tbuckley/cabot-search huggingface dataset:
G-Protein–Coupled Estrogen Receptor 1 and Pregnancy Confer Protection Against Hypertension in Older Females
Authors: Ravneet Singh, Supaporn Kulthinee, Victoria L. Nasci, Elvis A. Akwo, Chibundu Juliet Umunna, Rawan N. Almutlaq, Oleh M. Pochynyuk, Cassianne Robinson-Cohen, Eman Y. Gohar
Journal: Circulation (2025)
Virus-associated inflammation imprints an inflammatory profile on monocyte-derived macrophages in the human liver
Authors: Juan Diego Sanchez Vasquez, Shirin Nkongolo, Daniel Traum, Valentin Sotov, Samuel C Kim, Deeqa Mahamed, Aman Mehrotra, Anjali Patel, Diana Y Chen, Scott Fung, Anuj Gaggar, Jordan J Feld, Kyong-Mi Chang, Jeffrey J Wallin, Ben X Wang, Harry LA Janssen, Adam J Gehring
Journal: Journal of Clinical Investigation (2025)

Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating in an inflammatory environment can potentially imprint a phenotype that switches the liver from an immune-tolerant organ to one predisposed to tissue damage. We longitudinally sampled the liver of patients with chronic hepatitis B who had active liver inflammation and were starting antiviral therapy. Antiviral therapy suppressed viral replication and liver inflammation, which coincided with decreased myeloid activation markers. Single-cell RNA-Seq mapped peripheral inflammatory markers to a monocyte-derived macrophage population, distinct from Kupffer cells, with an inflammatory transcriptional profile. The inflammatory macrophages (iMacs) differentiated from blood monocytes and were unique from macrophage found in healthy or cirrhotic liver. iMacs retained their core transcriptional signature after inflammation resolved, indicating inflammation-mediated remodeling of the macrophage population in the human liver that may affect progressive liver disease and immunotherapy.
A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma
Authors: Heejae Kang, Lisa M Maurer, Jing Cheng, Mei Smyers, Linda R Klei, Dong Hu, Juliana Hofstatter Azambuja, Marcelo J Murai, Ahmed Mady, Ejaz Ahmad, Matthew Trotta, Hanna B Klei, Minda Liu, Prasanna Ekambaram, Zaneta Nikolovska-Coleska, Bill B Chen, Linda M McAllister-Lucas, Peter C Lucas
Journal: Journal of Clinical Investigation (2025)

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the activated B cell-like subtype (ABC-DLBCL) is associated with particularly poor outcome. Many ABC-DLBCLs harbor gain-of-function mutations that cause inappropriate assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, a cytoplasmic complex that drives downstream NF-κB signaling. MALT1 is the effector protein of the CBM signalosome such that its recruitment to the signalosome via interaction with BCL10 allows it to exert both protease and scaffolding activities that together synergize in driving NF-κB. Here, we demonstrate that a molecular groove located between two adjacent immunoglobulin-like domains within MALT1 represents a binding pocket for BCL10. Leveraging this discovery, we performed an in silico screen to identify small molecules that dock within this MALT1 groove and act as BCL10-MALT1 protein-protein interaction (PPI) inhibitors. We report the identification of M1i-124 as a first-in-class compound that blocks BCL10-MALT1 interaction, abrogates MALT1 scaffolding and protease activities, promotes degradation of BCL10 and MALT1 proteins, and specifically targets ABC-DLBCLs characterized by dysregulated MALT1. Our findings demonstrate that small-molecule inhibitors of BCL10-MALT1 interaction can function as potent agents to block MALT1 signaling in selected lymphomas, and provide a road map for clinical development of a new class of precision-medicine therapeutics.
Haptenization as the missing link between vasculitis and myeloperoxidase
Authors: Laura Santambrogio
Journal: Journal of Clinical Investigation (2025)

