tbuckley/cabot-search huggingface dataset:
Fluoropyrimidine Chemotherapy and the Risk of Death and Cardiovascular Events in Patients With Gastrointestinal Cancer
Authors: Aderonke T Abiodun, Chengsheng Ju, Catherine A Welch, Jennifer Lai, Freya Tyrer, Pinkie Chambers, Lizz Paley, Sally Vernon, John Deanfield, Mark de Belder, Mark J Rutherford, Paul C Lambert, Sarah Slater, Kai-Keen Shiu, Li Wei, Michael D Peake, David Adlam, Charlotte Manisty
Journal: JACC CardioOncology (2025)

Fluoropyrimidine chemotherapy is administered first-line for many gastrointestinal cancers. However, patients with cardiovascular disease commonly receive alternative treatment due to cardiotoxicity concerns. The study sought to assess the risks of all-cause mortality and acute cardiovascular events with fluoropyrimidine treatment. We conducted an observational cohort study applying a target trial emulation framework to linked national cancer, cardiac, and hospitalization registry data from the Virtual Cardio-Oncology Research Initiative. Adults diagnosed with tumors eligible for fluoropyrimidine-based chemotherapy as first-line therapy were included. All-cause mortality and a composite of hospitalization for acute cardiovascular events (acute coronary syndrome, heart failure, cardiac arrhythmia, cardiac intervention, cardiac arrest, and cardiac death) were compared in patients treated with fluoropyrimidine-based chemotherapy vs alternative management. Adjusted, weighted pooled logistic regression models were used to estimate the 1-year risk difference (RD). Among 103,110 patients (mean age 69.7 years, 59% male), the absolute risk of death at 1 year was significantly lower in fluoropyrimidine-treated patients (RD: -7.7%; 95% CI: -8.7% to -6.7%) with a small increased risk of acute cardiovascular events (RD: 0.9%; 95% CI: 0.0% to 1.9%). This was primarily due to arrhythmias (RD: 0.8%; 95% CI: 0.1% to 1.6%) and cardiac arrest (RD: 0.3%; 95% CI: 0.1% to 0.5%), with no increased risk of acute coronary syndromes including in the subgroup of patients with pre-existing coronary artery disease. The markedly improved overall survival with fluoropyrimidines in patients with gastrointestinal cancer significantly outweighs the small risk of cardiac arrhythmia and arrest. Oncologists should take this into consideration for decision making to avoid undue clinical conservatism, particularly in patients with cardiovascular disease.
Factors that affect the resilience of young adults to depression: a systematic review
Authors: Linda Theron, Dov J Stekel, Jan Höltge, Olufunmilayo I Fawole, Diane T Levine, Zainab Mai-Bornu, Kassa Maksudi, Olanrewaju Olaniyan, Caradee Y Wright, Michael Ungar
Journal: The Lancet Psychiatry (2025)
Utilising the Benefit Risk Assessment of Vaccines (BRAVE) toolkit to evaluate the benefits and risks of Vaxzevria in the EU: a population-based study
Authors: Hector Gonzalez Dorta, Johan Verbeeck, Jonas Crevecoeur, Daniel R Morales, Neilshan Loedy, Catherine Cohet, Lander Willem, Geert Molenberghs, Niel Hens, Xavier Kurz, Chantal Quinten, Steven Abrams
Journal: The Lancet Digital Health (2025)

Several COVID-19 vaccines have been licensed. To support the assessment of safety signals, we developed a toolkit to support COVID-19 vaccine monitoring and benefit-risk assessment. We aim to show the application of our toolkit in the EU using thrombosis with thrombocytopenia syndrome (TTS) associated with the Vaxzevria (AstraZeneca) vaccine as a use case. In this population-based study, we used a model incorporating data from multiple EU sources such as The European Surveillance System and EudraVigilance, and estimated the benefits of COVID-19 vaccines by comparing the observed COVID-19 confirmed cases, hospitalisations, intensive care unit (ICU) admissions, and deaths across Europe to the expected numbers in the absence of Vaxzevria vaccination. Risks of TTS associated with Vaxzevria were calculated by comparing the observed number of TTS events in individuals who received Vaxzevria to the expected number of events based on background incidence rates. To visualise the results, we developed a toolkit with an interactive web application. 62 598 505 Vaxzevria vaccines (32 763 183 to females and 29 835 322 to males) had been administered in Europe by Feb 10, 2021. Our results showed that a first dose of Vaxzevria provided benefits across all age groups. Based on vaccine effectiveness estimates and reported coverage in Europe, from Dec 13, 2020 to Dec 31, 2021, vaccination with Vaxzevria was estimated to prevent (per 100 000 doses) 12 113 COVID-19 cases, 1140 hospitalisations, 184 ICU admissions, and 261 deaths. Women aged 30-59 years and males aged 20-29 years had the highest frequency of TTS events. The benefits of vaccination outweighed the risks of TTS in all age groups, with the highest benefits and risks observed in individuals aged 60-69 years. Our toolkit and underlying model contextualised the risk of TTS associated with Vaxzevria relative to its benefits. The methodology employed could be applied to other serious adverse events related to COVID-19 or other vaccines. The adaptability and versatility of such toolkits might contribute to strengthening preparedness for future public health emergencies. European Medicines Agency.
