tbuckley/cabot-search huggingface dataset:
Prescribing Trends of Antidiabetes Medications Near End-of-Life Among Adults With Type 2 Diabetes: A Cohort Study
Authors: Alexander Kutz, Dae Hyun Kim, Jun Liu, Medha N. Munshi, Elisabetta Patorno
Journal: Diabetes Care (2025)

OBJECTIVE To assess prescribing trends of antidiabetes medications in the last year of life among older adults with type 2 diabetes (T2D) and explore whether frailty is associated with differential prescribing. RESEARCH DESIGN AND METHODS In this observational cohort study of Medicare beneficiaries aged ≥67 years (2015–2019) with T2D, we assessed temporal trends in prescribing an antidiabetes medication, stratified by frailty. The main outcome included antidiabetes medication fills within 1 year of death. RESULTS Among 975,407 community-dwelling Medicare beneficiaries with T2D, the use of antidiabetes medications within 1 year of death slightly increased from 71.4% during the first 6-month period in 2015 to 72.9% (standardized mean difference [SMD] −0.03) during the second 6-month period in 2019. The most pronounced increase in use was observed for metformin (40.7% to 46.5%, SMD −0.12), whereas the largest decrease was observed for sulfonylureas (37.0% to 31.8%, SMD 0.11). Overall antidiabetes medication use decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (SMD 0.11; P &amp;lt; 0.01), driven by reduced noninsulin medication use. The use of short-acting and long-acting insulin both increased near death, with frailer individuals more likely to receive insulin. Sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists, although less common, became more frequent in more recent years. CONCLUSIONS The use of antidiabetes medications declined in the last year of life, mainly due to reduced noninsulin use. Insulin use increased near death, particularly among frailer individuals, highlighting the need for careful end-of-life management.
The Association Between Cost-Related Insulin Rationing and Health Care Utilization in U.S. Adults With Diabetes
Authors: Caroline G. Borden, Baylee F. Bakkila, Laura M. Nally, Kasia J. Lipska
Journal: Diabetes Care (2025)

OBJECTIVE To examine the association between insulin rationing and health care utilization. RESEARCH DESIGN AND METHODS Cross-sectional study of all 2021 National Health Interview Survey respondents with diabetes using insulin. Logistic regression and zero-inflated negative binomial regression models examined associations between insulin rationing (skipping, delaying, or reducing insulin to save money) and 1) emergency department (ED) visit or hospitalization and 2) number of urgent care visits. All analyses were age-stratified and used survey weights. RESULTS Among 982 respondents representing 7,593,944 U.S. adults (median age 61, 47% women), 17% reported rationing. Among adults 18–64, rationing was not significantly associated with health care utilization. Among adults ≥65, rationing was associated with more urgent care visits (relative risk 2.1, 95% CI 1.2–3.6) but not with odds of ED visit or hospitalization (odds ratio 0.7, 95% CI 0.3–1.4). CONCLUSIONS Insulin rationing was not associated with higher health care utilization, but concurrent rationing of health care may mask a relationship.
LIPUS activated piezoelectric pPLLA/SrSiO3 composite scaffold promotes osteochondral regeneration through P2RX1 mediated Ca2+ signaling pathway
Authors: Chengxiao Liu, Bin Yu, Zhaowenbin Zhang, Lefeng Su, Ruiqing Wang, Yu Jin, Weiming Guo, Ruomei Li, Zhen Zeng, Peng Mei, Jiang Chang, Lunguo Xia, Chen Yang, Bing Fang
Journal: Biomaterials (2025)
Nanomedicine-Unlocked Radiofrequency Dynamic Therapy Dampens Incomplete Radiofrequency Ablation-Arised Immunosuppression to Suppress Cancer Relapse
Authors: Yan Fang, Feixiang Hu, Weiwei Ren, Lihua Xiang, Taixia Wang, Chunyan Zhu, Ruiqing He, Xiulin Dong, Chang Liu, Hong Ding, Kun Zhang
Journal: Biomaterials (2025)
Clinical Management of Human Herpesvirus-8 related illnesses in solid organ transplant recipients
Authors: Alessia Dalla Pria, Ines Ushiro-Lumb, Mark Bower
Journal: Journal of Infection (2025)

