tbuckley/cabot-search huggingface dataset:
Prolyl-tRNA synthetase inhibitor as a novel first-in-class keloid treatment: Downregulation of de novo collagen synthesis and inflammatory cascade
Authors: Sally Min, Ki-Myo Kim, Joseph Hwang, Jaewoo Kim, Jun Ho Park, Joon Seok Park, Caroline H Lee, Ji-Ung Park
Journal: British Journal of Dermatology (2025)

Abstract Background Keloids are severe dermal fibrotic disorders caused by excessive deposition of collagen. Current therapies have high recurrence rates, and there is a high clinical need for a new fundamental approach. We focused on inhibiting proline, an essential amino acid for collagen biosynthesis. We developed DWN12088, a drug that downregulates prolyl-tRNA synthetase (PRS), an enzyme involved in proline ligation with its tRNA. This study aims to evaluate the therapeutic efficacy of this drug on keloids. Objectives We investigated the anti-fibrotic activity of selective PRS inhibitors and elucidated the importance of DWN12088 as a first-in-class therapeutic agent for keloids. Methods Patient-derived keloid fibroblasts (KFs) and keloid tissues were obtained to observe the upregulation of PRS. In addition, the anti-fibrotic activity of selective PRS inhibitors was studied using KFs, and their treatment efficacy was further validated in vivo using a KF xenograft severe combined immune-deficient (SCID) mouse model. Histological and immunohistochemistry analyses were performed with human-derived keloid tissues. Additional experiments included immunocytochemistry, cell viability analysis, migration analysis, and western blotting on KFs. Human KFs were injected into SCID mice to study the nodule formation and histological characteristics. Results Compared to normal fibroblasts and normal skin tissues, PRS was overexpressed in both KF and keloid tissues. A selective PRS inhibitor downregulated fibrotic markers, reduced migration capacity, and lowered collagen production in KFs. In a KF xenograft SCID mouse model, a selective PRS inhibitor effectively suppressed keloid formation and mitigated inflammation and fibrosis. Conclusions DWN12088, a selective PRS inhibitor, may be a novel first-in-class treatment modality that effectively prevents keloid development. Further clinical trials are required to verify the safety and clinical efficacy of PRS inhibitors for keloids. We believe that our study has applicability across several fibrotic wound problems such as hypertrophic scars.
Cardiovascular therapeutic targets of sodium-glucose co-transporter 2 (SGLT2) inhibitors beyond heart failure
Authors: Matteo Armillotta, Francesco Angeli, Pasquale Paolisso, Marta Belmonte, Emanuel Raschi, Guido Di Dalmazi, Sara Amicone, Lisa Canton, Damiano Fedele, Nicole Suma, Alberto Foà, Luca Bergamaschi, Carmine Pizzi
Journal: Pharmacology & Therapeutics (2025)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy. In addition to glycemic control and the osmotic diuretic effect, the inhibition of SGLT2 improves endothelial function and vasodilation, optimizing myocardial energy metabolism and preserving cardiac contractility. Moreover, SGLT2 inhibitors may exhibit anti-inflammatory properties and attenuate acute myocardial ischemia/reperfusion injury, thereby reducing cardiac infarct size, enhancing left ventricular function, and mitigating arrhythmias. These pleiotropic effects have demonstrated efficacy across various cardiovascular conditions, ranging from acute to chronic coronary syndromes and extending to arrhythmias, valvular heart disease, cardiomyopathies, cardio-oncology, and cerebrovascular disease. This review provides an overview of the current literature on the potential mechanisms underlying the effectiveness of SGLT2 inhibitors across a wide range of cardiovascular diseases beyond HF.
