tbuckley/cabot-search huggingface dataset:
Cigarette smoke components modulate the MR1–MAIT axis
Authors: Wael Awad, Jemma R. Mayall, Weijun Xu, Matt D. Johansen, Timothy Patton, Xin Yi Lim, Izabela Galvao, Lauren J. Howson, Alexandra C. Brown, Tatt Jhong Haw, Chantal Donovan, Shatarupa Das, Gesa J. Albers, Tsung-Yu Pai, Elinor Hortle, Caitlin M. Gillis, Nicole G. Hansbro, Jay C. Horvat, Ligong Liu, Jeffrey Y.W. Mak, James McCluskey, David P. Fairlie, Alexandra J. Corbett, Philip M. Hansbro, Jamie Rossjohn
Journal: The Journal of Experimental Medicine (2025)

Tobacco smoking is prevalent across the world and causes numerous diseases. Cigarette smoke (CS) compromises immunity, yet little is known of the components of CS that impact T cell function. MR1 is a ubiquitous molecule that presents bacterial metabolites to MAIT cells, which are highly abundant in the lungs. Using in silico, cellular, and biochemical approaches, we identified components of CS that bind MR1 and impact MR1 cell surface expression. Compounds, including nicotinaldehyde, phenylpropanoid, and benzaldehyde-related scaffolds, bound within the A′ pocket of MR1. CS inhibited MAIT cell activation, ex vivo, via TCR-dependent and TCR-independent mechanisms. Chronic CS exposure altered MAIT cell phenotype and function and attenuated MAIT cell responses to influenza A virus infection in vivo. MR1-deficient mice were partially protected from the development of chronic obstructive pulmonary disease (COPD) features that were associated with CS exposure. Thus, CS can impair MAIT cell function by diverse mechanisms, and potentially contribute to infection susceptibility and disease exacerbations.
Mortality after cancer diagnosis among children with congenital heart disease in Denmark and Sweden
Authors: Christina-Evmorfia Kampitsi, Line Kenborg, Hanna Mogensen, Olof Broberg, Ingrid Glimelius, Friederike Erdmann, Jeanette Falck Winther, Maria Feychting, Giorgio Tettamanti
Journal: JNCI Journal of the National Cancer Institute (2025)

Recent decades have witnessed tangible improvements in childhood cancer survival. However, the prognosis for children with congenital heart disease (CHD), the most prevalent birth defect, remains unclear. Due to improved survival of CHD and childhood cancer, evaluating outcomes within this intersection is important for clinical practice. We aimed to assess mortality post-cancer diagnosis among children with CHD. We conducted a study on the population of Denmark and Sweden, born 1970-2014, with a cancer diagnosis before age 20 in the national cancer registers (end of follow-up 2015; n = 20,665). CHD diagnoses (n = 397) and recorded deaths were retrieved from national health registers. We evaluated the effect of CHD on five-year mortality post-cancer diagnosis fitting Cox proportional hazards regression. When excluding children with Down syndrome, children with CHD had a higher five-year mortality post-cancer diagnosis compared to children without (HR 1.48, 95% CI 1.18-1.86). This was particularly notable in children with lymphoma (HR 2.17, 95% CI 1.11-4.25) and neuroblastoma (HR 2.39, 95% CI 1.11-5.15). In more recent decades (post-1990), children with CHD had similar five-year mortality as their counterparts without, except for children diagnosed with lymphoma, where mortality remained elevated (HR 3.37, 95% CI 1.65-6.89). In this large, register-based cohort study, children with CHD fared worse post-cancer diagnosis-particularly lymphoma and neuroblastoma. While a more positive trend emerged in recent years, lymphoma-related mortality remained disproportionately high among children with CHD, underscoring the need for continued research and interventions to improve outcomes for this vulnerable group.
Combination Drug Therapy May Better Alleviate PTSD Symptoms Than SSRIs Alone
Authors: Samantha Anderer
Journal: JAMA (2025)

Lori L. Davis, MD; Saloni Behl, MS; Daniel Lee, MD; Hui Zeng, PhD; Taisa Skubiak, EdD; Shelley Weaver, PhD; Nanco Hefting, MSc; Klaus Groes Larsen, PhD; Mary Hobart, PhD
Study Reveals Variation in Case Exposure for Internal Medicine Residents in the Same Program
Authors: Samantha Anderer
Journal: JAMA (2025)