Hepatic encephalopathy and MELD-Na predict treatment benefit in autoimmune hepatitis-related decompensated cirrhosis
Authors: Pinelopi Arvaniti, Sergio Rodríguez-Tajes, Marlene Padilla, Ignasi Olivas, Ezequiel Mauro, Cautar El Maimouni, Ellina Lytvyak, Xavier Verhelst, Bastian Engel, Richard Taubert, Sara Lorente-Pérez, Isabel Conde, Mar Riveiro-Barciela, Juan-Carlos Ruiz-Cobo, Carmen Álvarez-Navascués, Magdalena Salcedo, Judith Gómez, Maciej K Janik, Beatriz Mateos, Cumali Efe, Alessandro Granito, Elton Datji, Francesco Azzaroli, Diana Horta, Carmen Vila, Inmaculada Castello, Indhira Pérez-Medrano, Ana Arencibia, Alessio Gerussi, Tony Bruns, Francesca Colapierto, Ana Lleo, Natalie Van den Ende, Jef Verbeek, Álvaro Díaz-González, Rosa Ma Morillas, Maria Torner-Simó, Vanesa Bernal, Eva-Maria Fernández, Tom Jg Gevers, Benedetta Terziroli Beretta-Piccoli, Elena Gómez, Paqui Cuenca, Ynte S de Boer, Nanda Kerkar, David N Assis, Rodrigo Liberal, Joost Ph Drenth, Michele M Tana, Marcial Sebode, Ida Schregel, Christoph Schramm, Ansgar W Lohse, Aldo J Montano-Loza, Kalliopi Zachou, Alejandra Villamil, George N Dalekos, María-Carlota Londoño
Journal: Clinical Gastroenterology and Hepatology (2025)
A multicenter validation study of Mohs micrographic surgery vs wide local excision in primary high-stage cutaneous squamous cell carcinoma
Authors: David M Wang, Nina A Ran, Emily E Granger, Shlomo Koyfman, Allison Vidimos, Ashley Wysong, David R Carr, Kathryn T Shahwan, Kelsey E Hirotsu, John A Carucci, Joi B Carter, Javier Cañueto, Fabio Muradás Girardi, Aaron R Mangold, Divya Srivastava, Rajiv I Nijhawan, David G Brodland, John A Zitelli, Tyler J Willenbrink, Emily S Ruiz
Journal: Journal of the American Academy of Dermatology (2025)
UBC9 ameliorates diabetic cardiomyopathy by modulating cardiomyocyte mitophagy through NEDD4/RUNX2/PSEN2 axis
Authors: Hanlin Wu, Zheming Yang, Ting Zhou, Jing Wang, Yuxin Bu, Haixu Song, Chenghui Yan, Dan Liu, Yaling Han
Journal: Metabolism (2025)
Assessment of the participation rate and effectiveness of upper gastrointestinal cancer screening in China: a multicenter population-based screening study
Authors: Song Song, Han Liu, Xianyi Geng, Ru Chen, Rongshou Zheng, Ni Li, Wanqing Chen, Wenqiang Wei, Jiansong Ren
Journal: Endoscopy (2025)

Abstract This study estimated the participation rate and effectiveness of endoscopic screening of upper gastrointestinal cancer (UGIC) in China. From 2014 to 2015, we recruited 192805 adults from seven cities in China to build a prospective cohort for UGIC screening, including esophageal cancer and gastric cancer. Overall, 39991 participants were at high risk for UGIC according to an established risk score system and were recommended for endoscopic examination. Participation rates were reported, and their associated factors were explored. After inverse probability of treatment weighting (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) and 95%CI for UGIC incidence and mortality between screened and non-screened groups from cohort entry until 31 December 2021. 