tbuckley/cabot-search huggingface dataset:
The trajectory of sedative adverse events caused by antipsychotics: a meta-analysis of individual participant data from randomised, placebo-controlled, clinical trials in acute phase schizophrenia
Authors: Nobuyuki Nomura, Spyridon Siafis, Johannes Schneider-Thoma, Lasse Brandt, Jinyoung Park, Orestis Efthimiou, Josef Priller, John M Davis, Hiroyoshi Takeuchi, Stefan Leucht
Journal: The Lancet Psychiatry (2025)

Sedative adverse events are common in patients with schizophrenia undergoing antipsychotic treatment, which affects treatment adherence and the patients' quality of life. Although tolerance to sedation is believed to develop, robust evidence documenting the timing of sedation onset and resolution remains elusive. To address this gap, we aimed to assess the dynamics of onset and resolution of sedation across various antipsychotics in patients with schizophrenia. In this meta-analysis, we included placebo-controlled, randomised controlled trials (RCTs) of antipsychotic monotherapy for the acute phase of schizophrenia and schizoaffective disorder. We searched PubMed for RCTs from inception until May 6, 2021 and obtained individual participant data of included trials through the Yale University Open Data Access project. We created Kaplan-Meier curves to assess the probability of onset of sedation and resolution from the incidence of sedation across time after treatment initiation. People with lived experience were not involved in this study. This study is registered with PROSPERO, CRD42022351647. We included a total of 6791 participants (4549 [67·0%] men and 2242 [33·0%] women, with a mean age of 38·0 years [SD 12·4, range 13-81], 1172 [17·3%] were Asian, 1626 [23·9%] were Black, 3654 [53·8%] were White, and 339 [5·0%] were other ethnicities) from 19 RCTs. Sedative adverse events were observed in 582 (8·6%) of 6791 participants and typically occurred shortly after treatment initiation. Among participants receiving antipsychotics, 418 (83%) of 505 sedation events occurred within the first 2 weeks of treatment. Following the onset of sedation, 50% of symptoms were resolved within 1 week. After 4 weeks of treatment, 24% (95% CI 19·7-29·3) continued to have sedation with oral agents and 22·3% (15·3-32·3) with long-acting injectables. The high incidence of sedation within the first 2 weeks of treatment with antipsychotics emphasises the importance of early monitoring. Half of the sedation resolved within 1 week and 75% within 1 month, suggesting that tolerance to sedation is acquired quickly. If sedation is sustained, contributing factors should be evaluated. German Federal Ministry of Education and Research.
Long-term efficacy and safety of sofosbuvir-based direct-acting antiviral regimens in paediatric patients with hepatitis C virus infection: an international registry study
Authors: Regino P Gonzalez-Peralta, Jessica W Wen, Winita Hardikar, Wikrom W Karnsakul, Suzanne Whitworth, Chuan-Hao Lin, Giuseppe Indolfi, Philip Rosenthal, William Balistreri, Kathleen B Schwarz, Jonathan R Honegger, Xu Zhang, Evguenia C Svarovskaia, Vithika Suri, Kathryn Kersey, Daniel H Leung
Journal: The Lancet Child & Adolescent Health (2025)
Healthy skin for children and young people with skin of colour starts with clinician knowledge and recognition: a narrative review
Authors: Bernadette M Ricciardo, Heather-Lynn Kessaris, Sarah Cherian, S Prasad Kumarasinghe, Ingrid Amgarth-Duff, Dasmesh Sron, Regina Oladokun, Artiene H Tatian, Asha C Bowen
Journal: The Lancet Child & Adolescent Health (2025)
Simplifying medicine dosing for children by harmonising weight bands across therapeutic areas
Authors: Hylke Waalewijn, Mounier Almett, Roeland E Wasmann, Tim R Cressey, Philippa Easterbrook, Peter Ehizibue Olumese, Anneke C Hesseling, Anthony J Garcia-Prats, Joel Tarning, Anna Turkova, Kerri Viney, Elin M Svensson, Angela Colbers, Wilson M Were, Paolo Denti, Martina Penazzato