In solid organ transplant recipients (SOTRs), the oncogenic virus human herpesvirus-8 (HHV-8) also named Kaposi sarcoma herpesvirus (KSHV) causes four clinical diseases: Kaposi Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman Disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). This review outlines these clinical scenarios and discusses their management. Although HHV8 related disease in SOTR was first described more than three decades ago, there is a lack of data on treatment so much of the guidance is based on evidence in other immunodeficient patients, particularly people living with HIV. Whilst reduction of immunosuppression and switch from calcineurin inhibitors to mTOR inhibitors may be sufficient in early stage post-transplant KS, systemic chemotherapy is necessary for advanced stage KS and in KSHV related lymphomas. For MCD and KICS,which usually follow primary HHV-8 infection, rituximab based immunochemotherapy regimens are the cornerstone of treatment for these potentially lethal diseases. Although HHV-8 infection in SOTR is well recognised it remains under reported and greater awareness of the different clinical presentations of HHV-8 in this context is fundamental to improve outcomes.
Time Below Range and Its Influence on Hypoglycemia Awareness and Severe Hypoglycemia: Insights From the Association of British Clinical Diabetologists Study
Authors: Harshal Deshmukh, Emma G. Wilmot, Pratik Choudhary, Emmanuel Ssemmondo, Dennis Barnes, Neil Walker, Chris Walton, Robert E.J. Ryder, Thozhukat Sathyapalan
Journal: Diabetes Care (2025)

OBJECTIVE This study aimed to explore the relationship between time below range (TBR), impaired awareness of hypoglycemia (IAH), and severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS This cross-sectional study analyzed data from individuals with diabetes using continuous glucose monitors (CGMs) in the Association of British Clinical Diabetologists audit. Hypoglycemia awareness was assessed via the Gold score (≥4 denoting IAH), and SH was defined as hypoglycemia requiring third-party assistance. Logistic regression was used to determine the association between TBR percentage (&amp;lt;70 mg/dL; 3.9 mmol/L) at first follow-up and follow-up Gold score and SH incidence. The Youden J index identified optimal TBR percentage cutoffs for detecting IAH and SH. RESULTS The study included 15,777 participants, with follow-up TBR and SH data available for 5,029. The median TBR percentage was 4% (interquartile range 2–6.6%), with 42% meeting the recommended TBR of ≤4%. Adjusted for age, sex, and BMI, TBR was significantly associated with SH (P &amp;lt; 0.001) and IAH (P = 0.005). Optimal TBR cutoffs for identifying IAH and SH were 3.35% and 3.95%, yielding negative predictive value (NPV) values of 85% and 97%, respectively. CONCLUSIONS Our findings support the international consensus recommending a TBR of &amp;lt;4% in type 1 diabetes, with high NPV values suggesting the utility of TBR in screening for SH.
Pan-cancer drivers of metastasis
Authors: Ryan Lusby, Engin Demirdizen, Mohammed Inayatullah, Paramita Kundu, Oscar Maiques, Ziyi Zhang, Mikkel Green Terp, Victoria Sanz-Moreno, Vijay K. Tiwari
Journal: Molecular Cancer (2025)

