tbuckley/cabot-search huggingface dataset:
The giant cell arteritis (GCA) ultrasound score (OGUS) at diagnosis and after initial treatment predicts future relapses in GCA patients: results of a multicentre prospective study
Authors: Sara Monti, Cristina Ponte, Valentin S Schäfer, Davide Rozza, Carlo Scirè, Giulia Franchi, Alessandra Milanesi, Nikita Khmelinskii, Simon M Petzinna, Greta Carrara, Cristina Di Nicola, João Eurico Fonseca, Carlomaurizio Montecucco, Wolfgang A Schmidt, Christian Dejaco, Raashid A Luqmani
Journal: Annals of the Rheumatic Diseases (2025)

To test the prognostic role of ultrasonography at diagnosis of giant cell arteritis (GCA) and the change of ultrasound abnormalities during the initial weeks of follow-up for the prediction of relapse, vascular complications, or initiation of disease-modifying antirheumatic drugs (DMARDs). Prospective, multicentre study of patients with new onset GCA undergoing serial ultrasound assessment at fixed time points. The Outcome Measures in Rheumatology (OMERACT) GCA ultrasonography score (OGUS) was used to quantify vessel wall abnormalities. Relapse was defined as recurrence of GCA-related symptoms or rise of inflammatory markers requiring treatment. A multivariable Poisson model with robust variance estimator was applied, including age, sex, large vessel GCA, glucocorticoid cumulative dose, and baseline OGUS as covariates. Ninety-seven patients were assessed in 849 visits. Thirty-five (36.1%) patients experienced a total of 66 relapses, with median time to relapse of 210 days (IQR, 94.5-323.5). Higher OGUS at diagnosis was associated with an increased risk of relapse within 12 months (incidence rate ratio [IRR] for each 1 point increase in OGUS: 1.85; 95% CI, 1.05-3.32). At multivariable analysis, OGUS normalisation (score <1) over the first 3 weeks was negatively associated with subsequent relapses (IRR, 0.44; 95% CI, 0.22-0.88) and predicted time to first relapse. OGUS reduction over the first 12 weeks was inversely associated with initiation of DMARDs. Ischaemic/aortic complications were rare. Ultrasonography has a prognostic role in GCA and can inform risk stratification. Higher OGUS at diagnosis is associated with relapse, while a higher degree and rapidity of improvement in the first weeks are linked with lower relapse rate.
Impact of clinical subtype and sex on first-line biologic therapy discontinuation in axial spondyloarthritis
Authors: Patricia Remalante-Rayco, Emmanuel S Baja, Zeynep Baskurt, Tina Chim, Carlo Irwin A Panelo, Evelyn Osio-Salido, Robert D Inman, Leonila F Dans, Nigil Haroon
Journal: Annals of the Rheumatic Diseases (2025)