The Imperative for Hazard and Place-Specific Assessment of Heat Vulnerability
Authors: Joseph Karanja, Jennifer Vanos, Matei Georgescu, Amy E. Frazier, David Hondula
Journal: Environmental Health Perspectives (2025)

Representing vulnerability is crucial for informing targeted interventions, but existing vulnerability conceptualizations are too general for heat hazard-specific and place-specific relevance. Examining the key decision criteria centering around data choices, selection of input variables, methodological approaches, and theoretical conceptualizations are integral to progressing toward hazard-specific and place-specific vulnerability assessment. Moreover, decisions touching on Geographic Information Science (GIScience)-related issues (e.g., the implications of scale choices and accounting for contextual effects) impact how people who are at risk for adverse heat-health outcomes are represented. In turn, these representations influence how critical interventions are implemented. Given the prospects of increases in adverse heat-health outcomes associated with planetary and urban warming, it is crucial to examine how the representation of heat vulnerability can be enhanced for tailored interventions. This commentary examines the assumptions underpinning the decision criteria for heat vulnerability analysis and identifies associated implications while recommending priority future research. Reorienting general hazard conceptualizations to reflect contextual, heat-specific nuances is crucial for attenuating heat-related health outcomes. Heat vulnerability studies lack consistent decision criteria, which undermines progress toward hazard-specific and place-specific vulnerability relevance. Some of these limitations are attributable to the persistent application of general, all-hazards conceptualizations to hazard-specific studies. Moreover, inconsistent decision criteria undermine the replicability and validity of studies and propagate uncertainty while compromising progress toward standardized, consistent, scalable approaches, and testing of existing assumptions that could strengthen heat vulnerability theory. Given GIScience technologies are central to representing spatial patterns of vulnerability, the epistemological foundation of vulnerability theory can be strengthened when GIScience concepts (e.g., the operational scale of social-environmental determinants of health and assumptions underpinning spatial relationships) are considered during vulnerability representation. Examining decision criteria for heat vulnerability assessment is crucial to identifying optimal sets of heat-specific and place-specific risk indicators, thereby enhancing the representation of vulnerability. https://doi.org/10.1289/EHP14801.
Efficacy following discontinuation of sonidegib 200 mg daily treatment in patients with locally advanced basal cell carcinoma: Post hoc analysis of the 42-month BOLT study
Authors: Michael R Migden, Meenal Kheterpal, Brent Moody, Kunal Patel, Leonard Lionnet, Sakthivel Sivam, Joe Conti, Nicholas Squittieri, Aaron S Farberg
Journal: Journal of the American Academy of Dermatology (2025)
Clinical Benefit and Safety of Reduced Elective Dose in Definitive Radiotherapy for Head and Neck Squamous Cell Carcinoma: The UPGRADE-RT Multicenter Randomized Controlled Trial
Authors: Sven van den Bosch, Patricia A.H. Doornaert, Frank J.P. Hoebers, Bas Kreike, Marije R. Vergeer, Ellen M. Zwijnenburg, Maurice C. Cox, Gerjon Hannink, Tim Dijkema, Johannes H.A.M. Kaanders
Journal: Journal of Clinical Oncology (2025)

PURPOSE Definitive radiotherapy (RT) for head and neck cancer (HNC) has significant long-term toxicity with elective neck irradiation (ENI) as a major contributor. In this multicenter randomized trial, the clinical benefit and safety of definitive RT with reduced versus standard elective dose were compared. METHODS Newly diagnosed patients with cT2-4N0-2M0 HNC were accrued and treated in five Dutch centers (definitive accelerated RT, 68 Gy in 34 fractions in 5.5 weeks). Patients receiving concurrent chemotherapy were not eligible. Dose for ENI was randomly assigned (2:1; dose reduction, 43 Gy, versus control, 50 Gy). The primary outcome was normalcy of diet score at 1 year. The secondary outcome was recurrence in electively irradiated nodes at 2 years in the dose reduction group with the null hypothesis rejected if the upper-bound one-sided 95% CI exceeded 9%. RESULTS Between 2016 and 2022, 300 patients were randomnly assigned, of whom 295 were evaluable and included in analysis (dose reduction, 196 and control, 99). The mean normalcy of diet score at 1 year was 91.6 (95% CI, 88.5 to 94.7) in the dose reduction group and 92.6 (95% CI, 88.2 to 97.1) in the control group (mean difference, –1.1 [95% CI, –6.5 to 4.4]). The 2-year recurrence rate in electively irradiated nodes in the dose reduction group was 4.9% (upper-bound one-sided 95% CI, 7.5%). In the control group, this was 4.3% (upper bound one-sided 95% CI, 7.7%). Exploratory analyses demonstrated less acute dysphagia grade ≥3 and better xerostomia-related quality of life in the dose reduction group. CONCLUSION This is the second randomized controlled trial demonstrating that reduced elective dose is safe in definitive RT for HNC.
