tbuckley/cabot-search huggingface dataset:
A TIM-3-Fc decoy secreted by engineered T cells improves CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia
Authors: Aïda Falgàs, Rodrigo Lázaro-Gorines, Samanta Romina Zanetti, Laura Rubio-Pérez, Alba Martinez-Moreno, Meritxell Vinyoles, Mercedes Guerrero-Murillo, Narcís Fernandez-Fuentes, Heleia Roca-Ho, Néstor Tirado, Carla Panisello, Talía Velasco-Hernandez, Andrea Mayado, Alba Pérez-Pons, Eulalia Genesca, Josep-Maria Ribera, Jordi Ribera, Mireia Camos, Manuel Ramírez-Orellana, Eduardo Anguita, Paola Ballerini, José Luis Fuster, Manel Juan, Europa Azucena Azucena González-Navarro, Franco Locatelli, Ronald W. W. Stam, Sergio Querol, Pablo Velasco, Valentín Ortiz-Maldonado, Nuria Martínez-Cibrian, Julio Delgado, Alberto Orfao, Luis Alvarez-Vallina, Clara Bueno, Pablo Menendez
Journal: Blood (2025)

Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging disease with a dismal prognosis. Despite the revolutionary impact of CD19-directed chimeric antigen receptor (CAR19)-T cell therapy, &amp;gt;50% of patients relapse within a year. Both leukemia cell-intrinsic factors favoring immune escape and poor CAR-T cell persistence contribute significantly to clinical failure. Moreover, the expression of immune checkpoint receptors (ICRs) and their ligands within the complex bone marrow (BM) microenvironment may contribute to leukemia progression and therapy resistance. Here, we comprehensively characterized the expression of ICRs and their ligands in leukemic blasts, T cells, and mesenchymal stromal cells (MSCs) from B-ALL BM samples at diagnosis (n=47) and relapse (n=38), comparing them with age-matched healthy BM controls. Our findings reveal a significant upregulated expression of TIM-3 in T cells, and its ligand galectin-9 in both blasts and MSCs throughout disease progression. The expression levels of galectin-9 in B-ALL blasts and TIM-3 in CAR19-T cells negatively correlate with clinical outcome. Furthermore, we demonstrate that galectin-9 impairs CAR19-T cell homeostasis and cytotoxicity. Notably, an engineered TIM-3-Fc decoy receptor, delivered either by primary T cells co-administered with CAR19-T cells or via a bicistronic all-in-one CAR19-TIM-3-Fc construct, improved the anti-leukemia efficacy and persistence of CAR19-T cells in B-ALL patient-derived xenograft models. Mechanistically, CAR19-TIM-3-Fc-T cell treatment promotes the in vivo expansion of both transduced and bystander effector and memory T cells, as determined by spectral flow cytometry. Collectively, these potent and persistent TIM-3-Fc decoy-armored CAR19-T cells offer a promising therapeutic strategy for R/R B-ALL patients.
Itacitinib for the Prevention of IEC Therapy-Associated CRS: Results From the Two-Part Phase 2 INCB 39110-211 Study
Authors: Matthew J. Frigault, Richard T. Maziarz, Jae H Park, Aleksandr Lazaryan, Nirav N Shah, Jakub Svoboda, Lazaros J. Lekakis, Ran Reshef, Christine L. Phillips, Lea Burke, Jing Lei, Michael Pratta, Rodica Morariu-Zamfir, John F. DiPersio
Journal: Blood (2025)