To estimate the main and interaction effects of axial spondyloarthritis (axSpA) subtype and sex on first biologic disease-modifying antirheumatic drug (bDMARD) discontinuation. This retrospective cohort study included nonradiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA) patients initiating tumour necrosis factor or interleukin-17 inhibitors. Modified Poisson regressions were used to estimate risk ratios (RRs) for the association of subtype and sex with discontinuation, adjusting for baseline covariates. Interaction was assessed using the relative excess risk due to interaction (RERI) and ratio of RRs. In addition, bDMARD survival rates were analysed using Kaplan-Meier curves. Among 469 patients, 64% discontinued their first bDMARD. Nr-axSpA (RR, 1.80; 95% CI, 1.26-2.59) and female sex (RR, 1.49; 95% CI, 1.081-2.045) were significantly associated with discontinuation. Positive interaction trends between subtype and sex were observed on additive (RERI 0.49, 95% CI, -0.78 to 1.75) and multiplicative (RR ratio, 1.05; 95% CI, 0.55-2.03) scales, though not statistically significant. Nr-axSpA females had twice the discontinuation risk of r-axSpA males (hazard ratio, 2.30; 95% CI, 1.68-3.15, P < .001). bDMARD survival over 20 years was significantly lower in nr-axSpA and female patients. Nr-axSpA and female patients face a significantly higher risk of bDMARD discontinuation and shorter bDMARD survival. Although the combined effect of subtype and sex trended higher, it was not statistically significant. These findings underscore the need to address potential treatment challenges in female nr-axSpA patients.
Prognostic Implications and Global Perspectives of Atrial Fibrillation in Patients Hospitalized for Heart Failure
Authors: Janice Y Chyou, Wan Ting Tay, Jasper Tromp, Wouter Ouwerkerk, Kai Hang Yiu, John G F Cleland, Sean P Collins, Christiane E Angermann, Georg Ertl, Ulf Dahlström, Kenneth Dickstein, Sergio V Perrone, Mathieu Ghadanfar, Anja Schweizer, Achim Obergfell, Gerasimos Filippatos, Carolyn S P Lam
Journal: JACC Heart Failure (2025)
Disparities Among Immigrants and Native Patients in Denmark With New-Onset Heart Failure With Reduced Ejection Fraction
Authors: Sam Aiyad Ali, Naja Emborg Vinding, Jawad H Butt, Johanna Krøll, Johan E Larsson, Morten Schou, Emil L Fosbøl, Brian B Løgstrup, Inge Schjødt, Pardeep S Jhund, Lars Køber, Finn Gustafsson, Naveed Sattar, John J V McMurray, Søren Lund Kristensen
Journal: JACC Heart Failure (2025)
Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF
Authors: Samir Patel, Venkatesh K Raman, Charles Faselis, Gregg C Fonarow, Phillip H Lam, Amiya A Ahmed, Paul A Heidenreich, Stefan D Anker, Prakash Deedwania, Charity J Morgan, Sijian Zhang, Hans Moore, Janani Rangaswami, George Bakris, Javed Butler, Helen M Sheriff, Richard M Allman, Qing Zeng-Treitler, Wen-Chih Wu, Ali Ahmed
Journal: JACC Heart Failure (2025)
Beta-Blockers and Long-Term Mortality in Takotsubo Syndrome
Authors: Sergio Raposeiras-Roubin, Francesco Santoro, Luca Arcari, Ravi Vazirani, Giuseppina Novo, Aitor Uribarri, Mariano Enrica, Javier Lopez-Pais, Federico Guerra, Fernando Alfonso, Toni Pätz, Clara Fernandez-Cordon, Roberta Montisci, Miguel Corbi-Pascual, Maria Francesca Marchetti, Manuel Almendro, Luca Cacciotti, Oscar Vedia, Ibrahim El-Battrawy, Emilia Blanco-Ponce, Natale Daniele Brunetti, Ibrahim Akin, Manuel Martinez-Sellés, Holger Thiele, Thomas Stiermaier, Ingo Eitel, Ivan J Nuñez-Gil
Journal: JACC Heart Failure (2025)
Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry
Authors: Cecilia Bonolo de Campos, Chantal E. McCabe, Laura A. Bruins, Daniel R. O’Brien, Sochilt Brown, Renee C. Tschumper, Cristine Allmer, Yuan Xiao Zhu, Kari G. Rabe, Sameer A. Parikh, Neil E. Kay, Huihuang Yan, James R. Cerhan, John N. Allan, Richard R. Furman, J. Brice Weinberg, Danielle M. Brander, Diane F. Jelinek, Marta Chesi, Susan L. Slager, Esteban Braggio
Journal: Blood Cancer Journal (2025)

Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestry (AA). To begin to address this gap, we evaluated whether differences exist in the genetic and transcriptomic features of 157 AA and 440 EA individuals diagnosed with CLL. We sequenced 59 putative driver genes and found an increased frequency of high-impact mutations in AA CLL, including genes of the DNA damage repair (DDR) pathway. Telomere erosion was also increased in AA CLL, amplifying the notion of increased genomic instability in AA CLL. Furthermore, we found transcription enrichment of the Tumor Necrosis Factor-alpha (TNFα) Signaling via NF-κB pathway in AA CLL compared to EA CLL, suggesting that tumor promoting inflammation plays an important role in AA CLL. In summary, these results suggest that genomic instability and NF-kB activation is more prevalent in AA CLL than EA CLL.
Artificial intelligence improves submucosal vessel detection during third space endoscopy
Authors: Markus Wolfgang Scheppach, Robert Mendel, Anna Muzalyova, David Rauber, Andreas Probst, Sandra Nagl, Christoph Römmele, Hon Chi Yip, Ho Shing Louis Lau, Stefan Karl Gölder, Arthur Schmidt, Konstantinos Kouladouros, Mohamed Abdelhafez, Benjamin M Walter, Michael Meinikheim, Philip Wai Yan Chiu, Christoph Palm, Helmut Messmann, Alanna Ebigbo
Journal: Endoscopy (2025)

