tbuckley/cabot-search huggingface dataset:
Impact of Genomic Classifiers on Risk Stratification and Treatment Intensity in Patients With Localized Prostate Cancer
Authors: Amir Alishahi Tabriz, Matthew J. Boyer, Adelaide M. Gordon, David J. Carpenter, Jeffrey R. Gingrich, Sudha R. Raman, Deepika Sirohi, Alexis Rompre-Brodeur, Joseph Lunyera, Fahmin Basher, Rhonda L. Bitting, Andrzej S. Kosinski, Sarah Cantrell, Belinda Ear, Jennifer M. Gierisch, Morgan Jacobs, Karen M. Goldstein
Journal: Annals of Internal Medicine (2025)

Tissue-based genomic classifiers (GCs) have been developed to improve prostate cancer (PCa) risk assessment and treatment recommendations. To summarize the impact of the Decipher, Oncotype DX Genomic Prostate Score (GPS), and Prolaris GCs on risk stratification and patient-clinician decisions on treatment choice among patients with localized PCa considering first-line treatment. MEDLINE, EMBASE, and Web of Science published from January 2010 to August 2024. Two investigators independently identified studies on risk classification and treatment choice after GC testing for patients with localized PCa considering first-line treatment. Relevant data extracted by 1 researcher and overread by a second. Risk of bias (ROB) was assessed in duplicate. Ten studies reported risk reclassification after GC testing. In low ROB observational studies, very low- or low-risk patients with PCa were more likely to have their risk levels classified as the same or lower (GPS, 100% to 88.1%; Decipher, 87.2% to 82.9%; Prolaris, 76.9%). However, 1 randomized trial found that GC testing with GPS reclassified 34.5% of very low-risk and 29.4% of low-risk patients to a higher risk category. Twelve observational studies indicated that treatment decisions after GC testing either remained unchanged or slightly favored active surveillance. In contrast, analyses from a single randomized trial found fewer choices for active surveillance after GPS testing. Heterogeneity in screening patterns, risk-determination cutoffs, pathology, and clinical practices. Studies on treatment choice were moderate to high ROB. Although GC tests do not consistently influence risk classification or treatment decisions, the differences observed between observational and randomized studies highlight a need for well-designed trials to explore the role of GC tests in patients with newly diagnosed PCa considering first-line treatment. U.S. Department of Veterans Affairs. (PROSPERO: CRD42022347950).
Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer’s disease
Authors: Andrew Octavian Sasmita, Erinne Cherisse Ong, Taisiia Nazarenko, Shuying Mao, Lina Komarek, Maik Thalmann, Veronika Hantakova, Lena Spieth, Stefan A Berghoff, Helena J Barr, Maximilian Hingerl, Friederike Börensen, Johannes Hirrlinger, Mikael Simons, Beth Stevens, Constanze Depp, Klaus-Armin Nave
Journal: Neuron (2025)

In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies. This effect was not due to gestation in or rearing by 5xFAD females. Immunoblotting suggested that transgenic inheritance modulates transgenic protein expression, potentially due to genomic imprinting of the Thy1.2 promoter. Surprisingly, fewer than 20% of 5xFAD studies report breeding schemes, suggesting that this factor might confound previous findings. Our data highlight a significant determinant of plaque burden in 5xFAD mice and underscore the importance of reporting the parental origin of the transgene to improve scientific rigor and reproducibility in AD research.
Stroke Rehabilitation: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines
Authors: Blessen C. Eapen, Johanna Tran, Jennifer Ballard-Hernandez, Andrew Buelt, Carrie W. Hoppes, Christine Matthews, Svetlana Pundik, James Reston, Zahari Tchopev, Lisa M. Wayman, Tyler Koehn
Journal: Annals of Internal Medicine (2025)