10442 participants underwent endoscopy, giving a participation rate of 26.1%. Higher participation was observed among individuals with higher education levels, history of upper gastrointestinal diseases, and family history of cancer. After a median follow-up of 6.8 years (interquartile range 6.7–6.9), UGIC incidences after IPTW were 94.64 per 100000 person-years in the screened group and 84.73 per 100000 person-years in the non-screened group. The weighted UGIC mortality rates were 13.1 and 33.40 per 100 000 person-years, respectively. The screened group had significantly lower UGIC mortality than the non-screened group, with a weighted IRR of 0.39 (95%CI 0.19–0.82). Participation in endoscopic screening among a high-risk UGIC population in China was low. We found that one-time endoscopic screening significantly reduced mortality caused by UGIC.
KpnK48 clone driving hypervirulent carbapenem-resistant Escherichia coli epidemics: Insights into its evolutionary trajectory similar to Klebsiella pneumoniae
Authors: Meng Wang, Longyang Jin, Ruobing Wang, Qi Wang, Shuyi Wang, Xingyu Wu, Chaoqun Yao, Jukka Corander, Hui Wang
Journal: Drug Resistance Updates (2025)
Opposite regulation of intestinal and intrahepatic CD8<sup>+</sup>T cells controls alcohol-associated liver disease progression
Authors: Luca Maccioni, Yukun Guan, Mariia Kim, Maria A Parra, Brandon Peiffer, Yaojie Fu, Yang Wang, Yu-Hong Lin, Bryan Mackowiak, Dechun Feng, Andrew Cameron, Zhaoli Sun, George Kunos, Peter Stärkel, Bin Gao
Journal: Gut (2025)

Background Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure. Objective We examined the regulation of intestinal and intrahepatic CD8 + T lymphocytes and their contribution to ALD. Design ALD patients were recruited for evaluation of intestinal and liver T cells. Single-cell RNA sequencing (scRNA seq) was performed to analyse intrahepatic and peripheral T cells in ALD. Wildtype, CD8-specific Bcl2 transgenic ( Cd8 Bcl-2 ), and Cd8 −/− mice were subjected to chronic-plus-binge ethanol feeding. Results In ALD patients, duodenal CD8 + T cells were selectively reduced and negatively correlated with liver injury and bacterial translocation markers, while intrahepatic CD8 + T cells were markedly increased. ScRNA seq analysis of ALD patient livers revealed several populations of CD8 + T cells expressing activation and survival genes (eg, Bcl2 ). Transcriptomics and functional studies revealed a key role of prosurvival BCL2 in this opposite regulation of CD8 + T cells. Mechanistically, chronic-plus-binge ethanol feeding reduced CD8 + T cells specifically in the duodenum where ethanol levels are high. Inducing BCL2 in CD8 + T cells reversed ethanol-induced loss of duodenal CD8 + T cells, improved gut barrier function and ameliorated ALD, while CD8 deficiency was linked to enhanced neutrophil and macrophage infiltration in the liver, exacerbating ALD in mice. Conclusions ALD is associated with loss of duodenal CD8 + T cells but elevation of intrahepatic CD8 + T cells, which aggravates and ameliorates ALD, respectively. Restoration of survival and functions of intestinal and intrahepatic CD8 + T cells may represent a novel therapeutic strategy for ALD patients.
