tbuckley/cabot-search huggingface dataset:
Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China
Authors: Anwen Xiong, Lei Wang, Jianhua Chen, Lin Wu, Baogang Liu, Jun Yao, Hua Zhong, Jie Li, Ying Cheng, Yulan Sun, Hui Ge, Jifang Yao, Qin Shi, Ming Zhou, Bolin Chen, Zhengxiang Han, Jinliang Wang, Qing Bu, Yanqiu Zhao, Junqiang Chen, Ligong Nie, Gaofeng Li, Xingya Li, Xinmin Yu, Yinghua Ji, Daqiang Sun, Xiaohong Ai, Qian Chu, Yu Lin, Jiqing Hao, Dingzhi Huang, Chengzhi Zhou, Jinlu Shan, Hongzhong Yang, Xuewen Liu, Jing Wang, Yanhong Shang, Xiaodong Mei, Jie Yang, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Caicun Zhou
Journal: The Lancet (2025)
Global epidemiology of acute kidney injury in hospitalised patients with decompensated cirrhosis: the International Club of Ascites GLOBAL AKI prospective, multicentre, cohort study
Authors: Kavish R Patidar, Ann T Ma, Adrià Juanola, Anna Barone, Simone Incicco, Anand V Kulkarni, José Luis Pérez Hernández, Brian Wentworth, Sumeet K Asrani, Carlo Alessandria, Nadia Abdelaaty Abdelkader, Yu Jun Wong, Qing Xie, Nikolaos T Pyrsopoulos, Sung-Eun Kim, Yasser Fouad, Aldo Torre, Eira Cerda, Javier Diaz Ferrer, Rakhi Maiwall, Douglas A Simonetto, Maria Papp, Eric S Orman, Giovanni Perricone, Cristina Solé, Christian M Lange, Alberto Queiroz Farias, Gustavo Pereira, Adrian Gadano, Paolo Caraceni, Thierry Thevenot, Nipun Verma, Jeong Han Kim, Julio D Vorobioff, Jacqueline Cordova-Gallardo, Vladimir Ivashkin, Juan Pablo Roblero, Raoel Maan, Claudio Toledo, Stefania Gioia, Eduardo Fassio, Monica Marino, Puria Nabilou, Victor Vargas, Manuela Merli, Luciana Lofego Goncalves, Liane Rabinowich, Aleksander Krag, Lorenz Balcar, Pedro Montes, Angelo Z Mattos, Tony Bruns, Abdulsemed Mohammed, Wim Laleman, Enrique Carrera, María Cecilia Cabrera, Marcos Girala, Hrishikesh Samant, Sarah Raevens, Joao Madaleno, Ray W Kim, Juan Pablo Arab, José Presa, Carlos Noronha Ferreira, Antonio Galante, Andrew S Allegretti, Bart Takkenberg, Sebastian Marciano, Shiv K Sarin, François Durand, Pere Ginès, Paolo Angeli, Elsa Solà, Salvatore Piano
Journal: The Lancet. Gastroenterology & hepatology (2025)
A systematic review of digital and imaging technologies for measuring fatigue in immune mediated inflammatory diseases
Authors: Haley Mozier, Philip S. Murphy, Robert L. Janiczek, Mark Morris, Jennifer G. Cox, Hung Nguyen
Journal: npj Digital Medicine (2025)

Chronic fatigue greatly impacts the quality of life in individuals with immune-mediated inflammatory disease (IMID). Currently, fatigue assessment relies on patient-reported outcome (PRO) questionnaires. A systematic review following PRISMA guidelines was conducted to explore how digital and imaging technologies have been used to measure fatigue. PubMed and Cochrane Library were searched from 2003 to June 2023. Study quality was assessed using the STROBE checklist for observational studies. The database search identified 1541 studies; 16 were selected for inclusion, including three clinical trial reports. Disease cohorts included in this review were rheumatoid arthritis, primary Sjögren's syndrome, systemic lupus erythematosus, and inflammatory bowel disease. The majority of the studies found significant associations between fatigue, as assessed by PROs, and various digital and imaging endpoints. However, the studies were limited by a small sample size and short duration. This review stresses the need for additional research on fatigue using innovative digital and imaging modalities.
Gut microbiome modulates the outcome in primary central nervous system lymphoma patients undergoing chemotherapy: an ancillary study from the BLOCAGE trial
Authors: Isaias Hernández-Verdin, Eva Kirasic, Karima Mokhtari, Noemie Barillot, Lucas Rincón de la Rosa, Elise Sourdeau, Yahse Abada, Magali Le Tarff-Tavernier, Lucia Nichelli, Laura Rozenblum, Aurélie Kas, Bertrand Mathon, Sylvain Choquet, Caroline Houillier, Khê Hoang-Xuan, Agusti Alentorn
Journal: Neuro-Oncology (2025)