In July 2024, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) released a joint update of their 2019 clinical practice guideline (CPG) for the management of stroke rehabilitation. This synopsis is a condensed version of the 2024 CPG, highlighting the key aspects of the guideline development process and describing the major recommendations. The VA/DOD Evidence-Based Practice Work Group convened a joint VA/DOD guideline development work group (WG) that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy CPGs. The guideline WG conducted a patient focus group, developed key questions, and systematically searched and evaluated the literature (English-language publications from 1 July 2018 to 2 May 2023). The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to evaluate the evidence. The WG developed 47 recommendations along with algorithms for stroke rehabilitation in the inpatient and outpatient settings. Stakeholders outside the WG reviewed the CPG before approval by the VA/DOD Evidence-Based Practice Work Group. This synopsis summarizes where evidence is strongest to support guidelines in crucial areas relevant to primary care physicians: transition to community (case management, psychosocial or behavioral interventions); motor therapy (task-specific practice, mirror therapy, rhythmic auditory stimulation, electrical stimulation, botulinum toxin for spasticity); dysphagia, aphasia, and cognition (chin tuck against resistance, respiratory muscle strength training); and mental health (selective serotonin reuptake inhibitor use, psychotherapy, mindfulness-based therapies for treatment but not prevention of depression).
The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care
Authors: Vedang Murthy, Giulia Marvaso, Barbara A Jereczek-Fossa, Stephanie A Thoma, Marco Vogel, Nina-Sophie Schmidt-Hegemann, Mohamed Shelan, Shankar Siva, Tobias Hoelscher, Amar U Kishan, Jan C Peeken, Silke Gillessen, Matthias Guckenberger, Ken Herrmann, Wolfgang P Fendler, Thomas Zilli, Simon K B Spohn, Constantinos Zamboglou
Journal: European Urology (2025)
Germline <i>UBA1</i> Variant With Somatic Amplification in a Woman With Inflammatory Diseases and Myelodysplastic Syndrome
Authors: Maria Creignou, Maria Sirenko, Pedro L. Moura, Teresa Mortera-Blanco, Marios Dimitriou, Birgitta Sander, Dylan Domenico, Juan E. Arango Ossa, Bianca Tesi, David B. Beck, Petter Woll, Sten-Eirik W. Jacobsen, Elli Papaemmanuil, Elsa Bernard, Eva Hellström-Lindberg
Journal: Annals of Internal Medicine (2025)
Safety of a co-designed cognitive behavioural therapy intervention for people with type 1 diabetes and eating disorders (STEADY): a feasibility randomised controlled trial
Authors: Marietta Stadler, Natalie Zaremba, Amy Harrison, Jennie Brown, Divina Pillay, Jacqueline Allan, Rachael Tan, Salma Ayis, Emmanouela Konstantara, Janet Treasure, David Hopkins, Khalida Ismail
Journal: The Lancet Regional Health - Europe (2025)
A Comprehensive Survey of Foundation Models in Medicine
Authors: Wasif Khan, Seowung Leem, Kyle B. See, Joshua K. Wong, Shaoting Zhang, Ruogu Fang
Journal: IEEE Reviews in Biomedical Engineering (2025)

Foundation models (FMs) are large-scale deeplearning models that are developed using large datasets and self-supervised learning methods. These models serve as a base for different downstream tasks, including healthcare. FMs have been adopted with great success across various domains within healthcare. Existing healthcare-based surveys have not yet included all of these domains. Therefore, we provide a detailed survey of FMs in healthcare. We focus on the history, learning strategies, flagship models, applications, and challenges of FMs. We explore how FMs such as the BERT and GPT families are reshaping various healthcare domains, including clinical large language models, medical image analysis, and omics. Furthermore, we provide a detailed taxonomy of healthcare applications facilitated by FMs, such as clinical NLP, medical computer vision, graph learning, and other biology-related tasks. Despite the promising opportunities FMs provide, they also have several associated challenges, which are explained in detail. We also outline open research issues and potential lessons learned to provide researchers and practitioners with insights into the capabilities of FMs in healthcare to advance their deployment and mitigate associated risks.
TractGraphFormer: Anatomically Informed Hybrid Graph CNN-Transformer Network for Interpretable Sex and Age Prediction from Diffusion MRI Tractography
Authors: Yuqian Chen, Fan Zhang, Meng Wang, Leo R Zekelman, Suheyla Cetin-Karayumak, Tengfei Xue, Chaoyi Zhang, Yang Song, Jarrett Rushmore, Nikos Makris, Yogesh Rathi, Weidong Cai, Lauren J O'Donnell
Journal: Medical Image Analysis (2025)
Characterization of Tumor Antigens from Multi-omics Data: Computational Approaches and Resources
Authors: Yunzhe Wang, James Wengler, Yuzhu Fang, Joseph Zhou, Hang Ruan, Zhao Zhang, Leng Han
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome. An increasing amount of bioinformatics tools and algorithms are being developed to predict tumor neoantigens derived from different sources, which may require inputs from different multi-omics data. In addition, calculating the peptide–major histocompatibility complex (MHC) affinity can aid in selecting putative neoantigens, as high binding affinities facilitate antigen presentation. Based on these approaches and previous experiments, many resources were developed to reveal the landscape of tumor neoantigens across multiple cancer types. Herein, we summarized these tools, algorithms, and resources to provide an overview of computational analysis for neoantigen discovery and prioritization, as well as the future development of potential clinical utilities in this field.
Bioactive Silk Cryogel Dressing with Multiple Physical Cues to Control Cell Migration and Wound Regeneration
Authors: Yaqian Chen, Xiaoyi Zhang, Mengting Wang, Yu Liang, Zhaozhu Zheng, Meng Liu, Qiang Lu
Journal: Advanced Healthcare Materials (2025)