Andrew C. L. Lam, MD; Brandon Tang, MD, MMSc; Chang Liu, BSc; Marwa F. Ismail, MD, MSc; Surain B. Roberts, PhD; Matthew Wankiewicz, BSc; Anushka Lalwani, MD; Daniel Schumacher, MD, PhD, MEd; Benjamin Kinnear, MD, MEd; Amol A. Verma, MD, MPhil; Fahad Razak, MD, MSc; Brian M. Wong, MD; Shiphra Ginsburg, MD, PhD
First WHO Report on Global Drowning Deaths Finds Substantial Improvements but Major Regional Disparities
Authors: Samantha Anderer
Journal: JAMA (2025)

Worldwide, the rate of deaths from drowning decreased by 38% over the past 2 decades, from 6.1 to 3.8 per 100 000 people. The first-ever status report on drowning prevention from the World Health Organization (WHO) estimated that 300 000 people died from drowning in 2021, down from 375 000 in 2000.
Errors in the Results, Table 2, Figures 2 and 3, and Supplement 1
Journal: JAMA Network Open (2025)

Errors in the Results, Table 2, Figures 2 and3, andSupplement 1 In the Original Investigation titled "Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care," 1 published December 2, 2024, in the third paragraph of the Results and in Table 2, the frequencies of myocardial infarction, stroke, stent thrombosis, and major bleeding in patients with any acute coronary syndrome in the ticagrelor and prasugrel groups were updated.In Table 2, the frequency of major bleeding was also updated for patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina.In Figures 2 and3, the numbers at risk were revised for both treatment groups in all panels.In eTable 5 in Supplement 1, the frequencies of myocardial infarction, stroke, stent thrombosis, and major bleeding were revised for both treatment groups.This article has been corrected. 1 The authors have explained what happened in a Comment. 2
A Tale of Two Treatments: A Randomised Controlled Trial of Mindfulness or Cognitive Behaviour Therapy Delivered Online for People with Rheumatoid Arthritis
Authors: Louise Sharpe, Madelyne A. Bisby, Rachel E. Menzies, Jack Benjamin Boyse, Bethany Richmond, Jemma Todd, Amy-Lee Sesel, Blake F. Dear
Journal: Psychotherapy and Psychosomatics (2025)

This study aimed to determine the relative efficacy of mindfulness-based stress reduction (MBSR) or cognitive behaviour therapy (CBT) in comparison to a waitlist control (WLC) for people with rheumatoid arthritis (RA). Participants completed assessments before and after treatment and at 6-month follow-up. Two hundred and sixty-nine participants with RA were recruited and randomised in a 2:2:1 ratio to MBSR:CBT:WLC. Participants completed a semi-structured clinical interview for depression and were stratified for history of recurrent depression. We measured the primary outcome of pain interference, as well as pain severity, depression, anxiety, functional ability, and fear of progression. We predicted that MBSR and CBT would result in improvements compared to WLC. We also predicted that those with a history of recurrent depression would benefit more from MBSR than CBT for depression. MBSR and CBT were equally efficacious in reducing pain interference compared to WLC. Similar results were found for depression. MBSR demonstrated superior outcomes to CBT for fear of progression at post-treatment and functional ability at 6-month follow-up. CBT only was better than WLC for pain severity at 6-month follow-up. Depressive status did not moderate the efficacy of treatment. MBSR and CBT resulted in statistically and clinically significant changes in pain interference compared to WLC. MBSR was more efficacious than CBT for functional ability and fear of progression, while CBT showed superiority for pain severity. The effect sizes were comparable to those achieved with face-to-face interventions, confirming both online treatments are effective for people with RA.
Use of a Context- and Equity-Focused Implementation Science Framework to Aid the Design of Clinical Trials
Authors: Lilia Cervantes, Katherine Rizzolo, Sri Lekha Tummalapalli, Marina Wainstein, Russell E. Glasgow, Mónica Pérez Jolles
Journal: Journal of the American Society of Nephrology (2025)