A wide variety of medications can induce adverse immune events and autoimmune responses such as vasculitis. Mechanistically, small molecule drugs known as haptens bind and modify endogenous proteins, triggering such immune reactions. In this issue of the JCI, Xi and colleagues investigated the immunological mechanism of autoimmune vasculitis associated with hydralazine. Notably, hydralazine-based haptenization modified myeloperoxidase (MPO), inducing the enzyme conformational change. The hydralazine-modified MPO induced IgM antibody specific for the modified enzyme, followed by immune complex precipitation, tissue deposition, and complement activation. These findings provide a mechanism by which hydralazine induces a type III hypersensitivity reaction associated with mild to severe vasculitis. The study serves as an example for understanding haptenation and may inform the development of diagnostics for determining susceptibility to drug-induced allergic or autoimmune responses.
Off-the-shelf invariant NKT cells expressing anti-PSCA CAR and IL-15 promote pancreatic cancer regression in mice
Authors: Zhenyu Dai, Zheng Zhu, Zhiyao Li, Lei Tian, Kun-Yu Teng, Hanyu Chen, Li-Shu Wang, Jianying Zhang, Laleh Melstrom, Michael A Caligiuri, Jianhua Yu
Journal: Journal of Clinical Investigation (2025)

Pancreatic ductal adenocarcinoma cancer (PDAC) continues to pose a significant health burden, with a 5-year survival rate of only 10%. Prostate stem cell antigen (PSCA) is highly expressed on the surface of tumor cells of most PDAC patients, with minimum expression in most normal tissues. Here, we generated cryopreserved, off-the-shelf, allogeneic PSCA chimeric antigen receptor (CAR) invariant NKT (iNKT) cells using human peripheral blood mononuclear cells as a cell source. In multiple in vitro and in vivo PDAC models, freshly manufactured PSCA CAR_sIL-15 iNKT cells and frozen-thawed, off-the-shelf PSCA CAR_sIL-15 iNKT cells demonstrate comparable efficacies, and both show remarkable suppression of PSCA-positive and gemcitabine-resistant PDAC. Importantly, off-the-shelf cryopreserved PSCA CAR_sIL-15 iNKT cells show equivalent efficacy when compared with PSCA CAR T cells using the same PSCA CAR and in the same PDAC model; however, PSCA CAR_sIL-15 iNKT cells do not appear to induce systemic toxicity or graft-versus-host disease, thus allowing for multiple infusions to control recurrent disease. Collectively, our study suggests that PSCA CAR_sIL-15 iNKT cells merit clinical investigation for PDAC patients exhibiting positive PSCA expression. The therapy could be given as a single agent or in combination with established therapeutic modalities for PDAC.
Patient-Reported Outcomes as End Points in Heart Failure Trials
Authors: Javed Butler, Muhammad Shariq Usman, Charu Gandotra, Ali Salman, Andrew Farb, Aliza M. Thompson, Norman Stockbridge, Cordula Zeller, Folke Folkvaljon
Journal: Circulation (2025)

Heart failure is a growing health-care concern affecting tens of millions of individuals globally. Although traditional therapeutic strategies have focused on reducing the risk for hospitalization and mortality, the importance of patient-reported outcomes (PROs) in patients with heart failure is increasingly being recognized. Regulatory agencies consider PROs part of their evaluation of drugs and devices, and professional society guidelines may recommend interventions that improve PROs. However, for several reasons, the effect of interventions on PROs reported in heart failure trials currently is difficult to interpret. There is no consensus on the timing and frequency of PRO assessments. Moreover, it has been difficult to establish a minimal clinically important difference, that is, the minimal change in a PRO score that is meaningful to a patient. In addition, traditional methods of analyzing and reporting PROs such as comparison of mean differences across groups or responder analysis are prone to statistical artifacts and misinterpretation. This article presents an in-depth discussion of these issues, with the Kansas City Cardiomyopathy Questionnaire used as an example, to facilitate the use of PROs in heart failure research, regulatory, and clinical settings.
Dose Response of Incidental Physical Activity Against Cardiovascular Events and Mortality
Authors: Emmanuel Stamatakis, Raaj K. Biswas, Nicholas A. Koemel, Angelo Sabag, Richard Pulsford, Andrew J. Atkin, Afroditi Stathi, Sonia Cheng, Cecilie Thøgersen-Ntoumani, Joanna M. Blodgett, Adrian Bauman, Carlos Celis-Morales, Mark Hamer, Jason M.R. Gill, Matthew N. Ahmadi
Journal: Circulation (2025)

