tbuckley/cabot-search huggingface dataset:
Mechanisms of receptor-mediated transcytosis at the blood-brain barrier
Authors: Habib Baghirov
Journal: Journal of Controlled Release (2025)

In receptor-mediated transcytosis (RMT) of large therapeutics across the blood-brain barrier (BBB), the construct - a macromolecule or a larger carrier with therapeutic payload - binds a protein on brain capillary endothelial cells (BCEC), with internalization and release into the brain parenchyma. The construct's internalization into, trafficking across and release from, but also possible entrapment within BCEC are affected by its engineered properties whose optimization has helped derive insights into transport mechanisms at BCEC. Furthermore, advances in multi-omics, as well as large-scale screening and directed evolution campaigns have helped identify new targets for RMT at BCEC. In this perspective, I raise and reflect on some fundamental questions one can arrive at by comparing the engineered properties of BBB-targeted constructs and the properties of different target proteins. These questions concern the underlying, transcytosis-promoting factors that the optimization of constructs' engineered properties appears to converge on, the precise role of target proteins in RMT, the different mechanisms through which these targets may mediate construct trafficking, and the tentative criteria for target selection on BCEC. Based on these considerations I propose several scenarios and strategies to interfere with the construct's trafficking for more efficient internalization, transport through the endosomal network toward the abluminal membrane, and release from BCEC, both for smaller macromolecules and for larger carriers.
Glucagon-like peptide-1 receptor agonists but not dipeptidyl peptidase-4 inhibitors reduce alcohol intake
Authors: Mehdi Farokhnia, John Tazare, Claire L. Pince, Nicolaus Bruns Vi, Joshua C. Gray, Vincent Lo Re III, David A. Fiellin, Henry R. Kranzler, George F. Koob, Amy C. Justice, Leandro F. Vendruscolo, Christopher T. Rentsch, Lorenzo Leggio
Journal: Journal of Clinical Investigation (2025)

Despite growing preclinical evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be repurposed to treat alcohol use disorder (AUD), clinical evidence is scarce. Additionally, the potential impact of dipeptidyl peptidase-4 inhibitors (DPP-4Is) on alcohol intake is largely unknown. We conducted a large cohort study using 2008-2023 electronic health records data from the U.S. Department of Veterans Affairs. Changes in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores were compared between propensity-score-matched GLP-1RA recipients, DPP-4I recipients, and unexposed comparators. We further tested the effects of two DPP-4Is, linagliptin and omarigliptin, on binge-like alcohol drinking in mice and operant oral alcohol self-administration in alcohol-dependent rats, models previously used to show a significant effect of the GLP-1RA semaglutide in reducing alcohol intake. GLP-1RA recipients reported a greater reduction in AUDIT-C scores than unexposed individuals [difference-in-difference: 0.09(0.03,0.14), p=0.0025] and DPP-4I recipients [difference-in-difference: 0.11(0.05,0.17), p=0.0002]. Reductions in drinking were more pronounced among individuals with baseline AUD [GLP-1RA vs. unexposed: 0.51(0.29,0.72), p<0.0001; GLP-1RA vs. DPP-4I: 0.65(0.43,0.88), p<0.0001] and baseline hazardous drinking [GLP-1RA vs. unexposed: 1.38(1.07,1.69), p<0.0001; GLP-1RA vs. DPP-4I: 1.00(0.68,1.33), p<0.0001]. There were no differences between DPP-4I recipients and unexposed individuals. The latter results were confirmed via a reverse translational approach. Specifically, neither linagliptin nor omarigliptin reduced alcohol drinking in mice or rats. The rodent experiments also confirmed target engagement as both DPP-4Is reduced blood glucose levels. Convergent findings across humans, mice, and rats indicate that GLP-1RAs but not DPP-4Is reduce alcohol consumption and may be efficacious in treating AUD.
IL33 protects from recurrent C. difficile infection by restoration of humoral immunity
Authors: Farha Naz, Md Jashim Uddin, Nicholas M. Hagspiel, Mary K. Young, David Tyus, Rachel Boone, Audrey C. Brown, Girija Ramakrishnan, Isaura Rigo, Claire Fleming, Gregory R. Madden, William A. Petri Jr.
Journal: Journal of Clinical Investigation (2025)

