{"gname":"Georgia Institute of Technology","grp_id":"20","rels":[{"rel_title":"Vitamin D Status and Supplementation in Patients Undergoing Spine Surgery: A Systematic Review and Meta-analysis","rel_doi":"10.64898\/2026.08.02.26359512","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359512","rel_abs":"Background Vitamin D may influence bone healing and recovery after spine surgery, but its clinical effects remain uncertain. Objective To evaluate clinical, functional, and bone-related outcomes associated with vitamin D status and supplementation in patients undergoing spine surgery. Methods This systematic review and meta-analysis was registered in PROSPERO (CRD420261467482) and reported according to PRISMA 2020. PubMed\/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library were searched from inception through 1 June 2026. Random-effects meta-analyses used mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes. Direct supplementation analyses were prioritized, while analyses combining supplementation, baseline vitamin D status, or co-interventions were considered exploratory. Risk of bias was assessed using design-specific Joanna Briggs Institute tools. Results Thirteen studies were included. Four supplementation studies involving 177 participants showed no significant reduction in postoperative pain (MD -0.82, 95% CI -2.50 to 0.86; I2 = 84.3%). Three studies involving 277 participants showed lower Oswestry Disability Index scores in an exploratory analysis (MD -6.40, 95% CI -10.41 to -2.39; I2 = 96.8%). Three supplementation studies involving 128 participants showed no significant improvement in fusion rate (RR 1.17, 95% CI 0.78 to 1.74; I2 = 31.5%). An exploratory four-study fusion analysis was also not statistically significant (RR 1.24, 95% CI 0.98 to 1.57; I2 = 45.5%). Conclusion Current evidence does not establish that vitamin D supplementation independently improves postoperative pain or fusion rates after spine surgery. Possible benefits for disability and other bone-related outcomes remain uncertain because of small study numbers, heterogeneity, co-interventions, and residual confounding. Larger randomized trials stratified by baseline vitamin D status are needed.","rel_num_authors":15,"rel_authors":[{"author_name":"Farzan Fahim","author_inst":"Shohada-e Tajrish Hospital"},{"author_name":"Fatemeh Vosoughian","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Amirmahdi Mojtahedzadeh","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Mahla Rakhshani","author_inst":"Tehran University of Medical Sciences"},{"author_name":"Barbod Mahdavi","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Kiana taghipoor","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Rauf Rostami","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Reihane Qahremani","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Fatemeh Gheibi","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Fatemeh Deldar","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Ramtin Shemshadigolafzani","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Saeed Rezaali","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Nahal Badavi","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Pardis Fathabadi","author_inst":"Shahid Beheshti University of Medical Sciences"},{"author_name":"Alireza Zali","author_inst":"Shohada-e Tajrish Hospital"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Effect of five years of biannual azithromycin mass drug administration on enteric fever seroincidence in Niger: A randomized control trial","rel_doi":"10.64898\/2026.08.03.26359544","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.03.26359544","rel_abs":"BACKGROUND Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi, remains a major cause of morbidity in low- and middle-income countries, yet burden estimation is challenging in regions without blood culture surveillance. Azithromycin is effective for treating enteric fever, and mass drug administration (MDA) to young children reduces all-cause mortality in sub-Saharan Africa, but its impact on community-level enteric fever burden is unknown. We assessed enteric fever seroincidence in rural Niger and evaluated the effect of biannual azithromycin MDA affected. PRINCIPAL FINDINGS This was a secondary analysis of the MORDOR trial (NCT02048007), a cluster-randomized, placebo-controlled study in 30 communities in Dosso Region, Niger. Children aged 1-59 months received biannual azithromycin or placebo. Dried blood spots collected at baseline (2015) and Year 5 (2020) were tested for IgA and IgG antibodies against Hemolysin E using kinetic ELISA. Seroincidence was estimated using maximum likelihood methods based on antibody kinetics from blood culture-confirmed enteric fever patients. Samples from 1,417 children were analyzed (423 baseline; 994 Year 5). Overall seroincidence approximately doubled from baseline to Year 5, increasing from 68.5 (95% CI 58.0-80.7) to 145.2 (95% CI 132.3-159.3) per 100 person-years in placebo communities and from 74.7 (95% CI 56.5-98.7) to 135.2 (95% CI 112.4-162.6) in azithromycin communities, with no significant difference between arms (difference-in-differences -16.2; 95% CI -53.1-20.8 ). Among children <2 years, the increase in seroincidence was smaller in the azithromycin arm (37.5; 95% CI: 1.3-73.6) compared to placebo (81.1; 95% CI 54.0-108.2), with a difference-in-differences of -43.7 per 100 person-years (95% CI -88.8 - 1.5  to 0.02). SIGNIFICANCE Enteric fever seroincidence among young children in rural Niger is high and increased substantially over the five-year study period. Biannual azithromycin MDA did not significantly reduce overall  seroincidence, though a potential attenuation was observed among children under 2 years of age. These findings underscore the importance of Niger's recent typhoid conjugate vaccine introduction and highlight the value of serosurveillance for monitoring enteric fever infection intensity in settings without blood culture surveillance.","rel_num_authors":19,"rel_authors":[{"author_name":"Kristen Aiemjoy","author_inst":"University of California Davis"},{"author_name":"Jessica Seidman","author_inst":"Albert B Sabin Vaccine Institute: Sabin Vaccine Institute"},{"author_name":"Ahmed  M Arzika","author_inst":"Centre de Recherche et d\u2019Intervention en Sant\u00e9 Publique"},{"author_name":"Ramatou Maliki","author_inst":"Centre de Recherche et d\u2019Intervention en Sant\u00e9 Publique"},{"author_name":"Amza Abdou","author_inst":"Programme Nationale de Sant\u00e9 Oculaire"},{"author_name":"Douglas  Ezra Morrison","author_inst":"University of California Davis"},{"author_name":"Kristina  W Lai","author_inst":"UC Davis: University of California Davis"},{"author_name":"Denise  O Garrett","author_inst":"Albert B Sabin Vaccine Institute: Sabin Vaccine Institute"},{"author_name":"Claire Munroe","author_inst":"Massachusetts General Hospital"},{"author_name":"Abel Gonzalez","author_inst":"Massachusetts General Hospital"},{"author_name":"Leah Sukri","author_inst":"University of Maryland School of Medicine"},{"author_name":"Elodie Lebas","author_inst":"UCSF: University of California San Francisco"},{"author_name":"Catherine Cook","author_inst":"UCSF: University of California San Francisco"},{"author_name":"Benjamin  F Arnold","author_inst":"UCSF: University of California San Francisco"},{"author_name":"Thomas  M Leitman","author_inst":"UCSF: University of California San Francisco"},{"author_name":"Kathleen  M Neuzil","author_inst":"University of Maryland School of Medicine"},{"author_name":"Jason  R Andrews","author_inst":"Stanford University School of Medicine"},{"author_name":"Jeremy  D Keenan","author_inst":"UCSF: University of California San Francisco"},{"author_name":"Richelle  C Charles","author_inst":"Massachusetts General Hospital"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Incidence and Management of Early Breakthrough HSV Infection Among Allogeneic Hematopoietic Stem Cell Transplant Recipients","rel_doi":"10.64898\/2026.08.02.26359522","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359522","rel_abs":"Background: Reactivation of herpes simplex viruses (HSV) can occur in the early post-allogeneic hematopoietic cell transplant (aHCT) period despite antiviral prophylaxis. Few studies have assessed HSV infection in the modern era, in which acyclovir\/valacyclovir is recommended for up to 1 year post aHCT. We evaluated the incidence and management of breakthrough HSV during the first 100 days post-aHCT over two decades. Methods: Patients who received their first aHCT at Fred Hutchinson Cancer Center between 2002-2022 were reviewed for breakthrough HSV infection within the first 100 days on prophylaxis (acyclovir 800 mg or valacyclovir 500 mg twice daily). Cases were identified via culture, polymerase chain reaction, and\/or direct fluorescent antibody testing; clinical records were reviewed for symptoms, outcomes, and prophylaxis\/treatment regimens. Refractory\/resistant (R\/R) infections were defined according to consensus guidelines. Results: We reviewed data from 4,357 aHCT recipients aged [&ge;]18 years, among whom 3,749 (86%) were HSV seropositive and 23 developed breakthrough HSV infection (observed probability = 0.6%). Among those who had an infection, the median time from transplant to first positive test was 46 days (IQR: 24.0-69.5). Oral and genital mucosa were the most common sites of infection. In total, 11 of 23 (47.8%) patients with breakthrough HSV developed R\/R infection. Conclusions: Breakthrough HSV infections are rare in the first 100 days after aHCT among patients receiving antiviral prophylaxis. Refractory\/resistant infections were uncommon but represented almost half of breakthrough cases. Our findings highlight the sustained effectiveness of universal prophylaxis in the early post-transplant period.","rel_num_authors":12,"rel_authors":[{"author_name":"Molly D Fischer","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Ria Mohan","author_inst":"Virginia Commonwealth University"},{"author_name":"Anna D Wald","author_inst":"University of Washington"},{"author_name":"Amanda I Phipps","author_inst":"University of Washington"},{"author_name":"Emily Ford","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Ted Gooley","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Frank Tverdek","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Melinda A Biernacki","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Denise J McCulloch","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Michael J Boeckh","author_inst":"Fred Hutchinson Cancer Center"},{"author_name":"Christine Johnston","author_inst":"University of Washington"},{"author_name":"Steven Pergam","author_inst":"Fred Hutchinson Cancer Center"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Twenty-site HDSS mapping after thoracoscopic sympathectomy for primary palmar hyperhidrosis: a secondary complete-case analysis of a multicenter randomized trial.","rel_doi":"10.64898\/2026.08.02.26359508","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359508","rel_abs":"Objective: To map, using the Hyperhidrosis Disease Severity Scale (HDSS), the preoperative distribution and six-month regional evolution of sweating severity across 20 anatomical sites after dominant-side unilateral versus one-stage bilateral R4 video-assisted thoracoscopic sympathectomy for primary palmar hyperhidrosis. Methods: This was a secondary complete-case, site-level analysis of a prospective multicenter randomized trial. Adults undergoing one-stage bilateral thoracic sympathectomy (BTS) or dominant-side unilateral sympathectomy (UniS) were eligible when baseline and six-month HDSS data were complete for all 20 prespecified sites. HDSS was grouped as 1, 2, or 3-4. Regional outcomes were classified as improvement, stability, or worsening and were stratified by baseline HDSS. Results: Ninety-two patients were included: 36 BTS and 56 UniS. Before surgery, severe sweating was present in 182 of 184 hand-site observations, 168 of 184 foot-site observations, and 75 of 184 axillary-site observations. At six months, improvement was more frequent after BTS than UniS in the hands (88.9% vs 52.7%) and axillae (72.2% vs 29.5%). Worsening was concentrated mainly in abdominal, hemidorsal, and thoracic sites. Among observations that were normal at baseline, progression to HDSS 3-4 occurred in 10.8% after BTS and 7.7% after UniS. Among observations with baseline HDSS 3-4, complete resolution to HDSS 1 occurred in 47.2% after BTS and 21.8% after UniS. Conclusion: Baseline-stratified 20-site HDSS mapping may improve preoperative counseling and postoperative outcome assessment by distinguishing true new-onset compensatory hyperhidrosis from worsening or persistence of pre-existing sweating.","rel_num_authors":16,"rel_authors":[{"author_name":"NELSON WOLOSKER","author_inst":"FACULDADE ISRAELITA DA SAUDE ALBERT EINSTEIN"},{"author_name":"Niura N Hamilton","author_inst":"Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil."},{"author_name":"Miguel L Tedde","author_inst":"Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil."},{"author_name":"Marina B Wolosker","author_inst":"Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil."},{"author_name":"Wolfgang W S Aguiar","author_inst":"Hospital Universitario Oswaldo Cruz, Recife, PE, Brazil."},{"author_name":"Hylas P C Ferreira","author_inst":"Hospital Liga Norte Riograndense Contra o Cancer, Natal, RN, Brazil."},{"author_name":"Fernando L Westphal","author_inst":"Hospital da Universidade Federal do Amazonas, Manaus, AM, Brazil."},{"author_name":"Alexandre M R Lima","author_inst":"Hospital Geral Dr. Cesar Cals, Fortaleza, CE, Brazil."},{"author_name":"Humberto A Oliveira","author_inst":"h: Hospital de Base, Brasilia, DF, Brazil."},{"author_name":"Sergio T L F Pereira","author_inst":"Hospital Santa Isabel, Salvador, BA, Brazil."},{"author_name":"Fabio O Riuto","author_inst":"Hospital da Universidade Federal de Grande Dourados, Dourados, MS, Brazil."},{"author_name":"Guilherme C Resende","author_inst":"Hospital da Universidade de Brasilia, Brasilia, DF, Brazil."},{"author_name":"Marina M K Brenner","author_inst":"l: Hospital Universitario de Santa Maria, Santa Maria, RS, Brazil."},{"author_name":"Daniel O Bonomi","author_inst":"Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil."},{"author_name":"Caroline E B Valero","author_inst":"Empresa Brasileira de Servicos Hospitalares, Brasilia, DF, Brazil."},{"author_name":"Paulo M Pego-Fernandes","author_inst":"Heart Institute (InCor), Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil."}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"The extent and durability of improvement in depressive symptoms, quality of life, and daily function with three years of vagus nerve stimulation in markedly treatment-resistant depression: A RECOVER study report","rel_doi":"10.64898\/2026.07.31.26358854","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26358854","rel_abs":"Background: Management of markedly treatment-resistant depression is characterized by low initial benefit and poor durability. Treatments with sustained benefits are needed. This report summarizes clinical outcomes and durability of both the active treatment arm (Early-Active) and the initially sham treatment arm (Delayed-Active) over the second and third years of the multicenter, prospective, implanted vagus nerve stimulation (VNS) RECOVER trial. Methods: A total of 436 participants (N=221 Early-Active and N=215 Delayed-Active, 65.8% females) were studied. Within each group, analyses of change in benefit (depressive symptoms, clinical impression, quality of life [QoL], daily function, and a composite measure) occurred with assessments at 12, 18, 24, 30, and 36 months. Two within-group methods of benefit appraisal over time were conducted: 1) a comparison of the degree of benefit change, and 2) a comparison of proportions of participants achieving benefit categories. Additionally, the degree of durability of benefit was assessed, comparing 12-24 months, 24-36 months, and 12-36 months. Results: For the Early-Active group: The 12-24-month and 12-36-month periods, but not the 24-36-month period, demonstrated significant improvement in benefit categories for depressive symptoms and clinical impression measures. Similarly, statistically significant increases in the proportions of participants achieving benefit during Year 2 for depressive and clinical impression measures occurred. For the Delayed-Active group: The 12-24-month (first exposure of this group to active VNS) and 12-36-month periods, but not the 24-36-month period, demonstrated statistically significant improvements in benefit categories for depressive symptoms and clinical impression measures. Additionally, statistically significant increases in the proportions of participants achieving benefit during Year 2 for depressive symptoms, clinical impression, QoL, daily function, and the composite measure were observed. Averaged across the depressive symptom and clinical impression measures, the Early-Active group demonstrated continued progression to higher benefit categories during Years 2 and 3, whereas the Delayed-Active group was characterized by the emergence of new benefit during Year 2 followed by further progression to higher benefit categories during Year 3. Durability: Robust durability of response was observed for both groups across all time intervals, with a median of 71.1% and 69.0% maintaining or improving benefit from 12 to 36 months for Early-Active and Delayed-Active, respectively. Conclusions: In a highly chronic and markedly resistant depressed sample, active VNS produced benefits that often emerged gradually, sometimes beyond one year after initiation, continued to improve in degree of benefit over time, and were highly durable. The time-associated benefit patterns observed in the sham group (Delayed-Active) closely resembled those of the initially active group (Early-Active) but were delayed by approximately one year, consistent with the delay in therapy activation.","rel_num_authors":31,"rel_authors":[{"author_name":"Charles R. Conway","author_inst":"Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States"},{"author_name":"Scott T. Aaronson","author_inst":"Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt Health System, Baltimore, MD, United States"},{"author_name":"A. John Rush","author_inst":"Duke-NUS Medical School, Singapore; Curbstone Consultant LLC, Dallas, TX, United States"},{"author_name":"Ying-Chieh (Lisa) Lee","author_inst":"LivaNova PLC (or a subsidiary), London, United Kingdom"},{"author_name":"Olivia Shy","author_inst":"LivaNova PLC (or a subsidiary), London, United Kingdom"},{"author_name":"Mark T. Bunker","author_inst":"LivaNova PLC (or a subsidiary), London, United Kingdom"},{"author_name":"Charles Gordon","author_inst":"LivaNova PLC (or a subsidiary), London, United Kingdom"},{"author_name":"Patricio Riva-Posse","author_inst":"Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States"},{"author_name":"Kevin Reeves","author_inst":"Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, United States"},{"author_name":"Mark S. George","author_inst":"Department of Psychiatry, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson VA Health Care System, Charleston, SC, United St"},{"author_name":"John Zajecka","author_inst":"Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States; Psychiatric Medicine Associates, LLC, Skokie, IL, "},{"author_name":"Ziad Nahas","author_inst":"Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States"},{"author_name":"David L. Dunner","author_inst":"Center for Anxiety and Depression, Mercer Island, WA, United States"},{"author_name":"Martijn Figee","author_inst":"Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY"},{"author_name":"Brian J. Mickey","author_inst":"Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, United States"},{"author_name":"Rebecca M. Allen","author_inst":"Seattle Neuropsychiatric Treatment Center, Seattle, WA, United States"},{"author_name":"Donald Bohnenkamp","author_inst":"Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States"},{"author_name":"Christopher L. Kriedt","author_inst":"Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States"},{"author_name":"Vasilis C. Hristidis","author_inst":"Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States"},{"author_name":"Joao Quevedo","author_inst":"Center for Interventional Psychiatry, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science"},{"author_name":"Charles F. Zorumski","author_inst":"Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States"},{"author_name":"Matthew Macaluso","author_inst":"UAB Department of Psychiatry and Behavioral Neurobiology, Birmingham, AL, United States"},{"author_name":"Walter Duffy","author_inst":"Alivation Research, Lincoln, NE, United States"},{"author_name":"Yvette Sheline","author_inst":"University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States"},{"author_name":"Gustavo Alva","author_inst":"ATP Clinical Research, Costa Mesa, CA, United States"},{"author_name":"Cristina Cusin","author_inst":"Depression Clinical & Research Program, Mass General Psychiatry, Boston, MA, United States"},{"author_name":"Jeffrey I. Bennett","author_inst":"Department of Psychiatry, SIU Neuroscience Institute, Springfield, IL, United States"},{"author_name":"Quyen Tran","author_inst":"LivaNova PLC (or a subsidiary), London, United Kingdom"},{"author_name":"Roger S. McIntyre","author_inst":"Department of Psychiatry, University of Toronto, Toronto, ON, Canada"},{"author_name":"Richard Hamish McAllister-Williams","author_inst":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern Centre for Mood Disorders, Newcastle Universi"},{"author_name":"Harold A. Sackeim","author_inst":"Department of Psychiatry, Medical University of South Carolina, Charleston, SC, United States"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Reduced option generation reveals distinct profiles of apathy in schizophrenia","rel_doi":"10.64898\/2026.08.03.26359552","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.03.26359552","rel_abs":"Apathy is a major driver of long-term disability in schizophrenia, yet existing accounts focus on how patients evaluate the cost of action while neglecting their capacity to generate options for action in the first place. Using a brief, culture-fair option generation task (OGT) within the international CHANSS study, we examined this process in 150 patients with different stages of schizophrenia and 100 healthy controls across the UK, Spain, and China. The OGT requires drawing as many different paths as possible between two points on a touchscreen, yielding two measures: fluency (the number of paths that they generate) and uniqueness (the distinctiveness of those paths). Patients drew as many paths as controls but produced options roughly half as unique. Across patients, uniqueness was positively associated with verbal fluency and depressive symptom severity, but negatively associated with self-reported behavioural apathy. This suggests that increased apathy is associated with reduced ability to generate unique options (paths on the task). To examine the cognitive mechanisms further, we decomposed uniqueness into four exploratory measures: roaming entropy (spatial breadth of exploration), option elaboration (within-path development), perseveration (local repetition), and novelty maintenance (sustaining diversity over time). Together these explained 69% of the variance in motor-residualised uniqueness and attenuated the group difference by 80%, with roaming entropy as the dominant contributor. K-means clustering revealed three distinct patient profiles, each with a different clinical signature. A small subgroup generated options much like the control group. A larger subgroup retained spatial exploration but developed each option less and reported more depressive symptoms. A third subgroup showed broadly impaired exploration and the lowest verbal fluency. These findings establish option generation as a measurable behavioural phenotype in schizophrenia that relates to apathy and can be decomposed into specific cognitive mechanisms. They suggest that an impoverished option space, marked by reduced generation of unique possibilities for action, may be a remediable component of apathy.","rel_num_authors":21,"rel_authors":[{"author_name":"Noham Wolpe","author_inst":"Department of Physical Therapy, The Stanley Steyer School of Health Professions, Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv 699780"},{"author_name":"Cheng-Lin Wu","author_inst":"Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University"},{"author_name":"Claudia Aymerich","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Department of Child and Adolescent Psychiatry, Inst"},{"author_name":"Marta Martin-Subero","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Instituto de Salud Mental, Parc de Salut Mar, Barce"},{"author_name":"Paloma Fuentes-Perez","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Instituto de Investigacion Sanitaria Valdecilla (ID"},{"author_name":"Claudia Ovejas-Catalan","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Instituto de Investigacion Sanitaria Valdecilla (ID"},{"author_name":"Renata Zirilli","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust"},{"author_name":"Sophie Shatford","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust"},{"author_name":"Rebecca Cox","author_inst":"Clinical Research Unit, South West London & St. George's Mental Health NHS Trust"},{"author_name":"Megan Cartier","author_inst":"Clinical Research Unit, South West London & St. George's Mental Health NHS Trust"},{"author_name":"Ana Catalan","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Department of Neuroscience, University of the Basqu"},{"author_name":"Anna Mane","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Grup MERITT, Institut de Recerca Sant Joan de Deu, "},{"author_name":"John Pratt","author_inst":"Research Team, Humber NHS Foundation Trust"},{"author_name":"Lisa Airey","author_inst":"Research Team, Humber NHS Foundation Trust"},{"author_name":"Javier Vazquez-Bourgon","author_inst":"Spanish Network for Research in Mental Health, Carlos III Institute (CIBERSAM, ISCIII), 28029 Madrid, Spain; Instituto de Investigacion Sanitaria Valdecilla (ID"},{"author_name":"Nuria Segarra","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust"},{"author_name":"Yi-Jie Zhao","author_inst":"Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University"},{"author_name":"Paul C Fletcher","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust; Department of Psychiatry, University of Cambridge, UK; Wellcome Trust MRC Institute of Metabolic Science, "},{"author_name":"Peter B Jones","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust; Department of Psychiatry, University of Cambridge, UK"},{"author_name":"Masud Husain","author_inst":"Department of Experimental Psychology, University of Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, UK"},{"author_name":"Emilio Fernandez-Egea","author_inst":"Cambridgeshire and Peterborough NHS Foundation Trust; Department of Psychiatry, University of Cambridge, UK"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Identifying leptospirosis hotspots in Fiji using a One Health model that incorporates watershed-scale pathogen transport","rel_doi":"10.64898\/2026.08.03.26359543","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.03.26359543","rel_abs":"Leptospirosis is a water-related zoonotic disease with complex transmission pathways, including direct transmission from infected animals and indirect transmission through contaminated soil and water. Identifying key areas to implement targeted infection prevention and control strategies is challenging, as a range of risk factors across different scales can drive human infection. We aimed to develop an epidemiological modelling approach to predict key transmission pathways driving leptospirosis infection, including risks ranging from household level factors to the movement of pathogens across watersheds. We combined a causal Bayesian network with a novel hydrological pathogen transport model to predict leptospirosis across Fiji and found key infection hotspots adjacent to rivers and within degraded watersheds; a dynamic overlooked by previous epidemiological models. We used a wide range of data for model parameterisation (e.g., expert elicitation, epidemiological surveys, and environmental data) and found that predictive validity improved when expert input on risk factors was used to guide model parameterisation, improving R2 for predicted versus observed seroprevalence from 0.71 to 0.91. Our One Health modelling approach can be used to support the design and evaluation of environment-based disease prevention strategies at national scales.","rel_num_authors":8,"rel_authors":[{"author_name":"Ama Ravindi Wakwella","author_inst":"The University of Queensland"},{"author_name":"Carissa  J Klein","author_inst":"The University of Queensland"},{"author_name":"Owen Woodberry","author_inst":"Monash University"},{"author_name":"Colleen  L Lau","author_inst":"The University of Queensland"},{"author_name":"Amelia Wenger","author_inst":"The University of Queensland"},{"author_name":"Stacy  D Jupiter","author_inst":"Wildlife Conservation Society"},{"author_name":"Aaron  P Jenkins","author_inst":"The University of Sydney"},{"author_name":"Helen  J Mayfield","author_inst":"The University of Queensland"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Inferring heterogeneous transmission and community introduction of antibiotic-resistant bacteria in hospital settings","rel_doi":"10.64898\/2026.08.02.26359521","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359521","rel_abs":"Antimicrobial-resistant organisms (AMROs) impose a major burden on healthcare systems, yet routine surveillance cannot readily distinguish colonization imported at admission from transmission acquired within hospitals. This gap is especially consequential because both processes may vary substantially across wards, while asymptomatic carriage, incomplete testing, imperfect diagnostic sensitivity, and patient movement obscure the underlying transmission dynamics. To address this challenge, we developed a blockwise agent-based iterated filter (BAIF) for inference in a patient-level transmission model on a dynamic ward co-location network. The model tracks susceptible and colonized patients as they move across wards, represents unobserved colonization histories, and incorporates the recorded testing schedule and imperfect diagnostic sensitivity. BAIF uses blockwise likelihood evaluation and resampling to estimate ward-block-specific transmission rates and importation probabilities in this high-dimensional latent system. Synthetic experiments showed that BAIF recovered these parameters from partially observed outbreaks. We then applied the framework to hospitalization and microbiological surveillance data collected from 2012 to 2016 at an urban quaternary care hospital in New York City for four AMROs. Transmission and importation were highly heterogeneous across ward blocks. Elevated transmission was repeatedly concentrated in the same ward groups, whereas blocks with the highest importation varied by pathogen. By distinguishing importation-dominated from transmission-dominated ward blocks, the framework can inform more targeted surveillance and infection-control strategies. More broadly, BAIF provides an effective inference framework for high-dimensional, partially observed agent-based models on dynamic contact networks.","rel_num_authors":4,"rel_authors":[{"author_name":"Jifan Li","author_inst":"Texas A&M University"},{"author_name":"Qing Yao","author_inst":"Columbia University Mailman School of Public Health"},{"author_name":"Sen Pei","author_inst":"Columbia University Mailman School of Public Health"},{"author_name":"Ning Ning","author_inst":"Texas A&M University"}],"rel_date":"2026-08-04","rel_site":"medrxiv"},{"rel_title":"Epitope-Focused Immunogens Confer Broad Protection against Coronaviruses","rel_doi":"10.64898\/2026.08.02.742375","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.742375","rel_abs":"Variable regions in coronavirus spike dominate antibody responses elicited by infection or conventional vaccination and limit induction of broad neutralization. In contrast, conserved S2 elements, including the stem helix (SH) and fusion peptide proximal region (FPPR), are promising but subdominant targets of protective immunity. Here, we employed computational design to generate de novo epitope-focused immunogens that precisely present the SH and FPPR epitopes. Formulated as combinatorial immunogens, this vaccine elicited consistent serum responses with broad reactivity across known human coronaviruses and induced epitope-specific antibodies with broad neutralizing activity. As a heterologous boost, epitope-focused immuno-gens protected mice against challenge with phylogenetically distinct coronaviruses, including bat SARS-related RsSHC014-CoV and MERS-CoV, establishing a generalizable strategy for precision immune focusing and advancing universal coronavirus vaccine development.","rel_num_authors":15,"rel_authors":[{"author_name":"Mingxi Li","author_inst":"Westlake University"},{"author_name":"Qing Chen","author_inst":"Westlake University"},{"author_name":"Junghwa Seo","author_inst":"Yale School of Medicine"},{"author_name":"Yaoming Liu","author_inst":"Guangzhou National Laboratory, Guangzhou International Bio-Island"},{"author_name":"Fred Peng","author_inst":"Westlake University, Duke University"},{"author_name":"Kexin Huang","author_inst":"Westlake University"},{"author_name":"Ziniu Dai","author_inst":"Westlake University"},{"author_name":"Changxu Chen","author_inst":"Westlake University"},{"author_name":"Zeli Zhang","author_inst":"Westlake University"},{"author_name":"Jincun Zhao","author_inst":"GIRD"},{"author_name":"Zhaoqian Wang","author_inst":"Westlake University"},{"author_name":"Fajie Yuan","author_inst":"Westlake University"},{"author_name":"Xiancai Ma","author_inst":"Guangzhou National Laboratory, Guangzhou International Bio-Island"},{"author_name":"David R. Martinez","author_inst":"Yale School of Medicine"},{"author_name":"Dapeng Li","author_inst":"Westlake University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"IFN\u03b3 and proinflammatory cytokines cooperatively license astrocytes to support antigen-dependent CD4+ T cell restimulation","rel_doi":"10.64898\/2026.07.29.741554","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741554","rel_abs":"We report that type 2 interferon with proinflammatory cytokines induces astrocytes to express multiple components required for attraction of and antigen presentation to CD4+ T cells via MHC-II molecules. Re-analysis of astrocyte-enriched single-cell sequencing from bacterial mimetic-injected mice revealed a transcriptionally distinct interferon-responsive astrocyte population enriched for antigen-presentation-associated genes 24 hours after peripheral immune challenge. In vivo, we identify MHC-II+GFAP+ astrocytes localized to the surface of the brain across multiple mouse models of neuroinflammation and in human neurological disease tissue. In a pure in vitro culture system, astrocytes stimulated with IFN{gamma} and proinflammatory cytokines express MHC-II, costimulatory molecules, and lymphocyte-recruiting chemokines, and support rapid antigen-dependent expansion of previously activated CD4+ T cells. Using human iPSC-derived CNS cultures, we additionally show induction of antigen-presentation-associated machinery in human astrocytes following inflammatory cytokine stimulation. Rather than inferring function solely from marker expression, we assessed astrocyte-supported T cell restimulation in vitro and separately characterized the emergence of antigen-presentation-associated astrocytes in vivo at neuroimmune interfaces during inflammation in mice and humans. Together, these findings support a conserved role for cytokine-stimulated astrocytes in expressing antigen-presentation-associated machinery and, in vitro, supporting antigen-dependent restimulation\/expansion of CD4+ T cells under inflammatory conditions.","rel_num_authors":13,"rel_authors":[{"author_name":"Theodore M Fisher","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Francesco Limone","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Matthew D Smith","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Chandler Wright","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Petra Kukanja","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Peiwen Lu","author_inst":"Yale School of Medicine"},{"author_name":"Kerry Limberg","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Nicolette Pirjanian","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Jimena Zulueta","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Valentina Fossati","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Akiko Iwasaki","author_inst":"Yale School of Medicine,"},{"author_name":"Peter A Calabresi","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Shane A Liddelow","author_inst":"NYU Grossman School of Medicine"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"IFN\u03b3 and proinflammatory cytokines cooperatively license astrocytes to support antigen-dependent CD4+ T cell restimulation","rel_doi":"10.64898\/2026.07.29.741554","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741554","rel_abs":"We report that type 2 interferon with proinflammatory cytokines induces astrocytes to express multiple components required for attraction of and antigen presentation to CD4+ T cells via MHC-II molecules. Re-analysis of astrocyte-enriched single-cell sequencing from bacterial mimetic-injected mice revealed a transcriptionally distinct interferon-responsive astrocyte population enriched for antigen-presentation-associated genes 24 hours after peripheral immune challenge. In vivo, we identify MHC-II+GFAP+ astrocytes localized to the surface of the brain across multiple mouse models of neuroinflammation and in human neurological disease tissue. In a pure in vitro culture system, astrocytes stimulated with IFN{gamma} and proinflammatory cytokines express MHC-II, costimulatory molecules, and lymphocyte-recruiting chemokines, and support rapid antigen-dependent expansion of previously activated CD4+ T cells. Using human iPSC-derived CNS cultures, we additionally show induction of antigen-presentation-associated machinery in human astrocytes following inflammatory cytokine stimulation. Rather than inferring function solely from marker expression, we assessed astrocyte-supported T cell restimulation in vitro and separately characterized the emergence of antigen-presentation-associated astrocytes in vivo at neuroimmune interfaces during inflammation in mice and humans. Together, these findings support a conserved role for cytokine-stimulated astrocytes in expressing antigen-presentation-associated machinery and, in vitro, supporting antigen-dependent restimulation\/expansion of CD4+ T cells under inflammatory conditions.","rel_num_authors":13,"rel_authors":[{"author_name":"Theodore M Fisher","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Francesco Limone","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Matthew D Smith","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Chandler Wright","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Petra Kukanja","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Peiwen Lu","author_inst":"Yale School of Medicine"},{"author_name":"Kerry Limberg","author_inst":"NYU Grossman School of Medicine"},{"author_name":"Nicolette Pirjanian","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Jimena Zulueta","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Valentina Fossati","author_inst":"New York Stem Cell Foundation Research Institute"},{"author_name":"Akiko Iwasaki","author_inst":"Yale School of Medicine,"},{"author_name":"Peter A Calabresi","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Shane A Liddelow","author_inst":"NYU Grossman School of Medicine"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Psychophysical validation of calibrated white-noise and tuned-noise auditory masks for transcranial