BACKGROUND: Few middle-aged and older adults engage in regular leisure-time exercise. Incidental physical activity (IPA) encompasses activities of daily living outside the leisure-time domain. No dose-response study is available to guide IPA-focused interventions and guidelines. We examined the associations of device-assessed IPA intensities (vigorous [VIPA], moderate [MIPA], light [LIPA]) with major adverse cardiovascular events (MACE) and mortality, and we estimated the “health equivalence” of LIPA and MIPA against 1 minute of VIPA. METHODS: A total of 24 139 nonexercisers from the 2013 to 2015 UK Biobank accelerometry substudy (56.2% women) with a mean±SD age of 61.9±7.6 years were analyzed using a prospective cohort design. IPA energy expenditure and daily durations of VIPA, MIPA, and LIPA were calculated with a validated machine learning-based intensity classifier. MACE included incident stroke, myocardial infarction, and heart failure; CVD death; CVD mortality; and all-cause mortality. RESULTS: Analyses included 22 107 (MACE), 22 174 (CVD mortality), and 24 139 (all-cause mortality) participants, corresponding to 908/223/1071 events over 7.9 years of follow-up. IPA volume exhibited an L-shaped association with a nadir at ≈35 to 38 kJ·kg −1 ·d −1 , corresponding to hazard ratios of 0.49 (95% CI, 0.39–0.61) for MACE, 0.33 (95% CI, 0.22–0.52) for CVD mortality, and 0.31 (95% CI, 0.25–0.38) for all-cause mortality. Any amounts of VIPA or MIPA were associated with lower risk, with a plateau of ≈14 minutes per day (VIPA) and 34 to 50 minutes per day (MIPA). The median VIPA (4.6 min/d) and MIPA (23.8 min/d) durations were associated with CVD mortality hazard ratio of 0.62 (95% CI, 0.46–0.83) and 0.50 (95% CI, 0.31–0.80), respectively. LIPA showed a subtle inverse gradient which was statistically significant only for CVD mortality at levels &gt;130 minutes per day. One minute of VIPA was equivalent to 2.8 (MACE) to 3.4 (CVD mortality) minutes of MIPA and 34.7 (CVD mortality) to 48.5 (MACE) minutes of LIPA. CONCLUSIONS: Any daily IPA amount of vigorous or moderate intensity was associated with lower CVD risk in a dose-response manner. LIPA had weak associations with all outcomes. One minute of vigorous or ≈3.0 to 3.5 minutes of moderate IPA was associated with a similar degree of lower CVD risk. Our findings highlight the potential cardiovascular health value of incidental physical activity, especially for people who struggle to do structured exercise.
Beyond binding: from modular to natural vision
Authors: H Steven Scholte, Edward H F de Haan
Journal: Trends in Cognitive Sciences (2025)