Clostridioides difficile infection (CDI) recurs in one of five patients. Monoclonal antibodies targeting the virulence factor TcdB reduce disease recurrence, suggesting that an inadequate anti-TcdB response to CDI leads to recurrence. In patients with CDI, we discovered that IL33 measured at diagnosis predicts future recurrence, leading us to test the role of IL33 signaling in the induction of humoral immunity during CDI. Using a mouse recurrence model, IL33 was demonstrated to be integral for anti-TcdB antibody production. IL33 acted via ST2+ ILC2 cells, facilitating germinal center T follicular helper (GC-Tfh) cell generation of antibodies. IL33 protection from reinfection was antibody-dependent, as mMT KO mice and mice treated with anti-CD20 mAb were not protected. These findings demonstrate the critical role of IL33 in generating humoral immunity to prevent recurrent CDI.
Tezepelumab inhibits highly functional truncated thymic stromal lymphopoietin in chronic rhinosinusitis
Authors: Aiko Oka, Aiko I Klingler, Masanori Kidoguchi, Julie A Poposki, Lydia A Suh, Junqin Bai, Whitney W Stevens, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Robert P Schleimer, Robert C Kern, Bruce K Tan, Shigeharu Fujieda, Mitsuhiro Okano, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2025)
Methodology Concerns Regarding Claims Data Studies in Transgender Health
Authors: Ole-Petter R. Hamnvik, Don S. Dizon, Alberto Giovanni Leone
Journal: JAMA Oncology (2025)

To the Editor The recent study by Manfredi et al1 found a lower prevalence of prostate cancer (PC) in transgender women undergoing gender-affirming hormone therapy (GAHT), but a correlation between GAHT and more aggressive PC. We have concerns regarding the analyses and conclusions.
Macrophage-mediated interleukin-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation
Authors: Joshua A. Keefe, Yuriana Aguilar-Sanchez, Jose Alberto Navarro-Garcia, Isabelle Ong, Luge Li, Amelie Paasche, Issam Abu-Taha, Marcel A. Tekook, Florian Bruns, Shuai Zhao, Markus Kamler, Ying H. Shen, Mihail G. Chelu, Li Na, Dobromir Dobrev, Xander H. T. Wehrens
Journal: Journal of Clinical Investigation (2025)

Postoperative atrial fibrillation (poAF) is AF occurring days after surgery with a prevalence of 33% among patients undergoing open-heart surgery. The degree of postoperative inflammation correlates with poAF risk, but less is known about the cellular and molecular mechanisms driving postoperative atrial arrhythmogenesis. We performed single-cell RNA sequencing comparing atrial non-myocytes from mice with versus without poAF, which revealed infiltrating CCR2+ macrophages to be the most altered cell type. Pseudotime trajectory analyses identified Il-6 as a top gene in macrophages, which we confirmed in pericardial fluid collected from human patients after cardiac surgery. Indeed, macrophage depletion and macrophage-specific Il6ra conditional knockout (cKO) prevented poAF in mice. Downstream STAT3 inhibition with TTI-101 and cardiomyocyte-specific Stat3 cKO rescued poAF, indicating a pro-arrhythmogenic role of STAT3 in poAF development. Confocal imaging in isolated atrial cardiomyocytes (ACMs) uncovered a novel link between STAT3 and CaMKII-mediated ryanodine receptor-2 (RyR2)-Ser(S)2814 phosphorylation. Indeed, non-phosphorylatable RyR2S2814A mice were protected from poAF, and CaMKII inhibition prevented arrhythmogenic Ca2+ mishandling in ACMs from mice with poAF. Altogether, we provide multiomic, biochemical, and functional evidence from mice and humans that IL-6-STAT3-CaMKII signaling driven by infiltrating atrial macrophages is a pivotal driver of poAF that portends therapeutic utility for poAF prevention.
Key Challenges in CAR T-Cell Therapy Access in Community Oncology
Authors: Michael T. Byrne, Aaron J. Lyss, Samyukta Mullangi
Journal: JAMA Oncology (2025)