focused ultrasound","rel_doi":"10.64898\/2026.07.29.741617","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741617","rel_abs":"Auditory confounds have proven to be a major hurdle in the elucidation of veridical neuromodulation effects with transcranial ultrasound stimulation (TUS). Auditory noise masks are an essential method to reduce the audibility of TUS and have shown promise in several studies. Here we describe a novel approach for design, calibration, and psychometric validation of auditory noise masks to reduce the perceptibility of TUS. White noise masks and spectrum-tuned masks matched to a TUS protocol that generates highly salient auditory costimulation (487.5 Hz pulse repetition frequency, 10% duty cycle, 68 W\/cm2 pulse-peak average intensity, 500 kHz acoustic frequency) were generated, and dB(A) levels were calibrated with an artificial ear. The masker levels needed to reduce TUS detection performance in a two-interval forced choice task were determined with an adaptive QUEST+ staircase in 20 neurotypical participants. Detection performance of this highly salient TUS protocol was driven to near chance performance (<55%) in 17\/20 participants with white-noise and 18\/20 participants with spectrum-tuned noise. However, high masker levels approaching safety limits were needed to render TUS inaudible for the majority of participants, indicating the need for formal masker calibration for these TUS settings. Additionally, against expectation the spectrum-tuned masker did not significantly outperform the white-noise masker, suggesting that perceptibility of TUS auditory costimulation does not lawfully follow the sound expected from its pulse envelope and the known spectrum of human hearing.","rel_num_authors":6,"rel_authors":[{"author_name":"Martin TW Scott","author_inst":"University of California, San Francisco"},{"author_name":"Patti N Limon","author_inst":"University of California, San Francisco"},{"author_name":"Gerald R Popelka","author_inst":"Stanford University"},{"author_name":"Kim Butts Pauly","author_inst":"Stanford University"},{"author_name":"Anthony M Norcia","author_inst":"Stanford University"},{"author_name":"Ryan T Ash","author_inst":"University of California, San Francisco"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Cell-free pathway prototyping enables cost-effective biomanufacturing of 1,2,4-butanetriol at the 1-L scale","rel_doi":"10.64898\/2026.08.03.742631","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742631","rel_abs":"Biomanufacturing offers sustainable alternatives to chemical synthesis under lower temperatures and pressures than traditional catalytic methods. However, the slow pace and iterative engineering bottlenecks of cell strain development restrict the feasible biological design space. Cell-free systems circumvent these constraints, providing a flexible and high-throughput screening approach to accelerate pathway prototyping and enzyme optimization but are not typically used for manufacturing scale-up. To understand the scalability of cell-free biosynthesis, we establish an end-to-end fully cell-free architecture to discover, develop, and scale the biosynthesis of 1,2,4-butanetriol (BT), a high-value industrial platform chemical. First, we systematically screened ~150 enzymes across the 4-step pathway from xylose to BT to identify highly active homologs for each reaction. Next, we applied statistical Design of Experiments to optimize reaction formulations for cost and titer. Finally, the maximum-titer and minimum-cost formulations were scaled up across five orders of magnitude, from 10-L to 1-L reactions. This resulted in peak volumetric productivities of ~1 g\/L\/h and yields over 13 g of BT in a single 1-L reaction, with raw substrate costs totaling just $3.00 per liter. This work expands the diversity of enzymes tested for BT synthesis and establishes a blueprint for advancing industrial biochemical manufacturing fully in vitro.","rel_num_authors":14,"rel_authors":[{"author_name":"Blake Rasor","author_inst":"North Carolina State University"},{"author_name":"Katherine Rhea","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"Isaiah Richardson","author_inst":"Northwestern University"},{"author_name":"John Tyler Lazar","author_inst":"Stanford University"},{"author_name":"Marilyn F S Lee","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"Ethan Walters","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"John Biondo","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"Frank Kragl","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"David Garcia","author_inst":"University of Maryland Baltimore County"},{"author_name":"Kyle Zolkin","author_inst":"Stanford University"},{"author_name":"John Davies","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"Matthew Lux","author_inst":"US Army DEVCOM Chemical Biological Center"},{"author_name":"Ashty Karim","author_inst":"Northwestern University"},{"author_name":"Michael Jewett","author_inst":"Stanford University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"ComBatFamQC: Streamlining Interactive Batch-Effect Diagnostics and Harmonization for Neuroimaging Data in R","rel_doi":"10.64898\/2026.07.29.741509","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741509","rel_abs":"As multisite and multi-study data aggregation becomes increasingly common for improving statistical power and sample diversity, robust harmonization methods are needed to address biases introduced by batch variation, particularly in neuroimaging research. Although a variety of harmonization approaches are available, the lack of systematic guidance for diagnosing batch effects and selecting appropriate methods remains a major challenge. To address this gap, we introduce ComBatFamQC, a comprehensive R package designed to streamline batch-effect diagnosis, harmonization, and post-harmonization analysis. ComBatFamQC integrates a user-friendly Shiny app for interactive batch-effect diagnostics, state-of-the-art harmonization methods from the ComBat family, including ComBat, longitudinal ComBat, ComBat-GAM, and CovBat, and tools for downstream analysis after harmonization. The package provides qualitative visualizations, statistical tests for batch-effect assessment, and a consistent interface that supports both in-sample and out-of-sample harmonization through the Shiny app, the R console, or the command line. In addition, it includes functions for post-harmonization analyses to facilitate downstream modeling. Its modular design also supports the systematic incorporation of future harmonization methods and expanded downstream analysis capabilities.","rel_num_authors":9,"rel_authors":[{"author_name":"Zheng Ren","author_inst":"Johns Hopkins University"},{"author_name":"Elizabeth Horwath","author_inst":"University of Pennsylvania"},{"author_name":"Siyan Wen","author_inst":"University of Pennsylvania"},{"author_name":"Randa Melhem","author_inst":"University of Pennsylvania"},{"author_name":"Jessica K. Anderson","author_inst":"Rutgers New Jersey Medical School"},{"author_name":"W. Evan Johnson","author_inst":"Rutgers New Jersey Medical School"},{"author_name":"Russell T. Shinohara","author_inst":"University of Pennsylvania"},{"author_name":"Andrew A. Chen","author_inst":"Medical University of South Carolina"},{"author_name":"Haochang Shou","author_inst":"University of Pennsylvania"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"ComBatFamQC: Streamlining Interactive Batch-Effect Diagnostics and Harmonization for Neuroimaging Data in R","rel_doi":"10.64898\/2026.07.29.741509","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741509","rel_abs":"As multisite and multi-study data aggregation becomes increasingly common for improving statistical power and sample diversity, robust harmonization methods are needed to address biases introduced by batch variation, particularly in neuroimaging research. Although a variety of harmonization approaches are available, the lack of systematic guidance for diagnosing batch effects and selecting appropriate methods remains a major challenge. To address this gap, we introduce ComBatFamQC, a comprehensive R package designed to streamline batch-effect diagnosis, harmonization, and post-harmonization analysis. ComBatFamQC integrates a user-friendly Shiny app for interactive batch-effect diagnostics, state-of-the-art harmonization methods from the ComBat family, including ComBat, longitudinal ComBat, ComBat-GAM, and CovBat, and tools for downstream analysis after harmonization. The package provides qualitative visualizations, statistical tests for batch-effect assessment, and a consistent interface that supports both in-sample and out-of-sample harmonization through the Shiny app, the R console, or the command line. In addition, it includes functions for post-harmonization analyses to facilitate downstream modeling. Its modular design also supports the systematic incorporation of future harmonization methods and expanded downstream analysis capabilities.","rel_num_authors":9,"rel_authors":[{"author_name":"Zheng Ren","author_inst":"Johns Hopkins University"},{"author_name":"Elizabeth Horwath","author_inst":"University of Pennsylvania"},{"author_name":"Siyan Wen","author_inst":"University of Pennsylvania"},{"author_name":"Randa Melhem","author_inst":"University of Pennsylvania"},{"author_name":"Jessica K. Anderson","author_inst":"Rutgers New Jersey Medical School"},{"author_name":"W. Evan Johnson","author_inst":"Rutgers New Jersey Medical School"},{"author_name":"Russell T. Shinohara","author_inst":"University of Pennsylvania"},{"author_name":"Andrew A. Chen","author_inst":"Medical University of South Carolina"},{"author_name":"Haochang Shou","author_inst":"University of Pennsylvania"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Epithelial-Intrinsic Alterations and Maladaptation to Luminal Metabolites Underlie Persistent Crohn's Disease Pathogenesis","rel_doi":"10.64898\/2026.07.29.741535","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741535","rel_abs":"In patients with Crohn's disease, the noninflamed intestinal epithelium exhibits inflammation-like transcriptional signatures that persist even during clinical remission. However, it is unclear whether this signature is due to sustained environmental triggers or to the epithelium's intrinsic immunological adaptions. To disentangle environmental and cell-intrinsic effects on disease signatures, we used noninflamed intestinal tissue biopsies from patients with active and inactive Crohn's disease, as well as control donors, to generate donor-matched organoids enriched for intestinal epithelial cells. We collected single-cell RNA-seq and single-cell ATAC-seq data from intestinal tissues, and from their matched organoids before and after stimulation with luminal metabolites of patients. This approach allowed us to distinguish between the effects of extrinsic factors and the intrinsic alterations that persist when cells are removed from their local environment. We found that organoid cells retained epithelial-autonomous disease phenotypes, even when derived from patients in remission, whereas signatures from tissue cells showed evidence of immune- and microbial-epithelial crosstalk. In contrast to healthy control organoids, organoids from Crohn's disease patients exhibited selective activation of disease-associated transcriptional changes and environment-responsive inflammatory chromatin remodeling after exposure to patient-derived luminal metabolites. Overall, our study suggests that disease-associated epithelial states are shaped by both cell-intrinsic dysregulation and microenvironmental cues.","rel_num_authors":10,"rel_authors":[{"author_name":"Jianqiao Liu","author_inst":"University of Chicago"},{"author_name":"Ran Zhou","author_inst":"University of Chicago"},{"author_name":"Jason Koval","author_inst":"University of Chicago"},{"author_name":"Peter Carbonetto","author_inst":"University of Chicago"},{"author_name":"Candace M Cham","author_inst":"University of Chicago"},{"author_name":"Ashley M Sidebottom","author_inst":"University of Chicago"},{"author_name":"Matthew Stephens","author_inst":"University of Chicago"},{"author_name":"Sebastian Pott","author_inst":"University of Chicago"},{"author_name":"Eugene B Chang","author_inst":"University of Chicago"},{"author_name":"Anindita Basu","author_inst":"University of Chicago"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Sperm whale foraging combines persistent search with flexible prey-capture tactics","rel_doi":"10.64898\/2026.07.29.741536","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741536","rel_abs":"Predators searching patchy environments must coordinate movements across scales, yet this behavioural hierarchy is not yet technically possible to observe in the deep ocean. Here we show that sperm-whale foraging is organized across two nested levels: directionally persistent search paths and flexible prey-capture tactics. We combine acoustic recordings with reconstructed three-dimensional trajectories from 34 sensor-tag deployments on 20 individual whales in both the eastern Caribbean and the mid-Atlantic. Complete foraging paths exhibit heavy-tailed step lengths and superdiffusive displacement, consistent with Levy-like search. Within these paths, echolocation buzzes resolve into two recurrent acoustic-kinematic tactics. Type A involves brief ramp-ups, slower and more oscillatory movement, and longer post-buzz pauses. Type B involves prolonged ramp-ups, faster and vertically persistent movement, greater roll, slightly straighter approaches, and an energy-model estimate approximately seven times higher. Every sampled whale used both tactics and switched between them within dives, showing that the contrast is not driven by specialization among individuals. An Azorean deployment with prey-field echograms links the tactics to local prey conditions, while independent Dominica deployments recover their core kinematic contrast. Together, these results reveal a foraging hierarchy in which flexible capture actions unfold within persistent, deliberate large-scale search.","rel_num_authors":11,"rel_authors":[{"author_name":"Lorenzo Zaffina","author_inst":"Intesa Sanpaolo AI Lab"},{"author_name":"Corrado Monti","author_inst":"University of Turin"},{"author_name":"Simone Poetto","author_inst":"Intesa SanPaolo AI Lab"},{"author_name":"Maxime Lucas","author_inst":"University of Namur"},{"author_name":"Henriques Joao Machado Borges","author_inst":"Northeastern University London"},{"author_name":"Raj Deshpande","author_inst":"Northeasten University London"},{"author_name":"Pernille Tonnesen","author_inst":"Aarhus University"},{"author_name":"David Gruber","author_inst":"City University of New York"},{"author_name":"Shane Gero","author_inst":"Carleton University"},{"author_name":"Andrea Santoro","author_inst":"ISI Foundation"},{"author_name":"Giovanni Petri","author_inst":"Northeastern University London"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Confinement considerations for CRISPR toxin-antidote gene drive systems","rel_doi":"10.64898\/2026.08.03.742636","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742636","rel_abs":"Gene drives are potentially powerful tools, able to spread throughout target populations. They could be used to modify or suppress disease vectors, invasive species, and agricultural pests. Yet, in many scenarios, confinement of the drive to only a target population is required. Several types of drives are capable of this, among the most promising of which are CRISPR toxin-antidote drives. Though showing good performance in simple models, such drives have not been thoroughly assessed in spatially structured populations. Here we evaluate three modification drive variants with varying levels of confinement. We find that Toxin-Antidote Recessive Embryo (TARE) drive and 2-locus TARE drives can usually spread in connected populations or from a single sufficiently large release. However, they can still be stopped by a migration corridor or by a sufficiently high population density gradient. 1-locus 2-drive TARE, on the other hand, will not be able to spread outside of release areas and indeed will often retreat in the face of wild-type alleles. When these drives arrive at a point source such as a port, only the standard TARE drive has a significant chance of establishing if releases occur at sufficiently high frequency and quantity. However, in models with parental care among a limited number of offspring, TARE drives become more invasive, with lower introduction thresholds. Overall, we find that spatial and other ecological factors can substantially affect the outcome of a confined CRISPR toxin-antidote drive release.","rel_num_authors":4,"rel_authors":[{"author_name":"Ziqian Xu","author_inst":"Peking University"},{"author_name":"Yuna I Cho","author_inst":"Peking University"},{"author_name":"Xinyue Zhang","author_inst":"Peking University"},{"author_name":"Jackson Champer","author_inst":"Peking University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Spectral Correlates of Encoding Distinguish Good from Poor Learners","rel_doi":"10.64898\/2026.07.29.741612","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741612","rel_abs":"Individuals vary in their ability to encode and recall new experiences, yet neural markers of memory have rarely been linked to these trait-level differences. Subsequent memory effects (SMEs) identify patterns of neural activity during encoding that predict whether an item will later be remembered or forgotten. In scalp EEG, SMEs are typically characterized by increased theta and gamma power with decreased alpha, a profile that has been interpreted as a signature of effective encoding. Here, we tested whether SMEs reflect individual differences in mnemonic ability by analyzing over 1.3 million encoding events from a large free recall dataset. At the group level, alpha suppression and theta enhancement predicted successful encoding, while gamma did not predict subsequent memory after controlling for serial position. Across individuals, better learners showed reduced SMEs in all three frequency bands. The neural contrast that defines successful encoding was therefore most pronounced among the poorest learners. These findings suggest that high-performing individuals are less reliant on phasic spectral activity for successful encoding, and that SMEs capture stable individual differences in encoding efficiency.","rel_num_authors":3,"rel_authors":[{"author_name":"Benjamin E Falkenburg","author_inst":"Brown University"},{"author_name":"Adam W Broitman","author_inst":"University of Pennsylvania"},{"author_name":"Michael J. Kahana","author_inst":"University of Pennsylvania"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"IKK\u03b2 as a putative non-covalent and quinone-mediated covalent target of 4-methylcatechol in RANKL\/NF-\u03baB signaling: a combined computational and experimental analysis","rel_doi":"10.64898\/2026.07.29.741661","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741661","rel_abs":"Excessive osteoclast activity contributes to pathological bone loss in osteoporosis, rheumatoid arthritis, and osteolytic malignancies. The effects of small catechol derivatives on receptor activator of nuclear factor-{kappa}B ligand (RANKL)-induced osteoclastogenesis remain poorly understood. This study investigated the effects of 4-methylcatechol (4-MC) on RANKL-induced NF-{kappa}B activation and osteoclast differentiation. 4-MC reduced RANKL-induced NF-{kappa}B luciferase activity in HEK-293T\/RANK cells. 4-MC also suppressed RANKL-induced TRAP activity in RAW264.7 cells in a concentration-dependent manner and reduced the number of TRAP-positive multinucleated osteoclasts, without affecting cell viability. Molecular docking predicted non-covalent binding of 4-MC within the ATP-binding hinge region of IKK{beta} (PDB: 4KIK), forming a close polar contact with Glu97, predicted hydrogen bonds with Cys99, and a hydrophobic contact with Ile165, within the pocket occupied by the co-crystallized inhibitor K252a. Covalent docking predicted that the oxidized quinone form of 4-MC engages Cys179 in the IKK{beta} activation loop. Quantum chemical calculations confirmed a markedly higher electrophilicity index for the oxidized quinone than for the parent catechol, supporting this mechanism. In silico ADMET profiling indicated favorable drug-likeness and safety. These findings identify IKK{beta} as a plausible molecular target of 4-MC through both non-covalent and covalent mechanisms.","rel_num_authors":10,"rel_authors":[{"author_name":"Chengxu Xie","author_inst":"Wenzhou-Kean University"},{"author_name":"Lifang Zhang","author_inst":"Wenzhou-Kean University"},{"author_name":"Xinyi Bao","author_inst":"Wenzhou-Kean University"},{"author_name":"Xiaohan Li","author_inst":"Wenzhou-Kean University"},{"author_name":"Yili Ding","author_inst":"Wenzhou-Kean University"},{"author_name":"Mojtaba Tabandeh","author_inst":"Wenzhou-Kean University"},{"author_name":"Farwa Basit","author_inst":"Wenzhou-Kean University"},{"author_name":"Heriberto Velez","author_inst":"Wenzhou-Kean University"},{"author_name":"Santosh Kumar","author_inst":"Wenzhou-Kean University"},{"author_name":"Vishwa Deepak","author_inst":"Wenzhou-Kean University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Evolutionary Design of Membrane-Lytic Antimicrobial Peptides with Mixture of Experts","rel_doi":"10.64898\/2026.07.29.741660","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741660","rel_abs":"Antimicrobial peptides (AMPs) hold great promise in combating drug-resistant pathogens, yet current design models do not explicitly account for their primary mode of action, membrane disruption. To address this gap, we propose AMPainterV2, a model that designs membrane-lytic AMPs using generative adversarial imitation learning. AMPainterV2 integrates a Mixture-of-Experts (MoE) policy network to support insertion, deletion, and mutation operations, thereby expanding the evolutionary design space. In vitro experiments demonstrate that all ten top-ranked peptides evolved from random sequences are active membrane-lytic AMPs, with the best candidate achieving a mean minimal inhibitory concentration (MIC) of 1.5 M and superior membrane-lytic activity compared to polymyxin B. Particularly, a deletion-only version of AMPainterV2 enables membrane-lytic AMP miniaturization, yielding six miniaturized peptides with comparable or improved activity and an average 36% length reduction. Collectively, AMPainterV2 advances mechanism-driven AMP design and offers a valuable tool for cost-effective AMP development.","rel_num_authors":2,"rel_authors":[{"author_name":"Ruihan Dong","author_inst":"Peking University"},{"author_name":"Chen Song","author_inst":"Peking University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Non-canonical Oncostatin M Signaling Provides Protection during Respiratory Viral and Bacterial infections","rel_doi":"10.64898\/2026.07.30.741615","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.30.741615","rel_abs":"Pneumonia remains a major global health burden, highlighting the need for host-directed therapies to complement antimicrobial treatment. Here, we identify Oncostatin M (OSM) as a critical regulator of pulmonary host responses during influenza and bacterial pneumonia. Loss of OSM shifted lung macrophages toward a pro-inflammatory phenotype during influenza infection and exacerbated lung injury during bacterial pneumonia, demonstrating an essential role for OSM in limiting immunopathology. Unexpectedly, OSM induced Signal Transducer and Activator of Transcription 3 (STAT3) activation in the absence of the canonical OSM receptor subunit OSMr{beta}, revealing previously unrecognized non-canonical OSM signaling in the mouse lungs. Consistent with this finding, loss of OSMr{beta} did not phenocopy the severe disease observed with loss of OSM. Together, these findings identify OSM as a key regulator of pulmonary immunity and reveal unexpected complexity in OSM signaling during pneumonia.","rel_num_authors":16,"rel_authors":[{"author_name":"Yewoo Lee","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Lilly J. Patneaude","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Kevyn R. Martins","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Riley M.F. Pihl","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Ernest L. Dimbo","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Marta P\u00e9rez-V\u00e1zquez","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Archana Jayaraman","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Erin Crossey","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Elise M.R. Armstrong","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Bradley E. Hiller","author_inst":"Boston University Chobanian & Avedisian School of Medicine,"},{"author_name":"Isabella Garza","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Markus Bosmann","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Matthew R. Jones","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Joseph P. Mizgerd","author_inst":"Boston University Chobanian & Avedisian School of Medicine"},{"author_name":"Lee J. Quinton","author_inst":"University of Massachusetts Chan Medical School"},{"author_name":"Katrina E. Traber","author_inst":"Boston University Chobanian & Avedisian School of Medicine"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Statistical factorization in motor control: Opposing biases from statistics on different timescales enable fast and accurate behavior","rel_doi":"10.64898\/2026.07.29.741609","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741609","rel_abs":"Motor planning is fundamentally constrained by the speed accuracy tradeoff: a single optimization that balances time and error costs, such that longer preparation yields more accurate movements while faster ones incur greater error. Here we propose that the motor system exploits environmental statistics to reshape this relationship, using two complementary computations that rely on distinct statistical information. The first leverages the marginal statistics of the target distribution, learned by integrating slowly over many trials, to modify the initial preparation state, accelerating planning for frequently encountered targets; this simultaneously speeds decisions and reduces planning variability, but introduces an attractive bias toward the mean of the target distribution. Strikingly, a second process tracks the sequential statistics of the environment over only the last few trials, producing a repulsive sequential bias whose persistence is tuned to the temporal autocorrelation and selectively counteracting the attractive bias introduced by the first. These results reveal that the motor system applies statistical factorization, estimating marginal and sequential statistics on their own timescales to shape movement preparation, thereby escaping the speed accuracy tradeoff and producing movements that are both faster and more accurate.","rel_num_authors":2,"rel_authors":[{"author_name":"Tianhe Wang","author_inst":"University of California"},{"author_name":"David Whitney","author_inst":"UC Berkeley"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"The Effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Cardiorespiratory Physiology: Four Waveforms Trial with Tragus vs Earlobe Stimulation","rel_doi":"10.64898\/2026.07.29.741582","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741582","rel_abs":"Background: Transcutaneous auricular vagus nerve stimulation (taVNS) depends on activating afferent vagal pathways, leading to central and physiological (parasympathetic) modulation. Explaining how taVNS changes cardiorespiratory physiology requires systematic characterization of the effects of electrode location and stimulation waveform using rigorous experimental controls. Objective: To determine the acute effects of four taVNS stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz) on physiological markers of parasympathetic activation compared with configuration-matched earlobe stimulation in healthy subjects at rest. Methods: Customized 8-mm ear-clip electrodes delivered monophasic 500 s pulses (anode anterior) to the tragus or a configuration-matched earlobe control across four stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz). Twenty-five healthy participants completed a randomized, single-blind, within-subject crossover study, undergoing both active and control stimulation for all four configurations (200 sessions total). Each session consisted of five 60-second stimulation blocks (1,000 stimuli total). Heart rate (HR), heart rate variability (HRV; RMSSD), and respiration were recorded continuously. Linear mixed-effects models compared physiological responses between tragus and earlobe stimulation during the first stimulation block (primary analysis), across 5-second HR intervals (secondary analysis), and averaged across all five stimulation blocks (post hoc analysis). Results: During the first stimulation block, HRV was significantly higher during unilateral left 25 Hz tragus stimulation than during the matched earlobe control ({beta} = -10.34, t(33) = -2.63, p = .01, 95% CI [-18.05, -2.64]), consistent with increased parasympathetic activity. No significant differences were observed for HRV with the other stimulation configurations, or for HR or respiration under any configuration. Analysis of 5-second HR intervals likewise revealed no significant temporal effects for block one. Analysis of 5-second heart rate intervals across the five blocks identified differences between tragus and earlobe at discrete time points but did not show a consistent temporal pattern across the stimulation period. Across all five stimulation blocks, unilateral left 25 Hz tragus stimulation remained associated with higher HRV ({beta} = -6.56, t(124) = -3.85, p < .01, 95% CI [-9.90, -3.22]) and also produced an increase in HR relative to earlobe stimulation ({beta} = -1.05, t(24) = -2.57, p = .01, 95% CI [-1.85, -0.24]). Respiration was unaffected throughout. Conclusion: In this systematic study, unilateral left 25 Hz tragus stimulation produced physiological modulation consistent with vagal target engagement. These findings underscore the importance of rigorous dose-specific taVNS studies to establish reproducible physiological biomarkers.","rel_num_authors":5,"rel_authors":[{"author_name":"Devin Killion Petty Adair","author_inst":"City College of New York"},{"author_name":"Jacob Itzhakov","author_inst":"City College of New York"},{"author_name":"Helen Borges-Delfino-De-Souza","author_inst":"City College of New York"},{"author_name":"Mohamad Fallah Rad","author_inst":"City College of New York"},{"author_name":"Marom Bikson","author_inst":"City College of New York"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"IL1 blockade attenuates E. coli induced intrauterine inflammation and preterm labor in Rhesus macaques","rel_doi":"10.64898\/2026.07.30.741586","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.30.741586","rel_abs":"Intrauterine infection and inflammation are major causes of preterm labor, yet antibiotics alone often fail to prevent preterm birth despite achieving microbial clearance. Interleukin1 (IL1) is a key mediator of intra-amniotic inflammation and functional progesterone withdrawal, processes linked to labor initiation. We tested whether IL1 blockade with the clinically approved IL1 receptor antagonist, anakinra, could reduce inflammation and preterm labor in a Rhesus macaque model of intra-amniotic Escherichia coli infection followed by delayed antibiotic treatment. Here we show that anakinra reduced the incidence of preterm labor by 40% (p=0.07), attenuated inflammation in the fetal membranes and cervix, and preserved progesterone receptor-B abundance in the fetal membranes. These effects were most pronounced in animals protected from preterm labor. Our findings in a relevant model support the translational potential of combining IL1 blockade with antibiotics for infection-associated preterm labor.","rel_num_authors":23,"rel_authors":[{"author_name":"Pietro Presicce","author_inst":"University of California Los Angeles"},{"author_name":"Daniel Short","author_inst":"Imperial College London"},{"author_name":"Monica Cappelletti","author_inst":"UCLA Medical School: University of California Los Angeles David Geffen School of Medicine"},{"author_name":"Natalia Perecki","author_inst":"University of California Los Angeles"},{"author_name":"Arne Gehlaar","author_inst":"Yale School of Medicine"},{"author_name":"Alzbeta Godarova","author_inst":"Cincinnati Childrens Hospital Research Foundation"},{"author_name":"Angela DeTomaso","author_inst":"Case Western Reserve University"},{"author_name":"Jaqueline Shauh","author_inst":"Case Western Reserve University"},{"author_name":"Liza Konnikova","author_inst":"Yale University"},{"author_name":"Sivan Bercovici","author_inst":"Karius"},{"author_name":"Shiv Kale","author_inst":"Karius"},{"author_name":"Paul Babb","author_inst":"Karius"},{"author_name":"Lisa Miller","author_inst":"University of California Davis"},{"author_name":"Sing Sing Way","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"William J Zacharias","author_inst":"Cincinnati Children's Hospital, University of Cincinnati School of Medicine"},{"author_name":"Hitesh Deshmukh","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Senad Divanovic","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Myung S Sim","author_inst":"University of California Los Angeles"},{"author_name":"Alan H Jobe","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Claire A Chougnet","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Mark R Johnson","author_inst":"Imperial College London"},{"author_name":"Sam Mesiano","author_inst":"Case Western Reserve University"},{"author_name":"Suhas G Kallapur","author_inst":"University of California Los Angeles"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"IL1 blockade attenuates E. coli induced intrauterine inflammation and preterm labor in Rhesus macaques","rel_doi":"10.64898\/2026.07.30.741586","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.30.741586","rel_abs":"Intrauterine infection and inflammation are major causes of preterm labor, yet antibiotics alone often fail to prevent preterm birth despite achieving microbial clearance. Interleukin1 (IL1) is a key mediator of intra-amniotic inflammation and functional progesterone withdrawal, processes linked to labor initiation. We tested whether IL1 blockade with the clinically approved IL1 receptor antagonist, anakinra, could reduce inflammation and preterm labor in a Rhesus macaque model of intra-amniotic Escherichia coli infection followed by delayed antibiotic treatment. Here we show that anakinra reduced the incidence of preterm labor by 40% (p=0.07), attenuated inflammation in the fetal membranes and cervix, and preserved progesterone receptor-B abundance in the fetal membranes. These effects were most pronounced in animals protected from preterm labor. Our findings in a relevant model support the translational potential of combining IL1 blockade with antibiotics for infection-associated preterm labor.","rel_num_authors":23,"rel_authors":[{"author_name":"Pietro Presicce","author_inst":"University of California Los Angeles"},{"author_name":"Daniel Short","author_inst":"Imperial College London"},{"author_name":"Monica Cappelletti","author_inst":"UCLA Medical School: University of California Los Angeles David Geffen School of Medicine"},{"author_name":"Natalia Perecki","author_inst":"University of California Los Angeles"},{"author_name":"Arne Gehlaar","author_inst":"Yale School of Medicine"},{"author_name":"Alzbeta Godarova","author_inst":"Cincinnati Childrens Hospital Research Foundation"},{"author_name":"Angela DeTomaso","author_inst":"Case Western Reserve University"},{"author_name":"Jaqueline Shauh","author_inst":"Case Western Reserve University"},{"author_name":"Liza Konnikova","author_inst":"Yale University"},{"author_name":"Sivan Bercovici","author_inst":"Karius"},{"author_name":"Shiv Kale","author_inst":"Karius"},{"author_name":"Paul Babb","author_inst":"Karius"},{"author_name":"Lisa Miller","author_inst":"University of California Davis"},{"author_name":"Sing Sing Way","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"William J Zacharias","author_inst":"Cincinnati Children's Hospital, University of Cincinnati School of Medicine"},{"author_name":"Hitesh Deshmukh","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Senad Divanovic","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Myung S Sim","author_inst":"University of California Los Angeles"},{"author_name":"Alan H Jobe","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Claire A Chougnet","author_inst":"Cincinnati Childrens Hospital Research Foundation, and the University of Cincinnati College of Medicine"},{"author_name":"Mark R Johnson","author_inst":"Imperial College London"},{"author_name":"Sam Mesiano","author_inst":"Case Western Reserve University"},{"author_name":"Suhas G Kallapur","author_inst":"University of California Los Angeles"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Genetic and stochastic basis of phenotypic discordance in 16p11.2 mouse model deletion","rel_doi":"10.64898\/2026.07.29.741187","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741187","rel_abs":"Recurrent copy number variations such as the 16p11.2 deletion (del\/+) represent a significant genetic risk for neurodevelopmental disorders, showing incomplete penetrance and variable expressivity. Here we describe a striking discordance in a genetic mouse model of human 16p11.2 deletion. Using electrocorticography experiments, we detected that approximately 50% of the isogenic del\/+ mice exhibited increased susceptibility to seizures from low doses of the convulsant drug pentylenetetrazole (PTZ). Some of these mice also displayed spontaneous epileptiform brain activity. Next, we used two-photon microscopy tomography (STPT) with c-Fos-GFP (c-Fos+) as a reporter of neuronal activity to obtain images of the entire mouse brain. We examined del\/+ mice that exhibited low or high responses to PTZ. Low responders exhibited minimal c-Fos+ activation. However, they had activating circuits that suggest the presence of compensatory mechanisms that suppress seizures. These circuits include the reticular nucleus of the thalamus, the pretectal region, the pedunculopontine nucleus, and the superior colliculus. In contrast, high-responder mice exhibited high c-Fos+ expression, corresponding to a fast seizure phenotype. Using whole-brain imaging, we analyzed brain volume and detected significant differences in the cortex between low-responder and high-responder del\/+ mice. In the group with higher seizure susceptibility, we observed a notable decrease in cortical volume with significant differences in several brain regions compared to low responders. Additionally, some high-responder mice showed null expansion areas compared to low-responder mice. During the longitudinal behavioral analysis, the high-responder group of mice exhibited more severe sleep disturbances and an increase in repetitive grooming. Finally, to identify transcriptional correlates of the low- versus high-response phenotypes in adulthood, we performed bulk RNA-seq on somatosensory cortex punches from adult del\/+ mice stratified by seizure response. Seizure-prone del\/+ mice exhibited reduced activity-dependent immediate early gene signatures and coordinated changes in regulatory programs, including decreased expression of transcriptional regulators and metabotropic glutamate receptor genes, compared to low responders. Together, these findings define two distinct adult del\/+ subgroups with convergent circuit, structural, behavioral, and molecular signatures.","rel_num_authors":13,"rel_authors":[{"author_name":"Julian Taranda","author_inst":"University of Bonn"},{"author_name":"Jana Veliskova","author_inst":"NYMC"},{"author_name":"Sukalp Muzumdar","author_inst":"Cold Spring Harbor laboratory"},{"author_name":"Kith Pradhan","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Kannan Umadevi Venkataraju","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Ramesh Palaniswamy","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Rhonda