tbuckley/cabot-search huggingface dataset:
Enfortumab Vedotin With or Without Pembrolizumab in Metastatic Urothelial Carcinoma
Authors: Shugo Yajima, Kohei Hirose, Hitoshi Masuda
Journal: JAMA Network Open (2025)

Importance Metastatic urothelial carcinoma (mUC) presents a therapeutic challenge with poor outcome. Enfortumab vedotin has emerged as a promising treatment, necessitating a comprehensive evaluation of its effectiveness and safety. Objective To synthesize the available evidence on enfortumab vedotin, both as monotherapy and in combination with pembrolizumab, as an mUC treatment for the purpose of guiding clinical decision-making and future research. Data Sources Cochrane Library, MEDLINE (via PubMed), Google Scholar, and Web of Science were searched from database inception to August 31, 2024. Major conference abstracts from 2019 to 2024 were also included. Search strategy used a combination of Medical Subject Heading terms and free-text keywords related to mUC and enfortumab vedotin. Study Selection Randomized clinical trials and prospective studies investigating enfortumab vedotin in adult patients with mUC were included. Eleven studies met the inclusion criteria. Data Extraction and Synthesis Two independent reviewers extracted data and assessed study quality using the Cochrane Risk of Bias tool 2 and Risk of Bias in Non-Randomized Studies of Interventions tool. The meta-analysis used a random effects model, while a network meta-analysis was performed using a frequentist approach. Main Outcomes and Measures Primary outcomes were disease control rate (DCR), objective response rate (ORR), and 1-year survival rate. Results The 11 included studies (3 randomized clinical trials [27.3%] and 8 nonrandomized prospective studies [72.7%]) involved 2128 patients. Of these patients, 563 (26.5%) received enfortumab vedotin plus pembrolizumab, 814 (38.3%) received enfortumab vedotin without pembrolizumab, and 751 (35.3%) received chemotherapy. Enfortumab vedotin plus pembrolizumab was associated with a pooled DCR of 86% (95% CI, 83%-89%), ORR of 68% (95% CI, 64%-71%), and a 1-year survival rate of 79% (95% CI, 75%-82%). Enfortumab vedotin monotherapy had a pooled DCR of 73% (95% CI, 70%-76%), ORR of 43% (95% CI, 40%-47%), and a 1-year survival rate of 52% (95% CI, 48%-56%). Network meta-analysis revealed that enfortumab vedotin plus pembrolizumab significantly outperformed chemotherapy in ORR (odds ratio [OR], 3.47; 95% CI, 1.49-8.09; P = .004) and 1-year survival (OR, 2.32; 95% CI, 1.75-3.06; P &amp;amp;lt; .001). Conclusions and Relevance In this systematic review and meta-analysis, enfortumab vedotin plus pembrolizumab showed high response rates in first-line settings, while enfortumab vedotin monotherapy was associated with clinical benefit in later lines of therapy. These findings underscore the importance of personalized treatment approaches, and future research is warranted to refine enfortumab vedotin–based therapies for mUC management.
Ethics in Patient Preferences for Artificial Intelligence–Drafted Responses to Electronic Messages
Authors: Joanna S. Cavalier, Benjamin A. Goldstein, Vardit Ravitsky, Jean-Christophe Bélisle-Pipon, Armando Bedoya, Jennifer Maddocks, Sam Klotman, Matthew Roman, Jessica Sperling, Chun Xu, Eric G. Poon, Anand Chowdhury
Journal: JAMA Network Open (2025)