Sequential Infusion of Mesenchymal Stem Cell for Graft-Versus-Host Disease Prevention in Haploidentical Hematopoietic Stem Cell Transplantation: An Open-Label, Multicenter, Randomized Controlled Clinical Trial
Authors: Han Yao, Ruihao Huang, Haixia Fu, Ren Lin, Yanqi Zhang, Yimei Feng, Yu Wang, Ting Chen, Xiaoqi Wang, Lidan Zhu, Jia Liu, Yuqing Liu, Lu Zhao, Lu Wang, Peiyan Kong, Qin Wen, Cheng Zhang, Li Gao, Lei Gao, Qifa Liu, Xiaohui Zhang, Xiaojun Huang, Xi Zhang
Journal: Journal of Clinical Oncology (2025)

PURPOSE The aim of this open-label, multicenter, randomized controlled trial was to determine the efficacy and safety of sequential umbilical cord–derived mesenchymal stem cell (UC-MSC) infusion for graft-versus-host disease (GVHD) prevention within 3 months of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS This open-label study evaluated UC-MSC infusion (administer 1 × 10 6 /kg 4 hours before the commencement of day 0, once weekly for the first month after transplantation, once every 2 weeks for the second month, and once during the third month, totaling eight doses). The primary end point was the 2-year cumulative incidence of severe chronic GVHD (cGVHD). RESULTS In the primary analysis, 192 qualified participants between age 18 and 60 years with haplo-HSCT in three transplant centers in China were enrolled and randomly assigned to the MSC and control groups. In the primary analysis, the estimated 2-year cumulative incidence of severe cGVHD and all grades of cGVHD was lower in the MSC group than in the control group ( P = .033 and P = .022). The cumulative incidence of grade 1 to 4, 2 to 4, and 3 to 4 acute GVHD (aGVHD) in patients in the MSC group significantly decreased (all P &lt; .001). The 3-year GVHD-free and relapse-free survival (GRFS) rate in the MSC group was 62.4%, which was significantly higher than that in the control group (32.0%, hazard ratio [HR], 0.34, P &lt; .001). MSC infusion did not influence the cumulative incidence of relapse ( P = .34) and nonrelapse mortality ( P = .45). CONCLUSION Our findings suggest that sequential infusion of MSCs within 3 months after haplo-HSCT significantly reduced both the incidence and severity of cGVHD and aGVHD, manifesting as a better GRFS rate for patients.
Network analysis of extraintestinal manifestations and associated autoimmune disorders in Crohn’s disease and ulcerative colitis
Authors: Daniel C Baumgart, C Hing Cheng, Tian X Du, Michael D Parkes, Daniel C Sadowski, Eytan Wine, Frank Hoentjen, Brendan P Halloran, Aldo Montano-Loza, Sergio Zepeda-Gomez, Karen Wong, Farhad Peerani, Randolph Goebel, J Ross Mitchell
Journal: npj Digital Medicine (2025)

Abstract We detect and interactively visualize occurrence, frequency, sequence, and clustering of extraintestinal manifestations (EIM) and associated immune disorders (AID) in 30,334 inflammatory bowel disease (IBD) patients (Crohn’s disease (CD) n = 15924, ulcerative colitis (UC) n = 11718, IBD unclassified, IBD-U n = 2692, 52% female, median age 40 years (IQR: 25)) with artificial intelligence (AI). 57% (CD &gt; UC 60% vs. 54%, p &lt; 0.00001) had one or more EIM and/or AID. Mental, musculoskeletal and genitourinary disorders were most frequently associated with IBD: 18% (CD vs. UC 19% vs. 16%, p &lt; 0.00001), 17% (CD vs. UC 20% vs. 15%, p &lt; 0.00001) and 11% (CD vs. UC 13% vs. 9%, p &lt; 0.00001), respectively. AI detected 4 vs. 5 vs. 5 distinct EIM/AID communities with 420 vs. 396 vs. 467 nodes and 11,492 vs. 9116 vs. 16,807 edges (links) in CD vs. UC vs. IBD, respectively. Our newly developed interactive free web app shows previously unknown communities, relationships, and temporal patterns—the diseasome and interactome.
