tbuckley/cabot-search huggingface dataset:
Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus
Authors: Wei Li, Antonios G. A. Kolios, Wenliang Pan, Catalina Burbano, Kohei Karino, Theodoros Vichos, Morgane Humbel, Vasileios C. Kyttaris, Maria G. Tsokos, George C. Tsokos
Journal: Science Translational Medicine (2025)

Systemic lupus erythematosus (SLE) is characterized by dysfunctional regulatory T cells (T regs ). We previously showed that protein phosphatase 2A (PP2A) plays a critical role in maintaining the suppressive function of T regs . Here, we analyzed phosphoproteomics and metabolomics data from PP2A–wild type and PP2A-deficient T regs and demonstrated that PP2A regulates T reg function through the pentose phosphate pathway (PPP). Furthermore, we proved that the PPP metabolite gluconolactone (GDL) enhances in vitro induced (i)T reg differentiation and function by promoting forkhead box protein 3 and phosphorylated signal transducer and activator of transcription 5 expression and inhibits T helper 17 (T H 17) differentiation in murine cells. In short-term imiquimod-induced autoimmunity in mice, treatment with GDL alleviates inflammation by inhibiting T H 17 cells. GDL promotes T regs function and alleviates skin lesions in MRL. lpr lupus-prone mice in vivo. It also promotes T regs differentiation and function in ex vivo experiments using cells from patients with SLE. Last, in patients suffering from cutaneous lupus erythematosus, topical application of a GDL-containing cream controlled skin inflammation and improved the clinical and histologic appearance of the skin lesions within 2 weeks. Together, we have identified GDL as a PPP metabolite and showed mechanistically that it restores immune regulation in vitro and in vivo by inducing T reg suppressive function and inhibiting T H 17 cells. GDL should be considered as a treatment approach for inflammatory and autoimmune diseases.
Health-related quality of life is impaired in people with autoimmune hepatitis: Results of a multicentre cross-sectional study within the European Reference Network
Authors: Romée J.A.L.M. Snijders, Maciej K. Janik, Meike Mund, Natalie Uhlenbusch, Joanna Raszeja-Wyszomirska, Alessio Gerussi, Francesca Bolis, Laura Cristoferi, Pietro Invernizzi, Patricia Kovats, Mária Papp, Lisbet Grønbæk, Henning Grønbæk, Eric T.T.L. Tjwa, Luise Aamann, Henriette Ytting, Vincenzo Ronca, Kathryn Olsen, Ye H. Oo, Adriaan J. van der Meer, João Madaleno, Bernardo Canhão, Bastian Engel, Alejandro Campos-Murguia, Richard Taubert, Özgür M. Koc, Matthijs Kramer, José A. Willemse, Bernd Löwe, Ansgar W. Lohse, Joost P.H. Drenth, Christoph Schramm, Piotr Milkiewicz, Tom J. Gevers
Journal: Hepatology (2025)

Background: Impaired health-related quality of life (HRQoL) contributes to the overall disease burden in autoimmune hepatitis (AIH). This study aimed to evaluate HRQoL in people with AIH and to identify potentially modifiable factors associated with impaired HRQoL using validated patient-reported outcome measures. Methods: Adult AIH patients diagnosed at 12 European centers were enrolled in this prospective, cross-sectional study from July 2020-June 2023. HRQoL was assessed using the Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-item Short Form Health Survey (SF-12), and the European Quality-of-life 5-Dimension 5-Level (EQ-5D-5L) utility index (UI) score. Mixed-model regression analyses identified factors associated with HRQoL and somatic symptom severity. Controls were recruited from the general population in five European countries. Results: A total of 882 patients with AIH (mean age: 51.0 y [SD 17.0]; 76.4% female) and 178 controls were included. Physical but not mental HRQoL was impaired in the AIH group compared with the control group (PCS: 46.3 vs. 51.9, p &lt;0.001; EQ-5D UI: 0.87 vs. 0.95, p &lt;0.001). HRQoL was associated with severe somatic symptoms (PCS β=−4.26, p &lt;0.001), fatigue (PCS β=−0.25, p &lt;0.001; MCS β=−0.25, p &lt;0.001), and depression/anxiety (PCS β=−3.37, p &lt;0.001; MCS β=−6.79, p &lt;0.001). A complete biochemical response was associated with a lower somatic symptom severity (odds ratio 0.69, p &lt;0.05). Conclusions: People with AIH had impaired HRQoL compared with controls, particularly in terms of physical well-being. HRQoL scores are associated with symptom burden, encompassing both somatic and psychosocial dimensions.
Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread
Authors: Felix Pahmeier, Stephanie R. Monticelli, Xinyi Feng, Christy K. Hjorth, Albert Wang, Ana I. Kuehne, Russell R. Bakken, Thomas G. Batchelor, Saeyoung E. Lee, Marissa Middlecamp, Lauren Stuart, Amaro N. Duarte-Neto, Dafna M. Abelson, Jason S. McLellan, Scott B. Biering, Andrew S. Herbert, Kartik Chandran, Eva Harris
Journal: Science Translational Medicine (2025)

Crimean-Congo hemorrhagic fever virus (CCHFV) is a priority pathogen transmitted by tick bites, with no vaccines or specific therapeutics approved to date. Severe disease manifestations include hemorrhage, endothelial dysfunction, and multiorgan failure. Infected cells release the viral glycoprotein GP38, whose extracellular function is presently unknown. GP38 is considered an important target for vaccine and therapeutic design because GP38-specific antibodies can protect against severe disease in animal models, albeit through an unknown mechanism of action. Here, we showed that GP38 induces endothelial barrier dysfunction in vitro by disrupting the endothelial glycocalyx layer and triggering hyperpermeability. We also demonstrated that GP38 alone can cause vascular leak in a mouse model. We found that CCHFV infection leads to vascular leak in vivo, which was exacerbated by exogenous administration of GP38, facilitating dissemination of CCHFV into target tissues such as the liver. Protective antibodies that recognized specific antigenic sites on GP38, but not a protective neutralizing antibody binding the structural protein Gc, potently inhibited endothelial hyperpermeability in vitro and vascular leak in vivo during CCHFV infection. This work uncovers a function of the circulating viral protein GP38 as a viral toxin in CCHFV pathogenesis and elucidates a potential mode of action of nonneutralizing yet protective GP38-specific antibodies.
β cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome
Authors: Kikuko Amo-Shiinoki, Katsuya Tanabe, Wataru Nishimura, Masayuki Hatanaka, Manabu Kondo, Syota Kagawa, Meng Zou, Shuntaro Morikawa, Yoshihiko Sato, Mitsuhisa Komatsu, Hiroki Mizukami, Naoki Nishida, Shun-Ichiro Asahara, Hiroshi Masutani, Yukio Tanizawa
Journal: Science Translational Medicine (2025)

Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by WFS1 gene mutations. However, the pathological process of ER stress–associated β cell failure remains to be fully elucidated. Our results indicate loss of β cell lineage and subsequent dedifferentiation as the mechanisms underlying functional and mass deficits in WS. An immunohistochemical analysis of human pancreatic sections from deceased individuals with WS revealed a near-complete loss of β cells and subsequent decrease in α cells, suggesting loss of endocrine function. Wfs1 -deficient mice displayed dysfunction, gradual loss, and dedifferentiation of β cells, leading to permanent hyperglycemia. Impairment of the β cell lineage was observed after weaning, leading to the mixed phenotype of insulin- and glucagon-producing cells in a subset of the lineage-traced β cells. Islets of Wfs1 -deficient mice increased the number of dedifferentiated cells that maintained general endocrine features but were no longer reactive with antisera against pancreatic hormones. Mechanistically, Wfs1 -null islets had a lower adenosine triphosphate content and impaired oxidative glycolysis, although mitochondrial oxidative function was maintained. The functional and metabolic alterations of WS β cells were recovered by deletion of thioredoxin-interacting protein (Txnip), an ER stress–induced protein up-regulated in Wfs1 deficiency. Txnip deletion preserved functional β cells and prevented diabetes progression in Wfs1 -deficient mice. Together, this study deciphered pathological mechanisms of β cell dedifferentiation in β cell failure and has implications for Txnip inhibition in WS therapy.
