tbuckley/cabot-search huggingface dataset:
Racial Disparities in Long-Term Outcomes After Endovascular Aortic Aneurysm Repair in Black and White Medicare Beneficiaries
Authors: Abena Appah-Sampong, Christina Marcaccio, Siling Li, Yang Song, Mohamad A. Hussain, Robert Yeh, Marc L. Schermerhorn, Eric A. Secemsky
Journal: Circulation (2025)

BACKGROUND: Despite reported racial disparities between Black and White adults in short-term outcomes after abdominal aortic aneurysmal intervention, there is a paucity of literature aimed at understanding long-term disparities. The present study aims to characterize racial disparities in long-term outcomes, perioperative outcomes, and health care use after endovascular aortic aneurysm repair. METHODS: We conducted a retrospective cohort study from 2011 to 2019 with outcome assessment through 2020. Using a 100% sample of national Medicare data, we identified beneficiaries ≥66 years of age who underwent intact infrarenal endovascular aortic aneurysm repair. The primary outcome was a composite of endovascular or open aortic reintervention, late aneurysm rupture, and all-cause mortality. Secondary outcomes included other reinterventions, perioperative outcomes, and annual rates of health care use. RESULTS: A cohort of 107 636 Black (3.9%) and White (96.1%) beneficiaries was identified. The cumulative incidence of the primary outcome was 72.9% (95% CI, 71.8%–73.9%) in White patients versus 80.0% (95% CI, 76.4–83.0) in Black patients ( P &lt;0.0001). The adjusted hazard of the primary outcome was not significantly different between Black and White adults (adjusted hazard ratio [HR] 1.04 [95% CI, 0.99–1.09]); however, when death was treated as a competing risk, a significantly higher hazard for the composite outcome was observed for Black patients (subdistribution HR, 1.56 [95% CI, 1.39–1.76]). Components of the primary outcome were also greater among Black compared with White patients. Black patients had higher rates of medical complications in the perioperative period, including acute renal failure (subdistribution HR, 1.18 [95% CI, 1.01–1.38]), dialysis initiation (subdistribution HR, 2.75 [95% CI, 2.03–3.7]), and deep vein thrombosis (subdistribution HR, 1.54 [95% CI, 1.05–2.26]). Black patients had lower rates of vascular office visits after intervention (adjusted rate ratio, 0.96 [95% CI, 0.93–0.99]) but higher rates of emergency department visits (adjusted rate ratio, 1.05 [95% CI, 1.02–1.09]) and hospital readmissions (adjusted rate ratio, 1.13 [95% CI, 1.08–1.18]). CONCLUSIONS: Black patients demonstrated increased risk of late aortic-related events after endovascular aortic aneurysm repair after accounting for the competing risk of death and controlling for baseline covariates. Further investigation into preoperative medical management and barriers to postoperative health care access is necessary to further elucidate underlying mechanisms for the observed disparities.
Mechanisms of hematopoietic clonal dominance in VEXAS syndrome
Authors: Raffaella Molteni, Martina Fiumara, Corrado Campochiaro, Roberta Alfieri, Guido Pacini, Eugenia Licari, Alessandro Tomelleri, Elisa Diral, Angelica Varesi, Alessandra Weber, Pamela Quaranta, Luisa Albano, Chiara Gaddoni, Luca Basso-Ricci, Davide Stefanoni, Laura Alessandrini, Sara Degl'Innocenti, Francesca Sanvito, Gregorio Maria Bergonzi, Andrea Annoni, Maddalena Panigada, Eleonora Cantoni, Daniele Canarutto, Stephanie Z Xie, Angelo D'Alessandro, Raffaella Di Micco, Alessandro Aiuti, Fabio Ciceri, Giacomo De Luca, Lorenzo Dagna, Marco Matucci-Cerinic, Ivan Merelli, Simone Cenci, Serena Scala, Giulio Cavalli, Luigi Naldini, Samuele Ferrari
Journal: Nature Medicine (2025)