Journal: The Lancet Child & Adolescent Health (2025)
Adjunctive dexamethasone and 30-day all-cause death after hospital admission in paediatric pneumococcal meningitis: a propensity score analysis
Authors: Anna Giolito, Corinne Levy, Emmanuelle Varon, Robert Cohen, Sidonie Hanna, Zein Assad, Léa Lenglart, Stephane Bechet, Stephane Bonacorsi, François Dubos, Elise Launay, Morgane Pelleter, Alexis Rybak, Francois Angoulvant, Michael Levy, Naïm Ouldali
Journal: The Lancet Child & Adolescent Health (2025)
Life-course socioeconomic position and the gut microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Monica A. Batalha, Madison N. LeCroy, Juan Lin, Brandilyn A. Peters, Qibin Qi, Zheng Wang, Tao Wang, Linda C. Gallo, Gregory A. Talavera, Amanda C. McClain, Bharat Thyagarajan, Martha L. Daviglus, Lifang Hou, Maria Llabre, Jianwen Cai, Robert C. Kaplan, Carmen R. Isasi
Journal: Gut Microbes (2025)

Socioeconomic position (SEP) in childhood and beyond may influence the gut microbiome, with implications for disease risk. Studies evaluating the relationship between life-course SEP and the gut microbiome are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SEP. We use the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based cohort study conducted in four field centers in the United States (U.S.), to evaluate the association between life-course SEP and gut microbiome composition. Life-course SEP indicators included parental education (proxy of childhood SEP), current SEP (n = 2174), and childhood (n = 988) and current economic hardship (n = 994). Shotgun sequencing was performed on stool samples. Analysis of Compositions of Microbiomes was used to identify associations of life-course SEP indicators with gut microbiome species and functions. Parental education and current SEP were associated with the overall gut microbiome composition; however, parental education and current education explained more the gut microbiome variance than the current SEP. A lower parental education and current SEP were associated with a lower abundance of species from genus Bacteroides. In stratified analysis by nativity, we found similar findings mainly among foreign-born participants. Early-life SEP may have long-term effects on gut microbiome composition underscoring another biological mechanism linking early childhood factors to adult disease.
Protein to biomaterials: Unraveling the antiviral and proangiogenic activities of Ac-Tβ1-17 peptide, a thymosin β4 metabolite, and its implications in peptide-scaffold preparation
Authors: Khandoker Asiqur Rahaman, Md Sofequl Islam Mukim, Md Lemon Hasan, Hyeok Kim, Cheol-Ho Pan, Oh-Seung Kwon, Dae-Geun Song, Hyung-Seop Han
Journal: Bioactive Materials (2025)
Core Outcome Set and Reporting Checklist for Studies on Vasa Previa
Authors: Tiffany Yeretsian, Nasrin Javid, Natasha Hirschhorn-Edwards, Rizwana Ashraf, Alisha Adams, John Kingdom, Rohan D’Souza
Journal: JAMA Network Open (2025)

Importance Vasa previa, although a rare condition affecting 0.46 per 1000 pregnancies, results in high rates of fetal and neonatal mortality and morbidity. Widespread use of a core outcome set and reporting checklist may enable data harmonization, enhance evidence synthesis, and ensure prioritization of patient-important outcomes in clinical practice, future research, and clinical practice guidelines. Objective To develop a core outcome set for studies on vasa previa that includes perinatal screening, diagnosis, and management of vasa previa. Design, Setting, and Participants This survey study involved a 2-round international and cross-disciplinary Delphi survey and virtual consensus meetings conducted between March 14, 2021, and October 4, 2022. Health care