Cervantes, Lilia; Rizzolo, Katherine; Tummalapalli, Sri Lekha; Wainstein, Marina; Glasgow, Russell E.; Jolles, Mónica Pérez Author Information
Fusing multispectral information for retinal layer segmentation
Authors: Xiang He, Fuwang Wu, Kaixuan Hu, Lizhen Cui, Weiye Song, Yi Wan
Journal: npj Digital Medicine (2025)

Extensive research on retinal layer segmentation (RLS) using deep learning (DL) is mostly approaching a performance plateau, primarily due to reliance on structural information alone. To address the present situation, we conduct the first study on the impact of multi-spectral information (MSI) on RLS. Our experimental results show that incorporating MSI significantly improves segmentation accuracy for retinal layer optical coherence tomography (OCT) images. Furthermore, we investigate the primary factors influencing MSI, including the number of multi-spectral images, spectral bandwidth, and the different spectral combinations, to assess their impacts on the accuracy of RLS. Building upon this foundation, we have incorporated MSI into RLS methods, yielding exceptional performance in segmentation outcomes, and these findings have been validated in OCT images across both the near-infrared and visible-light spectral ranges. Fusing MSI provides a novel approach to improving RLS accuracy, further demonstrating the importance of open-source MSI information in OCT devices.
Anti–immune complex antibodies are elicited during repeated immunization with HIV Env immunogens
Authors: Sharidan Brown, Aleksandar Antanasijevic, Leigh M. Sewall, Daniel Montiel Garcia, Philip J. M. Brouwer, Rogier W. Sanders, Andrew B. Ward
Journal: Science Immunology (2025)

Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated. Here, we use electron microscopy–based polyclonal epitope mapping (EMPEM) to elucidate how repeated immunization with HIV Env SOSIP immunogens results in the generation of Ab2α anti-idiotypic antibodies in rabbits and rhesus macaques. We present the structures of six anti–immune complex antibodies and find that they target idiotopes composed of framework regions of antibodies bound to Env. Examination of cryo–electron microscopy density enabled prediction of sequences for an anti–immune complex antibody, the paratope of which is enriched with aromatic amino acids. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens in which repeated exposure to antigen is required.
Architects of immunity: How dendritic cells shape CD8 <sup>+</sup> T cell fate in cancer
Authors: Vidit Bhandarkar, Teresa Dinter, Stefani Spranger
Journal: Science Immunology (2025)

Immune responses against cancer are dominated by T cell exhaustion and dysfunction. Recent advances have underscored the critical role of early priming interactions in establishing T cell fates. In this review, we explore the importance of dendritic cell (DC) signals in specifying CD8+ T cell fates in cancer, drawing on insights from acute and chronic viral infection models. We highlight the role of DCs in lymph nodes and tumors in maintaining stem-like CD8+ T cells, which are critical for durable antitumor immune responses. Understanding how CD8+ T cell fates are determined will enable the rational design of immunotherapies, particularly therapeutic cancer vaccines, that can modulate DC-T cell interactions to generate beneficial CD8+ T cell fates.
Dynamic single cell transcriptomics defines kidney FGF23/KL bioactivity and novel segment-specific inflammatory targets.
Authors: Rafiou Agoro, Jered Myslinski, Yamil G Marambio, Danielle Janosevic, Kayleigh N Jennings, Sheng Liu, Lainey M Hibbard, Fang Fang, Pu Ni, Megan L Noonan, Emmanuel Solis, Xiaona Chu, Yue Wang, Pierre C Dagher, Yunlong Liu, Jun Wan, Takashi Hato, Kenneth E White
Journal: Kidney International (2025)
G-protein coupled receptor GPR124 protects against podocyte senescence and injury in diabetic kidney disease.
Authors: Yujia Li, Yiqi Duan, Qingqing Chu, Hang Lv, Jing Li, Xiangyun Guo, Yanjiao Gao, Min Liu, Wei Tang, Huili Hu, Hong Liu, Jinpeng Sun, Xiaojie Wang, Fan Yi
Journal: Kidney International (2025)
Eligibility Criteria of Randomized Clinical Trials in Critical Care Medicine
Authors: Alya Heirali, Kiyan Heybati, Jariya Sereeyotin, Faizan Khan, Christopher Yarnell, Karla Krewulak, Srinivas Murthy, Karen E. A. Burns, Robert Fowler, Kirsten Fiest, Sangeeta Mehta, Bram N. Rochwerg, Jennifer LY Tsang
Journal: JAMA Network Open (2025)