Importance The rise of patient messages sent to clinicians via a patient portal has directly led to physician burnout and dissatisfaction, prompting uptake of artificial intelligence (AI) to alleviate this burden. It is important to understand patient preferences around AI in patient-clinician communication as ethical guidelines on appropriate use and disclosure (patient notification of AI use) are developed. Objective To analyze patient preferences regarding use of AI in electronic messages. Design, Setting, and Participants A survey study was conducted within the Duke University Health System’s patient advisory committee, consisting of individuals 18 years or older who participate in periodic surveys to inform health system patient care practices. Multiple surveys were administered to test the impact of different factors, including response author, disclosure (AI, human, or none), and seriousness of the topic. A follow-up survey assessed preferred disclosure verbiage. Surveys were administered from October 31 to December 11, 2023. Exposure Multiple surveys. Main Outcomes and Measures Participants rated their overall satisfaction, usefulness of the information, and perceived level of care on a 5-point Likert scale. Results Of the 2511 members surveyed, 1455 (57.9%) responded, with respondents being older (median age, 57 [IQR, 49-70] vs 53 [IQR, 41-62] years), more educated (872 of 1083 [80.5%] vs 319 of 440 [72.5%] with a college or graduate degree), and predominantly female (921 [63.3%]). Participants preferred AI- compared with human-drafted responses, with a mean difference for satisfaction of −0.30 (95% CI, −0.37 to −0.23) points, usefulness of −0.28 (95% CI, −0.34 to −0.22) points, and perception they were cared for of −0.43 (95% CI, −0.50 to −0.37) points. Participants tended to have higher satisfaction with a human disclosure over AI disclosure, with a mean difference of 0.13 (95% CI, 0.05-0.22) points, and with no disclosure over AI authorship disclosure, with a mean difference of 0.09 (95% CI, 0.01-0.17) points. Regardless of author or disclosure type, more than 75% of respondents were satisfied (agree or strongly agree) with the response. Conclusions and Relevance In this survey study, participants expressed a mild preference for messages written by AI but had a slightly decreased satisfaction when told AI was involved. Patient experience must be considered along with ethical implementation of AI. Although AI disclosure may slightly reduce satisfaction, disclosure should be maintained to uphold patient autonomy and empowerment.
Proteome-wide assessment of differential missense variant clustering in neurodevelopmental disorders and cancer
Authors: Jeffrey K Ng, Yilin Chen, Titilope M Akinwe, Hillary B Heins, Elvisa Mehinovic, Yoonhoo Chang, David H Gutmann, Christina A Gurnett, Zachary L Payne, Juana G Manuel, Rachel Karchin, Tychele N Turner
Journal: Cell Genomics (2025)
Screening for Food Insecurity
Authors: Wanda K. Nicholson, Michael Silverstein, John B. Wong, David Chelmow, Tumaini Rucker Coker, Alicia Fernandez, Ericka Gibson, Carlos Roberto Jaén, Marie Krousel-Wood, Sei Lee, Goutham Rao, John M. Ruiz, James Stevermer, Joel Tsevat, Sandra Millon Underwood, Sarah Wiehe
Journal: JAMA (2025)

Importance According to survey data, 12.8% of households experienced food insecurity in 2022, with 7.7% of households experiencing low food security and 5.1% experiencing very low food security. Nearly one-third of households with incomes below the federal poverty threshold are food insecure. Food insecurity is one among a multitude of medical, psychological, and social conditions common among economically disadvantaged households. Objective The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for food insecurity in the health care setting. Population Children, adolescents, and adults. Evidence Assessment The USPSTF concludes that the evidence is insufficient and the balance of benefits and harms for screening for food insecurity on health outcomes in the primary care setting cannot be determined. Recommendation The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for food insecurity on health outcomes in the primary care setting. (I statement)
Electronic Health Record Use During Paid Time Off Among Primary Care Physicians
Authors: Corey Obermiller, Richa Bundy, Lauren Witek, Adam Moses, Lindsey Carlasare, Gary Rosenthal, Christine Sinsky, Ajay Dharod
Journal: JAMA Network Open (2025)

This cohort study uses electronic health record data to quantitatively assess primary care physicians’ work during paid time off.
Integrating Artificial Intelligence Support in Patient Care While Respecting Ethical Principles
Authors: Marianne Sharko, Curtis L. Cole
Journal: JAMA Network Open (2025)

Joanna S. Cavalier, MD; Benjamin A. Goldstein, PhD; Vardit Ravitsky, PhD; Jean-Christophe Bélisle-Pipon, PhD; Armando Bedoya, MD, MMCi; Jennifer Maddocks, PT, MMCi; Sam Klotman, MPH; Matthew Roman, PT, MHA, MMCi; Jessica Sperling, PhD; Chun Xu, MB; Eric G. Poon, MD, MPH; Anand Chowdhury, MD, MMCi
US Preventive Services Task Force Recommendations for Screening for Food Insecurity
Authors: Arvin Garg, Claire E. Branley, Kimberly Montez
Journal: JAMA (2025)

US Preventive Services Task Force; Wanda K. Nicholson, MD, MPH, MBA; Michael Silverstein, MD, MPH; John B. Wong, MD; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Alicia Fernandez, MD; Ericka Gibson, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Marie Krousel-Wood, MD, MSPH; Sei Lee, MD, MAS; Goutham Rao, MD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; Joel Tsevat, MD, MPH; Sandra Millon Underwood, PhD, RN; Sarah Wiehe, MD, MPH
Navigating the Complexity of Food Insecurity Screening
Authors: Tumaini Coker, Michael Silverstein, Michael J. Barry, Wanda Nicholson
Journal: JAMA (2025)