Primary central nervous system lymphoma (PCNSL) treatment relies on a high-dose methotrexate based chemotherapy (HD-MTX-based CT) regimen; however, whether there is a specific microbiota composition association with treatment response and clinical outcomes remains incompletely understood. We conducted a prospective study of PCNSL patients, included in the clinical trial NCT02313389 and the ancillary study NCT04253496 from 2020 to 2023, where patients were treated with first line HD-MTX-based polychemotherapy without a consolidation treatment. Stool (n=52), cerebrospinal fluid (CSF, n=52), and plasma samples (n=35) were collected before and/or after therapy initiation to perform metagenomic, flow cytometry, and metabolomic analyses. Plasma metabolomic data of 90 patients also included in the BLOCAGE clinical trial was subsequently used as a validation cohort. Unsupervised clustering of microbial data identified two distinct gut microbial communities, differing in Parabacteroides distasonis abundance, which correlated with progression-free survival and overall survival in both uni- and multivariate analyses. Higher P. distasonis levels were linked to increased plasma betaine/valine metabolites and enhanced CD8 T cell infiltration in the CSF, suggesting a connection between gut microbiota and immune regulation. Stratifying the validation cohort by betaine/valine content confirmed these clinical associations. Our findings suggest that gut microbiome communities modulate clinical outcomes in PCNSL patients undergoing standard treatment. Moreover, after future validation in external cohorts, the quantification of Parabacteroides distasonis could potentially provide a basis for patient stratification and guide personalized therapeutic strategies in the near future.
Reply to Mario Terlizzi, Youssef Ghannam, and Pierre Blanchard’s Letter to the Editor re: Guillaume Ploussard, Patrick Coloby, Thierry Chevallier, et al. Whole-gland or Subtotal High-intensity Focused Ultrasound Versus Radical Prostatectomy: The Prospective, Noninferiority, Nonrandomized HIFI Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.11.006
Authors: Pascal Rischmann, Bob-Valéry Occéan, Guillaume Ploussard
Journal: European Urology (2025)
Compromised epigenetic robustness in cancer: fueling evolution, exposing weakness
Authors: Thomas Stuart Wilson, Paola Scaffidi
Journal: Trends in cancer (2025)

The complex network of proteins that regulate chromatin and DNA methylation landscapes is often disrupted in cancer. Clonal and subclonal mutations targeting a wide range of molecular functions are frequently observed across cancer types, and emerging evidence suggests that loss of robust epigenetic control promotes both cancer initiation and evolution, independently of context-specific effects. Here, we review how diverse genetic alterations that destabilize the epigenetic regulatory network (ERN) may converge into common phenotypes. We also discuss the implications of altered network topology and systemic epigenetic disorder for the evolution, vulnerability, and therapeutic resistance of cancers.
Characterizing the Rates and Patterns of <i>De Novo</i> Germline Mutations in the Aye-Aye (<i>Daubentonia madagascariensis</i>)
Authors: Cyril J Versoza, Erin E Ehmke, Jeffrey D Jensen, Susanne P Pfeifer
Journal: Molecular Biology and Evolution (2025)

Given the many levels of biological variation in mutation rates observed to date in primates-spanning from species to individuals to genomic regions-future steps in our understanding of mutation rate evolution will not only be aided by a greater breadth of species coverage across the primate clade but also by a greater depth as afforded by an evaluation of multiple trios within individual species. In order to help bridge these gaps, we here present an analysis of a species representing one of the most basal splits on the primate tree (aye-ayes), combining whole-genome sequencing of seven parent-offspring trios from a three-generation pedigree with a novel computational pipeline that takes advantage of recently developed pan-genome graphs, thereby circumventing the application of (highly subjective) quality metrics that has previously been shown to result in notable differences in the detection of de novo mutations and ultimately estimates of mutation rates. This deep sampling has enabled both a detailed picture of parental age effects and sex dependency in mutation rates, which we here compare with previously studied primates, but has also provided unique insights into the nature of genetic variation in one of the most endangered primates on the planet.
Addressing contemporary threats in anonymised healthcare data using privacy engineering
Authors: Sanjiv M. Narayan, Nitin Kohli, Megan M. Martin
Journal: npj Digital Medicine (2025)