Abstract Metastasis remains a leading cause of cancer-related mortality, irrespective of the primary tumour origin. However, the core gene regulatory program governing distinct stages of metastasis across cancers remains poorly understood. We investigate this through single-cell transcriptome analysis encompassing over two hundred patients with metastatic and non-metastatic tumours across six cancer types. Our analysis revealed a prognostic core gene signature that provides insights into the intricate cellular dynamics and gene regulatory networks driving metastasis progression at the pan-cancer and single-cell level. Notably, the dissection of transcription factor networks active across different stages of metastasis, combined with functional perturbation, identified SP1 and KLF5 as key regulators, acting as drivers and suppressors of metastasis, respectively, at critical steps of this transition across multiple cancer types. Through in vivo and in vitro loss of function of SP1 in cancer cells, we revealed its role in driving cancer cell survival, invasive growth, and metastatic colonisation. Furthermore, tumour cells and the microenvironment increasingly engage in communication through WNT signalling as metastasis progresses, driven by SP1. Further validating these observations, a drug repurposing analysis identified distinct FDA-approved drugs with anti-metastasis properties, including inhibitors of WNT signalling across various cancers.
Nanoplasmonic Rapid Antimicrobial‐Resistance Point‐of‐Care Identification Device: RAPIDx (Adv. Healthcare Mater. 1/2025)
Authors: Jong‐Hwan Lee, Jihwan Song, SoonGweon Hong, Yun Kim, Minsun Song, Byungrae Cho, Tiffany Wu, Lee W. Riley, Ulf Landegren, Luke P. Lee
Journal: Advanced Healthcare Materials (2025)
A Rational Approach to the Treatment of Acute Pulmonary Embolism
Authors: Michela Faggioni, Jay Giri, Lauren Glassmoyer, Taisei Kobayashi
Journal: Annual Review of Medicine (2025)

Over the past decade, new modalities have emerged to treat acute pulmonary embolism (PE). However, PE remains a leading cause of morbidity and mortality worldwide. In the absence of robust clinical trial data and definitive guidelines and recommendations for a variety of clinical situations, individual patient treatment decisions have become paradoxically more challenging as innovation in the space has grown. In this review, we discuss a practical and current approach to patients diagnosed with PE, focusing on their risk stratification and treatment selection.
TNF/TNFR Superfamily Members in Costimulation of T Cell Responses—Revisited
Authors: Tania H. Watts, Karen K.M. Yeung, Tianning Yu, Seungwoo Lee, Razieh Eshraghisamani
Journal: Annual Review of Immunology (2025)

Prosurvival tumor necrosis factor receptor (TNFR) superfamily (TNFRSF) members on T cells, including 4-1BB, CD27, GITR, and OX40, support T cell accumulation during clonal expansion, contributing to T cell memory. During viral infection, tumor necrosis factor superfamily (TNFSF) members on inflammatory monocyte-derived antigen-presenting cells (APCs) provide a postpriming signal (signal 4) for T cell accumulation, particularly in the tissues. Patients with loss-of-function mutations in TNFR/TNFSF members reveal a critical role for 4-1BB and CD27 in CD8 T cell control of Epstein-Barr virus and other childhood infections and of OX40 in CD4 T cell responses. Here, on the 20th anniversary of a previous Annual Review of Immunology article about TNFRSF signaling in T cells, we discuss the effects of endogenous TNFRSF signals in T cells upon recognition of TNFSF members on APCs; the role of TNFRSF members, including TNFR2, on regulatory T cells; and recent advances in the incorporation of TNFRSF signaling in T cells into immunotherapeutic strategies for cancer.
Next Steps in Efforts to Address the Obesity Epidemic
Authors: Yuilyn A. Chang Chusan, Ihuoma Eneli, Erin Hennessy, Nicolaas P. Pronk, Christina D. Economos
Journal: Annual Review of Public Health (2025)

Obesity prevalence continues to rise globally at alarming rates, with adverse health and economic implications. In this state-of-the-art review, we provide an analysis of selected evidence about the current knowledge in the obesity literature, including a synthesis of current challenges in obesity and its determinants. In addition, we review past and current efforts to combat the obesity epidemic, highlighting both successful efforts and areas for further development. Last, we offer insights into the next steps to address the obesity epidemic and advance the field of obesity through both research and practice by (
Aspirin is associated with lower risk of pancreatic cancer and cancer-related mortality in patients with diabetes mellitus
Authors: Jing Tong Tan, Xianhua Mao, Ho-Ming Cheng, Wai-Kay Seto, Wai-K Leung, Ka-Shing Cheung
Journal: Gut (2025)