This Viewpoint highlights primary care–based screening for food insecurity as the first social determinant of health topic to be addressed by the US Preventive Services Task Force; the potential benefit of food insecurity screening on access to other preventive services; and several challenges to making a recommendation for food insecurity screening.
Adjuvant Aspirin Treatment in PIK3CA Mutated Colon Cancer Patients: The SAKK 41/13 - Prospective Randomized Placebo-Controlled Double-Blind Trial
Authors: Ulrich Güller, Stefanie Hayoz, Daniel Horber, Wolfram Jochum, Sara De Dosso, Dieter Koeberle, Sabina Schacher, Roman Inauen, Michael Stahl, Thierry Delaunoit, Thomas Ettrich, György Bodoky, Pierre Michel, Thibaud Koessler, Karin Rothgiesser, Sandra Calmonte, Markus Joerger
Journal: Clinical Cancer Research (2025)

We assessed the benefit of adjuvant aspirin in resected PIK3CA-mutated colon cancer patients. This was a phase III, prospective, randomized, placebo-controlled, double-blind, multicenter, and multinational trial. Patients with resected colon cancer stage II and III harbouring an activating PIK3CA mutation were included. Due to financial constraints, the trial was prematurely closed. Randomization was 2:1 to aspirin 100mg versus placebo daily for 3 years. The primary endpoint was disease-free survival (DFS). Secondary endpoints included the time to disease recurrence (TTR), overall survival, and adverse events (AE). Overall, 1,040 patients were screened for PIK3CA mutations, with 112 randomized to aspirin (N=74) and placebo (N=38). Median age was 66 years and 42.9% were female. After a median follow-up of 4 years, 19 DFS events occurred, including 10 in the aspirin and nine in the placebo arm. The HR for DFS was 0.57 (90%CI: 0.27-1.22), in favor of aspirin (p=0.11). DFS rates at 5 years were 86.5% (90%CI: 77.7%-92.0%) in the aspirin and 72.9% (90%CI: 55.7%-84.3%) in the placebo arm. The HR for TTR was 0.49 (90%CI: 0.21-1.19, p=0.089) in favor of aspirin. No patient experienced aspirin-related serious AEs. The SAKK 41/13 is the first randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in resected PIK3CA-mutant colon cancer patients, with clinically relevant DFS and TTR improvements. Although results were not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III.
Circulating tumor DNA in lymphoma: technologies and applications
Authors: Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal: Journal of Hematology & Oncology (2025)

Lymphoma, a malignant tumor derived from lymphocytes and lymphoid tissues, presents with complex and heterogeneous clinical manifestations, requiring accurate patient classification for appropriate treatment. While invasive pathological examination of lymph nodes or lymphoid tissue remains the gold standard for lymphoma diagnosis, its utility is limited in cases of deep-seated tumors such as intraperitoneal and central nervous system lymphomas. In addition, biopsy procedures carry an inherent risk of complications. Computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) imaging are essential for treatment assessment and monitoring, but lack the ability to detect early clonal evolution and minimal residual disease (MRD). Liquid biopsy-based analysis of circulating tumor DNA (ctDNA) offers a non-invasive alternative that allows for repeated sampling and overcomes the limitations of spatial heterogeneity and invasive biopsies. ctDNA provides genetic and epigenetic insights into lymphoma and serves as a dynamic, quantifiable biomarker for diagnosis, risk stratification, and treatment response. This review comprehensively summarizes common genetic variations in lymphoma and systematically evaluates ctDNA detection technologies, including PCR-based assays and next-generation sequencing (NGS). Applications of ctDNA detection in noninvasive genotyping, risk stratification, therapeutic response monitoring, and MRD detection are discussed across various lymphoma subtypes, including diffuse large B-cell lymphoma, Hodgkin lymphoma, follicular lymphoma, and T-cell lymphoma. By integrating recent research findings, the review highlights the role of ctDNA profiling in advancing precision medicine, enabling personalized therapeutic strategies, and improving clinical outcomes in lymphoma.
Social Determinants of Health and Access to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
Authors: Natalie Wuliji, Salene M.W. Jones, Ted A Gooley, Aaron T Gerds, Bruno C. Medeiros, Paul J Shami, John P Galvin, Kehinde U.A. Adekola, Selina M. Luger, Maria R Baer, David A. Rizzieri, Tanya Wildes, Eunice S. Wang, Mikkael A. Sekeres, Sudipto Mukherjee, Julie Smith, Mitchell Garrison, Kiarash Kojouri, Jacob S Appelbaum, Mary-Elizabeth M. Percival, Brenda M Sandmaier, Stephanie J. Lee, Frederick Appelbaum, Rayne H. Rouce, Mohamed L. Sorror
Journal: Blood (2025)
Clonal Hematopoiesis Landscape in Frequent Blood Donors
Authors: Darja Karpova, Hector Huerga Encabo, Elisa Donato, Silvia Calderazzo, Michael Scherer, Miriam Llorian-Sopena, Aino-Maija Leppä, Roberto Würth, Patrick Stelmach, Despoina Papazoglou, Alessandra Ferrelli, Steven Ngo, Iuliia Kotova, Sabine Harenkamp, Kai Zimmer, Dominik Wolf, Jasper Panten, John Reed, Adriana Przybylla, Torsten Tonn, Annette Kopp-Schneider, Lars Velten, John F. DiPersio, Terrence N Wong, Dominique Bonnet, Halvard Bonig, Andreas Trumpp
Journal: Blood (2025)