Development of Australian mental health guidelines for community sport
Authors: Stewart Anthony Vella, Caitlin Liddelow, Simon M Rice, Richard Keegan, Kate Hall, Mark A Jones, David Revalds Lubans, Samantha McLeod, Anthony David Okely, Lisa S Olive, Rosemary Purcell, Lindsey J Reece, Simon Rosenbaum, Matthew J Schweickle, Kelsey Singh, Damien Stewart, Leisl Stimpson, Jordan T Sutcliffe, Megan Teychenne, Courtney C Walton, Christian Swann
Journal: British Journal of Sports Medicine (2025)

Objective The need for clear and actionable guidelines for the promotion and protection of mental health in organised community sport has previously been identified. This study aimed to provide guidelines to promote and protect mental health in organised community sport in Australia. Methods Guideline development was informed by (1) systematic reviews of the evidence pertaining to existing mental health guidelines in sport and mental health interventions in community sport; (2) an expert Delphi consensus study and (3) key stakeholder input via focus groups. A Guideline Development Committee comprising experts and key stakeholder representatives articulated nine distinct guidelines. Results These guidelines address the areas of: mental health literacy training; mental health support pathways and processes; responding to mental health emergencies; responding to major events that may impact mental health; having a mental health plan in place; reducing stigmatising attitudes; appointing a dedicated mental health champion; coach education and promoting well-being within the organisation. Conclusions We provide guidance for promoting and protecting mental health in community sport. Monitoring uptake and measuring the effectiveness of the guidelines are important areas of future work to advance positive mental health for everybody involved in community sport.
Synergistic role of gut-microbial L-ornithine in enhancing ustekinumab efficacy for Crohn’s disease
Authors: Zhenyu Wang, Li Tian, Yi Jiang, Lijun Ning, Xiaoqiang Zhu, Xuejie Chen, Baoqin Xuan, Yilu Zhou, Jinmei Ding, Yanru Ma, Ying Zhao, Xiaowen Huang, Muni Hu, Jing-Yuan Fang, Nan Shen, Zhijun Cao, Haoyan Chen, Xiaoyan Wang, Jie Hong
Journal: Cell Metabolism (2025)
Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation
Authors: Weijie Wu, Wenhai Sui, Sizhe Chen, Ziheng Guo, Xu Jing, Xiaolu Wang, Qun Wang, Xinshuang Yu, Wenjing Xiong, Jiansong Ji, Libo Yang, Yuan Zhang, Wenjing Jiang, Guohua Yu, Shuzhen Liu, Wei Tao, Chen Zhao, Yun Zhang, Yuguo Chen, Cheng Zhang, Yihai Cao
Journal: Cell Metabolism (2025)
Lymphatic transport in anti-tumor immunity and metastasis
Authors: Mengzhu Sun, Julien Angelillo, Stéphanie Hugues
Journal: The Journal of Experimental Medicine (2025)

Although lymphatic vessels (LVs) are present in many tumors, their importance in cancer has long been underestimated. In contrast to the well-studied tumor-associated blood vessels, LVs were previously considered to function as passive conduits for tumor metastasis. However, emerging evidence over the last two decades has shed light on their critical role in locally shaping the tumor microenvironment (TME). Here we review the involvement of LVs in tumor progression, metastasis, and modulation of anti-tumor immune response.
Native stem cell transcriptional circuits define cardinal features of high-risk leukemia
Authors: Qing Wang, Francesco Boccalatte, Jason Xu, Giovanni Gambi, Bettina Nadorp, Fatema Akter, Carea Mullin, Ashley F. Melnick, Elizabeth Choe, Anna C. McCarter, Nicole A. Jerome, Siyi Chen, Karena Lin, Sarah Khan, Rohan Kodgule, Jonathan H. Sussman, Petri Pölönen, Javier Rodriguez-Hernaez, Sonali Narang, Kleopatra Avrampou, Bryan King, Aristotelis Tsirigos, Russell J.H. Ryan, Charles G. Mullighan, David T. Teachey, Kai Tan, Iannis Aifantis, Mark Y. Chiang
Journal: The Journal of Experimental Medicine (2025)

While the mutational landscape across early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and ETP-like leukemia is known, establishing a unified framework that activates stem cell genes characteristic of these tumors remains elusive. Using complementary mouse and human models, chromatin mapping, and enhancer profiling, we show that the coactivator ZMIZ1 promotes normal and malignant ETP population growth by inducing the transcription factor MYB in feedforward circuits to convergently activate oncogenes (MEF2C, MYCN, and BCL2) through essential enhancers. A key superenhancer, the N-Myc regulating enhancer (NMRE), drives malignant ETP population growth but is dispensable for normal lymphopoiesis. This network of stem cell superenhancers identifies treatment-resistant tumors and poor survival outcomes; unifies diverse ETP-ALLs; and contributes to cardinal features of the recently genomically identified high-risk bone marrow progenitor-like (BMP-like) ETP-ALL tumor—stem cell/myeloid gene expression, inhibited NOTCH1-induced T-cell development, aggressive clinical behavior, and venetoclax sensitivity. Since ZMIZ1 is dispensable for essential homeostasis, it might be possible to safely target this network to treat high-risk diseases.
