","author_inst":"Madras Diabetes Research Foundation, ICMR-Collaborating Centre of Excellence, Chennai, India"},{"author_name":"Sandeep Mahajan","author_inst":"All India Institute of Medical Sciences, New Delhi, India"},{"author_name":"Nupur Lalvani","author_inst":"Blue Circle Diabetes Foundation"},{"author_name":"Sandeep Bansal","author_inst":"VMMC and Safdarjung Hospital, New Delhi, India"},{"author_name":"Dorairaj Prabhakaran","author_inst":"Centre for Chronic Disease Control"},{"author_name":"Jayagopal Pathiyil Balagopalan","author_inst":"Lakshmi Hospital, Palakkad, Kerala, India"},{"author_name":"Stephen Jan","author_inst":"The George Institute for Global Health"},{"author_name":"Mark D Huffman","author_inst":"Washington University in Saint Louis"},{"author_name":"Vivekanand Jha","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; School of Pub"},{"author_name":"Abdul Salam","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; The George In"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Effectiveness and safety of a New Standardised TrEatment Protocol based on initial\/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants","rel_doi":"10.64898\/2026.09.10.26362712","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362712","rel_abs":"Background Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. Objective To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. Methods The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness of the intervention. Results Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. Conclusions The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies.","rel_num_authors":23,"rel_authors":[{"author_name":"Rupasvi Dhurjati","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Rashmi Pant","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Amit Kumar","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Anshika Mittal","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Krishnaiah Chappidi","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Gautam Satheesh","author_inst":"University of Sydney"},{"author_name":"Parul Puri","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Sasi Kumar Tiruttani","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Shwetha Rajaram","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Aneesh Basheer","author_inst":"1.\tDepartment of Medicine, SRM Medical College Hospital and Research Centre, SRMIST, Kattankulathur, Chengalpet, Chennai, India"},{"author_name":"Prabhdeep kaur","author_inst":"IISc, Bengaluru, India"},{"author_name":"Andrew Moran","author_inst":"Resolve to Save Lives, New York, NY; Division of General Medicine, Columbia University Medical Center, New York, NY"},{"author_name":"Andres Rosende","author_inst":"Department of Noncommunicable Diseases and Mental Health, Pan American Health Organization, Washington, D.C., United States of America"},{"author_name":"Poongothai Subramani","author_inst":"Madras Diabetes Research Foundation, ICMR-Collaborating Centre of Excellence, Chennai, India"},{"author_name":"Sandeep Mahajan","author_inst":"All India Institute of Medical Sciences, New Delhi, India"},{"author_name":"Nupur Lalvani","author_inst":"Blue Circle Diabetes Foundation"},{"author_name":"Sandeep Bansal","author_inst":"VMMC and Safdarjung Hospital, New Delhi, India"},{"author_name":"Dorairaj Prabhakaran","author_inst":"Centre for Chronic Disease Control"},{"author_name":"Jayagopal Pathiyil Balagopalan","author_inst":"Lakshmi Hospital, Palakkad, Kerala, India"},{"author_name":"Stephen Jan","author_inst":"The George Institute for Global Health"},{"author_name":"Mark D Huffman","author_inst":"Washington University in Saint Louis"},{"author_name":"Vivekanand Jha","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; School of Pub"},{"author_name":"Abdul Salam","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; The George In"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Effectiveness and safety of a New Standardised TrEatment Protocol based on initial\/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants","rel_doi":"10.64898\/2026.09.10.26362712","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362712","rel_abs":"Background Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. Objective To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. Methods The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness of the intervention. Results Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. Conclusions The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies.","rel_num_authors":23,"rel_authors":[{"author_name":"Rupasvi Dhurjati","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Rashmi Pant","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Amit Kumar","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Anshika Mittal","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Krishnaiah Chappidi","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Gautam Satheesh","author_inst":"University of Sydney"},{"author_name":"Parul Puri","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Sasi Kumar Tiruttani","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Shwetha Rajaram","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India"},{"author_name":"Aneesh Basheer","author_inst":"1.\tDepartment of Medicine, SRM Medical College Hospital and Research Centre, SRMIST, Kattankulathur, Chengalpet, Chennai, India"},{"author_name":"Prabhdeep kaur","author_inst":"IISc, Bengaluru, India"},{"author_name":"Andrew Moran","author_inst":"Resolve to Save Lives, New York, NY; Division of General Medicine, Columbia University Medical Center, New York, NY"},{"author_name":"Andres Rosende","author_inst":"Department of Noncommunicable Diseases and Mental Health, Pan American Health Organization, Washington, D.C., United States of America"},{"author_name":"Poongothai Subramani","author_inst":"Madras Diabetes Research Foundation, ICMR-Collaborating Centre of Excellence, Chennai, India"},{"author_name":"Sandeep Mahajan","author_inst":"All India Institute of Medical Sciences, New Delhi, India"},{"author_name":"Nupur Lalvani","author_inst":"Blue Circle Diabetes Foundation"},{"author_name":"Sandeep Bansal","author_inst":"VMMC and Safdarjung Hospital, New Delhi, India"},{"author_name":"Dorairaj Prabhakaran","author_inst":"Centre for Chronic Disease Control"},{"author_name":"Jayagopal Pathiyil Balagopalan","author_inst":"Lakshmi Hospital, Palakkad, Kerala, India"},{"author_name":"Stephen Jan","author_inst":"The George Institute for Global Health"},{"author_name":"Mark D Huffman","author_inst":"Washington University in Saint Louis"},{"author_name":"Vivekanand Jha","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; School of Pub"},{"author_name":"Abdul Salam","author_inst":"The George Institute for Global Health, Hyderabad, Telangana, India; Prasanna School of Public Health, Manipal Academy of Higher Education, India; The George In"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Conserved roles of cardiac endothelial ETS factors in ventricular development and disease","rel_doi":"10.64898\/2026.09.08.26361286","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26361286","rel_abs":"We previously identified ETS1 as a candidate gene in the rare chromosomal deletion disorder, Jacobsen syndrome (JS, OMIM#147791). Here, we present data from four model systems that define roles for ETS factors in normal heart development and suggest how defects in these genes contribute to congenital heart disease. In frog, knockdown of Ets1 in cardiac mesoderm led to a hypoplastic ventricle with impaired cardiac function and loss of trabecular myocardium. Grafting of wildtype cardiac mesodermal tissue restored the integrity of the ventricular endocardial layer and normal development. In zebrafish, KD of ETS1 and two related ETS factor genes caused severely underdeveloped, poorly functioning ventricles with decreased numbers of endocardial cells that failed to contact the myocardium. Genetic ablation of the endocardium in mice also caused a hypoplastic ventricle with loss of the trabecular myocardium. In Drosophila, loss of the ETS1 ortholog pointed (pnt) affected specification of cardiac precursors and decreased Notch signaling, a pathway previously implicated in some forms of hypoplastic left heart syndrome (HLHS). We also demonstrated genetic interactions between pnt and tinman, the NKX2.5 ortholog, associated with HLHS. Finally, our examination of the heart from a newborn with JS\/HLHS showed myofibrillar disarray and myocardial maturation defects. Furthermore, there was a reduction in the coronary vascular endothelium in the LV myocardium from the JS\/HLHS patient compared to an age-matched normal heart. Taken together, our studies demonstrate a critical and conserved role of ETS factors for cardiac endothelial function and in ventricular morphogenesis.","rel_num_authors":15,"rel_authors":[{"author_name":"Lu Wang","author_inst":"University of California San Diego"},{"author_name":"Analyne Schroeder","author_inst":"SBP Medical Discovery Institute"},{"author_name":"Katya Marchetti","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Ingolf Reim","author_inst":"Philipps-Universitat Marburg"},{"author_name":"Matthias Blanc","author_inst":"Stanford University"},{"author_name":"K'leigh Guillotte","author_inst":"SBP Medical Discovery Institute"},{"author_name":"Amelie Muck","author_inst":"Philipps-Universitat Marburg"},{"author_name":"Elaina Bao","author_inst":"Rady Children's Health"},{"author_name":"Wenhao Liu","author_inst":"Georgia Institute of Technology"},{"author_name":"Shu Jia","author_inst":"Georgia Institute of Technology"},{"author_name":"Denise Malicki","author_inst":"Rady Children's Health"},{"author_name":"Rolf Bodmer","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Shuyi Nie","author_inst":"Georgia Institute of Technology"},{"author_name":"Karen Ocorr","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Paul Grossfeld","author_inst":"UCSD School of Medicine"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Conserved roles of cardiac endothelial ETS factors in ventricular development and disease","rel_doi":"10.64898\/2026.09.08.26361286","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26361286","rel_abs":"We previously identified ETS1 as a candidate gene in the rare chromosomal deletion disorder, Jacobsen syndrome (JS, OMIM#147791). Here, we present data from four model systems that define roles for ETS factors in normal heart development and suggest how defects in these genes contribute to congenital heart disease. In frog, knockdown of Ets1 in cardiac mesoderm led to a hypoplastic ventricle with impaired cardiac function and loss of trabecular myocardium. Grafting of wildtype cardiac mesodermal tissue restored the integrity of the ventricular endocardial layer and normal development. In zebrafish, KD of ETS1 and two related ETS factor genes caused severely underdeveloped, poorly functioning ventricles with decreased numbers of endocardial cells that failed to contact the myocardium. Genetic ablation of the endocardium in mice also caused a hypoplastic ventricle with loss of the trabecular myocardium. In Drosophila, loss of the ETS1 ortholog pointed (pnt) affected specification of cardiac precursors and decreased Notch signaling, a pathway previously implicated in some forms of hypoplastic left heart syndrome (HLHS). We also demonstrated genetic interactions between pnt and tinman, the NKX2.5 ortholog, associated with HLHS. Finally, our examination of the heart from a newborn with JS\/HLHS showed myofibrillar disarray and myocardial maturation defects. Furthermore, there was a reduction in the coronary vascular endothelium in the LV myocardium from the JS\/HLHS patient compared to an age-matched normal heart. Taken together, our studies demonstrate a critical and conserved role of ETS factors for cardiac endothelial function and in ventricular morphogenesis.","rel_num_authors":15,"rel_authors":[{"author_name":"Lu Wang","author_inst":"University of California San Diego"},{"author_name":"Analyne Schroeder","author_inst":"SBP Medical Discovery Institute"},{"author_name":"Katya Marchetti","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Ingolf Reim","author_inst":"Philipps-Universitat Marburg"},{"author_name":"Matthias Blanc","author_inst":"Stanford University"},{"author_name":"K'leigh Guillotte","author_inst":"SBP Medical Discovery Institute"},{"author_name":"Amelie Muck","author_inst":"Philipps-Universitat Marburg"},{"author_name":"Elaina Bao","author_inst":"Rady Children's Health"},{"author_name":"Wenhao Liu","author_inst":"Georgia Institute of Technology"},{"author_name":"Shu Jia","author_inst":"Georgia Institute of Technology"},{"author_name":"Denise Malicki","author_inst":"Rady Children's Health"},{"author_name":"Rolf Bodmer","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Shuyi Nie","author_inst":"Georgia Institute of Technology"},{"author_name":"Karen Ocorr","author_inst":"Sanford Burnham Prebys Medical Discovery Institute"},{"author_name":"Paul Grossfeld","author_inst":"UCSD School of Medicine"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"HemOncAgent: an artificial intelligence system for retrieving structured and narrative oncology knowledge","rel_doi":"10.64898\/2026.09.09.26362651","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362651","rel_abs":"Oncology knowledge spans structured and unstructured datasets of drugs, regimens, conditions, and identifiers, as well as clinician-authored narratives describing treatment sequencing across disease settings. Answering clinical questions may require accessing both databases and free-text narratives, but existing intelligent retrieval systems favor either relational facts or narrative context. We developed HemOncAgent, an artificial intelligence agent that selects among retrieval tools for the HemOnc knowledge ecosystem: HemOncKB, a curated knowledge graph for pharmacologic relationships, and HemOnc.org, a narrative resource for care pathways. Across structured and narrative benchmarks, HemOncAgent maintained high-fidelity retrieval across question types for which single-source systems showed domain-specific limitations, supporting hybrid tool-based retrieval for more reliable oncology knowledge access.","rel_num_authors":9,"rel_authors":[{"author_name":"Andrew J Yang","author_inst":"The Warren Alpert Medical School of Brown University"},{"author_name":"Hossam A Zaki","author_inst":"The Warren Alpert Medical School of Brown University"},{"author_name":"Aaron Seto","author_inst":"The Warren Alpert Medical School of Brown University"},{"author_name":"Taemin Kim","author_inst":"The Warren Alpert Medical School of Brown University"},{"author_name":"Irbaz Bin Riaz","author_inst":"Mayo Clinic Comprehensive Cancer Center"},{"author_name":"Andrew Srisuwananukorn","author_inst":"The Ohio State University Comprehensive Cancer Center"},{"author_name":"Andrew J Cowan","author_inst":"BC Cancer\/University of British Columbia"},{"author_name":"Peter C Yang","author_inst":"Massachusetts General Hospital"},{"author_name":"Jeremy L Warner","author_inst":"Center for Clinical Cancer Informatics and Data Science, Legorreta Cancer Center, Brown University"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study","rel_doi":"10.64898\/2026.09.09.26362686","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.09.26362686","rel_abs":"ABSTRACT Objective: To determine whether a multi-trait polygenic profile for dementia is associated with dementia- and disability-free survival in middle-aged and older adults. Background: Clinical trials of brain health and aging increasingly use holistic, patient-centered outcomes that capture overall health status. Survival free of dementia and disability is one such outcome. We hypothesized that adverse polygenic profiles for dementia would be associated with higher risk of dementia, disability, or death. Design\/Methods: We conducted a genetic association study within the Health and Retirement Study, a prospective, nationally representative longitudinal cohort of U.S. adults. Polygenic profiling used the previously validated integrated polygenic risk score for dementia (iPRS-DEM), which incorporates neurodegenerative and vascular genetic components. Participants were categorized as having favorable ([&le;]20th percentile), intermediate (20th-80th percentile), or poor (>80th percentile) polygenic profiles. The primary outcome was a composite of dementia, disability, or death. Cox proportional hazards models were adjusted for age, sex, genetic ancestry, and genetic principal components. Interaction between continuous iPRS-DEM and APOE {varepsilon}4 status was assessed for 31-year outcome risk. Results: Among 45,234 HRS participants, 15,620 provided DNA samples, 15,565 had genotype data after quality control and imputation, and 14,333 were free of dementia and disability at baseline (median age 55 years; 58% female). Compared with a favorable polygenic profile, intermediate and poor profiles were associated with higher risk of the composite outcome (HR 1.14, 95% CI 1.07-1.21 and HR 1.43, 95% CI 1.26-1.63, respectively). The relative association was strongest for dementia; for poor versus favorable profiles, HRs were 1.58 (95% CI 1.21-2.05) for dementia, 1.43 (95% CI 1.14-1.79) for disability, and 1.33 (95% CI 1.15-1.54) for death. An interaction between continuous iPRS-DEM and APOE {varepsilon}4 status was observed for 31-year dementia risk (P=0.016). Relative to favorable-profile APOE {varepsilon}4 non-carriers, dementia risk was highest among participants with a poor profile who were APOE {varepsilon}4 carriers (HR 2.32, 95% CI 1.73-3.12). Conclusions: Adverse polygenic profiles for dementia were associated with higher composite risk of dementia, disability, or death in a large population-based cohort, with the strongest association observed for dementia. Joint consideration of iPRS-DEM and APOE {varepsilon}4 further identified individuals at elevated dementia risk. These findings support the potential value of polygenic profiling for risk stratification while highlighting limitations related to ancestry, generalizability, and clinical translation.","rel_num_authors":10,"rel_authors":[{"author_name":"Yome Tawaldemedhen","author_inst":"Yale University"},{"author_name":"Santiago Clocchiatti-Tuozzo","author_inst":"Yale School of Medicine"},{"author_name":"Cyprien Rivier","author_inst":"Yale School of Medicine"},{"author_name":"Shufan Huo","author_inst":"Yale School of Medicine"},{"author_name":"Andrew Silberfeld","author_inst":"Yale School of Medicine"},{"author_name":"Tim D'Aoust","author_inst":"University of Bordeaux"},{"author_name":"Stephanie Debette","author_inst":"University of Bordeaux"},{"author_name":"Adam de Havenon","author_inst":"Yale School of Medicine"},{"author_name":"Thomas M. Gill","author_inst":"Yale School of Medicine"},{"author_name":"Guido J. Falcone","author_inst":"Yale School of Medicine"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer","rel_doi":"10.64898\/2026.09.10.26362669","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362669","rel_abs":"Objectives: To estimate the absolute benefit of adding and prolonging androgen deprivation therapy (ADT) to radiation therapy (RT) for men with localized prostate cancer by integrating cancer-specific risk, other-cause mortality (OCM) risk, and relative treatment efficacy. Subjects and Methods: Individualized risks were estimated by integrating cause-specific hazard estimates from a validated staging system (STAR-CAP) with those from a validated non-cancer mortality model (OCCAM). ADT treatment efficacy was then incorporated using published hazard ratio estimates from the MARCAP meta-analysis. Model utility was illustrated using the Prostate, Lung, Colon, and Ovarian (PLCO) cancer screening trial cohort (n=5468 prostate cancer patients with complete covariates). The primary outcome was the estimated 10-year absolute risk reduction (ARR) in distant metastasis (DM) from adding short-term ADT (STADT) to RT or extending STADT to long term ADT (LTADT). Results: Within PLCO, model estimated risk of DM at 10 years ranged from <1% to 56% under guideline concordant care and OCM risk ranged from 3% to 80% independent of treatment. For patients with NCCN unfavorable intermediate-risk (n=1814), adding STADT to RT reduced estimated 10 year DM risk by a median of 4%, but the ARR estimates for individuals ranged from <1% to almost 15%. Similar variation was seen within NCCN high-risk patients (n=1289) with a median ARR of 9% [Range: 0.4%-17.2%] when prolonging ADT treatment. Moreover, 25% of NCCN unfavorable intermediate-risk patients have less than a 2.4% ARR while 25% of NCCN high-risk patients experience less than a 5% ARR. Conclusion: An integrated model accounting for both prostate cancer aggressiveness and comorbidities demonstrates substantial heterogeneity in the estimated absolute benefit of ADT within conventional risk groups. This approach provides individualized estimates to support treatment discussions; external validation is needed before clinical implementation.","rel_num_authors":10,"rel_authors":[{"author_name":"Jessica Aldous","author_inst":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"},{"author_name":"William C Jackson","author_inst":"Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA"},{"author_name":"Elizabeth Chase","author_inst":"Department of Economics, Sociology, & Statistics, RAND Corporation, Arlington, VA, USA"},{"author_name":"Elise Covert","author_inst":"IQVIA, Madison, WI, USA"},{"author_name":"Joseph Tang","author_inst":"Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA"},{"author_name":"Udit Singhal","author_inst":"Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA"},{"author_name":"Todd M Morgan","author_inst":"Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA"},{"author_name":"Daniel E Spratt","author_inst":"Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine Cleveland, Cleveland, OH, USA"},{"author_name":"Robert T Dess","author_inst":"Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA"},{"author_name":"Matthew J Schipper","author_inst":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Relationship between mental health and unmet need for contraception and method type among women living with HIV in Kenya","rel_doi":"10.64898\/2026.09.10.26362702","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.10.26362702","rel_abs":"Contraception is important for preventing unintended pregnancies and reducing maternal and infant mortality. Among women living with HIV (WLHIV), it is also central to preventing vertical HIV transmission. Yet unmet need for contraception remains high among WLHIV in sub-Saharan Africa. Mental health symptoms may contribute to unmet need, but evidence among WLHIV remains limited. We examined the relationship between depression and anxiety and unmet need for contraception. We used baseline survey data from Kenyan WLHIV receiving routine HIV care participating in a cluster randomized clinical trial evaluating a reproductive health counselling intervention at 10 HIV clinics. Women who were fecund, did not desire a pregnancy within two years, and not using a modern method of contraception were considered to have unmet need for contraception and were eligible for this analysis. Surveys captured data on depression, anxiety, fertility intentions and contraceptive use. We constructed separate generalized linear models to assess the relationship between depression and\/or anxiety and unmet need for contraception.","rel_num_authors":11,"rel_authors":[{"author_name":"Agnes Karingo Karume","author_inst":"Kenyatta National Hospital"},{"author_name":"Aparna Seth","author_inst":"University of Washington Seattle Campus: University of Washington"},{"author_name":"Nancy Ngumbau","author_inst":"Kenyatta National Hospital"},{"author_name":"Celestine Atieno","author_inst":"Kenyatta National Hospital"},{"author_name":"June Moraa","author_inst":"Kenyatta National Hospital"},{"author_name":"Kristin Beima-Sofie","author_inst":"University of Washington Seattle Campus: University of Washington"},{"author_name":"Barbra  A. Richardson","author_inst":"University of Washington Seattle Campus: University of Washington"},{"author_name":"Jennifer  A. Unger","author_inst":"Warren Alpert Medical School of Brown University: Brown University Warren Alpert Medical School"},{"author_name":"Amritha Bhat","author_inst":"University of Washington Seattle Campus: University of Washington"},{"author_name":"John Kinuthia","author_inst":"Kenyatta National Hospital"},{"author_name":"Alison  L. Drake","author_inst":"University of Washington Seattle Campus: University of Washington"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Symptom burden, Psychosocial Distress, Resilience and Health-Related Quality of Life in Women with Metastatic Breast Cancer Receiving Contemporary Systemic Therapy","rel_doi":"10.64898\/2026.09.08.26362524","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26362524","rel_abs":"Aims: Targeted therapies and immunotherapies have extended survival of women with metastatic breast cancer. However, the role of resilience among women receiving those contemporary treatments remains understudied. We aimed to examine the interrelationships among physical symptom burden, psychosocial distress, resilience and health-related quality of life in women with metastatic breast cancer receiving contemporary systemic cancer treatment. Design: Cross-sectional study. Methods: Women with metastatic breast cancer receiving systemic treatment were recruited across the United States from February to September 2024. Data was collected using validated measures. Psychosocial distress was constructed as a latent variable indicated by anxiety, depression and uncertainty, using confirmatory factor analysis. We conducted structural equation modeling to examine multiple pathways between physical symptom burden, latent psychosocial distress, resilience and health-related quality of life. Results: Of 217 participants, 209 were included in the analysis (mean age = 50.1 years, SD=14.1). Physical symptom burden, psychosocial distress and resilience were significantly associated with health-related quality of life. Significant indirect associations of physical symptom burden and psychosocial distress with health-related quality of life through resilience were identified. Structural equation modeling showed indirect associations between physical symptom burden and health-related quality of life through psychosocial distress and resilience (B=-0.137, 95% CI: -0.217, -0.078, p<0.001). Conclusion: Psychosocial distress appeared to be more proximally associated with resilience than physical symptom burden among this population. Resilience interventions may be strengthened by identifying and addressing anxiety, depression and uncertainty as proximal intervention points for preserving resilience, rather than only including generic stress management components. Impact: This study highlighted the need of resilience interventions that prioritize anxiety and depression screening, mental health referral, and distress focused supportive care alongside symptom management for this population.","rel_num_authors":7,"rel_authors":[{"author_name":"Yan Zhan","author_inst":"Yale School of Nursing"},{"author_name":"Shelli Feder","author_inst":"Yale School of Nursing"},{"author_name":"Sangchoon Jeon","author_inst":"Yale School of Nursing"},{"author_name":"Maryam Lustberg","author_inst":"Yale School of Medicine, Medical Oncology Division, Yale Cancer Center"},{"author_name":"Margaret Rosenzweig","author_inst":"University of Pittsburgh School of Nursing"},{"author_name":"Djin Tay","author_inst":"University of Utah, College of Nursing"},{"author_name":"Tish Knobf","author_inst":"Yale School of Nursing"}],"rel_date":"2026-09-11","rel_site":"medrxiv"},{"rel_title":"Estimating Divergence Times and Diversification Rates with the Unresolved Fossilized Birth-Death Process","rel_doi":"10.64898\/2026.09.10.749957","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.749957","rel_abs":"Tip-dating using Fossilized Birth-Death (FBD) models offers a favorable alternative to conventional node-dating analyses of the evolutionary timescale, bypassing various conceptual and technical difficulties. However, despite their increasing popularity in phylogenetic studies, their use has remained rather limited in taxonomic scope because of the difficulty in collecting morphological data, which is often required for tip-dating analyses, and computational intractability when a large number of fossils are present. Recent studies, however, suggest that FBD models can also be used in a principled way as priors for molecular clock analyses, even in the absence of morphological data, relying only on temporal information and given clade assignments. Heath et al. (2014) introduced an \"unresolved\" FBD model in which uncertainty in fossil placements is analytically integrated out when morphological data are unavailable, providing a potential solution to this problem. Here, we show that the topological enumeration scheme used by Heath et al. (2014) to marginalize over unresolved fossil attachments overcounts configurations in which multiple fossil taxa can be resolved as a clade, and we provide a correction to this factor, yielding a valid marginalized unresolved likelihood. We apply our implementation to empirical datasets of Cetacea, Emydidae, and Palaeodictyopterida, and show that our method converges and yields reasonable estimates within a reasonable amount of time, even when hundreds of fossils are present.","rel_num_authors":5,"rel_authors":[{"author_name":"Wonseop Lim","author_inst":"University of California, Berkeley"},{"author_name":"Levi Yoder Raskin","author_inst":"University of California, Berkeley"},{"author_name":"Kaiyuan Li","author_inst":"University of California, Berkeley"},{"author_name":"John P. Huelsenbeck","author_inst":"University of California, Berkeley"},{"author_name":"Rasmus Nielsen","author_inst":"University of California, Berkeley"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Taxonomic and biogeographic insights into Australasian fingerworts in the Lepidozia ulothrix clade","rel_doi":"10.64898\/2026.09.09.750534","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750534","rel_abs":"The floras of Australia and New Zealand are characterised by very high endemism of bryophytes. The highly diverse genus Lepidozia (fingerworts; family Lepidoziaceae) is represented by more than 20 mostly endemic species in these countries. The genus has been monographed in New Zealand, but issues surrounding species circumscription remain. This study focused on the Lepidozia ulothrix clade, with members shared between Australia and New Zealand. We performed phylogenetic analyses of a multilocus data set and applied several methods for molecular species delimitation. Our results support the conspecificity of L. serrulata and L. ulothrix, which is compatible with patterns of morphological variation observed in Tasmanian and New Zealand populations. The distribution of L. septemfida extends to the Wet Tropics Bioregion of north-east Queensland, where the species is represented by a distinct subspecies rather than a completely different species. The morphological differences between the Queensland and south-east Australian populations, as well as the inconsistency among the species-delimitation results, support the division of the species into two subspecies. Tasmanian and Victorian specimens previously attributed to the New Zealand endemic L. hirta belong to a distinct and unnamed lineage. Our study shows that integrative taxonomic approaches can uncover overlooked diversity and refine existing species circumscriptions, even in relatively well-studied Australasian lineages such as Lepidozia.","rel_num_authors":3,"rel_authors":[{"author_name":"Antonio L. Rayos Jr.","author_inst":"Institute of Biological Sciences, University of the Philippines Los Banos, Los Banos, Laguna, Philippines"},{"author_name":"Simon Y.W. Ho","author_inst":"School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia"},{"author_name":"Matthew A.M. Renner","author_inst":"National Herbarium of New South Wales, Royal Botanic Gardens Sydney, Sydney, New South Wales, Australia"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Isolation, identification, and comparative genomic analysis of Vibrio harveyi as a causative agent for a skin ulcer disease of endangered fish Chinese bahaba (Bahaba taipingensis)","rel_doi":"10.64898\/2026.09.10.750546","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750546","rel_abs":"Chinese bahaba (Bahaba taipingensis) is a fish species endemic to China and listed as a Class I nationally protected wild animal. Although significant breakthroughs have been achieved in its artificial breeding, high mortality rates persist during cultivation. Beginning in August 2024, sustained mass mortalities occurred in artificially farmed Chinese bahaba at a farm in Guangdong Province. Diseased fish exhibited pronounced skin ulcers, ascites, gastroenteritis, and splenomegaly. Histopathological examination revealed severe necrotizing gastroenteritis, gill necrosis and edema, muscle congestion with inflammatory cell infiltration, hepatic congestion with marked vasculitis, renal interstitial necrosis with tubular atrophy, and abundant melanomacrophage centers in the spleen. Based on biochemical characterization and whole-genome phylogenomic analysis, the isolated strain HCY1 was identified as Vibrio harveyi. Artificial infection experiments with this strain resulted in 100% mortality and reproduced clinical signs similar to those in naturally infected fish. Antimicrobial susceptibility testing showed that HCY1 remained susceptible to florfenicol and trimethoprim-sulfamethoxazole, but was resistant to multiple antibiotics, including {beta}-lactams and tetracyclines. Comparative genomic analysis revealed that HCY1 carries various antimicrobial resistance genes primarily conferring resistance to {beta}-lactam and tetracycline antibiotics, consistent with the phenotypic resistance profile. The strain also harbored numerous virulence genes, including complete type III and type VI secretion systems (T3SS and T6SS), tlh, hap\/vvp, and rtxB. Its plasmids encoded multiple virulence-enhancing genes, such as mcpA, pal, and esiB. To our knowledge, this is the first systematic investigation of a disease outbreak in cultured Chinese bahaba, and provides valuable insights for disease control and population conservation of this endangered species.","rel_num_authors":7,"rel_authors":[{"author_name":"Liang Zhong","author_inst":"City University of Hong Kong"},{"author_name":"Ruoxi Zhu","author_inst":"City University of Hong Kong"},{"author_name":"Yuxuan Zhang","author_inst":"City University of Hong Kong"},{"author_name":"Lin Yan","author_inst":"City University of Hong Kong"},{"author_name":"Song Sun","author_inst":"Xiamen University"},{"author_name":"Kuoqiu Yan","author_inst":"Guangdong Bluegen Marine Biotechnology Co., Ltd"},{"author_name":"Wenlong Cai","author_inst":"City University of Hong Kong"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Efficacy of Flavobacterium spp. Vaccines in fish: A systematic review