Abstract Introducing multiple physical cues to control cell behaviors effectively is considered as a promising strategy in developing bioactive wound dressings. Silk nanofiber‐based cryogels are developed to favor angiogenesis and tissue regeneration through tuning hydrated state, microporous structure, and mechanical property, but remained a challenge to endow with more physical cues. Here, β ‐sheet rich silk nanofibers are used to develop cryogels with nanopore structure. Through optimizing crosslinking time and exposing the reactive group inside the nanofibers, the crosslinking reaction is improved to induce stable cryogel formation. Besides the hydrated state and macroporous structure, the nanopore structure formed on the macroporous walls, providing hierarchical microstructures to improve cell migration. Both in vitro and in vivo results reveal quicker cell migration inside the cryogels, which then accelerates angiogenesis and wound healing. The mechanical properties can further regulate to match with skin regeneration. The wound healing study in vivo reveals lower inflammatory factor secretion in the wounds treated with softer cryogels with nanopores, which then resulted in the best angiogenesis and wound healing with less scar. Therefore, the porous cryogels with multiple physical cues can be fabricated with silk nanofibers to control cell behaviors and tissue regeneration, providing a promising approach for designing bioactive wound dressings.
Genetic mapping of serum metabolome to chronic diseases among Han Chinese
Authors: Chunxiao Cheng, Fengzhe Xu, Xiong-Fei Pan, Cheng Wang, Jiayao Fan, Yunhaonan Yang, Yuanjiao Liu, Lingyun Sun, Xiaojuan Liu, Yue Xu, Yuan Zhou, Congmei Xiao, Wanglong Gou, Zelei Miao, Jiaying Yuan, Luqi Shen, Yuanqing Fu, Xiaohui Sun, Yimin Zhu, Yuming Chen, An Pan, Dan Zhou, Ju-Sheng Zheng
Journal: Cell Genomics (2025)
Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms
Authors: Eun‐Jin Lee, Peter Lialios, Micaila Curtis, James Williams, Yoontae Kim, Paul Salipante, Steven Hudson, Mandy B. Esch, Moshe Levi, Joanna Kitlinska, Stella Alimperti
Journal: Advanced Healthcare Materials (2025)

Abstract Glucocorticoids (GCs) are standard‐of‐care treatments for inflammatory and immune disorders, and their long‐term use increases the risk of osteoporosis. Although GCs decrease bone functionality, their role in bone microvasculature is incompletely understood. Herein, the study investigates the mechanisms of bone microvascular barrier function via osteoblast‐endothelial interactions in response to GCs. The animal data shows that prednisolone (Psl) downregulated the osteoblast function and microvessel number and size. To investigate the role of GCs in bone endothelial barrier function further, a bicellular microfluidic in vitro system is developed and utilized, which consists of three‐dimensional (3D) perfusable microvascular structures embedded in collagen I/osteoblast matrix. Interestingly, it is demonstrated that GCs significantly inhibit osteogenesis and microvascular barrier function by interfering with endothelial‐osteoblast interactions. This effect is triggered by MAPK‐induced phosphorylation of connexin43 (Cx43) at Ser282. Collectively, this study sheds light on microvascular function in bone disorders, as osteoporosis, and permits to capture dynamic changes in endothelial‐bone interactions under GCs by dissecting the MAPK/Cx43 mechanism and proposing this as a potential target for bone diseases.
First-in-Human clinical trial of a small molecule EBNA1 inhibitor, VK-2019, in patients with Epstein-Barr positive nasopharyngeal cancer, with pharmacokinetic and pharmacodynamic studies.
Authors: A. Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun. Lee, Maura L. Gillison, Saad A. Khan, Rong Lu, Benjamin A. Pinsky, Samantha S. Soldan, Olga Vladmirova, Paul M. Lieberman, Troy E. Messick
Journal: Clinical Cancer Research (2025)