Drewes","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Jianjun Sun","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Nicolas Dross","author_inst":"University of Heidelberg"},{"author_name":"Sevin Turcan","author_inst":"University of Bonn"},{"author_name":"Jesse Gillis","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Libor Velisek","author_inst":"NYMC"},{"author_name":"Pavel Osten","author_inst":"Cold Spring Harbor Laboratory"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Genetic and stochastic basis of phenotypic discordance in 16p11.2 mouse model deletion","rel_doi":"10.64898\/2026.07.29.741187","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741187","rel_abs":"Recurrent copy number variations such as the 16p11.2 deletion (del\/+) represent a significant genetic risk for neurodevelopmental disorders, showing incomplete penetrance and variable expressivity. Here we describe a striking discordance in a genetic mouse model of human 16p11.2 deletion. Using electrocorticography experiments, we detected that approximately 50% of the isogenic del\/+ mice exhibited increased susceptibility to seizures from low doses of the convulsant drug pentylenetetrazole (PTZ). Some of these mice also displayed spontaneous epileptiform brain activity. Next, we used two-photon microscopy tomography (STPT) with c-Fos-GFP (c-Fos+) as a reporter of neuronal activity to obtain images of the entire mouse brain. We examined del\/+ mice that exhibited low or high responses to PTZ. Low responders exhibited minimal c-Fos+ activation. However, they had activating circuits that suggest the presence of compensatory mechanisms that suppress seizures. These circuits include the reticular nucleus of the thalamus, the pretectal region, the pedunculopontine nucleus, and the superior colliculus. In contrast, high-responder mice exhibited high c-Fos+ expression, corresponding to a fast seizure phenotype. Using whole-brain imaging, we analyzed brain volume and detected significant differences in the cortex between low-responder and high-responder del\/+ mice. In the group with higher seizure susceptibility, we observed a notable decrease in cortical volume with significant differences in several brain regions compared to low responders. Additionally, some high-responder mice showed null expansion areas compared to low-responder mice. During the longitudinal behavioral analysis, the high-responder group of mice exhibited more severe sleep disturbances and an increase in repetitive grooming. Finally, to identify transcriptional correlates of the low- versus high-response phenotypes in adulthood, we performed bulk RNA-seq on somatosensory cortex punches from adult del\/+ mice stratified by seizure response. Seizure-prone del\/+ mice exhibited reduced activity-dependent immediate early gene signatures and coordinated changes in regulatory programs, including decreased expression of transcriptional regulators and metabotropic glutamate receptor genes, compared to low responders. Together, these findings define two distinct adult del\/+ subgroups with convergent circuit, structural, behavioral, and molecular signatures.","rel_num_authors":13,"rel_authors":[{"author_name":"Julian Taranda","author_inst":"University of Bonn"},{"author_name":"Jana Veliskova","author_inst":"NYMC"},{"author_name":"Sukalp Muzumdar","author_inst":"Cold Spring Harbor laboratory"},{"author_name":"Kith Pradhan","author_inst":"Albert Einstein College of Medicine"},{"author_name":"Kannan Umadevi Venkataraju","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Ramesh Palaniswamy","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Rhonda Drewes","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Jianjun Sun","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Nicolas Dross","author_inst":"University of Heidelberg"},{"author_name":"Sevin Turcan","author_inst":"University of Bonn"},{"author_name":"Jesse Gillis","author_inst":"Cold Spring Harbor Laboratory"},{"author_name":"Libor Velisek","author_inst":"NYMC"},{"author_name":"Pavel Osten","author_inst":"Cold Spring Harbor Laboratory"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Behavioural and neural mechanisms for stochastic choices in mixed strategy games","rel_doi":"10.64898\/2026.07.29.741515","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741515","rel_abs":"Real-life decisions are rarely made in isolation; outcomes depend not only on an individual's choices but also on the actions of others. In competitive settings, optimal decision-making often requires unpredictability: for example, a penalty taker in football randomises their kicks to avoid being predicted by the goalkeeper. Such stochastic strategies prevent opponents from exploiting predictable patterns. To probe the neural mechanisms underlying these game-theoretic behaviours, we trained head-fixed mice in a zero-sum game against a competitive computer opponent, and compared their choice patterns and dorsal cortical dynamics across learning. We fit an unsupervised hidden Markov model to characterise their strategy on each trial, revealing a shift from structured to stochastic strategies as animals learned to avoid predictable choice patterns. We validated this model using behavioural data from monkeys playing the same game against different levels of computer opponents, enabling direct cross-species comparison of decision strategies. This revealed fundamental computations shared across species as well as species-specific differences. We tracked dorsal cortical dynamics while mice transitioned from naive to expert players, and found that reward history information was reduced during stochastic choices compared to structured, reward-guided choices. Furthermore, the influence of immediate reward information on guiding upcoming choices was significantly diminished during stochastic choices. Together, these findings reveal a putative neural mechanism for behavioural stochasticity, where reward information is decoupled from future choice to maximise behavioural unpredictability and long-term gains in a competitive multi-agent game.","rel_num_authors":7,"rel_authors":[{"author_name":"Joanna Aloor","author_inst":"Sainsbury Wellcome Centre, University College London"},{"author_name":"Timothy PH Sit","author_inst":"Sainsbury Wellcome Centre, University College London"},{"author_name":"Oliver M Gauld","author_inst":"Sainsbury Wellcome Centre, University College London"},{"author_name":"Joseph Warren","author_inst":"Sainsbury Wellcome Centre, University College London"},{"author_name":"Matthew Mower","author_inst":"Sainsbury Wellcome Centre, University College London"},{"author_name":"Daeyeol Lee","author_inst":"Johns Hopkins University"},{"author_name":"Chunyu A. Duan","author_inst":"Sainsbury Wellcome Centre, University College London"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Scientific computing in the age of agentic AI: an exploratory field report","rel_doi":"10.64898\/2026.07.29.741496","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741496","rel_abs":"Scientific computing has become a central component of modern scientific discovery. Yet many computational tools are developed by small, specialized teams under incentives that encourage the release of rapidly prototyped tooling without commensurate attention to engineering concerns, including performance and maintainability. These gaps are particularly visible in the life sciences, where the advent of high-throughput sequencing and molecular profiling has made the production and processing of datasets routine at scales that strain reliability and cost. Recently, LLM-based agents have become increasingly capable, with publicly available systems possessing both significant domain knowledge in many scientific fields and the ability to autonomously operate over complex and specialized codebases in pursuit of well-defined goals. Together, these developments create a practical opportunity for scientific computing. Many of the persistent weaknesses of the scientific computing ecosystem stem from technical debt and a shortage of sustained engineering labor and expertise. Here, we examine coding agents as a potential way to address these weaknesses: we present an exploratory field report of eight early case studies in the application of LLM agents to scientific computing across a range of project scopes, from lightweight maintenance tasks to full performance-oriented rewrites of scientific libraries, with a focus on the life sciences. Each of these case studies is accompanied by reflections from the individual or group responsible for the work, including lessons from the process. Overall, we find that the use of coding agents in scientific computing holds great promise for accelerating scientific research and increasing the reliability of critical systems, but that outstanding concerns remain, including responsibility and ownership for such projects, and we suggest collaboration and stewardship with existing maintainers when feasible.","rel_num_authors":21,"rel_authors":[{"author_name":"Jeremy Li","author_inst":"OpenAI"},{"author_name":"Alex Rubinsteyn","author_inst":"Department of Genetics, University of North Carolina at Chapel Hill; Department of Computer Science, University of North Carolina at Chapel Hill; Department of "},{"author_name":"Sergey Feldman","author_inst":"Allen Institute for Artificial Intelligence"},{"author_name":"Timothy O'Donnell","author_inst":"Open Athena AI Foundation"},{"author_name":"James M. Ferguson","author_inst":"Garvan Institute of Medical Research"},{"author_name":"Rob Patro","author_inst":"University of Maryland"},{"author_name":"Ian Driver","author_inst":"Independent researcher"},{"author_name":"Philip A. Ewels","author_inst":"Seqera"},{"author_name":"Felix Krueger","author_inst":"Altos Labs"},{"author_name":"Philipp Angerer","author_inst":"Institute of Computational Biology, Helmholtz Munich; scverse"},{"author_name":"Ilan Gold","author_inst":"Institute of Computational Biology, Helmholtz Munich; scverse"},{"author_name":"Jonathan Manning","author_inst":"Seqera"},{"author_name":"Lukas Heumos","author_inst":"NVIDIA Corporation; scverse"},{"author_name":"Mamad Ahangari","author_inst":"MinosAI"},{"author_name":"Varun Goyal","author_inst":"MinosAI"},{"author_name":"Hassan Masoudi","author_inst":"MinosAI"},{"author_name":"Brent Pedersen","author_inst":"Independent researcher"},{"author_name":"Andrew Bai","author_inst":"Booth School of Business, University of Chicago"},{"author_name":"Heng Li","author_inst":"Department of Biomedical Informatics, Harvard Medical School; Department of Data Science, Dana-Farber Cancer Institute"},{"author_name":"Suyash Shringarpure","author_inst":"OpenAI"},{"author_name":"Andrew Ho","author_inst":"OpenAI"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Environment-dependent epistasis shapes adaptation to fluctuating resources.","rel_doi":"10.64898\/2026.07.31.742109","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.31.742109","rel_abs":"Microbial populations frequently experience fluctuations in resource availability, yet how these fluctuations reshape genetic interactions during adaptation remains unclear. Here, we identify the rapid evolution of latent antimicrobial susceptibility in Escherichia coli populations experimentally evolved under repeated feast-famine cycles. Longitudinal population genomics revealed recurrent mutations in the transport genes acrB and ompF , and reconstruction of these mutations demonstrated environment-dependent fitness effects characterized by positive epistasis after 1 day of culture and reciprocal sign epistasis after 10 days. Together, our results support a two-step adaptive trajectory in which mutations affecting efflux are followed by changes in porin permeability, generating genotypes that are jointly beneficial across feast and famine. More broadly, our findings demonstrate how fluctuating environments reshape adaptive genetic interactions, producing historically contingent evolutionary trajectories and latent phenotypes.","rel_num_authors":5,"rel_authors":[{"author_name":"Ashlynn G Bruder","author_inst":"Vanderbilt University"},{"author_name":"Nathan Fiedeldey","author_inst":"Vanderbilt University"},{"author_name":"Sarah B Worthan","author_inst":"Vanderbilt University"},{"author_name":"Zeer Cen","author_inst":"Vanderbilt University"},{"author_name":"Megan Grace Behringer","author_inst":"Vanderbilt University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"A pyramidal silicon nanopore for single misfolded Tau protein characterisation","rel_doi":"10.64898\/2026.08.04.742667","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.04.742667","rel_abs":"Solid-state nanopores offer a versatile platform for single-molecule sensing owing to their mechanical robustness, tuneable geometry, and compatibility with scalable fabrication. Here, we present a pyramidal silicon nanopore with a 40 nm sensing aperture for label-free characterisation of protein molecules by resistive pulse sensing. The nanopore operates stably over transmembrane voltages ranging from -2 to +2 V and across a broad range of electrolyte concentrations, enabling analysis under diverse experimental conditions. As molecules traverse the confined sensing region, transient ionic current modulations are generated that reflect their excluded volume and molecular geometry. Using this approach, we characterise unlabelled Tau species spanning monomeric proteins, intermediate aggregates, and mature fibrillar assemblies. Analysis of the resulting current signatures, together with simplified geometrical models, enables reconstruction of molecular dimensions and discrimination of distinct Tau populations based on their electrical fingerprints. These results demonstrate that pyramidal silicon nanopores provide a sensitive and scalable platform for label-free monitoring of structurally heterogeneous protein aggregation and establish a framework for investigating protein aggregation using solid-state nanopore sensing.","rel_num_authors":4,"rel_authors":[{"author_name":"Hoi Lam Cheung","author_inst":"The Chinese University of Hong Kong"},{"author_name":"Dehua Hu","author_inst":"The Chinese University of Hong Kong"},{"author_name":"Jianxin Yang","author_inst":"The Chinese University of Hong Kong"},{"author_name":"Ho Pui Ho","author_inst":"The Chinese University of Hong Kong"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Savings and interference following learning to reach with mirror reversed feedback","rel_doi":"10.64898\/2026.07.28.741240","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.28.741240","rel_abs":"Learning to reach with a visuomotor distortion has been shown to influence subsequent reaches with the same distortion and with a new distortion. Here, we examined whether learning to reach with a small 20 degree mirror reversed distortion leads to faster re-learning of the same distortion (i.e., demonstrates savings) and whether learning to reach with a mirror reversed distortion influences subsequent reaches with a 20 degree visuomotor rotation distortion. Thirty participants first learned to reach with the mirror reversed distortion. Following washout trials with aligned cursor feedback, 15 participants reached again with the mirror reversed distortion (MR-MR group), while the 15 other participants reached with a visuomotor rotation distortion (MR-VMR group). An additional twenty participants only reached with the visuomotor rotation distortion (VMR-only group). Implicit (unconscious) and explicit (conscious strategy) contributions to learning were assessed using the process dissociation procedure. Evidence of savings was evident in the MR-MR group, such that participants demonstrated reduced hand angles when re-introduced to the mirror reversed distortion. This savings was driven by explicit processes, consistent with the rapid retrieval of previously acquired task solutions. Additionally, learning to reach with the mirror reversed distortion interfered with learning to reach with the visuomotor rotation distortion, such that the MR-VMR group demonstrated increased reach variability and longer reaction times when reaching with the visuomotor rotation distortion compared to the VMR-only group. Reduced implicit contributions were also evident in the MR-VMR group compared to the VMR-only group. Together, results indicate that learning to reach with a mirror reversed distortion promotes savings and influences learning to reach with a visuomotor rotation distortion through engagement of explicit processes.","rel_num_authors":3,"rel_authors":[{"author_name":"Sarvenaz Heirani Moghaddam","author_inst":"University of Ottawa"},{"author_name":"Gerome  Aleandro Manson","author_inst":"Queen's University - Kingston Campus: Queen's University"},{"author_name":"Erin  Krista Cressman","author_inst":"University of Ottawa - Ottawa Campus: University of Ottawa"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Savings and interference following learning to reach with mirror reversed feedback","rel_doi":"10.64898\/2026.07.28.741240","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.28.741240","rel_abs":"Learning to reach with a visuomotor distortion has been shown to influence subsequent reaches with the same distortion and with a new distortion. Here, we examined whether learning to reach with a small 20 degree mirror reversed distortion leads to faster re-learning of the same distortion (i.e., demonstrates savings) and whether learning to reach with a mirror reversed distortion influences subsequent reaches with a 20 degree visuomotor rotation distortion. Thirty participants first learned to reach with the mirror reversed distortion. Following washout trials with aligned cursor feedback, 15 participants reached again with the mirror reversed distortion (MR-MR group), while the 15 other participants reached with a visuomotor rotation distortion (MR-VMR group). An additional twenty participants only reached with the visuomotor rotation distortion (VMR-only group). Implicit (unconscious) and explicit (conscious strategy) contributions to learning were assessed using the process dissociation procedure. Evidence of savings was evident in the MR-MR group, such that participants demonstrated reduced hand angles when re-introduced to the mirror reversed distortion. This savings was driven by explicit processes, consistent with the rapid retrieval of previously acquired task solutions. Additionally, learning to reach with the mirror reversed distortion interfered with learning to reach with the visuomotor rotation distortion, such that the MR-VMR group demonstrated increased reach variability and longer reaction times when reaching with the visuomotor rotation distortion compared to the VMR-only group. Reduced implicit contributions were also evident in the MR-VMR group compared to the VMR-only group. Together, results indicate that learning to reach with a mirror reversed distortion promotes savings and influences learning to reach with a visuomotor rotation distortion through engagement of explicit processes.","rel_num_authors":3,"rel_authors":[{"author_name":"Sarvenaz Heirani Moghaddam","author_inst":"University of Ottawa"},{"author_name":"Gerome  Aleandro Manson","author_inst":"Queen's University - Kingston Campus: Queen's University"},{"author_name":"Erin  Krista Cressman","author_inst":"University of Ottawa - Ottawa Campus: University of Ottawa"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"A durably colonizing engineered native symbiont enables sustained intestinal delivery for metabolic dysfunction and colitis","rel_doi":"10.64898\/2026.08.02.741375","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.741375","rel_abs":"Background: Engineered bacterial therapeutics represent a promising strategy for sustained intestinal delivery of therapeutic molecules, but their efficacy is limited by inefficient colonisation, safety concerns and the need for repeated administration or auxiliary delivery systems. Objective: To develop a safety-optimised native bacterial chassis capable of long-term gut colonisation and sustained therapeutic delivery for intestinal inflammatory and metabolic diseases. Design: Native murine Escherichia coli isolates were screened for antibiotic susceptibility, genetic tractability and long-term intestinal colonisation. The selected strain, MEc30, was further optimised by deleting the putative virulence-associated clb and irp loci. MEc30 was then engineered to deliver murine interleukin-10 (MEc30-mIL-10) or produce nicotinic acid (MEc30-NA), and therapeutic efficacy was evaluated in Il10-\/- colitis and high-fat diet-induced metabolic dysfunction models. Results: MEc30 achieved stable lifelong colonisation of the murine intestine after a single oral administration, without antibiotic preconditioning or auxiliary delivery systems, and did not detectably disturb host physiology or gut microbial ecology. Deletion of clb and irp abolished potential colibactin- and yersiniabactin-associated biosafety risks while preserving bacterial growth and colonisation capacity. MEc30-NA continuously produced nicotinic acid in the gut, activated epithelial GPR109a-associated barrier signalling, improved glucose and lipid metabolism, reduced systemic inflammation and avoided the sharp peak exposure associated with conventional nicotinic acid administration. MEc30-mIL-10 enabled sustained intestinal IL-10 delivery, suppressed inflammatory macrophage activation, improved barrier integrity and alleviated spontaneous colitis in Il10-\/- mice. Conclusion: This study identifies MEc30 as a durable and safety-optimised native E. coli chassis for sustained intestinal therapeutic delivery. Engineered native symbionts may provide a long-acting live biotherapeutic strategy for chronic intestinal inflammatory and metabolic diseases.","rel_num_authors":10,"rel_authors":[{"author_name":"Qixiang Zhao","author_inst":"Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, State Key Laboratory of Vascular Homeostasis and Remodeling, Sc"},{"author_name":"Yong Ding","author_inst":"Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University"},{"author_name":"Sen Yan","author_inst":"Institute of Advanced Clinical Medicine, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University"},{"author_name":"Haohan Ma","author_inst":"Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, State Key Laboratory of Vascular Homeostasis and Remodeling, Sc"},{"author_name":"Yicun Wang","author_inst":"Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, State Key Laboratory of Vascular Homeostasis and Remodeling, Sc"},{"author_name":"Siqi Guo","author_inst":"Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, State Key Laboratory of Vascular Homeostasis and Remodeling, Sc"},{"author_name":"Xi Luo","author_inst":"Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, State Key Laboratory of Vascular Homeostasis and Remodeling, Sc"},{"author_name":"Yanli Pang","author_inst":"Institute of Advanced Clinical Medicine, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University"},{"author_name":"Changtao Jiang","author_inst":"Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University"},{"author_name":"Kai Wang","author_inst":"Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Musical training-induced plasticity reflects melodic rather than instrumental expertise","rel_doi":"10.64898\/2026.07.29.741416","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.29.741416","rel_abs":"Musical training produces behavioral gains that extend beyond the practiced context. Yet, it is unclear whether such generalization is accompanied by broadly transferable neural changes or whether training-induced plasticity remains tied to the specific features of the learned material. In this study, 80 musically naive adults completed four piano-training sessions and underwent functional MRI before and after training. Twenty untrained participants served as passive controls. Participants performed a passive listening task in which they listened to the trained melody (Fur Elise) and an untrained melody (Ode to Joy), each played on a trained musical instrument (piano) and an untrained musical instrument (saxophone). Following training, participants demonstrated improved accuracy and rhythmic performance when playing an unfamiliar melody, indicating behavioral generalization. Training-induced neural changes, however, were predominantly associated with the learned melodic content. Listening to Fur Elise elicited increased activity in the intraparietal and supplementary motor cortex and in the cerebellum, as well as decreased activity in the superior temporal cortex. Consistently, pre- and post-training scans were most accurately classified based on brain activity to Fur Elise played on piano or saxophone, rather than brain response to Ode to Joy, suggesting that neural reorganization was driven more strongly by the practiced melody than by the trained instrumental timbre. Training also enhanced the neural separability of both melodic and instrumental information. Critically, pre-training responses to Fur Elise played on the piano predicted subsequent playing accuracy, whereas pre-training sensitivity to instrumental timbre predicted rhythmic performance in a novel melodic context. Together, these findings suggest that while acquired musical skills behaviorally transfer to novel material, practice-induced functional plasticity remains predominantly melody-specific. We conclude that musical skill acquisition reflects complementary contributions of pre-existing neural characteristics and learning-induced plasticity, with baseline auditory representations potentially supporting successful behavioral transfer.","rel_num_authors":8,"rel_authors":[{"author_name":"Tamar Ben-David","author_inst":"Tel Aviv University"},{"author_name":"Shachar Gal","author_inst":"Bar-Ilan University"},{"author_name":"Romi Kaplan","author_inst":"Tel Aviv University"},{"author_name":"Danielle Catalogna","author_inst":"Tel Aviv University"},{"author_name":"Asaf Madar","author_inst":"Tel Aviv University"},{"author_name":"Niv Tik","author_inst":"Tel Aviv University"},{"author_name":"Michal Bernstein-Eliav","author_inst":"Tel Aviv University"},{"author_name":"Ido Tavor","author_inst":"Tel Aviv University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Human CEBPA-N AML exhibits enhanced engraftment and a C\/EBP\u03b1-p30-driven leukemic stem cell program","rel_doi":"10.64898\/2026.08.03.742558","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742558","rel_abs":"Leukemic stem cells (LSCs) play a central role in disease progression, therapeutic resistance, and relapse in acute myeloid leukemia (AML). However, the identification and characterization of LSCs remain challenging because of their low abundance and their close phenotypic resemblance to normal hematopoietic stem and progenitor cells. Although patient-derived xenograft (PDX) models have provided important insights into AML biology and LSC heterogeneity, the relative engraftment potential of distinct CEBPA mutation subtypes and the immunophenotypic identity of LSCs in CEBPA N-terminal mutant AML (CEBPA-N-AML) remain poorly defined. To address these questions, we compared the engraftment characteristics of primary human CEBPA-mutated AML samples representing the major mutational subtypes using the highly permissive NSGS xenograft model. Primary CEBPA-N-AML samples exhibited markedly greater engraftment efficiency and leukemogenic potential than other CEBPA-mutated AML subtypes. Furthermore, we identified a CD366CD73CD123CD117CD371CD247 cell population that is highly enriched for functional LSCs in CEBPA-N-AML, demonstrating enhanced clonogenic activity, leukemia-initiating capacity, and long-term self-renewal. Collectively, our findings demonstrate that the leukemogenic potential of CEBPA-mutated AML is strongly influenced by mutation subtype, with CEBPA-N-AML exhibiting superior leukemia-propagating capacity in vivo. We further define a novel immunophenotypic LSC signature specific to CEBPA-N-AML, providing new insights into LSC heterogeneity in CEBPA-mutated AML and establishing a foundation for the development of LSC-directed therapeutic strategies.","rel_num_authors":16,"rel_authors":[{"author_name":"Philomina Sona Peramangalam","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Mayuresh Konde","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Onur Karakaslar","author_inst":"Leiden University Medical Center, Leiden, The Netherlands"},{"author_name":"Sebastian Wolf","author_inst":"University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany"},{"author_name":"Shikan Zheng","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Akmal Salimov","author_inst":"University of Pennsylvania, Philadelphia, PA"},{"author_name":"Sridevi Surapally","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Marieke Griffioen","author_inst":"Leiden University Medical Center, Leiden, The Netherlands."},{"author_name":"Tongjun Gu","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Sridhar Rao","author_inst":"Versiti Blood Research Institute, Milwaukee, WI"},{"author_name":"Daniel G Tenen","author_inst":"Harvard Stem Cell Institute, Harvard Medical School, Boston, MA."},{"author_name":"Thomas Oellerich","author_inst":"University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany"},{"author_name":"Erik van den Akker","author_inst":"Leiden University Medical Center, Leiden, The Netherlands."},{"author_name":"Martin Carroll","author_inst":"University of Pennsylvania, Philadelphia, PA"},{"author_name":"Caner Saygin","author_inst":"University of Chicago, Chicago, IL"},{"author_name":"John Anto Pulikkan","author_inst":"Versiti Blood Research Institute"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"FAM136A is an essential chaperone for mitochondrial membrane protein biogenesis","rel_doi":"10.64898\/2026.08.03.742567","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742567","rel_abs":"The metabolic and signaling function of mitochondria rely on a network of chaperones within the inner membrane space (IMS) that regulate the biogenesis of nascent mitochondrial proteins. Using a genome wide CRISPRi screen we found that in human cells FAM136A is required for biogenesis of all three voltage-dependent anion channel (VDAC) paralogs, an abundant and essential family of beta-barrel metabolite transporters in the outer mitochondrial membrane (OM). FAM136A is a ubiquitously expressed essential gene, that is conserved in metazoa and plants. Using a combination of experiments in human cells and in vitro reconstitution, we determined that FAM136A associates with unfolded VDACs in the IMS; solubilizes nascent VDAC through a direct interaction; and facilitates insertion of VDAC into the OM. FAM136A also binds and chaperones a subset of alpha-helical subunits of the electron transport chain. We therefore conclude that FAM136A is an IMS-resident chaperone, necessary and sufficient to maintain nascent membrane proteins in a folding-competent state to mediate their integration into the bilayer.","rel_num_authors":10,"rel_authors":[{"author_name":"Melanie Ernst","author_inst":"California Institute of Technology"},{"author_name":"Jichen Zhang","author_inst":"California Institute of Technology"},{"author_name":"Haoqi Xu","author_inst":"California Institute of Technology"},{"author_name":"Alexa Ma","author_inst":"California Institute of Technology"},{"author_name":"Lena A K Boegeholz","author_inst":"California Institute of Technology"},{"author_name":"Marton Szabo","author_inst":"California Institute of Technology"},{"author_name":"Ting-Yu Wang","author_inst":"California Institute of Technology"},{"author_name":"Tsui-Fen Chou","author_inst":"California Institute of Technology"},{"author_name":"Alina Guna","author_inst":"California Institute of Technology"},{"author_name":"Rebecca M Voorhees","author_inst":"California Institute of Technology"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"FAM136A is an essential chaperone for mitochondrial membrane protein biogenesis","rel_doi":"10.64898\/2026.08.03.742567","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742567","rel_abs":"The metabolic and signaling function of mitochondria rely on a network of chaperones within the inner membrane space (IMS) that regulate the biogenesis of nascent mitochondrial proteins. Using a genome wide CRISPRi screen we found that in human cells FAM136A is required for biogenesis of all three voltage-dependent anion channel (VDAC) paralogs, an abundant and essential family of beta-barrel metabolite transporters in the outer mitochondrial membrane (OM). FAM136A is a ubiquitously expressed essential gene, that is conserved in metazoa and plants. Using a combination of experiments in human cells and in vitro reconstitution, we determined that FAM136A associates with unfolded VDACs in the IMS; solubilizes nascent VDAC through a direct interaction; and facilitates insertion of VDAC into the OM. FAM136A also binds and chaperones a subset of alpha-helical subunits of the electron transport chain. We therefore conclude that FAM136A is an IMS-resident chaperone, necessary and sufficient to maintain nascent membrane proteins in a folding-competent state to mediate their integration into the bilayer.","rel_num_authors":10,"rel_authors":[{"author_name":"Melanie Ernst","author_inst":"California Institute of Technology"},{"author_name":"Jichen Zhang","author_inst":"California Institute of Technology"},{"author_name":"Haoqi Xu","author_inst":"California Institute of Technology"},{"author_name":"Alexa Ma","author_inst":"California Institute of Technology"},{"author_name":"Lena A K Boegeholz","author_inst":"California Institute of Technology"},{"author_name":"Marton Szabo","author_inst":"California Institute of Technology"},{"author_name":"Ting-Yu Wang","author_inst":"California Institute of Technology"},{"author_name":"Tsui-Fen Chou","author_inst":"California Institute of Technology"},{"author_name":"Alina Guna","author_inst":"California Institute of Technology"},{"author_name":"Rebecca M Voorhees","author_inst":"California Institute of Technology"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Disruption of interareal control during propofol anesthesia","rel_doi":"10.64898\/2026.07.28.741350","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.28.741350","rel_abs":"Anesthetic-induced unconsciousness may arise partly from a change in how brain areas can manipulate each other's activity. To quantify this change, we use control-theoretic tools that can precisely characterize how easily subsystems in complex networks can control each other. These tools rely on the Jacobian of the dynamics, an object that fully specifies how inputs to a function affect the outputs. We built on JacobianODE, a method for data-driven Jacobian learning, to enable its application to neural recordings. We developed a deep learning framework that recovers directional, nonlinear control from partially observed multi-area recordings by combining delay-coordinate embedding, a volume-preserving invertible encoder, and latent dynamics via JacobianODE. We validated our framework on the Lorenz system and a partially observed working-memory recurrent neural network. We then applied it to local field potential recordings from posterior parietal (PPC), superior temporal gyrus (STG), frontal eye fields (FEF), and ventrolateral prefrontal cortex (vlPFC) in two non-human primates, comparing wakefulness with propofol anesthesia. Anesthesia pervasively reduced the ability of areas to control each other, both in terms of driving towards novel states and stabilizing along existing trajectories. This change in ease of control was driven by a decrease in the magnitude of interareal coupling. Directional ease of driving control from PPC to vlPFC and FEF to vlPFC was increased under anesthesia, providing a potential mechanism for paradoxical excitation observed during propofol infusion. Together, these results recast anesthetic unconsciousness as a directional breakdown of cortical control.","rel_num_authors":7,"rel_authors":[{"author_name":"Adam J. Eisen","author_inst":"Massachusetts Institute of Technology"},{"author_name":"Andr\u00e9 M. Bastos","author_inst":"Vanderbilt University"},{"author_name":"Jacob A. Donoghue","author_inst":"Beacon Biosignals"},{"author_name":"Scott L. Brincat","author_inst":"Massachusetts Institute of Technology"},{"author_name":"Emery N. Brown","author_inst":"Massachusetts Institute of Technology"},{"author_name":"Ila R. Fiete","author_inst":"Massachusetts Institute of Technology"},{"author_name":"Earl K. Miller","author_inst":"Massachusetts Institute of Technology"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Synergistic cytotoxicity with Chk1\/Chk2-inhibitor prexasertib in small cell lung cancer following lurbinectedin-induced G2\/M-checkpoint activation","rel_doi":"10.64898\/2026.08.02.742299","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.742299","rel_abs":"Small cell lung cancer (SCLC) is an aggressive thoracic malignancy with a 5-year survival rate under 7%. Lack of meaningful improvement of survival rates despite advances in treatment highlights the need for novel therapeutic approaches to improve patient outcomes. Currently, carboplatin + etoposide chemotherapy is the backbone of treatment for most patients. Lurbinectedin is a cytotoxic drug with unique activity against small cell lung cancers in patients with extensive disease and acquired resistance to carboplatin + etoposide. Our preliminary experiments in human SCLC cell lines treated with lurbinectedin demonstrated a dose-dependent increase in Chk1 and Chk2 protein phosphorylation. A consequence of the frequent TP53 inactivation in SCLC is tumor cell reliance on G2\/M cell cycle checkpoints involving Chk1\/Chk2 to maintain genomic integrity and allow cell survival following DNA damage. We hypothesised that inhibition of Chk1\/Chk2-dependent responses with dual-inhibitor prexasertib (ACR-368), would potentiate tumor cell killing by lurbinectedin potentially in a synergistic manner. SCLC cells underwent cell death following single agent prexasertib exposure and this further increased with prexasertib + lurbinectedin combination. Highest Single Agent (HSA) synergy score calculations based on cell viability measurements suggested synergistic action between prexasertib and lurbinectedin at select dose combinations. Western blot analysis of intracellular proteins from SCLC cells treated with both drugs demonstrate dynamic, dose-dependent effects on Chk2, Chk1 and downstream effector Wee1, with lurbinectedin increasing intracellular levels of pChk1 and pChk2, while co-treatment with prexasertib deregulates this process across multiple human-derived cell lines. Synergistic killing was associated with elevated gamma-H2AX levels indicative of DNA double strand breaks and PARP-cleavage due to apoptotic caspase activation. Despite some heterogeneity among treated SCLC cells, the increased phosphorylation of Chk1 was noted at several kinase-activating sites including Serine 296, 317, and 345 while Chk2 Tyrosine 68 phosphorylation was consistently upregulated by lurbinectedin. The results provide a preclinical mechanistic rationale for overcoming a pro-survival, drug resistance-promoting checkpoint pathway to enhance the unique efficacy of single-agent lurbinectedin in patients with SCLC.","rel_num_authors":12,"rel_authors":[{"author_name":"Ashley F. Sanchez Sevilla Uruchurtu","author_inst":"Brown University"},{"author_name":"Audrey Y. Su","author_inst":"Brown University"},{"author_name":"Harshita Ganga","author_inst":"Penn State University"},{"author_name":"Shengliang Zhang","author_inst":"Brown University"},{"author_name":"Ameen Raissi","author_inst":"Johns Hopkins University"},{"author_name":"Kevin Kwon","author_inst":"Brown University"},{"author_name":"Tej Tummala","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Tyler Roady","author_inst":"Brown University"},{"author_name":"Jacqueline Moreno","author_inst":"University of Central Florida"},{"author_name":"Patrycja M Dubielecka-Szczerba","author_inst":"Brown University"},{"author_name":"Christopher G. Azzoli","author_inst":"Brown University"},{"author_name":"Wafik S. El-Deiry","author_inst":"Brown University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Synergistic cytotoxicity with Chk1\/Chk2-inhibitor prexasertib in small cell lung cancer following lurbinectedin-induced G2\/M-checkpoint activation","rel_doi":"10.64898\/2026.08.02.742299","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.742299","rel_abs":"Small cell lung cancer (SCLC) is an aggressive thoracic malignancy with a 5-year survival rate under 7%. Lack of meaningful improvement of survival rates despite advances in treatment highlights the need for novel therapeutic approaches to improve patient outcomes. Currently, carboplatin + etoposide chemotherapy is the backbone of treatment for most patients. Lurbinectedin is a cytotoxic drug with unique activity against small cell lung cancers in patients with extensive disease and acquired resistance to carboplatin + etoposide. Our preliminary experiments in human SCLC cell lines treated with lurbinectedin demonstrated a dose-dependent increase in Chk1 and Chk2 protein phosphorylation. A consequence of the frequent TP53 inactivation in SCLC is tumor cell reliance on G2\/M cell cycle checkpoints involving Chk1\/Chk2 to maintain genomic integrity and allow cell survival following DNA damage. We hypothesised that inhibition of Chk1\/Chk2-dependent responses with dual-inhibitor prexasertib (ACR-368), would potentiate tumor cell killing by lurbinectedin potentially in a synergistic manner. SCLC cells underwent cell death following single agent prexasertib exposure and this further increased with prexasertib + lurbinectedin combination. Highest Single Agent (HSA) synergy score calculations based on cell viability measurements suggested synergistic action between prexasertib and lurbinectedin at select dose combinations. Western blot analysis of intracellular proteins from SCLC cells treated with both drugs demonstrate dynamic, dose-dependent effects on Chk2, Chk1 and downstream effector Wee1, with lurbinectedin increasing intracellular levels of pChk1 and pChk2, while co-treatment with prexasertib deregulates this process across multiple human-derived cell lines. Synergistic killing was associated with elevated gamma-H2AX levels indicative of DNA double strand breaks and PARP-cleavage due to apoptotic caspase activation. Despite some heterogeneity among treated SCLC cells, the increased phosphorylation of Chk1 was noted at several kinase-activating sites including Serine 296, 317, and 345 while Chk2 Tyrosine 68 phosphorylation was consistently upregulated by lurbinectedin. The results provide a preclinical mechanistic rationale for overcoming a pro-survival, drug resistance-promoting checkpoint pathway to enhance the unique efficacy of single-agent lurbinectedin in patients with SCLC.","rel_num_authors":12,"rel_authors":[{"author_name":"Ashley F. Sanchez Sevilla Uruchurtu","author_inst":"Brown University"},{"author_name":"Audrey Y. Su","author_inst":"Brown University"},{"author_name":"Harshita Ganga","author_inst":"Penn State University"},{"author_name":"Shengliang Zhang","author_inst":"Brown University"},{"author_name":"Ameen Raissi","author_inst":"Johns Hopkins University"},{"author_name":"Kevin Kwon","author_inst":"Brown University"},{"author_name":"Tej Tummala","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Tyler Roady","author_inst":"Brown University"},{"author_name":"Jacqueline Moreno","author_inst":"University of Central Florida"},{"author_name":"Patrycja M Dubielecka-Szczerba","author_inst":"Brown University"},{"author_name":"Christopher G. Azzoli","author_inst":"Brown University"},{"author_name":"Wafik S. El-Deiry","author_inst":"Brown University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Longitudinal single cell RNA-sequencing of Pik3caH1047R-driven mammary tumorigenesis reveals coordinated transformation of epithelial and fibroblast transcriptional states","rel_doi":"10.64898\/2026.08.01.742267","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.01.742267","rel_abs":"Breast cancer is a heterogeneous disease in which a single oncogenic driver can give rise to divergent tumor phenotypes. How oncogenic mutations generate epithelial state plasticity and coordinately remodel the surrounding tissue remains incompletely understood. Here, we applied longitudinal single cell RNA-sequencing to trace the mammary landscape during Pik3caH1047R-driven tumor progression in the mouse. We identify an expansion of the epithelial transcriptional state space, in which luminal cells lose lineage fidelity and activate ciliated, basal, and squamous-like gene expression programs. While oncogene-expressing cells lose features of luminal identity, they retain expression of hormone-sensing genes such as Esr1, Pgr, and Foxa1. These transcriptional states are established early, and the transition to overt tumors is marked by the emergence of cancer-associated fibroblasts rather than new epithelial states. We identify a Postn+ fibroblast population enriched at the epithelial interface as a candidate progenitor of cancer-associated fibroblasts. Postn+ fibroblasts express an ECM-remodeling program and display altered epithelial crosstalk in oncogenic glands. Altogether, Pik3caH1047R activation initiates a tissue-level process beginning with epithelial lineage infidelity, followed by an altered stromal microenvironment, which together mark tumor initiation.","rel_num_authors":9,"rel_authors":[{"author_name":"Jennifer T Le","author_inst":"University of California, San Francisco"},{"author_name":"Eun K Kim","author_inst":"University of California, San Francisco"},{"author_name":"Vasudha T Srivastava","author_inst":"University of California San Francisco"},{"author_name":"Rachel Nakagawa","author_inst":"Genentech, Inc."