and meta-analysis","rel_doi":"10.64898\/2026.09.11.750515","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.11.750515","rel_abs":"Flavobacterium species cause substantial economic losses in aquaculture, but no quantitative synthesis of vaccine efficacy across species, hosts, and platforms has been evaluated yet. This systematic review and meta-analysis aimed to evaluate the efficacy of vaccines against Flavobacterium infections in fish. We systematically searched PubMed, Web of Science, and Scopus for controlled challenge trials. The pooled risk ratio was calculated using a random effects model. Heterogeneity was assessed, and publication bias was evaluated by funnel plot and Egger's test. Sixty studies were included in this study, 59 of which were included in the main meta-analysis (377 comparisons) after screening. The overall pooled risk ratio was 0.572 (95% confidence interval: 0.55-0.60), corresponding to a relative percent survival of 42.8%, with high heterogeneity. Efficacy differed significantly by pathogen species, fish host, vaccine type and administration route. The highest protection by pathogen species was against F. davisii in channel catfish (relative percent survival = 86.8%), and the lowest against F. columnare in grass carp (relative percent survival = 30.6%). Live attenuated vaccines induced the highest protection, followed by inactivated and subunit vaccines. Among administration routes, immersion and oral vaccination achieved comparable protection, both outperforming injection. Significant publication bias was detected (P<0.001). Vaccination effectively reduces fish mortality from Flavobacterium infections, but its efficacy is highly context dependent. Taken together, standardized challenge protocols and improved reporting are needed. Priority should be given to developing effective vaccines against F. oreochromis and F. columnare.","rel_num_authors":7,"rel_authors":[{"author_name":"Yuanwei GENG","author_inst":"City University of Hongkong"},{"author_name":"Zulqarnain Baqar","author_inst":"City University of Hongkong"},{"author_name":"Ruoxi Zhu","author_inst":"City University of Hong Kong"},{"author_name":"Yongtao Zhu","author_inst":"Xi'an Jiaotong-Liverpool University"},{"author_name":"Haitham Mohammed","author_inst":"The Agricultural and Mechanical College of Texas"},{"author_name":"Ibrahim Elsohaby","author_inst":"City University of Hongkong"},{"author_name":"Wenlong CAI","author_inst":"City University of Hong Kong"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Solid Foods Drive the Maturation of the Gut Microbiota During Infancy","rel_doi":"10.64898\/2026.09.09.750284","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750284","rel_abs":"The establishment of a healthy gut microbiota in early life is an important determinant of long-term health, yet how the introduction of solid foods as a key nutritional transition shapes the gut microbiota development remains understudied. We aimed to characterize the impact of solid food introduction (complementary feeding) on the compositional succession and functional maturation of the infant gut microbiota during weaning. Infant faecal samples and corresponding dietary data were collected at five time points: pre-weaning (PREW, 4-6 months of age) 4, 8, and 12 weeks after first solid food introduction (WK4, WK8, WK12), and the late weaning stage (LATW, ~12 months) when infants were transitioning to a family diet. Faecal microbiota composition was profiled using full-length 16S rRNA gene sequencing. Solid food introduction induced marked restructuring of the gut microbiota, characterized by significant increases in richness, evenness, and phylogenetic diversity (p < 0.01), together with the emergence of adult-associated taxa, including Faecalibacterium, Ruminococcus, and members of the Lachnospiraceae. These changes were most pronounced at late weaning and were strongly associated with increased intakes of plant-derived complex carbohydrates and dietary protein (Spearman correlation r > 0.30, FDR < 0.001). Butyrate-producing capability, a functional feature of gut microbiota maturation, was correlated with the establishment of key adult-like species, including Ruminococcus bromii and Faecalibacterium prausnitzii (Spearman correlation, r > 0.30, FDR < 0.001). Additionally, the reshaping of the gut microbiota by complementary feeding also attenuated microbial diversity associated with early-life factors, including delivery mode and household pet exposure. Together, these findings suggest that nutrient transitions during complementary feeding are key drivers of infant gut microbiota development and maturation, highlighting weaning as a critical window for shaping the gut microbiota and a potential target for early-life nutritional interventions to promote gut health and associated wellbeing.","rel_num_authors":8,"rel_authors":[{"author_name":"Yanan Wang","author_inst":"University of Melbourne"},{"author_name":"Heng Ku","author_inst":"CSIRO"},{"author_name":"Azadeh Safarchi","author_inst":"University of Sydney"},{"author_name":"Megan Rebuli","author_inst":"SA Health"},{"author_name":"Theodora Almond","author_inst":"CSIRO"},{"author_name":"Beverly Muhlhausler","author_inst":"CSIRO"},{"author_name":"Cuong D Tran","author_inst":"Adelaide University"},{"author_name":"Michael A Conlon","author_inst":"CSIRO"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Real-time accessible phylogenetics for every highly sampled virus","rel_doi":"10.64898\/2026.09.10.750728","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750728","rel_abs":"The scale of viral genome sequencing has outpaced the phylogenetic tools traditionally used to analyze it, as highlighted by the COVID-19 pandemic. We present viral_usher, a unified framework for scalable viral phylogenetics built on UShER. viral_usher is a containerized command-line tool that constructs mutation-annotated trees directly from public sequence repositories with minimal user input, building phylogenies of tens of thousands of genomes in minutes. Applying it across the International Nucleotide Sequence Database Collaboration, we assembled viral_usher_trees, a repository of 446 phylogenies spanning 163 well-sequenced viral species, rebuilt automatically monthly as new genomes are deposited. We extended Taxonium from a tree viewer into a web platform supporting in-browser phylogenetic placement and de novo tree construction, so that users can upload sequences and contextualize them within global phylogenies without local computational infrastructure. Because every tree is built by the same procedure, the repository enables comparative analyses across the breadth of viral diversity. We demonstrate the utility of this resource by asking what factors shape viral mutation spectra. We found that replication machinery, captured as Baltimore class, explains 46% of the variance across 162 viral genomes, while host taxon and envelope status together explain under 5%. These resources provide an extensible platform for real-time genomic epidemiology and for comparative evolutionary analysis across viral pathogens. Resources and code are freely available at https:\/\/taxonium.org\/, https:\/\/github.com\/lilymaryam\/spectrum_analysis, https:\/\/github.com\/AngieHinrichs\/viral_usher_trees, and https:\/\/github.com\/AngieHinrichs\/viral_usher.","rel_num_authors":5,"rel_authors":[{"author_name":"Angie S Hinrichs","author_inst":"UC Santa Cruz"},{"author_name":"Lily M Karim","author_inst":"UC Santa Cruz"},{"author_name":"Yatish Turakhia","author_inst":"University of California San Diego"},{"author_name":"Theo Sanderson","author_inst":"London School of Hygiene and Tropical Medicine"},{"author_name":"Russell Corbett-Detig","author_inst":"UC Santa Cruz"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Characterization of Host Cell Cytosol-filled Vesicles in the Human Malaria Parasite Plasmodium falciparum","rel_doi":"10.64898\/2026.09.10.750675","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750675","rel_abs":"Endocytosis of host cell cytosol is a key process in malaria blood stages. The endocytosed material consists mostly of haemoglobin (Hb) and is transported to the parasite's digestive vacuole (DV), where it is degraded. However, the endosomal transport pathway of the parasite is not well defined. A number of proteins are known that - when inactivated - lead to the appearance of Hb-filled vesicles (HbVs) in the parasite cytoplasm and prevent Hb from arriving in the DV, indicating they play a role in endosomal transport. However, despite the prominence of these HbVs, their morphology, molecular composition, and relationship to the endosomal transport pathway remain poorly understood. Here we carried out a morphological and surface proteome study of HbVs. CryoET showed HbVs are coatless, double membraned vesicles with a very narrow inter-membrane space devoid of larger protein densities. HbV surface proteomes generated by BioIDs most prominently detected DV proteases. Halo-based tracking of one of these DV protease confirmed it as a bona fide HbV cargo. The BioID also identified a number of vesicle trafficking proteins, including PfTBC8 and Rab11 proteins. Functional analysis of PfTBC8 showed its importance for the transport of Hb to the DV. This was due to a novel phenotype characterized by accumulation of diverse Hb-filled structures in the parasite cytosol and gradual decline of DV protease trafficking. PfTBC8 DiQ-BioID detected Rab11a and PfTBC8 inactivation altered Rab11a localization, suggesting it may be a Rab11a effector and that the new endosomal transport phenotype may result from a recycling defect. Together with the detection of VPS35 in the BioID and evidence from the CryoET of a disrupted inner HbV membrane in a proportion of vesicles, these findings support a model in which HbVs undergo maturation prior to fusion with the DV. Overall, our findings define morphological and molecular features of HbVs, identify protein cargo transported through this pathway, and reveal a previously unrecognized Rab-regulatory component required for endosomal trafficking in blood-stage P. falciparum parasites.","rel_num_authors":12,"rel_authors":[{"author_name":"Anna-Lena Rossmann","author_inst":"Bernhard Nocht Institute for Tropical Medicine"},{"author_name":"Jana Droege","author_inst":"Bernhard Nocht Institute for Tropical Medicine"},{"author_name":"Hanyu Wang","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Charlotte Duda","author_inst":"Bernhard Nocht Institute for Tropical Medicine"},{"author_name":"James Zhen","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Ricarda Sabitzki","author_inst":"Bernhard Nocht Institute for Tropical Medicine"},{"author_name":"Katharina Hoehn","author_inst":"Bernhard Nocht Institute of Tropical Medicine"},{"author_name":"Guilherme B. Farias","author_inst":"Centre for Structural Systems Biology"},{"author_name":"Andres Guillen Samander","author_inst":"Bernhard Nocht Institute for Tropical Medicine"},{"author_name":"Tim Gilberger","author_inst":"Bernhard-Nocht-Institut fur Tropenmedizin"},{"author_name":"Chi-Minh Ho","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Tobias Spielmann","author_inst":"Bernhard Nocht Institute for Tropical Medicine"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Large-Vessel Venous Signal Confounds Apparent Amygdala Activation in BOLD fMRI","rel_doi":"10.64898\/2026.09.04.749520","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.04.749520","rel_abs":"Amygdala responses are widely reported in BOLD fMRI studies of human emotions and mood disorders. Although modern acquisition methods have improved image quality, the hemodynamic nature of the BOLD signal continues to complicate interpretation of these responses. Across an array of both visual and auditory tasks, we here show that apparent amygdala BOLD signal is substantially confounded by signal from nearby deep veins, including the basal vein of Rosenthal. In contrast to prior work, we show that the amygdala, when engaged, is the leading but not exclusive contributor to this venous signal. Across the tested conditions, this signal was sensitive to, but not specific for, amygdala engagement. This confound mislocalizes apparent activation and prevents reliable attribution of signal to amygdala subnuclei with conventional BOLD fMRI. We further show that spatial smoothing exacerbates this mislocalization by merging peri-amygdalar venous signal with the anatomical amygdala. We reproduce our findings from precision imaging in a larger sample obtained from the Human Connectome Project. While broad conclusions about amygdala engagement remain largely valid when based on unsmoothed signal within the anatomical amygdala, further conclusions about subnuclear function drawn from conventional fMRI alone warrant considerable caution.","rel_num_authors":3,"rel_authors":[{"author_name":"Zachary Diamandis","author_inst":"California Institute of Technology"},{"author_name":"J. Michael Tyszka","author_inst":"California Institute of Technology"},{"author_name":"Ralph Adolphs","author_inst":"California Institute of Technology"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Flexible reorientation of conserved neural dynamics underlies grasp control","rel_doi":"10.64898\/2026.09.04.749537","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.04.749537","rel_abs":"Grasping objects is a complex behavior requiring high-dimensional hand control and dynamic interaction with the environment, yet its neural mechanisms remain poorly understood. Dynamical systems approaches have provided key insights into how neural populations generate control signals for arm movements such as reaching and cycling but have proven insufficient to account for neural population activity during grasping. Here, we re-analyzed multi-area neural recordings from rhesus monkeys performing a reach-to-grasp task to many objects and found two key population-level features. First, the component of the population trajectory that was common to all grasps formed a small angle with the subspace containing grasp condition-specific (object) tuning. Second, the neural activity was well fitted by a recent, flexible dynamical model developed for reaching, called location-dependent rotations (LDR). Neural activity in M1 and F5 during grasping exhibited conserved population-level rotational frequencies, but the state-space planes in which these rotations occurred varied systematically with grasp condition. The rotational center (the location) and the orientation of the rotations related both to each other and to the kinematics of movement. While these rotations were reoriented in high dimensional space, reflecting the high-dimensional nature of hand control, the extent of their tilt into additional dimensions were small, in contrast to reaching. This structure may reflect the nature of grasping as modulations of an overall open-close motif. Together, these results indicate that the LDR dynamics framework applies to grasping as well as reaching and provides an entry point to understanding how grasp commands are generated.","rel_num_authors":2,"rel_authors":[{"author_name":"Zulfar Ghulam-Jelani","author_inst":"The University of Chicago"},{"author_name":"Matthew T Kaufman","author_inst":"The University of Chicago"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Poor foam stability in gluten-free beers is associated with distinct protein composition compared with barley-malt beers","rel_doi":"10.64898\/2026.09.04.749538","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.04.749538","rel_abs":"Why was the work done?: Gluten-free (GF) beers typically exhibit poorer foam stability than conventional barley malt-based beers, yet the molecular basis underlying this difference remains poorly understood. This study aimed to investigate protein-level factors associated with foam stability in GF and barley beers. How was the work done?: Three commercially produced GF beers, comprising two lagers brewed from rice or sorghum, and one pale ale brewed from a millet-buckwheat-rice blend, were compared with two commercially produced barley-malt beers, comprising a lager and a pale ale. Soluble protein was isolated from freeze-dried beer powder using TCA-acetone. Protein profiles were examined using SDS-PAGE, and proteomes were characterised and compared using label-free quantitative LC-MS\/MS. What are the main findings?: GF beers showed lower soluble protein concentrations and significantly lower foam stability than the barley beers. SDS-PAGE revealed fewer and weaker protein bands in GF beers compared with barley beers. Proteomic analysis showed that barley beers were enriched in known foam-active proteins, particularly lipid transfer protein 1 (LTP1) and Protein Z (serpin family members), whereas these proteins were not detected or were detected only at very low levels in GF beers.","rel_num_authors":4,"rel_authors":[{"author_name":"Zesun Lyu","author_inst":"University of Sydney"},{"author_name":"Jacob Humphries","author_inst":"University of Sydney"},{"author_name":"Farhad Masoomi-Aladizgeh","author_inst":"University of Sydney"},{"author_name":"Thomas H. Roberts","author_inst":"University of Sydney"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Using stochastic dynamic programming for making decisions about invasive species","rel_doi":"10.64898\/2026.09.05.749566","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.05.749566","rel_abs":"1. Invasive species pose significant ecological, economic, and public health challenges. Their management requires repeated decisions under uncertainty about when, where and how intensively to intervene. Although structured decision-making and adaptive management provide conceptual frameworks for addressing these challenges, their practical implementation remains limited because optimization methods such as stochastic dynamic programming (SDP) are often perceived as mathematically complex, challenting to apply and difficult to interpret. 