Abstract Purpose: A first-in-human phase one study was conducted in nasopharyngeal carcinoma (NPC) patients to assess the safety and tolerability of VK-2019, a small molecule selective inhibitor of Epstein-Barr virus Nuclear Antigen 1 (EBNA1). Patients and Methods: Pharmacokinetic and pharmacodynamic studies, including circulating tumor EBV DNA plasma levels, were performed. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1800 mg using an accelerated titration design, with cohort expansion at 1800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment. Results: VK-2019 was well tolerated. One patient achieved a partial response. Pharmacokinetic results demonstrated good systemic exposure, with high intersubject variability. Decreases in circulating tumor EBV DNA plasma levels were observed in some patients. VK-2019 reduced EBV genome copy number and viral gene expression in patient tumor samples and induced changes in immune cell markers. Conclusions: VK-2019 at doses up to 1800 mg daily demonstrated an acceptable safety profile, achieved micromolar plasma concentrations, and showed on-target biological activity in tumors from patients with advanced EBV-positive nasopharyngeal carcinoma.
Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition
Authors: Alexander R Goldberg, Athanassios Dovas, Daniela Torres, Brianna Pereira, Ashwin Viswanathan, Sohani Das Sharma, Angeliki Mela, Edward M Merricks, Cristina Megino-Luque, Julie J McInvale, Markel Olabarria, Leila Abrishami Shokooh, Hanzhi T Zhao, Cady Chen, Corina Kotidis, Peter Calvaresi, Matei A Banu, Aida Razavilar, Tejaswi D Sudhakar, Ankita Saxena, Cole Chokran, Nelson Humala, Aayushi Mahajan, Weihao Xu, Jordan B Metz, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Elizabeth M C Hillman, Gunnar Hargus, Jose Javier Bravo-Cordero, Guy M McKhann, Brian J A Gill, Steven S Rosenfeld, Catherine A Schevon, Jeffrey N Bruce, Peter A Sims, Darcy S Peterka, Peter Canoll
Journal: Neuron (2025)
Photosynthesis‐Inspired NIR‐Triggered Fe₃O₄@MoS₂ Core–Shell Nanozyme for Promoting MRSA‐Infected Diabetic Wound Healing
Authors: Jiamu Xiao, Xuping An, Fei Tang, Xu Dai, Song Zhang, Xiaolong Zhu, Jian Shen, Jiang Yuan, Donglin Gan, Mingqian Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Bacterial infections can lead to severe medical complications, including major medical incidents and even death, posing a significant challenge in clinical trauma repair. Consequently, the development of new, efficient, and non‐resistant antimicrobial agents has become a priority for medical practitioners. In this study, a stepwise hydrothermal reaction strategy is utilized to prepare Fe 3 O 4 @MoS 2 core–shell nanoparticles (NPs) with photosynthesis‐like activity for the treatment of bacterial infections. The Fe 3 O 4 @MoS 2 NPs continuously catalyze the production of reactive oxygen species (ROS) from hydrogen peroxide through photosynthesis‐like reactions and convert light energy into heat with a photothermal efficiency of 30.30%. In addition, the photosynthetically generated ROS, combined with the iron‐induced cell death mechanism of the Fe 3 O 4 @MoS 2 NPs, confer them with exceptional and broad‐spectrum antibacterial properties, achieving antimicrobial activities of up to 98.62% for Staphylococcus aureus , 99.22% for Escherichia coli , and 98.55% for methicillin‐resistant Staphylococcus aureus . The composite exhibits good cell safety and hemocompatibility. Finally, a full‐thickness diabetic wound model validates the significant pro‐healing properties of Fe 3 O 4 @MoS 2 in chronic diabetic wounds. Overall, the design of photosynthesis‐inspired Fe 3 O 4 @MoS 2 presents new perspectives for developing efficient photothermal nano‐enzymatic compounds, offering a promising solution to the challenges of antimicrobial drug resistance and antibiotic misuse.
Closed-loop modulation of remote hippocampal representations with neurofeedback
Authors: Michael E Coulter, Anna K Gillespie, Joshua Chu, Eric L Denovellis, Trevor Thai K Nguyen, Daniel F Liu, Katherine Wadhwani, Baibhav Sharma, Kevin Wang, Xinyi Deng, Uri T Eden, Caleb Kemere, Loren M Frank
Journal: Neuron (2025)
Macro/Microgel‐Encapsulated, Biofilm‐Armored Living Probiotic Platform for Regenerating Bacteria‐Infected Diabetic Wounds
Authors: Huilong Xin, Zhe Cai, Jiahui Hao, Jing An, Yi Li, Min Wen, Zhaojun Jia
Journal: Advanced Healthcare Materials (2025)