professionals (HCPs) and health service users (HSUs) were invited to participate in the development of the core outcome set. Exposure Perinatal screening, diagnosis, and management of vasa previa. Main Outcome and Measures Core outcomes and reporting checklist items for future studies on vasa previa were developed using Delphi surveys, small group discussions, and a consensus meeting. Results An international group of 204 participants, comprising 115 HSUs and 89 HCPs representing 27 countries, rated 67 outcomes identified through a systematic review and qualitative interviews in a 2-round online Delphi survey. Through virtual small group discussions and a consensus meeting, 13 core outcomes were identified: pregnancy outcome (live birth, fetal loss [miscarriage or stillbirth], or neonatal death), severe neonatal morbidity, fetal/neonatal blood loss, neonatal intensive care unit admission for &amp;amp;gt;24 hours, gestational age at birth, third trimester confirmation of vasa previa diagnosis, neurocognitive and developmental outcomes, mode of birth, maternal death or severe morbidity, maternal quality of life, duration of antepartum admission, and antepartum or peripartum hemorrhage. A 22-item reporting checklist was simultaneously developed to include important items in studies on vasa previa when possible and/or relevant. Conclusions and Relevance The core outcome set and reporting checklist for vasa previa are hoped to encourage researchers to incorporate patient-important outcomes in future studies to enable data harmonization, improve evidence synthesis, and facilitate the development of clinical practice guidelines for this rare and highly lethal condition for which timely diagnosis and management may prevent fetal and maternal morbidity and mortality.
Safety and efficacy of gene therapy for RAG1-deficient SCID
Authors: Frank J T Staal, Karin Pike-Overzet, Sander de Kivit, Lisa Ott de Bruin, Lucia Mamede, Martine Pergent, Johan Prevot, Michael Rothe, Axel Schambach, Arjan Lankester
Journal: Molecular Therapy (2025)
Analysis of 30 chromosome-level Drosophila genome assemblies reveals dynamic evolution of centromeric satellite repeats
Authors: Daniel Gebert, Amir D Hay, Jennifer P Hoang, Adam E Gibbon, Ian R Henderson, Felipe Karam Teixeira
Journal: Genome biology (2025)

Abstract Background The Drosophila genus is ideal for studying genome evolution due to its relatively simple chromosome structure and small genome size, with rearrangements mainly restricted to within chromosome arms, such as Muller elements. However, work on the rapidly evolving repetitive genomic regions, composed of transposons and tandem repeats, have been hampered by the lack of genus-wide chromosome-level assemblies. Results Integrating long-read genomic sequencing and chromosome capture technology, here we produce and annotate 30 chromosome-level genome assemblies within the Drosophila genus. Based on this dataset, we reveal the evolutionary dynamics of genome rearrangements across the Drosophila phylogeny, including the identification of genomic regions that show comparatively high structural stability throughout evolution. Moreover, within the ananassae subgroup, we uncover the emergence of new chromosome conformations and the rapid expansion of novel satellite DNA sequence families, which form large and continuous pericentromeric domains with higher-order repeat structures that are reminiscent of those observed in the human and Arabidopsis genomes. Conclusions These chromosome-level genome assemblies present a valuable resource for future research, the power of which is demonstrated by our analysis of genome rearrangements and chromosome evolution. In addition, based on our findings, we propose the ananassae subgroup as an ideal model system for studying the evolution of centromere structure.