Cytokine release syndrome (CRS) and immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) are common complications following IEC therapy for hematologic malignancies. This two-part, phase 2 study (INCB 39110-211) investigated safety and efficacy of itacitinib, a potent, highly selective Janus kinase 1 inhibitor with broad anti-inflammatory activity, for prevention of CRS and ICANS in patients receiving commercial CD19-directed IEC therapy. Patients in part 1 received once-daily itacitinib 200 mg 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through Day 26, with guidelines for use of other CRS/ICANS interventions. In part 2 (double-blind), patients were randomized to receive twice-daily (bid) itacitinib 200 mg or placebo 3 days before IEC therapy with axi-cel. The primary endpoint was proportion of patients with CRS grade ≥2 by Day 14 using ASTCT consensus grading system. Overall, 111 patients were enrolled (63 in part 1; 48 in part 2), with 109 patients analyzed for efficacy and 110 for safety. Itacitinib 200 mg bid resulted in a significantly lower proportion of patients with grade ≥2 CRS by Day 14 versus placebo (17.4% vs 56.5%; P=0.003). The proportion of patients with grade ≥2 ICANS by Day 28 was lower than with placebo (8.7% vs 21.7%). Itacitinib was well tolerated, with pyrexia the most common TEAE (itacitinib 200 mg bid: 43.5%; placebo: 50.0%) and itacitinib-related cytopenias manageable. Importantly, itacitinib did not impact IEC therapy efficacy (objective response rate at 6 months: 39.1% for itacitinib 200 mg bid vs 26.1% for placebo). Trial registration: clinicaltrials.gov; #NCT04071366.
Impact of HLA Alloimmunization in Gene-Modified Autologous Stem Cell Transplant For Transfusion-Dependent Thalassemia
Authors: Nora M Gibson, Eugene Khandros, Caitlin W Elgarten, Elizabeth Worster, Dimitrios S. Monos, Alexis A. Thompson, Janet L. Kwiatkowski, Timothy Olson
Journal: Blood (2025)
Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome
Authors: Changya Chen, Jason Xu, Jonathan H Sussman, Tiffaney L Vincent, Joseph S Tumulty, Satoshi Yoshimura, Fatemeh Alikarami, Wenbao Yu, Yang-Yang Ding, Chia-Hui Chen, Elizabeth Y Li, Austin Yang, Xiaohuan Qin, Shovik Bandyopadhyay, Jacqueline Jiahui Peng, Petri Pölönen, Haley Newman, Brent Wood, Jianzhong Hu, Rawan Shraim, Andrew D Hughes, Caroline Diorio, Lahari Uppuluri, Gongping Shi, Theresa Ryan, Tori Fuller, Mignon L. Loh, Elizabeth A. Raetz, Stephen P Hunger, Stanley B Pounds, Charles G. Mullighan, David Frank, Jun J Yang, Kathrin Maria Bernt, David Trent Teachey, Kai Tan
Journal: Blood (2025)
Obesity substantially impacts rheumatic and musculoskeletal diseases: time to act
Authors: Naveed Sattar, Lindsey J Sattar, Iain B McInnes, Stefan Siebert, Lyn D Ferguson
Journal: Annals of the Rheumatic Diseases (2025)

Obesity is a major health problem and risk factor for many chronic health conditions, including rheumatic and musculoskeletal diseases (RMDs). Around 7 in 10 adults with RMD live overweight or with obesity. Obesity not only increases the risk of developing RMDs. It worsens disease activity, pain, and fatigue; impairs treatment responses; and thereby reduces quality of life and physical function. Further, obesity can amplify or drive several comorbidities that are more prevalent in RMDs including hypertension, cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Moreover, reciprocal risk arises since RMDs make it harder to be physically active and maintain a healthy weight, especially in the context of an obesogenic environment. In this viewpoint, we review relevant evidence to suggest obesity confers distinctive, important challenges in care and daily living for many patients with RMDs. With the advent of several highly effective drugs for obesity, we also highlight research needs including that for robust clinical trials to test the efficacy and effectiveness of these therapies as part of the management of inflammatory RMDs, as primary agent or adjuvant to immune targeted therapeutics. Implementing such weight management strategies should provide a much-needed holistic approach to the care of our patients.
Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut
Authors: Robert E. Steinert, Ateequr Rehman, Mehdi Sadaghian Sadabad, Alessio Milanese, Jonas Wittwer-Schegg, Jeremy P. Burton, Anneleen Spooren
Journal: Gut Microbes (2025)

In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.
Association of physical therapy care with utilization of intra‐articular injections in people with knee osteoarthritis: a real‐world cohort study
Authors: Tuhina Neogi, Maureen Dubreuil, Christine Peloquin, Lee Marinko, James Camarinos, David T. Felson, Deepak Kumar
Journal: Arthritis & Rheumatology (2025)

