tbuckley/cabot-search huggingface dataset:
Erythrocyte-derived extracellular vesicles induce endothelial dysfunction through arginase-1 and oxidative stress in type 2 diabetes
Authors: Aida Collado, Rawan Humoud, Eftychia Kontidou, Maria Eldh, Jasmin Swaich, Allan Zhao, Jiangning Yang, Tong Jiao, Elena Domingo, Emelie Carlestål, Ali Mahdi, John Tengbom, Ákos Végvári, Qiaolin Deng, Michael Alvarsson, Susanne Gabrielsson, Per Eriksson, Zhichao Zhou, John Pernow
Journal: Journal of Clinical Investigation (2025)

Red blood cells (RBCs) induce endothelial dysfunction in type 2 diabetes (T2D), but the mechanism by which RBCs communicate with the vessel is unknown. This study tested the hypothesis that extracellular vesicles (EVs) secreted by RBCs act as mediators of endothelial dysfunction in T2D. Despite a lower production of EVs derived from RBCs of T2D patients (T2D RBC-EVs), their uptake by endothelial cells was greater than that of EVs derived from RBCs of healthy individuals (H RBC-EVs). T2D RBC-EVs impaired endothelium-dependent relaxation and this effect was attenuated following inhibition of arginase in EVs. Inhibition of vascular arginase or oxidative stress also attenuated endothelial dysfunction induced by T2D RBC-EVs. Arginase-1 was detected in RBC-derived EVs, and arginase-1 and oxidative stress were increased in endothelial cells following co-incubation with T2D RBC-EVs. T2D RBC-EVs also increased arginase-1 protein in endothelial cells following mRNA silencing and in the endothelium of aortas from endothelial cell arginase 1 knockout mice. It is concluded that T2D-RBCs induce endothelial dysfunction through increased uptake of EVs that transfer arginase-1 from RBCs to the endothelium to induce oxidative stress and endothelial dysfunction. These results shed important light on the mechanism underlying endothelial injury mediated by RBCs in T2D.
Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression
Authors: Isidoro Cobo, Jessica Murillo-Saich, Mohnish Alishala, Stephen Calderon, Roxana Coras, Benjamin Hemming, Faith Inkum, Fiorella Rosas, Riku Takei, Nathan Spann, Thomas A Prohaska, Paulo V G Alabarse, Se-Jin Jeong, Christian K Nickl, Anyan Cheng, Benjamin Li, Andrea Vogel, Thomas Weichhart, José J Fuster, Thomas Le, Tara R Bradstreet, Ashlee M Webber, Brian T Edelson, Babak Razani, Benjamin L Ebert, Reshma Taneja, Robert Terkeltaub, Ru Liu Bryan, Monica Guma, Christopher K Glass
Journal: Immunity (2025)
Preclinical characterization of the anti-leukemia activity of the CD123 antibody-drug conjugate, pivekimab sunirine (IMGN632)
Authors: Frances M. Cole, George S. Laszlo, Margaret C. Lunn-Halbert, Allie R. Kehret, Patrick A. Zweidler-McKay, Eduardo Rodríguez-Arbolí, David Wu, Kyle Nyberg, Junyang Li, Sheryl Y. T. Lim, Camryn M. Pettenger-Willey, Sribalaji Lakshmikanthan, Roland B. Walter
Journal: Leukemia (2025)
ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis
Authors: Shelley Herbrich, Mehdi Chaib, Padmanee Sharma
Journal: Journal for ImmunoTherapy of Cancer (2025)

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models. These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models. This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T therapy against solid tumors and underscores the critical role of ICOS signaling in enhancing therapeutic outcomes. Here, we discuss the implications of these findings for TNBC treatment, the importance of understanding and exploiting ICOS biology in immunotherapies, and future directions for optimizing ICOS CAR-T cell therapies in solid tumor immunotherapy.
Anti-interleukin-23 treatment linked to improved <i>Clostridioides difficile</i> infection survival
Authors: Gregory R. Madden, Robert Preissner, Saskia Preissner, William A. Petri
Journal: Gut Microbes (2025)