This Viewpoint discusses the need to bring chimeric antigen receptor T-cell (CAR-T) therapy to community oncology, which will allow an uninterrupted continuum of care for patients.
Intentional Weight Loss, Waist Circumference Reduction, and Mortality Risk Among Postmenopausal Women
Authors: Michael Hendryx, JoAnn E. Manson, Robert J. Ostfeld, Rowan T. Chlebowski, Erin S. LeBlanc, Molly E. Waring, Wendy E. Barrington, Marisa A. Bittoni, Sylvia Wassertheil-Smoller, Jackie Gofshteyn Herold, Juhua Luo
Journal: JAMA Network Open (2025)

Research investigating weight loss and mortality risk often fails to differentiate between intentional and unintentional weight loss and typically uses body mass index (BMI) as the measure of excess body weight. To evaluate associations between weight loss and waist circumference (WC) reduction and mortality, considering weight loss intentionality. This cohort study used data from the Women's Health Initiative Observational Study, which had a prospective cohort with mean follow-up of 18.6 years ending in February 2023. The study included women aged 50 to 79 years at 40 clinical centers in the US. Women with missing data, cancer at baseline, or considered underweight at baseline were excluded. Data were collected from September 1993 to February 2023 and were analyzed from June to December 2024. Measured weight loss and WC reduction between baseline and year 3, stratified by women who reported intentional weight loss or not. Outcomes included adjudicated all-cause, cancer, cardiovascular, and other mortality through the end of follow-up. Cox proportional hazards regression models were used to evaluate the associations (hazard ratios [HRs] and 95% CIs) between weight loss, WC reduction, and mortality over 18.6 years of follow-up. This study included 58 961 women at baseline (mean [SD] age, 63.3 [7.2] years; mean [SD] BMI, 27.0 [5.6]; mean [SD] WC, 84.1 [13.0] cm). As of February 28, 2023, 29 183 women (49.5%) died from all causes. Intentional weight loss measured by questionnaire was associated with lower subsequent mortality rates for all-cause mortality (HR, 0.88; 95% CI, 0.86-0.90), cancer mortality (HR, 0.87; 95% CI, 0.82-0.92), cardiovascular mortality (HR, 0.87; 95% CI, 0.83-0.91), and other mortality (HR, 0.89; 95% CI, 0.86-0.92), comparing loss of 5 pounds or more to stable weight. Reported intentional weight loss coupled with actual weight reduction of 5% or more was associated only with lower cardiovascular mortality (HR, 0.90; 95% CI, 0.81-0.99). Reported intentional weight loss coupled with measured WC loss was associated with lower rates of all-cause mortality (HR, 0.91; 95% CI, 0.86-0.95), cancer mortality (HR, 0.85; 95% CI, 0.76-0.95), and cardiovascular mortality (HR, 0.79; 95% CI, 0.72-0.87). Unintentional weight loss or unintentional WC loss were each associated with increased mortality risk for all groups, as were weight gain and WC gain. In this cohort study, reported intentional weight loss efforts that were coupled with measured WC reductions were associated with lower risk of all-cause, cancer, and cardiovascular mortality. Attention to diet and exercise that promote reductions in central adiposity should be encouraged.
Recompensation of decompensated cirrhosis in hepatitis C patients after SVR: Prognostic implications
Authors: Yolanda Sánchez-Torrijos, Paula Fernández-Álvarez, Jose Miguel Rosales, Celia Pérez-Estrada, Paloma Alañón-Martínez, Manuel Rodríguez-Perálvarez, Carlota Jimeno, Pilar Del Pino, Alberto García-García, Ángeles López-Garrido, Miren García-Cortés, Gema Romero, Manuel Romero-Gómez, Marta Casado, Isabel Carmona, Javier Ampuero
Journal: Journal of Hepatology (2025)
Disparities in End-of-Life Symptom Burden Linked to Complex Interplay Among Wealth, Health, and Social Support
Authors: Peter A. Boling
Journal: JAMA Network Open (2025)