},{"author_name":"Kiet T Phong","author_inst":"Max Planck Institute for Molecular Biomedicine"},{"author_name":"Gabriela Childree","author_inst":"University of California, San Francisco"},{"author_name":"Brittany A Moser","author_inst":"University of California, San Francisco"},{"author_name":"Andrei Goga","author_inst":"University of California, San Francisco"},{"author_name":"Zev J Gartner","author_inst":"University of California, San Francisco"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Longitudinal single cell RNA-sequencing of Pik3caH1047R-driven mammary tumorigenesis reveals coordinated transformation of epithelial and fibroblast transcriptional states","rel_doi":"10.64898\/2026.08.01.742267","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.01.742267","rel_abs":"Breast cancer is a heterogeneous disease in which a single oncogenic driver can give rise to divergent tumor phenotypes. How oncogenic mutations generate epithelial state plasticity and coordinately remodel the surrounding tissue remains incompletely understood. Here, we applied longitudinal single cell RNA-sequencing to trace the mammary landscape during Pik3caH1047R-driven tumor progression in the mouse. We identify an expansion of the epithelial transcriptional state space, in which luminal cells lose lineage fidelity and activate ciliated, basal, and squamous-like gene expression programs. While oncogene-expressing cells lose features of luminal identity, they retain expression of hormone-sensing genes such as Esr1, Pgr, and Foxa1. These transcriptional states are established early, and the transition to overt tumors is marked by the emergence of cancer-associated fibroblasts rather than new epithelial states. We identify a Postn+ fibroblast population enriched at the epithelial interface as a candidate progenitor of cancer-associated fibroblasts. Postn+ fibroblasts express an ECM-remodeling program and display altered epithelial crosstalk in oncogenic glands. Altogether, Pik3caH1047R activation initiates a tissue-level process beginning with epithelial lineage infidelity, followed by an altered stromal microenvironment, which together mark tumor initiation.","rel_num_authors":9,"rel_authors":[{"author_name":"Jennifer T Le","author_inst":"University of California, San Francisco"},{"author_name":"Eun K Kim","author_inst":"University of California, San Francisco"},{"author_name":"Vasudha T Srivastava","author_inst":"University of California San Francisco"},{"author_name":"Rachel Nakagawa","author_inst":"Genentech, Inc."},{"author_name":"Kiet T Phong","author_inst":"Max Planck Institute for Molecular Biomedicine"},{"author_name":"Gabriela Childree","author_inst":"University of California, San Francisco"},{"author_name":"Brittany A Moser","author_inst":"University of California, San Francisco"},{"author_name":"Andrei Goga","author_inst":"University of California, San Francisco"},{"author_name":"Zev J Gartner","author_inst":"University of California, San Francisco"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Identifying and engineering the molecular origins of lignin color for predictive staining of plant tissues.","rel_doi":"10.64898\/2026.08.03.742431","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742431","rel_abs":"Lignins in plant biomass are carbon-negative aromatic biopolymers which hold tremendous potential as multipurpose resources for sustainable bioeconomy, limited only by their chemical heterogeneity. Plant lignified tissues, such as sapwood and seed coats, vary in colors within and between species, indicating that specific lignin topochemistries determine the different colors. Yet, the responsible lignin chromogen(s) are unknown. We developed chemical imaging using UV-Vis microspectroscopy to link lignin color to topochemistry in isolates and plant samples. Using synthetic and technical lignins, we identified the different stable chromogens as homomeric lignin substructures varying in size, unit chemistry and interunit linkages. We controlled the accumulation of specific lignin chromogens using genetic engineering to similarly stain lignified tissues from different plant species. We established plant tissue engineering to cast plant tissues with pre-determined color by adjusting lignin topochemistries. We proved that biotechnological manipulation of the identified lignin chromogens predictably and stably stains lignified plant tissues.","rel_num_authors":9,"rel_authors":[{"author_name":"Andr\u00e9 G\u00fcndel","author_inst":"Stockholm University, Department of Ecology, Environment and Plant Science"},{"author_name":"Delphine M\u00e9nard","author_inst":"Stockholm University, Department of Ecology, Environment and Plant Science"},{"author_name":"Marije Nillessen","author_inst":"Stockholm University, Department of Ecology, Environment and Plant Science"},{"author_name":"Antoine Champagne","author_inst":"Stockholm University, Department of Ecology, Environment and Plant Science"},{"author_name":"Leonidas Matsakas","author_inst":"Lule\u00e5 University of Technology, Department of Civil, Environmental and Natural Resources Engineering"},{"author_name":"Mika H. Sipponen","author_inst":"Stockholm University, Department of Chemistry \/ Wallenberg Wood Science Center \/ Center for Circular and Sustainable Systems"},{"author_name":"Scott E. Sattler","author_inst":"United States Department of Agriculture - Agriculture Research Department (USDA-ARS)"},{"author_name":"Shinya Kajita","author_inst":"Tokyo University of Agriculture and Technology, Graduate School of Bio-Applications and Systems Engineering"},{"author_name":"Edouard Pesquet","author_inst":"Stockholm University, Department of Ecology, Environment and Plant Science \/ Bolin Center of Climate Research \/ Center for Circular and Sustainable Systems \/ Sc"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Microtubule Lattice Spacing Governs MAP-Motor Regulation","rel_doi":"10.64898\/2026.08.03.742653","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742653","rel_abs":"Microtubules (MTs) serve as intracellular tracks that enable molecular motors to transport cargos to specific cellular destinations. It has been proposed that the signals directing motor-driven transport are encoded on MTs through different isotypes, lattice conformations, and post-translational modifications (PTMs) of tubulin, or MT-associated proteins (MAPs) that decorate the MT surface. However, molecular predictions of these models have not been rigorously tested in vitro. Using isotypically pure recombinant tubulin and biochemical reconstitution, we examined how tubulin PTMs and MT lattice spacing influence MAP binding and kinesin-1 motility. We found that kinesin-1 is largely insensitive to tubulin PTMs but is strongly regulated by MT lattice spacing. Likewise, the MAPs tau, MAP7, MAP4, DCX, and MAP9 exhibit little sensitivity to tubulin PTMs, whereas the MT-binding affinities of tau, DCX, and MAP7 depend on lattice spacing. In the presence of activating (MAP7) and inhibitory (tau) MAPs, lattice spacing determines MAP occupancy and thereby controls kinesin-1 motility. These findings support a two-layer transport code in which MT lattice spacing directs MAP binding, and MAPs determine which motors can move along individual MT tracks.","rel_num_authors":8,"rel_authors":[{"author_name":"Jonathan Fernandes","author_inst":"UC Berkeley"},{"author_name":"Joseph Slivka","author_inst":"UC Berkeley"},{"author_name":"Aryan Taheri","author_inst":"UC Berkeley"},{"author_name":"Qikai Zhang","author_inst":"UC Berkeley"},{"author_name":"Viola Zhao","author_inst":"UC Berkeley"},{"author_name":"Chuzida Chen","author_inst":"UC Berkeley"},{"author_name":"Parnika Kant","author_inst":"UC Berkeley"},{"author_name":"Ahmet Yildiz","author_inst":"University of California Berkeley"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Microtubule Lattice Spacing Governs MAP-Motor Regulation","rel_doi":"10.64898\/2026.08.03.742653","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742653","rel_abs":"Microtubules (MTs) serve as intracellular tracks that enable molecular motors to transport cargos to specific cellular destinations. It has been proposed that the signals directing motor-driven transport are encoded on MTs through different isotypes, lattice conformations, and post-translational modifications (PTMs) of tubulin, or MT-associated proteins (MAPs) that decorate the MT surface. However, molecular predictions of these models have not been rigorously tested in vitro. Using isotypically pure recombinant tubulin and biochemical reconstitution, we examined how tubulin PTMs and MT lattice spacing influence MAP binding and kinesin-1 motility. We found that kinesin-1 is largely insensitive to tubulin PTMs but is strongly regulated by MT lattice spacing. Likewise, the MAPs tau, MAP7, MAP4, DCX, and MAP9 exhibit little sensitivity to tubulin PTMs, whereas the MT-binding affinities of tau, DCX, and MAP7 depend on lattice spacing. In the presence of activating (MAP7) and inhibitory (tau) MAPs, lattice spacing determines MAP occupancy and thereby controls kinesin-1 motility. These findings support a two-layer transport code in which MT lattice spacing directs MAP binding, and MAPs determine which motors can move along individual MT tracks.","rel_num_authors":8,"rel_authors":[{"author_name":"Jonathan Fernandes","author_inst":"UC Berkeley"},{"author_name":"Joseph Slivka","author_inst":"UC Berkeley"},{"author_name":"Aryan Taheri","author_inst":"UC Berkeley"},{"author_name":"Qikai Zhang","author_inst":"UC Berkeley"},{"author_name":"Viola Zhao","author_inst":"UC Berkeley"},{"author_name":"Chuzida Chen","author_inst":"UC Berkeley"},{"author_name":"Parnika Kant","author_inst":"UC Berkeley"},{"author_name":"Ahmet Yildiz","author_inst":"University of California Berkeley"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Humanized Anti-PD-1 Antibodies Generated Using The Conditional Kernel-Elastic Autoencoder","rel_doi":"10.64898\/2026.08.03.742579","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742579","rel_abs":"The human immune system excels at generating highly effective antibodies through natural selection and somatic hypermutation, but adapting these antibodies for therapeutic use, referred to as \"antibody medicine-likeness\", requires careful consideration of biochemical and physiological properties. Traditional redesign methods are often slow and limited in scope. In this study, we introduce a machine learning-based approach to evolve new anti-PD-1 antibodies within a chemically informed latent space using a conditional kernel-elastic autoencoder (CKEA) between nivolumab and pembrolizumab, both of which bind the FG-loop \"hotspot\" of PD-1 in the most distantly related orientations, differing by 174 degrees. This generative framework is designed to preserve favorable therapeutic features while exploring variants with different potency, ultimately for improved potency. To evaluate structural and functional viability, we performed molecular dynamics (MD) simulations of the generated antibody - PD-1 complexes and described their MD properties. These simulations reveal detailed free-energy landscapes and identify stable binding conformations, providing a strong basis for experimental validation. To validate our designs, we expressed and experimentally tested the antibodies for binding affinity to PD-1. Upon expression and purification, three out of six designed antibodies exhibited some binding to PD-1, whose properties could likely be improved using other computational saturation mutagenesis or laboratory evolution. Our results demonstrate the potential of artificial intelligence (AI)-guided interpolation methods to generate novel, high-affinity antibodies with therapeutic promise, offering a powerful strategy for next-generation antibody development.","rel_num_authors":7,"rel_authors":[{"author_name":"Yuanjun Shi","author_inst":"Yale University"},{"author_name":"Haote Li","author_inst":"Yale University"},{"author_name":"Pulan Liu","author_inst":"Yale University"},{"author_name":"Christopher Gerard Bunick","author_inst":"Yale University"},{"author_name":"Shaogeng Tang","author_inst":"Yale University"},{"author_name":"Jimin Wang","author_inst":"Yale University"},{"author_name":"Victor S Batista","author_inst":"Yale University"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Improved cross-presentation enabled by fusion-dependent mini-proteins that efficiently reach the dendritic cell cytosol","rel_doi":"10.64898\/2026.08.01.742242","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.01.742242","rel_abs":"Cross-presentation is the process by which dendritic cells communicate to CD8+ T-cells the detection of exogenous foreign substances known as antigens. This process primes naive CD8+ T-cells to eradicate antigen-expressing pathogens and tumors. It is CD8+ T-cell immunity by reducing well known that pathogens and tumors evade antigen uptake into the endocytic pathway and\/or limiting endosomal escape of the antigen to the cytosol. Here we employ biophysical and cell biology tools to separately and quantitatively probe the efficiency of antigen uptake, internalization, display, and activity in the context of both model and tumor-derived antigens. We show that substantive improvements in cytosolic antigen delivery provided by the fusion-dependent mini-protein ZF5.3 result in concomitant improvements in MHC-I-mediated antigen presentation and B3Z T-cell activation. The insights provided by the stepwise assessment and improvement of cross-presentation efficiency could improve the design of peptide vaccines for immunotherapy.","rel_num_authors":3,"rel_authors":[{"author_name":"Teresia Chen","author_inst":"UC Berkeley"},{"author_name":"Michel DuPage","author_inst":"University of California, Berkeley"},{"author_name":"Alanna Schepartz","author_inst":"UC Berkeley"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Phylogenetic conservation of bacterial environmental responses predicts soil bacterial biogeographic patterns","rel_doi":"10.64898\/2026.08.03.742428","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742428","rel_abs":"Soil bacterial communities exhibit biogeographic patterns along environmental gradients, yet why some environmental factors contribute more strongly to community turnover than others remains poorly understood. Here, we tested whether this variation can be explained by the phylogenetic depth at which bacterial responses to each environmental factor are conserved. Across 40 forest sites in Japan spanning multiple soil and climatic gradients, environmental factors whose bacterial responses were conserved at deeper phylogenetic levels contributed more strongly to bacterial community turnover. We further asked whether phylogenetic clades that share similar environmental responses represent ecologically meaningful units for understanding bacterial community responses. Using soil pH as a focal test case, we found that response-defined clades improved prediction of taxon-level abundance shifts and community-level compositional shifts compared with models that treated taxa as independent units. Together, these findings show that the phylogenetic depth of bacterial environmental responses links trait conservation, community turnover and soil bacterial biogeographic patterns.","rel_num_authors":3,"rel_authors":[{"author_name":"Mingming Xia","author_inst":"Peking University"},{"author_name":"Kazuo Isobe","author_inst":"Peking University"},{"author_name":"Jennifer B.H. Martiny","author_inst":"University of California - Irvine"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Physics-Guided Neural Reconstruction of Cellular Membranes for 3D Electron Microscopy","rel_doi":"10.64898\/2026.08.01.742159","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.01.742159","rel_abs":"With advances in three-dimensional electron microscopy modalities, quantitative characterization of membrane ultrastructure has emerged as an approach to interrogate how organization of proteins and other components around the membrane drive structure and function. Hindering these efforts, the confident reconstruction of geometric features such as membrane curvature is challenging since it requires the calculation of higher-order derivatives from discrete membrane representations. Modern advances in using neural networks to learn continuous implicit representations of complex shapes present a promising solution to this problem. This work presents a physics-informed neural network framework for reconstructing membrane geometries to curvature-order accuracy from images using an implicit neural representation. Benchmarking using synthetic data illustrates that physics-based regularization during training improves accuracy of recovered curvatures, improving robustness to image noise. Application to experimental datasets demonstrate that the framework generalizes to complex cellular structure, such as the Golgi apparatus and mitochondria. We further perform three-dimensional curvature analysis of endocytic pits in cells to reveal anisotropic curvatures at the pit neck, previously predicted to be a lower-energy pathway for neck constriction. This work provides a unified framework for reconstructing three-dimensional membrane shape, including curvature, from volumetric imaging data. By capturing membrane geometry more accurately, our approach yields mechanical insights that can be linked to molecular-scale interactions.","rel_num_authors":4,"rel_authors":[{"author_name":"Atsushi Matsuda","author_inst":"University of Washington"},{"author_name":"Se Min Kim","author_inst":"University of Washington"},{"author_name":"Mathew Akamatsu","author_inst":"University of Washington"},{"author_name":"Christopher T Lee","author_inst":"University of California San Diego"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Automated inference of respiratory and syringeal biomechanical trajectories from birdsong acoustics","rel_doi":"10.64898\/2026.08.03.742634","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.03.742634","rel_abs":"Songbirds, in particular zebra finches (Taeniopygia guttata), provide a powerful model for investigating the neural mechanisms of learned vocal behavior. Researchers typically rely on the acoustic structure of birdsong to quantify vocal behavior. As a more direct measure of motor control, we present VIBE: Vocal acoustic Inversion to Biomechanical Estimates, an open-source pipeline that recovers the biomechanical control parameters of song production directly from the acoustic waveform. Biomechanical models of the songbird syrinx describe vocal production with two continuously varying parameters:  and {beta}, representing subsyringeal air sac pressure and syringeal muscle tension, respectively. Recovering these parameters from song acoustics provides a motor-based coordinate system against which neural activity or other dependent variables can be directly compared. Because  and {beta} are the coupled control parameters of a nonlinear oscillator, their joint recovery is non-trivial. VIBE addresses this through iterative optimization of the governing normal-form equations. We validate VIBE against recorded air sac pressure across 44 songs from twelve birds, showing that the recovered  corresponds to empirically measured air sac pressure. Pairing VIBE with Neuropixels recordings from RA in five birds, we find that RA activity is well predicted by the recovered parameters, and that  and {beta} add predictive power beyond the acoustic features of song. By recovering biomechanical control parameters from the acoustic signal, VIBE makes the biomechanical coordinate system of song production accessible to the broader songbird research community.","rel_num_authors":5,"rel_authors":[{"author_name":"Lauren M Ostrowski","author_inst":"University of California San Diego"},{"author_name":"Jorge M M\u00e9ndez","author_inst":"Minnesota State University-Mankato"},{"author_name":"Pablo Tostado-Marcos","author_inst":"University of California San Diego"},{"author_name":"Brenton G Cooper","author_inst":"Texas Christian University"},{"author_name":"Timothy Q Gentner","author_inst":"University of California San Diego"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"TRIM9 Determines Sex-Specific \u03b2-Amyloid\/Cellular Prion Protein\/mGluR5 Complex Formation and Pathological Signaling in Alzheimer's Disease Mice","rel_doi":"10.64898\/2026.07.30.741783","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.30.741783","rel_abs":"Biological sex is a major determinant of Alzheimer's disease prevalence, yet the molecular mechanisms underlying sex-specific vulnerability remain largely unknown. Metabotropic glutamate receptor 5 (mGluR5) functions as a co-receptor for {beta}-amyloid (A{beta}42) oligomer\/cellular prion protein (PrPC)-mediated pathogenic signaling in males but not females, establishing a sex-dimorphic node in {beta}-amyloid pathophysiology whose regulatory basis is undefined. Using quantitative proteomic analysis, we identify the E3 ubiquitin ligase TRIM9 as a novel mGluR5-interacting protein and a previously unrecognized sex-specific regulator of the A{beta}42\/PrPC\/mGluR5 complex. TRIM9 selectively associates with mGluR5 in male but not female APP\/PS1 mouse brain and is required for mGluR5 to serve as a co-receptor for PrPC-dependent A{beta}42 oligomer binding. Genetic deletion of TRIM9 abolishes A{beta}42\/PrPC\/mGluR5 complex assembly in male APP\/PS1 mice demonstrating that TRIM9 is an essential scaffold for male-specific A{beta}42 signal transduction. Loss of TRIM9 in males further reduces {beta}-amyloid pathology by restoring Akt\/GSK3{beta}\/ZBTB16-dependent autophagic flux, linking disruption of this complex to a defined downstream proteostatic mechanism. Together, these findings establish TRIM9 as a critical molecular determinant coupling male-specific A{beta}42\/PrPC\/mGluR5 complex assembly to downstream neurodegenerative signaling and {beta}-amyloid pathology. They reveal an unappreciated layer of sex-dependent complexity in mGluR5 pharmacology and identify disruption of the TRIM9\/mGluR5 interaction as a potential male-specific therapeutic strategy for Alzheimer's disease.","rel_num_authors":10,"rel_authors":[{"author_name":"Fatemeh Babaei","author_inst":"University of Ottawa"},{"author_name":"Fatemeh Panahi Arasi","author_inst":"University of Ottawa"},{"author_name":"Tash-Lynn L Colson","author_inst":"University of Ottawa"},{"author_name":"Hang Cheng","author_inst":"University of Ottawa"},{"author_name":"Mario Tiberi","author_inst":"Ottawa Hospital Research Institute"},{"author_name":"Rony Chidiac","author_inst":"University of Sherbrooke"},{"author_name":"Stephane Angers","author_inst":"University of Toronto"},{"author_name":"Stephanie L Gupton","author_inst":"University of North Carolina at Chapel Hill"},{"author_name":"Khaled S. Abd-Elrahman","author_inst":"University of British Columbia"},{"author_name":"Stephen S. G. Ferguson","author_inst":"University of Ottawa"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"TRIM9 Determines Sex-Specific \u03b2-Amyloid\/Cellular Prion Protein\/mGluR5 Complex Formation and Pathological Signaling in Alzheimer's Disease Mice","rel_doi":"10.64898\/2026.07.30.741783","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.30.741783","rel_abs":"Biological sex is a major determinant of Alzheimer's disease prevalence, yet the molecular mechanisms underlying sex-specific vulnerability remain largely unknown. Metabotropic glutamate receptor 5 (mGluR5) functions as a co-receptor for {beta}-amyloid (A{beta}42) oligomer\/cellular prion protein (PrPC)-mediated pathogenic signaling in males but not females, establishing a sex-dimorphic node in {beta}-amyloid pathophysiology whose regulatory basis is undefined. Using quantitative proteomic analysis, we identify the E3 ubiquitin ligase TRIM9 as a novel mGluR5-interacting protein and a previously unrecognized sex-specific regulator of the A{beta}42\/PrPC\/mGluR5 complex. TRIM9 selectively associates with mGluR5 in male but not female APP\/PS1 mouse brain and is required for mGluR5 to serve as a co-receptor for PrPC-dependent A{beta}42 oligomer binding. Genetic deletion of TRIM9 abolishes A{beta}42\/PrPC\/mGluR5 complex assembly in male APP\/PS1 mice demonstrating that TRIM9 is an essential scaffold for male-specific A{beta}42 signal transduction. Loss of TRIM9 in males further reduces {beta}-amyloid pathology by restoring Akt\/GSK3{beta}\/ZBTB16-dependent autophagic flux, linking disruption of this complex to a defined downstream proteostatic mechanism. Together, these findings establish TRIM9 as a critical molecular determinant coupling male-specific A{beta}42\/PrPC\/mGluR5 complex assembly to downstream neurodegenerative signaling and {beta}-amyloid pathology. They reveal an unappreciated layer of sex-dependent complexity in mGluR5 pharmacology and identify disruption of the TRIM9\/mGluR5 interaction as a potential male-specific therapeutic strategy for Alzheimer's disease.","rel_num_authors":10,"rel_authors":[{"author_name":"Fatemeh Babaei","author_inst":"University of Ottawa"},{"author_name":"Fatemeh Panahi Arasi","author_inst":"University of Ottawa"},{"author_name":"Tash-Lynn L Colson","author_inst":"University of Ottawa"},{"author_name":"Hang Cheng","author_inst":"University of Ottawa"},{"author_name":"Mario Tiberi","author_inst":"Ottawa Hospital Research Institute"},{"author_name":"Rony Chidiac","author_inst":"University of Sherbrooke"},{"author_name":"Stephane Angers","author_inst":"University of Toronto"},{"author_name":"Stephanie L Gupton","author_inst":"University of North Carolina at Chapel Hill"},{"author_name":"Khaled S. Abd-Elrahman","author_inst":"University of British Columbia"},{"author_name":"Stephen S. G. Ferguson","author_inst":"University of Ottawa"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"EOLA1 functions in nucleotide salvage through deacetylating free N4-acetylcytidine","rel_doi":"10.64898\/2026.08.01.741249","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.01.741249","rel_abs":"RNA-based medicines rely on modified nucleotides to promote immune evasion and in vivo efficacy. Nucleotides generated from RNA degradation are either exported or recycled through metabolically favorable salvage pathways, though whether modified nucleotides are efficiently recycled remains unclear. N4-acetylcytidine (acC) is a naturally occurring modification in rRNA and tRNA that has shown promise in therapeutic mRNA applications. However, N4-acetylation impairs cytidine deamination, the first step in cytidine salvage. Here, we investigate the endogenous mechanisms that enable acC metabolism. Through sensitive sequence and structural analyses, we identify the uncharacterized human ASCH domain protein EOLA1 as a key acC deacetylase in nucleotide salvage. EOLA1 inactivation leads to free intracellular acC accumulation and increased cytotoxicity upon nucleotide export inhibition. While steady-state acC levels in cellular RNAs remain unchanged, EOLA1-dependent regulation of free acC is evident basally and is exacerbated by exogenous mRNA delivery. Proteomic analyses place EOLA1 in proximity to ribosomal proteins, adjacent to endogenous acC sources. In vitro assays confirm EOLA1 specificity for acC, and structural analysis reveals a narrow nucleotide-binding pocket consistent with mononucleotide selectivity. These findings identify EOLA1 as a bona fide acC eraser and uncover a previously unrecognized pathway for recycling modified nucleotides with relevance to therapeutic RNA design.","rel_num_authors":10,"rel_authors":[{"author_name":"Shalini Oberdoerffer","author_inst":"National Cancer Institute"},{"author_name":"Sebastien Relier","author_inst":"National Institutes of Health"},{"author_name":"Sarah Schiffers","author_inst":"National Institutes of Health"},{"author_name":"Hamid Beiki","author_inst":"National Institutes of Health"},{"author_name":"Maria Prigge","author_inst":"National Institutes of Health"},{"author_name":"Nishu Tyagi","author_inst":"National Institutes of Health"},{"author_name":"Cyrinne Achour","author_inst":"National Institutes of Health"},{"author_name":"Ayush Raman","author_inst":"National Institutes of Health"},{"author_name":"A. Maxwell Burroughs","author_inst":"National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health"},{"author_name":"L. Aravind","author_inst":"National Center of Biotechnology Information"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Inflammatory Fibroblasts Promote Repair After Injury Through Epithelial Proliferation","rel_doi":"10.64898\/2026.08.02.742235","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.742235","rel_abs":"Fibroblast heterogeneity after lung injury is a well observed phenomenon made highly relevant by the widespread application of single cell RNA-sequencing. The characterization of homeostatic and injury associated states has led to the identification of a population of fibroblasts that emerge during inflammation and express cytokines that may potentially amplify the inflammatory circuit. However, whether these cells actively contribute to inflammation or serve an alternative function within the broader injury-repair cascade remains unclear. By integrating several robust murine lung injury data sets we establish the persistence of the inflammatory fibroblast across multiple injury models and identify a role for these cells in lung repair after injury through effects on alveolar epithelial proliferation. We validate this observation in-vivo using a genetic model of spontaneous lung fibrosis and in-vitro with mixed alveolar organoid cultures of various homeostatic and injury associated fibroblasts wherein we identify a mesenchymal-epithelial BMP signaling axis as a key driver of the AT2 cell injury repair response. Finally, we present supporting evidence from human disease, reinforcing the relevance of this fibroblast subset in pathological settings. These findings extend critical observations made prior to the single-cell era and contribute to our evolving understanding of fibroblast heterogeneity as a key feature of lung repair.","rel_num_authors":16,"rel_authors":[{"author_name":"Luis R Rodriguez","author_inst":"The George Washington University"},{"author_name":"Willy Roque Barboza","author_inst":"University of Pennsylvania"},{"author_name":"Aditi Murthy","author_inst":"University of Pennsylvania"},{"author_name":"Niran Hadad","author_inst":"Translational Genomics Research Institute"},{"author_name":"Sarah Bui","author_inst":"University of Pennsylvania"},{"author_name":"Dakota L Jones","author_inst":"University of Iowa"},{"author_name":"Yaniv Tomer","author_inst":"University of Pennsylvania"},{"author_name":"Charlotte H Cooper","author_inst":"University of Pennsylvania"},{"author_name":"Ana Reineberg","author_inst":"University of Pennsylvania"},{"author_name":"Rea Chroneos","author_inst":"University of Pennsylvania"},{"author_name":"Evan T Hoffman","author_inst":"University of Pennsylvania"},{"author_name":"Srafel Mulugeta","author_inst":"University of Pennsylvania"},{"author_name":"Jeremy Katzen","author_inst":"University of Pennsylvania"},{"author_name":"Jonathan A Kropski","author_inst":"Vanderbilt University"},{"author_name":"Nicholas E Banovich","author_inst":"Translational Genomics Research Institute"},{"author_name":"Michael F Beers","author_inst":"University of Pennsylvania"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"Inflammatory Fibroblasts Promote Repair After Injury Through Epithelial Proliferation","rel_doi":"10.64898\/2026.08.02.742235","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.08.02.742235","rel_abs":"Fibroblast heterogeneity after lung injury is a well observed phenomenon made highly relevant by the widespread application of single cell RNA-sequencing. The characterization of homeostatic and injury associated states has led to the identification of a population of fibroblasts that emerge during inflammation and express cytokines that may potentially amplify the inflammatory circuit. However, whether these cells actively contribute to inflammation or serve an alternative function within the broader injury-repair cascade remains unclear. By integrating several robust murine lung injury data sets we establish the persistence of the inflammatory fibroblast across multiple injury models and identify a role for these cells in lung repair after injury through effects on alveolar epithelial proliferation. We validate this observation in-vivo using a genetic model of spontaneous lung fibrosis and in-vitro with mixed alveolar organoid cultures of various homeostatic and injury associated fibroblasts wherein we identify a mesenchymal-epithelial BMP signaling axis as a key driver of the AT2 cell injury repair response. Finally, we present supporting evidence from human disease, reinforcing the relevance of this fibroblast subset in pathological settings. These findings extend critical observations made prior to the single-cell era and contribute to our evolving understanding of fibroblast heterogeneity as a key feature of lung repair.","rel_num_authors":16,"rel_authors":[{"author_name":"Luis R Rodriguez","author_inst":"The George Washington University"},{"author_name":"Willy Roque Barboza","author_inst":"University of Pennsylvania"},{"author_name":"Aditi Murthy","author_inst":"University of Pennsylvania"},{"author_name":"Niran Hadad","author_inst":"Translational Genomics Research Institute"},{"author_name":"Sarah Bui","author_inst":"University of Pennsylvania"},{"author_name":"Dakota L Jones","author_inst":"University of Iowa"},{"author_name":"Yaniv Tomer","author_inst":"University of Pennsylvania"},{"author_name":"Charlotte H Cooper","author_inst":"University of Pennsylvania"},{"author_name":"Ana Reineberg","author_inst":"University of Pennsylvania"},{"author_name":"Rea Chroneos","author_inst":"University of Pennsylvania"},{"author_name":"Evan T Hoffman","author_inst":"University of Pennsylvania"},{"author_name":"Srafel Mulugeta","author_inst":"University of Pennsylvania"},{"author_name":"Jeremy Katzen","author_inst":"University of Pennsylvania"},{"author_name":"Jonathan A Kropski","author_inst":"Vanderbilt University"},{"author_name":"Nicholas E Banovich","author_inst":"Translational Genomics Research Institute"},{"author_name":"Michael F Beers","author_inst":"University of Pennsylvania"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"The Fontan EV Score: A Circulating Extracellular Vesicle-Based Risk Stratification Tool for Fontan-Associated Liver Disease","rel_doi":"10.64898\/2026.07.31.742169","rel_link":"http:\/\/biorxiv.org\/content\/10.64898\/2026.07.31.742169","rel_abs":"Background: Fontan-associated