tbuckley/cabot-search huggingface dataset:
Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study
Authors: Xin Zhao, Jing Sun, Zhihua Zhang, Miao Chen, Tiejun Gong, Guangsheng He, Yingmei Li, Hong Liu, Fei Li, Xin Li, Hu Zhou, Xiaoqin Wang, Mei Hong, Lei Lei, Hongyan Yin, Xian Luo, Yang Li, Songhua Fan, Xiaojun Guo, Michael M Shi, Weiguo Su, Liansheng Zhang, Bing Han, Fengkui Zhang
Journal: The Lancet Haematology (2025)
Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial
Authors: Armin Ghobadi, Veronika Bachanova, Krish Patel, Jae H Park, Ian Flinn, Peter A Riedell, Carlos Bachier, Catherine S Diefenbach, Carol Wong, Cara Bickers, Lilly Wong, Deepa Patel, Jode Goodridge, Matthew Denholt, Bahram Valamehr, Rebecca L Elstrom, Paolo Strati
Journal: The Lancet (2025)
Traumatic injury mortality in the Gaza Strip from Oct 7, 2023, to June 30, 2024: a capture–recapture analysis
Authors: Zeina Jamaluddine, Hanan Abukmail, Sarah Aly, Oona M R Campbell, Francesco Checchi
Journal: The Lancet (2025)

Accurate mortality estimates help quantify and memorialise the impact of war. We used multiple data sources to estimate deaths due to traumatic injury in the Gaza Strip between Oct 7, 2023, and June 30, 2024. We used a three-list capture-recapture analysis using data from Palestinian Ministry of Health (MoH) hospital lists, an MoH online survey, and social media obituaries. After imputing missing values, we fitted alternative generalised linear models to the three lists' overlap structure, with each model representing different possible dependencies among lists and including covariates predictive of the probability of being listed; we averaged the models to estimate the true number of deaths in the analysis period (Oct 7, 2023, to June 30, 2024). Resulting annualised age-specific and sex-specific mortality rates were compared with mortality in 2022. We estimated 64 260 deaths (95% CI 55 298-78 525) due to traumatic injury during the study period, suggesting the Palestinian MoH under-reported mortality by 41%. The annualised crude death rate was 39·3 per 1000 people (95% CI 35·7-49·4), representing a rate ratio of 14·0 (95% CI 12·8-17·6) compared with all-cause mortality in 2022, even when ignoring non-injury excess mortality. Women, children (aged <18 years), and older people (aged ≥65 years) accounted for 16 699 (59·1%) of the 28 257 deaths for which age and sex data were available. Our findings show an exceptionally high mortality rate in the Gaza Strip during the period studied. These results underscore the urgent need for interventions to prevent further loss of life and illuminate important patterns in the conduct of the war. None.
Clinical trials for implantable neural prostheses: understanding the ethical and technical requirements
Authors: Marcello Ienca, Giacomo Valle, Stanisa Raspopovic
Journal: The Lancet Digital Health (2025)

SummaryNeuroprosthetics research has entered a stage in which animal models and proof-of-concept studies are translated into clinical applications, often combining implants with artificial intelligence techniques. This new phase raises the question of how clinical trials should be designed to scientifically and ethically address the unique features of neural prostheses. Neural prostheses are complex cyberbiological devices able to acquire and process data; hence, their assessment is not reducible to only third-party safety and efficacy evaluations as in pharmacological research. In addition, assessment of neural prostheses requires a causal understanding of their mechanisms, and scrutiny of their information security and legal liability standards. Some neural prostheses affect not only human behaviour, but also psychological faculties such as consciousness, cognition, and affective states. In this Viewpoint, we argue that the technological novelty of neural prostheses could generate challenges for technology assessment, clinical validation, and research ethics oversight. To this end, we identify a set of methodological and research ethics challenges specific to this medical technology innovation. We provide insights into relevant ethical guidelines and assess whether oversight mechanisms are well equipped to ensure adequate clinical and ethical use. Finally, we outline patient-centred research ethics requirements for clinical trials involving implantable neural prostheses.
Impact of COVID-19 pandemic on elective care backlog trends, recovery efforts, and capacity needs to address backlogs in Scotland (2013–2023): a descriptive analysis and modelling study
Authors: Syed Ahmar Shah, Karen Jeffrey, Chris Robertson, Aziz Sheikh
Journal: The Lancet Regional Health - Europe (2025)

SummaryBackgroundPrioritisation of COVID-19 care led to widespread cancellations of elective care, creating a substantial backlog for healthcare systems worldwide. While the pandemic's impacts on elective hospital waiting lists during the early phase of the pandemic have been described in multiple countries, there is limited research on longer-term impacts and recovery efforts.MethodsWe conducted a country-wide analysis of Scotland's healthcare system over an 11-year period (January 1, 2013–December 31, 2023) to assess the pandemic's impact on the elective care backlog, evaluate recovery efforts, and estimate the capacity increase required to clear the backlog. Our analysis involved assessments at national, elective type, regional, and specialty levels. We used descriptive statistics to compare trends and a statistical modelling approach (Vector Autoregressive model with exogenous variables) to estimate capacity increases needed.FindingsWaiting lists gradually increased before the pandemic (2013: n = 285,149; 2019: n = 385,859; 35.3% increase over six years) and then rose rapidly during the pandemic (2023: n = 667,749; 73.1% increase over four years). Capacity for elective care dropped substantially during the initial lockdown period (April–June 2020) and had not fully recovered by the end of 2023. These patterns were broadly consistent across Scotland and similar trends were observed when stratified by elective type, region, and specialty. The number of referrals waiting over a year increased from 3056 on December 31, 2019, to 78,243 (>2400% increase) by December 31, 2023. To eliminate the backlog created during the pandemic, a gradual increase in capacity, accumulating to 20% over three years is required. This corresponds to an annual increase of approximately 6.67%, translating to an additional 32,302 cases per year.InterpretationScotland's healthcare system struggled to meet elective care demand pre-pandemic, and the pandemic has worsened an already difficult situation. Pre-pandemic elective care capacity had not been restored by the end of 2023. While substantial additional capacity is necessary, it is crucial to adopt broader system-level strategies to effectively address waiting list backlogs.FundingUniversity of Edinburgh's Chancellor Fellowship; Health Data Research UK.
Long-term risk of chronic liver disease in patients with celiac disease: a nationwide population-based, sibling-controlled cohort study
Authors: Jialu Yao, Jiangwei Sun, Fahim Ebrahimi, David Bergman, Peter H.R. Green, Hannes Hagström, Benjamin Lebwohl, Daniel A. Leffler, Jonas F. Ludvigsson
Journal: The Lancet Regional Health - Europe (2025)

SummaryBackgroundCeliac disease (CeD) may be associated with elevated liver enzymes. However, little is known about the risk of chronic liver disease (CLD) of various etiologies or major adverse liver outcomes (MALO) in CeD. We aimed to investigate the long-term risk of CLD in patients with CeD.MethodsSwedish nationwide cohort study. We identified 48,027 patients with biopsy-confirmed CeD between 1969 and 2017. Each patient was exactly matched with ≤5 general population reference individuals (n = 231,909) and followed through 2021. Flexible parametric survival models estimated adjusted hazard ratios (aHRs) of any and specific CLD (i.e., viral hepatitis, metabolic dysfunction-associated steatotic liver disease [MASLD], alcohol-related liver disease, and autoimmune liver disease) and MALO (compensated/decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death).FindingsDuring a median follow-up of 16.0 years, 649 patients with CeD and 1571 reference individuals developed any CLD (incidence rate: 79.4 vs. 39.5/100,000 person-years). CeD patients had a higher risk of developing any CLD than reference individuals (aHR = 2.01, 95%CI:1.82−2.22). This risk remained elevated ≥25 years after diagnosis, giving one extra CLD case per 110 CeD patients until then. Positive associations were present for autoimmune liver disease (aHR = 4.86), MASLD (aHR = 2.54), and alcohol-related liver disease (aHR = 1.51). Individuals with CeD were at significantly higher risk of incident MALO (aHR = 1.54). Sibling comparisons and sensitivity analyses confirmed the main findings.InterpretationCeD is associated with a persistently increased risk of any incident CLD, although the absolute risk is low. Physicians should be vigilant to early signs of liver dysfunction in patients with CeD.FundingEuropean Crohn's and Colitis Organisation, the Swedish Society for Medical Research (project#: PG-23-0315-H-02), FORTE (project#: 2016-00424), Takeda, and the Swiss National Science Foundation (project#: P500PM_210866).
CSI-GEP: A GPU-based unsupervised machine learning approach for recovering gene expression programs in atlas-scale single-cell RNA-seq data
Authors: Xueying Liu, Richard H Chapple, Declan Bennett, William C Wright, Ankita Sanjali, Erielle Culp, Yinwen Zhang, Min Pan, Paul Geeleher
Journal: Cell Genomics (2025)

Exploratory analysis of single-cell RNA sequencing (scRNA-seq) typically relies on hard clustering over two-dimensional projections like uniform manifold approximation and projection (UMAP). However, such methods can severely distort the data and have many arbitrary parameter choices. Methods that can model scRNA-seq data as non-discrete "gene expression programs" (GEPs) can better preserve the data's structure, but currently, they are often not scalable, not consistent across repeated runs, and lack an established method for choosing key parameters. Here, we developed a GPU-based unsupervised learning approach, "consensus and scalable inference of gene expression programs" (CSI-GEP). We show that CSI-GEP can recover ground truth GEPs in real and simulated atlas-scale scRNA-seq datasets, significantly outperforming cutting-edge methods, including GPT-based neural networks. We applied CSI-GEP to a whole mouse brain atlas of 2.2 million cells, disentangling endothelial cell types missed by other methods, and to an integrated scRNA-seq atlas of human tumors and cell lines, discovering mesenchymal-like GEPs unique to cancer cells growing in culture.
BRD4-targeted photodegradation nanoplatform for light activatable melanoma therapy
Authors: Shiman Lu, Zhaoqing Shi, Chendi Ding, Wenyan Wang, Weilang Zhang, Li Huang, Jiachan Lin, Xinpei Wang, Ran Luo, Xiaowei Zeng, Wenhu Zhou, Hongzhong Chen, Qiangsong Wang, Lin Mei
Journal: Biomaterials (2025)
Functional rescue of F508del-CFTR through revertant mutations introduced by CRISPR base editing
Authors: Irene Carrozzo, Giulia Maule, Carmelo Gentile, Alessandro Umbach, Matteo Ciciani, Daniela Guidone, Martina De Santis, Gianluca Petris, Luis Juan Vicente Galietta, Daniele Arosio, Anna Cereseto
Journal: Molecular Therapy (2025)
Triple-action cancer therapy using laser-activated NO-releasing metallomicellar nanophotosensitizer for pyroptosis-driven immune reprogramming
Authors: Ayeskanta Mohanty, Adityanarayan Mohapatra, Aravindkumar Sundaram, Padmanaban Sathiyamoorthy, Woongkyu Park, Santhosh Kalash Rajendrakumar, In-Kyu Park
Journal: Journal of Controlled Release (2025)
Twelve weeks of exercise training improves cognitive status, physical performance and quality of life in Alzheimer's disease: a systematic review and meta-analysis
Authors: Cauã Viana Fernandes de Sá Leitão, Bernardo de Faria Moraes, Gabriel André Pedral Diniz Leite, Amanda Gonçalves Duarte, Marcos Vinícius Gonçalves da Silva, Gabriel Moraes de Oliveira, Fernando Augusto Barcelos Andrade, Jair Antônio Bessa da Silva, Renata Campos Correa Dos Santos, Gustavo Soares Figueiredo, Helton Oliveira Campos, Laura Hora Rios Leite, Lucas Rios Drummond, Cândido Celso Coimbra
Journal: Ageing Research Reviews (2025)
Effect of Immunoadsorption on clinical presentation and immune alterations in COVID-19–induced and/or aggravated ME/CFS
Authors: Moritz Anft, Lea Wiemers, Kamil S Rosiewicz, Adrian Doevelaar, Sarah Skrzypczyk, Julia Kurek, Sviatlana Kaliszczyk, Maximilian Seidel, Ulrik Stervbo, Felix S Seibert, Timm H Westhoff, Nina Babel
Journal: Molecular Therapy (2025)

Autoreactive antibodies (AAB) are currently being investigated as causative or aggravating factors during post-COVID. In this study we analyze the effect of immunoadsorption therapy on symptom improvement and the relationship with immunological parameters in post-COVID patients exhibiting symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) induced or aggravated by an SARS-CoV-2 infection. This observational study includes 12 post-COVID patients exhibiting a predominance of ME/CFS symptoms alongside increased concentrations of autonomic nervous system receptors (ANSR) autoantibodies and neurological impairments. We found that following immunoadsorption therapy, the ANSR autoantibodies were nearly eliminated from the patients' blood. The removal of IgG antibodies was accompanied by a decrease of pro-inflammatory cytokines including IL4, IL2, IL1β, TNF and IL17A serum levels, and a significant reduction of soluble spike protein. Notably, a strong positive correlation between pro-inflammatory cytokines and ASNR-AABs β1, β2, M3, and M4 was observed in spike protein-positive patients, whereas no such correlation was evident in spike protein-negative patients. 30 days post-immunoadsorption therapy, patients exhibited notable improvement in neuropsychological function and a modest but statistically significant amelioration of hand grip strength was observed. However, neither self-reported symptoms nor scores on ME/CFS questionnaires showed a significant improvement and a rebound of the removed proteins occurring within a month.
Scalable control of stem cell fate by riboswitch-regulated RNA viral vector without genomic integration
Authors: Narae Kim, Yohei Yokobayashi
Journal: Molecular Therapy (2025)

Transgene expression in stem cells is a powerful means of regulating cellular properties and differentiation into various cell types. However, existing vectors for transgene expression in stem cells suffer from limitations such as the need for genomic integration, the transient nature of gene expression, and the inability to temporally regulate transgene expression, which hinder biomedical and clinical applications. Here we report a new class of RNA virus-based vectors for scalable and integration-free transgene expression in mouse embryonic stem cells (mESCs). The vector is equipped with a small molecule-regulated riboswitch and a drug selection marker that allow temporal regulation of transgene expression and stable maintenance of the vector in proliferating stem cells. We demonstrated the utility of the vector by maintaining the pluripotency of mESCs in a differentiation induction medium by expressing Nanog and inducing myogenic differentiation by triggering Myod1 expression, without altering the mESC genome.
Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates
Authors: Maureen Buckley, Mariluz Araínga, Laura Maiorino, Ivan S Pires, B J Kim, Katarzyna Kaczmarek Michaels, Jonathan Dye, Kashif Qureshi, Yiming J Zhang, Howard Mak, Jon M Steichen, William R Schief, Francois Villinger, Darrell J Irvine
Journal: Molecular Therapy (2025)

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following intramuscular injection, we observed LNPs distributing through injected muscle tissue, simultaneous with rapid trafficking to draining lymph nodes (dLNs). Deltoid injection of LNPs mimicking human vaccine administration led to stochastic LNP delivery to three different sets of dLNs. LNP uptake in dLNs was confirmed by histology, and cellular analysis of tissues via flow cytometry identified antigen-presenting cells as the primary immune cell type responsible for early LNP uptake and mRNA translation. These results provide insights into the biodistribution of mRNA vaccines administered at clinically relevant doses, injection volumes, and injection sites in an important large animal model for vaccine development.
The high efficacy of claudin18.2-targeted CAR-T cell therapy in advanced pancreatic cancer with a strategy to ensure the safety of patients
Authors: Guocheng Zhong, Xiaomin Zhang, Ruocong Zhao, Zheng Guo, Chenguang Wang, Chuan Yu, Dongzhe Liu, Ke Hu, Yujie Gao, Bochen Zhao, Xianhao Liu, Xuanren Shi, Lei Chen, Yisheng Li, Li Yu
Journal: Molecular Therapy (2025)
Antigens and adjuvants co-stabilized Pickering emulsions amplify immune responses of subunit vaccines
Authors: Zhaofei Guo, Chenqi Guo, Yuanshuai Song, Chunting He, Penghui He, Fuhua Wu, Xue Tang, Yanhua Xu, Yangsen Ou, Rui Hu, Ming Qin, Guangsheng Du, Xun Sun
Journal: Journal of Controlled Release (2025)
Genomic features underlying meningioma sex-specificity
Authors: David R Raleigh
Journal: Neuro-Oncology (2025)