Background Patients with type 2 diabetes mellitus (T2DM) have higher pancreatic cancer (PC) risk. While aspirin has chemopreventive effects on digestive cancers, its effect on PC among patients with T2DM is unclear. Methods This retrospective cohort study identified newly diagnosed adult patients with T2DM in Hong Kong between 2001 and 2015 from a territory-wide healthcare registry. Exclusion criteria were history of PC, pancreatic cyst, IgG4 disease, or pancreatectomy. To address reverse causality between PC and T2DM, we excluded patients with PC diagnosed within 1 year of T2DM. We also excluded patients with less than 1 year of observation. Primary outcome was PC, and secondary outcomes were PC-related and all-cause mortality. Aspirin use was treated as time-varying variable (≥180 day-use/year) to address immortal-time bias, and multivariable Cox regression model was employed to derive adjusted HR (aHR). Propensity-score (PS) matching was used as secondary analysis. Results Among 343 966 newly diagnosed patients with T2DM (median follow-up: 10.5 years; IQR: 7.7–14.5 years), 1224 (0.36%) developed PC. There were 51 151 (14.9%) deaths from any cause, and 787 (0.2%) died from PC. Aspirin use was associated with lower PC risk in both time-dependent (aHR: 0.58; 95% CI 0.49 to 0.69) and PS matching analysis (aHR: 0.61; 95% CI 0.48 to 0.77). An inverse relationship was observed with increasing dose and duration of aspirin use ( P trend &lt;0.001). Aspirin was also associated with a lower risk of PC-related mortality (aHR: 0.43; 95% CI 0.34 to 0.53) and all-cause mortality (aHR: 0.78; 95% CI 0.76 to 0.80). Conclusion Aspirin use may be an oncopreventive strategy to reduce PC risk in patients with T2DM. Further studies are warranted to validate the study findings.
Clinical benefit of chronic non-invasive ventilation in severe stable COPD: a matter of persistent hypercapnia improvement
Authors: Tim Raveling, Renzo Boersma, Peter J Wijkstra, Marieke L Duiverman
Journal: Thorax (2025)

In patients with chronic obstructive pulmonary disease (COPD) treated with chronic non-invasive ventilation (NIV), the relation between improvements in nocturnal transcutaneous partial pressure of CO
Restoring Speech Using Brain–Computer Interfaces
Authors: Sergey D. Stavisky
Journal: Annual Review of Biomedical Engineering (2025)