Objective To assess the relation of physical therapy (PT) timing, dose, and type with risk of future intra‐articular therapy use in people with knee osteoarthritis (OA) who receive PT. Methods We used data from a de‐identified claims database (Optum Labs Data Warehouse) from American adults with incident knee OA referred for PT within the first year of their knee OA diagnosis. We categorized people as having previously had intra‐articular therapies or not. We examined the association of timing of PT initiation, number of PT sessions, and the type of PT (predominantly active or passive) to the relation of intra‐articular therapy use over a period of 1 year following the first year of diagnosis. Results Of the 67,245 individuals with knee OA (age 61.5±11 years, 61% female, 10% Black, 6% Hispanic) 34,804 and 32,441 did and did not have prior intra‐articular therapies, respectively. Among those who had prior intra‐articular therapies, initiating PT at 9‐12 months post‐diagnosis was associated with an adjusted risk ratio of 1.44 for future intra‐articular therapy (95% CI 1.35‐1.55) compared with those who initiated within a month. For both groups, 13+ PT sessions were associated with a 10% and 12% lower risk, respectively, compared with 1‐5 sessions. Active PT was not related to lower risk compared to passive PT interventions. Conclusion Initiating PT earlier and more than 12 PT sessions were significantly associated with lower risk of future intra‐articular therapy use in people with newly diagnosed knee OA.
Shifting landscapes of gender equity in oncology journals: a decade of authorship trends
Authors: Hang Yi, Mingzhong Wan, Xu Ou-Yang, Yang Wang, Yan Wang, Yinyan Gao, Qihao Leng, Shuangping Zhang, Yousheng Mao, Guochao Zhang
Journal: Molecular Cancer (2025)

Gender disparities persist in academic oncology, particularly in authorship and senior academic roles. This study evaluates trends in authorship gender representation over the past decade across top oncology journals, focusing on regional, journal-specific, and citation-based disparities. A cross-sectional analysis was conducted on 29,005 articles published between 2014 and 2023 in the top 20 oncology journals, identified through the Web of Science database. Author gender was determined using the NamSor tool. Temporal trends were analyzed using linear regression, and multivariate logistic regression identified factors contributing to gender disparities. Regional and citation analyses explored geographic variations and citation count differences. Among analyzed articles, 41.81% of first authors and 29.93% of last authors were female. Female first authorship showed a significant upward trend (P < 0.01), with gender parity projected by 2034, while parity for last authors is expected by 2055. Regional differences were notable, with North America and Europe leading in female representation. Certain journals, such as CA: A Cancer Journal for Clinicians and Molecular Cancer, exhibited higher female authorship proportions, while Journal of Clinical Oncology had the lowest. Citation analysis revealed female-authored articles received significantly fewer citations than male-authored ones (P < 0.01). Although female authorship in oncology journals has increased over the past decade, disparities remain, particularly in senior roles and citation impact. Addressing these issues requires targeted strategies, including mentorship programs, greater female representation in editorial boards, and institutional policies promoting gender equity.
How to handle polypharmacy in heart failure. A clinical consensus statement of the Heart Failure Association of the <scp>ESC</scp>
Authors: Davide Stolfo, Massimo Iacoviello, Ovidiu Chioncel, Markus S. Anker, Antoni Bayes‐Genis, Frieder Braunschweig, Antonio Cannata, Seif El Hadidi, Gerasimos Filippatos, Pardeep Jhund, Alexandre Mebazaa, Brenda Moura, Massimo Piepoli, Robin Ray, Arsen D. Ristic, Petar Seferovic, Maggie Simpson, Hadi Skouri, Carlo Gabriele Tocchetti, Sophie Van Linthout, Cristiana Vitale, Maurizio Volterrani, Kalliopi Keramida, Sven Wassmann, Basil S. Lewis, Marco Metra, Giuseppe M.C. Rosano, Gianluigi Savarese
Journal: European Journal of Heart Failure (2025)