Abstract Infectious diabetic wounds pose an arduous threat to contemporary healthcare. The combination of refractory biofilms, persistent inflammation, and retarded angiogenesis can procure non‐unions and life‐threatening complications, calling for advanced therapeutics potent to orchestrate anti‐infective effectiveness, benign biocompatibility, pro‐reparative immunomodulation, and angiogenic regeneration. Herein, embracing the emergent “living bacterial therapy” paradigm, a designer probiotic‐in‐hydrogel wound dressing platform is demonstrated. The platform is constructed employing a “macrogel/microgel/biofilm” hierarchical encapsulation strategy, with Lactobacillus casei as the model probiotic. Alginate gels, in both macro and micro forms, along with self‐produced probiotic biofilms, served as encapsulating agents. Specifically, live probiotics are enclosed within alginate microspheres, embedded into an alginate bulk matrix, and cultivated to facilitate biofilm self‐encasing. This multiscale confinement protected the probiotics and averted their inadvertent escape, while enabling sustained secretion, proper reservation, and localized delivery of therapeutically active probiotic metabolites, such as lactic acid. The resulting biosystem, as validated in vitro/ovo/vivo, elicited well‐balanced antibacterial activities and biological compatibility, alongside prominent pro‐healing, vasculogenic and anti‐inflammatory potencies, thus accelerating the regeneration of infected full‐thickness excisional wounds in diabetic mice. Such multiple encapsulation‐engineered “all‐in‐one” probiotic delivery tactic may shed new light on the safe and efficient adoption of live bacteria for treating chronic infectious diseases.
Acid‐Triggered Cascaded Responsive Supramolecular Peptide Alleviates Myocardial Ischemia‒Reperfusion Injury by Restoring Redox Homeostasis and Protecting Mitochondrial Function
Authors: Xu Liao, Min Tang, Jiejing Li, Runze Guo, Chongbin Zhong, Xiangzhou Chen, Xuwei Zhang, Hongwei Mo, Dongdong Que, Wenjie Yu, Xudong Song, Hekai Li, Yanbin Cai, Pingzhen Yang
Journal: Advanced Healthcare Materials (2025)

Abstract Redox imbalance, including excessive production of reactive oxygen species (ROS) caused by mitochondrial dysfunction and insufficient endogenous antioxidant capacity, is the primary cause of myocardial ischemia‒reperfusion (I/R) injury. In the exploration of reducing myocardial I/R injury, it is found that protecting myocardial mitochondrial function after reperfusion not only reduces ROS bursts but also inhibits cell apoptosis triggered by the release of cytochrome c. Additionally, nuclear factor erythroid 2‐related factor 2 (Nrf2) is considered a potential therapeutic target for treating myocardial I/R injury by enhancing the cellular antioxidant capacity through the induction of endogenous antioxidant enzymes. In this study, a peptide‒drug conjugate OI‐FFG‐ss‐SS31(ISP) is developed by integrating the Nrf2 activator 4‐octyl itaconate (OI) and the mitochondria‐targeting protective peptide elamipretide (SS31), and its therapeutic potential for myocardial I/R injury is explored. The results showed that ISP could self‐assemble into nanofibers in response to the acidic microenvironment and bind to Keap‐1 with high affinity, thereby activating Nrf2 and enhancing antioxidant capacity. Simultaneously, the release of SS31 could improve mitochondrial function and reduce ROS, ultimately providing a restoration of redox homeostasis to effectively alleviate myocardial I/R injury. This study presents a promising acid‐triggered peptide‐drug conjugate for treating myocardial I/R injury.