The classical view of visual cortex organization as a collection of specialized modules processing distinct features like color and motion has profoundly influenced neuroscience for decades. This framework, rooted in historical philosophical distinctions between qualities, gave rise to the 'binding problem': how the brain integrates these separately processed features into coherent percepts. We present converging evidence from electrophysiology, neuroimaging, and lesion studies that challenges this framework. We argue that the binding problem may be an artifact of theoretical assumptions rather than a real computational challenge for the brain. Drawing insights from deep neural networks (DNNs) and recent empirical findings, we propose a framework where the visual cortex represents naturally co-occurring patterns of information rather than processing isolated features that need binding.
AS-1277 Mitral Valve Replacement Is Tactically Preferable Than Mitral Valve Repair in Patients Suffering From Infective Endocarditis With Vegetation
Authors: Sudhir Rajbhandari, Shubo Song, Menghao Li, Yunkun Pan, Jingjing Hei, Chunhong Gu, Taofu Wang, Jianchao Li, Wenping Zhang, Taibing Fan
Journal: Journal of the American College of Cardiology (2025)
AS-1325 Impact of Atrial Shunt Device on Prognosis and Risk Factors in Heart Failure With Reduced Ejection Fraction (SUSTAIN-HF): A National, Multicenter, Phase III, Single Group Clinical Study
Authors: ChangDong Zhang, Yucheng Zhong, Qiaozhen Li, Guangyuan Song, Jian Yang, Xiaoping Peng, Yan Li, Qingwei Ji, Geng Li, Jun Tian, Mei Liu, ChangYu Qin, Qing Wang, XueLi Wang, Song Chen, Ming Sun, Xiaoke Shang, NianGuo Dong
Journal: Journal of the American College of Cardiology (2025)
AS-1185 Association Between Biological Age Acceleration and All-Cause Mortality in Patients With Moderate and Severe Aortic Valve Stenosis: A Prospective Cohort Study
Authors: Yiqi Zheng, Xinghao Xu, Bingzhen Li, Shaozhao Zhang, Han Wen, Yue Guo, Zhenyu Xiong, Menghui Liu, Huimin Zhou, Xingfeng Xu, Rihua Huang, Ruijie Li, Xiaodong Zhuang, Xinxue Liao
Journal: Journal of the American College of Cardiology (2025)
AS-1085 Transcatheter Aortic Valve-in-Transcatheter Aortic Valve: Clinical Characteristics and Outcomes
Authors: Fang Hai Yang, Ewe See Hooi, Rizwan Amanullah Mohammed, Abdul Aziz Zameer, Govindasamy Sivaraj Pillai, Victor Chao, Jonathan Yap, Ho Kay Woon
Journal: Journal of the American College of Cardiology (2025)
AS-1249 Application of Transcatheter Edge-to-Edge Repair in the Treatment of Papillary Muscle Rupture of Mitral Valve After Acute Myocardial Infarction
Authors: Xiang Chen, Yingwen Lin, Maolong Su, Xu Chen, Fanqi Meng, Huaibin Huang, Yaner Yao, Pianpian Yan, Hongmei Wen, Xijie Wu, Bin Wang, Yan Wang
Journal: Journal of the American College of Cardiology (2025)
Patterns of U.S. Firearm Injury Emergency Department Visits by Month, Day, and Time During 2018 to 2023
Authors: Adam Rowh, Marissa Zwald, Steven Sumner, Nisha George, Michael Sheppard, Kristin Holland
Journal: Annals of Internal Medicine (2025)

Monitoring temporal trends in firearm injury-related emergency department (ED) visits is challenging because traditional surveillance systems lack detailed temporal information. To describe temporal patterns of ED visits for firearm injury using data from the Centers for Disease Control and Prevention's (CDC) Firearm Injury Surveillance Through Emergency Rooms (FASTER) program. Cross-sectional analysis of firearm injury-related ED visits. 9 states (Florida, Georgia, New Mexico, North Carolina, Oregon, Utah, Virginia, Washington, and West Virginia) and the District of Columbia from 1 January 2018 to 31 August 2023. ED visits for firearm injury (n = 93 022) from CDC's FASTER program. ED visits for firearm injury per 100 000 ED visits, analyzed by time of day (in 30-minute intervals), day of the week, day of the year, and holidays. From January 2018 through August 2023, there were 93 022 firearm injury ED visits (73.9 per 100 000 ED visits), or approximately 1 firearm injury every 30 minutes overall. Rates of firearm injury ED visits were highest between 2:30 and 3:00 a.m. and lowest between 10:00 and 10:30 a.m. Nighttime peaks and daily rates were highest on Friday and Saturday. Monthly rates were highest in July and lowest in February; daily rates were disproportionately high on most holidays, especially Independence Day and New Year's Eve. Data are limited to 9 states and the District of Columbia and are not nationally representative. The analysis of ED visits for firearm injury does not distinguish injury intent and is based on arrival time rather than actual injury time. Distinct temporal patterns in firearm injury ED visits highlight resource allocation considerations for prevention and response efforts. Centers for Disease Control and Prevention.
Trends in Utilization of Glucose- and Weight-Lowering Medications After Tirzepatide Approval in the United States
Authors: John W. Ostrominski, Janinne Ortega-Montiel, Helen Tesfaye, Caroline Alix, Elyse DiCesare, Sara J. Cromer, Deborah J. Wexler, Julie M. Paik, Elisabetta Patorno
Journal: Annals of Internal Medicine (2025)