liver disease (FALD) is a universal complication of the Fontan palliation characterized by chronic congestion and progressive hepatic fibrosis. Current diagnostics rely on invasive biopsies or non-specific biomarkers that fail to capture early fibrogenesis, creating a need for non-invasive biomarkers to stratify disease severity. Methods: We utilized an ovine Fontan model (n = 19) to investigate circulating serum extracellular vesicles (sEVs) as reporters of hepatic pathology. Longitudinal samples paired with liver elastography were collected, and sEVs were subjected to multi-omic profiling including small RNA sequencing and proteomics. Regularized regression was used to identify transcriptomic predictors, which were integrated with time post-surgery into an ordinal logistic regression framework to construct the Fontan EV Score (FES). Model performance was evaluated on a held-out test cohort and benchmarked against established fibrosis indices. To validate the biological relevance of the FES , TGF-{beta}-treated human liver organoids were generated and scored miRNA expression was assessed. Results: The sEV proteome exhibited robust separation by surgical physiology, while the small RNA cargo was primarily stratified by fibrotic status. Bioinformatics confirmed a high hepatic origin for these transcripts and identified enrichment of inflammatory pathways including Toll-like receptor and Interleukin-17 cascades in fibrotic subjects. The FES, incorporating time post-surgery and eleven small RNA biomarkers, demonstrated high predictive accuracy in the independent testing cohort with an AUC of 0.876 for moderate and 0.963 for severe fibrosis, substantially outperforming APRI (AUC = 0.618) and FIB-4 (AUC = 0.731). In human liver organoids, several scoring miRNAs, including miR-125a-5p and miR-193b-5p, were directionally responsive to profibrotic stimulation. Conclusions: Circulating sEVs carry a liver-associated cargo that can be leveraged for the non-invasive prediction of FALD severity. The FES provides a biologically validated scoring system that substantially outperforms existing serological indices and offers a new avenue for early detection and risk stratification of FALD.","rel_num_authors":21,"rel_authors":[{"author_name":"Felipe Takaesu","author_inst":"Emory University"},{"author_name":"Xinlei Li","author_inst":"Nationwide Children's Hospital"},{"author_name":"Jennifer Kievert","author_inst":"Nationwide Children's Hospital"},{"author_name":"Ashley Zhou","author_inst":"Emory University Emory College of Arts and Sciences"},{"author_name":"Sherri Kemper","author_inst":"Nationwide Children's Hospital"},{"author_name":"Satoshi Yuhara","author_inst":"Nationwide Children's Hospital"},{"author_name":"Syed Hussain","author_inst":"Nationwide Children's Hospital"},{"author_name":"Tatsuya Watanabe","author_inst":"Nationwide Children's Hospital"},{"author_name":"Junya Matsuda","author_inst":"Nationwide Children's Hospital"},{"author_name":"Fahd Taha","author_inst":"Nationwide Children's Hospital"},{"author_name":"Adrienne Morrison","author_inst":"Nationwide Children's Hospital"},{"author_name":"Kirsten Nelson","author_inst":"Nationwide Children's Hospital"},{"author_name":"Jocelyhnn Zucco","author_inst":"Nationwide Children's Hospital"},{"author_name":"Aymen Naguib","author_inst":"Nationwide Children's Hospital"},{"author_name":"Christopher McKee","author_inst":"Nationwide Children's Hospital"},{"author_name":"Jordan Hill","author_inst":"Nationwide Children's Hospital"},{"author_name":"Sergio A. Carrillo","author_inst":"Nationwide Children's Hospital"},{"author_name":"Christopher K Breuer","author_inst":"Nationwide Children's Hospital"},{"author_name":"John M. Kelly","author_inst":"The Research Institute at Nationwide Children's Hospital"},{"author_name":"David Brigstock","author_inst":"Nationwide Children's Hospital Medical Library"},{"author_name":"Michael Davis","author_inst":"Emory University School of Medicine"}],"rel_date":"2026-08-04","rel_site":"biorxiv"},{"rel_title":"VPM1002 for tuberculosis prevention in India: a 1,296-compartment dynamic model with disaggregated pulmonary and extrapulmonary efficacy, Bayesian evidence synthesis, and dual-perspective health economics","rel_doi":"10.64898\/2026.07.31.26359434","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359434","rel_abs":"Abstract Background Tuberculosis (TB) kills 1.3 million people annually. Global efforts focus on ending pulmonary TB (PTB); however, extrapulmonary TB (EPTB) is rising and poses significant health and economic burden. The PreVenTB Phase III trial evaluated VPM1002 in household contacts aged [&ge;]6 years across India, and did not meet its primary composite endpoint for all TB. Disaggregated prespecified secondary endpoints revealed a substantially stronger EPTB signal (vaccine efficacy 42.3%, 95% CI (-9.1 to 69.4, p=0.09) in the modified intention-to-treat (mITT) population. No existing TB model translates these disaggregated hazard ratios into population-level effectiveness across heterogeneous demographics, or against a dynamic baseline accounting for ongoing National Tuberculosis Elimination Programme (NTEP)-driven incidence decline. Methods We developed a 1,296-compartment deterministic dynamic compartmental model (4 age x 2 HIV x 3 BMI x 3 socioeconomic strata x 18 states). Separate PTB and EPTB vaccine-efficacy posteriors were derived by Bayesian evidence synthesis of the PreVenTB trial's per-protocol and mITT analyses (power-prior-adjusted conjugate normal-normal update; =0.082) and propagated through Monte Carlo simulation (n=1,000 iterations per scenario). A dynamic no-vaccine baseline was constructed by fitting time-varying case-detection-rate CDR(t) and treatment-success-rate TSR(t) logistic curves to WHO\/NTEP data (2015 to 2024; incidence validation R2=0.896, RMSE 4.90 per 100,000), projecting PTB and EPTB incidence to 2050. Economic analysis used societal (value-of-statistical-life-inclusive BCR) and health-system (cost-effectiveness acceptability curves) perspectives, discounted at 3% annually. Findings Posterior vaccine effectiveness was substantially higher against EPTB than PTB (EPTB 40.0% [95% CI -5.6 to 69.1%] vs PTB 12.8% [-19.0 to 37.9%]; all-TB 16.2% [-11.7 to 38.6%]). EPTB accounted for 74% of deaths averted (381 of 513) and 73% of DALYs averted (5,347 of 7,308) in the 10-year\/dynamic scenario. EPTB cases averted exceeded PTB and concurrent disease combined in every scenario. Mean cases averted ranged from 2,047 (3-year protection, dynamic baseline) to 3,394 (10-year, static) per 1,000,000 vaccinated; mean disability-adjusted life years (DALYs) averted ranged from 4,792 to 8,125. The benefit-cost ratio (BCR; societal perspective) ranged from 3.4 (3-year protection, dynamic baseline) to 8.2 (10-year protection, static baseline), exceeding break-even in every scenario. Median gross incremental cost-effectiveness ratio (ICER) ranged from US$647 (10-year static) to US$1,568 (3-year dynamic) per DALY averted, below India's 3x gross domestic product (GDP)-per-capita threshold (approximately US$8,084) in every scenario. Interpretation This 1,296-compartment model provides the first dynamically-baselined, dual-perspective health-economic evaluation of VPM1002 to separately track pulmonary and extrapulmonary outcomes. EPTB protection is VPM1002's proportionally larger and more statistically reliable efficacy signal and drives a majority of averted cases, mortality, and DALYs. Policy assessments anchored to composite pulmonary endpoints systematically underestimate this vaccine's population value. Funding In part funded by Serum Life Science Europe GmbH.","rel_num_authors":5,"rel_authors":[{"author_name":"M. Revathy","author_inst":"Narsee Monjee Institute of Management Studies, Bengaluru, India"},{"author_name":"Vidya Niranjan","author_inst":"MIT Vishwaprayag University, Solapur, Maharashtra, India"},{"author_name":"Varun Swaminathan","author_inst":"Aseesa Inc."},{"author_name":"Alessandro Carrese","author_inst":"Aseesa Inc."},{"author_name":"Aditi Bhargava","author_inst":"Aseesa Inc., and UCSF"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Effects of Social Prescribing on Mental, Physical, and Social Health Outcomes: A Systematic Review and Meta-Analysis of Randomised Trials","rel_doi":"10.64898\/2026.08.02.26359484","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359484","rel_abs":"Importance: Social prescribing is implemented to address unmet social needs and improve health, but expansion has outpaced evidence from randomized trials. Objective: To quantify the effects of social prescribing on mental, physical, and social health outcomes in adults. Data Sources: Medline, Embase, Cochrane Central, AMED, CINAHL, PsycInfo, Web of Science, NHS EED, CEA registry, clinicaltrials.gov, OpenGrey, and WHO ICTRP (English language). Trials published from 1992 through 2022 were identified from 23 reviews, supplemented by searches from January 2023 through September 2025. Study Selection: Randomized trials comparing usual care or waitlist with interventions facilitating connection to community-based resources delivered by non-health care professionals. Data Extraction and Synthesis: Pairs of reviewers screened studies, extracted data, and assessed risk of bias using Cochrane Risk of Bias 2. Random-effects meta-analyses pooled mean differences or standardized mean differences as Hedges g with 95% CIs. Main Outcomes and Measures: Mental health, blood pressure, metabolic and anthropometric outcomes, physical activity, loneliness and social isolation, quality of life, health care use, and adverse events. Results: Thirty-three randomized trials involving 13 714 participants were included. High risk of bias was identified in 40% of trials. Social prescribing was associated with reduced depressive symptoms (7 trials; 1087 participants; standardized mean difference [SMD], -0.23; 95% CI, -0.38 to -0.08), lower systolic blood pressure (11 trials; 2817 participants; mean difference, -2.69 mm Hg; 95% CI, -5.36 to -0.02), increased physical activity (7 trials; 3409 participants; SMD, 0.16; 95% CI, 0.06-0.25), and improved quality of life (10 trials; 3134 participants; SMD, 0.15; 95% CI, 0.01-0.29). No clear benefit was found for anxiety, loneliness and social isolation, glycemic control, blood lipids, anthropometric outcomes, or health care use. One trial reported a process evaluation, 7 included economic evaluations, and adverse events were infrequently reported. Conclusions and Relevance: Social prescribing was associated with modest improvements in depressive symptoms, systolic blood pressure, physical activity, and quality of life. Evidence was lacking for other claimed benefits, and process and economic evaluations were uncommon, identifying priorities for future trials.","rel_num_authors":8,"rel_authors":[{"author_name":"Xiaoqi Feng","author_inst":"UNSW"},{"author_name":"Raju Kanukula","author_inst":"University of Sydney"},{"author_name":"Nicole Evangelidis","author_inst":"University of Sydney"},{"author_name":"Bruce Neal","author_inst":"The George Institute for Global Health"},{"author_name":"Patricia Davidson","author_inst":"UNSW"},{"author_name":"Bogda Koczwara","author_inst":"UNSW"},{"author_name":"Kheng Hock Lee","author_inst":"SingHealth"},{"author_name":"Thomas Astell-Burt","author_inst":"University of Sydney"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Effects of Social Prescribing on Mental, Physical, and Social Health Outcomes: A Systematic Review and Meta-Analysis of Randomised Trials","rel_doi":"10.64898\/2026.08.02.26359484","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359484","rel_abs":"Importance: Social prescribing is implemented to address unmet social needs and improve health, but expansion has outpaced evidence from randomized trials. Objective: To quantify the effects of social prescribing on mental, physical, and social health outcomes in adults. Data Sources: Medline, Embase, Cochrane Central, AMED, CINAHL, PsycInfo, Web of Science, NHS EED, CEA registry, clinicaltrials.gov, OpenGrey, and WHO ICTRP (English language). Trials published from 1992 through 2022 were identified from 23 reviews, supplemented by searches from January 2023 through September 2025. Study Selection: Randomized trials comparing usual care or waitlist with interventions facilitating connection to community-based resources delivered by non-health care professionals. Data Extraction and Synthesis: Pairs of reviewers screened studies, extracted data, and assessed risk of bias using Cochrane Risk of Bias 2. Random-effects meta-analyses pooled mean differences or standardized mean differences as Hedges g with 95% CIs. Main Outcomes and Measures: Mental health, blood pressure, metabolic and anthropometric outcomes, physical activity, loneliness and social isolation, quality of life, health care use, and adverse events. Results: Thirty-three randomized trials involving 13 714 participants were included. High risk of bias was identified in 40% of trials. Social prescribing was associated with reduced depressive symptoms (7 trials; 1087 participants; standardized mean difference [SMD], -0.23; 95% CI, -0.38 to -0.08), lower systolic blood pressure (11 trials; 2817 participants; mean difference, -2.69 mm Hg; 95% CI, -5.36 to -0.02), increased physical activity (7 trials; 3409 participants; SMD, 0.16; 95% CI, 0.06-0.25), and improved quality of life (10 trials; 3134 participants; SMD, 0.15; 95% CI, 0.01-0.29). No clear benefit was found for anxiety, loneliness and social isolation, glycemic control, blood lipids, anthropometric outcomes, or health care use. One trial reported a process evaluation, 7 included economic evaluations, and adverse events were infrequently reported. Conclusions and Relevance: Social prescribing was associated with modest improvements in depressive symptoms, systolic blood pressure, physical activity, and quality of life. Evidence was lacking for other claimed benefits, and process and economic evaluations were uncommon, identifying priorities for future trials.","rel_num_authors":8,"rel_authors":[{"author_name":"Xiaoqi Feng","author_inst":"UNSW"},{"author_name":"Raju Kanukula","author_inst":"University of Sydney"},{"author_name":"Nicole Evangelidis","author_inst":"University of Sydney"},{"author_name":"Bruce Neal","author_inst":"The George Institute for Global Health"},{"author_name":"Patricia Davidson","author_inst":"UNSW"},{"author_name":"Bogda Koczwara","author_inst":"UNSW"},{"author_name":"Kheng Hock Lee","author_inst":"SingHealth"},{"author_name":"Thomas Astell-Burt","author_inst":"University of Sydney"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"An Integrative Multimodal Model for Early Diagnosis of Dementia and Differential Diagnosis of Alzheimer's Disease Using Neuroimaging, Polygenic Risk, and Cognitive Assessments","rel_doi":"10.64898\/2026.07.31.26359317","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359317","rel_abs":"Background: Early diagnosis and etiological classification of dementia remain challenging, as clinicians typically lack tools to integrate cognitive, neuroimaging, and genetic data quantitatively. We developed and validated multimodal risk models to support early diagnosis of dementia and differential diagnosis of Alzheimer's disease (AD) versus non-AD dementias in real-world clinical settings and translated model outputs into individualized risk reports. Methods: Utilizing real-world clinical cohorts (n = 1,100 for early diagnosis of dementia, using clinical diagnoses up to three years after clinical assessment; n = 788 for AD differential diagnosis) from Norwegian Memory Clinics, we trained and validated the Multimodal Hazard Score for Real-World Data (MHS-RWD) model integrating demographics (age, sex), cognitive assessments (MMSE-NR3 or CERAD 10-word delayed recall), the MRI-derived Imaging Hazard Score, and the Polygenic Hazard Score. Discrimination performance was examined using the area under the receiver operating characteristic curve (AUC). Results: In real-world clinical data, the MHS-RWD consistently outperformed any single predictor used alone. For early diagnosis of dementia, the full model achieved an AUC of 0.89 in females and 0.84 in males. For the differential diagnosis of AD from other dementias, the multimodal model yielded an AUC of 0.91 in females and 0.83 in males. A patient-level risk report was designed to present individualized risk estimates. Conclusions: Multimodal integration of cognitive, neuroimaging, and polygenic data in the MHS-RWD tool yields strong discrimination for both early diagnosis of dementia and AD differential diagnosis. The tool relies on data obtainable in clinical care, and genetic information that is becoming increasingly available in routine practice. Delivered through intuitive patient-level risk reports, it could support etiologically informed dementia decisions in real-world settings, with potential utility in primary care.","rel_num_authors":18,"rel_authors":[{"author_name":"Tahir Tekin Filiz","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Vera Fominykh","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Karin Persson","author_inst":"Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway"},{"author_name":"Mona Michelet","author_inst":"Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway"},{"author_name":"Iris J. Broce","author_inst":"Center for Multimodal Imaging and Genetics, J. Craig Venter Institute, La Jolla, CA, USA"},{"author_name":"Ingrid T\u00f8ndel Medb\u00f8en","author_inst":"Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway"},{"author_name":"Stina Aam","author_inst":"Department of Geriatric Medicine, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway"},{"author_name":"Alexey Shadrin","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Dag Aln\u00e6s","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Lavinia Athanasiu","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Xin Wang","author_inst":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"},{"author_name":"Gisele Sanda","author_inst":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"},{"author_name":"Ingvild Tina Saltvedt","author_inst":"Department of Geriatric Medicine, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway"},{"author_name":"Anne-Brita Knapskog","author_inst":"Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway"},{"author_name":"Geir Selb\u00e6k","author_inst":"Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway"},{"author_name":"Anders M. Dale","author_inst":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"},{"author_name":"Ole A. Andreassen","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"author_name":"Oleksandr Frei","author_inst":"Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Electroencephalographic Transient Beta Event Rates in Autism and Related Neurogenetic Conditions","rel_doi":"10.64898\/2026.08.02.26359366","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359366","rel_abs":"Transient beta events (TBE) during electroencephalography (EEG) reflect thalamocortical activity, bridging genotype to phenotype and impacting sensory responsivity. Compared to typically developing controls, we found elevated TBE rate in some children with idiopathic Autism Spectrum Disorder (ASD) and a majority of children with Phelan-McDermid Syndrome, Rett Syndrome, and SYNGAP1-related disorder. TBE rate thus offers promise as a stratification biomarker with divergent and convergent properties across ASD and neurogenetic conditions, respectively.","rel_num_authors":52,"rel_authors":[{"author_name":"Gerardo Parra","author_inst":"Boston Children's Hospital"},{"author_name":"Klara Szilagyi","author_inst":"Boston Children's Hospital"},{"author_name":"Yael Braverman","author_inst":"Boston Children's Hospital"},{"author_name":"Devorah Kranz","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"E Martina Bebin","author_inst":"University of Alabama School of Medicine"},{"author_name":"Raphael A Bernier","author_inst":"University of Washington"},{"author_name":"Jonathan A Bernstein","author_inst":"Stanford University School of Medicine"},{"author_name":"Elizabeth Berry-Kravis","author_inst":"Rush University Medical Center"},{"author_name":"Joseph D Buxbaum","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Katarzyna Chawarska","author_inst":"Yale University"},{"author_name":"Emma E Condy","author_inst":"National Institutes of Health"},{"author_name":"Laura Cornelissen","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Geraldine Dawson","author_inst":"Duke University"},{"author_name":"Abigail Dickinson","author_inst":"University of California, Los Angeles"},{"author_name":"James Dziura","author_inst":"Yale University"},{"author_name":"Charis Eng","author_inst":"Cleveland Clinic; Lerner College of Medicine of Case Western Reserve University"},{"author_name":"Susan Faja","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Jennifer H Foss-Feig","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Antonio Y Hardan","author_inst":"Stanford University"},{"author_name":"Ellen Hanson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Shafali Jeste","author_inst":"University of California, Los Angeles"},{"author_name":"Linnea Joffe-Nelson","author_inst":"Boston Children's Hospital"},{"author_name":"Alexander Kolevzon","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Darcy A Krueger","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Balu Krishnan","author_inst":"Cleveland Clinic"},{"author_name":"Robert Law","author_inst":"Boston Children's Hospital"},{"author_name":"David N Lieberman","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Claire MacKay","author_inst":"Boston Children's Hospital"},{"author_name":"Julian A Martinez-Agosto","author_inst":"David Geffen School of Medicine, University of California, Los Angeles"},{"author_name":"Adam J Naples","author_inst":"Yale University"},{"author_name":"Charles A Nelson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Hope Northrup","author_inst":"McGovern Medical School, University of Texas Health Science Center at Houston"},{"author_name":"Ernest Pedapati","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Annapurna Poduri","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Vineet Punia","author_inst":"Cleveland Clinic"},{"author_name":"Rajsekar R Rajaraman","author_inst":"UCLA Mattel Children's Hospital, David Geffen School of Medicine"},{"author_name":"David M Ritter","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Celine Saulnier","author_inst":"Neurodevelopmental Assessment and Consulting Services"},{"author_name":"Frederick Shic","author_inst":"Seattle Children's Research Institute; University of Washington"},{"author_name":"Latha Valluripalli Soorya","author_inst":"Rush University Medical Center"},{"author_name":"Catherine A Sugar","author_inst":"University of California, Los Angeles"},{"author_name":"Kyle E Takach","author_inst":"Boston Children's Hospital; Loyola Medical School"},{"author_name":"Audrey Thurm","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Sara J Webb","author_inst":"Seattle Children's Research Institute"},{"author_name":"Kimberly Wiltrout","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Damla \u015eent\u00fcrk","author_inst":"University of California, Los Angeles"},{"author_name":"Jeffrey P Gavornik","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Stephanie Jones","author_inst":"Brown University; Providence VA Medical Center"},{"author_name":"Michela Fagiolini","author_inst":"Boston Children's Hospital; Harvard Medical School; Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University; International Research Center"},{"author_name":"James C McPartland","author_inst":"Yale University"},{"author_name":"Mustafa Sahin","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"April R Levin","author_inst":"Boston Children's Hospital; Harvard Medical School"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Electroencephalographic Transient Beta Event Rates in Autism and Related Neurogenetic Conditions","rel_doi":"10.64898\/2026.08.02.26359366","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359366","rel_abs":"Transient beta events (TBE) during electroencephalography (EEG) reflect thalamocortical activity, bridging genotype to phenotype and impacting sensory responsivity. Compared to typically developing controls, we found elevated TBE rate in some children with idiopathic Autism Spectrum Disorder (ASD) and a majority of children with Phelan-McDermid Syndrome, Rett Syndrome, and SYNGAP1-related disorder. TBE rate thus offers promise as a stratification biomarker with divergent and convergent properties across ASD and neurogenetic conditions, respectively.","rel_num_authors":52,"rel_authors":[{"author_name":"Gerardo Parra","author_inst":"Boston Children's Hospital"},{"author_name":"Klara Szilagyi","author_inst":"Boston Children's Hospital"},{"author_name":"Yael Braverman","author_inst":"Boston Children's Hospital"},{"author_name":"Devorah Kranz","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"E Martina Bebin","author_inst":"University of Alabama School of Medicine"},{"author_name":"Raphael A Bernier","author_inst":"University of Washington"},{"author_name":"Jonathan A Bernstein","author_inst":"Stanford University School of Medicine"},{"author_name":"Elizabeth Berry-Kravis","author_inst":"Rush University Medical Center"},{"author_name":"Joseph D Buxbaum","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Katarzyna Chawarska","author_inst":"Yale University"},{"author_name":"Emma E Condy","author_inst":"National Institutes of Health"},{"author_name":"Laura Cornelissen","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Geraldine Dawson","author_inst":"Duke University"},{"author_name":"Abigail Dickinson","author_inst":"University of California, Los Angeles"},{"author_name":"James Dziura","author_inst":"Yale University"},{"author_name":"Charis Eng","author_inst":"Cleveland Clinic; Lerner College of Medicine of Case Western Reserve University"},{"author_name":"Susan Faja","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Jennifer H Foss-Feig","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Antonio Y Hardan","author_inst":"Stanford University"},{"author_name":"Ellen Hanson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Shafali Jeste","author_inst":"University of California, Los Angeles"},{"author_name":"Linnea Joffe-Nelson","author_inst":"Boston Children's Hospital"},{"author_name":"Alexander Kolevzon","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Darcy A Krueger","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Balu Krishnan","author_inst":"Cleveland Clinic"},{"author_name":"Robert Law","author_inst":"Boston Children's Hospital"},{"author_name":"David N Lieberman","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Claire MacKay","author_inst":"Boston Children's Hospital"},{"author_name":"Julian A Martinez-Agosto","author_inst":"David Geffen School of Medicine, University of California, Los Angeles"},{"author_name":"Adam J Naples","author_inst":"Yale University"},{"author_name":"Charles A Nelson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Hope Northrup","author_inst":"McGovern Medical School, University of Texas Health Science Center at Houston"},{"author_name":"Ernest Pedapati","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Annapurna Poduri","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Vineet Punia","author_inst":"Cleveland Clinic"},{"author_name":"Rajsekar R Rajaraman","author_inst":"UCLA Mattel Children's Hospital, David Geffen School of Medicine"},{"author_name":"David M Ritter","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Celine Saulnier","author_inst":"Neurodevelopmental Assessment and Consulting Services"},{"author_name":"Frederick Shic","author_inst":"Seattle Children's Research Institute; University of Washington"},{"author_name":"Latha Valluripalli Soorya","author_inst":"Rush University Medical Center"},{"author_name":"Catherine A Sugar","author_inst":"University of California, Los Angeles"},{"author_name":"Kyle E Takach","author_inst":"Boston Children's Hospital; Loyola Medical School"},{"author_name":"Audrey Thurm","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Sara J Webb","author_inst":"Seattle Children's Research Institute"},{"author_name":"Kimberly Wiltrout","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Damla \u015eent\u00fcrk","author_inst":"University of California, Los Angeles"},{"author_name":"Jeffrey P Gavornik","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Stephanie Jones","author_inst":"Brown University; Providence VA Medical Center"},{"author_name":"Michela Fagiolini","author_inst":"Boston Children's Hospital; Harvard Medical School; Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University; International Research Center"},{"author_name":"James C McPartland","author_inst":"Yale University"},{"author_name":"Mustafa Sahin","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"April R Levin","author_inst":"Boston Children's Hospital; Harvard Medical School"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Electroencephalographic Transient Beta Event Rates in Autism and Related Neurogenetic Conditions","rel_doi":"10.64898\/2026.08.02.26359366","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359366","rel_abs":"Transient beta events (TBE) during electroencephalography (EEG) reflect thalamocortical activity, bridging genotype to phenotype and impacting sensory responsivity. Compared to typically developing controls, we found elevated TBE rate in some children with idiopathic Autism Spectrum Disorder (ASD) and a majority of children with Phelan-McDermid Syndrome, Rett Syndrome, and SYNGAP1-related disorder. TBE rate thus offers promise as a stratification biomarker with divergent and convergent properties across ASD and neurogenetic conditions, respectively.","rel_num_authors":52,"rel_authors":[{"author_name":"Gerardo Parra","author_inst":"Boston Children's Hospital"},{"author_name":"Klara Szilagyi","author_inst":"Boston Children's Hospital"},{"author_name":"Yael Braverman","author_inst":"Boston Children's Hospital"},{"author_name":"Devorah Kranz","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"E Martina Bebin","author_inst":"University of Alabama School of Medicine"},{"author_name":"Raphael A Bernier","author_inst":"University of Washington"},{"author_name":"Jonathan A Bernstein","author_inst":"Stanford University School of Medicine"},{"author_name":"Elizabeth Berry-Kravis","author_inst":"Rush University Medical Center"},{"author_name":"Joseph D Buxbaum","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Katarzyna Chawarska","author_inst":"Yale University"},{"author_name":"Emma E Condy","author_inst":"National Institutes of Health"},{"author_name":"Laura Cornelissen","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Geraldine Dawson","author_inst":"Duke University"},{"author_name":"Abigail Dickinson","author_inst":"University of California, Los Angeles"},{"author_name":"James Dziura","author_inst":"Yale University"},{"author_name":"Charis Eng","author_inst":"Cleveland Clinic; Lerner College of Medicine of Case Western Reserve University"},{"author_name":"Susan Faja","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Jennifer H Foss-Feig","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Antonio Y Hardan","author_inst":"Stanford University"},{"author_name":"Ellen Hanson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Shafali Jeste","author_inst":"University of California, Los Angeles"},{"author_name":"Linnea Joffe-Nelson","author_inst":"Boston Children's Hospital"},{"author_name":"Alexander Kolevzon","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Darcy A Krueger","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Balu Krishnan","author_inst":"Cleveland Clinic"},{"author_name":"Robert Law","author_inst":"Boston Children's Hospital"},{"author_name":"David N Lieberman","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Claire MacKay","author_inst":"Boston Children's Hospital"},{"author_name":"Julian A Martinez-Agosto","author_inst":"David Geffen School of Medicine, University of California, Los Angeles"},{"author_name":"Adam J Naples","author_inst":"Yale University"},{"author_name":"Charles A Nelson","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Hope Northrup","author_inst":"McGovern Medical School, University of Texas Health Science Center at Houston"},{"author_name":"Ernest Pedapati","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Annapurna Poduri","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Vineet Punia","author_inst":"Cleveland Clinic"},{"author_name":"Rajsekar R Rajaraman","author_inst":"UCLA Mattel Children's Hospital, David Geffen School of Medicine"},{"author_name":"David M Ritter","author_inst":"Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine"},{"author_name":"Celine Saulnier","author_inst":"Neurodevelopmental Assessment and Consulting Services"},{"author_name":"Frederick Shic","author_inst":"Seattle Children's Research Institute; University of Washington"},{"author_name":"Latha Valluripalli Soorya","author_inst":"Rush University Medical Center"},{"author_name":"Catherine A Sugar","author_inst":"University of California, Los Angeles"},{"author_name":"Kyle E Takach","author_inst":"Boston Children's Hospital; Loyola Medical School"},{"author_name":"Audrey Thurm","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Sara J Webb","author_inst":"Seattle Children's Research Institute"},{"author_name":"Kimberly Wiltrout","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Damla \u015eent\u00fcrk","author_inst":"University of California, Los Angeles"},{"author_name":"Jeffrey P Gavornik","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"Stephanie Jones","author_inst":"Brown University; Providence VA Medical Center"},{"author_name":"Michela Fagiolini","author_inst":"Boston Children's Hospital; Harvard Medical School; Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University; International Research Center"},{"author_name":"James C McPartland","author_inst":"Yale University"},{"author_name":"Mustafa Sahin","author_inst":"Boston Children's Hospital; Harvard Medical School"},{"author_name":"April R Levin","author_inst":"Boston Children's Hospital; Harvard Medical School"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Household Transmission of Human Metapneumovirus and Human Parainfluenza Viruses 1-4 in the United States, 2022-2024","rel_doi":"10.64898\/2026.08.02.26359491","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.08.02.26359491","rel_abs":"Human metapneumovirus (HMPV) and human parainfluenza viruses (HPIV 1-4) are common causes of seasonal respiratory illness, but their household transmission dynamics remain poorly defined. We analyzed weekly symptom data and nasal swabs from a prospective household surveillance study in Washington and Oregon from June 2022 to March 2024. Swabs were tested for HMPV and HPIV, and a subset underwent whole-genome sequencing. Distinct index cases occurred in 236 (23%) and 341 (36%) of 1,040 households for HMPV and HPIV, respectively. Household secondary attack rates (SAR) and median generation times were similar for HMPV (8.7%, 7 days) and HPIV (7.3%, 7 days). Sequenced samples reflected contemporaneous circulating strains during the same period, with household sequences clustering closely together. High-quality viral whole genome sequences were recovered for two or more individuals within a household in a total of 26 households for HMPV and 45 households for HPIV. Intra-household pairwise nucleotide (nt) distance ranged from 0 to 14 nt (median 0) for HMPV and 0-8 nt (median 1) for HPIV when cases occurred 0-15 days apart. Transmission occurred primarily from children to adults, emphasizing the importance of childcare- and school-associated spread and supporting child-focused prevention strategies to reduce household transmission.","rel_num_authors":31,"rel_authors":[{"author_name":"Pavitra Roychoudhury","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, "},{"author_name":"Anna Elias-Warren","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Erica Wetzler","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Hyeong Geon Kim","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Kevin Kong","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Hong Xie","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Cassey Spring","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Margaret G. Mills","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Alex Harteloo","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Collrane Frivold","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Madison Hollcroft","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Mark Drummond","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Tara Hatchie","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Erica Clark","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Brenna Ehmen","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Peter D. Han","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Luis Gamboa","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Sally Grindstaff","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Jeremy Stone","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Katherine L. Hoffman","author_inst":"Department of Biostatistics, University of Washington, Seattle, WA"},{"author_name":"Alexander L. Greninger","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, "},{"author_name":"Lea M. Starita","author_inst":"Brotman Baty Institute for Precision Medicine, Seattle, WA"},{"author_name":"Christina Lockwood","author_inst":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA"},{"author_name":"Janet A. Englund","author_inst":"Department of Pediatrics, University of Washington, and Seattle Children's Research Institute"},{"author_name":"Ana A. Weil","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"},{"author_name":"Sacha L. Reich","author_inst":"Kaiser Permanente Center for Health Research, Portland, OR"},{"author_name":"Richard A. Mularski","author_inst":"Kaiser Permanente Center for Health Research, Portland, OR"},{"author_name":"Mark A. Schmidt","author_inst":"Kaiser Permanente Center for Health Research, Portland, OR"},{"author_name":"Jennifer L. Kuntz","author_inst":"Kaiser Permanente Center for Health Research, Portland, OR"},{"author_name":"Allison L. Naleway","author_inst":"Kaiser Permanente Center for Health Research, Portland, OR"},{"author_name":"Helen Y. Chu","author_inst":"Departments of Medicine and Epidemiology, University of Washington, Seattle, WA"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Harmonized Carceral Mortality Database: a dataset on mortality in state-operated correctional facilities","rel_doi":"10.64898\/2026.07.29.26359256","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359256","rel_abs":"Documenting and measuring mortality in correctional facilities is essential for understanding the health consequences of incarceration, identifying preventable deaths, and informing policy interventions. We undertook a compilation of publicly available mortality records in state-operated correctional facilities, encompassing data gathered from administrative, nonprofit, and public records. The Harmonized Carceral Mortality Database (HCMD) standardizes decedent characteristics, facility identifiers, locations, dates of death, and causes of death to enable epidemiologic analyses of mortality in U.S. prisons, outside of federal reporting. At the time of writing, the HCMD includes 49,682 deaths from at least 1,089 prisons in 50 states, spanning 1996 - 2024, with regular updates annually. The HCMD supports carceral health research across a range of disciplines from environmental health to sociology to criminology and supports use beyond the scientific community, including journalists, lawyers, and community-based organizers.","rel_num_authors":3,"rel_authors":[{"author_name":"Ufuoma Ovienmhada","author_inst":"University of Arizona"},{"author_name":"Gabriela Daza","author_inst":"Columbia University"},{"author_name":"Robbie Parks","author_inst":"Columbia University"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Beyond the Red Complex: De Novo Marker Discovery Uncovers Novel Periodontitis-Associated Taxa and Enables Non-Invasive Machine Learning Diagnosis","rel_doi":"10.64898\/2026.07.31.26359396","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359396","rel_abs":"Background: Periodontitis affects over 1 billion people worldwide, yet diagnosis relies on clinical measures that capture tissue destruction rather than underlying microbial dysbiosis. Most microbial-biomarker studies use 16S rRNA sequencing or reference-database mapping, systematically under-detecting uncultivated or divergent taxa. Methods: We assembled 341 supra- and subgingival shotgun metagenomes (218 periodontitis, 123 health) across nine countries\/regions. Using MetaMarker, a de novo, reference-free pipeline, we identified conserved genomic markers directly from reads in a 305-sample discovery pool without database mapping. Markers were taxonomically annotated against the Human Oral Microbiome Database, functionally annotated with Prodigal\/eggNOG-mapper, and used for eight machine-learning classifiers, externally validated on three independent held-out cohorts (36 samples). Results: We recovered 2,142 significant markers (1,999 periodontitis-enriched, 143 health-enriched; q<0.05), recapitulating the canonical red\/orange-complex dysbiotic shift. Beyond established pathogens, 128 periodontitis markers (6.4%) were novel, including an uncultivated Paludibacteraceae genus and divergent Fretibacterium fastidiosum strains. Case markers encoded a coherent virulence programme spanning proteolysis, haem\/iron acquisition, and Type IX secretion. On external validation, boosted-tree classifiers generalized best (XGBoost and gradient boosting, AUC=0.96), and a compact SHAP-ranked 20-marker panel spanning five taxa reproduced full-set directionality. Conclusions: Reference-free metagenomic marker discovery recovers known periodontal pathobiology while revealing unrecognized candidate biomarkers and supports an accurate, externally validated, non-invasive classifier with translational potential as a compact diagnostic panel.","rel_num_authors":2,"rel_authors":[{"author_name":"Mohamad Koohi-Moghadam","author_inst":"The University of Hong Kong"},{"author_name":"Wai Keung Leung","author_inst":"University of Hong Kong"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Power and sample size calculations for evaluating spillover effects in networks with non-randomized interventions","rel_doi":"10.64898\/2026.07.31.26359421","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359421","rel_abs":"Determining the appropriate sample size for desired statistical power is crucial for obtaining reliable research outcomes. While methods exist for multiple types of studies, the method for evaluating power of estimating spillover effects in sociometric network-based studies with non randomized interventions remain inadequately explored. We conducted a simulation study to assess how the design parameters (i.e., number of components, number of nodes, node degree, transitivity, and effect size) affects the statistical power for estimating spillover effects in non randomized, network-based studies. Both simulated networks and a real-world network from Transmission Reduction Intervention Project (TRIP) were used in this study. Our simulation results suggests that: (1) power increases with more nodes or a larger effect size, but not necessarily with more components when the number of nodes is fixed; (2) A higher node degree or greater transitivity results in reduced power; (3) Highly unbalanced networks (e.g., most of the nodes are in one component) can drastically reduce power. Furthermore, the power calculated using a closed-form expression developed in this work also shows that power remained the same or even decreases slightly with more components when the number of nodes are fixed, aligning with the simulation findings. All the results were specific to the inverse probability weighting estimator we employed in this study and assumptions it required. An alternative estimator or interference assumption may lead to different results.","rel_num_authors":6,"rel_authors":[{"author_name":"Ke Zhang","author_inst":"University of Rhode Island"},{"author_name":"Ashley Buchanan","author_inst":"University of Rhode Island"},{"author_name":"Natallia Katenka","author_inst":"University of Rhode Island"},{"author_name":"Jing Wu","author_inst":"University of Rhode Island"},{"author_name":"Youjin Lee","author_inst":"Brown University"},{"author_name":"Georgios Nikolopoulos","author_inst":"University of Cyprus"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Systematic Integration of genomics with transcriptomics for the Study of Coronary Artery Disease and Subclinical Atherosclerosis","rel_doi":"10.64898\/2026.07.31.26357396","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26357396","rel_abs":"IntroductionCoronary artery disease (CAD) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWAS) have identified over 300 loci associated with CAD risk, the molecular mechanisms linking these variants to disease and subclinical atherosclerosis are not fully understood.