Abstract The multiplicity of coexisting comorbidities affecting patients with heart failure ( HF) , together with the availability of multiple treatments improving prognosis in HF with reduced ejection fraction, has led to an increase in the number of prescribed medications to each patient. Polypharmacy is defined as the regular use of multiple medications, and over the last years has become an emerging aspect of HF care, particularly in older and frailer patients who are more frequently on multiple treatments, and are therefore more likely exposed to tolerability issues, drug–drug interactions and practical difficulties in management. Polypharmacy negatively affects adherence to treatment, and is associated with a higher risk of adverse drug reactions, impaired quality of life, more hospitalizations and worse prognosis. It is important to adopt and implement strategies for the management of polypharmacy from other medical disciplines, including medication reconciliation, therapeutic revision and treatment prioritization. It is also essential to develop new HF ‐specific strategies, with the primary goal of avoiding the use of redundant treatments, minimizing adverse drug reactions and interactions, and finally improving adherence. This clinical consensus statement document from the Heart Failure Association of the European Society of Cardiology proposes a rationale, pragmatic and multidisciplinary approach to drug prescription in the current era of multimorbidity and ‘multi‐medication’ in HF .
LW-CTrans: A lightweight hybrid network of CNN and Transformer for 3D medical image segmentation
Authors: Hulin Kuang, Yahui Wang, Xianzhen Tan, Jialin Yang, Jiarui Sun, Jin Liu, Wu Qiu, Jingyang Zhang, Jiulou Zhang, Chunfeng Yang, Jianxin Wang, Yang Chen
Journal: Medical Image Analysis (2025)
AI Image Generation Technology in Ophthalmology: Use, Misuse and Future Applications
Authors: Benjamin Phipps, Xavier Hadoux, Bin Sheng, J Peter Campbell, T Y Alvin Liu, Pearse A Keane, Carol Y Cheung, Tham Yih Chung, Tien Y Wong, Peter van Wijngaarden
Journal: Progress in Retinal and Eye Research (2025)
Factors associated with the use of guideline‐directed medical therapy in patients with left ventricular assist device
Authors: Michel Chedid El Helou, Phoo Pwint Nandar, Larisa G. Tereshchenko, Miriam Jacob, Pavan Bhat, Amanda R. Vest, Sanjeeb Bhattacharya, Eileen Hsich, Patrick Collier, W.H. Wilson Tang, Edward Soltesz, Michael Z. Tong, Randall C. Starling, Trejeeve Martyn
Journal: European Journal of Heart Failure (2025)

Abstract Aims Societal guidelines have recently supported the use of guideline‐directed medical therapy (GDMT) in patients with left ventricular assist device (LVAD) to promote ventricular recovery. We sought to characterize patient factors associated with use of GDMT in durable LVAD recipients. Methods and results We performed a retrospective analysis of patients with a HeartMate 3 (HM3) LVAD at our institution, including comprehensive data from the past 12 months. The GDMT score (0–8) factored in doses of beta‐blocker (BB), angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), mineralocorticoid receptor antagonist (MRA), sodium–glucose cotransporter 2 inhibitor (SGLT2i), angiotensin receptor–neprilysin inhibitor (ARNI), isosorbide dinitrate/hydralazine (ISDN/HYD). Our cohort consisted of 270 patients (mean age 63 years, 77% male). Median GDMT score was 3 ± 1.7, and 155 patients (57.4%) had a score of 3 or lower. Prescription rates were 50% for BB, 74.1% for ACEi/ARB/ARNI, 14.8% for SGLT2i, 47% for MRA, and 19.6% for ISDN/HYD. On univariable logistic regression, increasing age, right ventricular dysfunction, estimated glomerular filtration rate &lt;60 ml/min/1.7 3 m 2 , and destination therapy strategy were associated with a GDMT score below the median. Only age remained a significant predictor after adjustment. In multivariable analysis for individual drugs, right ventricular dysfunction was linked to non‐use of BB, and age and Black race were associated with non‐use of MRA and use of ISDN/HYD, but no significant predictors were identified for other therapies. Conclusion While advancing age is associated with lower use of GDMT in HM3 recipients, other patient factors do not adequately explain low prescription rates. This highlights significant opportunity to improve the use of GDMT in LVAD patients.
Extracellular Vesicles Delivered by a Nanofiber‐Hydrogel Composite Enhance Healing In Vivo in a Model of Crohn's Disease Perianal Fistula (Adv. Healthcare Mater. 7/2025)
Authors: Ling Li, Zhicheng Yao, Kevan J. Salimian, Jiayuan Kong, Atif Zaheer, Alyssa Parian, Susan L. Gearhart, Hai‐Quan Mao, Florin M. Selaru
Journal: Advanced Healthcare Materials (2025)
Overexpression of Wild-Type TMEM43 Improves Cardiac Function in Arrhythmogenic Right Ventricular Cardiomyopathy Type 5
Authors: Laura Lalaguna, María Arévalo-Núñez de Arenas, Marina López-Olañeta, María Villalba-Orero, Rafael J. Jiménez-Riobóo, María Victoria Gómez-Gaviro, Joan Isern, Pura Muñoz-Cánoves, Barry J. Byrne, Juan Pablo Ochoa, Pablo García-Pavía, Enrique Lara-Pezzi
Journal: Circulation Research (2025)