Irena Cenzer, PhD; Kenneth E. Covinsky, MD, MHP; Sarah H. Cross, PhD, MSW, MPH; Claire K. Ankuda, MD, MPH; Lauren J. Hunt, RN, PhD, FNP-BC; Melissa D. Aldridge, PhD, MBA; Krista L. Harrison, PhD
HIV Viral Suppression With Use of Long-Acting Antiretroviral Therapy in People With and Without Initial Viremia
Authors: Matthew A. Spinelli, Megan J. Heise, Nathanial Gistand, Chesa Cox, Janet Grochowski, Jon Oskarsson, David V. Glidden, Monica Gandhi
Journal: JAMA (2025)

This study uses electronic medical record data to compare 48-week viral load outcomes after starting long-acting antiretroviral therapy among people in the US with HIV with or without viremia from January 2021 through September 2024.
Financial Rewards for Smoking Cessation During Pregnancy and Birth Weight
Authors: David Tappin, Jiyoung Lee, Alex McConnachie, Loren Kock, Stephen T. Higgins, Sarah H. Heil, Ivan Berlin, Steven J. Ondersma, Frank Kee, Ira Bernstein, Linda Bauld
Journal: JAMA Network Open (2025)

Offering pregnant women financial rewards to stop smoking is associated with a more than 2-fold increase in smoking cessation and is cost-effective; however, it is possible that the association is the result of gaming of the outcome measure (eg, not smoking for 24 hours before outcome measurement using a carbon monoxide breath test). Birth weight is an outcome measure that is independent of the rewards process. To examine birth weight change associated with offering financial rewards for smoking cessation to pregnant women, and to estimate the average expected birth weight change for neonates born to those who quit smoking because of the rewards. Medline, American Psychological Association PsycInfo, Embase, Cochrane (the Cochrane Central Register of Controlled Trials, the Cochrane Tobacco Addiction Group Specialized Register, and the Cochrane Database of Systematic Reviews), and PubMed were searched from their inception until December 5, 2023, for published reports of trials of incentives for abstinence from substance use among pregnant women. Only trials using an experimental design allowing treatment effects to be attributed to the reward intervention were included. For this review update, potentially relevant studies retrieved were screened by a reviewer. Data were pooled using both fixed-effects and random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The primary outcomes were mean (SD) birth weight, birth weight for gestational age z score, and numbers of newborns with low birth weight (<2.5 kg) and who were small for gestational age (<10th percentile). Fixed-effects intention-to-treat analysis including 8 trials (2351 participants)-2 trials from the UK (1475 participants), 1 trial from France (407 participants), and 5 trials from the US (469 participants)-estimated a statistically significant mean 46.30 g (95% CI, 0.05 to 92.60 g) birth weight increase associated with adding financial rewards for smoking cessation. Complier average causal effects analysis (2239 participants) estimated a mean 206.00 g (95% CI, -69.12 to 481.14 g) increase for neonates born to smokers who quit because of rewards, but the increase was not statistically significant. There was no association with low birth weight or birth weight adjusted for gestational age, although fewer neonates were born small for gestational age, particularly if cessation was associated with rewards (complier average causal effects risk difference -17.70%; 95% CI, -34.90% to -0.42%). In this meta-analysis, neonates were significantly heavier when pregnant women were offered the addition of financial rewards contingent on smoking cessation, supporting the effectiveness and, therefore, cost-effectiveness of financial rewards in this health care setting.
A perspective from U.S. Environmental Protection Agency (EPA) scientists: how your epidemiologic analyses can inform the human health risk assessment process
Authors: Rachel M. Shaffer, Alexandra L. Lee, Rebecca Nachman, Krista Christensen, Thomas F. Bateson
Journal: Environmental Health Perspectives (2025)