Response to: Correspondence on ‘2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria’ by Yeng et al
Authors: Medha Barbhaiya, Stephane Zuily, Alison Hendry, Florian Manneville, Francis Guillemin, Karen Costenbader, Doruk Erkan
Journal: Annals of the Rheumatic Diseases (2025)
Multiomics approaches for identifying the PANoptosis signature and prognostic model via a multimachine-learning computational framework for intrahepatic cholangiocarcinoma
Authors: Yanxi Yu, Yan You, Yuxin Duan, Meiqing Kang, Baoyong Zhou, Jian Yang, Kunli Yin, Wentao Ye, Ranning Xu, Hao Wang, Ziqi Zhang, Zuotian Huang, Yanyao Liu, Zhongjun Wu, Rui Tao, Rui Liao
Journal: Hepatology (2025)

Background &amp; Aims: The aims of the present study were to characterize the PANoptosis signature in intrahepatic cholangiocarcinoma (ICC) patients, construct a novel model to guide clinical diagnosis and treatment, and further explore the associated molecular mechanisms of drug resistance. Approach &amp; Results: In total, 85 PANoptosis-related genes that possess both PANoptosis and multiomics features were respectively screened from transcriptomic data from the OEP001105 public cohort and from transcriptomic and proteomic sequencing data from The First Affiliated Hospital of Chongqing Medical University. A novel framework integrating Cox regression analysis and five machine learning algorithms was developed to identify the five hub genes (POSTN, SFN, MYOF, HOGA1, and PECR), The subsequently constructed PANoptosis risk score (PANRS) demonstrate outstanding performance in predicting prognosis and clinical translation across multicenter cohorts with multiomics profiling. Bulk and single-cell transcriptome profiling were used to investigate the tumor microenvironment (TME), emphasizing the crucial role of macrophages in the TME of ICCs. Moreover, a positive spatial correlation of CAFs-derived POSTN expression with TAMs infiltration and PD-L1/PD-L2 expression in ICC patients was observed, suggesting that overexpression of POSTN may lead to resistance to ICB therapy in ICC patients. Conclusion: The present study identified a precise prognostic and treatment strategy for ICC patients prone to PANoptosis, investigated the molecular mechanisms of PANoptosis in ICC cells, and highlighted the potential clinical relevance of the PANRS in predicting prognosis and therapy response. These findings will help guide clinical treatment strategies for ICC.
Evidence-based personalised medicine in critical care: a framework for quantifying and applying individualised treatment effects in patients who are critically ill
Authors: Elizabeth S Munroe, Alexandra Spicer, Andrea Castellvi-Font, Ann Zalucky, Jose Dianti, Emma Graham Linck, Victor Talisa, Martin Urner, Derek C Angus, Elias Baedorf-Kassis, Bryan Blette, Lieuwe D Bos, Kevin G Buell, Jonathan D Casey, Carolyn S Calfee, Lorenzo Del Sorbo, Elisa Estenssoro, Niall D Ferguson, Rachel Giblon, Anders Granholm, Michael O Harhay, Anna Heath, Carol Hodgson, Timothy Houle, Cong Jiang, Lina Kramer, Patrick R Lawler, Aleksandra Leligdowicz, Fan Li, Kuan Liu, Amelia Maiga, David Maslove, Colin McArthur, Daniel F McAuley, Ary Serpa Neto, Charissa Oosthuysen, Anders Perner, Hallie C Prescott, Bram Rochwerg, Sarina Sahetya, Mariia Samoilenko, Mireille E Schnitzer, Kevin P Seitz, Faraaz Shah, Manu Shankar-Hari, Pratik Sinha, Arthur S Slutsky, Edward T Qian, Steve A Webb, Paul J Young, Fernando G Zampieri, Ryan Zarychanski, Eddy Fan, Matthew W Semler, Matthew Churpek, Ewan C Goligher