Background and study aims: While artificial intelligence (AI) shows high potential in decision support for diagnostic gastrointestinal endoscopy, its role in therapeutic endoscopy remains unclear. Third space endoscopic procedures pose the risk of intraprocedural bleeding. Therefore, we aimed to develop an AI algorithm for intraprocedural blood vessel detection. Patients and Methods: Using a test dataset with 101 standardized video clips containing 200 predefined submucosal blood vessels, 19 endoscopists were evaluated for the vessel detection rate (VDR) and time (VDT) with and without support of an AI algorithm. Test subjects were grouped according to experience in ESD. Results: With AI support, endoscopists VDR increased from 56.4% [CI 54.1–58.6] to 72.4% [CI 70.3–74.4]. Endoscopists‘ VDT dropped from 6.7sec [CI 6.2-7.1] to 5.2sec [CI 4.8-5.7]. False positive (FP) readings appeared in 4.5% of frames and were marked significantly shorter than true positives (6.0sec [CI 5.28-6.70] vs. 0.7sec [CI 0.55-0.87]). Conclusions: AI improved the vessel detection rate and time of endoscopists during third space endoscopy. While these data need to be corroborated by clinical trials, AI may prove to be an invaluable tool for the improvement of endoscopic interventions.
From barbiturates to ganaxolone: The importance of chirality in drug development and in understanding the actions of old and new antiseizure medications
Authors: Meir Bialer, Emilio Perucca
Journal: Pharmacology & Therapeutics (2025)

Out of 37 antiseizure medications (ASMs) currently in the market, 17 are chiral molecules and an additional one (oxcarbazepine) is a prodrug of the chiral compound licarbazepine. Of the 17 chiral ASMs, six (ethosuximide, fenfluramine, methsuximide, mephobarbital, stiripentol and vigabatrin) are marketed as racemates, and the remainder are licensed as enantiomerically pure medicines. Of note, all chiral ASMs introduced prior to 1990 were marketed as racemates. Stiripentol, fenfluramine and vigabatrin are the only racemic ASMs approved by the FDA >10 years after the release of regulatory guidelines on the development of chiral medicines. Despite the fact that pharmacokinetic and pharmacodynamic differences between enantiomers have been recognized for decades, the importance of chirality in understanding the biological actions of ASMs is not widely appreciated, and many recent publications on racemic ASMs refer to these medications as if they were a single molecular entity. In the present article, we provide a critical review of chiral ASMs developed between the 1920s, when mephobarbital was introduced, and 2022, when the last chiral ASM (ganaxolone) was approved. We summarize available data on stereoselective differences in pharmacokinetics and pharmacodynamics of ASMs marketed as racemates. We also discuss regulatory aspects related to the introduction of racemic medicines within the current regulatory scenario in Europe and the U.S., focusing on stiripentol, vigabatrin and fenfluramine as examples of different approaches. We identified a number of critical knowledge gaps that are relevant to the use of chiral drugs in epilepsy, including a remarkable lack of published information on the comparative pharmacokinetics, toxicity and antiseizure activity of the enantiomers of most racemic ASMs. The importance of chirality aspects in understanding the clinical actions of racemic ASMs is discussed, together with the rationale for the development of enantiomerically pure follow-up compounds with potentially improved efficacy, safety and commercial viability.
Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy
Authors: Hongzhen Li, Zhiheng Zhang, Zhao Shi, Siqi Zhou, Shuang Nie, Yuanyuan Yu, Lingling Zhang, Yifeng Sun, Chao Fang, Jingxiong Hu, Yiqi Niu, Kathleen Schuck, Lei Wang, Kuirong Jiang, Zipeng Lu, Christoph Kahlert, Susanne Roth, Martin Loos, Ingrid Herr, Yoshiaki Sunami, Jörg Kleeff, Helmut Friess, Maximilian Reichert, Zahra Dantes, Xiaoping Zou, Christoph W Michalski, Shanshan Shen, Bo Kong
Journal: Cell Reports Medicine (2025)

