tbuckley/cabot-search huggingface dataset:
Characteristic immune cell interactions in livers of children with acute hepatitis revealed by spatial single-cell analysis identify a possible postacute sequel of COVID-19
Authors: Felix Röttele, Andreas Zollner, Carolin Mogler, Muhammed Yuksel, Cigdem Arikan, Vivien Karl, Judith Helene Aberle, Stephan W Aberle, Hubert Kogler, Andreas Vécsei, Julia Vodopiutz, Henrike Salié, Anne Gräser, Laurenz Krimmel, Pius Martin, Eberhard Lurz, Felix Immanuel Maier, Lena Woelfle, Susana Nobre, Isabel Goncalves, Lisa Kern, Martin Schwemmle, Tobias Boettler, Maike Hofmann, Peter Hasselblatt, Robert Thimme, Herbert Tilg, Thomas Müller, Georg Friedrich Vogel, Bertram Bengsch
Journal: Gut (2025)

Background A rise in paediatric cases of acute hepatitis of unknown origin (AHUO) was observed in 2022, some requiring liver transplantation. A link to adeno-associated virus 2 infection and CD4 + T-cell mediated disease was reported in cohorts in the UK and USA but does not explain all cases. Objective To determine the intrahepatic immune cell interactions in the inflamed liver and a possible contribution of SARS-CoV-2 infection. Design Patients with acute non-A non-E hepatitis (10/12 AHUO, 2/12 subacute) during February 2022–December 2022 undergoing liver biopsy were recruited in a European patient cohort. Hepatological, virological, histopathological and highly multiplexed spatial and single-cell analyses of liver biopsies were performed. Results Patients were negative for adenoviral and SARS-CoV-2 PCR. Three patients had a positive adenoviral serology and 10/12 patients had a history or serological evidence of SARS-CoV-2 infection. Imaging mass cytometry identified significant intrahepatic immune infiltration with an enrichment of CD8 + T-cells. The highest CD8 infiltration and concomitant peripheral immune activation were observed in patients with the most severe hepatitis. CD8 + T-cell infiltration was connected to histomorphological interface hepatitis and bridging necrosis. Cellular neighbourhood analysis indicated disease-associated microanatomic interactions between CX3CR1 + endothelial and myeloid cell populations, interacting with effector CD8 + T-cells suggesting a pathogenic cellular triad. Of note, we detected intrahepatic SARS-CoV-2 antigens in ACE2-expressing cells in the areas with significant pathology in 11/12 samples using several different detection methods. 10/12 patients were treated with corticosteroid therapy and no liver transplantation was required. Conclusions We identified a possible manifestation of an immune-mediated postacute sequel to COVID-19 associated with a characteristic immune infiltrate in children with AHUO. COVID-19 testing should be considered in paediatric AHUO.
The neurobiology of overeating
Authors: Garret D Stuber, Valerie M Schwitzgebel, Christian Lüscher
Journal: Neuron (2025)