\n\nMethodsWe performed integration of multi-ancestry CAD GWAS with transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (MESA) obtained through the Trans-Omics for Precision Medicine (TOPMed) program. For integration, we applied Bayesian colocalization analysis with and without statistical fine-mapping to identify genes whose expression levels colocalize with CAD-associated loci. We further applied causal weighted gene co-expression network analysis (cWGCNA) to identify gene co-expression modules and key driver genes associated with subclinical atherosclerosis traits in MESA.\n\nResultsWe identified 108 genes showing evidence of colocalization with CAD loci, including 24 shared between the two colocalization approaches and 48 novel genes not previously reported in CAD GWAS. Follow-up replication and validation analyses prioritized 5 novel (CCDC30, ZEB1-AS1, ZPR1, PLEKHJ1 and AC018816.3) and 8 previously reported genes (DHDDS, DDX59, LNPEP, DAGLA, ZKSCAN1, LIPA, OPRL1 and EIF2B2) with putative roles in both CAD and subclinical atherosclerosis. cWGCNA identified five gene modules significantly associated with subclinical atherosclerosis in MESA. Additionally, three key driver genes (ATG9B, PRAM1 and ZBTB46) identified by cWGCNA were also identified as CAD-colocalized genes.\n\nDiscussionOur integrative analysis highlights key genetic drivers and regulatory networks underlying CAD and subclinical atherosclerosis. These findings underscore the value of incorporating statistical fine-mapping in colocalization studies and demonstrate the utility of combining colocalization with co-expression network analysis to prioritize functional genes and pathways.","rel_num_authors":30,"rel_authors":[{"author_name":"Chaojie Yang","author_inst":"University Of Virginia"},{"author_name":"Francois Aguet","author_inst":"Broad Institute"},{"author_name":"Gaelle Auguste","author_inst":"University of Virginia"},{"author_name":"Kristin G Ardlie","author_inst":"The Broad Institute of Harvard and MIT"},{"author_name":"Robert E Gerszten","author_inst":"Beth Israel Deaconess Medical Center"},{"author_name":"Wendy S. Post","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Heather E Wheeler","author_inst":"Loyola University Chicago Department of Biology"},{"author_name":"Kent D. Taylor","author_inst":"Harbor-UCLA  Medical Center,"},{"author_name":"Silva Kasela","author_inst":"New York Genome Center Inc"},{"author_name":"Tuuli Lappalainen","author_inst":"New York Genome Center Inc"},{"author_name":"Hae Kyung lm","author_inst":"Section of Genetic Medicine, Department of Medicine, University of Chicago"},{"author_name":"Peter Durda","author_inst":"University of Vermont Department of Pathology and Laboratory Medicine"},{"author_name":"W. Craig Johnson","author_inst":"University of Washington"},{"author_name":"Xiuqing Guo","author_inst":"Harbor-UCLA Medical Center"},{"author_name":"Yongmei Liu","author_inst":"Duke University"},{"author_name":"Joseph F. Polak","author_inst":"Tufts Medical Center"},{"author_name":"David M. Herrington","author_inst":"Wake Forest University"},{"author_name":"Clary B. Clish","author_inst":"Broad Institute"},{"author_name":"David Van Den Berg","author_inst":"Keck School of Medicine of the University of Southern California"},{"author_name":"Russell P. Tracy","author_inst":"University Of Vermont"},{"author_name":"Elaine Cornell","author_inst":"University Of Vermont"},{"author_name":"Thomas W. Blackwell","author_inst":"University of Michigan"},{"author_name":"George J Papanicolaou","author_inst":"National Institutes of Health"},{"author_name":"Jose D. Vargas","author_inst":"Washington DC VA Medical Center"},{"author_name":"Stefan Bekiranov","author_inst":"University of Virginia Library"},{"author_name":"Coleen A McNamara","author_inst":"University of Virginia"},{"author_name":"Clint L Miller","author_inst":"University of Virginia Library"},{"author_name":"Jerome I. I. Rotter","author_inst":"The Lundquist Institute"},{"author_name":"Stephen S. S. Rich","author_inst":"University of Virginia"},{"author_name":"Ani W. Manichaikul","author_inst":"University of Virginia Library"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Systematic Integration of genomics with transcriptomics for the Study of Coronary Artery Disease and Subclinical Atherosclerosis","rel_doi":"10.64898\/2026.07.31.26357396","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26357396","rel_abs":"IntroductionCoronary artery disease (CAD) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWAS) have identified over 300 loci associated with CAD risk, the molecular mechanisms linking these variants to disease and subclinical atherosclerosis are not fully understood.\n\nMethodsWe performed integration of multi-ancestry CAD GWAS with transcriptomic data from the Multi-Ethnic Study of Atherosclerosis (MESA) obtained through the Trans-Omics for Precision Medicine (TOPMed) program. For integration, we applied Bayesian colocalization analysis with and without statistical fine-mapping to identify genes whose expression levels colocalize with CAD-associated loci. We further applied causal weighted gene co-expression network analysis (cWGCNA) to identify gene co-expression modules and key driver genes associated with subclinical atherosclerosis traits in MESA.\n\nResultsWe identified 108 genes showing evidence of colocalization with CAD loci, including 24 shared between the two colocalization approaches and 48 novel genes not previously reported in CAD GWAS. Follow-up replication and validation analyses prioritized 5 novel (CCDC30, ZEB1-AS1, ZPR1, PLEKHJ1 and AC018816.3) and 8 previously reported genes (DHDDS, DDX59, LNPEP, DAGLA, ZKSCAN1, LIPA, OPRL1 and EIF2B2) with putative roles in both CAD and subclinical atherosclerosis. cWGCNA identified five gene modules significantly associated with subclinical atherosclerosis in MESA. Additionally, three key driver genes (ATG9B, PRAM1 and ZBTB46) identified by cWGCNA were also identified as CAD-colocalized genes.\n\nDiscussionOur integrative analysis highlights key genetic drivers and regulatory networks underlying CAD and subclinical atherosclerosis. These findings underscore the value of incorporating statistical fine-mapping in colocalization studies and demonstrate the utility of combining colocalization with co-expression network analysis to prioritize functional genes and pathways.","rel_num_authors":30,"rel_authors":[{"author_name":"Chaojie Yang","author_inst":"University Of Virginia"},{"author_name":"Francois Aguet","author_inst":"Broad Institute"},{"author_name":"Gaelle Auguste","author_inst":"University of Virginia"},{"author_name":"Kristin G Ardlie","author_inst":"The Broad Institute of Harvard and MIT"},{"author_name":"Robert E Gerszten","author_inst":"Beth Israel Deaconess Medical Center"},{"author_name":"Wendy S. Post","author_inst":"Johns Hopkins University School of Medicine"},{"author_name":"Heather E Wheeler","author_inst":"Loyola University Chicago Department of Biology"},{"author_name":"Kent D. Taylor","author_inst":"Harbor-UCLA  Medical Center,"},{"author_name":"Silva Kasela","author_inst":"New York Genome Center Inc"},{"author_name":"Tuuli Lappalainen","author_inst":"New York Genome Center Inc"},{"author_name":"Hae Kyung lm","author_inst":"Section of Genetic Medicine, Department of Medicine, University of Chicago"},{"author_name":"Peter Durda","author_inst":"University of Vermont Department of Pathology and Laboratory Medicine"},{"author_name":"W. Craig Johnson","author_inst":"University of Washington"},{"author_name":"Xiuqing Guo","author_inst":"Harbor-UCLA Medical Center"},{"author_name":"Yongmei Liu","author_inst":"Duke University"},{"author_name":"Joseph F. Polak","author_inst":"Tufts Medical Center"},{"author_name":"David M. Herrington","author_inst":"Wake Forest University"},{"author_name":"Clary B. Clish","author_inst":"Broad Institute"},{"author_name":"David Van Den Berg","author_inst":"Keck School of Medicine of the University of Southern California"},{"author_name":"Russell P. Tracy","author_inst":"University Of Vermont"},{"author_name":"Elaine Cornell","author_inst":"University Of Vermont"},{"author_name":"Thomas W. Blackwell","author_inst":"University of Michigan"},{"author_name":"George J Papanicolaou","author_inst":"National Institutes of Health"},{"author_name":"Jose D. Vargas","author_inst":"Washington DC VA Medical Center"},{"author_name":"Stefan Bekiranov","author_inst":"University of Virginia Library"},{"author_name":"Coleen A McNamara","author_inst":"University of Virginia"},{"author_name":"Clint L Miller","author_inst":"University of Virginia Library"},{"author_name":"Jerome I. I. Rotter","author_inst":"The Lundquist Institute"},{"author_name":"Stephen S. S. Rich","author_inst":"University of Virginia"},{"author_name":"Ani W. Manichaikul","author_inst":"University of Virginia Library"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Pain-Reporting Variability and Reliability as Predictors of Placebo Effects: A Cross-Sectional Experimental Pain Study","rel_doi":"10.64898\/2026.07.31.26359372","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359372","rel_abs":"Placebo analgesia varies substantially across individuals, yet the sources of this heterogeneity remain incompletely understood. Pain-reporting variability may represent an underrecognized predictor of placebo responsiveness. This study examined whether variability and reliability of pain reporting predict placebo analgesia in an experimental pain setting. Eight hundred and three participants (401 individuals with temporomandibular disorder and 400 healthy controls) completed a standardized thermal pain paradigm involving calibration, placebo conditioning, and testing phases. We obtained repeated heat temperatures (four) during thermal calibration and pain ratings during conditioning test (24 trials). We used these measurements to quantify within-person pain-reporting variability using standard deviation (SD) and coefficient of variation (CoV), and reliability using intraclass correlation coefficients (ICC). Placebo analgesia was calculated as the difference in pain ratings between control and placebo cue trials during testing. Regression models examined associations between reporter characteristics and placebo analgesia controlling for age, sex, race and experimenters. Variability of thermal pain responses during calibration did not predict placebo analgesia. Greater pain-reporting variability during conditioning was associated with reduced placebo analgesia (higher SD and CoV), and this effect was mediated by slower acquisition of the cue pain contingency. Conditioning-phase reliability was not associated with placebo analgesia, whereas three clusters of learning profiles predicted placebo effects. Thus, individual differences in pain-reporting variability during conditioning, rather than baseline sensory variability, contribute to heterogeneity in placebo analgesia. These findings suggest that variability during acquisition processing matters more than general sensory variability influencing the magnitude of placebo effects.","rel_num_authors":11,"rel_authors":[{"author_name":"James Arthur Rene Cottam","author_inst":"University of Maryland Baltimore"},{"author_name":"Yang Wang","author_inst":"University of Maryland, Baltimore"},{"author_name":"Titilola Akintola","author_inst":"University of Maryland, Baltimore"},{"author_name":"John Farrar","author_inst":"University of Pennsylvania"},{"author_name":"Chixiang Chen","author_inst":"University of Maryland, Baltimore"},{"author_name":"Patrick McArdle","author_inst":"University of Maryland Baltimore"},{"author_name":"Seth A Ament","author_inst":"University of Maryland School of Medicine"},{"author_name":"Philip A Corlett","author_inst":"Yale University"},{"author_name":"Susan G Dorsey","author_inst":"University of Maryland Baltimore"},{"author_name":"Roi Treister","author_inst":"University of Haifa"},{"author_name":"Luana Colloca","author_inst":"University of Maryland School of Nursing"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Natural History and Post-transplant Outcomes Among Patients with Kidney Leukocyte Cell- Derived","rel_doi":"10.64898\/2026.07.31.26359278","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359278","rel_abs":"Background: ALECT2 is the third most common cause of renal amyloidosis in the United States, with a strong predilection for Hispanic patients in the Southwest. (PMID:24522497) Despite its regional prevalence, the data on the trajectory of kidney function decline and post-transplant outcomes remain poorly characterized. Methods: This is a retrospective study of patients diagnosed with ALECT2 by kidney biopsy at UNM from January 2014 to April 2024. Pre- and post-biopsy eGFR trajectories and post-transplant allograft function were analyzed. Results: 12 patients had pre-biopsy data available, with the mean age at diagnosis 64 SD 12.0 years, 8(67%) were females, and 8 identified as Hispanic. Mean eGFR at diagnosis was 31 (SD 29) indicating advanced kidney disease with 67% diagnosed as CKD stage 4 or 5. Concomitant kidney pathology was identified in 50% with diabetic nephropathy being present in 2\/3 of those. A significant change in the eGFR trajectory identified at the time of biopsy through change point analysis [Figures A,C,D] Among four patients who underwent kidney transplantation, allograft eGFR remained stable over more than 60 months of follow-up [Figure D] Conclusion: In this cohort of predominantly Hispanic patients, ALECT2 amyloidosis presented with advanced CKD and accelerated loss of kidney function, which prompted a biopsy that detected the disease. Post- transplant allograft function was well maintained, supporting kidney transplantation as a viable treatment strategy for ALECT2-associated kidney disease.","rel_num_authors":8,"rel_authors":[{"author_name":"Iqra Fatima Munawar Ali","author_inst":"Aga Khan University"},{"author_name":"Pedro A Lopez-Gutierrez","author_inst":"University of New Mexico"},{"author_name":"Nimra Iftikhar","author_inst":"University of New Mexico"},{"author_name":"Valeria Hanson","author_inst":"University of New Mexico"},{"author_name":"Shumaila Afrin","author_inst":"University of Texas Southwestern"},{"author_name":"Lorena Saelices Gomez","author_inst":"University of Texas Southwestern"},{"author_name":"Pablo R Garcia","author_inst":"University of New Mexico"},{"author_name":"Christos P Argyropoulos","author_inst":"University of New Mexico"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Establishing a physiological normative value of area-based hypoxic burden in obstructive sleep apnea","rel_doi":"10.64898\/2026.07.31.26359352","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359352","rel_abs":"Background and ObjectivesArea-based hypoxic burden, termed as hypoxic dip area (HDA) has been studied as a novel obstructive sleep apnea (OSA) metric that may better characterize intermittent hypoxemia in OSA and thereby better predict outcomes. However, to be of use in routine clinical care, a physiological normative value is necessary. Here we attempt to use several large cohorts to establish a percentile-based threshold that can classify individuals with normal vs. abnormal physiological profiles.\n\nMethodsData from 10 cohorts (EPISONO, FINS, Dayfun, MrOS, MESA, SHHS, APPLES, WSC, CFS, and AIRS [Mount Sinai Clinical Cohort]; n=14,031 subjects) were included. HDA was defined as the area bounded by SpO2 nadirs ([&ge;]2% desaturation) flanking left\/right peaks. The 97.5th percentile of HDA among asymptomatic subjects (n=136) from EPISONO, FINS, and DAYFUN (aged 20-52 years; 46 [33.8%] male) was used to define normal and elevated HDA levels. Physiological features, clinical comorbidities, and incident cardiovascular disease (CVD) events and mortality were compared between normal\/elevated HDA groups. Sensitivity analyses were conducted using age-, sex-, and BMI-adjusted threshold derived from multivariable regression model.\n\nResultsThe 97.5% percentile cutoff of HDA was 8.6%min\/h, classifying 4,500 individuals as normal HDA and 9,531 as elevated HDA. Individuals with elevated HDA ([&ge;]8.6%min\/h) demonstrated greater nocturnal hypoxemia (lower baseline SpO2, higher T90, T85, T80 and oxygen desaturation index), higher AHI (apnea-hypopnea index) and arousal index, and greater daytime sleepiness as well as a higher prevalence of lifetime CVD and hypertension across cohorts. Elevated HDA was related with a higher prevalence of incident CVD events and mortality in unadjusted analyses, although these associations were attenuated after adjustment for confounding factors. Results were similar using alternative thresholds derived from multivariable regression analyses.\n\nConclusionsA physiologically derived cutoff of 8.6% min\/h for HDA effectively distinguishes physiological profiles across respiratory, arousal, and oxygenation domains and generalizes across multiple cohorts. Those with elevated HDA had a higher prevalence of incident CVD outcomes, although observed relationships were attenuated after further adjustment. Our findings provide a physiologically interpretable threshold for HDA that can be readily used in clinical use.","rel_num_authors":19,"rel_authors":[{"author_name":"Li Zhou","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Siyun Yang","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Sajila D Wickramaratne","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Pavel Boulgakov","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Zachary Roberts","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Sarah Chu","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Ankita kumar","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Eriko Hamada","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Thomas M. Tolbert","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Korey Kam","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Andrew W. Varga","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Luciana B. M. de Godoy","author_inst":"Universidade Federal de Sao Paulo (UNIFESP\/EPM)"},{"author_name":"Luciana O. Palombini","author_inst":"Universidade Federal de Sao Paulo (UNIFESP\/EPM)"},{"author_name":"Monica L. Andersen","author_inst":"Universidade Federal de Sao Paulo (UNIFESP\/EPM)"},{"author_name":"Sergio Tufik","author_inst":"Universidade Federal de Sao Paulo (UNIFESP\/EPM)"},{"author_name":"Katie L Stone","author_inst":"California Pacific Medical Center Research Institute"},{"author_name":"Indu Ayappa","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"David M. Rapoport","author_inst":"Icahn School of Medicine at Mount Sinai"},{"author_name":"Ankit Parekh","author_inst":"Icahn School of Medicine at Mount Sinai"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Stress-Related Methylation Risk Scores Predict Coronary Heart Disease","rel_doi":"10.64898\/2026.07.31.26359423","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.31.26359423","rel_abs":"Background: Psychosocial stress is a key risk factor for coronary heart disease (CHD), particularly in postmenopausal women who face both a high stress burden and elevated cardiovascular risk. DNA methylation (DNAm), a critical epigenetic modification bridging environment and health, remains understudied as a contributor to stress-related CHD. Methods: We conducted an epigenome-wide association study (EWAS) of stress in the Women's Health Initiative (WHI), an ancestrally diverse cohort of postmenopausal women (n=3,857). At screening visit, participants completed a questionnaire assessing stressful life events and provided whole blood for DNAm. Incident CHD was then longitudinally ascertained (follow-up mean\/SD: 16.7\/8.4 years), and DNAm signatures were evaluated as CHD predictors using Cox regression. Predictive models were independently validated in the Jackson Heart Study (JHS; n=3,053) and Multi-Ethnic Study of Atherosclerosis (MESA; n=870). The bulk-level DNAm associations were computationally deconvolved at the cell-type-specific level using tensor composition analysis (TCA). Results: The EWAS in WHI identified 841 stress-related DNAm sites (99 hypermethylated, 742 hypomethylated with stress) after FDR correction, with 13 significant after Bonferroni correction, including sites located on immune and CHD-related genes (e.g., TNF, ALDH2). Methylation risk scores (MRSs) integrating the 841 FDR-significant sites (MRS841) and 13 Bonferroni-significant sites (MRS13) predicted incident CHD (HR=1.33-1.37; p[&le;]0.0008) and mediated 16.5-17.7% of the association between stress and CHD. In JHS and MESA, MRS13 independently predicted CHD (HR=1.34; p=0.036), whereas MRS841 was suggestively associated with CHD (HR=1.27; p=0.087). TCA indicated that the greatest number of stress-related sites predictive of CHD was specifically in monocytes (133 total), with directions consistent with bulk-level associations (9 hypermethylated, 124 hypomethylated with stress). Conclusion: Our study supports methylation risk scores as novel biomarkers of stress-related CHD and uncovers epigenetic regulation in monocytes as a potential underlying mechanism. These findings highlight biological pathways linking stress and disease and may promote personalized interventions in high-risk populations.","rel_num_authors":21,"rel_authors":[{"author_name":"Sofia Benavides","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel H"},{"author_name":"Hazel Milla","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, "},{"author_name":"Helena Palma-Gudiel","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA"},{"author_name":"David Checknita","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA, AbbVie Corporation, Saint-Laurent, Canada"},{"author_name":"Bjoernar Tuftin","author_inst":"Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"author_name":"Kai Xia","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA"},{"author_name":"Charles Kooperberg","author_inst":"Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA"},{"author_name":"Alexander P. Reiner","author_inst":"Department of Epidemiology, University of Washington & Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA"},{"author_name":"JoAnn E. Manson","author_inst":"Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA"},{"author_name":"Themistocles L. Assimes","author_inst":"Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA, VA Palo Alto Healthcare System, Palo Alt"},{"author_name":"Parveen Bhatti","author_inst":"Population Health Sciences, BC Cancer Research Institute, Vancouver, British Columbia, Canada, School of Population and Public Health, University of British Col"},{"author_name":"Kent D. Taylor","author_inst":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Med"},{"author_name":"W. Craig Johnson","author_inst":"Department of Biostatistics, University of Washington, Seattle, WA, USA"},{"author_name":"Stephen S. Rich","author_inst":"Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA"},{"author_name":"Jerome I. Rotter","author_inst":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Med"},{"author_name":"Linda C. Gallo","author_inst":"Department of Psychology, San Diego State University, San Diego, CA, USA"},{"author_name":"David R. Rubinow","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA"},{"author_name":"Elior Rahmani","author_inst":"Division of Computational Medicine, Department of Medicine, Stanford University, Stanford, CA, USA"},{"author_name":"Laura M. Raffield","author_inst":"Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"author_name":"Eric A. Whitsel","author_inst":"Department of Epidemiology, UNC Gillings School of Public Health, Chapel Hill, NC, USA, Department of Medicine, UNC School of Medicine, Chapel Hill, NC, USA"},{"author_name":"Anthony S. Zannas","author_inst":"Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel H"}],"rel_date":"2026-08-03","rel_site":"medrxiv"},{"rel_title":"Employing Data-Driven Techniques to Explore the Lay Public's Health Concerns with Vaping E-Cigarettes","rel_doi":"10.64898\/2026.07.29.26359262","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359262","rel_abs":"While the public perceives e-cigarettes as less harmful than combustible tobacco, little is known about their specific health concerns regarding vaping. We demonstrate a data-driven strategy to discover the publics health concerns about vaping e-cigarettes expressed on social media. We obtained all public posts from the largest e-cigarette-related subreddit, r\/electronic_cigarette, from its inception on September 17, 2008, through April 1, 2022 (N = 10,403,433). We identified health concerns attributed to vaping by (a) selecting all cause phrases containing \"cause\" and its inflections, (b) calculating the empirical frequency ratio of words and bi-grams occurring in these phrases relative to random phrases, (c) retaining the 10% of words with the greatest empirical frequency of occurring in cause phrases, and (d) annotating this sample for health-relevant concerns and their subjects. In total, 76,342 posts contained cause phrases, with increased volume over time. Of the 425 words most strongly associated with cause phrases compared to random phrases, 53.4% (95%CI, 48.7-58.1) were identified as health-relevant. The top health-related concern was lipoid pneumonia, cited in 5.9% (95%CI, 5.0-6.8) of all cause phrases, followed by pneumonia (4.1%; 95%CI, 3.3-4.9), and nausea (2.7%;95%CI, 2.0-3.4). The top health concern subjects were respiratory, representing 23.7% (95%CI, 18.5-29.5) of all cause phrases, followed by gastrointestinal (12.7%; 95%CI, 8.8-17.2) and cardiovascular (8.5%; 95%CI, 5.3-12.3) concerns. Other subjects included neurological, dermatological, oral health, sexual health, psychiatric, oncologic, addiction, and sleep concerns. Because our strategy relies on data-driven techniques, our analysis can be integrated into routine social media monitoring and applied across different types of social media and text data, potentially leading to more timely identification of emerging concerns and a broader understanding across platforms. As a result, experts can craft messaging that accounts for current perceptions held by the public using our method.","rel_num_authors":8,"rel_authors":[{"author_name":"John  W. Ayers","author_inst":"Harvard Medical School"},{"author_name":"Adam Poliak","author_inst":"Bryn Mawr College"},{"author_name":"Alexandra DeLucia","author_inst":"JHU"},{"author_name":"Zechariah Zhu","author_inst":"UCSD"},{"author_name":"Stephanie Pitts","author_inst":"FDA"},{"author_name":"Mario Navarro","author_inst":"FDA: US Food and Drug Administration"},{"author_name":"Sharareh Shojaie","author_inst":"FDA"},{"author_name":"Mark Dredze","author_inst":"JHU"}],"rel_date":"2026-08-02","rel_site":"medrxiv"},{"rel_title":"Smartphone Imaging for Remote Monitoring of Inflammatory Arthritis in a Real-World Cohort: Longitudinal Evaluation of a Machine Learning-Based Finger Fold Biomarker","rel_doi":"10.64898\/2026.07.30.26359295","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.30.26359295","rel_abs":"BackgroundSmartphone enabled remote patient monitoring has the potential to complement conventional follow-up in inflammatory arthritis. We previously presented the finger fold index (FFI) derived from hand photographs as ratio of automated detected proximal interphalangeal (PIP) joint diameter and surface of dorsal finger folds as a digital biomarker for clinical joint swelling and disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).\n\nObjectiveTo evaluate the feasibility, image quality, patient engagement, and clinical utility of both HCP- and patient-collected hand photographs integrated into a national rheumatology registry, and to assess the performance of the FFI as an image-derived digital biomarker for clinical joint swelling of the proximal interphalangeal joints in a real-world arthritis cohort.\n\nMethodsIn this longitudinal multicenter study, a photo function with written instructions were integrated into the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry and their mySCQM mobile application, respectively. Patients with RA or PsA contributed longitudinal smartphone photographs together with patient-reported outcomes (PROs) via the mySCQM mobile application while health care professionals (HCPs) acquired images during routine visits. After manual quality assessment, images were processed using an automated computer vision pipeline to derive the FFI, a digital biomarker based on dorsal finger-fold morphology. Image quality was evaluated for both HCP- and participant-collected photographs, and patient engagement was assessed. Associations between FFI, clinical proximal interphalangeal (PIP) joint swelling, RADAI-5, DAS28-CRP and longitudinal changes were assessed. A generalized linear mixed model was used to estimate the association between FFI and joint swelling while accounting for repeated measures and within-subject correlations.\n\nResultsBetween 2023 and 2025, 374 RA and PsA patients were included. HCPs captured 977 hand images while 174 patients collected 1228 hand images via the mySCQM app. Patients demonstrated sustained engagement after instruction, contributing a mean of seven images during data collection. Following quality control, 1729 hand images comprising 4048 PIP joints were included for analysis. Image quality was comparable between patient-acquired and HCP-acquired photographs; 78.3% of the patient-acquired vs. 73.5% of the HCP-acquired hand images were suitable to run the ML-model. 23.1% of the cropped joints had to be removed after the running of the FFI algorithm due to false diameter or finger fold detection e.g. due to wrong hand positioning. In images taken by HCPs, mean FFI and DAS28-CRP were weakly but significantly correlated (Spearmans {rho} = 0.164; 95% CI [0.004 to 0.317]; p = 0.039). Conversely, RADAI-5 scores did not correlate with the mean FFI in RA patients (r = 0.007, p = 0.932, 95% CI [-0.169-0.183]). At follow-up visits, clinical swelling resolved in 40 joints, of which in 68.0% the direction of the delta FFI was concordant with the clinical change. In contrast, 13 joints developed incident clinical swelling, of which 87.5% had a direction of the delta FFI that was concordant with the clinical change. However, the GLMM showed no significant associations between swelling and joint location or time-varying FFI, and no evidence of interaction between FFI and PIP joint.\n\nConclusionIntegration of patient self-imaging into a remote monitoring application for inflammatory arthritis is feasible and achieves image quality comparable to clinician acquired photographs. The FFI derived from collected images shows association with clinical joint swelling and disease activity scores, but not PROs. In a substantial proportion of images, the FFI algorithm could not be applied because of insufficient image quality. More standardized image acquisition and further refinement of the FFI algorithm are warranted.","rel_num_authors":18,"rel_authors":[{"author_name":"Cinja Nadana Koller","author_inst":"University Hospital Lausanne (CHUV)"},{"author_name":"Jules Maglione","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"},{"author_name":"Marc Blanchard","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"},{"author_name":"Alexandre Dumusc","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"},{"author_name":"Diana Dan","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"},{"author_name":"Laure Brulhart","author_inst":"Department of Rheumatology, Reseau Hospitalier Neuchateloise de la Chaux de fonds, Switzerland"},{"author_name":"Michael Nissen","author_inst":"Department of Rheumatology, University Hospital of Geneva (HUG) and University of Geneva, Geneva, Switzerland"},{"author_name":"Michael Andor","author_inst":"Rheumatologie im Zuercher Oberland (RZO), Uster, Switzerland"},{"author_name":"Raphael Micheroli","author_inst":"Department of Rheumatology, University Hospital of Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"},{"author_name":"Almut Scherer","author_inst":"SCQM Foundation, Zurich, Switzerland"},{"author_name":"Christos Polysopoulos","author_inst":"SCQM Foundation, Zurich, Switzerland"},{"author_name":"Andrea Rubbert-Roth","author_inst":"Department of Rheumatology, Health Ostschweiz, Kantonsspital St. Gallen (HOCH), Switzerland"},{"author_name":"Christof Iking-Konert","author_inst":"Department of Rheumatology, Stadtspital Zurich, Zurich, Switzerland"},{"author_name":"Tobias Manigold","author_inst":"Rheumatology Inselspital, Bern, Switzerland"},{"author_name":"Burkhard Moeller","author_inst":"Rheumatology Inselspital, Bern, Switzerland"},{"author_name":"Chrisa Manolarki","author_inst":"Rheumabasel, Basel, Switzerland"},{"author_name":"Jeroen Geurts","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"},{"author_name":"Thomas Huegle","author_inst":"Department of Rheumatology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"The Case for Interpretable Geometry: Statistical Shape Models vs. Curvature-Based Descriptors in Aortic Disease Classification","rel_doi":"10.64898\/2026.07.29.26359299","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359299","rel_abs":"PurposeQuantifying aortic morphology is central to surgical planning for thoracic endovascular aortic repair (TEVAR), yet no consensus exists on how best to represent three-dimensional aortic shape for outcome prediction. Two broad strategies have emerged: statistical shape analysis (SSA), which relies on statistical methods and dimensionality reduction to capture the most significant shape modes, and geometrically-informed approaches that extract descriptors grounded in differential geometry. Here, we directly compare these paradigms on a cohort of 290 CTA scans classified by surgical outcome (non-pathological, successful TEVAR, failed TEVAR).\n\nMethodsFor the geometrically-informed approach, we use a two-dimensional feature space using normalized fluctuation in integrated Gaussian curvature [Formula] and mean aortic radius R. For SSA, we construct a point-cloud shape model with dimensionality reduction using Principal Component Analysis (PCA) and evaluate classification performance as a function of the number of retained principal components.\n\nResultsSSAs leading principal components encode variations in global aortic size and are statistically redundant with (R, [Formula]), yet they lack a one-to-one correspondence with interpretable anatomical quantities. Testing on an unseen, independent dataset reveals that the geometrically-informed approach provided better generalizability than SSA. Using Gaussian process classification with 10-fold cross-validation, we find that the geometrically-informed approach achieves a higher weighted F1 score than SSA achieves with up to 20 principal components. While SSAs full-dataset accuracy rises above 90% with increasing dimensionality, this gain is driven by overfitting rather than genuine discriminative power.