People who have lost the ability to speak due to neurological injuries would greatly benefit from assistive technology that provides a fast, intuitive, and naturalistic means of communication. This need can be met with brain–computer interfaces (BCIs): medical devices that bypass injured parts of the nervous system and directly transform neural activity into outputs such as text or sound. BCIs for restoring movement and typing have progressed rapidly in recent clinical trials; speech BCIs are the next frontier. This review covers the clinical need for speech BCIs, surveys foundational studies that point to where and how speech can be decoded in the brain, describes recent progress in both discrete and continuous speech decoding and closed-loop speech BCIs, provides metrics for assessing these systems’ performance, and highlights key remaining challenges on the road toward clinically useful speech neuroprostheses.
An Intersectional Analysis of Behavioral Financial Hardship and Healthcare Utilization among LGBTQ+ Cancer Survivors
Authors: Austin R Waters, Stephanie B Wheeler, Jeremey Fine, Christabel K Cheung, Kelly R Tan, Donald L Rosenstein, Mya L Roberson, Erin E Kent
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background lesbian, gay, bisexual, transgender, queer, or another non-heterosexual or cisgender identity (LGBTQ+) cancer survivors experience high financial hardship. However, structural drivers of inequities do not impact all LGBTQ+ individuals equally. Using All of Us data, we conducted an intersectional analysis of behavioral financial hardship among LGBTQ+ cancer survivors. Methods LGBTQ+ inequities in behavioral financial hardship (ie, cost-related foregone care, delayed care, and medication alterations) and non-cost-related delayed care were estimated using All of Us Data. Multivariable logit models were used to generate predicted probabilities, average marginal effects (AME), and 95% confidence intervals. Models were then used to estimate inequities when disaggregating LGBTQ+ status and combing LGBTQ+ status with age, race, ethnicity, and treatment status. Results This analysis included N = 36,217 cancer survivors (6.6%, n = 2,399 LGBTQ+). In multivariable models, LGBTQ+ identity was associated with higher probabilities of and significant AME for all types of behavioral financial hardship (foregone care 31.1% vs. 19.4%; delayed care 22.6% vs. 15.6%; medication alterations 19.2% vs. 11.9%) and non-cost delayed care (14.3% vs. 7.2%). Within the disaggregated analysis, cisgender bisexual and another/multiple orientation women and gender minority survivors had the highest predicted probabilities of all outcomes. In intersectional analyses, survivors who were aged 18-39 and LGBTQ+, Black and LGBTQ+, or Hispanic/Latine and LGBTQ+ had the highest predicted probabilities of all outcomes. Conclusions LGBTQ+ cancer survivors experience significantly more behavioral financial hardship and non-cost-related delayed care then non-LGBTQ+ cancer survivors. Interventions at the individual, system, and policy level are needed to address LGBTQ+ inequities in financial hardship.
Timing of depression in relation to risk of ovarian cancer
Authors: Andrea L Roberts, Mary K Townsend, Lori B Chibnik, Laura D Kubzansky, Shelley S Tworoger
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Objective Several studies have suggested that depression may be associated with increased risk of ovarian cancer. Less is known about whether timing matters regarding when depression occurs. To provide evidence for an etiologically relevant exposure period, we examined depression occurring during the time in which precursor lesions develop and progress to invasive carcinoma with risk of developing ovarian cancer. Methods Using data from two prospective cohorts (1992-2015), we divided follow-up into consecutive two-year periods for analytic purposes, referred to as “cancer ascertainment periods.” We estimated associations of depression in the 10 years before each cancer ascertainment period with incident cancer, using Cox proportional hazards models. Next, we estimated associations of depression occurring up to 18 years before each ascertainment period, in two-year increments, with incident cancer. We adjusted for demographic, health, and behavioral factors. All tests of statistical significance were 2-sided, with a p-value threshold of &amp;lt; 0.05. Results Depression occurring in the 10 prior years was associated with 30% greater risk of cancer (hazard ratio (HR)=1.30, 95% confidence interval (CI)=1.15-1.46). Associations were similar in fully adjusted models (HR = 1.27). Depression occurring in the 14 years before ascertainment was associated with elevated risk, although only estimates for depression 0-2, 6-8, and 8-10 years before ascertainment reached statistical significance (HR range, 1.20-1.36). Conclusion Depression occurring up to 14 years before cancer ascertainment was associated with greater cancer risk. This is the time of precursor progression to invasive ovarian carcinoma, suggesting depression may be an ovarian cancer promoting agent.
Treatment of Relapsed/Refractory <scp>CLL</scp> Patients With <scp>PI3Kδ</scp> Inhibitor and Anti‐<scp>CD20</scp> Antibody Rapidly Decreases Tumor Burden but Could Induce Resistance
Authors: Jennifer E. Bruno, Christine A. Herne, Andrea M. Baran, Karl R. VanDerMeid, Paul M. Barr, Alyssa R. Williams, Sally A. Quataert, Tim R. Mosmann, Clive S. Zent, Charles C. Chu
Journal: American Journal of Hematology (2025)