Donor blood saves lives, yet the potential impact of recurrent large-volume phlebotomy on donor health and hematopoietic stem cells (HSCs) remains largely unexplored. In our study, we conducted a comprehensive screening of 217 older male volunteer donors with a history of extensive blood donation (&amp;gt;100 life-time donations) to investigate the phenomenon of clonal hematopoiesis (CH). No significant difference in the overall incidence of CH was found in frequent donors (FD) compared to sporadic donors (&amp;lt;10 life-time donations, 212 donors). However, upon deeper analysis of mutations in DNMT3A, the most commonly affected gene in CH, we observed distinct mutational patterns between the FD and age/sex matched control donor (CD) cohorts. Functional analysis of FD enriched DNMT3A variants examined in CRISPR-edited human HSCs demonstrated their competitive outgrowth potential upon stimulation with erythropoietin (EPO), a hormone which increases in response to blood loss. In contrast, clones harboring leukemogenic DNMT3A R882 mutations increase upon stimulation with IFNy. Through concurrent mutational and immunophenotypic profiling of primary samples at single cell resolution, a myeloid bias of premalignant R882 mutant HSCs was found, while no significant lineage bias was observed in HSCs harboring EPO responsive DNMT3A variants. The latter exhibited preferential erythroid differentiation when persistent erythropoietic stress was applied to CRISPR-edited human HSC xenografts. Our data demonstrate a nuanced ongoing Darwinian evolution at the somatic stem cell level, with EPO identified as a novel environmental factor that favors HSCs carrying certain DNMT3A mutations.
Correction: Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer
Authors: Brennah Murphy, Taito Miyamoto, Bryan S. Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P. Zhu, Daniel T. Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang
Journal: The Journal of Experimental Medicine (2025)
<scp><i>TP53</i></scp>‐Mutated Myeloid Neoplasms: 2024 Update on Diagnosis, Risk‐Stratification, and Management
Authors: Mithun Vinod Shah, Daniel A. Arber, Devendra K. Hiwase
Journal: American Journal of Hematology (2025)

ABSTRACT Alterations in the tumor suppressor gene TP53 are common in human cancers and are associated with an aggressive nature. Approximately 8%–12% of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) harbor TP53 mutations ( TP53 mut ) and present immense challenges due to inherent chemoresistance and poor outcomes. As TP53 mut are more common in older individuals and those with secondary/therapy‐related myeloid neoplasms (MN), their incidence is expected to increase with an aging population and rising proportion of cancer survivors. Treatments used for other MN—intensive chemotherapy, hypomethylating agents, and the BCL‐2 inhibitor venetoclax—do not improve the survival of TP53 mut MN patients meaningfully. Additionally, further development of many promising agents has been discontinued, highlighting the challenges. Widespread acknowledgment of these problems led to the recognition of TP53 mut MN as a distinct entity in the 5th edition of the World Health Organization and International Consensus Classifications. However, critical discrepancies between the two classifications may lead to under‐ or overestimation of the prognostic risk. Here, we review recent advances in the biology, diagnosis, and treatment of TP53 mut MN. The development of TP53 mut MN is positioned at the intersection of age, hereditary predisposition, and anti‐cancer therapies. Precursor TP53 mut clones can be detected years prior to the eventual leukemic transformation—raising the possibility of early intervention. We discuss the two classification systems and the bearing of the discrepancies between the two on timely and effective management. We provide novel evidence in the areas of discrepancies. Finally, we review the current therapeutic landscape and the obvious limitations of the currently used therapies.
Real world evidence for altered communication patterns in individuals with autism spectrum disorder
Authors: Mehran Turna, Johannes Eckert, Kristina Meier-Böke, Mamaka Narava, Irini Chaliani, Simon B. Eickhoff, Leonhard Schilbach, Juergen Dukart
Journal: npj Digital Medicine (2025)