2. Here, we provide a practical guide to using SDP and its extensions for invasive species management. Using coypu (*Myocastor coypus*) management as a running case study, we introduce the framework through a minimal working example before progressively extending it to spatial dynamics, imperfect detection using partially observable Markov decision processes (POMDPs), adaptive management under model uncertainty, and value-of-information analyses that quantify the benefits of learning before acting. 3. All examples are accompanied by reproducible implementations in R, together with recommendations on model formulation, parameterization and interpretation. We also discuss the strengths and limitations of SDP. 4. By lowering the technical barrier to SDP, this guide aims to help ecologists and wildlife managers integrate decision theory into invasive species management, enabling transparent, reproducible and objective-driven management strategies under uncertainty. More broadly, the methods presented here are applicable to a wide range of ecological decision problems beyond invasive species, wherever management requires balancing immediate actions against uncertain future outcomes.","rel_num_authors":5,"rel_authors":[{"author_name":"Olivier Gimenez","author_inst":"CNRS"},{"author_name":"Abby Keller","author_inst":"University of California, Berkeley"},{"author_name":"Lucile Marescot","author_inst":"CIRAD"},{"author_name":"Carl Boettinger","author_inst":"University of California Berkeley"},{"author_name":"Cassie Speakman","author_inst":"RMIT University"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"High-dimensional population codes reveal interpretable and diverse features underlying visual perception","rel_doi":"10.64898\/2026.09.05.748439","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.05.748439","rel_abs":"Despite large-scale recordings, neuroscience has identified representations for only a small fraction of visual features distinguishable by humans. This is increasingly attributed to mixed selectivity, where individual neurons respond to multiple stimuli, requiring population-level readouts of human-recognizable ('interpretable') representations. To identify interpretable representations at scale, we 1)computationally extract population codes from macaque electrophysiology datasets spanning V4 and IT cortex and vision models and 2) introduce an automated method to measure representation interpretability and diversity, then isolate a set of unique, meaningful features encoded by neurons versus populations. Across datasets, populations represent more interpretable, diverse features than neurons. This advantage grows with the number of sampled neurons and image diversity. Finally, we demonstrate through targeted ablations that interpretable representations play a causal role in downstream behavior. Overall, our framework enables a more comprehensive account of the features represented across biological and artificial visual systems and their contributions to visual perception.","rel_num_authors":4,"rel_authors":[{"author_name":"Habon Issa","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Sunny Liu","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Jona Ball\u00e9","author_inst":"New York University"},{"author_name":"David Klindt","author_inst":"Cold Spring Harbor Laboratory"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"H-NS silences antiviral immunity through 3D chromatin compaction","rel_doi":"10.64898\/2026.09.05.749240","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.05.749240","rel_abs":"Bacterial antiviral immunity systems can be toxic to their hosts and must be tightly regulated. Immunity genes are often encoded by AT-rich mobile genetic elements subjected to silencing by nucleoid binding protein H-NS. Using RNA-seq, ChIP-seq, and chromosome 3D reconstruction with Micro-C, we find that H-NS binds and compacts bacterial immunity loci. H-NS deletion reveals anti-phage activity in model Escherichia coli strains generally considered phage-sensitive. Extending this approach to environmental isolates, we show that removal of H-NS silencing enhances defense, allowing bacteria to restrict phages with anti-defense proteins. We also discover Madara, a novel immunity system that complements the co-regulated BREX defense. Our results establish H-NS as a master regulator of bacterial immunity and highlight the importance of expression levels for anti-phage activity in native hosts.","rel_num_authors":13,"rel_authors":[{"author_name":"Timofey Khvostikov","author_inst":"Center for Bio- and Medical Technologies, Moscow, Russia"},{"author_name":"Polina Iarema","author_inst":"Center for Bio- and Medical Technologies, Moscow, Russia"},{"author_name":"Alexey Gavrilov","author_inst":"Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA"},{"author_name":"Ilya Shamovsky","author_inst":"Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA"},{"author_name":"Vitaly Epshtein","author_inst":"Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA"},{"author_name":"Alexandr Andriianov","author_inst":"Center for Bio- and Medical Technologies, Moscow, Russia"},{"author_name":"Polina Baikuzina","author_inst":"Genomic and Bioimaging Core Facility, Moscow, Russia"},{"author_name":"Elena Shagimardanova","author_inst":"Genomic and bioimaging core facility, Skolkovo Institute of Science and technology, Moscow, Russia"},{"author_name":"Dmitry Senko","author_inst":"Center for Bio- and Medical Technologies, Moscow, Russia"},{"author_name":"Thomas K Wood","author_inst":"Department of Chemical Engineering, Pennsylvania State University, University Park, Pennsylvania, 16802-4400, USA"},{"author_name":"Konstantin Severinov","author_inst":"Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia"},{"author_name":"Evgeny Nudler","author_inst":"Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA"},{"author_name":"Artem Isaev","author_inst":"Center for Bio- and Medical Technologies, Moscow, Russia"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Neoadjuvant chemotherapy induces transient, regimen-specific immune stromal reprogramming in pancreatic ductal adenocarcinoma","rel_doi":"10.64898\/2026.09.07.749769","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.07.749769","rel_abs":"Background: Neoadjuvant chemotherapy (NAC) is increasingly incorporated into the management of pancreatic ductal adenocarcinoma (PDAC), yet how treatment regimen and timing reshape the tumour-immune microenvironment remains poorly defined. Methods: Targeted immune transcriptomic profiling was performed using NanoString on spatially annotated tumour, stromal, and immune-enriched regions from resected PDAC specimens from 23 patients, including NAC-treated and treatment-naive cohorts. Key findings were validated and spatially localised using Xenium in situ transcriptomics. Results: NAC induced extensive transcriptional remodelling of the tumour microenvironment in a regimen- and time-dependent manner. Tumours resected shortly after FOLFIRINOX exhibited coordinated upregulation and strong spatial coupling of the CXCL12-CXCR4 axis. These correlations were attenuated or reversed at longer post-treatment intervals and following gemcitabine-based therapy. Disrupted stromal coordination of the CCL2-CCR2 axis further highlighted context-dependent effects of chemotherapy on chemokine signalling. Across regions, NT5E (CD73) expression inversely correlated with CD8A, consistent with spatially restricted T cell exclusion. Conclusions: NAC dynamically reprograms the immunestromal landscape of PDAC in a regimen- and timing-dependent manner, revealing a transient post-chemotherapy window of immune remodelling. The clinical significance of this phenomenon requires further investigation to determine whether temporally optimised integration of immunomodulatory and stroma-targeted therapies with NAC can improve patient outcomes.","rel_num_authors":16,"rel_authors":[{"author_name":"Elahe Minaei","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia."},{"author_name":"Dezerae Cox","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia."},{"author_name":"Amarinder Singh Thind","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia."},{"author_name":"Gary Tincknell","author_inst":"Illawarra Cancer Care Centre, Wollongong, NSW, Australia."},{"author_name":"Leo A. Coleman","author_inst":"Prince of Wales Hospital, School of Clinical Medicine, Randwick Clinical Campus, University of New South Wales, Sydney, NSW, Australia."},{"author_name":"Samantha  J Wade","author_inst":"University of Wollongong"},{"author_name":"Naila Islam","author_inst":"New South Wales Health Pathology, Wollongong, NSW, Australia."},{"author_name":"Dale Waring","author_inst":"New South Wales Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia."},{"author_name":"Mona Ahuja","author_inst":"New South Wales Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia."},{"author_name":"Joanne La Malfa","author_inst":"New South Wales Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia."},{"author_name":"Koroush S Haghighi","author_inst":"School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Sydney, NSW, Australia."},{"author_name":"Marie Ranson","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia."},{"author_name":"Morteza Aghmesheh","author_inst":"Prince of Wales Hospital, School of Clinical Medicine, Randwick Clinical Campus, University"},{"author_name":"Ronald Sluyter","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia"},{"author_name":"Eileen M. OReilly","author_inst":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Weill Cornell Medicine, New York, NY, USA"},{"author_name":"Kara  L Vine-Perrow","author_inst":"School of Science, Faculty of Science Medicine and Health, University of Wollongong, Wollongong, NSW, Australia"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"CIDER: detecting changes in gene regulatory networks that are associated with changes in phenotype","rel_doi":"10.64898\/2026.09.08.750185","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750185","rel_abs":"Changes in gene regulatory networks may drive quantitative traits, or may transmit the effects of one trait, such as blood lipid level, on another, such as cardiovascular health. Yet the standard tools, differential correlation and differential network analysis, compare two discrete groups, while the contexts of interest - circulating lipids, inflammation, and blood glucose - vary continuously; applying them forces dichotomization, discarding within-trait variation. We introduce Continuous Interaction-based Differential Edge Regulation (CIDER), which tests whether a gene regulatory network edge, the relationship between a transcription factor and its target gene, varies with a continuous trait: the target gene's expression is modeled as a function of the TF's expression level, the trait, and their interaction, with the interaction coefficient measuring the trait dependence. To limit multiple testing, CIDER tests only the edges of a reference regulatory network. A generalized additive extension detects interactions that change the shape of the relationship, not only its slope, including forms that cannot be expressed as a difference between two correlations. In simulations it outperformed four two-group methods across sample sizes, effect sizes, and noise levels, with most of its advantage from keeping the trait continuous. In whole-blood transcriptomes from four independent human cohorts across ten quantitative health traits, CIDER identified 63 replicated cases in which a TF's regulation of its target varies with the trait, including coupling of the glucocorticoid-receptor (NR3C1) to the granulocyte colony-stimulating-factor receptor (CSF3R) that strengthens as triglycerides rise, and a pair whose regulation reverses direction across the observed range of C-reactive protein.","rel_num_authors":5,"rel_authors":[{"author_name":"Wooseok J Jung","author_inst":"Washington University in St. Louis"},{"author_name":"Mingyue Ding","author_inst":"Washington University in St. Louis"},{"author_name":"Shu Liao","author_inst":"Washington University in St. Louis"},{"author_name":"Zolboo Erdenebaatar","author_inst":"Washington University in St. Louis"},{"author_name":"Michael Brent","author_inst":"Washington University in St. Louis"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"A Pooled CRISPR Screen Protocol for Comparative Pathway Analysis Across Multiple Stressors","rel_doi":"10.64898\/2026.09.07.749902","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.07.749902","rel_abs":"High content CRISPR screens have become a leading method for the identification of new cellular pathways, proteins functions, and drug targets. However, as the complexity of these screens increase, so does the possibility of artifacts. Here, we describe a refined CRISPR screening protocol that can compare acute cellular responses across multiple cellular treatments and timepoints, while reducing false positives by up to 40% compared to conventional screening approaches. This is achieved through the use of a fluorescence-based reporter line responsive to multiple stressors, as well as a fixation step to preserve acute response differences and avoid sorting-related false positives. We recently performed a version of this workflow to compare kinases regulating different types of selective autophagy, including starvation-induced autophagy, ERphagy, and pexophagy. Beyond autophagy research, this screen approach can be implemented for any fluorescence-based screen where preservation of acute cellular responses is important. Here we present a complete workflow of this optimized screening protocol using our selective autophagy screen as a specific example throughout. Implementation of these strategies should allow researchers to increase the number of stressors tested within a single screen without sacrificing cell health, reliability, or statistical power.","rel_num_authors":5,"rel_authors":[{"author_name":"Truc Losier","author_inst":"University of Ottawa"},{"author_name":"Karyn King","author_inst":"University of Ottawa"},{"author_name":"James Taylor","author_inst":"University of Ottawa"},{"author_name":"Maxime Rousseaux","author_inst":"University of Ottawa"},{"author_name":"Ryan Russell","author_inst":"University of Ottawa"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"A Pooled CRISPR Screen Protocol for Comparative Pathway Analysis Across Multiple Stressors","rel_doi":"10.64898\/2026.09.07.749902","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.07.749902","rel_abs":"High content CRISPR screens have become a leading method for the identification of new cellular pathways, proteins functions, and drug targets. However, as the complexity of these screens increase, so does the possibility of artifacts. Here, we describe a refined CRISPR screening protocol that can compare acute cellular responses across multiple cellular treatments and timepoints, while reducing false positives by up to 40% compared to conventional screening approaches. This is achieved through the use of a fluorescence-based reporter line responsive to multiple stressors, as well as a fixation step to preserve acute response differences and avoid sorting-related false positives. We recently performed a version of this workflow to compare kinases regulating different types of selective autophagy, including starvation-induced autophagy, ERphagy, and pexophagy. Beyond autophagy research, this screen approach can be implemented for any fluorescence-based screen where preservation of acute cellular responses is important. Here we present a complete workflow of this optimized screening protocol using our selective autophagy screen as a specific example throughout. Implementation of these strategies should allow researchers to increase the number of stressors tested within a single screen without sacrificing cell health, reliability, or statistical power.","rel_num_authors":5,"rel_authors":[{"author_name":"Truc Losier","author_inst":"University of Ottawa"},{"author_name":"Karyn King","author_inst":"University of Ottawa"},{"author_name":"James Taylor","author_inst":"University of Ottawa"},{"author_name":"Maxime Rousseaux","author_inst":"University of Ottawa"},{"author_name":"Ryan Russell","author_inst":"University of Ottawa"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Causal variant underestimation is a major overlooked driver of sequence-to-function model underperformance","rel_doi":"10.64898\/2026.09.08.750172","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750172","rel_abs":"Deep learning sequence-to-function (S2F) models represent tremendous promise for functionally fine-mapping causal variants associated with traits and disease. Yet it remains unclear precisely how effective they are at this task. Generally, S2F models perform well at classifying putatively causal expression quantitative trait loci (eQTL) SNVs, yet dramatically underperform linear baselines at ranking different individuals' gene expression values from their whole genome sequence, which directly calls into question their ability to fine-map a locus by properly weighting the effects of variants onto gene expression. Here, using the state-of-the-art S2F model AlphaGenome, we systematically compared predicted effect sizes for fine-mapped eQTLs to nearby putatively