Ibrutinib, lenalidomide, and rituximab in relapsed mantle cell lymphoma: Long‐term follow‐up of the Nordic Lymphoma Group MCL6 Philemon trial
Authors: Elin Forsgren, Rasmus R. K. Jørgensen, Hans Bentzen, Jon Riise, Jacob Haaber, Annika Pasanen, Hanne Kuitunen, Karin F. Wader, Tarec C. El‐Galaly, Martin Hutchings, Ingrid Glimelius, Mats Jerkeman
Journal: HemaSphere (2025)

Abstract Relapsed or refractory mantle cell lymphoma (R/R MCL) remains difficult to treat, with outcomes dependent on the treatment regimen and remission duration after first‐line therapy. Several non‐chemotherapeutic regimens are under evaluation in R/R, but few studies report long‐term outcomes. In this study, we present the long‐term outcomes of the 50 patients treated with ibrutinib, lenalidomide, and rituximab (IR2) in the Nordic Lymphoma Group MCL6 Philemon phase 2 trial. Survival outcomes were compared with a matched cohort from the Swedish MCL complete study. After 5 years, 14 patients (28%) remained relapse‐free, including one with a TP53 mutation. The median progression‐free survival (PFS) was 17.4 months, with the longest PFS of 8.1 years. Thirty‐two patients had died, primarily from MCL (72%). Poorer survival was associated with intermediate or high‐risk Mantle Cell Lymphoma International Prognostic Index and impaired health‐related quality of life (HRQoL). While TP53 mutations ( n = 11) did not significantly impact survival, a trend toward poorer outcomes was observed in multivariable Cox regression analyses (PFS hazard ratio: 2.09, 95% confidence interval: 0.95–4.62, p = 0.068). The IR2 regimen demonstrated superior survival compared to the MCL complete cohort both before and after matching. In conclusion, this study highlights the role of non‐chemotherapeutic agents in R/R MCL and demonstrates the prognostic impact of HRQoL on overall survival. Although IR2 showed initial activity in TP53‐mutated patients, it did not completely overcome their poor prognosis. However, the IR2 regimen may serve as a bridge to allogeneic stem cell transplantation or chimeric antigen receptor T‐cell therapy.
Inhibition of the NLRP3 inflammasome using MCC950 reduces vincristine‐induced adverse effects in an acute lymphoblastic leukemia patient‐derived xenograft model
Authors: Hana Starobova, Hannah McCalmont, Svetlana Shatunova, Nicolette Tay, Christopher M. Smith, Avril Robertson, Ingrid Winkler, Richard B. Lock, Irina Vetter
Journal: HemaSphere (2025)

Abstract Vincristine is one of the most important chemotherapeutic drugs used to treat acute lymphoblastic leukemia (ALL). Unfortunately, vincristine often causes severe adverse effects, including sensory–motor neuropathies, weight loss, and overall decreased well‐being, that are difficult to control and that decrease the quality of life and survival of patients. Recent studies demonstrate that sensory–motor adverse effects of vincristine are driven by neuroinflammatory processes, including the activation of the Nod‐like receptor 3 (NLRP3) inflammasome. In this study, we aimed to test the effects of MCC950, a specific NLRP3 inhibitor, on the prevention of vincristine‐induced adverse effects as well as tumor progression and vincristine efficacy in NOD/SCID/interleukin‐2 receptor γ ‐negative mice patient‐derived xenografts of ALL. We demonstrate that co‐administration of MCC950 effectively prevented the development of mechanical allodynia, motor impairment, and weight loss and significantly improved the overall well‐being of the animals without negatively impacting the in vivo efficacy of vincristine as a single agent or in combination with standard‐of‐care drugs. These results provide proof of principle that the adverse effects of vincristine chemotherapy can be prevented using NLRP3 inflammasome inhibitors and provide new options for the development of effective treatment strategies.
The paradigm shifts of periodontal regeneration strategy: From reparative manipulation to developmental engineering
Authors: Guanqi Liu, Junlong Xue, Xuan Zhou, Mixiao Gui, Ruidi Xia, Yanshu Zhang, Yihua Cai, Shuhua Li, Songtao Shi, Xueli Mao, Zetao Chen
Journal: Bioactive Materials (2025)
Cytosolic Phospholipase A2 determines Intercellular Heterogeneity of Stress Granules and Chemotherapy Response
Authors: Alexandra Redding, Guillaume Fonteneau, Stefan Heinrich, Matthias M. Gaida, Elda Grabocka
Journal: Cancer Discovery (2025)

Abstract Cancer cell heterogeneity is a major therapeutic challenge. Here, we identify that individual cells within cancer cell populations show significant heterogeneity in the levels of the stress-adaptive organelles, stress granules (SGs), and demonstrate that SG heterogeneity is dictated by cell-cycle state. Specifically, SG-formation is distinctively heightened in cells in G2-phase due to the interplay between a non-apoptotic function of Caspase 3 and calcium-dependent phospholipase A2 (cPLA2)-mediated production of the SG-promoting molecule, 15-deoxy-delta-prostaglandin-J2 (15d-PGJ2). We demonstrate that in G1/S phase, Caspase 3 cleaves and inactivates cPLA2, whereas in G2-phase, Caspase 3 activity is suppressed, resulting in enhanced cPLA2 activity and 15d-PGJ2 upregulation. We show that cell-cycle-dependent SG heterogeneity is a property of pancreatic ductal adenocarcinoma (PDAC) and targeting G2-SGs by inhibiting cPLA2 sensitizes PDAC to G2-arrest-inducing chemotherapeutics. Our findings highlight cell-cycle-dependent SG formation as a fundamental property of SGs, a key aspect of cancer heterogeneity, and a target for cancer treatment.
An Enhanced Long‐Term Wet Adhesion Strategy of Spatial Control the Emergence of Dual Covalent Cross‐Linking for Sutureless Cornea Transplant
Authors: Zhuhao Tan, Wenfang Liu, Siqi Jiang, Jia Liu, Jingjie Shen, Xiaoyun Peng, Baolei Huang, Hailin Zhang, Wenjing Song, Li Ren
Journal: Advanced Healthcare Materials (2025)

Abstract Corneal transplantation regeneration requires bioadhesives to perform long‐term and stable adhesion functions in a wet environment. However, many current studies focus on the instantaneous or short‐term adhesion persistence of bioadhesives, and ignore the evaluation of their long‐term wet adhesion behaviors which is urgent for keratoplasty repair process. In view of this situation, a dual covalent cross‐linking hydrogel (ASO) bioadhesive is developed. The ASO bioadhesive comprised acrylated gelatin(G‐AA), thiolated gelatin(G‐SH), and oxidized dextran (OD). Introduction of thiol chemistry made the emergence of ASO dual covalent cross‐linking controllable by UV light irradiation. The analysis of this feature revealed an intriguing phenomenon. The ASO bioadhesive demonstrated spatially specific control over cross‐linking behavior by first penetrating the tissue and then initiating cross‐linking, thereby significantly enhancing its long‐term wet adhesion ability. The ASO bioadhesive can maintain more than 50% adhesion after being immersed in wet environment for one month. Subsequently, ASO bioadhesive demonstrated long‐term wet adhesive stability once again on corneal lamellar transplantation model through maintaining strong anchorage of corneal donor to recipient bed and promoting their integration. The unprecedented adhesive mechanism presented in this study provided innovated theoretical basis for designing bioadhesives with superior long‐term wet adhesion.
Bimetallic NiCu‐MOF Protects DOX‐Induced Myocardial Injury and Cardiac Dysfunction by Suppressing Ferroptosis and Inflammation
Authors: Lu Liu, Daiyong Chao, Qing Dong, Xianli Zhang, Kai Zhang, Zhenyu Ju
Journal: Advanced Healthcare Materials (2025)

Abstract Doxorubicin (DOX), a potent anthracycline chemotherapeutic agent, is widely used in cancer treatment but is associated with significant adverse effects, particularly DOX‐induced cardiomyopathy (DIC). DIC pathogenesis involves the generation of reactive oxygen species (ROS) and ferroptosis induction. Novel therapeutic strategies targeting antioxidant defenses and ferroptosis inhibition are essential for mitigating DIC. An innovative bimetallic metal‐organic framework (MOF), NiCu‐MOF (NCM), is developed, exhibiting multifaceted antioxidant enzyme‐mimicking activities that effectively scavenge a broad spectrum of ROS. Additionally, the bimetallic NCM exhibits excellent iron‐chelating ability. In vitro experiments demonstrate that NCM significantly reduces cardiomyocyte death by attenuating ROS levels and inhibiting ferroptosis. Furthermore, in a mouse model of DIC, NCM treatment results in substantial myocardial protection, evidenced by improved cardiac function and structural integrity. This protective effect is attributed to suppression of ferroptosis, preservation of mitochondrial function, and attenuation of inflammatory responses. Collectively, these findings highlight biocompatible NCM's potential as a novel cardioprotective agent and offer a promising therapeutic strategy for managing DIC.
Smart Health Monitoring: Review of Electrochemical Biosensors for Cortisol Monitoring
Authors: Zhijie Li, Dan Luo, Yaqian Zhang, Xin Niu, Hao Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Cortisol, also known as the stress hormone, is a crucial corticosteroid hormone that significantly increases secretion in the human body when facing notable stress. Monitoring cortisol levels is crucial for personal stress management and the diagnosis and treatment of certain diseases. Electrochemical biosensors combine the efficient sensitivity of electrochemical technology with the high specificity of biological recognition processes, making them widely applicable in the analysis of human body fluid components. This work outlines the working mechanism of cortisol electrochemical biosensors, focusing particularly on sensing elements such as antibodies, aptamers, and molecularly imprinted polymers. It provides detailed explanations of the operational principles of these different recognition elements. This work summarizes and evaluates the latest advancements in electrochemical biosensors for detecting cortisol in human body fluids, discussing the influence of different recognition elements on sensor design and electrochemical performance. Subsequently, through a comparative analysis of various sensor performances, the work further discusses the challenges in translating laboratory achievements into practical applications, including enhancing key metrics such as sensor reusability, reproducibility, long‐term stability, continuous monitoring capability, and response time. Finally, it offers insights and recommendations for achieving real‐time, continuous, and long‐term monitoring with cortisol electrochemical biosensors.
Quantitative characterization of cell niches in spatially resolved omics data
Authors: Sebastian Birk, Irene Bonafonte-Pardàs, Adib Miraki Feriz, Adam Boxall, Eneritz Agirre, Fani Memi, Anna Maguza, Anamika Yadav, Erick Armingol, Rong Fan, Gonçalo Castelo-Branco, Fabian J. Theis, Omer Ali Bayraktar, Carlos Talavera-López, Mohammad Lotfollahi
Journal: Nature Genetics (2025)

Abstract Spatial omics enable the characterization of colocalized cell communities that coordinate specific functions within tissues. These communities, or niches, are shaped by interactions between neighboring cells, yet existing computational methods rarely leverage such interactions for their identification and characterization. To address this gap, here we introduce NicheCompass, a graph deep-learning method that models cellular communication to learn interpretable cell embeddings that encode signaling events, enabling the identification of niches and their underlying processes. Unlike existing methods, NicheCompass quantitatively characterizes niches based on communication pathways and consistently outperforms alternatives. We show its versatility by mapping tissue architecture during mouse embryonic development and delineating tumor niches in human cancers, including a spatial reference mapping application. Finally, we extend its capabilities to spatial multi-omics, demonstrate cross-technology integration with datasets from different sequencing platforms and construct a whole mouse brain spatial atlas comprising 8.4 million cells, highlighting NicheCompass’ scalability. Overall, NicheCompass provides a scalable framework for identifying and analyzing niches through signaling events.
mRNA-based seasonal influenza and SARS-CoV-2 multicomponent vaccine in healthy adults: a phase 1/2 trial
Authors: Amanda K Rudman Spergel, Jintanat Ananworanich, Ruiting Guo, Weiping Deng, Lizbeth Carmona, Kristin Schaefers, Yamuna D Paila, Boris Kandinov, Charles H Eger, Melissa Sinkiewicz, Sarah Shao, Carole Henry, Christine A Shaw
Journal: Nature Medicine (2025)