Food intake serves to maintain energy homeostasis; however, overeating can result in obesity, which is associated with serious health complications. In this review, we explore the intricate relationship between overeating, obesity, and the underlying neurobiological mechanisms. We review the homeostatic and hedonic feeding systems, highlighting the role of the hypothalamus and reward systems in controlling food intake and energy balance. Dysregulation in both these systems leads to overeating, as seen in genetic syndromes and environmental models affecting appetite regulation when consuming highly palatable food. The concept of "food addiction" is examined, drawing parallels to drug addiction. We discuss the cellular substrate for addiction-related behavior and current pharmacological obesity treatments-in particular, GLP-1 receptor agonists-showcasing synaptic plasticity in the context of overeating and palatable food exposure. A comprehensive model integrating insights from addiction research is proposed to guide effective interventions for maladaptive feeding behaviors. Ultimately, unraveling the neurobiological basis of overeating holds promise for addressing the pressing public health issue of obesity.
Circulating tumor DNA Clearance as a Predictive Biomarker of Pathologic Complete Response in Patients with Solid Tumors Treated with Neoadjuvant Immune-Checkpoint Inhibitors: a Systematic Review and Meta-Analysis
Authors: C Valenza, E F Saldanha, Y Gong, P De Placido, D Gritsch, H Ortiz, D Trapani, F Conforti, C Cremolini, S Peters, J Mateo, V Subbiah, H A Parsons, A H Partridge, G Curigliano
Journal: Annals of Oncology (2025)
Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures
Authors: Zhonghui Tang, Yinqi Bai, Qi Fang, Yuchen Yuan, Qianwen Zeng, Shuling Chen, Tianyi Xu, Jianyu Chen, Li Tan, Chunqing Wang, Qian Li, Jinpei Lin, Zhuoxuan Yang, Xia Wu, Guowei Shi, Ji Wang, Changjun Yin, Jianping Guo, Shiping Liu, Sui Peng, Ming Kuang
Journal: Cancer Cell (2025)
Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion
Authors: Yinghua Zhu, Ziwei Zhou, Xin Du, Xiaorong Lin, Zhi-Mei Liang, Si Chen, Yiwei Sun, Yue Wang, Zhenkun Na, Zhiyong Wu, Jiaxin Zhong, Beinan Han, Xiangping Zhu, Wenkui Fu, Hongde Li, Man-Li Luo, Hai Hu
Journal: Cancer Cell (2025)
Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups
Authors: Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Fei Wang, Yan Wang, Tian Ding, Desheng Jing, Guixiong Fan, Zhiyun Gong, Renquan Lu, Yi Qin, Jie Chen, Xiaowu Xu, Pei Wang, Bing Zhang, Li Ding, Ana I Robles, Henry Rodriguez, David K Chang, Ralph H Hruban, Dong Gao, Daming Gao, Gang Jin, Hu Zhou, Jianmin Wu, Xianjun Yu
Journal: Cancer Cell (2025)
Development of Polygenic Risk Score for Persistent Albuminuria in Children and Adults With Sickle Cell Anemia
Authors: Rima S. Zahr, Guolian Kang, Xu Zhang, Sara R. Rashkin, Csaba P. Kovesdy, Clifford Takemoto, Mitch Weiss, Jeffrey Lebensburger, Kenneth I. Ataga, Santosh L. Saraf
Journal: American Journal of Hematology (2025)

ABSTRACT Albuminuria is associated with high‐risk apolipoprotein‐L1 variants ( APOL1 G1/G2) in patients with sickle cell anemia (SCA). However, this gene variant does not account for all chronic kidney disease (CKD) risk. We hypothesized that we could develop a polygenic risk score (PRS) for CKD in SCA, combining APOL1 G1/G2 with other candidate genes that modify SCA severity and further stratify patients into risk categories based on this risk score. Variants in APOL1 , HMOX1 (rs743811), BCL11A (rs1424407), and α‐thalassemia ( α −3.7 ) were identified in children with SCA enrolled in the Sickle Cell Clinical Research and Intervention Program longitudinal cohort (SCCRIP). We individually tested the association of these variants with persistent albuminuria, tested a three‐variant PRS (PRS‐3) ( APOL1 , BCL11A (rs1424407), and α −3.7 ), and developed a four‐variant PRS (PRS‐4) after adding HMOX1 (rs743811) to PRS‐3 using the summation of high‐risk alleles. An adult SCA cohort from the University of Illinois, Chicago (UIC), was used for validation. Persistent albuminuria was defined as having a urine albumin‐to‐creatinine ratio (UACR) ≥ 30 mg/g on at least 2 of 3 consecutive measurements. In both cohorts, APOL1 risk variants increased the risk while α‐thalassemia protected against persistent albuminuria. PRS‐4 was significantly associated with persistent albuminuria (SCCRIP: p = 0.004; UIC: p = 0.00016). When stratifying patients into three and four risk categories based on the PRS, 58% and 86% of the high‐risk (PRS‐3) and 54% and 89% of very high‐risk (PRS‐4) categories developed persistent albuminuria cases in the SCCRIP and UIC cohorts, respectively. A PRS may identify high‐risk SCA patients for albuminuria. Applying this PRS to guide the early implementation of disease modifiers and renoprotective therapies may help reduce the burden of SCA‐related CKD. Trial Registration: NCT02098863
A Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders: State of the Art and Challenges Toward Clinical Translation
Authors: Rudolf L. Z. Ganzoni, Sofie S. Bournons, Erick M. Carreira, Dimitri De Bundel, Ilse Smolders
Journal: Medicinal Research Reviews (2025)