Recent trends in use of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist (RA), versus other glucose-lowering medications (GLMs) and weight-lowering medications (WLMs) remain unexplored. To describe trends in insurance claims for GLMs and WLMs after tirzepatide approval. Population-based cohort study. Claims data from a large U.S. commercial database (January 2021 to December 2023). Adults (aged ≥18 years) with type 2 diabetes (T2D) and without diabetes with dispensations for GLMs and WLMs. Any use was defined as medication dispensation regardless of prior use. Incident use was defined as dispensation without use in the preceding year. Monthly trends in medication dispensations before and after tirzepatide market entry. Tirzepatide uptake was additionally compared with initial postapproval uptake of other GLMs and WLMs. Tirzepatide dispensations increased markedly among adults with T2D prescribed GLMs, reaching 12.3% of all GLM dispensations by December 2023. Similar patterns were observed for sodium-glucose cotransporter-2 inhibitors (14.5% to 24.4%) and GLP-1 RAs (19.5% to 28.5%). Dispensations of other GLMs, including metformin, declined. Among adults without diabetes but prescribed WLMs, tirzepatide (0.0% to 40.6%) and semaglutide (2.4 mg) (0.0% to 32.2%) dispensations increased sharply, but semaglutide (2.0 mg) was the most frequently dispensed WLM, increasing from 37.8% to 45.7%. Dispensations of other WLMs declined. Similar trends were observed among incident users. Tirzepatide uptake was more rapid and sustained compared with initial postapproval periods for other medications. Generalizability to U.S. adults without commercial health insurance is uncertain. These findings highlight the sharp uptake of tirzepatide after U.S. market entry and enhance understanding of the rapidly shifting landscape of prescribing patterns for GLMs and WLMs. National Institute of Diabetes and Digestive and Kidney Diseases.
Impacts of Communication Type and Quality on Patient Safety Incidents
Authors: Leila Keshtkar, Amber Bennett-Weston, Ahmad S. Khan, Shaan Mohan, Max Jones, Keith Nockels, Sarah Gunn, Natalie Armstrong, Jennifer Bostock, Jeremy Howick
Journal: Annals of Internal Medicine (2025)