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal dominance are unknown. Moreover, the lack of disease models hampers the development of disease-modifying therapies. In the present study, we performed immunophenotype characterization of hematopoiesis and single-cell transcriptomics in a cohort of nine male patients with VEXAS syndrome, revealing pervasive inflammation across all lineages. Hematopoietic stem and progenitor cells (HSPCs) in patients are skewed toward myelopoiesis and acquire senescence-like programs. Humanized models of VEXAS syndrome, generated by inserting the causative mutation in healthy HSPCs through base editing, recapitulated proteostatic defects, cytological alterations and senescence signatures of patients' cells, as well as hematological and inflammatory disease hallmarks. Competitive transplantations of human UBA1-mutant and wild-type HSPCs showed that, although mutant cells are more resilient to the inflammatory milieu, probably through the acquisition of the senescence-like state, wild-type ones are progressively exhausted and overwhelmed by VEXAS clones, overall impairing functional hematopoiesis and leading to bone marrow failure. Our study unveils the mechanism of clonal dominance and provides models for preclinical studies and preliminary insights that could inform therapeutic strategies.
Precision microbiota therapy for IBD: premise and promise
Authors: Manabu Nagayama, Lasha Gogokhia, Randy S. Longman
Journal: Gut Microbes (2025)

Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.
Role of Technology in Promoting Heart Healthy Behavior Change to Increase Equity in Optimal Cardiovascular Health: A Scientific Statement From the American Heart Association
Authors: Tiffany M. Powell-Wiley, LaPrincess C. Brewer, Lora E. Burke, Rosalba Hernandez, Jill Landsbaugh Kaar, Maura Kepper, Christopher E. Kline, Keila N. Lopez, Shamarial Roberson, Colleen K. Spees, Gerald J. Jerome
Journal: Circulation (2025)

Populations most affected by cardiovascular health disparities, including underrepresented populations with lower socioeconomic status, people with disabilities, and those living in underserved rural communities, are disproportionately exposed to adverse social determinants of health. Specifically, economic instability and suboptimal living conditions within the neighborhood and built environment directly determine access to resources and opportunities for healthful behaviors. In this scientific statement, we examined the technology-enabled interventions that address cardiovascular health behaviors from adolescence to adulthood in populations most affected by health disparities. We used a broad definition of technology, including wearables, applications, and telehealth, for behavior tracking. Aligning with Life’s Essential 8, we focused on interventions targeting behavior change related to physical activity, sedentary time, dietary intake, tobacco cessation, and sleep health to improve cardiovascular health. The digital determinants of health are important adjuncts to the social determinants and operate at the individual, interpersonal, community, and societal levels. The digital determinants of health include the impact of digital technologies (eg, wearables, telemedicine) across health outcomes. Evidence of effective interventions using technology to improve cardiovascular health through positive behavior change is critical for preventing cardiovascular disease events. Stronger evidence is needed to inform and implement effective approaches that are scalable and cost-effective across communities and health care institutions to advance digital equity in cardiovascular health. Dissemination of digital solutions to improve cardiovascular health in communities or across health care systems must ensure effective, feasible, available, and affordable solutions for populations most in need.
Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial
Authors: Olivier Trédan, Damien Pouessel, Nicolas Penel, Sylvie Chabaud, Carlos Gomez-Roca, Jean-Pierre Delord, Diane Pannier, Mehdi Brahmi, Michel Fabbro, Marie-Eve Garcia, Delphine Larrieu-Ciron, Isabelle Ray-Coquard, Marie Viala, Antoine Italiano, Diego Tosi, Philippe Cassier, Armelle Dufresne, Valery Attignon, Sandrine Boyault, Isabelle Treilleux, Alain Viari, David Pérol, Jean Yves Blay
Journal: Nature Medicine (2025)