Journal Article Accepted manuscript Genomic features underlying meningioma sex-specificity Get access David R Raleigh David R Raleigh Department of Radiation Oncology, Neurological Surgery, and Pathology, University of California San Francisco, San Francisco, CA, USA Correspondence: David R. Raleigh, MD, PhD, Associate Professor, Michael McDermott, MD, Professor, Meningioma Program Director, Brain Tumor Center Principal Investigator and Preclinical Therapeutics Core Director, Departments of Radiation Oncology, Neurological Surgery, and Pathology, University of California San Francisco, Helen Diller Family Cancer Research Building, 1450 3rd Street, HD481, San Francisco, CA 94158, [email protected] https://orcid.org/0000-0001-9299-8864 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noaf002, https://doi.org/10.1093/neuonc/noaf002 Published: 08 January 2025 Article history Received: 29 December 2024 Published: 08 January 2025
Governance of national public health agencies: a crucial yet neglected aspect of health emergency preparedness and response
Authors: Kumanan Rasanathan, Sara Hersey, Zubin Cyrus Shroff, Geoffrey Namara
Journal: BMJ (2025)

Despite innovations and some impressive national responses, the covid-19 pandemic revealed limitations and gaps in efforts at national and global levels to prepare for and respond to health emergencies. 1 2National public health agencies are "government agencies or closely networked group of agencies that provide science-based leadership, expertise, and coordination for a country's public health activities." 3 The impact of the governance of these agencies on the provision of essential public health functions has drawn greater attention in the wake of the covid-19 pandemic. 4 5Similar attention to the role and structure of national public health agencies occurred after previous infectious disease pandemics and outbreaks such as the 1918 influenza pandemic, the SARS outbreak of 2003-2004, and the West Africa Ebola epidemic.
Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey
Authors: Christian S. Scheer, Evangelos J. Giamarellos-Bourboulis, Ricard Ferrer, Evgeny A. Idelevich, Djillali Annane, Antonio Artigas, Abdullah Tarik Aslan, Gabriella Bottari, Hjalmar R. Bouma, Vladimir Černy, Renata Curić Radivojević, Konstantina Dakou, Ken Dewitte, Mohamed Elbahnasawy, Matthias Gründling, Mohan Gurjar, Johanna Hästbacka, Miltiadis Kyprianou, Said Laribi, Annmarie Lassen, Konstantin Lebedinskii, Jan Máca, Manu L. N. G. Malbrain, Gianpaola Monti, Marlies Ostermann, Michael Osthoff, José Artur Paiva, Michela Sabbatucci, Jakub Śmiechowicz, Mihai Gabriel Ştefan, Marcus Vollmer, Natalija Vuković, Kyriakos Zaragkoulias, Konrad Reinhart, Adam Linder, Daniela Filipescu
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals. A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives in hospitals. 1023 hospitals in 69 countries were included. Most of them, 835 (81.6%) were from Europe. Sepsis screening was used in 54.2% of emergency departments(EDs), 47.9% of wards, and 61.7% of intensive care units(ICUs). Sepsis management was standardized in 57.3% of EDs, 45.2% of wards and in 70.7% of ICUs. The implementation of comprehensive quality improvement initiatives(QIIs) was associated with increased screening (EDs +33.3%; wards +44.4%; ICUs +23.8% absolute difference) and increased standardized sepsis management (EDs +33.6%; wards +40.0%; ICUs: +17.7% absolute difference) compared to hospitals without QIIs. 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regards to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.
Effect of Individualized PEEP Titrated by EIT in Patients with Acute Respiratory Distress Syndrome
Authors: Xueyan Yuan, Dongyu Chen, Yali Chao, Rui Zhang, Lanqi Guo, Jianfeng Xie, Songqiao Liu, Zhanqi Zhao, Yingzi Huang, Yi Yang, Tommaso Mauri, Haibo Qiu, Ling Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2025)