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is the most aggressive type of ARVC, caused by a fully penetrant missense mutation (p.S358L) in TMEM43 (transmembrane protein 43). Pathologically, the disease is characterized by dilation of the cardiac chambers and fibrofatty replacement of the myocardium, which results in heart failure and sudden cardiac death. Current therapeutic options are limited, and no specific therapies targeting the primary cause of the disease have been proposed. METHODS: We investigated whether overexpression of wild-type (WT) TMEM43 could overcome the detrimental effects of the mutant form. We used transgenic mouse models overexpressing either WT or mutant (S358L) TMEM43 to generate a double transgenic mouse line overexpressing both forms of the protein. In addition, we explored if systemic delivery of a codon-optimized self-complementary adeno-associated virus bearing WT-TMEM43 could improve disease progression assessed by ECG and echocardiography. RESULTS: Double transgenic mice overexpressing both WT and mutant TMEM43 forms showed delayed ARVC5 onset, improved cardiac contraction, and reduced ECG abnormalities compared with mice expressing S358L-TMEM43. In addition, cardiomyocyte death and myocardial fibrosis were reduced, with an overall increase in survival. Finally, we demonstrated that a single systemic administration of an adeno-associated virus carrying codon-optimized WT-TMEM43 prevents ventricular dysfunction and ECG abnormalities induced by S358L-TMEM43. CONCLUSIONS: Overexpression of WT-TMEM43 improves the pathological phenotype in a mouse model of ARVC5. Adeno-associated virus-mediated delivery of WT-TMEM43 offers a promising and specific therapy for patients suffering from this highly lethal disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT05885412, NCT06109181, and NCT06228924.
Withdrawal of Guideline-Directed Medical Therapy in Patients With Heart Failure and Improved Ejection Fraction
Authors: Christian Basile, Felix Lindberg, Lina Benson, Federica Guidetti, Ulf Dahlström, Massimo Francesco Piepoli, Peter Mol, Raffaele Scorza, Aldo Pietro Maggioni, Lars H. Lund, Gianluigi Savarese
Journal: Circulation (2025)

BACKGROUND: Limited evidence exists on the prognostic role of continuing medical therapy in patients with heart failure (HF) and an ejection fraction (EF) that has improved over time. This study assessed rates of, patient profiles, and associations with morbidity/mortality of renin-angiotensin inhibitors (RASi), angiotensin receptor–neprilysin inhibitors (ARNi), beta-blockers (BBL), and mineralocorticoid receptor antagonists (MRA) withdrawal in patients with HF with improved EF. METHODS: Patients with a first recorded EF &lt;40% and a later EF ≥40% from the Swedish HF registry between June 11, 2000, and December 31, 2023, were included in this retrospective observational study. Withdrawal was defined as a patient on treatment at the first (reduced) but not at the second (improved) registration. The association between withdrawal and time to first cardiovascular mortality/hospitalization for HF with censoring at 1 year was assessed by Cox regression model using overlap weighting. RESULTS: Of 8728 patients with HF with improved EF (median age, 70 years [25th to 75th percentile, 61–78], 2611 [29.9%] women), 96%, 94%, and 46% received RASi/ARNi, BBL, and MRA, respectively, when EF was &lt;40%. The withdrawal rates at the time of the improved EF registration were 4.4% for RASi/ARNi, 3.3% for BBL, and 17.2% for MRA. Predictors of withdrawal included lower use of other HF medications, higher EF at the later EF registration, and a longer time between the 2 EF assessments. After weighting, withdrawal was independently associated with a higher risk of cardiovascular mortality/hospitalization for HF by 38% for RASi/ARNi and 36% for MRA, but not for BBL. Withdrawal of BBL was associated with a higher risk of the primary outcome in the subgroup of patients with an improved EF of 40% to 49% versus ≥50% ( P -interaction 0.03). CONCLUSIONS: In patients with HF with improved EF, HF therapy withdrawal was rare. Withdrawing RASi/ARNi and MRA was associated with higher mortality/morbidity at 1 year. No association was found for BBL withdrawal, albeit with a significant heterogeneity for EF at improvement, suggesting better outcomes with continuing BBL only until EF improves up to 50%. These results are hypothesis-generating and highlight the need for randomized controlled trials testing BBL withdrawal in patients with HF with improved EF.
Boosting mRNA‐Engineered Monocytes via Prodrug‐Like Microspheres for Bone Microenvironment Multi‐Phase Remodeling (Adv. Healthcare Mater. 7/2025)
Authors: Yuansheng Wu, Yingjie Zhu, Jie Chen, Lili Song, Chunping Wang, Yanglin Wu, Yanyang Chen, Jiancheng Zheng, Yuankun Zhai, Xiang Zhou, Youwen Liu, Yawei Du, Wenguo Cui
Journal: Advanced Healthcare Materials (2025)