Large genomic programs have contributed to improving drug development in cancer. To assess the potential benefit of using larger gene panels to guide molecular-based treatments, we conducted a multicenter randomized trial in patients with advanced and/or metastatic solid cancer. Molecular alterations were determined using either a panel of 324 cancer-related genes (Foundation OneCDX (F1CDX)) or a limited panel of 87 single-nucleotide/indel genes and genome-wide copy number variations (CTL) and reviewed by a molecular tumor board to identify molecular-based recommended therapies (MBRTs). Using paired data from both panels for each patient, the primary endpoint was the proportion of patients with an MBRT identified. Main secondary endpoints included the number of patients with at least one actionable alteration leading to MBRT identification, the number of patients with and without MBRTs initiated, progression-free survival, best overall response, duration of response and safety. Among the 741 patients screened, 45.7% had quality-checked tumor samples. MBRTs were identified with F1CDX in 175 (51.6%) patients and with CTL in 125 (36.9%) patients, translating to a significant increase of 14.8 percentage points (P < 0.001) with the more comprehensive gene panel versus the more limited panel, meeting the primary endpoint. However, no differences in clinical outcomes were observed in these patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations. These findings illustrate the potential for larger gene panels to increase the number of molecularly matched therapies. Larger studies are needed to assess the clinical benefit of expanded MBRTs. ClinicalTrials.gov registration: NCT03163732 .
Sociodemographic biases in medical decision making by large language models
Authors: Mahmud Omar, Shelly Soffer, Reem Agbareia, Nicola Luigi Bragazzi, Donald U Apakama, Carol R Horowitz, Alexander W Charney, Robert Freeman, Benjamin Kummer, Benjamin S Glicksberg, Girish N Nadkarni, Eyal Klang
Journal: Nature Medicine (2025)
Common-variant and rare-variant genetic architecture of heart failure across the allele-frequency spectrum
Authors: David S M Lee, Kathleen M Cardone, David Y Zhang, Noah L Tsao, Sarah Abramowitz, Pranav Sharma, John S DePaolo, Mitchell Conery, Krishna G Aragam, Kiran Biddinger, Ozan Dilitikas, Lily Hoffman-Andrews, Renae L Judy, Atlas Khan, Iftikhar J Kullo, Megan J Puckelwartz, Nosheen Reza, Benjamin A Satterfield, Pankhuri Singhal, Zoltan Arany, Thomas P Cappola, Eric D Carruth, Sharlene M Day, Ron Do, Christopher M Haggerty, Jacob Joseph, Elizabeth M McNally, Girish Nadkarni, Anjali T Owens, Daniel J Rader, Marylyn D Ritchie, Yan V Sun, Benjamin F Voight, Michael G Levin, Scott M Damrauer
Journal: Nature Genetics (2025)
Microglia heterogeneity, modeling and cell-state annotation in development and neurodegeneration
Authors: Laura Fumagalli, Alma Nazlie Mohebiany, Jessie Premereur, Paula Polanco Miquel, Baukje Bijnens, Pieter Van de Walle, Nicola Fattorelli, Renzo Mancuso
Journal: Nature Neuroscience (2025)
CNRein: an evolution-aware deep reinforcement learning algorithm for single-cell DNA copy number calling
Authors: Stefan Ivanovic, Mohammed El-Kebir
Journal: Genome biology (2025)

Abstract Low-pass single-cell DNA sequencing technologies and algorithmic advancements have enabled haplotype-specific copy number calling on thousands of cells within tumors. However, measurement uncertainty may result in spurious CNAs inconsistent with realistic evolutionary constraints. We introduce evolution-aware copy number calling via deep reinforcement learning (CNRein). Our simulations demonstrate CNRein infers more accurate copy-number profiles and better recapitulates ground truth clonal structure than existing methods. On sequencing data of breast and ovarian cancer, CNRein produces more parsimonious solutions than existing methods while maintaining agreement with single-nucleotide variants. Additionally, CNRein shows consistency on a breast cancer patient sequenced with distinct low-pass technologies.
Association between the advanced lung cancer inflammation index and all-cause mortality in the US MASLD/MetALD patient population: a cohort study
Authors: Hang Li, Gaohui Chen, Shiting Bao, Guotai Lin, Fengwei Xie, Xiaoyu Tan, Mingyi Li, Shuo Fang, Wei Dai
Journal: International Journal of Surgery (2025)