non-causal SNVs, finding that AlphaGenome pervasively underestimates the effects of most causal variants and fails to successfully fine-map eQTLs in most loci for this reason. We show that misdirected variant effect predictions and negative cross-individual correlations, widely cited as major challenges facing S2F expression modeling, are not egregious errors but a chance consequence of weak, noisy attributions when causal variants are underestimated. Our results suggest that a failure to detect local variant effects onto enhancer activity is a cause of underestimation. Additionally, we find that underestimated variants are enriched far from their target gene, suggesting inadequate enhancer-gene linking causes underestimation even when local effects are well-detected. Finally, our results clarify when S2F models are reliable for fine-mapping objectives: while they pervasively underestimate most causal variants, demonstrating limited fine-mapping utility for most loci, the top 0.1 most prominent variant effect predictions are strongly enriched for causal variants with directionally correct predictions that are consistent across model replicates, suggesting extremely strong predictions are broadly trustworthy. Our results demonstrate that causal variant underestimation is a core issue facing S2F expression predictors, with future improvements dependent on better local activity detection and enhancer-gene linking.","rel_num_authors":2,"rel_authors":[{"author_name":"Shiron Drusinsky","author_inst":"Gladstone Institutes"},{"author_name":"Katherine S. Pollard","author_inst":"Gladstone Institutes"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Candida albicans promotes self-adhesion and tumor cell progression of colorectal cancer cells.","rel_doi":"10.64898\/2026.09.09.750446","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750446","rel_abs":"Candida albicans, a benign commensal yeast in the healthy gut, is increasingly being recognized as a tumor-promoting component of the gut mycobiome that is linked to worse patient outcomes in colorectal cancer (CRC). Emerging evidence suggests that in the tumor microenvironment, C. albicans drives tumor progression in its pathogenic hyphal form with the secretion of its peptide toxin, candidalysin, enhancing tumor cell evolution. CRC cells differentially express transglutaminase 2 (TG2), which mediates covalent binding to C. albicans and can promote tumor adaptability and metastases. However, mechanistic insight into how C. albicans infection leads to CRC progression is incomplete. CRC lines that express high (SW480) and low (LoVo, HCT 116) TG2 were infected with C. albicans and examined for effects on epithelial to mesenchymal transition (EMT) and cell migration. Parallel studies were also conducted using a candidalysin-deficient C. albicans strain. C. albicans invasion stimulated TG2 activity that allowed covalent crosslinking of the hyphae adhesin, Hwp1, to SW480 cells in a candidalysin-dependent manner. Independent of TG2 expression, infection of SW480, LoVo, and HCT 116 cells induced EMT-like changes including downregulation of E-cadherin, altered N-glycosylation of N-cadherin, and variable Snail1 expression. Infection increased MGAT5 activity, which raised levels of branched {beta}(1-6) N-glycans. Infection promoted CRC cell motility that was blocked by pharmacological inhibition of MGAT5. Thus, C. albicans engages CRC cells through separable mechanisms: a candidalysin-TG2-Hwp1 axis that may stabilize fungal attachment in TG2-high tumor cells, and a TG2-independent program of epithelial plasticity, altered N-glycosylation and migration-associated behavior that requires validation in vivo.","rel_num_authors":4,"rel_authors":[{"author_name":"Janet F. Staab","author_inst":"Johns Hopkins University"},{"author_name":"Olivia K. A. Paulin","author_inst":"King's College London"},{"author_name":"Julian R. Naglik","author_inst":"King's College London"},{"author_name":"Nicholas C. Zachos","author_inst":"Vanderbilt University Medical Center"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Candida albicans promotes self-adhesion and tumor cell progression of colorectal cancer cells.","rel_doi":"10.64898\/2026.09.09.750446","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750446","rel_abs":"Candida albicans, a benign commensal yeast in the healthy gut, is increasingly being recognized as a tumor-promoting component of the gut mycobiome that is linked to worse patient outcomes in colorectal cancer (CRC). Emerging evidence suggests that in the tumor microenvironment, C. albicans drives tumor progression in its pathogenic hyphal form with the secretion of its peptide toxin, candidalysin, enhancing tumor cell evolution. CRC cells differentially express transglutaminase 2 (TG2), which mediates covalent binding to C. albicans and can promote tumor adaptability and metastases. However, mechanistic insight into how C. albicans infection leads to CRC progression is incomplete. CRC lines that express high (SW480) and low (LoVo, HCT 116) TG2 were infected with C. albicans and examined for effects on epithelial to mesenchymal transition (EMT) and cell migration. Parallel studies were also conducted using a candidalysin-deficient C. albicans strain. C. albicans invasion stimulated TG2 activity that allowed covalent crosslinking of the hyphae adhesin, Hwp1, to SW480 cells in a candidalysin-dependent manner. Independent of TG2 expression, infection of SW480, LoVo, and HCT 116 cells induced EMT-like changes including downregulation of E-cadherin, altered N-glycosylation of N-cadherin, and variable Snail1 expression. Infection increased MGAT5 activity, which raised levels of branched {beta}(1-6) N-glycans. Infection promoted CRC cell motility that was blocked by pharmacological inhibition of MGAT5. Thus, C. albicans engages CRC cells through separable mechanisms: a candidalysin-TG2-Hwp1 axis that may stabilize fungal attachment in TG2-high tumor cells, and a TG2-independent program of epithelial plasticity, altered N-glycosylation and migration-associated behavior that requires validation in vivo.","rel_num_authors":4,"rel_authors":[{"author_name":"Janet F. Staab","author_inst":"Johns Hopkins University"},{"author_name":"Olivia K. A. Paulin","author_inst":"King's College London"},{"author_name":"Julian R. Naglik","author_inst":"King's College London"},{"author_name":"Nicholas C. Zachos","author_inst":"Vanderbilt University Medical Center"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Discovery of a molecular glue inhibitor that stabilises a non-productive Kalirin-Rac1 complex","rel_doi":"10.64898\/2026.09.08.749156","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.749156","rel_abs":"Rho guanosine triphosphatases (GTPases) are molecular-switches implicated in neurodegenerative diseases, yet targeting them through competitive inhibition remains a challenge due to their high affinity for guanine nucleotides. Guanine nucleotide exchange factors (GEFs) catalyse GDP-to-GTP nucleotide exchange to activate GTPases, providing an alternative opportunity for GTPase modulation. Herein, we describe a complex-targeted strategy to inhibit nucleotide exchange with covalent molecular glues that engage the Kalirin-Rac1 GEF-GTPase complex at the nucleotide binding site are sequester the GEF Kalirin. Fragment hits were identified through XChem and in silico screening, and a fragment merging approach resulted in the generation of covalent inhibitors RS-009 and MC-278. Multiple analyses demonstrate our compounds inhibit nucleotide exchange both through competition with the nucleotides and by stabilising a ternary inhibitor-Rac1-Kalirin complex, thereby trapping Kalirin in a non-productive state and reducing GEF turnover. Biochemical selectivity screening and cellular activity-based protein profiling (ABPP) show that selectivity can be achieved across distinct GEF-GTPase complexes, which may result in improved spatiotemporal control over targeting the GTPase alone. This work provides evidence for targeting GTPase signalling via stabilization of the GEF-GTPase complex in a unique covalent molecular glue mechanism and provides the basis of a chemical probe or therapeutic.","rel_num_authors":19,"rel_authors":[{"author_name":"Janine L. Gray","author_inst":"University of Oxford"},{"author_name":"Mia C. Callens","author_inst":"University of Oxford"},{"author_name":"Amelia Henley","author_inst":"University of Oxford"},{"author_name":"Daniel Zaidman","author_inst":"Weizmann Institute of Science"},{"author_name":"Carmen Jimenez Antunez","author_inst":"University of Oxford"},{"author_name":"Andrew P. Thompson","author_inst":"Walter and Eliza Hall Institute of Medical Research (WEHI)"},{"author_name":"Zhihe Lei","author_inst":"University of Oxford"},{"author_name":"Rachael Skyner","author_inst":"Diamond Light Source"},{"author_name":"Michael Miller","author_inst":"University of Oxford"},{"author_name":"Eleanor P. Williams","author_inst":"University of Oxford"},{"author_name":"Anya Robinson","author_inst":"University of Oxford"},{"author_name":"Raina Seupal","author_inst":"University of Oxford"},{"author_name":"Matt T. Fry","author_inst":"University of Oxford"},{"author_name":"Mihajlo Filep","author_inst":"Weizmann Institute of Science"},{"author_name":"Frank von Delft","author_inst":"Diamond Light Source"},{"author_name":"Michael P. Willis","author_inst":"University of Oxford"},{"author_name":"Annette R. von Delft","author_inst":"University of Oxford"},{"author_name":"Nir London","author_inst":"Weizmann Institute of Science"},{"author_name":"Paul E. Brennan","author_inst":"University of Oxford"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"The phage shock protein A (PspA) maintains membrane potential and supports NADH dehydrogenase function in mycobacteria","rel_doi":"10.64898\/2026.09.09.750162","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750162","rel_abs":"Maintenance of membrane integrity and proton motive force (PMF) is critical for bacterial survival. The phage shock protein (Psp) system, conserved across bacterial species, stabilizes the membrane, maintains PMF, and protects against envelope damage. However, how the conserved effector PspA contributes to PMF maintenance remains unclear. Here, using the mycobacterial Psp system as a genetically tractable model, we provide mechanistic insight into this process. We show that PspA and the accessory protein PspM jointly sustain membrane potential, with PspM required to maintain a ~70 kDa PspA isoform at the membrane during envelope stress. Loss of PspA increases susceptibility to thioridazine, which targets type II NADH dehydrogenase (NDH-2), and to Ro 48-8071, an inhibitor of menaquinone biosynthesis. Notably, hypersusceptibility to thioridazine is rescued by exogenous menaquinone. Consistent with these phenotypes, a pspA-deficient mutant exhibits impaired NADH dehydrogenase activity despite unchanged abundance of NDH-2 and menaquinone (MK-9). Together, these findings identify a functional link between PspA and NADH dehydrogenase-dependent respiration and suggest that PspA contributes to PMF maintenance by supporting respiratory electron transfer.","rel_num_authors":13,"rel_authors":[{"author_name":"Pratik Datta","author_inst":"Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ 07103"},{"author_name":"Roberta Provvedi","author_inst":"Department of Molecular Medicine, University of Padova, Italy 35122"},{"author_name":"Charles D Sohaskey","author_inst":"Department of Veterans Affairs Medical Center, Long Beach, California 90822"},{"author_name":"Rahul Ukey","author_inst":"Rutgers University, Newark"},{"author_name":"Julia Puffal","author_inst":"University of Massachusetts Amherst"},{"author_name":"Malavika Prithviraj","author_inst":"Department of Microbiology, University of Massachusetts, Amherst, MA 01003"},{"author_name":"Andrea Tellez","author_inst":"Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10021"},{"author_name":"Anas Saleh","author_inst":"NewYork-Presbyterian Weill Cornell Medical Center"},{"author_name":"Rasel Khan","author_inst":"Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ 07103"},{"author_name":"Riccardo Manganelli","author_inst":"University of Padova"},{"author_name":"Yasu S Morita","author_inst":"Department of Microbiology, University of Massachusetts, Amherst, MA 01003"},{"author_name":"Kyu Young Rhee","author_inst":"Weill Cornell Medical College"},{"author_name":"Maria Laura Gennaro","author_inst":"Rutgers University, Newark"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Postnatal maturation of putamen microstructure accompanies topographic white matter connectivity and altered circuits in autism","rel_doi":"10.64898\/2026.09.09.750447","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.09.750447","rel_abs":"The putamen is a major hub of the basal ganglia that emerges early in gestation. However, whether its mature organization is established before birth or emerges postnatally remains unknown. Using cross-sectional and longitudinal quantitative MRI (R1 and R2*, related to tissue density and iron, respectively) and diffusion MRI, we characterized the development of putamen's microstructure and its white matter connectivity with cortex from birth to 12 months and compared their trajectories with those in adults. Despite its prenatal emergence, the putamen undergoes substantial postnatal development. R1 increases from birth to 12 months, producing a prominent anterior-posterior gradient, whereas R2* increases primarily between age one and adulthood, producing a medial-lateral gradient. Cortico-putamen white matter connectivity is diffuse in infants but becomes topographic in adults, with anterior putamen linked to frontal cortex and posterior putamen to sensorimotor cortex. In autism spectrum disorder, this organization is largely preserved and accompanied by increased anterior putamen-prefrontal connectivity. Our findings reveal distinct spatial developmental trajectories of putamen microstructure and cortical connectivity providing a developmental framework for understanding the organization of the putamen in infancy, which has implications for assessing neurodevelopmental disorders of the basal ganglia.","rel_num_authors":14,"rel_authors":[{"author_name":"Vaidehi S Natu","author_inst":"Stanford University"},{"author_name":"Christina Tyagi","author_inst":"Stanford University"},{"author_name":"Xiaoqian Yan","author_inst":"Fudan University"},{"author_name":"Sarah S Tung","author_inst":"Stanford University"},{"author_name":"Emily Kubota","author_inst":"Stanford University"},{"author_name":"Seda Karakose-Akbiyik","author_inst":"Stanford University"},{"author_name":"Hua Wu","author_inst":"Stanford University"},{"author_name":"Aviv Mezer","author_inst":"The Hebrew University of Jerusalem, Jerusalem, Israel"},{"author_name":"Elior Drori","author_inst":"The Hebrew University of Jerusalem"},{"author_name":"Nan Wang","author_inst":"Stanford University"},{"author_name":"Congyu Liao","author_inst":"University of California, San Francisco"},{"author_name":"Xiaozhi Cao","author_inst":"Stanford University"},{"author_name":"Kawin Setsompop","author_inst":"Stanford University"},{"author_name":"Kalanit Grill-spector","author_inst":"Stanford University"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Temporal Indexing of Motor Memory","rel_doi":"10.64898\/2026.09.10.750443","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.10.750443","rel_abs":"Humans must store and retrieve distinct implicit motor memories in different contexts. Recent research has revealed the motor adaptation system's sensitivity to contextual cues related to posture, spatial goals, and visual inputs. However, to date, the role of one critical variable in implicit motor memory retrieval - the passage of time - remains underexplored, even though it is arguably more fundamental. Here we ask if different temporal intervals can act as effective contextual cues for retrieving competing motor adaptation memories at the subsecond level. We combined a visuomotor dual adaptation paradigm with a 'set-go' task to link opposite perturbation contexts with different movement preparation intervals. The preparation intervals (and their associated perturbations) were randomly interleaved during training, leading to consistent interference. After training, a testing phase revealed robust contextual modulation effects, such that distinct implicit motor memories were retrieved based on the time elapsed during the pre-movement preparatory interval. These contextual memory effects generalized to novel preparatory intervals in a highly structured fashion. Contextual motor memory separation was seen both when elapsed time had to be internally tracked (high uncertainty) and when it was aided by visual and symbolic cues (low uncertainty). Learning and generalization data across experiments could be parsimoniously explained by a computational model that indexed motor memories via a cerebellar granule-cell-like temporal basis set that tiled the delay interval. Our findings suggest that intrinsic timing processes in the cerebellum may function to index motor memories and generalize those memories to new temporal contexts.","rel_num_authors":3,"rel_authors":[{"author_name":"Apoorva Sharma","author_inst":"Yale University"},{"author_name":"Hanna Hillman","author_inst":"Yale University"},{"author_name":"Samuel D. McDougle","author_inst":"Yale University"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Phenotypic screens identify biologic regulators of nanoparticle uptake in diffuse midline glioma","rel_doi":"10.64898\/2026.09.08.749175","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.749175","rel_abs":"Nanoparticle