Multi-drug combination strategy targeting three different molecules involved in different pathways to overcome single-agent resistance in relapsed/refractory CLL patients. The clinical trial utilized 1)a therapeutic anti-CD20 monoclonal antibody (mAb), ublituximab, which destroys CLL cells by an antibody-dependent cellular phagocytosis (ADCP) mechanism; 2)a B cell receptor (BCR) signaling inhibitor, umbralisib, which blocks PI3Kẟ; 3)and an anti-apoptosis inhibitor, venetoclax, which blocks cell survival promoted by BCL-2 that stops mitochondria from initiating apoptosis. Our correlative study focused on the first two treatments prior to venetoclax addition. We found that patients respond to anti-CD20 antibody and BCR signaling inhibition with rapid reductions in CLL cell counts and CD20 levels. Standard high dose (375 mg/m2) anti-CD20 antibody treatment significantly decreased CLL surface CD20 levels, potentially limiting treatment efficacy. Anti-CD20 antibody plus B cell receptor signaling inhibition reduced CLL cell counts and lymph node tumors, enabling BCL-2 inhibitor treatment to avoid tumor lysis syndrome.
Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding
Authors: Jiancheng Gao, Danling Gu, Kailin Yang, Junxia Zhang, Qiankun Lin, Wei Yuan, Xu Zhu, Deobrat Dixit, Ryan C Gimple, Hao You, Qian Zhang, Zhumei Shi, Xiao Fan, Qiulian Wu, Chenfei Lu, Zhangchun Cheng, Daqi Li, Linjie Zhao, Bin Xue, Zhu Zhu, Zhe Zhu, Hui Yang, Ningwei Zhao, Wei Gao, Yingmei Lu, Junfei Shao, Chuandong Cheng, Dapeng Hao, Shuo Yang, Yun Chen, Xiaoming Wang, Chunsheng Kang, Jing Ji, Jianghong Man, Sameer Agnihotri, Qianghu Wang, Fan Lin, Xu Qian, Stephen C Mack, Zhibin Hu, Chaojun Li, Michael D Taylor, Yan Li, Nu Zhang, Jeremy N Rich, Yongping You, Xiuxing Wang
Journal: Cancer Cell (2025)
Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets
Authors: Kyle Ellrott, Christopher K Wong, Christina Yau, Mauro A A Castro, Jordan A Lee, Brian J Karlberg, Jasleen K Grewal, Vincenzo Lagani, Bahar Tercan, Verena Friedl, Toshinori Hinoue, Vladislav Uzunangelov, Lindsay Westlake, Xavier Loinaz, Ina Felau, Peggy I Wang, Anab Kemal, Samantha J Caesar-Johnson, Ilya Shmulevich, Alexander J Lazar, Ioannis Tsamardinos, Katherine A Hoadley, A Gordon Robertson, Theo A Knijnenburg, Christopher C Benz, Joshua M Stuart, Jean C Zenklusen, Andrew D Cherniack, Peter W Laird
Journal: Cancer Cell (2025)

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic. We validate select classifiers using external datasets. Predictive performance and classifier-selected features yield insight into the different machine-learning approaches and genomic data platforms. For each cancer and data type we provide containerized versions of the top-performing models as a public resource.
Exploring Treatment-Driven Subclonal Evolution of Prognostic Triple Biomarkers: Dual Gene Fusions and Chimeric RNA Variants in Novel Subtypes of Acute Myeloid Leukemia Patients with KMT2A Rearrangement
Authors: Yi Xu, Shengwen Calvin Li, Jeffrey Xiao, Qian Liu, Durga Cherukuri, Yan Liu, Saied Mirshahidi, Jane Xu, Xuelian Chen, Dadrastoussi Homa, Julian Olea, Kaijin Wu, Kevin R Kelly, Fengzhu Sun, Ruihao Huang, Xiaoqi Wang, Qin Wen, Xi Zhang, Cristina M Ghiuzeli, Esther Chong, Hisham Abdel-Azim, Mark E Reeves, David J Baylink, Huynh Cao, Jiang F Zhong
Journal: Drug Resistance Updates (2025)