\n\nConclusionThese results demonstrate that geometrically-informed descriptors offer a more interpretable, robust, and clinically translatable framework for aortic disease classification than data-driven statistical shape representations.","rel_num_authors":3,"rel_authors":[{"author_name":"Luka Pocivavsek","author_inst":"The University of Chicago"},{"author_name":"Duc Manh Nguyen","author_inst":"University of Chicago"},{"author_name":"Joseph Pugar","author_inst":"University of Chicago"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Accelerometer-derived Step Metrics and Quality of Life in Individuals with and without Cardiovascular Diseases","rel_doi":"10.64898\/2026.07.30.26359231","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.30.26359231","rel_abs":"Background and AimsSteps are increasingly used to prescribe physical activity, but their impact on quality of life (QoL) remains unclear. We examined the dose-response association between step metrics and QoL, and whether cardiovascular disease (CVD) status moderates this association.\n\nMethodsIndividual-level data of five studies were pooled. Physical activity was measured with thigh-worn accelerometry. We assessed steps\/day, daily minutes of fast stepping ([&ge;]100 steps\/min), peak 1- and 30- min cadence. We investigated the association of step metrics and QoL (questionnaire-based; standardized) with multivariable (non-)linear regression, and the interaction with CVD status.\n\nResultsWe included 9,371 participants (62 [54-68] years; 47% female), comprising 1,977 individuals with and 7,394 without CVD. Significant, curvilinear dose-response associations between step metrics and QoL were found. The optimal step volume was 6,561 steps\/day which associated with a 0.35 SD (95%CI: 0.28-0.42) higher QoL compared to the referent 4,000 steps\/day. The optimal doses for peak 1-min and peak 30-min cadence were 107 steps\/minute (+0.34 SD; 95%CI: 0.28-0.41) and 74 steps\/minute (+0.29 SD; 95%CI: 0.24-0.34) respectively, compared to references of 90 and 60 steps\/minute. Only fast stepping interacted with CVD status, with a lower optimum in those with versus without CVD (4 minutes\/day, +0.20 SD, 95%CI: 0.12-0.28 versus 9 minutes\/day, +0.19 SD, 95%CI: 0.12-0.25), compared to the referent 2 minutes\/day.\n\nConclusionsStep metrics were curvilinearly associated with QoL with optimal benefits at [~]6,500 steps\/day. Optimal QoL benefits can be reached at feasible stepping targets, and at slightly fewer daily minutes of fast stepping in CVD versus non-CVD.\n\nStructured graphical abstractO_ST_ABSKey QuestionsC_ST_ABSO_LIIs there a dose-response association between step metrics and health-related quality of life (QoL)?\nC_LIO_LIDoes the cardiovascular disease (CVD) health status moderate this association?\nC_LI\n\nKey FindingsO_LIMore steps\/day and time spent at fast stepping are associated with better QoL following a curvilinear dose-response curve.\nC_LIO_LIThe optimal step volume is 6,561 steps\/day, which was independent of CVD status.\nC_LIO_LIIndividuals with CVD may gain optimal QoL levels at slightly less time of fast stepping (4 min\/day) than those without CVD (9 min\/day).\nC_LI\n\nTake Home MessageMore steps and steps at a higher intensity are associated with better QoL. Optimal QoL benefits could be gained at feasible stepping targets (i.e. 4 min\/day of fast stepping for CVD, 9 min\/day for those without CVD).\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC=\"FIGDIR\/small\/26359231v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@1229fdforg.highwire.dtl.DTLVardef@2e1730org.highwire.dtl.DTLVardef@1f489d9org.highwire.dtl.DTLVardef@18637cc_HPS_FORMAT_FIGEXP  M_FIG C_FIG","rel_num_authors":16,"rel_authors":[{"author_name":"Sabine Schootemeijer","author_inst":"Radboudumc"},{"author_name":"Sophie H. Kroesen","author_inst":"Radboud university medical center"},{"author_name":"Niels A. Stens","author_inst":"Radboud university medical center"},{"author_name":"Milou Netten","author_inst":"Radboud university medical center"},{"author_name":"Inge P. Salzmann","author_inst":"Radboud university medical center"},{"author_name":"Annemarie Koster","author_inst":"Maastricht University"},{"author_name":"Neeltje E.A. Allard","author_inst":"Radboud university medical center"},{"author_name":"Bram M.A. van Bakel","author_inst":"Radboud university medical center"},{"author_name":"Francisco B. Ortega","author_inst":"University of Granada, CIBEROBN Physiopathology of Obesity and Nutrition"},{"author_name":"Emmanuel Stamatakis","author_inst":"Monash University, Victorian Heart Institute, University of Sydney"},{"author_name":"Matthew Ahmadi","author_inst":"Monash University, Victorian Heart Institute, University of Sydney"},{"author_name":"Janna N. Vrijsen","author_inst":"Radboud university medical center, Pro Persona Mental Health Care"},{"author_name":"Dick Thijssen","author_inst":"Radboud university medical center"},{"author_name":"Thijs M.H. Eijsvogels","author_inst":"Radboud university medical center"},{"author_name":"Esmee A. Bakker","author_inst":"Radboud university medical center"},{"author_name":"- STEP COACH collaborators","author_inst":"-"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Association of a Serum Proteomic Signature With Survival and Immune-Related Adverse Events in Patients With NSCLC Treated With Immune Checkpoint Inhibitors","rel_doi":"10.64898\/2026.07.29.26358704","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26358704","rel_abs":"Background: Serum proteomic signatures may reflect tumor- and host-related biology and serve as prognostic biomarkers in patients receiving immune checkpoint inhibitors (ICIs). We evaluated the association of the VeriStrat serum proteomic classification with survival outcomes and immune-related adverse events (irAEs) in patients with non-small cell lung cancer (NSCLC) treated with ICIs. Methods: We retrospectively reviewed patients with NSCLC who received ICI-containing therapy and underwent VeriStrat testing at Northwestern Memorial Hospital from October 2015 through June 2023. Patients were classified as proteomic signature Good (PS-Good) or Poor (PS-Poor). Progression-free survival (PFS) and overall survival (OS) were assessed among patients receiving palliative-intent ICI therapy. First any-grade and grade 3 or higher irAEs were evaluated in all ICI-treated patients using cumulative incidence functions and Fine-Gray competing-risk regression. Results: Among 162 ICI-treated patients included in the toxicity analysis, 129 received palliative-intent therapy and were included in the survival analysis; 91 (71%) were PS-Good and 38 (29%) were PS-Poor. PS-Good status was associated with longer PFS (median, 6 vs 3 months; hazard ratio [HR], 0.50; 95% CI, 0.33-0.77; P<0.01) and OS (median, 20 vs 8 months; HR, 0.59; 95% CI, 0.39-0.91; P=0.02). These associations remained significant after multivariable adjustment for PFS (adjusted HR, 0.46; 95% CI, 0.26-0.82; P<0.01) and OS (adjusted HR, 0.50; 95% CI, 0.28-0.87; P=0.01). Any-grade irAEs showed a nonsignificant trend toward a higher cumulative incidence in PS-Good patients. At 12 months, the cumulative incidence was 32.6% for PS-Good versus 22.5% for PS-Poor (subdistribution HR, 1.53; 95% CI, 0.77-3.02; P=0.23). The cumulative incidence of grade 3 or higher irAEs was similar between groups (16.3% vs 15.0%; subdistribution HR, 1.12; 95% CI, 0.48-2.62; P=0.79). Conclusions: PS-Good classification was independently associated with improved survival in patients with NSCLC receiving ICI-containing therapy. Although any-grade irAEs were numerically more frequent among PS-Good patients, proteomic classification was not significantly associated with any-grade or high-grade irAE risk. Prospective validation is warranted.","rel_num_authors":6,"rel_authors":[{"author_name":"Leeseul Kim","author_inst":"The University of Chicago Medical Center, Chicago, Illinois, USA"},{"author_name":"Donghoon Shin","author_inst":"MetroWest Medical Center\/Tufts University School of Medicine, Framingham, Massachusetts, USA"},{"author_name":"Taegyu Um","author_inst":"Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"},{"author_name":"Jeeyeon Lee","author_inst":"Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea"},{"author_name":"Allen Cho","author_inst":"Weiss Memorial Hospital, Chicago, Illinois, USA"},{"author_name":"Young Kwang Chae","author_inst":"Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Association of total and brain-derived Alzheimer's disease plasma biomarkers with brain amyloid deposition in a community-based sample","rel_doi":"10.64898\/2026.07.29.26359150","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359150","rel_abs":"Background and ObjectivesPlasma biomarkers, particularly brain-derived phosphorylated-tau (BD-p-tau) species, hold promise as screening tools for Alzheimers disease (AD). However, their ability to reflect AD pathology remains understudied in community settings. In a community-based sample, we examined associations between plasma biomarkers and cerebral amyloid (A{beta}) deposition, and whether kidney function modified these associations.\n\nMethodsThis cohort study included cognitively unimpaired, late middle-aged adults with18F-Florbetaben PET imaging and NULISAseq-derived plasma biomarker measurements. Analyses were restricted to NULISAseq biomarkers related to AD pathology (A{beta}38, A{beta}40, A{beta}42, ACHE, BACE1, BASP1, BD-p-tau181, BD-p-tau217, CD63, IGFBP7, KLK6, MAPT-tau, PSEN1, SFRP1, total p-tau181, p-tau217, and p-tau231). As a measure of kidney function, cystatin C-based estimated glomerular filtration rate was calculated and categorized by chronic kidney disease (CKD) stage as normal\/high ([&ge;]90 mL\/min\/1.73 m2); mildly decreased (60-89 mL\/min\/1.73 m2); and moderately\/severely decreased or failure (<60 mL\/min\/1.73 m2). Bidirectional stepwise linear regression analysis was performed to identify plasma biomarkers associated with brain A{beta} deposition. Linear regression models including plasma biomarker-by-CKD stage interactions tested effect modification by kidney function.\n\nResultsA total of 541 Hispanic, non-Hispanic Black, and non-Hispanic White participants were included. Stepwise linear regression retained plasma BD-p-tau217 (B = 0.22; 95% CI 0.19 to 0.25; p < 0.001), which was positively associated with brain A{beta} deposition, alongside A{beta}42 (B = -0.08; 95% CI -0.11 to -0.06; p < 0.001), IGFBP7 (B = -0.05; 95% CI -0.08 to -0.02; p = 0.004), and BACE1 (B = -0.04; 95% CI -0.07 to -0.01; p = 0.009), which were negatively associated with brain A{beta} deposition. A significant BD-p-tau217-by-CKD stage interaction demonstrated a weaker association between BD-p-tau217 and brain A{beta} deposition among individuals with moderately\/severely decreased kidney function or failure than those with normal\/high kidney function (B = -0.17; 95% CI -0.25 to -0.08; p < 0.001).\n\nDiscussionIn a real-world sample, BD-p-tau217 emerged as the plasma biomarker most strongly associated with brain A{beta} deposition, although this association may be attenuated in the presence of moderate\/severe kidney dysfunction or kidney failure. IGFBP7 and BACE1 were identified as candidate plasma biomarkers of brain A{beta} deposition, warranting replication in independent cohorts.","rel_num_authors":12,"rel_authors":[{"author_name":"Muge Akinci","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Froogh Aziz","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Diana Guzman","author_inst":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University"},{"author_name":"Lina Cheung","author_inst":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University"},{"author_name":"Jian X. Kong","author_inst":"Morris Stroud III Center for Study of Quality of Life in Health and Aging, Columbia University"},{"author_name":"Stephanie Silver","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Joseph Eimicke","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Sabrina Simoes","author_inst":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University"},{"author_name":"Jeanne A. Teresi","author_inst":"Columbia University Irving Medical Center"},{"author_name":"Adam M. Brickman","author_inst":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University"},{"author_name":"Patrick Lao","author_inst":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University"},{"author_name":"Jos\u00e9 A. Luchsinger","author_inst":"Columbia University Irving Medical Center"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Clinical Evaluation of a Multimodal On-Body Sensor Array","rel_doi":"10.64898\/2026.07.29.26359254","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359254","rel_abs":"Continuous, noninvasive blood pressure monitoring remains an unmet clinical need, particularly in the intensive care unit (ICU) where hemodynamically unstable patients need high-frequency monitoring. Invasive arterial catheterization represents the current standard of care for continuous blood pressure (BP) monitoring, but it carries risks and limits patient mobility. In this study, we evaluate the MOSAIC system, a novel multi-modal, multi-nodal wearable, wireless sensor system placed on multiple locations on the body, for continuous noninvasive BP estimation in a cohort of ICU patients. Unlike existing continuous BP sensors, the MOSAIC system offers an ideal form factor for continuous BP monitoring, enabling a fully untethered setup which minimally impacts activities of daily living. Leveraging sensor-derived biosignals to compute continuous BP, we determine the accuracy of our BP regression models using arterial line-derived blood pressure reading as a ground truth. Using a Light gradient boosted machine (LGBM)-based regression model, we demonstrate strong beat-to-beat agreement with a mean absolute error (MAE) of 5.66 {+\/-} 5.94 mmHg for systolic BP (SBP) prediction and 2.45 {+\/-} 2.87 mmHg for diastolic BP (DBP) prediction, and average ratio variability (ARV) of 0.527 {+\/-} 0.185 and 0.489 {+\/-} 0.170 for SBP and DBP, respectively, compared to linear and deep-learning regression baselines. Our findings demonstrate strong agreement between the predicted BP values and invasive, arterial-line BP measurements, supporting the feasibility of wearable, wireless, and cuffless blood pressure monitoring in high-acuity clinical settings.","rel_num_authors":8,"rel_authors":[{"author_name":"Bright Nnadi","author_inst":"Johns Hopkins University"},{"author_name":"Sampath Rapuri","author_inst":"Johns Hopkins University"},{"author_name":"Carl Harris","author_inst":"Johns Hopkins University"},{"author_name":"John Rattray","author_inst":"Johns Hopkins University"},{"author_name":"Francesco Tenore","author_inst":"Applied Physics Laboratory"},{"author_name":"Charlene Gamaldo","author_inst":"Johns Hopkins University"},{"author_name":"Ralph Etienne-Cummings","author_inst":"Johns Hopkins University"},{"author_name":"Robert Stevens","author_inst":"Johns Hopkins University"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"A Supervised Text-Embedded Transformer Matching Model to Detect Fall Injuries in Medicare Data","rel_doi":"10.64898\/2026.07.29.26359258","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359258","rel_abs":"ObjectiveTo develop and validate a supervised text-embedded transformer matching model to identify fall injuries in Medicare data, and evaluate the models performance -- alongside a validated rule-based algorithm-- against \"ground truth\" from an external reference standard (self-reported fall injuries leading to medical attention).\n\nMaterials and MethodsText embeddings of ICD-10-CM and CPT codes in Medicare claims\/encounters from participants in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial served as model inputs. Trained on annotated claims\/encounters occurring within +\/- one month of self-reported fall injuries leading to medical attention, the transformer model generated a continuous 0-1 probability that each claim\/encounter was for a fall injury. The model was then applied to all claims\/encounters in STRIDE and compared alongside the rule-based algorithm to the external reference standard.\n\nResultsThe model achieved an area under the curve (AUC) of > 0.96 against annotated claims\/encounters in 9 out of 10 holdout folds and 0.85 in the remaining fold. In the full STRIDE dataset, the model achieved a peak AUC of 0.86 (95% CI, 0.84-0.87) against the external reference standard, with results comparable to the rule-based algorithm.\n\nDiscussionRelative to rule-based approaches, which typically generate binary outcomes, the continuous event probability generated by the transformer model could support clinical endpoint adjudication, with high-probability predictions treated as events, moderate-probability predictions being adjudicated, and low-probability predictions treated as non-events.\n\nConclusionA text-embedded transformer model identified fall injuries with comparable accuracy to a rule-based algorithm, demonstrating \"proof of concept\" for use in endpoint adjudication.","rel_num_authors":6,"rel_authors":[{"author_name":"Michael Kane","author_inst":"The University of Texas, MD Anderson Cancer Center"},{"author_name":"Erich J Greene","author_inst":"Yale University School of Public Health"},{"author_name":"Denise Esserman","author_inst":"Yale University School of Public Health"},{"author_name":"Nancy K Latham","author_inst":"Brigham and Women's Hospital"},{"author_name":"Lillian C. Min","author_inst":"The University of Michigan"},{"author_name":"David A. Ganz","author_inst":"David Geffen School of Medicine at UCLA"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Uromodulin T62P variant causes kidney tubular stress and injury modulated by age and polygenic risk","rel_doi":"10.64898\/2026.07.29.26359269","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359269","rel_abs":"While ultra-rare missense variants in UMOD cause highly penetrant autosomal dominant tubulointerstitial kidney disease, a more frequent UMOD T62P variant conveys intermediate risk with variable penetrance. To determine whether age or polygenic risk contributes to the variable penetrance of T62P, we combined genotype and phenotype data from 882,306 individuals across the UK Biobank (discovery cohort) and the All of Us and MyCode biobanks (validation cohorts). We also analyzed the impact of aging on uromodulin processing and cellular stress in stably transfected kidney tubular cells expressing wild-type or mutant UMOD. We compared the effects of the GPS on risk of CKD between T62P carriers and non-carriers and tested for the GPS-by-T62P interaction. The UMOD T62P variant was reproducibly associated with increased risk of CKD in an age-dependent manner. Compared to wild-type, clones of T62P-expressing cells exhibited a defective uromodulin maturation profile, causing endoplasmic reticulum retention and stress. We also observed significant T62P-by-GPS interaction, with T62P carriers in the top quintile of the GPS having over 5-fold higher risk of CKD compared to population average (OR 5.17, 95%CI: 2.94-9.08, P=1.0E-08). In summary, we demonstrate that the penetrance of kidney disease in T62P carriers is strongly modified by both age and polygenic risk.","rel_num_authors":12,"rel_authors":[{"author_name":"Atlas Khan","author_inst":"Columbia University"},{"author_name":"Andrea Gresch","author_inst":"University of Zurich"},{"author_name":"Eric Olinger","author_inst":"Cliniques universitaires Saint-Luc"},{"author_name":"Marta Mariniello","author_inst":"University of Zurich"},{"author_name":"Ning Shang","author_inst":"Columbia University"},{"author_name":"Maria Vanessa Perez-Gomez","author_inst":"Fundacion Jimenez Diaz University Hospital"},{"author_name":"Ian Dinsmore","author_inst":"Geisinger"},{"author_name":"Holly Mabillard","author_inst":"Newcastle University"},{"author_name":"Tooraj Mirshahi","author_inst":"Geisinger"},{"author_name":"Alex R Chang","author_inst":"Geisinger"},{"author_name":"Olivier Devuyst","author_inst":"University of Zurich"},{"author_name":"Krzysztof Kiryluk","author_inst":"Columbia University"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Pandemic risk in the Shared Socioeconomic Pathways","rel_doi":"10.64898\/2026.07.29.26359250","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359250","rel_abs":"For over a decade, the Shared Socioeconomic Pathways (SSPs) have served as the principal framework for quantitative modeling of the socioeconomic dimensions of global environmental change. The SSP scenarios describe many of the ecological and social processes thought to shape pandemic risk, including the emergence of novel pathogens (accelerated by processes such as deforestation, livestock intensification, and land-use change) and their subsequent spread (mediated by factors such as inequality, human mobility, and health system capacity). However, the SSP framework has not been widely incorporated into pandemic risk assessment. Here, we assess how pandemic risk is embedded in the SSP framework, and find that the framework captures most of the social-environmental drivers of pathogen spillover, and many of the social-economic drivers of pandemic spread and impacts. Because climate change and pandemics share many drivers and risk factors--including ecosystem degradation, animal agriculture, and weak governance--SSP scenarios characterized by higher barriers to climate adaptation also generally imply lower chances of outbreak containment, and greater pandemic impacts on vulnerable populations. Pandemic risk is therefore lowest in SSP1 and highest in SSP3, but SSP5 shows that frequent spillover and effective containment can coexist. These findings suggest that pandemic risk can be understood as part of a broader polycrisis, linking climate change, biodiversity loss, and global health. We suggest that new scenario extensions, or entirely novel frameworks, will ultimately be needed to capture possible shifts in the global health landscape; however, in the meantime, scenario frameworks from the environmental sciences could be valuable tools for initiatives to quantify future pandemic risks.","rel_num_authors":14,"rel_authors":[{"author_name":"Torre Lavelle","author_inst":"Yale University"},{"author_name":"Cecilia Sanchez","author_inst":"Yale University"},{"author_name":"Marina Andrijevic","author_inst":"International Institute for Applied Systems Analysis"},{"author_name":"Daniel J. Becker","author_inst":"University of Oklahoma"},{"author_name":"Rory Gibb","author_inst":"University College London"},{"author_name":"Gregg S. Gonsalves","author_inst":"Yale School of Public Health"},{"author_name":"Zoe ODonoghue","author_inst":"Yale School of Public Health"},{"author_name":"Shonali Pachauri","author_inst":"International Institute for Applied Systems Analysis"},{"author_name":"Laura Pereira","author_inst":"Global Change Institute, Wits University"},{"author_name":"Timothee Poisot","author_inst":"University of Montreal"},{"author_name":"Sadie J. Ryan","author_inst":"University of Florida"},{"author_name":"Stephanie N. Seifert","author_inst":"Washington State University"},{"author_name":"Charles Whittaker","author_inst":"University of California, Berkeley"},{"author_name":"Colin J. Carlson","author_inst":"Yale University School of Public Health"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Pandemic risk in the Shared Socioeconomic Pathways","rel_doi":"10.64898\/2026.07.29.26359250","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359250","rel_abs":"For over a decade, the Shared Socioeconomic Pathways (SSPs) have served as the principal framework for quantitative modeling of the socioeconomic dimensions of global environmental change. The SSP scenarios describe many of the ecological and social processes thought to shape pandemic risk, including the emergence of novel pathogens (accelerated by processes such as deforestation, livestock intensification, and land-use change) and their subsequent spread (mediated by factors such as inequality, human mobility, and health system capacity). However, the SSP framework has not been widely incorporated into pandemic risk assessment. Here, we assess how pandemic risk is embedded in the SSP framework, and find that the framework captures most of the social-environmental drivers of pathogen spillover, and many of the social-economic drivers of pandemic spread and impacts. Because climate change and pandemics share many drivers and risk factors--including ecosystem degradation, animal agriculture, and weak governance--SSP scenarios characterized by higher barriers to climate adaptation also generally imply lower chances of outbreak containment, and greater pandemic impacts on vulnerable populations. Pandemic risk is therefore lowest in SSP1 and highest in SSP3, but SSP5 shows that frequent spillover and effective containment can coexist. These findings suggest that pandemic risk can be understood as part of a broader polycrisis, linking climate change, biodiversity loss, and global health. We suggest that new scenario extensions, or entirely novel frameworks, will ultimately be needed to capture possible shifts in the global health landscape; however, in the meantime, scenario frameworks from the environmental sciences could be valuable tools for initiatives to quantify future pandemic risks.","rel_num_authors":14,"rel_authors":[{"author_name":"Torre Lavelle","author_inst":"Yale University"},{"author_name":"Cecilia Sanchez","author_inst":"Yale University"},{"author_name":"Marina Andrijevic","author_inst":"International Institute for Applied Systems Analysis"},{"author_name":"Daniel J. Becker","author_inst":"University of Oklahoma"},{"author_name":"Rory Gibb","author_inst":"University College London"},{"author_name":"Gregg S. Gonsalves","author_inst":"Yale School of Public Health"},{"author_name":"Zoe ODonoghue","author_inst":"Yale School of Public Health"},{"author_name":"Shonali Pachauri","author_inst":"International Institute for Applied Systems Analysis"},{"author_name":"Laura Pereira","author_inst":"Global Change Institute, Wits University"},{"author_name":"Timothee Poisot","author_inst":"University of Montreal"},{"author_name":"Sadie J. Ryan","author_inst":"University of Florida"},{"author_name":"Stephanie N. Seifert","author_inst":"Washington State University"},{"author_name":"Charles Whittaker","author_inst":"University of California, Berkeley"},{"author_name":"Colin J. Carlson","author_inst":"Yale University School of Public Health"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"A Neuro-Symbolic Knowledge Graph and Large Language Model Hybrid Architecture for Multi-Modality Mental Health Counseling","rel_doi":"10.64898\/2026.07.29.26359268","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359268","rel_abs":"BackgroundDepression and anxiety are managed largely between clinical visits, yet outpatient care lacks scalable, accountable mechanisms for between-visit support. Large language models converse fluently but fuse clinical reasoning with language generation in one opaque process, so they cannot reliably deliver evidence-based psychotherapy and typically operate outside clinician oversight.\n\nObjectiveTo evaluate C-Mind, a provider-supervised neuro-symbolic system in which a Clinical Knowledge Graph (KG) governs therapeutic decisions for a large language model across eight psychotherapy modalities.\n\nMethodsTwo simulation regimes addressed eight pre-specified governance questions: a structural validation of KG routing against 117 guideline-anchored vignettes, and a governance battery using progressively disclosing LLM patient agents to evaluate decision traceability, repeatability, provenance auditability, adversarial crisis-detection robustness (277 probes), provider treatment-goal governance, and counselor technique adherence. Crisis detection was additionally validated externally against an independent, clinician-annotated corpus (CRADLE Bench).\n\nResultsThe KG routed 116\/117 vignettes (99.1%) to guideline-appropriate care and detected all 18 high-risk presentations, firing a therapy-suppressing hard halt on 16\/18. Adversarial crisis-detection sensitivity was 96.7% and specificity 95.4% (277 probes); on external validation, the system detected 98.5% of 600 dialogues with ongoing suicidal ideation or self-harm at or before the annotators confirming turn. Decisions were 99.1% repeatable, 100% reconstructable per turn, and 100% provenance-auditable across all 354 KG nodes. Provider-set diagnosis, goals, and safety context governed behavior deterministically. Stripped of governance, the same model produced unsolicited clinical monologues on 100% of turns (vs 9% governed) and delivered diagnoses and medication advice the governed system never produced.\n\nConclusionsA neuro-symbolic architecture achieves near-perfect guideline-appropriate routing with a governance profile -- traceability, reproducibility, machine-traceable provenance, externally validated crisis detection, and deterministic provider control -- aligned with requirements for regulated clinical AI.\n\nHighlightsO_LIClinical Knowledge Graph governs LLM psychotherapy without fine-tuning\nC_LIO_LI100% crisis-detection sensitivity across 18 high-risk vignettes\nC_LIO_LIPer-turn KG decisions fully traceable and reconstructable for audit\nC_LIO_LI100% guideline provenance on all 354 nodes; 99.1% five-run repeatability\nC_LI","rel_num_authors":8,"rel_authors":[{"author_name":"Jun Tao","author_inst":"Brown University"},{"author_name":"Natalie Fenn","author_inst":"Brown University"},{"author_name":"Hannah Parent","author_inst":"The Miriam Hospital, Brown University Health"},{"author_name":"Hao Wu","author_inst":"C-Mind LLC"},{"author_name":"Trisha Arnold","author_inst":"Brown University"},{"author_name":"Jennifer Etue","author_inst":"Open Door Health"},{"author_name":"Elizabeth Chen","author_inst":"Brown University"},{"author_name":"Philip Chan","author_inst":"Brown University"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"From Polio to COVID-19: Factors Sustaining Community Influencer Motivation in the CORE Group Partners Project's Social Mobilization Initiatives for Vaccination in India","rel_doi":"10.64898\/2026.07.22.26358734","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.22.26358734","rel_abs":"IntroductionEngaging Community Influencers (CIs) was a key strategy for polio eradication in India, also contributing to routine vaccination and COVID-19 vaccination. CIs were high status individuals selected for their pre-existing reach into vaccine-hesitant communities. This paper describes the factors that kept the CIs engaged over time. The findings add to our understanding of what drives CHW motivation.\n\nMethodsWe performed a thematic analysis of 65 in-depth interviews conducted across six study districts of Uttar Pradesh, involving 36 CIs, 18 CGPP field staff, nine project managers and two representatives from other stakeholders.\n\nFindingsThe most important motivational factors that emerged from the research were improved social status, altruism, and effective working relationships. The inputs required to foster these were information support; providing respect and visibility; and fostering robust working relationships between program staff, CIs, CHWs, and government functionaries.\n\nConclusionsCIs engagement in the program maintained and bolstered their pre-existing status. Deploying and sustaining this cadre requires a strategic approach to maintaining motivation over time. Providing respect and visibility and maintaining effective working relationships is key to sustaining the CIs motivation.\n\nKey MessagesO_LIThe Community Influencer approach, initially introduced for polio eradication, has evolved over time into a vital strategy for increasing routine immunization and COVID-19 vaccination coverage.\nC_LIO_LICommunity Influencers are high status individuals, selected by program (CGPP) staff for their pre-existing status in vaccine-hesitant communities.\nC_LIO_LIThis study looks at how the motivation and engagement for this cadre was sustained over a 20-year period.\nC_LIO_LISeveral key factors sustained the Community Influencers engagement over time, including a pre-existing commitment to their community, the program successes, visibility and respect; the working relationships with program staff and government functionaries; and, finally, the Influencers status within the community.\nC_LIO_LIConsidering that many health systems struggle with a demotivated workforce, these findings provide practical guidance for fostering health worker engagement.\nC_LI","rel_num_authors":11,"rel_authors":[{"author_name":"Anna Schurmann","author_inst":"London School of Hygiene & Tropical Medicine"},{"author_name":"Arup Kumar Das","author_inst":"Government of Uttar Pradesh"},{"author_name":"Sanjna Sinha","author_inst":"Independent"},{"author_name":"Pankaj Mishra","author_inst":"Jawaharlal Nehru University"},{"author_name":"Balkrishnan Yadav","author_inst":"Tattva Foundation"},{"author_name":"Parul Ratna","author_inst":"Independent"},{"author_name":"Jitendre Awale","author_inst":"CORE Group Partners Project"},{"author_name":"Manojkumar Choudhary","author_inst":"CORE Group Partners Project"},{"author_name":"Kathy Vassos Stamidis","author_inst":"CORE Group Partner Project"},{"author_name":"Hibret Tilahun","author_inst":"CORE Group Partners Project"},{"author_name":"Henry Perry","author_inst":"JHU SPH: Johns Hopkins University Bloomberg School of Public Health"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Phased amplicon multiplex sequencing for cost-effective detection of high-risk human papillomavirus from cervical samples","rel_doi":"10.64898\/2026.07.27.26359029","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.27.26359029","rel_abs":"Access to accurate cost-effective technologies for typing high-risk human papillomaviruses (hrHPV) is critical to expand cervical cancer screening and inform vaccination strategies. Compared with clinical-standard quantitative polymerase chain reaction (qPCR) assays, HPV genotyping by next-generation sequencing (NGS) provides greater flexibility, scalability, and genotype specificity. We have developed a method for HPV genotyping, HPV Phased Amplicon Multiplex Sequencing (PhAM-Seq), that uses combinatorial barcoding of amplicons with short, variable-length inline sequences to enable higher throughput and lower per-sample costs than conventional amplicon sequencing approaches. We evaluated HPV PhAM-Seq using degenerate and type-specific primers targeting the L1 and E6-E7 gene loci in a blinded cohort of 170 cervical samples previously typed by the Seegene Anyplex II HPV28 Detection qPCR assay. Across eight common hrHPV types (HPV16, 18, 31, 33, 35, 45, 52, and 58), HPV PhAM-Seq demonstrated >80% overall agreement with qPCR using degenerate L1-targeting primers, with the highest sensitivity for HPV16, 31, 33, and 58. Sensitivity for HPV35, 45, and 52 improved to [&ge;]85% with type-specific primers targeting genes E6\/E7. Parallel processing and sequencing enables a single technician to assay hundreds of samples per week at a reagent cost of around $10 USD per sample, with laboratory automation and sequencing on higher-output platforms enabling further scaling and cost reduction to a scale amenable to population-level surveillance. We include a detailed SOP; tools for primer design, sequencing library construction, and sample tracking; and all scripts needed for data analysis to ensure HPV PhAM-Seq can be readily implemented for scalable, cost-effective hrHPV genotyping or extended to other similar applications.","rel_num_authors":10,"rel_authors":[{"author_name":"Dipesh Solanky","author_inst":"The Broad Institute of MIT and Harvard"},{"author_name":"Charlotte Low","author_inst":"The Broad Institute of MIT and Harvard"},{"author_name":"Christine L. Hathaway","author_inst":"Massachusetts General Hospital"},{"author_name":"Stephen Cherne","author_inst":"University of Washington"},{"author_name":"Elizabeth Brown","author_inst":"University of Washington"},{"author_name":"Thesla Palanee-Phillips","author_inst":"University of Washington"},{"author_name":"Ruanne V. Barnabas","author_inst":"Massachusetts General Hospital"},{"author_name":"Roby Paul Bhattacharyya","author_inst":"The Broad Institute of MIT and Harvard"},{"author_name":"Brittany Berdy","author_inst":"The Broad Institute of MIT and Harvard"},{"author_name":"Jonathan Livny","author_inst":"The Broad Institute of MIT and Harvard"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Use of additional therapies after minimally invasive therapies among women with overactive bladder","rel_doi":"10.64898\/2026.07.29.26359239","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359239","rel_abs":"ObjectiveTo evaluate the rate, timing, and predictors of additional therapy among women with idiopathic overactive bladder (OAB) following initial minimally invasive treatments (MIT).\n\nStudy DesignRetrospective single center cohort study of women with idiopathic OAB treated between 2012 and 2021. Using ICD and procedural codes, we identified women who underwent posterior tibial nerve stimulation (PTNS), sacral neuromodulation (SNM), or intradetrusor onabotulinumtoxinA (BTX). The primary outcome was receipt of additional OAB treatments,OAB medication initiation or a different MIT. Kaplan-Meier analysis estimated time to additional therapies; Cox proportional hazards and random survival forest models identified predictors.\n\nResults1,007 women were included (PTNS: 459; SNM: 192; BTX: 356). At three years, 75% of PTNS patients, 58% of BTX patients, and 40% of SNM women required additional therapies with most patients choosing additional pharmacotherapy rather than crossover to a different MIT. Median time to additional treatments was 10 months (PTNS), 19 months (BTX), and 53 months (SNM). Higher BMI was associated with increased risk of further treatment after SNM (HR 2.1, 95% CI: 1.1-4.2), while recurrent urinary tract infections were associated with needing additional therapies in the BTX cohort (HR 1.8, 95% CI: 1.1-3.2). Random survival forest models resulted in poor model performance.\n\nConclusionsFollowing initial MIT for idiopathic OAB, many women required additional treatment within three years, many choosing pharmacotherapy rather than transition to another MIT.\n\nWhy This MattersOveractive bladder (OAB) affects over 20% of women in the United States, and current AUA\/SUFU guidelines have shifted from traditional stepwise therapy toward shared decision-making and multimodal treatment. While minimally invasive therapies (MIT) are effective options for OAB, real-world data on patient trajectories after MIT initiation, including rates of treatment augmentation, crossover, or return to pharmacotherapy, remain limited.\n\nThis retrospective cohort of 1,007 women with idiopathic OAB provides novel data on post-MIT care-seeking, with 40-75% of patients requiring additional therapy within three years. SNM demonstrated the longest interval before additional therapy and the lowest rate of subsequent care-seeking. Notably, most women who required additional treatment chose pharmacotherapy rather than crossing over to a different MIT. Modifiable risk factors associated with additional care-seeking included higher BMI after SNM and recurrent urinary tract infections after BTX, though whether addressing these factors would reduce the need for additional therapy remains unclear.