Journal: The Lancet Respiratory Medicine (2025)
Priorities for addressing mental health conditions and substance use disorders in prisons in sub-Saharan Africa: expert consensus from a Delphi panel
Authors: Helen E Jack, Aish Lovett, Hiwot Weldemariam, Atalay Alem, Serge Dali, Sakios Muduma, Murugi Micheni, Letitia Pienaar, Charlene Sunkel, Zoë Senter, Maryia Shaban, Lydia Chwastiak, Sarah Walker, Adegboyega Ogunwale
Journal: The Lancet Psychiatry (2025)
Clinical validation of droplet digital PCR assays in detecting BRAFV600-mutant circulating tumour DNA as a prognostic biomarker in patients with resected stage III melanoma receiving adjuvant therapy (COMBI-AD): a biomarker analysis from a double-blind, randomised phase 3 trial
Authors: Mahrukh M Syeda, Georgina V Long, James Garrett, Victoria Atkinson, Mario Santinami, Dirk Schadendorf, Axel Hauschild, Michael Millward, Mario Mandala, Vanna Chiarion-Sileni, Michael Smylie, Georgy M Manikhas, Reinhard Dummer, Jennifer M Wiggins, Saim Ali, Sachin Bajirao Adnaik, Monique Tan, Maya Dajee, David Polsky
Journal: The Lancet Oncology (2025)
Development of a question prompt list for people living with primary biliary cholangitis - A Delphi Study –
Authors: Ellen Werner, Maria C B van Hooff, Gemma H X Weijsters, Nadir Abbas, Alessio Gerussi, José A Willemse, Robert Mitchell-Thain, Angela Leburgue, Gideon M Hirschfield, Christophe Corpechot, Christoph Schramm, Cynthia Levy, Frederik Nevens, Jef Verbeek, Andrew L Mason, George Dalekos, Nora Cazzagon, George F Mells, Kris V Kowdley, Marco Carbone, David E Jones, Bettina E Hansen, Palak J Trivedi, Adriaan J van der Meer
Journal: Clinical Gastroenterology and Hepatology (2025)

Clinical practice guidelines support caregivers to manage liver diseases. However, people with lifelong conditions often lack guidance to understand what aspects of care are most important and how their disease should be managed. This study aimed to create a question prompt list (QPL) for individuals with primary biliary cholangitis (PBC) including key questions (directed) to their treating physician which are most likely to improve their outcome. International PBC-professionals including patient representatives rated and ranked questions related to 9 aspects of PBC care. Questions rated by >70% as moderately/very important were considered best candidate questions (BCQs) for the QPL. Results of the survey were discussed during two in-person meetings, upon which the questions and/or QPL were amended. Based on 108 respondents, 11 out of 43 questions were considered BCQs. After two in-person meetings (64 attendees), the final QPL contained 8 questions and was unanimously approved by 19 members of the study team during the consensus meeting. The included questions referred to the risk of disease progression, presence of cirrhosis, need of second-line therapy, need of repeated liver stiffness measurements, bone health, and availability of patient information and support. Two BCQs addressing options to manage pruritus and fatigue were combined on the QPL. In addition, one question regarding first-line therapy was included despite being rated as moderately/very important by 68.5%. The PBC patient question prompt list serves as a user-facing document, to enhance the patient experience, and drive value-based healthcare in routine clinical practice.
Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial.