Combo Drugs Therapy Improves Restoration of Patency of Culprit Vessel in Acute ST-Elevation Myocardial Infarction – A case report of 3 patients
Authors: SKS Lairikyengbam
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Acute ST-Elevation Myocardial Infarction (STEMI) usually results from an occlusive coronary thrombus at the site of a ruptured atherosclerotic plaque. Thrombolysis has a role in the management of patient with acute STEMI and restoration of culprit vessel arterial flow as normal as possible. Early thrombolytic therapy in acute STEMI reduced mortality by the time of hospital discharge and better functional outcomes at 6 months. Thrombolytic therapy when given within 10 minutes of arrival at the Emergency Room helped restore the patency of culprit vessel patency to 0-30% in our 3 patients with acute STEMI. This may indicate that thrombolytic therapy augmented with loading anti-platelet drugs and bolus intravenous drug enoxaparin given in ≤ 10 minutes may be a viable alternative to primary percutaneous coronary intervention when the later is not available or not possible within Door-to-Balloon time of 120 minutes.
Association between End-Stage Renal Disease and Abdominal Aortic Aneurysm: A Nationwide Population-Based Cohort Study
Authors: Jeong-kye Hwang
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Background Abdominal aortic aneurysm (AAA) and end-stage renal disease (ESRD), defined by need for chronic renal replacement therapy, have similar epidemiological profiles and pathogenic mechanisms. However, studies testing for a connection between these two illnesses are rare. In this research, we tested the hypothesis that there is an association between AAA and ESRD. Materials and Methods Data from 2009 to 2015 were extracted from the Korean National Health Insurance Service database for this investigation. The study encompassed 16,671 individuals who had received a new AAA diagnosis. To form a control group, 50,013 participants without the diseases were selected using propensity score matching based on age and sex. The primary endpoint of this study was newly diagnosed ESRD. Results The hazard ratio (HR) of ESRD incidence in the AAA group was 2.5 (95% CI 2.0-3.2); in addition, when the AAA group was divided into surgical and non-surgical groups, the HR of the non-surgical group was 2.0 (95% CI 1.5-2.6). When AAA, chronic kidney disease (CKD), and proteinuria co-occurred, the HR of ESRD incidence increased to 128.7 compared to the cases without AAA. There were interactions of diabetes mellitus (DM), CKD, and proteinuria with incidence of ESRD (p &lt; 0.05). In the absence of these comorbidities, the HR for ESRD was higher in the presence of AAA [1.6 vs. 3.8 (DM), 2.3 vs. 3.4 (CKD), and 1.8 vs. 3.0 (proteinuria)]. Conclusions Our findings revealed a significant correlation between AAA and ESRD even after adjusting for several health conditions. This discovery suggests the need for regular monitoring of AAA patients. This proactive approach can aid in promptly identifying signs of ESRD and addressing modifiable risk factors at an early stage through timely interventions.
Stemi in Dakar Registry: Evaluation of Data at 06 Months
Authors: Momar Dioum
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Introduction: ST-elevation myocardial infarction (STEMI) remains a worldwide scourge with dramatic consequences both functionally and prognostically. In Senegal, since 2014, enormous progress has been made to improve the management of this disease. However, some challenges remain. The overall objective of this study was to assess the overall management of patients with STEMI. Methodology: This is a prospective, descriptive and analytical study over a period of 06 months from April 1st, 2023 to September 31th, 2023. All patients admitted to the four major cardiology departments in Dakar for STEMI were included. The socio-demographic, diagnostic, therapeutic and evolutionary parameters were studied. We entered the data with the Kobotoolbox software and analyzed the results using the SPSS software. The threshold of significance was a value of p &lt; 0.05. Results: We included 157 patients, the hospital prevalence was 11.7%. The sex ratio H/F was 2.48. The mean age of patients was 58 years. The average time between onset of pain and first medical contact (FMC) was 10.57 hours. The proportion of patients received before the first 12 hours was 79.6%. The coronary angiography rate was 66.5% and it was abnormal for 96.3%. It was predominantly one-vessel coronary artery disease (51%). The rate of completion of primary percutaneous coronary intervention (PCI) was 24.2%. Thrombolysis was performed in 32.5% of patients with a success rate of 49%. Hospital mortality was 10.8% or 17 patients. The factors of poor prognosis identified were: number of medical facilities consulted before admission to cardiology (p value = 0.04), presence of conductive disorders (p value = 0.006) and absence of PCI (p value = 0.04). Conclusion: STEMI is on the rise in our country. Diagnostic delays remain long. The management is suboptimal and sometimes dramatic consequences.