drug delivery systems hold considerable promise for locoregional administration to central nervous system tumors, yet the biological determinants of nanoparticle-cancer cell interactions remain poorly understood. Using patient-derived histone-mutant diffuse midline glioma (DMG) models, we performed a pooled CRISPR-Cas9 perturbation screen to systematically identify regulators of liposomal nanoparticle delivery. The screen identified candidate genes spanning endocytosis, vesicle transport, and metabolic signaling, revealing that nanoparticle delivery is governed by a broader landscape than previously appreciated. Among these, CTNNB1, or {beta}-catenin, emerged as a common negative regulator across two independent DMG models and two distinct nanoparticle surface chemistries. Transcriptomic profiling of CTNNB1-depleted DMG cells revealed upregulation of membrane remodeling and extracellular matrix gene programs, accompanied by reduced cell stiffness measured by a microfluidic acoustic scattering assay. This resulted in a shift in endocytic activity characterized by decreased bulk-phase macropinocytosis and increased receptor-mediated endocytosis. We further identified MAPK and mTOR pathway members as nanoparticle trafficking modulators, and demonstrated concordance between genetic and pharmacologic perturbations in modulating the liposomal nanoparticle interactions in pediatric DMG cells. These findings establish a biology-first screening approach for identifying previously unappreciated regulators with potential relevance to nanoparticle-based therapeutic strategies in pediatric brain tumors.","rel_num_authors":26,"rel_authors":[{"author_name":"Emmeline L Cheng","author_inst":"Ben Towne Center, Seattle Children's Research Institute"},{"author_name":"Sangita Pal","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center, Department of Pediatrics, Harvard Medical School; Broad Institute of MIT and Harvard"},{"author_name":"Jessica W Tsai","author_inst":"Dana-Farber Boston Children's Cancer and Blood Disorders Center; Department of Pediatrics, Harvard Medical School; Broad Institute  of MIT and Harvard; Children"},{"author_name":"Clara B Yampanis","author_inst":"Ben Towne Center, Seattle Children's Research Institute"},{"author_name":"Shriya Rangaswamy","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center; Broad Institute of MIT and Harvard"},{"author_name":"Julianna Kenny-Serrano","author_inst":"Koch Institute for Integrative Cancer Research"},{"author_name":"Marissa Coppola","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center; Childrens Hospital Los Angeles"},{"author_name":"Merve Ozdemir","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center"},{"author_name":"Kelly Y Cai","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center"},{"author_name":"Ethan VanGosen","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center"},{"author_name":"Emma Bateman","author_inst":"Dana-Farber\/Boston Children's Cancer and Blood Disorders Center"},{"author_name":"Kimberly R Bennett","author_inst":"Koch Institute for Integrative Cancer Research; Harvard-MIT Division of Health Sciences & Technology"},{"author_name":"Margaret M Billingsley","author_inst":"Koch Institute for Integrative Cancer Research"},{"author_name":"Charles A Whittaker","author_inst":"Koch Institute for Integrative Cancer Research"},{"author_name":"Ye Zhang","author_inst":"Koch Institute for Integrative Cancer Research"},{"author_name":"Myra Dada","author_inst":"Koch Institute for Integrative Cancer Research; Biological Engineering, MIT"},{"author_name":"Sonam Bhatia","author_inst":"Department of Pathology, Dana-Farber Cancer Institute"},{"author_name":"Cong Fu","author_inst":"Department of Pathology, Dana-Farber Cancer Institute"},{"author_name":"Yeji Bae","author_inst":"Research Scientific Computing, Seattle Children's Research Institute"},{"author_name":"Neerja Katiyar","author_inst":"Ben Towne Center, Research Scientific Computing, Seattle Children's Research Institute"},{"author_name":"John G Doench","author_inst":"Broad Institute of MIT and Harvard"},{"author_name":"Keith L Ligon","author_inst":"Department of Pathology, Dana-Farber Cancer Institute; Department of Pathology, Brigham and Women's Hospital; Department of Pathology, Boston Children's Hospita"},{"author_name":"Scott R Manalis","author_inst":"Koch Institute for Integrative Cancer Research; Biological Engineering, MIT;  Broad Institute of MIT and Harvard"},{"author_name":"Paula T Hammond","author_inst":"Koch Institute for Integrative Cancer Research; Department of Chemical Engineering, MIT;  Broad Institute of MIT and Harvard"},{"author_name":"Pratiti Bandopadhayay","author_inst":"Dana-Farber Boston Children's Cancer and Blood Disorders Center; Department of Pediatrics, Harvard Medical School; Broad Institute of MIT and Harvard"},{"author_name":"Joelle P Straehla","author_inst":"Ben Towne Center, Seattle Childrens Research Institute; Department of Pediatrics, University of Washington; Department of Bioengineering, University of Washingt"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Poor survival after myocardial infarction in immune deficient NXG B2m mice is alleviated by transplantation of induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) formulated as spheres, but not single cells","rel_doi":"10.64898\/2026.09.08.748837","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.748837","rel_abs":"The human heart lacks cardiac stem cells and the ability to reestablish the loss of ventricular cardiomyocytes (vCMs) after myocardial infarction (MI) resulting in heart dysfunction. vCM replacement using intracardiac transplantation of human induced pluripotent stem cell (iPSC) derived vCMs represent a promising strategy for targeting MI, but low engraftment remains a challenge. Herein, we investigated whether formulation of ventricular iPSC-CMs (iPSC-vCM) as spheres (iPSC-vCMSphere) improves cell retention and cardiac function as directly compared to single-cells (iPSC-vCMSC) after transplantation in a new severely immunocompromised mouse model with MI. Recipient survival immediately after MI and intervention was poor for both Vehicle (50%) and iPSC-vCMSC (36%) groups, whereas 92% of iPSC-vCMSphere treated mice survived, which is comparable to non-immune deficient C57bl\/6 mice (91%). All surviving and engrafted animals retained iPSC-vCMs in the infarct border zone at 8-weeks, and heart function remained similar between groups, although minor improvements were observed for iPSC-vCMSphere animals. Surprisingly, iPSC-vCMSpheres were less mature than iPSC-vCMSCs. Thus, our data suggest that iPSC-vCM sphere formulation may offer some benefits for intracardiac delivery as compared with single cell formulated iPSC-vCMs, and thus remains a promising candidate for reestablishing the lost CMs after MI in the future.","rel_num_authors":10,"rel_authors":[{"author_name":"Anne Kathrine S\u00f8gaard Terp","author_inst":"University of Southern Denmark"},{"author_name":"Ditte Gry Ellman","author_inst":"University of Southern Denmark"},{"author_name":"Sabrina Bech Mathiesen","author_inst":"University of Southern Denmark"},{"author_name":"Sara Munk Laursen","author_inst":"University of southern Denmark"},{"author_name":"Frederik Adam Bjerre","author_inst":"University of southern Denmark"},{"author_name":"Barbara \u00e1 Gr\u00f6mma Ammentorp","author_inst":"University of Southern Denmark"},{"author_name":"Frederikke Gaardsvig Willadsen","author_inst":"University of Southern Denmark"},{"author_name":"Ellen Ngar Yun Poon","author_inst":"The Chinese University of Hong Kong"},{"author_name":"Charlotte Harken Jensen","author_inst":"University of Southern Denmark"},{"author_name":"Ditte Caroline Andersen","author_inst":"University of Southern Denmark"}],"rel_date":"2026-09-11","rel_site":"biorxiv"},{"rel_title":"Association between Plasmodium falciparum Kelch13 mutations and malaria parasite clearance half-life after artemisinin-based therapy: an updated WWARN systematic review and individual patient data meta-analysis","rel_doi":"10.64898\/2026.09.08.26362414","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26362414","rel_abs":"Background: Artemisinin-based combination therapies remain the first-line treatment for uncomplicated Plasmodium falciparum malaria. Plasmodium falciparum Kelch13 mutations emerge and spread within distinct malaria epidemiological and immunological contexts, shaping the expression of artemisinin resistance (ART-R). Understanding the clinical phenotypes of these mutations requires evaluation across diverse transmission settings and geographic regions. Methods: A systematic review (SR) and individual patient data meta-analysis (IPDMA) were conducted (PROSPERO: CRD42019133366) to identify studies that included serial parasite density measurements and Kelch13 genotyping. Associations between Kelch13 mutations and parasite clearance half-lives (PC1\/2) and Day 3 parasite positivity were assessed. Receiver operating characteristic (ROC) analyses identified PC1\/2 thresholds most strongly associated with relevant Kelch13 mutations. Findings: The SR identified 86 eligible studies, and individual patient data were obtained from 45 studies (n=16,823 patients from 539 study sites in 33 countries). After excluding hyperparasitaemia, Day 3 parasite positivity exceeded 10% overall across all WHO-validated, candidate, and potential mutations, but not for other Kelch13 mutations. Parasite clearance rates were consistently shorter in moderate-to-high-transmission than in lower-transmission areas. The WHO threshold PC1\/2>5h had a sensitivity of 36% (27.9-44.6) for detecting WHO-validated mutations in moderate-to-high transmission areas and 81% (78.5-82.8) in lower transmission areas. In moderate-to-high transmission settings, a PC1\/2 threshold of 3.1h optimally discriminated WHO-validated mutations (ROC AUC 0.78; 95% CI 0.74-0.82; sensitivity 75% (95% CI:67%-82%); specificity 71%, 95% CI: 69%-73%). Additional emerging Kelch13 mutations associated with delayed parasite clearance were identified in relatively small African and Asian sample sets. Interpretation: Compared with WT parasites, parasites carrying WHO-validated ART-R mutations were associated with a 34%- 59% longer mean PC1\/2, regardless of endemicity, treatment regimen, or age. Given the low sensitivity of the PC1\/2>5h threshold for identifying WHO-validated ART-R parasites in moderate-to-high transmission settings, where its recalibration is indicated. Broader genotyping is warranted for identifying emerging Kelch13 mutations associated with delayed parasite clearance.","rel_num_authors":7,"rel_authors":[{"author_name":"Stephanie van Wyk","author_inst":"University of Cape Town"},{"author_name":"- WWARN KELCH13 STUDY GROUP","author_inst":"-"},{"author_name":"Philip J. Rosenthal","author_inst":"University of California, San Francisco"},{"author_name":"Philippe Guerin","author_inst":"University of Oxford"},{"author_name":"Mehul Dhorda","author_inst":"University of Oxford"},{"author_name":"Karen I Barnes","author_inst":"University of Cape Town"},{"author_name":"Prabin Dahal","author_inst":"University of Oxford"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant","rel_doi":"10.64898\/2026.09.04.26361573","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26361573","rel_abs":"GM1 gangliosidosis is an inherited and progressively neurodegenerative lysosomal storage disorder with no approved therapy. We report 5-year safety and 3-year clinical, biochemical, and neuroimaging efficacy outcomes following expanded-access intravenous AAV9-GLB1 gene therapy in GT01, a 6-10-year-old female with juvenile-onset GM1 gangliosidosis. During participation in a natural history study before gene transfer, GT01 developed seizures, dysarthria, loss of ambulation, and progressive neurodegeneration. She received a single intravenous administration of AAV9-GLB1 at 1.5x1013 vector genomes per kilogram of body weight. Early improvements included the resolution of dysphagia, increased interactions with others, assisted ambulation, and gains in specific domains of adaptive functioning. She was seizure-free without anti-epileptic drugs 18 months post dosing with sustained seizure freedom at the study completion. Cerebrospinal fluid concentrations of GM1 ganglioside and H3N2b (a pentasaccharide biomarker indicative of biochemical improvement in this disorder) concentrations decreased by 50% and {beta}-galactosidase reached normal activity. Brain, thalamic, and net fiber tract volume assessed by differential tractography increased and ventriculomegaly improved three years post-dosing. These results indicate that meaningful benefit can be achieved even in advanced neurologic disease.","rel_num_authors":22,"rel_authors":[{"author_name":"Connor J Lewis","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Hera Akmal","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Precilla D'Souza","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Jean M Johnston","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Sumaiya Ashraf","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Gilbert Vezina","author_inst":"Childrens National Hospital"},{"author_name":"Selby I Chipman","author_inst":"National Human Genome Research Institute"},{"author_name":"Meghan Blackwood","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Muhammad H Yousef","author_inst":"National Institutes of Health Clinical Center"},{"author_name":"Zenaide Quezado","author_inst":"National Institutes of Health Clinical Center"},{"author_name":"William A Gahl","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Barry J Byrne","author_inst":"University of Florida"},{"author_name":"Terence R Flotte","author_inst":"UMass Chan Medical School"},{"author_name":"Xuntian R Jiang","author_inst":"Washington University In St Louis"},{"author_name":"Audrey Thurm","author_inst":"National Institute of Mental Health (NIMH)"},{"author_name":"Amanda L Gross","author_inst":"Auburn University"},{"author_name":"Allison Keeler","author_inst":"UMass Chan Medical School"},{"author_name":"Douglas R Martin","author_inst":"Auburn University"},{"author_name":"Miguel Sena-Esteves","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Heather L Gray-Edwards","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Raymond Y Wang","author_inst":"Childrens Hospital of Orange County"},{"author_name":"Cynthia J Tifft","author_inst":"National Human Genome Research Institute (NHGRI)"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Expanded Access use of Intravenous Gene Transfer with AAV9-GLB1 in a Juvenile GM1 Gangliosidosis Participant","rel_doi":"10.64898\/2026.09.04.26361573","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26361573","rel_abs":"GM1 gangliosidosis is an inherited and progressively neurodegenerative lysosomal storage disorder with no approved therapy. We report 5-year safety and 3-year clinical, biochemical, and neuroimaging efficacy outcomes following expanded-access intravenous AAV9-GLB1 gene therapy in GT01, a 6-10-year-old female with juvenile-onset GM1 gangliosidosis. During participation in a natural history study before gene transfer, GT01 developed seizures, dysarthria, loss of ambulation, and progressive neurodegeneration. She received a single intravenous administration of AAV9-GLB1 at 1.5x1013 vector genomes per kilogram of body weight. Early improvements included the resolution of dysphagia, increased interactions with others, assisted ambulation, and gains in specific domains of adaptive functioning. She was seizure-free without anti-epileptic drugs 18 months post dosing with sustained seizure freedom at the study completion. Cerebrospinal fluid concentrations of GM1 ganglioside and H3N2b (a pentasaccharide biomarker indicative of biochemical improvement in this disorder) concentrations decreased by 50% and {beta}-galactosidase reached normal activity. Brain, thalamic, and net fiber tract volume assessed by differential tractography increased and ventriculomegaly improved three years post-dosing. These results indicate that meaningful benefit can be achieved even in advanced neurologic disease.","rel_num_authors":22,"rel_authors":[{"author_name":"Connor J Lewis","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Hera Akmal","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Precilla D'Souza","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Jean M Johnston","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Sumaiya Ashraf","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Gilbert Vezina","author_inst":"Childrens National Hospital"},{"author_name":"Selby I Chipman","author_inst":"National Human Genome Research Institute"},{"author_name":"Meghan Blackwood","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Muhammad H Yousef","author_inst":"National Institutes of Health Clinical Center"},{"author_name":"Zenaide Quezado","author_inst":"National Institutes of Health Clinical Center"},{"author_name":"William A Gahl","author_inst":"National Human Genome Research Institute (NHGRI)"},{"author_name":"Barry J Byrne","author_inst":"University of Florida"},{"author_name":"Terence R Flotte","author_inst":"UMass Chan Medical School"},{"author_name":"Xuntian R Jiang","author_inst":"Washington University In St Louis"},{"author_name":"Audrey Thurm","author_inst":"National Institute of Mental Health (NIMH)"},{"author_name":"Amanda L Gross","author_inst":"Auburn University"},{"author_name":"Allison Keeler","author_inst":"UMass Chan Medical School"},{"author_name":"Douglas R Martin","author_inst":"Auburn University"},{"author_name":"Miguel Sena-Esteves","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Heather L Gray-Edwards","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Raymond Y Wang","author_inst":"Childrens Hospital of Orange County"},{"author_name":"Cynthia J Tifft","author_inst":"National Human Genome Research Institute (NHGRI)"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Childhood Anemia and Maternal Media Exposure in Sub-Saharan Africa: A Multi-Country Cross-Sectional Analysis Across Ghana, Nigeria, and Tanzania","rel_doi":"10.64898\/2026.09.08.26362530","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26362530","rel_abs":"ObjectivesTo examine the association between maternal media exposure and childhood anemia in three sub-Saharan African countries, and to develop a two-stage multiple imputation approach for substantial hemoglobin outcome missingness in Demographic and Health Survey (DHS) data.