ABSTRACT Photopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising for the treatment of neurological disorders. Despite the enticing prospects of photopharmacology, its application to treat human central nervous system (CNS) diseases remains to be demonstrated. In this review, we provide an overview of prominent strategies for the design and activation of photopharmaceutical agents in the field of neuroscience. Photocaged and photoswitchable drugs and bioactive molecules are discussed, and an instructive list of examples is provided to highlight compound design strategies. Special emphasis is placed on photoactivatable compounds for the modulation of glutamatergic, GABAergic, dopaminergic, and serotonergic neurotransmission for the treatment of neurological conditions, as well as various photoresponsive molecules with potential for improved pain management. Compounds holding promise for clinical translation are discussed in‐depth and their potential for future applications is assessed. Neurophotopharmaceuticals have yet to achieve breakthrough in the clinic, as both light delivery and drug design have not reached full maturity. However, by describing the current state of the art and providing illustrative case studies, we offer a perspective on future opportunities in the field of neurophotopharmacology focused on addressing CNS disorders.
Recommendations from the 10th European Conference on Infections in Leukaemia for the management of cytomegalovirus in patients after allogeneic haematopoietic cell transplantation and other T-cell-engaging therapies
Authors: Per Ljungman, Sophie Alain, Roy F Chemaly, Hermann Einsele, Federica Galaverna, Hans H Hirsch, Alicja Sadowska-Klasa, David Navarro, Jan Styczynski, Rafael de la Camara
Journal: The Lancet Infectious Diseases (2025)
The future of tumor organoids in precision therapy
Authors: Seok-Young Kim, Marc van de Wetering, Hans Clevers, Karin Sanders
Journal: Trends in cancer (2025)

Tumoroids are cultures of patient-derived tumor cells, which are grown in 3D in the presence of an extracellular matrix extract and specific growth factors. Tumoroids can be generated from adult as well as pediatric cancers, including epithelial cancers, sarcomas, and brain cancers. Tumoroids retain multi-omic characteristics of their corresponding tumor and recapitulate interpatient and intratumor heterogeneity. Retrospective and prospective studies have demonstrated that tumoroids predict patient responses to anticancer therapies, making them a promising tool for precision oncology. However, several challenges remain before tumoroids can be fully integrated into clinical decision-making, including success rates of tumoroid establishment and turnaround times. This review discusses the current advances, challenges, and future directions of tumoroid-based models in cancer research and precision therapy.
Mobilising national and regional assets and non-state actors for pandemic preparedness
Authors: Louisa Sun, Duncan Selbie, Ali S Khan, Salim S Abdool Karim, Helena Legido-Quigley, Folasade T Ogunsola, Gwendolen Eamer, Malebona Precious Matsoso, Daniel G Bausch, Dale Fisher
Journal: The Lancet (2025)
Nirmatrelvir–ritonavir versus placebo–ritonavir in individuals with long COVID in the USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial
Authors: Mitsuaki Sawano, Bornali Bhattacharjee, César Caraballo, Rohan Khera, Shu-Xia Li, Jeph Herrin, Dany Christian, Andreas Coppi, Frederick Warner, Julie Holub, Yashira Henriquez, Maria A Johnson, Theresa B Goddard, Erica Rocco, Amy C Hummel, Mohammad Al Mouslmani, William Brenham Hooper, David F Putrino, Kevin D Carr, Lawrence Charnas, Magdia De Jesus, Dale Nepert, Paula Abreu, Frank W Ziegler, John A Spertus, Akiko Iwasaki, Harlan M Krumholz
Journal: The Lancet Infectious Diseases (2025)
Incorporation of cellular membrane protein extracts into lipid nanoparticles enhances their cellular uptake and mRNA delivery efficiency
Authors: Diego A Rodríguez, Gaspard P R Lefebvre, Qiangbing Yang, Arjan D Barendrecht, Cor W Seinen, Raymond M Schiffelers, Pieter Vader
Journal: Journal of Controlled Release (2025)