Cyber-attacks on healthcare entities and leaks of personal identifiable information (PII) are a growing threat. However, it is now possible to learn sensitive characteristics of an individual without PII, by combining advances in artificial intelligence, analytics, and online repositories. We discuss privacy threats and privacy engineering solutions, emphasizing the selection of privacy enhancing technologies for various healthcare cases. Future solutions must consider dynamic flows of data throughout their lifecycle.
Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301)
Authors: Adi Diab, Paolo A. Ascierto, Michele Maio, Reham Abdel-Wahab, Sylvie Negrier, Laurent Mortier, Petr Arenberger, Stephane Dalle, Ivana Krajsova, Luis de la Cruz, Marie-Therese Leccia, Michele Guida, Celeste Lebbe, Jean-Jacques Grob, Marcus O. Butler, Gino K. In, Carmen Loquai, John W.T. Walker, Victoria Atkinson, Ellen Kapiteijn, Sebastian Haferkamp, Srinivas Chunduru, Shahram Rahimian, Massimo Guidoboni, Caroline Robert
Journal: Journal of Clinical Oncology (2025)

There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma. Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS). A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; P = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively. Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.
Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases
Authors: Sarah A. Weiss, Dijana Djureinovic, Wei Wei, Thuy Tran, Matthew Austin, Joseph Markowitz, Zeynep Eroglu, Nikhil I. Khushalani, Upendra Hegde, Justine Cohen, Mario Sznol, Gail Anderson, Barbara Johnson, Cecily Piteo, Amit Mahajan, Adebowale Adeniran, Lucia Jilaveanu, Sarah Goldberg, Veronica Chiang, Peter Forsyth, Harriet M. Kluger
Journal: Journal of Clinical Oncology (2025)

Anti-vascular endothelial growth factor therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema and radiation necrosis. We conducted a two-institution phase II trial of bevacizumab and pembrolizumab in patients with untreated melanoma brain metastasis (MBM) (ClinicalTrials.gov identifier: NCT02681549). Patients were anti-PD-(L)-1-naïve, and had ≥one asymptomatic, nonhemorrhagic 5-20 mm MBM, not requiring immediate local therapy or steroids. Thirty-seven patients received four doses of bevacizumab and pembrolizumab every 3 weeks followed by up to 2 years of pembrolizumab. The brain metastasis response rate (primary end point) was 54.1% (95% CI, 36.9 to 70.5). The extracranial response rate was 56.3% (95% CI, 37.7 to 73.6). Median intracranial progression-free survival was 2.2 years (95% CI, 0.41 to not reached [NR]). Median overall survival (OS) was 4.3 years (95% CI, 1.6 to NR). Four-year OS rate was 51.6%. Grade 3 treatment-related adverse event rates from bevacizumab and pembrolizumab were 10.8% and 18.9%, respectively. Higher pretreatment vessel density in metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were associated with response. Pembrolizumab with bevacizumab was well tolerated and demonstrated substantial activity in patients with untreated MBM with promising OS, justifying further evaluation of this regimen.
Erratum: Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study
Authors: Odile Oberlin, Annie Rey, José Sanchez de Toledo, Hélène Martelli, Meriel E.M. Jenney, Marcelo Scopinaro, Christophe Bergeron, Johannes H.M. Merks, Nathalie Bouvet, Caroline Ellershaw, Anna Kelsey, David Spooner, Michael C.G. Stevens
Journal: Journal of Clinical Oncology (2025)
Investigation of the Protein Corona and Biodistribution Profile of Polymeric Nanoparticles for Intra-Amniotic Delivery
Authors: Anna Y Lynn, Kwangsoo Shin, David A Eaton, Micky Rose, Xianzhi Zhang, Madalina Ene, Julian Grundler, Emily Deschenes, Rachel Rivero, Laura G Bracaglia, Peter M Glazer, David H Stitelman, W Mark Saltzman
Journal: Biomaterials (2025)
Identification of Atrial Myopathy and Atrial Fibrillation Recurrence after Ablation using 3D Left Atrial Phasic Strain from Retrospective Gated Computed Tomography
Authors: Charles Sillett, Orod Razeghi, Tiffany M G Baptiste, Angela W C Lee, Jose Alonso Solis Lemus, Cristobal Rodero, Caroline H Roney, Ruibin Feng, Prasanth Ganesan, Hui Ju Chang, Paul Clopton, Nick Linton, Ronak Rajani, A J Rogers, Sanjiv M Narayan, Steven A Niederer
Journal:  (2025)