\n\nDesignMulti-country cross-sectional analysis of nationally representative DHS data.\n\nSettingCommunity-based household surveys in Ghana (2022), Nigeria (2023-24), and Tanzania (2022).\n\nParticipants42,944 children aged 6-59 months across 2,621 clusters.\n\nPrimary and secondary outcome measuresThe primary outcome was anemia (altitude-adjusted hemoglobin <11.0 g\/dL, WHO criteria); the primary exposure was a composite maternal media score (0-4 channels). Given 61.5% hemoglobin missingness, we imputed altitude-adjusted hemoglobin using multilevel Gaussian models and derived anemia deterministically, then estimated associations using population-averaged generalized estimating equations (pre-specified primary analysis), with six sensitivity analyses and exploratory mediation analysis.\n\nResultsMedia exposure was significantly associated with reduced anemia odds (OR 0.946, 95% CI 0.917 to 0.976, p<0.001; FMI 32.5%), a 5.4% reduction per additional weekly channel. Estimates were consistent across six sensitivity analyses (OR range 0.914-0.961), with no heterogeneity by country (I{superscript 2}=0%, p=0.482). Media exposure predicted antenatal care attendance and iron supplementation (both p<0.001), but neither mediated the anemia association.\n\nConclusionsMaternal media exposure was consistently associated with reduced childhood anemia across three sub-Saharan African settings. A two-stage multiple imputation approach addressed substantial (61.5%) outcome missingness while maintaining stable estimates, offering a transferable framework for DHS-based analyses. Prospective and intervention studies are needed before media-based communication can be recommended as a complementary anemia-control strategy.\n\nStrengths and Limitations of This StudyO_LIThis is among the first multi-country analyses to directly examine maternal media exposure and childhood anemia using nationally representative biomarker data from three sub-Saharan African countries.\nC_LIO_LIA validated two-stage multiple imputation approach addressed substantial (61.5%) hemoglobin missingness, with robustness confirmed across six pre-specified sensitivity analyses.\nC_LIO_LIThe cross-sectional design precludes establishing temporality and cannot rule out reverse causation or residual confounding from unmeasured household factors.\nC_LIO_LIMaternal media exposure was measured as frequency of channel use only, without capturing content, quality, or health-specific programming.\nC_LIO_LIMediation analysis relied on a single imputed dataset with non-clustered models, limiting direct comparability with the primary GEE-based estimate.\nC_LI","rel_num_authors":3,"rel_authors":[{"author_name":"Enock Adu Bonsu","author_inst":"University of Arizona"},{"author_name":"Daniel Ebo","author_inst":"Georgia State University"},{"author_name":"Dorcas Doku","author_inst":"University of Iowa"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Epigenetic misprogramming of progenitor cells links transient viral infection to chronic diseases across tissues","rel_doi":"10.64898\/2026.09.08.26362522","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26362522","rel_abs":"Chronic diseases are increasingly linked to a transient viral exposure, yet known mechanisms do not explain how this exposure eventually leads to chronic pathologies in unrelated tissues. Using Epstein-Barr virus (EBV) as a model, I show that diverse EBV-associated diseases arise from epigenetic misprogramming of progenitor cells. These alterations persist independently of active infection and propagate across cell lineages, generating latent vulnerabilities later unmasked by secondary insults. Breast cancer provided an unresolved test case for EBV involvement: invasive tumors carried EBV-like methylation signatures already present in precursor lesions, independent of lymphocytic infiltration. In EBV-associated multiple sclerosis, three independent cohorts (brain, white matter, and blood) each revealed progenitor-cell methylation anomalies at sites shared with breast and classic EBV-associated cancers. Epigenetic vulnerability in progenitor cells thus emerges as a shared mechanism linking fundamentally different diseases, offering a candidate biomarker and a new target for early intervention.","rel_num_authors":1,"rel_authors":[{"author_name":"Bernard Friedenson","author_inst":"University of Illinois Chicago"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Genetic discovery using deep learning-derived optic nerve integrity phenotypes","rel_doi":"10.64898\/2026.09.08.26362398","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.08.26362398","rel_abs":"The peripapillary retinal nerve fibre layer (pRNFL) thickness and Bruch's membrane opening-minimum rim width (BMO-MRW) are three-dimensional retinal biomarkers for glaucoma. We aimed to demonstrate that AI-derived thickness from two-dimensional fundus images can act as proxies, enabling the discovery of novel neurodegenerative loci. AI-derived pRNFL and BMO-MRW strongly correlated with OCT-derived thickness (r: 0.69 and 0.79, respectively). After validation, these phenotypes were predicted in two cohorts lacking disc-centred OCT: UK Biobank and the Canadian Longitudinal Study on Aging. The predicted phenotypes showed strong genetic correlations with directly measured phenotypes from a previous study for both phenotypes (0.70 and 0.96, respectively). This data increased statistical power, identifying 29 loci for pRNFL thickness and 122 loci for BMO-MRW, including 14 loci that were independent of VCDR. We observed shared and sector-specific thickness loci overlapping glaucoma loci and revealed loci independent of known risk factors. Together, these results emphasise that multidimensional inferences can be drawn from 2D imaging, enabling downstream genetic analyses.","rel_num_authors":48,"rel_authors":[{"author_name":"Asma M Aman","author_inst":"QIMR Berghofer"},{"author_name":"Eslam Zaher","author_inst":"ARC Training Centre for Information Resilience (CIRES)"},{"author_name":"Santiago Diaz-Torres","author_inst":"QIMR Berghofer"},{"author_name":"Sjoerd J Driessen","author_inst":"Erasmus Medical Center"},{"author_name":"Victor A de Vries","author_inst":"Erasmus Medical Center"},{"author_name":"Frank CT van der Heide","author_inst":"Maastricht University"},{"author_name":"Antonia Kolovos","author_inst":"Flinders University"},{"author_name":"Joshua M Schmidt","author_inst":"Flinders University"},{"author_name":"Henry N Marshall","author_inst":"Flinders University"},{"author_name":"Lania Saleh","author_inst":"King's College London"},{"author_name":"Alicia Schulze","author_inst":"University Medical Center of the Johannes Gutenberg-University Mainz"},{"author_name":"Gabriella AM Blokland","author_inst":"Faculty of Health, Medicine and Life Sciences, Maastricht University"},{"author_name":"Carroll A.B Webers","author_inst":"Maastricht University Medical Center +"},{"author_name":"Carla J.H van der Kallen","author_inst":"Maastricht University Medical Center+"},{"author_name":"Anke Wesselius","author_inst":"Maastricht University"},{"author_name":"Ilja Arts","author_inst":"Maastricht University"},{"author_name":"Freekje van Asten","author_inst":"Maastricht University Medical Center +"},{"author_name":"Mathias Gorski","author_inst":"University of Regensburg"},{"author_name":"Martina E Zimmermann","author_inst":"University of Regensburg"},{"author_name":"Klaus J Stark","author_inst":"University of Regensburg"},{"author_name":"Iris M Heid","author_inst":"University of Regensburg"},{"author_name":"Terri L Young","author_inst":"University of Wisconsin-Madison"},{"author_name":"Louis R Pasquale","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Ayellet V Segre","author_inst":"Harvard Medical School"},{"author_name":"Janey L Wiggs","author_inst":"Harvard Medical School"},{"author_name":"Anthony P Khawaja","author_inst":"Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology"},{"author_name":"Donald J Zack","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Raymond C.B Wong","author_inst":"Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital"},{"author_name":"Alex W Hewitt","author_inst":"University of Tasmania"},{"author_name":"Alexander K Schuster","author_inst":"University Medical Center of the Johannes Gutenberg-University Mainz"},{"author_name":"Tos T.J.M Berendschot","author_inst":"Maastricht University Medical Center +"},{"author_name":"Alberta A.H.J Thiadens","author_inst":"Erasmus Medical Center"},{"author_name":"Karin A van Garderen","author_inst":"Erasmus Medical Center"},{"author_name":"Caroline C.W Klaver","author_inst":"Erasmus Medical Center"},{"author_name":"Pirro G Hysi","author_inst":"King's College London"},{"author_name":"Christopher J Hammond","author_inst":"King's College London"},{"author_name":"Caroline Brandl","author_inst":"University Hospital Regensburg"},{"author_name":"Jamie E Craig","author_inst":"Flinders University"},{"author_name":"Wishal D Ramdas","author_inst":"Erasmus Medical Center"},{"author_name":"Ya Xing Wang","author_inst":"Beijing Tsinghua Changgung Hospital, Tsinghua Medicine, Tsinghua University"},{"author_name":"Jost B Jonas","author_inst":"Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science"},{"author_name":"Fred Roosta","author_inst":"ARC Training Centre for Information Resilience (CIRES)"},{"author_name":"Michael L Hunter","author_inst":"Busselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital"},{"author_name":"Stuart MacGregor","author_inst":"QIMR Berghofer"},{"author_name":"Samantha Sze-Yee Lee","author_inst":"University of Western Australia, Lions Eye Institute"},{"author_name":"David A Mackey","author_inst":"University of Tasmania"},{"author_name":"Maciej Trzaskowski","author_inst":"Profenso Pty Ltd"},{"author_name":"Puya Gharahkhani","author_inst":"QIMR Berghofer"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Discovery and Validation of Gut Microbiome Features Associated with Dietary Patterns in U.S. Black\/African and Hispanic\/Latino Populations","rel_doi":"10.64898\/2026.09.04.26362286","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26362286","rel_abs":"Background: Large-scale studies examining dietary patterns and gut microbiome have focused predominantly on European ancestry populations; evidence from other ancestry groups remains limited. Objectives: We conducted a two-stage study to evaluate associations of multiple dietary patterns with gut microbiome diversity and composition among Black\/African American adults and validate significant findings in a Hispanic\/Latino population in the US. Methods: Included were 514 Black participants from the Southern Community Cohort Study (SCCS) and 2,133 participants from the Hispanic Community Health Study\/Study of Latinos (HCHS\/SOL). Diet was collected by food frequency questionnaires or 24-h dietary recalls at cohort enrollment. Gut microbiome profiling was performed by shotgun metagenomic sequencing of stool samples collected during cohort follow-up. Five dietary patterns - Healthy Eating Index (HEI), Dietary Approaches to Stop Hypertension (DASH), Empirical Dietary Inflammatory Potential (EDIP), Empirical Dietary Index for Hyperinsulinemia (EDIH), and Ultra-Processed Foods (UPF) - were examined for associations with microbiome diversity and composition by linear regression after data transformation and confounders adjustment. Microbial taxa with FDR<0.1 and their constituent lower-level features identified in SCCS were targeted for validation in HCHS\/SOL. Results: In SCCS, HEI, DASH, EDIP, or EDIH were associated with the relative abundances of 14 microbial taxa, primarily members of families Coriobacteriaceae and unclassified Firmicutes, as well as species Lactococcus lactis and Clostridium sp. AF20-17LB. Among these, the inverse associations of genus Collinsella and its species C. aerofaciens with HEI or DASH were validated in HCHS\/SOL (all P<0.05). Additionally, Collinsella and C. aerofaciens were associated with higher odds of obesity in SCCS (BMI[&ge;] 30 kg\/m2; OR [95%CI]:1.24 [1.01, 1.53] and 1.32 [1.07, 1.63], respectively). Conclusions: Healthier dietary patterns were consistently associated with lower abundances of Collinsella and C. aerofaciens in Black\/African and Hispanic\/Latino Americans. Further research should clarify causal pathway linking diet, gut microbiome, and health outcomes across diverse populations.","rel_num_authors":15,"rel_authors":[{"author_name":"Lei Wang","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Yanbo Zhang","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Sang M Nguyen","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Brandilyn A Peters","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Qibin Qi","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Robert D Burk","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Robert Kaplan","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Bharat Thyagarajan","author_inst":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA"},{"author_name":"Martha Daviglus","author_inst":"Institute for Minority Health Research, University of Illinois-Chicago"},{"author_name":"Xiao-Ou Shu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Siyuan Ma","author_inst":"Division of Biostatistics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Qi Dai","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Martha J Shrubsole","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Wei Zheng","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Danxia Yu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Discovery and Validation of Gut Microbiome Features Associated with Dietary Patterns in U.S. Black\/African and Hispanic\/Latino Populations","rel_doi":"10.64898\/2026.09.04.26362286","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26362286","rel_abs":"Background: Large-scale studies examining dietary patterns and gut microbiome have focused predominantly on European ancestry populations; evidence from other ancestry groups remains limited. Objectives: We conducted a two-stage study to evaluate associations of multiple dietary patterns with gut microbiome diversity and composition among Black\/African American adults and validate significant findings in a Hispanic\/Latino population in the US. Methods: Included were 514 Black participants from the Southern Community Cohort Study (SCCS) and 2,133 participants from the Hispanic Community Health Study\/Study of Latinos (HCHS\/SOL). Diet was collected by food frequency questionnaires or 24-h dietary recalls at cohort enrollment. Gut microbiome profiling was performed by shotgun metagenomic sequencing of stool samples collected during cohort follow-up. Five dietary patterns - Healthy Eating Index (HEI), Dietary Approaches to Stop Hypertension (DASH), Empirical Dietary Inflammatory Potential (EDIP), Empirical Dietary Index for Hyperinsulinemia (EDIH), and Ultra-Processed Foods (UPF) - were examined for associations with microbiome diversity and composition by linear regression after data transformation and confounders adjustment. Microbial taxa with FDR<0.1 and their constituent lower-level features identified in SCCS were targeted for validation in HCHS\/SOL. Results: In SCCS, HEI, DASH, EDIP, or EDIH were associated with the relative abundances of 14 microbial taxa, primarily members of families Coriobacteriaceae and unclassified Firmicutes, as well as species Lactococcus lactis and Clostridium sp. AF20-17LB. Among these, the inverse associations of genus Collinsella and its species C. aerofaciens with HEI or DASH were validated in HCHS\/SOL (all P<0.05). Additionally, Collinsella and C. aerofaciens were associated with higher odds of obesity in SCCS (BMI[&ge;] 30 kg\/m2; OR [95%CI]:1.24 [1.01, 1.53] and 1.32 [1.07, 1.63], respectively). Conclusions: Healthier dietary patterns were consistently associated with lower abundances of Collinsella and C. aerofaciens in Black\/African and Hispanic\/Latino Americans. Further research should clarify causal pathway linking diet, gut microbiome, and health outcomes across diverse populations.","rel_num_authors":15,"rel_authors":[{"author_name":"Lei Wang","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Yanbo Zhang","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Sang M Nguyen","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Brandilyn A Peters","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Qibin Qi","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Robert D Burk","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Robert Kaplan","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Bharat Thyagarajan","author_inst":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA"},{"author_name":"Martha Daviglus","author_inst":"Institute