Best Practices for Dental Care in High-Risk Cardiac Patients
Authors: Ashish Pandey
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally, and managing dental care in high-risk cardiac patients presents unique challenges. The relationship between oral health and cardiovascular conditions highlights the importance of preventive and therapeutic dental interventions to optimize patient outcomes. This article reviews best practices for dental care in high-risk cardiac patients, focusing on pre-treatment assessment, oral hygiene protocols, antibiotic prophylaxis, and the management of co-existing conditions such as diabetes and hypertension.
From Detection to Recovery: How Artificial Intelligence is Changing the Landscape of Oral Cancer Management
Authors: Ashish Pandey
Journal: Clinical Cardiology and Cardiovascular Interventions (2025)

Oral cancer is a significant global health challenge, with rising incidences and high mortality rates, particularly in the late stages. Early detection and effective management are crucial for improving patient outcomes. Artificial intelligence (AI) is rapidly transforming oral cancer management by enhancing early detection, improving treatment planning, optimizing post-operative care, and supporting rehabilitation. This article explores the integration of AI into various stages of oral cancer management, including diagnosis, surgical treatment, post-operative care, and rehabilitation. It also addresses the ethical and regulatory challenges associated with the adoption of AI technologies in clinical practice, providing a comprehensive review of the current state and future prospects in this field.
Longitudinal Patient-Reported Outcomes in Older Adults With Aggressive Lymphomas Receiving Chemoimmunotherapy
Authors: P. Connor Johnson, Jeremy S. Abramson, Ann S. LaCasce, Philippe Armand, Jeffrey Barnes, Reid W. Merryman, Jacob Soumerai, Ephraim Hochberg, Ronald W. Takvorian, Caron A. Jacobson, Jennifer L. Crombie, David C. Fisher, Joel Schwartz, Robb S. Friedman, Julia Stacey, Daniel Yang, Bridget Coffey, Netana Markowitz, Oreofe O. Odejide, Areej El-Jawahri
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Aggressive non-Hodgkin lymphoma (aNHL) is more common in older adults. Although chemoimmunotherapy can yield durable remissions, it is also associated with significant toxicities. Despite this, longitudinal studies assessing patient-reported outcomes (PROs) with chemoimmunotherapy in this population are lacking. Patients and Methods: We conducted a longitudinal study of 105 adults aged ≥65 years who initiated up-front chemoimmunotherapy for aNHL across 2 academic centers and their community affiliates between September 2020 and January 2023. Quality of life (QoL) was assessed using the Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym), physical symptoms via the revised Edmonton Symptom Assessment Scale (ESAS-r), and psychological symptoms with the Hospital Anxiety and Depression Scale (HADS). Assessments were performed at baseline; 6, 12, 18, and 24 weeks post–therapy initiation; and 1 year post–therapy initiation. Frailty status was evaluated at baseline using the Fondazione Italiana Linfomi geriatric assessment (GA) and the Vulnerable Elders Survey-13 (VES-13). Linear mixed models were used to examine the trajectory of PROs over time, and linear regression was employed to identify factors associated with QoL at 1 year. Results: The median patient age was 73 years (range, 64–99), with 41.9% aged ≥75 years. Most patients (53.8%) had an age-adjusted International Prognostic Index (IPI) of 2/3, and 70.5% had diffuse large B-cell lymphoma. Overall, 50.5% and 45.7% were identified as frail or vulnerable on GA and VES-13, respectively. Longitudinal QoL, physical symptoms, anxiety, and depression all significantly improved over time (all P ≤.001). QoL improved regardless of age category (65–74 vs ≥75 years) or frailty status. In multivariate analyses, being married/living with partner was associated with better QoL at 1 year (β=11.6; P =.026), whereas frailty on GA (β= −9.90; P =.036) was associated with worse QoL. Conclusions: Older adults with aNHL receiving chemoimmunotherapy experienced significant and durable improvement in QoL, physical symptoms, and psychological health up to 1 year post–therapy initiation, irrespective of age or frailty status. However, frailty was associated with worse QoL at 1 year post–therapy initiation. These findings underscore the importance of integrating GAs into treatment planning for older adults with aNHL.