Reduced left atrial (LA) mechanical function associates with atrial myopathy and adverse clinical endpoints in atrial fibrillation (AF) patients; however, conventional 2D imaging modalities are limited by atrial foreshortening and sub-optimally capture 3D LA motion. We set out to test the hypothesis that 3D LA motion features from 4D (3D + time) retrospective gated computed tomography (RGCT) associate with AF phenotypes and predict AF recurrence in patients undergoing catheter ablation. Sixty-nine AF patients (60.8 ± 12.2 years, 39% female, 30% non-paroxysmal AF) who were indicated for CT coronary angiography including a RGCT protocol in sinus rhythm prior to ablation were included. We measured 3D LA endocardial motion by optimized 3D feature tracking and calculated 3D global and regional phasic strain and peak strain rates (SRs). AF recurrence was observed in 18 patients (26%) at 1-year. Global reservoir strain (P < 0.05) and contractile strain and SR (both P < 0.01) were reduced in patients with vs. those without recurrent AF. Global and anterior wall contractile SR were more predictive of recurrent AF than LA volume index (area under the curve, AUC: 0.74, 0.77, and 0.68, respectively). Reduced global conduit SR and septal reservoir strain were more strongly associated with non-paroxysmal AF than CHADS2-VASc (AUCs: 0.74, 0.75, and 0.59, respectively). Reduced passive and active 3D LA motion from 4D RGCT associates with more advanced AF and AF recurrence post-ablation, respectively. Future work should extend this approach to larger populations, with new low-radiation CT technologies to widen its applicability.
Shared decision making with older people on treatment escalation planning for acute deterioration in the emergency medical setting: a UK-based qualitative study of patient perspectives (STREAMS-P)
Authors: Bronwen E Warner, Mary Wells, Cecilia Vindrola, Stephen J Brett
Journal: The Lancet Healthy Longevity (2025)