Abstract Adults with autism spectrum disorder (ASD) may compensate for their social difficulties by resorting to more sequential forms of communication. Here, we study communication preferences in individuals with ASD and neurotypical controls by monitoring smartphone-based communication for verbal, written, and mixed app categories over a period of four months. We find ASD participants to prefer written over verbal communication, underscoring the importance of considering these preferences to facilitate social integration.
Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing
Authors: Mingyao Wang, Pengchong Fu, Ziheng Chen, Xiangnan Wang, Hanhui Ma, Xuedi Zhang, Guanjun Gao
Journal: Genome biology (2025)

Abstract Chromosomal rearrangements, such as translocations, deletions, and inversions, underlie numerous genetic diseases and cancers, yet precise engineering of these rearrangements remains challenging. Here, we present a CRISPR-based homologous recombination-mediated rearrangement (HRMR) strategy that leverages homologous donor templates to align and repair broken chromosome ends. HRMR improves efficiency by approximately 80-fold compared to non-homologous end joining, achieving over 95% homologous recombination. Validated across multiple loci and cell lines, HRMR enables efficient and accurate chromosomal rearrangements. Live-cell imaging reveals that homologous donors mediate chromosome end proximity, enhancing rearrangement efficiency. Thus, HRMR provides a powerful tool for disease modeling, chromosomal biology, and therapeutic applications.
Resistance to quorum sensing inhibition spreads more slowly during host infection than antibiotic resistance
Authors: Tom Defoirdt
Journal: Gut Microbes (2025)

Antibiotic resistance is a rising problem and new and sustainable strategies to combat bacterial (intestinal) infections are therefore urgently needed. One promising strategy under intense investigation is the inhibition of quorum sensing, bacterial cell-to-cell communication with small molecules. A key question with respect to the application of quorum sensing inhibition is whether it will impose selective pressure for the spread of resistance. It was recently shown that resistance to quorum sensing inhibition will spread more slowly during infection of a host than resistance to traditional antibiotics.
RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression
Authors: Augusto Bleve, Martina Incerti, Francesca Maria. Consonni, Valentina Garlatti, Giulia Ballerini, Chiara Pandolfo, Marta Noemi. Monari, Simone Serio, Daniela Pistillo, Marina Sironi, Chiara Alì, Marcello Manfredi, Elettra Barberis, Giovanna Finocchiaro, Marco Antonio. Cassatella, Cristina Panico, Gianluigi Condorelli, Antonio Sica
Journal: Cancer Discovery (2025)

Abstract Despite well-documented metabolic and hematopoietic alterations during tumor development, the mechanisms underlying this crucial immunometabolic intersection remain elusive. Of particular interest is the connection between lipid metabolism and the retinoic-acid-related orphan receptor (RORC1/RORγ), whose transcriptional activity modulates cancer-related emergency myelopoiesis and is boosted by cholesterol metabolites, while hypercholesterolemia itself is associated with dysregulated myelopoiesis. Here, we show that cancer and hypercholesterolemic diet independently or cooperatively activate RORγ-dependent expansion of myeloid-derived suppressor cells (MDSCs) and M2-polarized tumor-associated macrophages (TAMs), supporting cancer spread. Moreover, we report that tumor-induced expression of IL-1b and IL-6 promotes hepatic expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) in preclinical models and patients. Importantly, lowering cholesterol levels, by genetic or pharmacological inhibition of PCSK9, prevents MDSC expansion, M2 TAM accumulation and tumor progression in a RORγ-dependent manner, unleashing specific anti-tumor immunity. Overall, we identify RORγ as a key sensor of lipid disorders, bridging hypercholesterolemia and pro-tumor myelopoiesis.