Poor communication in health care increases the risk for patient safety incidents. However, there is no up-to-date synthesis of these data. To synthesize studies investigating how poor communication between health care practitioners and patients (and between different groups of practitioners) affects patient safety. Ovid MEDLINE, CINAHL, APA PsycInfo, CENTRAL, Scopus, and the ProQuest Dissertations & Theses Citation Index from 1 January 2013 to 7 February 2024. Studies published in any language that quantified the effects of poor communication on patient safety. Two independent reviewers extracted data, assessed risk of bias, and appraised strength of evidence. Study heterogeneity precluded meta-analysis, so results were reported with narrative description, reporting medians and interquartile ranges (IQRs). Forty-six eligible studies (67 826 patients) were included. Risk of bias was low for 20, moderate for 16, and high for 10 studies. Four studies investigated whether poor communication was the only identified cause of a patient safety incident; here, poor communication caused 13.2% (IQR, 6.1% to 24.4%) of safety incidents. Forty-two studies investigated whether poor communication contributed to patient safety incidents alongside other causes; here, poor communication contributed to 24.0% (IQR, 12.0% to 46.8%) of safety incidents. Study heterogeneity was high in terms of setting, continent, health care staff, and safety incident type. The strength of the evidence was low or very low. There was important study heterogeneity, generally low study quality, and poor reporting of essential data. Poor communication is a major cause of patient safety incidents. Research is needed to develop effective interventions and to learn more about how poor communication leads to patient safety incidents. Stoneygate Trust. (PROSPERO: CRD42024507578).
Soluble-microneedle enhance three T-cell activation signals as efficient tumor vaccines for melanoma prevention and treatment
Authors: Nan Li, Weiwei Mu, Zhenxing Xia, Qingping Ma, Ruihua Feng, Panpan Gu, Qinglin Yang, Shuying Gao, Weihan Zhang, Suyun Wei, Yi Zheng, Wei Zhao, Yongjun Liu, Na Zhang
Journal: Journal of Controlled Release (2025)
In vivo delivery of antioxidant enzymes with multi-functionalized lipid nanoparticles for sepsis therapy
Authors: Hiroyuki Koide, Shinya Hirata, Midori Watanabe, Hiroki Ochiai, Tatsuya Kobayashi, Go Yasuno, Hajime Mizuno, Eiji Sugiyama, Shohei Kojima, Takehisa Dewa, Hiromichi Egami, Sei Yonezawa, Naoto Oku, Tomohiro Asai
Journal: Journal of Controlled Release (2025)
Sonopermeation combined with stroma normalization enables complete cure using nano-immunotherapy in murine breast tumors
Authors: Constantina Neophytou, Antonia Charalambous, Chrysovalantis Voutouri, Stella Angeli, Myrofora Panagi, Triantafyllos Stylianopoulos, Fotios Mpekris
Journal: Journal of Controlled Release (2025)

Nano-immunotherapy shows great promise in improving patient outcomes, as seen in advanced triple-negative breast cancer, but it does not cure the disease, with median survival under two years. Therefore, understanding resistance mechanisms and developing strategies to enhance its effectiveness in breast cancer is crucial. A key resistance mechanism is the pronounced desmoplasia in the tumor microenvironment, which leads to dysfunction of tumor blood vessels and thus, to hypoperfusion, limited drug delivery and hypoxia. Ultrasound sonopermeation and agents that normalize the tumor stroma have been employed separately to restore vascular abnormalities in tumors with some success. Here, we performed in vivo studies in two murine, orthotopic breast tumor models to explore if combination of ultrasound sonopermeation with a stroma normalization drug can synergistically improve tumor perfusion and enhance the efficacy of nano-immunotherapy. We found that the proposed combinatorial treatment can drastically reduce primary tumor growth and in many cases tumors were no longer measurable. Overall survival studies showed that all mice that received the combination treatment survived and rechallenge experiments revealed that the survivors obtained immunological memory. Employing ultrasound elastography and contrast enhanced ultrasound along with proteomics analysis, flow cytometry and immunofluorescene staining, we found the combinatorial treatment reduced tumor stiffness to normal levels, restoring tumor perfusion and oxygenation. Furthermore, it increased infiltration and activity of immune cells and altered the levels of immunosupportive chemokines. Finally, using machine learning analysis, we identified that tumor stiffness, CD8+ T cells and M2-type macrophages were strong predictors of treatment response.
Skincare Ingredients Recommended by Cosmetic Dermatologists: A Delphi Consensus Study
Authors: Gabriella V Alvarez, Bianca Y Kang, Alexandra M Richmond, Elika Hoss, Ronald Sulewski, Kira Minkis, Suzanne S Rozenberg, Diana Antonovich, Alison Boucher, Eric F Bernstein, Vince Bertucci, Anne M Chapas, Joel L Cohen, M Laurin Council, Jeffrey S Dover, Roy Geronemus, Katherine Ml Given, Hayley S Goldbach, Mitchel P Goldman, Deirdre Hooper, Joely Kaufman, Girish Munavalli, Theresa R Pacheco, Anthony M Rossi, Sarah Wilson, Murad Alam
Journal: Journal of the American Academy of Dermatology (2025)