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and characterized by pronounced desmoplasia. PDAC cells communicate with cancer-associated fibroblasts (CAFs) in a paracrine/reciprocal manner, substantially promoting tumor growth and desmoplastic responses. This study highlights the critical role of anterior gradient 2 (AGR2), an endoplasmic reticulum protein disulfide isomerase, secreted by PDAC cells to activate CAFs via the Wnt signaling pathway. Activated CAFs, in turn, secrete insulin-like growth factor 1 (IGF1), which enhances AGR2 expression and secretion in PDAC cells through the IGF1 receptor (IGF1R)/c-JUN axis. Within PDAC cells, AGR2 acts as a thioredoxin, aiding the folding and cell surface presentation of IGF1R, essential for PDAC's response to CAF-derived IGF1. This reciprocal AGR2/IGF1 signaling loop intensifies desmoplasia, immunosuppression, and tumorigenesis, creating a harmful feedback loop. Targeting both pathways disrupts this interaction, reduces desmoplasia, and restores anti-tumor immunity in preclinical models, offering a promising therapeutic strategy against PDAC.
GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica
Authors: William F Jiemy, Anqi Zhang, Wayel H Abdulahad, Rosanne D Reitsema, Yannick van Sleen, Maria Sandovici, Guillermo Carvajal Alegria, Divi Cornec, Valérie Devauchelle-Pensec, Patrice Hemon, Baptiste Quéré, Sara Boukhlal, Caroline Roozendaal, Thomas Christian Kwee, Bhaskar Dasgupta, Arjan Diepstra, Peter Heeringa, Elisabeth Brouwer, Kornelis S M van der Geest
Journal: Annals of the Rheumatic Diseases (2025)

Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR. Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7). Monocytes (CD14highCD16- and CD14highCD16+) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF. The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.
Biocompatible and Size-Dependent Melanin-Like Nanocapsules for Efficient Therapy in Hyperoxia-Induced Acute Lung Injury
Authors: Yahong Han, Jie Dong, Liyan Zhang, Tao Yue, Wenjing Zhao, Caifang Gao, Jinghua Sun, Ruiping Zhang
Journal: Biomaterials (2025)
FUTURE-AI: international consensus guideline for trustworthy and deployable artificial intelligence in healthcare
Authors: Karim Lekadir, Alejandro F Frangi, Antonio R Porras, Ben Glocker, Celia Cintas, Curtis P Langlotz, Eva Weicken, Folkert W Asselbergs, Fred Prior, Gary S Collins, Georgios Kaissis, Gianna Tsakou, Irène Buvat, Jayashree Kalpathy-Cramer, John Mongan, Julia A Schnabel, Kaisar Kushibar, Katrine Riklund, Kostas Marias, Lameck M Amugongo, Lauren A Fromont, Lena Maier-Hein, Leonor Cerdá-Alberich, Luis Martí-Bonmatí, M Jorge Cardoso, Maciej Bobowicz, Mahsa Shabani, Manolis Tsiknakis, Maria A Zuluaga, Marie-Christine Fritzsche, Marina Camacho, Marius George Linguraru, Markus Wenzel, Marleen De Bruijne, Martin G Tolsgaard, Melanie Goisauf, Mónica Cano Abadía, Nikolaos Papanikolaou, Noussair Lazrak, Oriol Pujol, Richard Osuala, Sandy Napel, Sara Colantonio, Smriti Joshi, Stefan Klein, Susanna Aussó, Wendy A Rogers, Zohaib Salahuddin, Martijn P A Starmans
Journal: BMJ (2025)