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.
Cannabinoid receptor 1 ligands: Biased signaling mechanisms driving functionally selective drug discovery
Authors: Lei Tian, Taotao Qiang, Sundian Liu, Boxin Zhang, Yunfei Zhang, Bingxing Zhang, Jinrong Hu, Jiayun Zhang, Qi Lu, Changhua Ke, Juan Xia, Chengyuan Liang
Journal: Pharmacology & Therapeutics (2025)
Advances in the structural understanding of opioid allostery
Authors: Nokomis Ramos-Gonzalez, Balazs R Varga, Susruta Majumdar
Journal: Trends in Pharmacological Sciences (2025)

Activation of the μ opioid receptor (MOR) can give analgesia, but also has dangerous side effects. Drugs that target MOR through an allosteric site, meaning they bind outside of the usual pocket, present a novel mode of receptor activation with different pharmacology relative to orthosteric drugs. Recent structural studies give valuable new information on how allosteric modulators interact with MOR.
Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine
Authors: Kaan Sel, Andrea Hawkins-Daarud, Anirban Chaudhuri, Deen Osman, Ahmad Bahai, David Paydarfar, Karen Willcox, Caroline Chung, Roozbeh Jafari
Journal: npj Digital Medicine (2025)

Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes. VVUQ frameworks are essential for integrating digital twins into clinical practice.
Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow
Authors: Jacques Fantini, Fodil Azzaz, Coralie Di Scala, Anaïs Aulas, Henri Chahinian, Nouara Yahi
Journal: Pharmacology & Therapeutics (2025)

The traditional model of protein structure determined by the amino acid sequence is today seriously challenged by the fact that approximately half of the human proteome is made up of proteins that do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered proteins (IDPs), are involved in numerous physiological functions and are associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), and type 2 diabetes. Targeting these proteins is challenging for two reasons: i) we need to preserve their physiological functions, and ii) drug design by molecular docking is not possible due to the lack of reliable starting conditions. Faced with this challenge, the solutions proposed by artificial intelligence (AI) such as AlphaFold are clearly unsuitable. Instead, we suggest an innovative approach consisting of mimicking, in short synthetic peptides, the conformational flexibility of IDPs. These peptides, which we call adaptive peptides, are derived from the domains of IDPs that become structured after interacting with a ligand. Adaptive peptides are designed with the aim of selectively antagonizing the harmful effects of IDPs, without targeting them directly but through selected ligands, without affecting their physiological properties. This"target the target, not the arrow" strategy is promised to open a new route to drug discovery for currently undruggable proteins.
Third-Generation Nanopore Sequencing for Rapid Diagnosis of Pneumocystis Jirovecii Pneumonia and Co-Pathogens
Authors: Chun-Yan Zhao, Chang Song, Fei-Yi Du, Chang-Yue Jiang, Hang-Biao Qiang, Chao-Yan Xu, Zhou-Hua Xie, Qing-Dong Zhu
Journal: Journal of Infection (2025)
Clonal Hematopoiesis in Women With Breast Cancer
Authors: Christina Mayerhofer, Rachel A. Freedman, Heather A. Parsons, Ann H. Partridge, Peter G. Miller
Journal: Journal of Clinical Oncology (2025)

Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer. We summarize data from multiple studies, including a series of cohorts of patients with breast cancer, to assess the prevalence of CH, the relationship between CH and exposure to cytotoxic therapy, and the correlation between CH and breast cancer-specific outcomes. Our findings indicate that CH is prevalent among patients with breast cancer, particularly those treated with cytotoxic therapies. However, there are no definitive data to support an association between the presence of CH and breast cancer-specific outcomes. Current data do not support routine CH testing in patients with breast cancer, nor should the presence of CH influence decisions regarding breast cancer therapy in most patients. However, larger, long-term studies are necessary to further define the implications of CH in patients with breast cancer and guide clinical decision making.
Unraveling the dynamics of B7-H3-targeting therapeutic antibodies in cancer through PET imaging and antibody pharmacokinetics
Authors: Bruna Fernandes, Colleen P Olkowski, Behnaz Ghaemi, Falguni Basuli, Jianfeng Shi, Dale O Kiesewetter, Lixin Lang, Edmondson Elijah, Rolf Swenson, Peter L Choyke, Frank I Lin, Orit Jacobson
Journal: Journal of Controlled Release (2025)
Targeted delivery of polymeric NO-donor micelles to hepatic stellate cells for restoration of liver function and inhibition of hepatic fibrosis
Authors: Rui Yang, Lifen Yang, Ni Zhang, Yuqing Wan, Shineng Chen, Yiqing Xiao, Xiaoping Liang, Shangjie Yang, Yinan Zhong, Dechun Huang, Wei Chen, Bingbing Zhao
Journal: Journal of Controlled Release (2025)
Anticoagulation and Antiplatelet Therapy for Atrial Fibrillation and Stable Coronary Disease: Meta-analysis of Randomized Trials
Authors: Sina Rashedi, Mohammad Keykhaei, Alyssa Sato, Philippe Gabriel Steg, Gregory Piazza, John W Eikelboom, Renato D Lopes, Marc P Bonaca, Satoshi Yasuda, Hisao Ogawa, Satoshi Shizuta, Takeshi Kimura, Yasuo Okumura, Felicita Andreotti, Laurent Bertoletti, Gregg W Stone, Roxana Mehran, David J Cohen, Gregory Y H Lip, Behnood Bikdeli
Journal: Journal of the American College of Cardiology (2025)
Decrease in Fracture Rate with Mandatory Bone-protecting Agents in the EORTC 1333/PEACE-3 Trial Comparing Radium-223 Combined with Enzalutamide Versus Enzalutamide Alone: A Safety Analysis
Authors: Silke Gillessen, Bertrand Tombal, Fabio Turco, Ananya Choudhury, Alejo Rodriguez-Vida, Enrique Gallardo, Pedro Isaacsson Velho, Franco Nolè, Felipe Cruz, Yohann Loriot, Ray McDermott, Thierry Roumeguere, Gedske Daugaard, Rosley Yamamura, Emmanuelle Bompas, Pablo Maroto, Manuel Herrero Polo, Karine Martins da Trindade, Daniel D'Almeida Preto, Iwona Skoneczna, Frederic Lecouvet, Corneel Coens, Beatrice Fournier, Fred Saad
Journal: European Urology (2025)
Intravesical Administration of Durvalumab for High-risk Non–muscle-invasive Bladder Cancer: A Phase 2 Study by the Hellenic GU Cancer Group
Authors: Charalampos Fragkoulis, Aristotelis Bamias, Nikos Gavalas, Kimon Tzannis, Evangelos Fragiadis, Alexandros Pinitas, Panayiotis V Stamatakos, George Papadopoulos, George Stathouros, Xanthippi Grammatoglou, Penelope Korkolopoulou, Christina Zoubouli, Konstantinos Stravodimos, Konstantinos Ntoumas, Dionysios Mitropoulos, Andreas Skolarikos, Athanasios Papatsoris
Journal: European Urology (2025)
Rationally Manipulating Molecular Planarity to Improve Molar Absorptivity, NIR-II Brightness, and Photothermal Effect for Tumor Phototheranostics
Authors: Chaoqi Song, Shiping Yang, Yajing Chi, Tingxing Zhao, Ruili Zhang, Hongbo Li, Jinting Wu, Jianguo Zhang, Jacky W Y Lam, Qian Jia, Ben Zhong Tang, Zhongliang Wang
Journal: Biomaterials (2025)
Development of a Treatment Decision Aid for Patients with Dysplastic Nevi Who Are Candidates for Re-Excision
Authors: Jaclyn N Roland-McGowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Clara Curiel-Lewandrowski, Emily Y Chu, Erin L Foster, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu
Journal: Journal of the American Academy of Dermatology (2025)