Articulating the JACC Journals’ Direction in Times of Global Change
Authors: Harlan M. Krumholz, Biykem Bozkurt, Y. Chandrashekhar, Bonnie Ky, Douglas L. Mann, David J. Moliterno, Kalyanam Shivkumar, Candice K. Silversides, Gilbert H.L. Tang, Jian’an Wang
Journal: JACC Heart Failure (2025)
Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy
Authors: Giorgio Ottaviano, Waseem Qasim
Journal: Leukemia (2025)

Abstract Malignant transformation of gene modified haematopoietic stem cells caused anxiety following adverse events in early clinical trials using gamma-retroviral vectors (γRV) to correct haematopoietic stem cells (HSC) in monogenic immune disorders. Adoption of HIV-derived lentiviral vectors (LV) with SIN (self-inactivating) configurations greatly reduced risks and subsequently hundreds of patients have been dosed with HSC gene therapy for blood, immune and metabolic conditions. Nevertheless, as experience builds, it’s now well recognised that vector integration can drive clonal expansions and these may carry long term safety risks. Documented cases of haematological malignancy after SIN-LV gene therapy have recently emerged, in particular where heterologous retroviral promoters were employed and there are concerns around certain insulator elements and other possible contributors to clonal expansions. Similarly, tens of thousands of subjects have now received engineered T cell products, and longstanding dogma that mature T cells cannot be transformed is being questioned, with reports of a small number of malignant transformation events and wider concerns around secondary malignancies in some groups of patients. We summarize current clinical information and revisit genotoxicity risks following ex-vivo gene modification of HSC and T cells.
Reactive cholangiocyte-derived ORM2 drives a pathogenic modulation of the injured biliary niche through macrophage reprogramming
Authors: Hanyang Liu, Guo Yin, Bianca Franco Leonardi, Tian Lan, Yeni Ait Ahmed, Hilmar Berger, Marlene Sophia Kohlhepp, Natalja Amiridze, Natalia Martagón Calderón, Carla Frau, Ludovic Vallier, Milad Rezvani, Frank Tacke, Adrien Guillot
Journal: Gut (2025)

Background Injured or reactive biliary epithelial cells participate in most chronic liver injuries in a process referred to as ductular reaction, which involves multicellular interactions with marked local infiltration of macrophages and fibrogenic cell activation. The direct roles of biliary epithelial cells in shaping their cellular niche remain unknown. Objective We aimed at investigating the effects of biliary epithelial cell-derived acute phase response protein orosomucoid 2 (ORM2) in shaping monocyte/macrophage response to liver injury. Design Transcriptome data sets from human and mouse livers were used, results were confirmed with multiplex immunofluorescence. A multicellular biliary-niche-on-a-chip derived from primary liver and blood cells (wild-type, Mdr2 −/− mice) was established to model ductular reaction. Human blood cells collected from healthy donors and intrahepatic cholangiocyte organoids derived from normal and cirrhotic liver patients were used. Results Our transcriptome data set and multiplex immunofluorescence analyses indicated a previously unrecognised involvement of the acute phase response protein ORM2 in ductular reactions in both human and mouse livers. ORM2 gene expression was increased in biliatresone-challenged, bile acid-challenged and acetaminophen-challenged cholangiocytes. Cholangiocyte-derived ORM2 induced unique transcriptome changes and functional adaptation of liver macrophages. ORM2-activated macrophages exacerbated cholangiocyte cell stress and Orm2 expression, but also tended to promote fibrogenic activation of hepatic stellate cells. Mechanistically, ORM2 effects were mediated by an inositol 1,4,5-trisphosphate receptor type 2-dependent calcium pathway. Conclusion This study reveals a paracrine communication circuit during ductular reaction, in which reactive cholangiocyte-derived ORM2 reprogrammes liver macrophages, participating in a pathogenic remodelling of the immune biliary niche.
Pre-infusion 18F-FDG PET/CT for Prognostic and Toxicity Prediction in B-cell Non-Hodgkin Lymphoma Patients Undergoing Chimeric Antigen Receptor T-cell Therapy
Authors: Xilan Yao, Hongrong Wang, Xiao Lei, Shuang Yao, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2025)

Purpose: The aim of this study was to evaluate the value of 18 F-FDG PET/CT in predicting outcomes and toxicity for patients with B-cell non-Hodgkin lymphoma (B-NHL) who underwent chimeric antigen receptor T (CAR-T) cell therapy. Methods: This retrospective study included B-NHL patients who underwent CAR-T therapy and had pre-infusion 18 F-FDG PET/CT images. We recorded SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and various clinical and laboratory indexes. The primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated using the Kaplan-Meier method. In addition, we reported the correlation between PET/CT parameters and the objective response (OR), as well as cytokine release syndrome (CRS). Results: A total of 133 patients were enrolled in this study. The median follow-up duration was 20.8 months. SUVmax (with a cutoff value of 15.65) emerged as an independent metabolic parameter associated with PFS, OS, and OR. Patients with SUVmax ≥15.65 had a median PFS of 9.13 months (95% CI: 0.11–18.16), while the PFS for those with SUVmax&lt;15.65 was not reached ( P =0.006). Furthermore, patients with SUVmax ≥15.65 exhibited significantly shorter average OS compared with those with SUVmax&lt;15.65 (26.89 mo vs. 45.14 mo, P =0.010). In addition, the odds ratio for achieving an OR in patients with SUVmax ≥15.65 was found to be lower at 0.173 (95% CI: 0.056–0.539). Other factors associated with PFS included ECOG-PS, B symptoms, bulky mass, and extranodal sites, whereas IPI and LDH were associated with OS. Furthermore, SUVmax and Deauville scores showed a weak positive correlation with the occurrence of CRS. Conclusions: The pretreatment PET/CT parameter SUVmax appears to be a promising predictive factor for efficacy and prognosis, as well as being associated with the occurrence of CRS. Consequently, we can conclude that this metabolic parameter from pretreatment PET/CT scans may serve as a valuable tool in guiding patient selection for CAR-T therapy and predicting potential side effects.
Leptin acutely increases hepatic triglyceride secretion in patients with lipodystrophy
Authors: Marianna Beghini, Matthäus Metz, Clemens Baumgartner, Peter Wolf, Magdalena Bastian, Martina Hackl, Sabina Baumgartner-Parzer, Rodrig Marculescu, Michael Krebs, Jürgen Harreiter, Stephanie Brandt, Konstanze Miehle, Giovanni Ceccarini, Silvia Magno, Caterina Pelosini, Christel Tran, Alessandra Gambineri, Carolina Cecchetti, Liliana-Imi Gard, Robert Risti, Aivar Lõokene, Martin Krššák, Lorenz Pfleger, Michael Trauner, Alexandra Kautzky-Willer, Michael Stumvoll, Martin Wabitsch, Ferruccio Santini, Ihsan Turan, Baris Akinci, Florian Frommlet, Herbert Stangl, Clemens Fürnsinn, Thomas Scherer
Journal: Metabolism (2025)
The Society for Immunotherapy of Cancer Perspective on Liquid Biopsy and Radiomics Based Technologies for Immuno-Oncology Biomarker Discovery and Application
Authors: Anne Monette, Adriana Aguilar-Mahecha, Emre Altinmakas, Mathew G. Angelos, Nima Assad, Gerald Batist, Praveen K. Bommareddy, Diana L. Bonilla, Christoph H. Borchers, Sarah E. Church, Gennaro Ciliberto, Alexandria P. Cogdill, Luigi Fattore, Nir Hacohen, Mohammad Haris, Vincent Lacasse, Wen-Rong Lie, Arnav Mehta, Marco Ruella, Sam Sater, Alan Spatz, Bachir Taouli, Imad Tarhoni, Edgar Gonzalez-Kozlova, Itay Tirosh, Xiaodong Wang, Sacha Gnjatic
Journal: Clinical Cancer Research (2025)

Abstract Immuno-oncology is increasingly becoming the standard of care for cancers, with the identification of biomarkers that reliably classify ICI response, resistance, and toxicity becoming the next frontier towards improvements in immunomodulatory treatment regimens. Recent advances in multi-parametric, multi-omics, and computational data platforms generating an unprecedented depth of data may assist in the discovery of increasingly robust biomarkers for enhanced patient selection and more personalized or longitudinal treatment approaches. Which emerging technologies to implement in future research and clinical settings, used alone or in combination, relies on weighing pros and cons that aid in maximizing data outputs whilst minimizing patient sampling, with high reproducibility and representativeness, and minimal turnaround time and data fragmentation towards later private and public dataset harmonization strategies. The Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify important advances in biomarker technologies and to highlight advances in biomarker discovery using liquid biopsy and in vivo imaging technologies. We address advances in liquid biopsy technologies monitoring cells, proteins, nucleic acids, antibodies, and drugs or analytes, and radiomics technologies monitoring at the whole host-level imaging methods including immuno-PET and MRI technologies able to couple biomarker with physical location. We include a summary of key metrics obtained by these technologies, and their ease of interpretation, limitations and dependencies, technical improvements, and outward comparisons. By highlighting some of the most interesting recent examples contributed by these technologies, and providing examples improving outputs, we hope to guide correlative research directions and assist in their becoming clinically useful in immuno-oncology.