mRNA therapeutics enable transient expression of desired proteins within cells, holding great potential for advancements in vaccines, protein replacement therapies and gene editing approaches. Lipid nanoparticles (LNPs) are arguably the leading nanoplatform for mRNA delivery due to their scalability and transfection efficiency. However, their limited ability to target specific cell types, inefficient cellular uptake by many cell types, and endosomal entrapment represent challenges for improving targeted mRNA delivery. To address this, we evaluated a novel class of LNPs functionalized with cell-derived membrane proteins, that we refer to as hybrisomes. Membrane protein extracts (MPEs) were isolated from cultured cells using a mild detergent-based extraction protocol. Cy5-labeled mRNA encoding for eGFP was used to form LNPs and hybrisomes to investigate their internalization efficiency and mRNA delivery via flow cytometry and microscopy, with MPE content incorporated into hybrisomes during microfluidic mixing. MPEs were successfully incorporated into the lipid membrane of hybrisomes. Remarkably, the cellular uptake of hybrisomes was up to 15-fold higher than LNPs, while the mRNA delivery efficiency improved up to 8-fold depending on the MPE content incorporated into the hybrisomes. Further studies confirmed that the enhanced cellular uptake of hybrisomes and mRNA is partially explained by the presence of membrane proteins and hybrisomes' unique morphology including bleb-like structures. Moreover, the versatility of hybrisomes was demonstrated by producing formulations using MPEs isolated from different cell types, which led to variations in cellular uptake and mRNA delivery, suggesting that the cell type from which MPEs are derived influences their biological function. These findings pave the way for the development of more targeted and effective nanotherapeutic strategies.
Apigenin-loaded nanoparticles for obesity intervention through immunomodulation and adipocyte browning
Authors: Neda Mohaghegh, Anjali Iyer, Ethan Wang, Narges Zargar Balajam, Heemin Kang, Mohsen Akbari, Michele S Barnhill, Ali Khademhosseini, Ryan M Pearson, Alireza Hassani Najafabadi
Journal: Journal of Controlled Release (2025)
Engineered Gold Nanoparticles for Accurate and Full-scale Tumor Treatment via pH-dependent Sequential Charge-Reversal and Copper Triggered Photothermal-Chemodynamic-Immunotherapy
Authors: Jie Liu, Wenjuan Tang, Li Chen, Qianqian Zhang, Tao Liu, Longyu Qin, Yanmin Zhang, Xin Chen
Journal: Biomaterials (2025)
Splenic B cell-targeting lipid nanoparticles for safe and effective mRNA vaccine delivery
Authors: Yuichi Suzuki, Mai Yakuwa, Mina Sato, Eleni Samaridou, Moritz Beck-Broichsitter, Masatoshi Maeki, Manabu Tokeshi, Yuma Yamada, Hideyoshi Harashima, Yusuke Sato
Journal: Journal of Controlled Release (2025)
Engineered extracellular vesicles with surface FGF21 and enclosed miR-223 for treating metabolic dysfunction-associated steatohepatitis
Authors: Hanchae Cho, Hyunji Ju, Yongdeok Ahn, Juhee Jang, Juhyeong Cho, Eunju Park, Sung-Min Kang, Jaemin Lee, Daeha Seo, Moon-Chang Baek, Kyungmoo Yea
Journal: Biomaterials (2025)
Advances in plant-derived vesicle like nanoparticles-based therapies for inflammatory diseases
Authors: Zhifei Cheng, Wengui Lu, Wei Shao, Chuan Zhang, Yunfei She, Rui Song, Ruohan Qi, Jiajia Song, Wenjing Zhang, Xiangwei Chang, Ning Wang, Qi Liu, Shuangying Gui, Qi Wang
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Deceased donor liver utilisation and assessment: Consensus guidelines from the European Liver and Intestine Transplant Association
Authors: Amelia J Hessheimer, Hermien Hartog, Francesca Marcon, Andrea Schlegel, René Adam, Ian Alwayn, Roberta Angelico, Corinne Antoine, Gabriela Berlakovich, Isabel Bruggenwirth, David Calatayud, Benno Cardini, Umberto Cillo, Pierre-Alain Clavien, Zoltan Czigany, Riccardo De Carlis, Jeroen de Jonge, Vincent E De Meijer, Daniele Dondossola, Beatriz Domínguez-Gil, Philipp Dutkowski, Janina Eden, Dilmurodjon Eshmuminov, Yiliam Fundora, Mikel Gastaca, Davide Ghinolfi, Iago Justo, Mickael Lesurtel, Henri Leuvenink, Pal-Dag Line, Laura Lladó, Víctor López López, Georg Lurje, Luís Miguel Marín, Diethard Monbaliu, Xavier Muller, Silvio Nadalin, David Nasralla, Gabriel Oniscu, Damiano Patrono, Jacques Pirenne, Markus Selzner, Christian Toso, Roberto Troisi, Cornelius Van Beekum, Christopher Watson, Annemarie Weissenbacher, Krzysztof Zieniewicz, Stefan Schneeberger, Wojciech G Polak, Robert J Porte, Constantino Fondevila
Journal: Journal of Hepatology (2025)
Elytra-inspired zirconium phosphate nanonetwork: Toward high-quality osseointegration and physical-chemical-mechanical bond at the interface for zirconia-based dental materials
Authors: Shuyi Wu, Yingyue Sun, Qihong Zhang, Wen Si, Peng Gao, Lei Lu, Zhennan Deng, Lihua Xu, Xinkun Shen, Jinsong Liu
Journal: Bioactive Materials (2025)
Generating evidence to support the role of AI in diabetic eye screening: considerations from the UK National Screening Committee
Authors: Trystan Macdonald, Zhivko Zhelev, Xiaoxuan Liu, Christopher Hyde, Jiri Fajtl, Catherine Egan, Adnan Tufail, Alicja R Rudnicka, Bethany Shinkins, Rosalind Given-Wilson, J Kevin Dunbar, Steve Halligan, Peter Scanlon, Anne Mackie, Sian Taylor-Philips, Alastair K Denniston
Journal: The Lancet Digital Health (2025)