Clostridioides difficile is a leading cause of healthcare-associated infection, and an unacceptably high proportion of patients with C. difficile infection die despite conventional antibiotic treatment. Host-directed immunotherapy has been proposed as an ideal treatment modality for C. difficile infection to mitigate the underlying toxin-mediated pathogenic immune response while sparing protective gut microbes. Interleukin-23 monoclonal antibody inhibitors are used extensively to control pro-inflammatory Th17 immune pathways in psoriasis and inflammatory bowel disease that are similarly important during C. difficile infection. We used a large retrospective electronic health record database to test the hypothesis that hospitalized patients with C. difficile infection who are on anti-IL-23 treatment will have improved survival compared to patients without anti-IL-23. A total of 9,301 anti-IL-23 patients had significantly lower probability of all-cause death within 30 d (0.54%) compared with 1:1 propensity-matched control patients (3.1%). IL-23 inhibition is a promising adjunct to C. difficile treatment, and further clinical trials repositioning anti-IL-23 monoclonal antibodies from psoriasis and inflammatory bowel disease to C. difficile infection are warranted.
NK cells link immune-checkpoint blockade immunotherapy and response in melanoma brain metastases
Authors: Gary Kohanbash, Stephen C Frederico, Itay Raphael
Journal: Journal for ImmunoTherapy of Cancer (2025)

Melanoma brain metastases (BMs) pose a significant clinical challenge. This commentary highlights the emerging understanding of the mechanisms behind immune-checkpoint blockade (ICB) efficacy in melanoma BMs. Specifically, we focus on a recent study by Fife et al , which revealed a non-canonical role for natural killer (NK) cells in shaping the tumor microenvironment following ICB therapy against melanoma BMs. Instead of direct tumor cell killing, this study demonstrates that ICB triggers NK cell chemokine release, CD8 T cell recruitment and enhanced antitumor immunity. The findings from this study highlight that the ICB mechanisms of action are complex and extend beyond the direct interference of inhibitor receptor–ligand interactions between cytotoxic CD8 T cells and tumor cells.
Spatial immune remodeling of the liver metastases: discovering the path to antimetastatic therapy
Authors: Wenchao Xu, Yibo Wang, Nanzhou Wang, Jianzhou Liu, Li Zhou, Junchao Guo
Journal: Journal for ImmunoTherapy of Cancer (2025)

The intrinsic characteristics of metastatic tumors are of great importance in terms of the development of antimetastatic treatment strategies. Elucidation from a spatial immune perspective has the potential to provide a more comprehensive understanding of the mechanisms underlying immune escape, effectively addressing the limitations of relying solely on the analysis of immune cell subpopulation transcriptional profiles. Advances in spatial omics technology enable researchers to precisely analyze precious liver metastasis samples in a high-throughput manner, revealing spatial alterations in immune cell distribution induced by metastasis and exploring the molecular basis of the remodeling process. The aggregation of specific cell subpopulations in distinct regions not only modifies local immune characteristics but also concurrently affects global biological behaviors of liver metastatic tumors. Identifying specific spatial immune characteristics in pretreatment or early-stage treatment tissue samples may achieve accurate clinical predictions. Moreover, developing strategies that target spatial immune remodeling is a promising avenue for future antimetastatic therapy.
Cardiac MRI study of adverse events in patients treated with immune checkpoint inhibitors: a prospective cohort study of cardiac adverse events
Authors: Agnese Losurdo, Cristina Panico, Chiara Catalano, Simone Serio, Laura Giordano, Lorenzo Monti, Federica Catapano, Stefano Figliozzi, Carla D'Andrea, Angelo Dipasquale, Pasquale Persico, Antonio Di Muzio, Marco Cremonesi, Alessandro Marchese, Maria Chiara Tronconi, Matteo Perrino, Giovanna Finocchiaro, Enrico Lugli, Marco Francone, Armando Santoro, Gianluigi Condorelli, Matteo Simonelli, Marinos Kallikourdis
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immune checkpoint inhibitors (ICIs) revolutionized cancer therapy, yet require management of immune-related adverse events (irAEs). Fulminant myocarditis is a rare irAE, but lower-severity cardiac events are being reported more frequently, leading to an unmet need for irAE prevention, early diagnosis, and treatment, especially for long-life-expectancy patients. We recruited 57 patients, stratified according to therapy regime (monotherapy (30%) or combination (33%) cohort) or history of cardiac disease or presence of at least two cardiovascular risk factors other than prior or active smoking (cardiovascular cohort (37%)). We performed a complete cardiological assessment with clinical visit, 12-lead ECG, multiparametric cardiac MRI as well as peripheral blood mononuclear cell immunophenotyping, prior to ICI initiation and around 2 months later. ICI treatment was associated with a significant left ventricular ejection function (LVEF) reduction pre-ICI versus post-ICI treatment (60.1±8% to 58.1±8%, p=0.002, paired t-test) and more than 3% LVEF loss in a substantial proportion of patients (18; 32%). These patients also showed significantly higher T2 values (p=0.037, unpaired t-test), putative sign of cardiac edema. The loss of cardiac function did not differ among patients with different tumor types, therapy regimes or history of cardiac disease. Immunophenotyping analyses showed a reduction of programmed cell death protein 1 staining on both CD4 + and CD8 + T cells, and an upregulation of HLA-DR on CD8 + T cells. Using a very sensitive and comprehensive approach in patients unselected for cardiac history, we found a subclinical but significant LVEF decrease. These findings may inform ongoing discussions on optimal management of cardiac irAEs in patients undergoing ICI treatment and warrant further evaluation.
Sonolysis during carotid endarterectomy: randomised controlled trial
Authors: David Školoudík, Tomáš Hrbáč, Martin Kovář, Vladimír Beneš, Jiří Fiedler, Mattia Branca, Jean-Benoit Rossel, David Netuka
Journal: BMJ (2025)

Abstract Objective To evaluate the effectiveness and safety of sonolysis using a low intensity 2 MHz pulsed wave ultrasound beam during carotid endarterectomy. Design Multicentre, phase 3, double blind, randomised controlled trial. Setting 16 European centres. Participants 1004 patients (mean age 68 years; 312 (31%) female) were enrolled in the study between 20 August 2015 and 14 October 2020 until the interim analysis was performed. Interventions Sonolysis (n=507) versus sham procedure (n=497). Main outcome measures The primary endpoint was the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. The incidence of new ischaemic lesions on follow-up brain magnetic resonance imaging was the main substudy endpoint, and incidence of intracranial bleeding was the main safety endpoint. Results The results favoured the sonolysis group for the primary endpoint (11 (2.2%) v 38 (7.6%); risk difference −5.5%, 95% confidence interval (CI) −8.3% to −2.8%; P&lt;0.001), as well as in the substudy for magnetic resonance imaging detected new ischaemic lesions (20/236 (8.5%) v 39/224 (17.4%); risk difference −8.9%, −15% to −2.8%; P=0.004). Sensitivity analysis resulted in a risk ratio for sonolysis of 0.25 (95% CI 0.11 to 0.56) for ischaemic stroke and 0.23 (0.07 to 0.73) for transient ischaemic attack within 30 days. Sonolysis was found to be safe, and 94.4% of patients in the sonolysis group were free from serious adverse events 30 days after the procedure. Conclusion Sonolysis was safe for patients undergoing carotid endarterectomy and resulted in a significant reduction in the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. Trial registration Clinicaltrials.gov NCT02398734 .
Tuberculosis rates in migrants in low-incidence European countries, according to country of origin, reporting country and recency of immigration, 2014 to 2020
Authors: Teresa Domaszewska, Anders Koch, Sarah Jackson, Brit Häcker, Jerker Jonsson, Kristina Langholz Kristensen, Hanna Soini, Wouter Arrazola de Oñate, Jean-Paul Guthmann, Barbara Hauer, Mary O´Meara, Karine Nordstrand, Vinciane Sizaire, Gerard de Vries
Journal: Eurosurveillance (2025)

Background As tuberculosis (TB) incidence rates decrease faster in native than migrant populations in European countries, addressing migrant health becomes increasingly important in TB programmes. Aim To inform European TB prevention and control policies, we analysed data on TB in migrants in low TB-incidence European countries (TB incidence &lt; 10/100,000 population) during 2014–2020 by migrant origin, destination, and recent vs non-recent immigration. Methods Data on migrant TB patients were derived from the European Surveillance System (TESSy) and data on migrant populations from Eurostat or national statistical offices. We calculated annual migrant TB crude incidence rates (CIRs) per country of origin, destination country and year, for all migrants with TB and recently arrived migrants with TB, the latter defined by TB diagnosis within 1 year after arrival in the destination country. Results In 2014–2020, 104,371 migrants with TB were reported to TESSy by 20 destination countries. Average annual migrant CIRs were highest in the United Kingdom (43/100,000). Origin countries of most migrant TB patients were India (n = 9,561), Romania (n = 8,345), and Pakistan (n = 7,300). The highest CIRs were found among migrants from Eritrea (480/100,000), Somalia (414/100,000) and The Gambia (343/100,000), and were higher than estimated World Health Organization incidences for those countries. The CIRs among recently arrived migrants appeared higher than in the overall migrant population. Conclusions We found substantially higher CIRs in certain migrant subpopulations than others. TB rates in recent migrants appeared to be up to 11 times higher than in corresponding origin countries. Tailored and regularly adapted TB prevention and control strategies are needed.
Increase in tuberculosis among children and young adolescents, European Union/European Economic Area, 2015 to 2023
Authors: Veronica Cristea, Csaba Ködmön, Joana Gomes Dias, Senia Rosales-Klintz
Journal: Eurosurveillance (2025)

As tuberculosis (TB) in children is an indicator of ongoing transmission, we analysed surveillance data to understand the increase in notified TB cases among individuals aged &lt; 15 years in the European Union/European Economic Area countries between 2015 and 2023. Several factors may have contributed to this increase, such as improved diagnosis and reporting, migration and the COVID-19 pandemic. The observed increasing trend, albeit low in absolute numbers, emphasises the importance of early case finding and timely prevention.
Global meta-analysis of short-term associations between ambient temperature and pathogen-specific respiratory infections, 2004 to 2023
Authors: Xue Shang, Ruhao Zhang, Junyao Zheng, Yi Luo, Kangle Guo, Qingqing Zhou, Xu Guang, Ning Zhang, Hao Xue, Haidong Wang, Chunfu Yang, Zhen Zhang, Bin Zhu
Journal: Eurosurveillance (2025)

Background Ambient temperature may affect respiratory health, while the temperature sensitivity of respiratory infections may be pathogen-dependent. Aims We sought to explore pathogen-specific associations between ambient temperature and respiratory infections. Methods We searched nine databases for a random-effects meta-analysis to pool the relative risk (RR) of respiratory infection by pathogen per 1° C temperature rise, compared to populations unexposed to the same temperature. We conducted pathogen-specific analyses, sensitivity analyses, subgroup analyses and meta-regression. Results A total of 137 studies were eligible for meta-analysis. The pooled and single-study estimates revealed that the incidence of respiratory syncytial virus (RR = 0.14; 95% confidence interval (CI): 0.09–0.23), influenza virus (IV) (RR = 0.40; 95% CI: 0.27–0.61), human metapneumovirus (RR = 0.48; 95% CI: 0.32–0.73), human coronavirus (HCoV) (RR = 0.21; 95% CI: 0.07–0.61) and SARS-CoV-2 (RR = 0.52; 95% CI: 0.35–0.78) decreased per 1° C temperature rise, while that of human parainfluenza virus (HPIV) (RR = 2.35; 95% CI: 1.46–3.77), human bocavirus (HBoV) (RR = 1.86; 95% CI: 1.04–3.32) and MERS-CoV (RR = 1.05; 95% CI: 1.04–1.07) increased. The risk of infection was lower for IVA, IVB, HCoV-229E and HCoV-OC43, while HPIV-3, and HBoV-1 were at increased risk. The risk of Streptococcus pyogenes pharyngitis (RR = 0.46; 95% CI: 0.30–0.69) decreased per 1° C temperature rise, while Pseudomonas aeruginosa (RR = 1.04; 95% CI: 1.03–1.05) and Legionella pneumophila infections (RR = 2.69; 95% CI: 1.11–6.53) increased. Conclusions Temperature sensitivity of respiratory infections can vary with the specific pathogen type and subtype that causes the infection. As the climatic conditions will become warmer, public health policy makers should act to develop pathogen adaptation strategies.
Epidemiology of Staphylococcus haemolyticus nosocomial bacteraemia in neonatal intensive care units, France, 2019 to 2023: predominance of the ST29 (CC3) multidrug-resistant lineage
Authors: Patricia Martins Simões, Nathalie van der Mee-Marquet, Benjamin Youenou, Anne-Gaelle Ranc, Céline Dupieux-Chabert, Guillaume Menard, Clarisse Dupin, Marine Butin, François Vandenesch, Frédéric Laurent, Anne Berger-Carbonne, Camille Kolenda, Anne Tristan
Journal: Eurosurveillance (2025)

Background Staphylococcus haemolyticus (SH) is an opportunistic pathogen associated with nosocomial infections, particularly bacteraemia in neonates. Epidemiological trends and genetic diversity of these infections worldwide are largely unknown. Aim To investigate an increase in SH vascular catheter-related bacteraemia in neonates and describe the molecular epidemiology in France between 2019 and 2023. Methods We analysed clinical and microbiological surveillance data from the French national surveillance network for central catheter-related (venous and umbilical) infections between 2019 and 2023. We also performed genomic and phylogenetic analyses of 496 strains isolated both inside (n = 383 from neonates, staff and environmental samples) and outside (n = 113 from adults) the neonatal intensive care unit (NICU) settings. Results The proportion of SH among the 474 reported cases of nosocomial bacteraemia increased from about 20% to 30% over 5 years, mainly affecting very low birth weight preterm neonates (≤ 1,500 g). The ST29 sequence type (ST) not prevalent in previous studies was predominant, accounting for 74% of NICU strains. ST29 was characterised by phenotypic multidrug resistance to at least six classes of antibiotics (oxacillin, quinolones, gentamicin, cotrimoxazole, clindamycin and rifampicin), which distinguished it with good sensitivity and specificity from other prevalent multidrug-resistant STs identified (ST1 and ST25). ST29 strains more frequently harboured the drfG , vga-LC and mupA genes and a triple point mutation (D471E, I527M and S532N) in the rpoB gene. Conclusions The present study highlights the success of a highly resistant ST29 lineage in French NICUs mainly affecting very low birth weight premature neonates.
Healthcare-associated malaria: a systematic review, 1997 to 2023
Authors: Céline M Gossner, Luisa K Hallmaier-Wacker, Harold Noel, Beatriz Fernández Martínez, Danai Pervanidou, Maria Tseroni, Julia Enkelmann, Daniela Boccolini, Diamantis Plachouras
Journal: Eurosurveillance (2025)

Background Malaria is primarily transmitted through mosquito bites; occasionally, direct transmission through blood has been reported. Healthcare-associated infections refer to infections acquired in a hospital or another healthcare setting. Aim This systematic review aims to explore determinants of healthcare-associated malaria (HAM) cases. Method This review follows the PRISMA guidelines and was registered in PROSPERO (CRD42022309701). We searched five databases for publications on HAM cases published between 1 January 2000 and 7 December 2023. We initiated a data call for HAM cases to public health authorities from 37 European countries. We performed a backward and forward search, reviewed health authorities’ websites, performed searches on Google and the European Scientific Conference on Applied Infectious Disease Epidemiology (ESCAIDE) conference abstracts book. Results We identified 37 studies on HAM comprising 55 HAM cases, of which 35 (64%) were infected in Europe, primarily in Spain (nine cases), France and Italy (seven cases each). All cases were infected with Plasmodium falciparum except one individual. Fifty HAM cases were hospital inpatients and five were healthcare workers. Five patients died. Flushing of vascular catheters with contaminated heparin/saline solution and manipulation of intravenous catheters were the most frequently reported procedures leading to infection among patients. Conclusions While rare, HAM transmission can be fatal. Healthcare-associated malaria is preventable through strict adherence to infection prevention and control procedures. Despite extensive investigations, the procedure leading to infection often remained unknown, highlighting the complexity of investigations. Guidance and protocols for conducting investigations may improve the success rate of such inquiries.
scVAEDer: integrating deep diffusion models and variational autoencoders for single-cell transcriptomics analysis
Authors: Mehrshad Sadria, Anita Layton
Journal: Genome biology (2025)

Abstract Discovering a lower-dimensional embedding of single-cell data can improve downstream analysis. The embedding should encapsulate both the high-level features and low-level variations. While existing generative models attempt to learn such low-dimensional representations, they have limitations. Here, we introduce scVAEDer, a scalable deep-learning model that combines the power of variational autoencoders and deep diffusion models to learn a meaningful representation that retains both global structure and local variations. Using the learned embeddings, scVAEDer can generate novel scRNA-seq data, predict perturbation response on various cell types, identify changes in gene expression during dedifferentiation, and detect master regulators in biological processes.
Shifting tuberculosis dynamics in the EU/EEA: geographical and drug resistance trends among people of foreign origin, 2019 to 2023
Authors: Anca Vasiliu, Veronica Cristea, Krista Stoycheva, Senia Rosales-Klintz, Christoph Lange, Dominik Zenner, Csaba Ködmön
Journal: Eurosurveillance (2025)

We observed shifting trends in tuberculosis (TB) epidemiology in the EU/EEA between 2019 and 2023. In 2023, TB notifications among people of foreign origin increased by 24.6% after decreasing between 2019 and 2020. The majority originated from African and East Mediterranean regions, with a 316.4% upsurge in TB among Ukrainians in 2022–23. Rifampicin-resistant/multidrug-resistant TB increased by ≥ 60% in 2019–23, mainly among Ukrainians. Rapid response to shifting epidemiological patterns is crucial for efficient TB prevention and control within the EU/EEA.