Environmental epidemiologists strive to conduct research that will lead to actions that improve public health outcomes. The risk assessment process is the bridge between scientific research and policies that can impact public health. Historically, epidemiologic studies have not frequently been used to inform U.S. Environmental Protection Agency (EPA) assessments outside of the context of air pollution. There are certain practices that can be adopted by the epidemiology community to facilitate the integration of epidemiologic studies into policy-relevant assessments. The central objective of this commentary is to provide guidance to epidemiologists that will enhance the value of their studies for EPA assessments. First, we provide an overview of EPA dose-response and toxicity value derivation to increase literacy about these processes across the environmental epidemiology community. Second, we provide suggestions for modeling and reporting to facilitate the use of epidemiologic studies in EPA dose-response assessments that form the basis for decision-making. Epidemiologic research can be utilized in all aspects of dose-response assessment, which involves identifying a point of departure followed by specific adjustments and/or extrapolations to identify a toxicity value intended to prevent adverse effects across the population. To facilitate integration of epidemiologic research into the dose-response assessment process, we provide specific recommendations for additional modeling (e.g., modeling in the low exposure range; exploring non-linearity) and reporting (e.g., sufficient information to conduct study evaluation; details on exposure levels in the population) in published epidemiologic research. Many of these suggestions require only additional reporting in the final manuscript or associated appendices but would have substantial impact on the contribution of the published work to the assessment process. https://doi.org/10.1289/EHP15203.
Changes in Respiratory Viral Testing Before and After the COVID-19 Pandemic
Authors: Todd W. Lyons, Caroline G. Kahane
Journal: JAMA Network Open (2025)

Matthew J. Molloy, MD, MPH; Matthew Hall, PhD; Jessica L. Markham, MD, MSc; Jillian M. Cotter, MD, MSCS; Elisha McCoy, MD; Michael J. Tchou, MD, MSc; Megan E. Collins, MD, MPH; Michael J. Steiner, MD, MPH; John R. Stephens, MD; Andrew G. Yu, MD; Irma T. Ugalde, MD, MBE; Rustin B. Morse, MD; Monika K. Goyal, MD, MSCE; Samantha A. House, DO, MPH
Methodology Concerns Regarding Claims Data Studies in Transgender Health—Reply
Authors: Celeste Manfredi, Marco De Sio, Riccardo Autorino
Journal: JAMA Oncology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Network Analysis Reveals Protein Modules Associated with Childhood Respiratory Diseases
Authors: Nicole Prince, Sofina Begum, Kevin M Mendez, Lourdes G Ramirez, Yulu Chen, Qingwen Chen, Su H Chu, Priyadarshini Kachroo, Ofer Levy, Joann Diray-Arce, Paolo Palma, Augusto A Litonjua, Scott T Weiss, Rachel S Kelly, Jessica A Lasky-Su
Journal: Journal of Allergy and Clinical Immunology (2025)
Hematologic Cancers Among Patients With Type 2 Diabetes Prescribed GLP-1 Receptor Agonists
Authors: Omer S. Ashruf, Jasmin Hundal, Ali Mushtaq, David C. Kaelber, Faiz Anwer, Abhay Singh
Journal: JAMA Network Open (2025)

This cohort study compares the risks of developing different hematologic cancers in patients with type 2 diabetes treated with glucagon-like peptide–1 receptor agonists (GLP-1RAs) compared with metformin and insulin.
Financial Incentives for Smoking Cessation in Pregnancy and Outcomes for Infants
Authors: Caitlin Notley
Journal: JAMA Network Open (2025)

David Tappin, Doctor of Medicine; Jiyoung Lee, MSc; Alex McConnachie, PhD; Loren Kock, PhD; Stephen T. Higgins, PhD; Sarah H. Heil, PhD; Ivan Berlin, PhD; Steven J. Ondersma, PhD; Frank Kee, Doctor of Medicine; Ira Bernstein, MD; Linda Bauld, PhD
Methodology Concerns Regarding Claims Data Studies in Transgender Health
Authors: Alison M. Berner, Stewart O’Callaghan, Sarah S. Jackson
Journal: JAMA Oncology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal