tbuckley/cabot-search huggingface dataset:
Predictors of arthritis development in individuals at risk of rheumatoid arthritis: a 5-year follow-up study from a large cohort
Authors: Giulia Frazzei, Robert B M Landewé, Carlijn Wagenaar, Lotte A van de Stadt, Dirkjan van Schaardenburg, Sander W Tas, Ronald F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2025)

The aim of this study was to predict rheumatoid arthritis (RA) development in a cohort of at-risk individuals with arthralgia positive for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (IgM-RF), followed for up to 5 years. In total, 617 seropositive arthralgia individuals were included in the study. The ability of clinically and biologically relevant baseline characteristics to predict RA development was assessed using Cox proportional hazard regression analysis. Thirty-eight percent of study population was IgM-RF-positive, 31% was ACPA-positive, and 30% was positive for both ACPA and IgM-RF. Mean (SD) time till arthritis was 19.6 (19.0) months in 33.7% of participants; mean (SD) follow-up time of individuals who did not develop arthritis was 47.3 (24.5) months. We found that first-degree relatives of RA (hazard ratio [HR] = 1.50), individuals who had intermittent symptoms (HR = 1.64), symptoms for less than 12 months at inclusion (HR for symptom duration >12 months = 0.71), morning stiffness ≥1 hour (HR = 1.63), or reported joint swelling (HR = 1.51) independently had higher risk to develop arthritis. Moreover, individuals with high ACPA titres (HR = 4.65) or double positivity for ACPA and IgM-RF (HR = 6.83) had the highest risk of developing RA, as compared to those with only IgM-RF or low ACPA titres. The risk of developing arthritis was 58.2% when at least 3 variables were present. Baseline characteristics can be used to predict future RA development in seropositive arthralgia individuals. These results will aid in the identification of individuals at highest risk of developing RA, who could potentially benefit from additional follow-ups in clinical practice and recruitment in preventive trials.
Self supervised artificial intelligence predicts poor outcome from primary cutaneous squamous cell carcinoma at diagnosis
Authors: Nicolas Coudray, Michelle C. Juarez, Maressa C. Criscito, Adalberto Claudio Quiros, Reason Wilken, Stephanie R. Jackson Cullison, Mary L. Stevenson, Nicole A. Doudican, Ke Yuan, Jamie D. Aquino, Daniel M. Klufas, Jeffrey P. North, Siegrid S. Yu, Fadi Murad, Emily Ruiz, Chrysalyne D. Schmults, Cristian D. Cardona Machado, Javier Cañueto, Anirudh Choudhary, Alysia N. Hughes, Alyssa Stockard, Zachary Leibovit-Reiben, Aaron R. Mangold, Aristotelis Tsirigos, John A. Carucci
Journal: npj Digital Medicine (2025)

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. Using whole-slide images (WSI) from 163 patients from 3 institutions, we developed a self supervised deep-learning model to predict poor outcomes in cSCC patients from histopathological features at initial diagnosis, and validated it using WSI from 563 patients, collected from two other academic institutions. For disease-free survival prediction, the model attained a concordance index of 0.73 in the development cohort and 0.84 in the Mayo cohort. The model's interpretability revealed that features like poor differentiation and deep invasion were strongly associated with poor prognosis. Furthermore, the model is effective in stratifying risk among BWH T2a and AJCC T2, known for outcome heterogeneity.
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: Francesco Montorsi, Giorgio Gandaglia, Armando Stabile
Journal: European Urology (2025)
Self-supervised identification and elimination of harmful datasets in distributed machine learning for medical image analysis
Authors: Raissa Souza, Emma A. M. Stanley, Anthony J. Winder, Chris Kang, Kimberly Amador, Erik Y. Ohara, Gabrielle Dagasso, Richard Camicioli, Oury Monchi, Zahinoor Ismail, Matthias Wilms, Nils D. Forkert
Journal: npj Digital Medicine (2025)

Distributed learning enables collaborative machine learning model training without requiring cross-institutional data sharing, thereby addressing privacy concerns. However, local quality control variability can negatively impact model performance while systematic human visual inspection is time-consuming and may violate the goal of keeping data inaccessible outside acquisition centers. This work proposes a novel self-supervised method to identify and eliminate harmful data during distributed learning model training fully-automatically. Harmful data is defined as samples that, when included in training, increase misdiagnosis rates. The method was tested using neuroimaging data from 83 centers for Parkinson's disease classification with simulated inclusion of a few harmful data samples. The proposed method reliably identified harmful images, with centers providing only harmful datasets being easier to identify than single harmful images within otherwise good datasets. While only evaluated using neuroimaging data, the presented method is application-agnostic and presents a step towards automated quality control in distributed learning.
Sanfetrinem, an oral β-lactam antibiotic repurposed for the treatment of tuberculosis
Authors: Santiago Ramón-García, Rubén González Del Río, María Pilar Arenaz-Callao, Helena I Boshoff, Joaquín Rullas, Sara Anca, Mónica Cacho Izquierdo, Esther Porras de Francisco, Esther Pérez Herrán, Angel Santos-Villarejo, Alfonso Mendoza-Losana, Santiago Ferrer-Bazaga, Charles J Thompson, David Barros Aguirre, Robert H Bates
Journal: Drug Resistance Updates (2025)
Does drug repurposing bridge the gaps in management of Parkinson’s disease? Unravelling the facts and fallacies
Authors: Bushra Bashir, Sukriti Vishwas, Gaurav Gupta, Keshav Raj Paudel, Harish Dureja, Puneet Kumar, Hyunah Cho, Vrashabh V Sugandhi, Popat Kumbhar, John Disouza, Muralikrishnan Dhanasekaran, Bey Hing Goh, Monica Gulati, Kamal Dua, Sachin Kumar Singh
Journal: Ageing Research Reviews (2025)
How to treat undifferentiated arthritis today or tomorrow? A consideration of treatment recommendations in light of current evidence
Authors: Annette H M van der Helm-van Mil, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2025)

Patients with undifferentiated arthritis (UA) have clinically apparent inflammatory arthritis but no evident diagnosis or classification. Considering UA as a definition 'per exclusionem' implies that the population designated by this term is affected by changes in the way other diseases, eg, rheumatoid arthritis (RA), are classified or diagnosed. Current treatment recommendations for UA are largely similar to recommendations for RA. The recommendations are based on the idea that UA is an early stage of RA and on literature generated in the 2000s before the development of the 2010 classification criteria for RA. However, conventional UA (so-called '1987-UA') is presumably different than contemporary UA ('2010-UA'). Strikingly, there are no randomised placebo-controlled trials done on '2010-UA,' and this poses questions on whether the recommendations for UA are still valid. In this absence, we assume that treatment recommendations from '1987-UA' can be extrapolated to '2010-UA' if (1) essential patient characteristics are the same, (2) long-term outcomes are similar, (3) prognostic factors are largely the same, and (4) there are indications from research other than placebo-controlled randomized clinical trials (RCTs) that disease modifying antirheumatic drug (DMARD) treatment in 2010-UA is effective. We evaluate these requirements one by one based on the literature on 2010-UA. This reveals that 2010-UA is milder in initial presentation and disease outcomes than 1987-UA. Today's UA population is >95% anticitrullinated protein antibody-negative, presents with mono- or oligoarthritis, frequently achieves spontaneous remission, and rarely progresses to RA. We suggest that 2010-UA is a distinct patient group within the early arthritis spectrum, requiring additional research, after which recommendations may need to be updated.
Immunological responses and clinical outcomes in pet dogs with osteosarcoma receiving standard of care therapy and a recombinant Listeria vaccine expressing HER2/neu
Authors: Nicola J Mason, Laura Selmic, Audrey Ruple, C A London, L Barber, K Weishaar, J A Perry, J Mahoney, B Flesner, J N Bryan, J L Willcox, J H Burton, D M Vail, W C Kisseberth, C E Balkman, A L McCleary-Wheeler, K M Curran, H Leeper, J P Woods, A J Mutsaers, M L Higginbotham, R M Wouda, H Wilson-Robles, N Dervisis, C Saba, V S MacDonald-Dickinson, P R Hess, A Cherukuri, A Rotolo, J A Beck, S Patkar, C Mazcko, A K LeBlanc
Journal: Molecular Therapy (2025)
Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia
Authors: Alberto Ouro, Amanda Rodríguez-Díaz, Tania López-González, Daniel Romaus-Sanjurjo, Ánxela Estévez-Salguero, Ramón Iglesias-Rey, Mariña Rodríguez-Arrizabalaga, Paola Fernández Sanmartín, Mónica Castro-Mosquera, Manuel Debasa-Mouce, Antía Custodia, Marta Aramburu-Núñez, María Muñoz-González, Pablo Aguiar, Ismael González-García, Marc Schneeberger, Rubén Nogueiras, Carlos Diéguez, José Castillo, Tomás Sobrino, Miguel López
Journal: Metabolism (2025)
Single-cell RNA sequencing identifies molecular biomarkers predicting late progression to CDK4/6 inhibition in patients with HR+/HER2- metastatic breast cancer
Authors: Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M. Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K. Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi
Journal: Molecular Cancer (2025)
Clinical Relevance of ATRX/DAXX Gene Mutations and ALT in Functioning Pancreatic Neuroendocrine Tumors
Authors: Brenna R. van ´t Veld, Wenzel M. Hackeng, Claudio Luchini, Lodewijk A. A. Brosens, Koen M. A. Dreijerink
Journal: Endocrine Pathology (2025)

Functioning pancreatic neuroendocrine tumors (PanNETs) represent a subset of PanNETs that cause symptoms due to hormonal activity. Insulinoma is the most common functioning PanNET type. Mutations in the alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes result in genomic instability. ATRX/DAXX mutations and associated alternative lengthening of telomeres (ALT) are common in non-functioning PanNETs and associated with aggressive tumor behavior. Recent reports have shown that ATRX/DAXX mutations and ALT are also present in functioning PanNETs. In this review, we summarize the literature addressing ATRX/DAXX mutations and ALT in functioning PanNETs and discuss the clinical relevance with regard to distinguishing aggressive and indolent functioning tumors. ATRX/DAXX gene mutations and/or ALT have been reported in insulinoma, glucagonoma, gastrinoma, VIPoma and calcitoninoma. In insulinoma, the presence of ATRX/DAXX mutations and ALT are associated with aggressive behavior and could therefore be used as prognostic biomarkers. Although ATRX/DAXX mutation and ALT assessment may currently not be the standard of care in routine diagnostic pathology practice, the use of DAXX/ATRX immunohistochemistry at least can be encouraged not only for non-functioning but also for functioning PanNETs.
Baseline characteristics of contemporary trial participants with heart failure and reduced ejection fraction: The <scp>VICTOR</scp> trial
Authors: Clara I. Saldarriaga, Faiez Zannad, Ciaran J. McMullan, Aiwen Xing, Davis Gates, Kevin J. Anstrom, Marc P. Bonaca, Stefano Corda, Justin A. Ezekowitz, Carolyn S.P. Lam, Eldrin F. Lewis, JoAnn Lindenfeld, Robert J. Mentz, Christopher O'Connor, Mahesh Patel, Piotr Ponikowski, Yogesh N.V. Reddy, Giuseppe M.C. Rosano, Michele Senni, James Udelson, Adriaan A. Voors, Javed Butler
Journal: European Journal of Heart Failure (2025)

To describe the baseline characteristics of the participants in the VICTOR (Vericiguat Global Study in Patients with Chronic Heart Failure; NCT05093933) trial and compare them to recent trials in patients with heart failure and reduced ejection fraction (HFrEF). Baseline characteristics were evaluated in 6105 patients randomized to vericiguat or placebo. The mean age of the participants was 67 ± 11 years, 23.6% were women, 64.4% were White, and 10.7% were self-identified Black. Overall, 29.1% of participants were enrolled in Latin and South America, 27.8% and 18.5% in Eastern and Western Europe, 14.0% in Asia-Pacific and 10.6% in North America. The mean left ventricular ejection fraction was 30 ± 7% and 79% had New York Heart Association class II symptoms. Mean estimated glomerular filtration rate was 70.9 ± 24.0 ml/min/1.73 m2. Median N-terminal pro-B-type natriuretic peptide level was 1476 (970-2495) pg/ml and 47.5% of participants had no prior hospitalization for heart failure. Baseline therapy included 94.4% beta-blockers, 94.3% renin-angiotensin system modulation (including 56.0% on an angiotensin receptor-neprilysin inhibitor), 77.7% mineralocorticoid receptor antagonists, 59.1% sodium-glucose cotransporter 2 inhibitors, and 32.9% implantable cardioverter-defibrillators. Overall characteristics were relatively similar to other recent HFrEF trials but the VICTOR trial enrolled a higher proportion of participants receiving contemporary drug and device therapy. The VICTOR trial enrolled the most optimally treated population in a phase III heart failure trial. These features will facilitate assessment of the benefit of vericiguat and elucidate the outcomes of patients on up-to-date medical therapy.
Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease
Authors: Han Gao, Mingming Sun, Ai Li, Qiaoyan Gu, Dengfeng Kang, Zhongsheng Feng, Xiaoyu Li, Xuehong Wang, Liang Chen, Hong Yang, Yingzi Cong, Zhanju Liu
Journal: Gut Microbes (2025)

The gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on mucosal CD4+ T cell functions in inflammatory bowel disease (IBD) remain elusive. Here we investigated the roles of IPA in modulating mucosal CD4+ T cells and its therapeutic potential in treatment of human IBD. Leveraging metabolomics and microbial community analyses, we observed that the levels of IPA-producing microbiota (e.g. Peptostreptococcus, Clostridium, and Fournierella) and IPA were decreased, while the IPA-consuming microbiota (e.g. Parabacteroides, Erysipelatoclostridium, and Lachnoclostridium) were increased in the feces of IBD patients than those in healthy donors. Dextran sulfate sodium (DSS)-induced acute colitis and CD45RBhighCD4+ T cell transfer-induced chronic colitis models were then established in mice and treated orally with IPA to study its role in intestinal mucosal inflammation in vivo. We found that oral administration of IPA attenuated mucosal inflammation in both acute and chronic colitis models in mice, as characterized by increased body weight, and reduced levels of pro-inflammatory cytokines (e.g. TNF-α, IFN-γ, and IL-17A) and histological scores in the colon. We further utilized RNA sequencing, molecular docking simulations, and surface plasmon resonance analyses and identified that IPA exerts its biological effects by interacting with heat shock protein 70 (HSP70), leading to inducing Th1/Th17 cell apoptosis. Consistently, ectopic expression of HSP70 in CD4+ T cells conferred resistance to IPA-induced Th1/Th17 cell apoptosis. Therefore, these findings identify a previously unrecognized pathway by which IPA modulates intestinal inflammation and provide a promising avenue for the treatment of IBD.
FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging
Authors: Hanjun Li, Pei Liu, Shuqin Xu, Yinghua Li, Joseph D. Dekker, Baojie Li, Ying Fan, Zhenlin Zhang, Yang Hong, Gong Yang, Tingting Tang, Yongxin Ren, Haley O. Tucker, Zhengju Yao, Xizhi Guo
Journal: Journal of Clinical Investigation (2025)
High IgG titers against EBV glycoprotein 42 correlate with lower risk of nasopharyngeal carcinoma
Authors: Benjamin E Warner, Kathy Hy Shair
Journal: Journal of Clinical Investigation (2025)

Serologic biomarkers for the early diagnosis of EBV-associated nasopharyngeal carcinoma (NPC) have been identified from population studies, but a protective antibody signature in cancer-free seropositive carriers remains undefined. In this issue of the JCI, Kong et al. show that high levels of IgG against EBV glycoprotein 42 (gp42) were associated with reduced NPC risk in three independent prospective cohorts from southern China. EBV virions contain gp42, which complexes with gH-gL to facilitate fusion with B cells by binding to HLA class II (HLA-II). In this study, HLA-II was detected on non-antigen-presenting cells in a proportion of premalignant nasopharyngeal tissues, which may prime the nasopharyngeal epithelium for infection. In vitro, HLA-II expression in a nasopharyngeal cell line encouraged infection by EBV derived from B cells or epithelial cells. These findings suggest that a vaccine that stimulates gp42-IgG production may reduce the risk of EBV-associated NPC in endemic regions.
Microbial influencers: the airway microbiome’s role in asthma
Authors: Young Jin Kim, Supinda Bunyavanich
Journal: Journal of Clinical Investigation (2025)

Asthma is a common chronic respiratory disease affecting people of all ages globally. The airway hosts diverse microbial communities increasingly recognized as influential in the development and disease course of asthma. Here, we review recent findings on the airway microbiome in asthma. As relationships between the airway microbiome and respiratory health take root early in life, we first provide an overview of the early-life airway microbiome and asthma development, where multiple cohort studies have identified bacterial genera in the infant airway associated with risk of future wheeze and asthma. We then address current understandings of interactions between environmental factors, the airway microbiome, and asthma, including the effects of rural/urban environments, pet ownership, smoking, viral illness, and antibiotics. Next, we delve into what has been observed about the airway microbiome and asthma phenotypes and endotypes, as airway microbiota have been associated with asthma control, severity, obesity-related asthma, and treatment effects as well as with type 2 high, type 2 low, and more newly described multi-omic asthma endotypes. We then discuss emerging approaches to shape the microbiome for asthma therapy and conclude the Review with perspectives on future research directions.
NIR‐II Cyazulene Fluorophores with Adjustable Cycloalkenes and Spectroscopic Properties for Imaging Applications
Authors: Wenjie Gao, Diankai Liu, He Li, Zixu He, Ya Liu, Xiaohua Li, Huimin Ma, Wen Shi
Journal: Advanced Healthcare Materials (2025)

Abstract NIR‐II fluorescence imaging has shown broad application prospects in life science because of its deeper tissue penetration and higher spatiotemporal resolution. Developing NIR‐II fluorophores with special spectroscopic properties and analytical functions has become a cutting‐edge but challenging topic in this field. Herein, a series of azulene‐based NIR‐II fluorophores (called cyazulenes) with adjustable cycloalkenes and spectroscopic properties for imaging applications is reported. Cyazulenes (CA965, CA985, and CA1025) are constructed via the convenient coupling of cycloalkenes with azulene derivatives. They exhibit different H‐aggregation and J‐aggregation. Particularly noteworthy is that CA985 can form significant J‐aggregates with strong and sharp NIR‐II emission in biological media, and can be used for in vivo imaging of blood vessels and fine structures of collecting lymphatics in mice. Moreover, CA985 displays passive bone‐targeted capacity, thereby enabling bone imaging. This study demonstrates the chemical impact of varying cycloalkenes on the aggregate formation and spectral properties of cyazulenes, which will advance azulene‐based NIR‐II fluorophores.
3D Bioprinted Coaxial Testis Model Using Human Induced Pluripotent Stem Cells:A Step Toward Bicompartmental Cytoarchitecture and Functionalization
Authors: Meghan A Robinson, Sonia HY Kung, Khaled YM Youssef, Kali M Scheck, Robert H Bell, Funda Sar, Anne M Haegert, M Mahdi Asmae, Changfeng Cheng, Salina V Yeack, Bhairvi T Mathur, Feng Jiang, Colin C Collins, Faraz Hach, Stephanie M Willerth, Ryan K Flannigan
Journal: Advanced Healthcare Materials (2025)

Abstract Fertility preservation following pediatric cancer therapy programs has become a major avenue of infertility research. In vitro spermatogenesis (IVS) aims to generate sperm from banked prepubertal testicular tissues in a lab setting using specialized culture conditions. While successful using rodent tissues, progress with human tissues is limited by the scarcity of human prepubertal testicular tissues for research. This study posits that human induced pluripotent stem cells (hiPSCs) can model human prepubertal testicular tissue to facilitate the development of human IVS conditions. Testicular cells derived from hiPSCs are characterized for phenotype markers and profiled transcriptionally. HiPSC‐derived testicular cells are bioprinted into core–shell constructs representative of testis cytoarchitecture and found to capture functional aspects of prepubertal testicular tissues within 7 days under xeno‐free conditions. Moreover, hiPSC‐derived Sertoli cells illustrate the capacity to mature under pubertal‐like conditions. The utility of the model is tested by comparing 2 methods of supplementing retinoic acid (RA), the vitamin responsible for inducing spermatogenesis. The model reveals a significant gain in activity under microsphere‐released RA compared to RA medium supplementation, indicating that the fragility of free RA in vitro may be a contributing factor to the molecular dysfunction observed in human IVS studies to date.
Non‐Surgical, In‐Stent Membrane Bioelectronics for Long‐Term Intracranial Pressure Monitoring
Authors: Jimin Lee, Allison Bateman, Mi Hyeon Kim, Bruno Rigo, Hodam Kim, Jaeho Lee, Yun Hyeok Choi, Robert Herbert, Deok Hee Lee, Woon‐Hong Yeo
Journal: Advanced Healthcare Materials (2025)

Abstract Traditional intracranial pressure (ICP) monitoring methods, using intraventricular catheters, face significant limitations, including high invasiveness, discrete data, calibration complexities, and drift issues, which hinder long‐term and stable monitoring. Here, a non‐surgical, in‐stent membrane bioelectronic system is presented for continuous and reliable ICP monitoring. This platform integrates a capacitive thin‐film sensor with a stent, enabling precise real‐time detection of pressure fluctuations directly within the dural venous sinus without requiring skull penetration or frequent recalibration. The sensor demonstrates a high sensitivity of 0.052%/mmHg and a broad, readable pressure range of 3–30 mmHg while maintaining calibration‐free and drift‐free performance. A series of in vivo studies highlight the system's superior sensitivity, rapid sampling rate, and long‐term stability compared to conventional microcatheters. Statistical analyses reveal a strong agreement between the device and clinical reference, underscoring its potential to revolutionize ICP monitoring. These advancements pave the way for broader clinical applications, minimizing complications and improving patient outcomes in neurocritical care.