\n\nThese findings reinforce that OAB management is a dynamic, ongoing process rather than a one-time intervention, and that multimodal therapy is often necessary for optimal improvement. Clinicians can use these data to set realistic expectations during counseling, framing additional therapy as a common and anticipated part of the treatment trajectory rather than a treatment failure.","rel_num_authors":10,"rel_authors":[{"author_name":"Yu Zheng","author_inst":"Department of Urology, Brigham and Women s Hospital, Boston MA"},{"author_name":"Mahir Maruf","author_inst":"The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD"},{"author_name":"Franco Alchiede Simonato","author_inst":"Urology Clinic, Department of Precision Medicine in Medical, Surgical and Critical Care, University of Palermo, 90127 Palermo, Italy"},{"author_name":"Whitney K Hendrickson","author_inst":"Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT"},{"author_name":"David Sheyn","author_inst":"Division of Urogynecology and Reconstructive Pelvic Surgery, Urology Institute, University Hospitals, Cleveland OH"},{"author_name":"James Hokanson","author_inst":"Joint Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, WI"},{"author_name":"Caitlin Seibel","author_inst":"Department of Urology, University of Michigan, Ann Arbor, MI"},{"author_name":"Quentin Clemens","author_inst":"Department of Urology, University of Michigan, Ann Arbor, MI"},{"author_name":"Aruna Sarma","author_inst":"Department of Urology, University of Michigan, Ann Arbor, MI"},{"author_name":"Giulia Maria Rosa Ippolito","author_inst":"Department of Urology, University of Michigan, Ann Arbor, MI"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Evaluation of Type 2 Diabetes Like Subtypes in Gestational Diabetes","rel_doi":"10.64898\/2026.07.29.26359198","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.29.26359198","rel_abs":"IntroductionGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance that is first identified during pregnancy and typically resolves after childbirth. This condition can lead to various complications, both prenatal and postnatal, including type 2 diabetes (T2D). However, not all women with GDM progress to T2D, and the molecular mechanisms underlying this heterogeneity remain poorly understood. Here, we hypothesized that GDM participants could be clustered into T2D-like subtypes.\n\nMethodsTo derive T2D-like subtypes, we applied K-means clustering to GDM participants using the predefined T2D subtype cluster centers established in the QPHI cohort. Differential methylation analysis was performed, and the top-ranked sites were used for further analysis. Additionally, we estimated system-specific age acceleration and its association with subtype-specific complications.\n\nResultsOur study demonstrated the effectiveness of the novel clustering approach, originally developed for T2D, in GDM. Additionally, the exploratory analysis of the top-ranked CpG sites suggested potential subtype-related methylation patterns. The identified pathways also suggested overlapping molecular mechanisms underlying both GDM and T2D.\n\nConclusionThese findings support the feasibility of classifying GDM into T2D-like clinical subtypes and suggest potential epigenetic differences that warrant validation in larger longitudinal cohorts.","rel_num_authors":5,"rel_authors":[{"author_name":"Luma Srour","author_inst":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar"},{"author_name":"Nayra Al-Thani","author_inst":"Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University"},{"author_name":"Eleni Fthenou","author_inst":"Qatar Precision Health Institute, Qatar Foundation for Education, Science, and Community, Doha, Qatar"},{"author_name":"Omar Albagha","author_inst":"Hamad Bin Khalifa University"},{"author_name":"Nady El Hajj","author_inst":"Hamad Bin Khalifa University"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Moving Past Tonsil Position: Craniocervical Junction Crowding Shapes Cerebrospinal Fluid Effective Motility in Chiari I Malformation","rel_doi":"10.64898\/2026.07.28.26358336","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26358336","rel_abs":"Chiari I malformation (CM-I) is conventionally defined by cerebellar tonsil position, yet tonsil position is an indirect surrogate for the anatomic obstruction that impairs cerebrospinal fluid (CSF) flow across the craniocervical junction (CCJ). We hypothesized that CCJ crowding, quantified as subarachnoid space narrowing at the foramen magnum and C1, would explain CSF flow impairment more directly than tonsil position. Using non-invasive low b-value diffusion-weighted MRI (low-b dMRI), we quantified effective CSF motility, indexed by mean pseudo-diffusivity (M{Psi}), across the upper cervical spine, CCJ, and posterior fossa. Voxel-wise CCJ CSF pseudo-diffusion spatial statistics were integrated with CSF Waterways atlas-based regional analyses. We applied this approach in 81 pediatric and adult participants with CM-I to determine how CCJ structural features shape regional CSF dynamics and clinical outcomes. Voxel-wise analyses revealed that crowding at the foramen magnum was the dominant structural determinant of reduced intracranial CSF effective motility across the CCJ, basilar cisterns, and fourth ventricular outflow pathways (family-wise error corrected p < 0.05). While lower tonsil position and C1 level crowding were also associated with reduced CSF effective motility across the CCJ and fourth ventricular outflow pathways, but their associations within the basilar cisterns were spatially restricted to regions adjacent to the Liliequist membrane. Atlas-based region-of-interest analyses confirmed that greater foramen magnum crowding was associated with lower M{Psi} across multiple basilar cisterns, but with higher M{Psi} in the ventral spinal CSF compartment. Mediation analyses indicated that CCJ crowding at the foramen magnum and C1 accounted for the majority of the relationship between tonsil position and reduced CSF motility in the basilar cisterns. Multivariate M{Psi} profiles across the CSF regions identified data-driven foramen magnum crowding thresholds of 69.5% and 77.5%, stratifying patients into mild, moderate, and severe physiological crowding groups. Exploratory analyses linked lower pre-operative CSF M{Psi} to greater pain-related functional impairment, reduced cognitive function, and a higher likelihood of subsequent decompression surgery. Together, these findings demonstrate that CCJ crowding, particularly at the foramen magnum, exerts a quantifiable, region-specific impact on CSF effective motility in CM-I, and that low-b dMRI provides a sensitive, complementary marker of CSF flow impairment. This integrative CCJ structural and CSF flow imaging framework establishes a mechanistic link between CCJ anatomy, CSF dynamics, and symptom burden, offering a scalable tool for phenotyping CM-I and informing clinical decision-making.","rel_num_authors":12,"rel_authors":[{"author_name":"Helia Hosseini","author_inst":"Washington University in St. Louis"},{"author_name":"Amir H Shaker","author_inst":"Washington University in St. Louis"},{"author_name":"Connor A Sierra","author_inst":"Washington University in St. Louis"},{"author_name":"Wan-Yun Shen","author_inst":"Washington University in St. Louis"},{"author_name":"Zhouqiao Zhao","author_inst":"Washington University in St. Louis"},{"author_name":"Farrell Landwehr","author_inst":"Washington University in St. Louis"},{"author_name":"Aristeidis Sotiras","author_inst":"University of Pennsylvania"},{"author_name":"Joshua S Shimony","author_inst":"Washington University in St. Louis"},{"author_name":"Bryn A Martin","author_inst":"University of Idaho"},{"author_name":"David D Limbrick Jr.","author_inst":"Virginia Commonwealth University"},{"author_name":"Jennifer M Strahle","author_inst":"Washington University in St. Louis"},{"author_name":"Arash Nazeri","author_inst":"Washington University in St. Louis"}],"rel_date":"2026-07-31","rel_site":"medrxiv"},{"rel_title":"Altered T1w\/T2w-FLAIR Ratio in White Matter Hyperintensities as an Indicator of Structural Integrity Loss: Association with Alzheimer's Disease and Vascular Dementia","rel_doi":"10.64898\/2026.07.28.26359139","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26359139","rel_abs":"BackgroundWhite matter hyperintensities (WMH) are prevalent in dementia, but lesion volume does not capture their microstructural heterogeneity. The T1-weighted to fluid-attenuated inversion recovery (T1w\/T2w-FLAIR) ratio is sensitive to myelin, gliosis, and tissue water. We tested whether lesion-specific T1w\/T2w-FLAIR ratio, referenced to each participants normal-appearing white matter (NAWM), differs by diagnosis and reflects distinct amyloid and vascular mechanisms in Alzheimers disease (AD) and vascular dementia (VD).\n\nMethodsWe analyzed 576 participants from the multicentre BICWALZS cohort (seven South Korean sites), spanning subjective cognitive impairment (SCI, n=71), mild cognitive impairment (n=270), AD (n=125) and VD (n=88). WMH T1w\/T2w-FLAIR ratio was regressed on NAWM ratio, yielding standardized residuals as the outcome. Regression and mediation models tested diagnosis, plasma biomarkers, APOE genotype, amyloid PET and vascular risk burden, adjusting for age, sex, education and site. We conducted regression and mediation analyses after multiple imputation for missing variables. We adjusted for hierarchical models using Bonferroni correction. We tested for insensitivity to site effects by applying ComBat harmonization.\n\nResultsOlder age, AD, VD, and high vascular risk burden were associated with higher residualized T1w\/T2w-FLAIR ratios relative to SCI. Lower plasma amyloid-beta 42 (greater amyloid burden) was associated with lower T1w\/T2w-FLAIR ratios. Greater vascular burden was associated with greater T1w\/T2w-FLAIR ratios, which partially mediated the VD association with T1w\/T2w-FLAIR. Lower amyloid-beta 42 (greater amyloid) was associated with lower T1w\/T2w-FLAIR, which partially mediated the effect between AD and T1w\/T2w-FLAIR ratio. Findings were robust to harmonization.\n\nConclusionsResidualized WMH T1w\/T2w-FLAIR ratio captures lesion-specific microstructural variation missed by volumetric measures, consistent with vascular-gliotic injury in VD and coexisting amyloid-linked demyelination in AD. Limitations include the cross-sectional design, no cognitively normal comparison group, and a predominantly Korean sample.","rel_num_authors":30,"rel_authors":[{"author_name":"Rushil Srirambhatla","author_inst":"Johns Hopkins University"},{"author_name":"Jacques-Yves Campion","author_inst":"Universite de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France Department of Psychiatry, School of Medicine, University of Pitt"},{"author_name":"Thomas Desmidt","author_inst":"Universite de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France Centre Hospitalier Regional Universitaire (CHRU) de Tours, Tours"},{"author_name":"Yiyan Pan","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Department of Bioengineering, University of Pittsburgh, Pittsburgh,"},{"author_name":"Carmen Andreescu","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Pamela C.L. Ferreira","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Guilherme Povala","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Bruna Bellaver","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Joao Pedro Ferrari-Souza","author_inst":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil"},{"author_name":"Douglas T. Leffa","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Firoza Z. Lussier","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Marina Scop Medeiros","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Emma Ruppert","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Francieli Rohden","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Graduate Program in Biological Sciences: Biochemistry, Universidade"},{"author_name":"Chang Hyung Hong","author_inst":"Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Hyun Woong Roh","author_inst":"Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Bumhee Park","author_inst":"Department of Biomedical Informatics, Ajou University School of Medicine, Suwon Republic of Korea (South Korea) Office of Biostatistics, Ajou Research Institute"},{"author_name":"Jin Wook Choi","author_inst":"Department of Radiology, Ajou University School of Medicine, Seoul, South Korea"},{"author_name":"Sang Won Seo","author_inst":"Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (South Korea)"},{"author_name":"Seong Hye Choi","author_inst":"Department of Neurology, Inha University School of Medicine, Incheon, Republic of Korea (South Korea)"},{"author_name":"So Young Moon","author_inst":"Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Eun-Joo Kim","author_inst":"Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Kor"},{"author_name":"Byeong C. Kim","author_inst":"Department of Neurology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Republic of Korea (South Korea)"},{"author_name":"Young-Sil An","author_inst":"Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Republic of Korea (South Korea)"},{"author_name":"Yong Hyuk Cho","author_inst":"Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Sunhwa Hong","author_inst":"Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Thomas K. Karikari","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"author_name":"Tharick A. Pascoal","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Department of Neurology, School of Medicine, University of Pittsbur"},{"author_name":"Sang Joon Son","author_inst":"Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea)"},{"author_name":"Helmet T. Karim","author_inst":"Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Department of Bioengineering, University of Pittsburgh, Pittsburgh,"}],"rel_date":"2026-07-30","rel_site":"medrxiv"},{"rel_title":"Benchmarking sex and gender incorporation into health and medical research, policy and education in Victoria prior to 2026","rel_doi":"10.64898\/2026.07.27.26358999","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.27.26358999","rel_abs":"ObjectiveTo investigate and establish a baseline for sex and gender considerations in policy, research and curricula across the state of Victoria.\n\nDesign and settingVictoria was selected as a case study for Australia, using a mixed-methods approach to examine health and medical university curricula, research organisation policies and research funding between 2020-2025 prior to mandated inclusion.\n\nMain outcome measuresPrimary outcomes include identification of predefined sex- and gender-related terms in university curricula descriptors and funded grant descriptions; and questionnaire responses from university course coordinators and organisational leads.\n\nResultsData mining across nine Victorian universities (318 courses\/3383 units) identified [~]93% of units and [~]60% of healthcare courses lacked sex and gender terms in their descriptors. Among medical research organisations operating in Victoria, including peak bodies, research institutes, hospitals and universities, [~]70% (18\/26) of the survey responders reported having no sex and gender policy. Rates of sex- and gender-term inclusion in research grants allocated in Victoria (3388) and Australia-wide (8974) validated Victoria as a case study for Australia for National Health and Medical Research Council (9.5%\/8.9% respectively), Medical Research Future Funds (11%\/10.2%), and Australian Research Council (4.8%\/4.1%). One in nine Victorian awards from five government initiatives and one in ten from 12 non-government agencies included sex- and gender-term related terms in their guidelines.\n\nConclusionsThese baseline metrics indicate that sex and gender are still not widely considered in the education and research ecosystems. These findings support the need to build inclusive research policy at a national and state level, and accreditation standards across university education.","rel_num_authors":12,"rel_authors":[{"author_name":"Sue Haupt","author_inst":"The George Institute for Global Health, University of New South Wales (UNSW), Sydney, NSW, Australia"},{"author_name":"Tomer Parkiet","author_inst":"Tel Aviv Sourasky Medical Centre, Tel Aviv University, Israel"},{"author_name":"Inzela Mirza","author_inst":"Faculty of Science, Engineering and Built Environment, Deakin University, Geelong, Australia"},{"author_name":"Kyria Webster","author_inst":"The Victorian Department of Health, Melbourne, Australia"},{"author_name":"Mila Waise","author_inst":"The Victorian Department of Health, Melbourne, Australia"},{"author_name":"Zoe Wainer","author_inst":"Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, Australia"},{"author_name":"Kim Kwan","author_inst":"Science in Australia Gender Equity (SAGE), Melbourne, Australia"},{"author_name":"Saraid Billiards","author_inst":"Association of Australian Medical Research Institute, Melbourne, Australia"},{"author_name":"Bronwyn Graham","author_inst":"The George Institute for Global Health, University of New South Wales (UNSW), Sydney, NSW, Australia"},{"author_name":"Cara Tannenbaum","author_inst":"Faculty of Medicine, University of Montreal, Montreal, Canada"},{"author_name":"Rachel Huxley","author_inst":"Faculty of Health, Deakin University, Geelong, Australia"},{"author_name":"Severine Lamon","author_inst":"Faculty of Health, Deakin University, Geelong, Australia"}],"rel_date":"2026-07-30","rel_site":"medrxiv"},{"rel_title":"Benchmarking sex and gender incorporation into health and medical research, policy and education in Victoria prior to 2026","rel_doi":"10.64898\/2026.07.27.26358999","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.27.26358999","rel_abs":"ObjectiveTo investigate and establish a baseline for sex and gender considerations in policy, research and curricula across the state of Victoria.\n\nDesign and settingVictoria was selected as a case study for Australia, using a mixed-methods approach to examine health and medical university curricula, research organisation policies and research funding between 2020-2025 prior to mandated inclusion.\n\nMain outcome measuresPrimary outcomes include identification of predefined sex- and gender-related terms in university curricula descriptors and funded grant descriptions; and questionnaire responses from university course coordinators and organisational leads.\n\nResultsData mining across nine Victorian universities (318 courses\/3383 units) identified [~]93% of units and [~]60% of healthcare courses lacked sex and gender terms in their descriptors. Among medical research organisations operating in Victoria, including peak bodies, research institutes, hospitals and universities, [~]70% (18\/26) of the survey responders reported having no sex and gender policy. Rates of sex- and gender-term inclusion in research grants allocated in Victoria (3388) and Australia-wide (8974) validated Victoria as a case study for Australia for National Health and Medical Research Council (9.5%\/8.9% respectively), Medical Research Future Funds (11%\/10.2%), and Australian Research Council (4.8%\/4.1%). One in nine Victorian awards from five government initiatives and one in ten from 12 non-government agencies included sex- and gender-term related terms in their guidelines.\n\nConclusionsThese baseline metrics indicate that sex and gender are still not widely considered in the education and research ecosystems. These findings support the need to build inclusive research policy at a national and state level, and accreditation standards across university education.","rel_num_authors":12,"rel_authors":[{"author_name":"Sue Haupt","author_inst":"The George Institute for Global Health, University of New South Wales (UNSW), Sydney, NSW, Australia"},{"author_name":"Tomer Parkiet","author_inst":"Tel Aviv Sourasky Medical Centre, Tel Aviv University, Israel"},{"author_name":"Inzela Mirza","author_inst":"Faculty of Science, Engineering and Built Environment, Deakin University, Geelong, Australia"},{"author_name":"Kyria Webster","author_inst":"The Victorian Department of Health, Melbourne, Australia"},{"author_name":"Mila Waise","author_inst":"The Victorian Department of Health, Melbourne, Australia"},{"author_name":"Zoe Wainer","author_inst":"Faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, Australia"},{"author_name":"Kim Kwan","author_inst":"Science in Australia Gender Equity (SAGE), Melbourne, Australia"},{"author_name":"Saraid Billiards","author_inst":"Association of Australian Medical Research Institute, Melbourne, Australia"},{"author_name":"Bronwyn Graham","author_inst":"The George Institute for Global Health, University of New South Wales (UNSW), Sydney, NSW, Australia"},{"author_name":"Cara Tannenbaum","author_inst":"Faculty of Medicine, University of Montreal, Montreal, Canada"},{"author_name":"Rachel Huxley","author_inst":"Faculty of Health, Deakin University, Geelong, Australia"},{"author_name":"Severine Lamon","author_inst":"Faculty of Health, Deakin University, Geelong, Australia"}],"rel_date":"2026-07-30","rel_site":"medrxiv"},{"rel_title":"Global Programmatic Survey on Governance and Surveillance of Nontuberculous Mycobacteria","rel_doi":"10.64898\/2026.07.27.26358874","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.27.26358874","rel_abs":"BackgroundNontuberculous mycobacteria (NTM) are clinically important pathogens but often weakly positioned within health systems, with unclear institutional ownership, variable notification arrangements, and limited surveillance visibility.\n\nMethodsWe conducted a multilingual online survey among programme-facing national and subnational mycobacterial stakeholders from November to December 2025. Using an adaptive hierarchical recruitment strategy, we targeted 217 countries and jurisdictions. One response per programme was requested. We assessed institutionalisation, notification, agenda maturity, thematic discussion priorities, and barriers to action. We also derived relative policy momentum from three urgency domains (diagnostics, clinical management, and surveillance) using within-WHO region hierarchical clustering. Findings were used to develop a heuristic roadmap for staged NTM governance and system visibility.\n\nResultsWe received 193 programme-level responses, including from subnational jurisdictions, representing 171 of 217 targeted countries (78.8% jurisdictional coverage). NTM institutionalisation status was heterogeneous: 34% reported NTM integration within the NTP, while 37% expressed intents to institutionalise within the NTP in nearest future. Mandatory notification was reported by 21% of programme units, voluntary notification by 10%, and notification under consideration by 24%. NTM appeared to enter policy discussions along a gradient, with clinical management and diagnostics attracting earlier attention than surveillance, training needs, and financing. Globally, pulmonary NTM was discussed more frequently than extrapulmonary disease. Across WHO regions, policy momentum clustering separated programmes into higher and lower profiles, with surveillance consistently being the weakest domain. Financing and lack of epidemiological data were identified as the most actionable barriers. There was broad support for TB-NTM surveillance integration.\n\nConclusionsNTM governance is heterogeneous and frequently weakly anchored globally. The findings do not support a single universal institutional model; rather, existing mycobacterial platforms may provide pragmatic starting points for improving programme visibility, coordination, and reporting. The proposed heuristic roadmap outlines staged governance options according to burden, capacity, and institutional context.","rel_num_authors":14,"rel_authors":[{"author_name":"Nityanand Jain","author_inst":"KU Leuven, Belgium"},{"author_name":"Liga Kuksa","author_inst":"Riga East Clinical University Hospital, Latvia"},{"author_name":"Dissou Affolabi","author_inst":"WHO Tuberculosis Supranational Reference Laboratory, Benin"},{"author_name":"Fabiola Eliosa Arias Munoz","author_inst":"WHO Tuberculosis Supranational Reference Laboratory, Chile"},{"author_name":"Angelica Scappaticcio","author_inst":"WHO Tuberculosis Supranational Reference Laboratory, Chile"},{"author_name":"Sushil Pandey","author_inst":"Queensland Mycobacterium Reference Laboratory, Australia"},{"author_name":"Lisa Shepherd","author_inst":"WHO Tuberculosis Supranational Reference Laboratory, Australia"},{"author_name":"Rumina Hasan","author_inst":"Aga Khan University"},{"author_name":"Lorenzo Guglielmetti","author_inst":"IRCCS Sacro Cuore Don Calabria Hospital, Italy"},{"author_name":"Gert-Jan Wijnant","author_inst":"KU Leuven, Belgium"},{"author_name":"Emmanuel Andre","author_inst":"KU Leuven, Belgium"},{"author_name":"Leen Rigouts","author_inst":"Institute of Tropical Medicine Antwerp, Belgium"},{"author_name":"Natalie Lorent","author_inst":"KU Leuven, Belgium"},{"author_name":"- NTM Global Policy Study Group","author_inst":""}],"rel_date":"2026-07-30","rel_site":"medrxiv"},{"rel_title":"Learning Ophthalmologist Clinical Reasoning for Glaucoma Diagnosis from Fundus Images","rel_doi":"10.64898\/2026.07.28.26359057","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26359057","rel_abs":"Glaucoma is a leading cause of irreversible blindness worldwide. Ophthalmologists diagnose glaucoma through a structured reasoning process by sequentially evaluating optic nerve head characteristics before reaching a final diagnosis, whereas existing AI systems typically perform direct image classification without providing clinically meaningful reasoning. We present the first clinically annotated fundus reasoning dataset, comprising 1,077 fundus photographs paired with expert-authored six-step diagnostic reports. Building on this dataset, we develop a reasoning-driven vision-language framework that explicitly models the ophthalmologists diagnostic workflow by generating structured clinical reasoning prior to diagnosis. The generated reports are clinically validated, achieving the best performance across all evaluated clinical findings, including a cup-to-disc ratio mean absolute error of 0.070, an ISNT Kendall distance of 1.73, and the highest semantic agreement with expert reports (BERTScore-F1 = 0.874). The resulting framework also improves glaucoma diagnosis, achieving a balanced accuracy of 94.7% and precision of 94.8%, demonstrating that explicitly modeling expert clinical reasoning simultaneously improves interpretability and diagnostic performance. Code and data are available at https:\/\/glaucoma-cot.github.io\/.","rel_num_authors":14,"rel_authors":[{"author_name":"kaichen zhou","author_inst":"Harvard University"},{"author_name":"yuzhen chen","author_inst":"Harvard University"},{"author_name":"Elif YILDIZ","author_inst":"Harvard University"},{"author_name":"Min Shi","author_inst":"University of Louisiana at Lafayette"},{"author_name":"David Dai","author_inst":"MIT"},{"author_name":"Grace Chen","author_inst":"Harvard University"},{"author_name":"Jiale Zheng","author_inst":"Harvard University"},{"author_name":"He Wang","author_inst":"Harvard University"},{"author_name":"Fangneng Zhan","author_inst":"MIT"},{"author_name":"Chhavi Saini","author_inst":"Harvard University"},{"author_name":"Lucy Q. Shen","author_inst":"Harvard University"},{"author_name":"Yike Guo","author_inst":"Hong Kong University of Science and Technology"},{"author_name":"Paul Pu Liang","author_inst":"MIT"},{"author_name":"Mengyu Wang","author_inst":"Harvard University"}],"rel_date":"2026-07-29","rel_site":"medrxiv"},{"rel_title":"Circulating tumor DNA concentration at diagnosis is a modifiable prognostic factor for distant metastatic recurrence in patients with high-risk breast cancer receiving neoadjuvant therapy","rel_doi":"10.64898\/2026.07.28.26358343","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26358343","rel_abs":"BackgroundCirculating tumor DNA (ctDNA) is an emerging biomarker of treatment response and recurrence risk, while residual cancer burden (RCB) after neoadjuvant treatment (NAT) is a well-established risk factor for distant recurrence. Here, we examined the association between high ctDNA concentration at diagnosis and risk of distant recurrence after neoadjuvant treatment (NAT), in the context of RCB.\n\nMethodsThe study included 712 patients with high-risk breast cancer in the neoadjuvant I-SPY2 trial. Tumor- informed ctDNA test results at diagnosis were used to stratify patients into ctDNA-negative and ctDNA-positive groups. For this analysis, the ctDNA-positive group was divided into tertiles (low, intermediate, high) based on ctDNA concentration reported as mean tumor molecules per mL [MTM\/mL] of plasma. Correlations between MTM\/mL at diagnosis and ctDNA dynamics during NAT, residual cancer burden (RCB), and distant recurrence-free survival (DRFS) were examined across all subtypes.\n\nResultsIn all subtypes, high ctDNA concentration at diagnosis was associated with worse DRFS, whereas low ctDNA concentration or ctDNA-negative status was associated with improved DRFS, even with high tumor burden after NAT (RCB-II\/RCB-III). We also found that patients with high ctDNA concentration, regardless of subtype, were less likely to experience early ctDNA clearance; however, those who did had a significantly higher likelihood of achieving a favorable response (RCB-0\/RCB-I) than those with late or no ctDNA clearance. Furthermore, across all subtypes, patients with early ctDNA clearance, including those with substantial residual cancer (RCB-II\/RCB-III) after NAT, had improved DRFS, irrespective of the ctDNA concentration at diagnosis.\n\nConclusionsAcross all subtypes, pathologic response and ctDNA clearance reduce the risk of distant recurrence associated with high ctDNA concentration at diagnosis. ctDNA concentration at diagnosis and ctDNA clearance dynamics during NAT may facilitate the prediction of treatment response and further stratify the risk of metastatic recurrence in non-responders.\n\nTrial Registration: NCT01042379","rel_num_authors":24,"rel_authors":[{"author_name":"Mark Jesus M. Magbanua","author_inst":"University of California San Francisco"},{"author_name":"Denise M. Wolf","author_inst":"University of California San Francisco"},{"author_name":"Christina Yau","author_inst":"University of California San Francisco"},{"author_name":"Nayelis A. Manon","author_inst":"University of California San Francisco"},{"author_name":"Rosalyn W. Sayaman","author_inst":"University of California San Francisco"},{"author_name":"Lamorna Brown Swigart","author_inst":"University of California San Francisco"},{"author_name":"Gillian Hirst","author_inst":"University of California San Francisco"},{"author_name":"Wen Li","author_inst":"University of California San Francisco"},{"author_name":"Claudine Isaacs","author_inst":"Georgetown University Medical Center"},{"author_name":"Rebecca Shatsky","author_inst":"University of California San Diego"},{"author_name":"Amy S. Clark","author_inst":"University of Pennsylvania"},{"author_name":"Alexandra Zimmer","author_inst":"Oregon Health and Science University"},{"author_name":"Rita Mukhtar","author_inst":"University of California San Francisco"},{"author_name":"Amy L. Delson","author_inst":"University of California San Francisco"},{"author_name":"Jane Perlmutter","author_inst":"University of California San Francisco"},{"author_name":"Paula R. Pohlmann","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Nola M. Hylton","author_inst":"University of California San Francisco"},{"author_name":"Rita Nanda","author_inst":"University of Chicago"},{"author_name":"Douglas Yee","author_inst":"University of Minnesota"},{"author_name":"W. Fraser Symmans","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Laura J. Esserman","author_inst":"University of California San Francisco"},{"author_name":"Hope S. Rugo","author_inst":"City of Hope Comprehensive Cancer Center"},{"author_name":"Angela DeMichele","author_inst":"University of Pennsylvania"},{"author_name":"Laura J. van 't Veer","author_inst":"University of California San Francisco"}],"rel_date":"2026-07-29","rel_site":"medrxiv"},{"rel_title":"Circulating tumor DNA concentration at diagnosis is a modifiable prognostic factor for distant metastatic recurrence in patients with high-risk breast cancer receiving neoadjuvant therapy","rel_doi":"10.64898\/2026.07.28.26358343","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26358343","rel_abs":"BackgroundCirculating tumor DNA (ctDNA) is an emerging biomarker of treatment response and recurrence risk, while residual cancer burden (RCB) after neoadjuvant treatment (NAT) is a well-established risk factor for distant recurrence. Here, we examined the association between high ctDNA concentration at diagnosis and risk of distant recurrence after neoadjuvant treatment (NAT), in the context of RCB.\n\nMethodsThe study included 712 patients with high-risk breast cancer in the neoadjuvant I-SPY2 trial. Tumor- informed ctDNA test results at diagnosis were used to stratify patients into ctDNA-negative and ctDNA-positive groups. For this analysis, the ctDNA-positive group was divided into tertiles (low, intermediate, high) based on ctDNA concentration reported as mean tumor molecules per mL [MTM\/mL] of plasma. Correlations between MTM\/mL at diagnosis and ctDNA dynamics during NAT, residual cancer burden (RCB), and distant recurrence-free survival (DRFS) were examined across all subtypes.\n\nResultsIn all subtypes, high ctDNA concentration at diagnosis was associated with worse DRFS, whereas low ctDNA concentration or ctDNA-negative status was associated with improved DRFS, even with high tumor burden after NAT (RCB-II\/RCB-III). We also found that patients with high ctDNA concentration, regardless of subtype, were less likely to experience early ctDNA clearance; however, those who did had a significantly higher likelihood of achieving a favorable response (RCB-0\/RCB-I) than those with late or no ctDNA clearance. Furthermore, across all subtypes, patients with early ctDNA clearance, including those with substantial residual cancer (RCB-II\/RCB-III) after NAT, had improved DRFS, irrespective of the ctDNA concentration at diagnosis.\n\nConclusionsAcross all subtypes, pathologic response and ctDNA clearance reduce the risk of distant recurrence associated with high ctDNA concentration at diagnosis. ctDNA concentration at diagnosis and ctDNA clearance dynamics during NAT may facilitate the prediction of treatment response and further stratify the risk of metastatic recurrence in non-responders.\n\nTrial Registration: NCT01042379","rel_num_authors":24,"rel_authors":[{"author_name":"Mark Jesus M. Magbanua","author_inst":"University of California San Francisco"},{"author_name":"Denise M. Wolf","author_inst":"University of California San Francisco"},{"author_name":"Christina Yau","author_inst":"University of California San Francisco"},{"author_name":"Nayelis A. Manon","author_inst":"University of California San Francisco"},{"author_name":"Rosalyn W. Sayaman","author_inst":"University of California San Francisco"},{"author_name":"Lamorna Brown Swigart","author_inst":"University of California San Francisco"},{"author_name":"Gillian Hirst","author_inst":"University of California San Francisco"},{"author_name":"Wen Li","author_inst":"University of California San Francisco"},{"author_name":"Claudine Isaacs","author_inst":"Georgetown University Medical Center"},{"author_name":"Rebecca Shatsky","author_inst":"University of California San Diego"},{"author_name":"Amy S. Clark","author_inst":"University of Pennsylvania"},{"author_name":"Alexandra Zimmer","author_inst":"Oregon Health and Science University"},{"author_name":"Rita Mukhtar","author_inst":"University of California San Francisco"},{"author_name":"Amy L. Delson","author_inst":"University of California San Francisco"},{"author_name":"Jane Perlmutter","author_inst":"University of California San Francisco"},{"author_name":"Paula R. Pohlmann","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Nola M. Hylton","author_inst":"University of California San Francisco"},{"author_name":"Rita Nanda","author_inst":"University of Chicago"},{"author_name":"Douglas Yee","author_inst":"University of Minnesota"},{"author_name":"W. Fraser Symmans","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Laura J. Esserman","author_inst":"University of California San Francisco"},{"author_name":"Hope S. Rugo","author_inst":"City of Hope Comprehensive Cancer Center"},{"author_name":"Angela DeMichele","author_inst":"University of Pennsylvania"},{"author_name":"Laura J. van 't Veer","author_inst":"University of California San Francisco"}],"rel_date":"2026-07-29","rel_site":"medrxiv"},{"rel_title":"Circulating tumor DNA concentration at diagnosis is a modifiable prognostic factor for distant metastatic recurrence in patients with high-risk breast cancer receiving neoadjuvant therapy","rel_doi":"10.64898\/2026.07.28.26358343","rel_link":"http:\/\/medrxiv.org\/content\/10.64898\/2026.07.28.26358343","rel_abs":"BackgroundCirculating tumor DNA (ctDNA) is an emerging biomarker of treatment response and recurrence risk, while residual cancer burden (RCB) after neoadjuvant treatment (NAT) is a well-established risk factor for distant recurrence. Here, we examined the association between high ctDNA concentration at diagnosis and risk of distant recurrence after neoadjuvant treatment (NAT), in the context of RCB.\n\nMethodsThe study included 712 patients with high-risk breast cancer in the neoadjuvant I-SPY2 trial. Tumor- informed ctDNA test results at diagnosis were used to stratify patients into ctDNA-negative and ctDNA-positive groups. For this analysis, the ctDNA-positive group was divided into tertiles (low, intermediate, high) based on ctDNA concentration reported as mean tumor molecules per mL [MTM\/mL] of plasma. Correlations between MTM\/mL at diagnosis and ctDNA dynamics during NAT, residual cancer burden (RCB), and distant recurrence-free survival (DRFS) were examined across all subtypes.\n\nResultsIn all subtypes, high ctDNA concentration at diagnosis was associated with worse DRFS, whereas low ctDNA concentration or ctDNA-negative status was associated with improved DRFS, even with high tumor burden after NAT (RCB-II\/RCB-III). We also found that patients with high ctDNA concentration, regardless of subtype, were less likely to experience early ctDNA clearance; however, those who did had a significantly higher likelihood of achieving a favorable response (RCB-0\/RCB-I) than those with late or no ctDNA clearance. Furthermore, across all subtypes, patients with early ctDNA clearance, including those with substantial residual cancer (RCB-II\/RCB-III) after NAT, had improved DRFS, irrespective of the ctDNA concentration at diagnosis.\n\nConclusionsAcross all subtypes, pathologic response and ctDNA clearance reduce the risk of distant recurrence associated with high ctDNA concentration at diagnosis. ctDNA concentration at diagnosis and ctDNA clearance dynamics during NAT may facilitate the prediction of treatment response and further stratify the risk of metastatic recurrence in non-responders.\n\nTrial Registration: NCT01042379","rel_num_authors":24,"rel_authors":[{"author_name":"Mark Jesus M. Magbanua","author_inst":"University of California San Francisco"},{"author_name":"Denise M. Wolf","author_inst":"University of California San Francisco"},{"author_name":"Christina Yau","author_inst":"University of California San Francisco"},{"author_name":"Nayelis A. Manon","author_inst":"University of California San Francisco"},{"author_name":"Rosalyn W. Sayaman","author_inst":"University of California San Francisco"},{"author_name":"Lamorna Brown Swigart","author_inst":"University of California San Francisco"},{"author_name":"Gillian Hirst","author_inst":"University of California San Francisco"},{"author_name":"Wen Li","author_inst":"University of California San Francisco"},{"author_name":"Claudine Isaacs","author_inst":"Georgetown University Medical Center"},{"author_name":"Rebecca Shatsky","author_inst":"University of California San Diego"},{"author_name":"Amy S. Clark","author_inst":"University of Pennsylvania"},{"author_name":"Alexandra Zimmer","author_inst":"Oregon Health and Science University"},{"author_name":"Rita Mukhtar","author_inst":"University of California San Francisco"},{"author_name":"Amy L. Delson","author_inst":"University of California San Francisco"},{"author_name":"Jane Perlmutter","author_inst":"University of California San Francisco"},{"author_name":"Paula R. Pohlmann","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Nola M. Hylton","author_inst":"University of California San Francisco"},{"author_name":"Rita Nanda","author_inst":"University of Chicago"},{"author_name":"Douglas Yee","author_inst":"University of Minnesota"},{"author_name":"W. Fraser Symmans","author_inst":"University of Texas MD Anderson Cancer Center"},{"author_name":"Laura J. Esserman","author_inst":"University of California San Francisco"},{"author_name":"Hope S. Rugo","author_inst":"City of Hope Comprehensive Cancer Center"},{"author_name":"Angela DeMichele","author_inst":"University of Pennsylvania"},{"author_name":"Laura J. van 't Veer","author_inst":"University of California San Francisco"}],"rel_date":"2026-07-29","rel_site":"medrxiv"}]}