Screening for diabetic retinopathy has been shown to reduce the risk of sight loss in people with diabetes, because of early detection and treatment of sight-threatening disease. There is long-standing interest in the possibility of automating parts of this process through artificial intelligence, commonly known as automated retinal imaging analysis software (ARIAS). A number of such products are now on the market. In the UK, Scotland has used a rules-based autograder since 2011, but the diabetic eye screening programmes in the rest of the UK rely solely on human graders. With more sophisticated machine learning-based ARIAS now available and greater challenges in terms of human grader capacity, in 2019 the UK's National Screening Committee (NSC) was asked to consider the modification of diabetic eye screening in England with ARIAS. Following up on a review of ARIAS research highlighting the strengths and limitations of existing evidence, the NSC here sets out their considerations for evaluating evidence to support the introduction of ARIAS into the diabetic eye screening programme.
Variant-to-function approaches for adipose tissue: Insights into cardiometabolic disorders
Authors: Sophia Metz, Jonathan Robert Belanich, Melina Claussnitzer, Tuomas Oskari Kilpeläinen
Journal: Cell Genomics (2025)

Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with cardiometabolic disorders. However, the functional interpretation of these loci remains a daunting challenge. This is particularly true for adipose tissue, a critical organ in systemic metabolism and the pathogenesis of various cardiometabolic diseases. We discuss how variant-to-function (V2F) approaches are used to elucidate the mechanisms by which GWAS loci increase the risk of cardiometabolic disorders by directly influencing adipose tissue. We outline GWAS traits most likely to harbor adipose-related variants and summarize tools to pinpoint the putative causal variants, genes, and cell types for the associated loci. We explain how large-scale perturbation experiments, coupled with imaging and multi-omics, can be used to screen variants' effects on cellular phenotypes and how these phenotypes can be tied to physiological mechanisms. Lastly, we discuss the challenges and opportunities that lie ahead for V2F research and propose a roadmap for future studies.
Gut microbiota and metabolites are linked to disease progression in multiple sclerosis
Authors: Luke A Schwerdtfeger, Federico Montini, Toby B Lanser, Millicent N Ekwudo, Jonathan Zurawski, Shahamat Tauhid, Bonnie I Glanz, Renxin Chu, Rohit Bakshi, Tanuja Chitnis, Laura M Cox, Howard L Weiner
Journal: Cell Reports Medicine (2025)

Progressive multiple sclerosis (MS) is a neurological disease with limited understanding of the biology associated with transition from relapsing to progressive disease. Intestinal microbes and metabolites are altered in MS, but relation to disease progression is largely unknown. We investigate microbiota and metabolites in subjects with stable MS, those who worsened, and in those with relapsing MS who became progressive over 2 years. We find that Eubacterium hallii, Butyricoccaceae, Blautia, and other short-chain fatty-acid-producing microbes have beneficial associations with worsening of disability, 3T magnetic resonance imaging (MRI) measures, cognition, and quality of life, while Alistipes is detrimentally associated. Global metabolomics identified serum and stool metabolites that are altered in progressive MS and in relapsing subjects who transitioned to progressive disease. Most fecal metabolites associated with disease progression are decreased, suggesting a deficiency of protective factors in the gut. Using a unique MS cohort, our findings identify gut microbiome and metabolite pathways influencing progressive MS.