Shared decision making (SDM) in treatment escalation planning (TEP) involves patients and clinicians determining together a contingency for future health deterioration. Patients' role in health-care decision making is subject to ongoing debate. This study aimed to understand the perspectives of older patients in the UK on SDM in TEP for the acute hospital setting. In this qualitative study, we recruited older adults with varying levels of frailty and diverse ethnicity via primary care in an Inner London borough. We excluded individuals who did not have the capacity to make TEP decisions, could not be interviewed in English, or whose main chronic clinical problem was cancer or an established severe single organ failure. We used purposive stratified sampling to capture a variety of age, frailty, and ethnicity. We conducted semistructured interviews from March 31 to Dec 19, 2023, and audiorecorded them. We then performed a reflexive thematic analysis. We conducted 27 interviews with 32 participants. Participants were aged 63-101 years, clinical frailty ranged from none to severe and was distributed across age groups, and 19 participants were female and 13 participants were male. We identified four themes from the interviews: (1) Focusing on a Natural Life Lived Well, which reflects participants' ideas around expected life and death trajectory; (2) Making Sense of an Unfamiliar Medical Narrative, where detailed planning for medical intervention was not expected; (3) My Body, My Decision, in which there was emphasis on retaining control over health-care decisions; and (4) Expert, Imperfect Doctors in an Essential, Imperfect System, in which the context of decision making involving health-care professionals in a stretched UK health service was considered. Patients did not immediately perceive the relevance of detailed planning for future treatment, but nonetheless showed determination to be final arbiters on health-care decisions. Viewed in the context of increasing emphasis on patient autonomy, future steps include public education on possibilities and limitations for intensive medical intervention, clinician reflection on approaches to TEP conversations and policy-level deliberation to define expectations for patient involvement in TEP decisions. HCA International and NIHR Imperial Biomedical Research Centre.
USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells
Authors: Yang Ou, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi, Min Guo, Zhaoxian Li, Jie Shi, Yuxin Liu, Siyu Zuo, Xiao Chen, Yanjing Wang, Mengdan Feng, Hang Wang, Peiqing Sun, Yi Shi, Guang Yang, Shuang Yang
Journal: Acta Pharmaceutica Sinica B (2025)
Evaluation of FXR Activity in Pollutants Identified in Sewage Sludge and Subsequent <i>in vitro</i> and <i>in vivo</i> Characterization of Metabolic Effects of Triphenyl Phosphate
Authors: Yi Yang, Ling Jiao, Yixuan Huang, Hailin Shang, Enrui Li, Hong Chang, Hongyang Cui, Yi Wan
Journal: Environmental Health Perspectives (2025)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and increasing evidence suggests that exposure to environmental pollutants is associated with the increased incidence of MASLD. The farnesoid X receptor (FXR) plays an important role in the development of MASLD by regulating bile acids (BAs) and lipid metabolism. However, whether FXR-active pollutants are the environmental drivers of MASLD remains unclear. This study aimed to determine whether FXR-active pollutants exist in the environment and evaluate their ability to trigger MASLD development in mice. An FXR protein affinity pull-down assay and nontargeted mass spectrometry analysis were used to identify environmental FXR ligands in sewage sludge. A homogeneous time-resolved fluorescence coactivator recruitment assay and cell-based dual-luciferase reporter assay were used to determine the FXR activities of the identified pollutants. Targeted analysis of BAs, mass spectrometry imaging, lipidomic analysis, 16S rRNA sequencing, and quantitative polymerase chain reaction were conducted to assess the ability of FXR-active pollutants to induce metabolic disorders of BAs and lipids and to contribute to MASLD development in C57BL/6N mice. We identified 19 compounds in the sewage sludge that had FXR-antagonistic activity, and triphenyl phosphate (TPHP) was the FXR antagonist with the highest efficacy. Mice exposed to either 10 or 50 mg/kg TPHP for 30 days had higher levels of conjugated primary BAs in enterohepatic circulation, and the BA pool showed FXR antagonistic activities. The exposed mice also had greater lipogenesis (more Oil Red O staining and high triglyceride levels) in liver. 19 FXR-antagonistic pollutants were identified in sewage sludge. FXR inhibition by the strongest antagonist TPHP may have a role in promoting MASLD development in mice by inducing a positive feedback loop between the FXR and BAs. https://doi.org/10.1289/EHP15435.
Advances in the management of endometrial cancer
Authors: Bradley R Corr, Britt K Erickson, Emma L Barber, Christine M Fisher, Brian Slomovitz
Journal: BMJ (2025)

Endometrial cancer is now the most lethal gynecologic malignancy, with incidence rates rising globally. Treatment strategies have historically been focused on a combination of surgery, radiation, and/or chemotherapy based primarily on histology and extent of tumor. Advances in the evaluation and treatment of endometrial cancers are occurring at a rapid pace, with a new focus on genomic profiling and targeted therapies. Surgical removal of the tumor remains the mainstay of therapy, but adjuvant treatments are a shifting paradigm. In the realm of gynecologic malignancies, endometrial cancer leads in the evolution of precision medicine. The ability to analyze patients, tumors, and therapy has increased over the past 10 years. Gaps in knowledge about racial and ethnic disparities, as well as pre-invasive disease prevention, are closing. This review describes the advances in endometrial cancer with a focus on people at risk, molecular classification, and modern therapeutic strategies.
Author Correction: Neuronal polyunsaturated fatty acids are protective in ALS/FTD
Authors: Ashling Giblin, Alexander J. Cammack, Niek Blomberg, Sharifah Anoar, Alla Mikheenko, Mireia Carcolé, Magda L. Atilano, Alex Hull, Dunxin Shen, Xiaoya Wei, Rachel Coneys, Lele Zhou, Yassene Mohammed, Damien Olivier-Jimenez, Lian Y. Wang, Kerri J. Kinghorn, Teresa Niccoli, Alyssa N. Coyne, Rik van der Kant, Tammaryn Lashley, Martin Giera, Linda Partridge, Adrian M. Isaacs
Journal: Nature Neuroscience (2025)