Background: The relationship between the Advanced Lung Cancer Inflammation Index (ALI) and all-cause mortality in patients with Metabolic Dysfunction-Associated Steatohepatitis and Metabolic-Associated Alcoholic Liver Disease and other combination etiology of steatosis (MASLD/MetALD &amp; Mixed Etiology Steatosis) is not well-understood. Current evidence is insufficient to establish this association, yet it holds critical importance for healthcare and public health. Research into the link between ALI and all-cause mortality in MASLD/MetALD &amp; Mixed Etiology Steatosis remains a topic of interest. Objective: This study investigated the association between ALI and all-cause mortality in MASLD/MetALD &amp; Mixed Etiology Steatosis patients, and explored the clinical significance of this association. Methods: We conducted a cohort study using data from the National Health and Nutrition Examination Survey between 2007 and 2018, involving 4502 adult participants with MASLD/MetALD &amp; Mixed Etiology Steatosis in the United States. Data collected included age, sex, race, education, marital status, poverty-to-income ratio, alanine aminotransferase levels, aspartate aminotransferase levels, high-density lipoprotein cholesterol, total cholesterol, diabetes mellitus, coronary heart disease, and stroke. Cox proportional hazards regression models were used to assess the relationship between ALI and all-cause mortality, with follow-up through 31 December 2019, from the National Center for Health Statistics. Results: The study found that ALI in patients was significantly negatively associated with the risk of all-cause mortality in U.S. adults with MASLD/MetALD &amp; Mixed Etiology Steatosis. Participants with higher ALI levels had a significantly lower risk of all-cause mortality compared to those with lower ALI levels. After full adjustment, moderate ALI levels were associated with a 42% reduced risk (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.41–0.81), and high ALI levels were associated with a 49% reduced risk (HR: 0.51, 95% CI: 0.35–0.73) of all-cause mortality. No significant interactions were observed in subgroup analyses ( P &gt; 0.05). Conclusion: This study suggested that high ALI levels are associated with a reduced risk of all-cause mortality in MASLD/MetALD &amp; Mixed Etiology Steatosis patients. These findings may have important clinical implications for healthcare providers managing MASLD/MetALD &amp; Mixed Etiology Steatosis patients, emphasizing the potential role of ALI as a prognostic marker for all-cause mortality.
Prediction of 1 and 2 week nonelective hospitalization and sepsis hospitalization risk in adults
Authors: Vincent X Liu, Gabriel J Escobar, Liam O'Suilleabhain, Khanh K Thai, David Schlessinger, Laura C Myers, John D Greene, Fernando Barreda, Lawrence D Gerstley, Patricia Kipnis
Journal: npj Digital Medicine (2025)

We developed and validated models to predict 1- and 2-week risk of non-elective hospitalization (NEH) and sepsis hospitalization following outpatient clinic, emergency department treat and release (EDTR), or hospitalization encounters. We employed data from 4,488,579 adults with 1,481,430 hospital, 6,035,296 EDTR, and 86,013,893 clinic encounters. Predictors included administrative, clinical (laboratory tests, vital signs), utilization, and prescription pattern data. We employed 2012-2018 data for development and 2019 data for validation. In validation datasets, discrimination (area under the receiver operator characteristic curve) ranged from 0.687 for NEH within 1 week of hospital discharge to 0.904 for sepsis hospitalization within 2 weeks of clinic visits. At a sensitivity of 40%, numbers needed to evaluate (NNE) ranged from 4.3 for NEH within 2 weeks of hospitalization to 45 for sepsis hospitalization within 1 week of a clinic visit. Our models have potentially clinically actionable NNEs and could support clinical programs for the prevention of short-term hospitalizations and sepsis.
Salvage therapies for first relapse of SHH medulloblastoma in early childhood
Authors: Craig Erker, Martin Mynarek, Marie Simbozel, Brandon T Craig, Virginia L Harrod, Andrea M Cappellano, Kenneth J Cohen, Vicente Santa-Maria Lopez, Andres Morales-La Madrid, Chantel Cacciotti, Lorena Baroni, Ralph Salloum, Ashley S Margol, George Michaiel, Dolly Aguilera, Claire M Mazewski, Cassie N Kline, Jonathan L Finlay, Mohamed S Abdelbaki, Jeffrey C Murray, Kathleen Dorris, Bruce Crooks, Kevin F Ginn, Nisreen Amayiri, Stephan Tippelt, Gudrun Fleischhack, Svenja Tonn, Nicolas U Gerber, Alvaro Lassaletta, Jordan R Hansford, Sara Khan, Stephen W Gilheeney, Lindsey M Hoffman, Michal Zapotocky, Valérie Larouche, Shafqat Shah, Vijay Ramaswamy, Amar Gajjar, Sébastien Perreault, Sabine Mueller, Juliette Hukin, Sylvia Cheng, Zhihong J Wang, Kara Matheson, Simon Bailey, Eric Bouffet, Steven C Clifford, Giles Robinson, Christelle Dufour, Stefan Rutkowski, Lucie Lafay-Cousin
Journal: Neuro-Oncology (2025)

Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB. This international retrospective study included 147 subjects diagnosed with relapsed Nodular Desmoplastic/SHH iMB between 1995 and 2017, < 6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort. The 3-year PRS was 61.6% (95% CI, 52.2 to 69.6). The median age at relapse was 3.4 years (IQR, 2.6-4.1). Those with local relapse (40.8%) more often received salvage surgery (p <0.001), low-dose CSI (≤ 24 Gy; p < 0.001), or focal radiotherapy (p = 0.008). Patients not receiving CSI (40.5%) more often received salvage marrow-ablative chemotherapy (HDC+AuHCR [p <0.001]). On multivariable analysis, CSI was associated with improved survival (Hazard Ratio [HR] 0.33 [95% CI, 0.13 to 0.86], p =0.04). Salvage HDC+AuHCR, while clinically important, did not reach statistical significance (HR 0.24 [95% CI, 0.0054 to 1.025], p =0.065). Survival of patients with relapsed SHH iMB is not satisfactory and relies on treatments associated with toxicities including CSI and/or HDC+AuHCR. Upfront cure to avoid relapse is crucial. For patients with localized relapse undergoing resection, alternative salvage regimens that avoid high-dose CSI (> 24 Gy) can be considered.
SAPIEN 3 versus Myval transcatheter heart valves for transcatheter aortic valve implantation (COMPARE-TAVI 1): a multicentre, randomised, non-inferiority trial
Authors: Christian Juhl Terkelsen, Philip Freeman, Jordi Sanchez Dahl, Troels Thim, Bjarne Linde Nørgaard, Nils Sofus Borg Mogensen, Mariann Tang, Ashkan Eftekhari, Jonas Agerlund Povlsen, Steen Hvitfeldt Poulsen, Lars Pedersen, Jakob Hjort, Julia Ellert, Evald Høj Christiansen, Henrik Toft Sørensen, Henrik Nissen
Journal: The Lancet (2025)
MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
Authors: Chengyue Wu, Ernesto A B F Lima, Casey E Stowers, Zhan Xu, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov
Journal: npj Digital Medicine (2025)

We developed a practical framework to construct digital twins for predicting and optimizing triple-negative breast cancer (TNBC) response to neoadjuvant chemotherapy (NAC). This study employed 105 TNBC patients from the ARTEMIS trial (NCT02276443, registered on 10/21/2014) who received Adriamycin/Cytoxan (A/C)-Taxol (T). Digital twins were established by calibrating a biology-based mathematical model to patient-specific MRI data, which accurately predicted pathological complete response (pCR) with an AUC of 0.82. We then used each patient's twin to theoretically optimize outcome by identifying their optimal A/C-T schedule from 128 options. The patient-specifically optimized treatment yielded a significant improvement in pCR rate of 20.95-24.76%. Retrospective validation was conducted by virtually treating the twins with AC-T schedules from historical trials and obtaining identical observations on outcomes: bi-weekly A/C-T outperforms tri-weekly A/C-T, and weekly/bi-weekly T outperforms tri-weekly T. This proof-of-principle study demonstrates that our digital twin framework provides a practical methodology to identify patient-specific TNBC treatment schedules.
Molecular characteristics and clinical implications of TP53 mutations in therapy-related myelodysplastic syndromes
Authors: Zefei Bao, Bing Li, Tiejun Qin, Zefeng Xu, Shiqiang Qu, Yujiao Jia, Chengwen Li, Lijuan Pan, Qingyan Gao, Meng Jiao, Huijun Wang, Qi Sun, Zhijian Xiao
Journal: Blood Cancer Journal (2025)
Fe/Cu Bimetallic Nanozyme Co‐Assembled with <sup>177</sup>Lu and Tanshinone for Quadruple‐Synergistic Tumor‐Specific Therapy (Adv. Healthcare Mater. 9/2025)
Authors: Xianyu Zhu, Lingling Zheng, Pengfei Zhao, Lingli Gao, Liang Wang, Jun Liu, Xu Yang, Hanrui Wei, Mingyu Zhang, Liang Yan, Han Lv, Jianhua Gong, Ji gang Yang, Zhenchang Wang
Journal: Advanced Healthcare Materials (2025)
Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem Cells In Vitro (Adv. Healthcare Mater. 9/2025)
Authors: Prannoy Seth, Jens Friedrichs, Yanuar Dwi Putra Limasale, Nicole Fertala, Uwe Freudenberg, Yixin Zhang, Ayala Lampel, Carsten Werner
Journal: Advanced Healthcare Materials (2025)
Sodium Butyrate‐Loaded Microspheres With Enhanced Bioavailability for Targeted Treatment of Intestinal Barrier Injury (Adv. Healthcare Mater. 9/2025)
Authors: Yanwei Lv, Mengni Jiang, Yongliang Ouyang, Xiaoyi Zheng, Liang Zhang, Jinpeng Yao, Lianghao Hu, Jiulong Zhao, Zhaoshen Li, Shige Wang
Journal: Advanced Healthcare Materials (2025)