Authors: Lucía Guilabert, James L Buxbaum, Ana García García de Paredes, Edgard E Lozada-Hernández, Rodrigo Jover, Enrique de-Madaria
Journal: Clinical Gastroenterology and Hepatology (2025)
Copenhagen Prospective Personalized Oncology (CoPPO) – Impact of comprehensive genomic profiling in more than 2000 patients in a Phase I setting
Authors: L Belcaid, M Højgaard, I Tuxen, I Spanggaard, U Lassen, L Robinson, M Rossing, F Bagger, L B Ahlborn, A Y Schmidt, J P Hasselby, E Santoni-Rugiu, F C Nielsen, C W Yde, K Rohrberg
Journal: Annals of Oncology (2025)
Abrocitinib versus dupilumab: impact on skin barrier function and proteomics in atopic dermatitis
Authors: Jui-Wen Chang, Xiaobao Huang, Wenjing Jiang, Lerong Lun, Wenhui Liu, Rui Xu, Rui Tang, Xinyang Xie, Wanying Zhai, Huilin Su, Jiande Han, Ruzeng Xue, Fang Wang
Journal: Journal of the American Academy of Dermatology (2025)
Innovative Sarcoma Therapy Using Multifaceted Nano-PROTAC-Induced EZH2 Degradation and Immunity Enhancement
Authors: Zhihao Chen, Yi Tai, Chuangzhong Deng, Yameng Sun, Hongmin Chen, Tianqi Luo, Jiaming Lin, Weiqing Chen, Huaiyuan Xu, Guohui Song, Qinglian Tang, Jinchang Lu, Xiaojun Zhu, Shijun Wen, Jin Wang
Journal: Biomaterials (2025)
Linoleic acid co-administration promotes oral delivery of exenatide-loaded butyrate-decorated nanocapsules
Authors: Haoyang Yuan, Peifu Xiao, Fan Wang, Chen Guo, Shu Pan, Mai Jiang, Shicheng Hou, Yunong Sun, Yibo Wang, Yu Zhang, Tian Yin, Haibing He, Jingxin Gou, Xing Tang
Journal: Journal of Controlled Release (2025)
The impact of dosage timing for inhaled corticosteroids in asthma: a randomised three-way crossover trial
Authors: Ran Wang, Robert Maidstone, Dave Singh, David Ray, Andrew S Loudon, Angela Simpson, Hannah Jane Durrington
Journal: Thorax (2025)

Background Asthma demonstrates a robust daily rhythm, with airflow obstruction and airway inflammation peaking overnight. Aligning the timing of drug administration with rhythms in disease (chronotherapy) may improve therapeutic efficacy. We aimed to evaluate the impact of dosage timing for inhaled corticosteroids in asthma. Methods This is a randomised three-way crossover trial. Participants with mild to moderate atopic asthma were randomised to beclometasone dipropionate: (1) 400 µg once daily between 08:00 and 09:00 (OD AM ); (2) 400 µg once daily between 15:00 and 16:00 (OD PM ); and (3) 200 µg twice daily between 08:00 and 09:00 and between 20:00 and 21:00 (BD) for 28 days, with a 2 week washout period in between treatment periods. Six-hourly spirometry and biomarkers were measured over 24 hours following the run-in period and at the end of each treatment period. Results Of 25 participants, 21 completed all regimens. OD PM was superior in improving 22:00 FEV 1 (median (IQR): +160 (+70, +270) ml) compared with OD AM (−20 (−80, +230) ml) and BD (+80 (−20, +200) ml). OD PM resulted in better overnight (22:00 and 04:00) suppression in blood eosinophil counts compared with BD and OD AM . All regimens improved asthma control and reduced fractional exhaled nitric oxide and serum cortisol levels with no difference among dosing regimens. Conclusion OD PM better suppresses the nocturnal dip in lung function and peak of blood eosinophil counts compared with BD and OD AM ; this was without an increase in adverse events. Future trials are warranted to validate these findings in real-life settings and to determine which population may best benefit from chronotherapy.
TCTAP C-114 A Challenging Case Report: Primary PCI to Left Main Coronary Artery Stenosis in a Patient With Acute Coronary Syndrome [qRBBB] Post Cardiac Arrest Caused by Extrinsic Mediastinal Mass [Synovial Sarcoma] Compression
Authors: Dasarath Boppana, Gopalakrishna Koduru, Raghuram Palaparthi, Chowdary Parvathaneni Sarada Srinivasa, Purnachandrarao Kondru, Somasekhar Ghanta, Venkata R.S. Subrahmanya Sarma Palaparthi, Mounika Boppana, Ramkishore Y, Sasidhar Yendapalli, Prasad Maganti
Journal: Journal of the American College of Cardiology (2025)
TCTAP C-131 The Peril of Coronary Perforation in Acute STEMI
Authors: Dena Karina Firmansyah, Dafsah Arifa Juzar, Nanda Iryuza, Arwin Saleh Mangkuanom, Amir Aziz Alkatiri, Doni Firman
Journal: Journal of the American College of Cardiology (2025)