Despite major advances in artificial intelligence (AI) research for healthcare, the deployment and adoption of AI technologies remain limited in clinical practice. This paper describes the FUTURE-AI framework, which provides guidance for the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI Consortium was founded in 2021 and comprises 117 interdisciplinary experts from 50 countries representing all continents, including AI scientists, clinical researchers, biomedical ethicists, and social scientists. Over a two year period, the FUTURE-AI guideline was established through consensus based on six guiding principles—fairness, universality, traceability, usability, robustness, and explainability. To operationalise trustworthy AI in healthcare, a set of 30 best practices were defined, addressing technical, clinical, socioethical, and legal dimensions. The recommendations cover the entire lifecycle of healthcare AI, from design, development, and validation to regulation, deployment, and monitoring.
Endothelial cell pY397-FAK expression predicts risk of breast cancer recurrences after radiotherapy in SweBCG91-RT cohort
Authors: Rebecca J .G. Drake, Amalia H. Landén, Erik Holmberg, Axel Stenmark Tullberg, Fredrika Killander, Emma Niméus, Alexander Jordan, Jennifer McGuinness, Per Karlsson, Kairbaan Hodivala-Dilke
Journal: Clinical Cancer Research (2025)

Abstract PURPOSE: Identifying biomarkers of radiotherapy (RT) response is important for optimising the treatment of early breast cancer (BC). Here we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomised study. Preclinical data suggests an enhanced effect of RT with low EC_ pY397-FAK expression. METHODS: We analysed tissue microarrays (TMAs) from the SweBCG91-RT (stage I-II, lymph node-negative) BC cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT. TMA sections were immunostained for pY397-FAK, CD31, α-smooth-muscle-actin (αSMA) and pan-cytokeratin (panCK). HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, panCK+ tumour epithelial cells (TCs) and αSMA+ mural/stromal cells per core. For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence (LRR) and ‘all recurrence’, respectively, as dependent variables, and RT and EC_pY397-FAK as independent variables. RESULTS: EC_ pY397-FAK expression was not predictive for the primary endpoint, LRR (p=0.098), but the direction of the RT effect was in line with preclinical findings. For the secondary endpoint, all recurrence, there was a significant interaction (p=0.026) between EC_ pY397-FAK and RT. Without RT, higher EC_ pY397-FAK expression resulted in lower risk for all recurrence (HR 0.74 per SD, CI 95% 0.57-0.96, p=0.026). CONCLUSION: Within the first 5-years post-BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression. However, without RT low EC_pY397-FAK expression is associated with a higher risk of recurrence.
Rezafungin in special populations with candidaemia and/or invasive candidiasis
Authors: Oliver A. Cornely, Hervé Dupont, Malgorzata Mikulska, Riina Rautemaa-Richardson, Carolina Garcia-Vidal, George R. Thompson, Martin Hoenigl
Journal: Journal of Infection (2025)

Highlights•Pharmacokinetics/pharmacodynamics of antifungals can be impacted by various factors•Special populations with candidaemia/invasive candidiasis may need dose alterations•Such special populations include the elderly, obese or those with organ dysfunction•Rezafungin appears suitable for many special populations without dose modifications•Future research should aim to generate data on rezafungin in other populationsSummaryAchieving and maintaining therapeutic drug exposures with antifungals can be challenging in special patient populations, such as those with organ dysfunction (liver or kidney) or obesity, or elderly patients, due to dose–exposure relationships and potential drug–drug interactions. Dose adjustments may be needed in these populations to maintain therapeutic efficacy and/or prevent toxicity. We reviewed specific dosing considerations for antifungals in special populations with candidaemia and/or invasive candidiasis, focusing on those relating to echinocandins (based on prescribing information), and then explored the utility of the second-generation echinocandin rezafungin in treating these populations (based on currently available data identified from a PubMed and congress abstract search). Available data showed that echinocandins may sometimes require dosing modifications for special populations with candidaemia/invasive candidiasis, primarily due to decreases in pharmacokinetic exposures. Rezafungin appears to be suitable for use in a variety of special populations without the need for dose modifications based on available data, including patients with organ dysfunction or obesity, and elderly and critically ill patients. Further research is needed in populations where rezafungin data are not available including children, people living with HIV, patients receiving ECMO and those with underlying neurological conditions.