for Minority Health Research, University of Illinois-Chicago"},{"author_name":"Xiao-Ou Shu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Siyuan Ma","author_inst":"Division of Biostatistics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Qi Dai","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Martha J Shrubsole","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Wei Zheng","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Danxia Yu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Discovery and Validation of Gut Microbiome Features Associated with Dietary Patterns in U.S. Black\/African and Hispanic\/Latino Populations","rel_doi":"10.64898\/2026.09.04.26362286","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26362286","rel_abs":"Background: Large-scale studies examining dietary patterns and gut microbiome have focused predominantly on European ancestry populations; evidence from other ancestry groups remains limited. Objectives: We conducted a two-stage study to evaluate associations of multiple dietary patterns with gut microbiome diversity and composition among Black\/African American adults and validate significant findings in a Hispanic\/Latino population in the US. Methods: Included were 514 Black participants from the Southern Community Cohort Study (SCCS) and 2,133 participants from the Hispanic Community Health Study\/Study of Latinos (HCHS\/SOL). Diet was collected by food frequency questionnaires or 24-h dietary recalls at cohort enrollment. Gut microbiome profiling was performed by shotgun metagenomic sequencing of stool samples collected during cohort follow-up. Five dietary patterns - Healthy Eating Index (HEI), Dietary Approaches to Stop Hypertension (DASH), Empirical Dietary Inflammatory Potential (EDIP), Empirical Dietary Index for Hyperinsulinemia (EDIH), and Ultra-Processed Foods (UPF) - were examined for associations with microbiome diversity and composition by linear regression after data transformation and confounders adjustment. Microbial taxa with FDR<0.1 and their constituent lower-level features identified in SCCS were targeted for validation in HCHS\/SOL. Results: In SCCS, HEI, DASH, EDIP, or EDIH were associated with the relative abundances of 14 microbial taxa, primarily members of families Coriobacteriaceae and unclassified Firmicutes, as well as species Lactococcus lactis and Clostridium sp. AF20-17LB. Among these, the inverse associations of genus Collinsella and its species C. aerofaciens with HEI or DASH were validated in HCHS\/SOL (all P<0.05). Additionally, Collinsella and C. aerofaciens were associated with higher odds of obesity in SCCS (BMI[&ge;] 30 kg\/m2; OR [95%CI]:1.24 [1.01, 1.53] and 1.32 [1.07, 1.63], respectively). Conclusions: Healthier dietary patterns were consistently associated with lower abundances of Collinsella and C. aerofaciens in Black\/African and Hispanic\/Latino Americans. Further research should clarify causal pathway linking diet, gut microbiome, and health outcomes across diverse populations.","rel_num_authors":15,"rel_authors":[{"author_name":"Lei Wang","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Yanbo Zhang","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Sang M Nguyen","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Brandilyn A Peters","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Qibin Qi","author_inst":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"},{"author_name":"Robert D Burk","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Robert Kaplan","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Bharat Thyagarajan","author_inst":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA"},{"author_name":"Martha Daviglus","author_inst":"Institute for Minority Health Research, University of Illinois-Chicago"},{"author_name":"Xiao-Ou Shu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Siyuan Ma","author_inst":"Division of Biostatistics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Qi Dai","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Martha J Shrubsole","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Wei Zheng","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"},{"author_name":"Danxia Yu","author_inst":"Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Multi-Herbal Extracellular Vesicle and Growth Factor Serum for Eyelash Care: A Pilot Randomized, Double Blind, Placebo-Controlled Clinical Study","rel_doi":"10.64898\/2026.09.06.26360639","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.06.26360639","rel_abs":"Beyond their cosmetic significance, eyelashes are critical for retaining ocular moisture and protection against mechanical debris, environmental stressors, and excessive light. While recombinant growth factors support hair growth through activating key follicular signaling pathways, plant-derived EVs modulate local inflammatory and oxidative stress pathways to optimize the follicular microenvironment. Here we conducted a randomized, double-blind, placebo-controlled pilot study to investigate the synergistic effects of a serum containing recombinant Fc-fusion growth factors (rIGF-1, rFGF-7) and extracellular vesicles (EVs) derived from Zingiber officinale (ginger) and Curcuma longa (turmeric). Thirty healthy female participants were recruited and allocated to Group A (active serum) or Group B (placebo) at a ratio of 1:1. Participants applied the intervention twice daily for 8 weeks. The VISIA Skin Analysis System was used during clinical visits to objectively measure eyelash density and average length at baseline, Week 4, and Week 8. Group A exhibited a mean density increase of 3.3% at Week 4 and 4.4% at Week 8 relative to baseline. Eyelash length in Group A exhibited significant increases, reaching 8.1% at Week 4 and 11.0% by Week 8. In contrast, Group B showed slight reductions in length (-1.7% and -3.7% at Weeks 4 and 8, respectively) and a negligible change in density (+0.8% and -1.0% at Week 4 and 8, respectively). Notably, no periocular skin hyperpigmentation, a frequent adverse event associated with pharmacologic agents such as bimatoprost, was observed. These findings demonstrated the potential of combining long-acting recombinant growth factors with plant-derived EVs as an effective, highly tolerable, non-pharmaceutical cosmetic strategy for eyelash enhancement.","rel_num_authors":12,"rel_authors":[{"author_name":"Tsong-Min Chang","author_inst":"Department of Applied Cosmetology, HungKuang University, Taichung City, Taiwan"},{"author_name":"Chung-Chin Wu","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Huey-Chun Huang","author_inst":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City, Taiwan"},{"author_name":"Ji-Ying Lu","author_inst":"Department of Applied Cosmetology, HungKuang University, Taichung City, Taiwan"},{"author_name":"Yu-San Chen","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Pei-Lun Kao","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Wei-Hsuan Tang","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Wang-Ju Hsieh","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Luke Tzu-Chi Liu","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Ivona Percec","author_inst":"Division of Plastic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA"},{"author_name":"Charles Chen","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"},{"author_name":"Tsun-Yung Kuo","author_inst":"Schweitzer Biotech Company, Taipei City, Taiwan"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Comparing physical activity policy evaluations across 27 EU member states: Diverse indicators, inconsistent findings","rel_doi":"10.64898\/2026.09.04.26361720","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.09.04.26361720","rel_abs":"Background: Physical inactivity remains a major public health challenge, and policy action across sectors is needed to create environments that enable active lifestyles. Several tools have been developed to evaluate national physical activity policies, but it remains unclear whether they assess similar policy aspects or produce comparable results. This study compared evaluation results across the 27 EU member states and examined the indicators used by these tools. Methods: Eight physical activity policy evaluation tools were included that (a) assess national physical activity policies and (b) had been applied in multiple countries. For five tools covering at least half of the EU member states, aggregate scores were extracted or calculated and converted into country rankings. A total of 202 indicators were coded and mapped by category (policy content, process, structure), and data type (audit, content, implementation, impact assessment). Results: Country rankings varied considerably, with a mean difference of 13.0 positions between highest and lowest ranks. Some countries displayed consistent results (e.g., Austria, France, Germany), while others showed large discrepancies (e.g., Hungary, Spain). Indicator mapping revealed a focus on policy content (47.6%), followed by structure (21.6%) and process (13.7%) (6.2% other). Across tools, 20.3% of indicators audited policies, 26.0% assessed policy content, and 26.4% assessed policy implementation (16.3% other). Conclusion: The systematic comparison of indicators across physical activity policy evaluation tools provided insights into differences in country rankings. Future evaluations should clearly communicate their purpose, identify synergies between tools, address gaps in policy evaluation, and strengthen the reproducibility of evaluation processes.","rel_num_authors":7,"rel_authors":[{"author_name":"Sven Messing","author_inst":"Physical Activity for Health Research Centre, Health Research Institute, Department of Physical Education and Sport Sciences, University of Limerick, Ireland"},{"author_name":"Antonina Tcymbal","author_inst":"Department of Sport Science and Sport, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Germany"},{"author_name":"Leonie Birkholz","author_inst":"Department of Sport Science and Sport, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Germany"},{"author_name":"Adrian Bauman","author_inst":"School of Public Health, Faculty of Medicine and Health, University of Sydney, Australia"},{"author_name":"Stephen Whiting","author_inst":"World Health Organization Regional Office for Europe, Copenhagen, Denmark"},{"author_name":"Colin O'Hehir","author_inst":"Department of Health, Ireland"},{"author_name":"Catherine Woods","author_inst":"Physical Activity for Health Research Centre, Health Research Institute, Department of Physical Education and Sport Sciences, University of Limerick, Ireland"}],"rel_date":"2026-09-10","rel_site":"medrxiv"},{"rel_title":"Non-contact optical imaging of tissue deformation enables in vivo cardiovascular monitoring","rel_doi":"10.64898\/2026.09.04.749131","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.04.749131","rel_abs":"Significance: Continuous, non-invasive monitoring of cardiovascular physiology provides critical information for clinical decision-making and patient care. Emerging optical sensors enable non-contact measurement of physiological parameters such as heart rate and respiratory rate, but current methods are limited in their ability to capture spatially resolved physiological waveforms. Aim: We aimed to extend the capabilities of non-contact cardiovascular monitoring by using an imaging-based approach from which spatially resolved physiological waveforms can be extracted and cardiovascular biomarkers can be derived in vivo. Approach: We implemented a digital holographic imaging sensor to continuously measure calibrated tissue motion for in vivo assessment of cardiovascular biomarkers in six adult male Sprague-Dawley rats, with validation against electrocardiographic and invasive arterial blood pressure measurements. Results: Heart rate and pulse arrival time-derived pulse wave velocity calculated from digital holographic imaging demonstrate strong agreement with reference-derived metrics (concordance correlation coefficient [&ge;] 0.98). Heart rate variability shows moderate agreement with reference-derived metrics (concordance correlation coefficient [&ge;] 0.59).","rel_num_authors":9,"rel_authors":[{"author_name":"Austen T Lefebvre","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Nicole E Steiner","author_inst":"Johns Hopkins Applied Physics Laboratory"},{"author_name":"Siyu Wang","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Carissa L Rodriguez","author_inst":"Johns Hopkins Applied Physics Laboratory"},{"author_name":"Eyal Bar-Kochba","author_inst":"Johns Hopkins Applied Physics Laboratory"},{"author_name":"Yanrong Shi","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Sung-Min Cho","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"David W Blodgett","author_inst":"Johns Hopkins Applied Physics Laboratory"},{"author_name":"Marek Mirski","author_inst":"Johns Hopkins University School of Medicine"}],"rel_date":"2026-09-10","rel_site":"biorxiv"},{"rel_title":"Nucleic Acid Capture from Human Blood Plasma Uncovers G-Quadruplex Structures","rel_doi":"10.64898\/2026.09.05.747829","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.05.747829","rel_abs":"Ultrashort (US) cell-free DNA (cfDNA) is a population of approximately 50-nucleotide single-stranded DNA molecules in human plasma.1-3 Although it holds biological and diagnostic potential, US cfDNA escapes detection by conventional double-stranded library preparation methods.1-3 Independent studies have linked US cfDNA to regulatory genomic regions and to sequences predicted to form noncanonical structures, prompting the hypothesis that higher-order DNA structure contributes to its molecular properties. This interpretation, however, has so far rested on computational prediction rather than experimental evidence. Here we test this hypothesis using computational, biophysical and biochemical approaches. In silico size-selected US cfDNA from 20 healthy donors was selectively enriched at putative quadruplex sequences (PQS) that overlap both experimentally observed quadruplex sequences and accessible chromatin of blood cells. Synthetic oligonucleotides corresponding to the most enriched of these loci adopted predominantly parallel G-quadruplex (G4) structures, as revealed by circular dichroism. Endogenous nucleic acids captured directly from pooled plasma by poly(A)-tailing and immobilization, without extraction, denaturation or annealing at any step, displayed folded G4 structures. Two orthogonal probes detected these structures: the BG4 antibody and the fluorogenic ligand N-methyl mesoporphyrin IX. Reciprocal competition with a third, chemically unrelated G4 ligand, pyridostatin, confirmed the signal. Together, these experiments provide direct experimental evidence for the presence of folded G4 structures in human blood plasma.","rel_num_authors":8,"rel_authors":[{"author_name":"Martin Gajarsky","author_inst":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"author_name":"Olivia van Ray","author_inst":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"author_name":"Thomas Akkermann","author_inst":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"author_name":"Pascal Hunold","author_inst":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"author_name":"Anne Cucchiarini","author_inst":"Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, 91120 Palaiseau, France"},{"author_name":"Jean-Louis Mergny","author_inst":"Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, 91120 Palaiseau, France"},{"author_name":"Lukas Trantirek","author_inst":"Central European Institute of Technology (CEITEC), Masaryk University, 625 00 Brno, Czech Republic"},{"author_name":"Robert Haensel-Hertsch","author_inst":"Center for Molecular Medicine Cologne"}],"rel_date":"2026-09-10","rel_site":"biorxiv"},{"rel_title":"Gluconate acts as a signal to induce biofilm in Bacillus subtilis","rel_doi":"10.64898\/2026.09.08.750294","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.09.08.750294","rel_abs":"Bacillus subtilis is the best-studied Gram-positive microorganism, but little is known about how the presence and utilization of diverse carbon sources impacts its production of biofilm. Here, we have identified gluconate as a carbon source that induces biofilm wrinkling in B. subtilis colony biofilms. Targeted phenotypic analysis revealed that the genes encoding the canonical structural biofilm components (tasA, epsA-O, and bslA) are required for this response. Import and metabolism of gluconate, however, are not required to induce these phenotypic changes. We show that the effect of gluconate on B. subtilis is linked to iron availability: production of the siderophore bacillibactin is decreased by gluconate and B. subtilis mutants unable to import bacillibactin grow better and wrinkle more in the presence of gluconate. In addition, supplementation of single-carbon media with iron dramatically increased growth and wrinkling of a B. subtilis bacillibactin mutant grown on gluconate but did not impact B. subtilis grown on glucose. We conclude that gluconate acts as a signal to increase biofilm in B. subtilis and increases iron availability in a bacillibactin-independent manner.","rel_num_authors":5,"rel_authors":[{"author_name":"Courtney Price","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Amelia Sadlon","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Amina Bradley","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Claudia Perez","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Elizabeth Anne Shank","author_inst":"University of Massachusetts Chan Medical School"}],"rel_date":"2026-09-10","rel_site":"biorxiv"}]}