Personalised therapeutic approaches for asthma
Authors: Ioana Agache, Ian M Adcock, Federico Baraldi, Kian Fan Chung, Ibon Eguiluz-Gracia, Sebastian L Johnston, Marek Jutel, Parameswaran Nair, Alberto Papi, Celeste Porsbjerg, Omar S Usmani, Deborah A Meyers, Magdalena Zemelka-Wiacek, Eugene R Bleecker
Journal: Journal of Allergy and Clinical Immunology (2025)
The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand breaks
Authors: Wafaa S Ramadan, Samrein B M Ahmed, Iman M Talaat, Lama Lozon, Soraya Mouffak, Timo Gemoll, Wael Y Mansour, Raafat El-Awady
Journal: Genome biology (2025)

Spatial and temporal control of DNA damage response pathways after DNA damage is crucial for maintenance of genomic stability. Ataxia telangiectasia mutated (ATM) protein plays a central role in DNA damage response pathways. The chain of events following induction of DNA damage that results in full activation of ATM is still evolving. Here we set out to explore the role of CREB-binding protein (CBP), a histone acetyltransferase (HAT), in DNA damage response, particularly in the ATM activation pathway. In response to DNA damage, CBP is stabilized and is recruited at sites of DNA double-strand breaks where it acetylates ATM and promotes its kinase activity. Cells deficient in CBP display an impairment in DNA double-strand break repair and high sensitivity to chemo- and radiotherapy. Importantly, re-expressing CBP's HAT domain in CBP-deficient cells restores the DNA repair capability, demonstrating the essential role of CBP's HAT domain in repairing DNA double-strand breaks. Together, our findings shed the light on CBP as a key participant in the ATM activation pathway and in the subsequent repair of DNA double-strand breaks, which may serve as a potential target to modulate the cellular response to DNA damaging agents in cancer.
Cardiac Troponins and Cardiovascular Disease Risk Prediction
Authors: Anoop S V Shah, Spencer J Keene, Lisa Pennells, Stephen Kaptoge, Dorien M Kimenai, Matthew Walker, Julianne D Halley, Sara Rocha, Ron C Hoogeveen, Vilmundur Gudnason, Stephan J L Bakker, Sasiwarang G Wannamethee, Manan Pareek, Kai M Eggers, J Wouter Jukema, Graeme J Hankey, James A deLemos, Ian Ford, Torbjørn Omland, Magnus Nakrem Lyngbakken, Bruce M Psaty, Christopher R deFilippi, Angela M Wood, John Danesh, Paul Welsh, Naveed Sattar, Nicholas L Mills, Emanuele Di Angelantonio
Journal: Journal of the American College of Cardiology (2025)
Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy
Authors: Seyedeh Sahar Mortazavi Farsani, Jignesh Soni, Lu Jin, Anil Kumar Yadav, Shivani Bansal, Tian Mi, Leena Hilakivi-Clarke, Robert Clarke, Benjamin Youngblood, Amrita Cheema, Vivek Verma
Journal: Cell Metabolism (2025)