tbuckley/cabot-search huggingface dataset:
N-glycosylation of PD-L1 modulates the efficacy of immune checkpoint blockades targeting PD-L1 and PD-1
Authors: Bar Kaufman, Muhammad Abu-Ahmad, Olga Radinsky, Eman Gharra, Tal Manko, Baisali Bhattacharya, Daniela Gologan, Nofar Erlichman, Tsipi Meshel, Yoav Nuta, Tomer Cooks, Moshe Elkabets, Adit Ben-Baruch, Angel Porgador
Journal: Molecular Cancer (2025)

Abstract Background The PD-L1/PD-1 pathway is crucial for immune regulation and has become a target in cancer immunotherapy. However, in order to improve patient selection for immune checkpoint blockade (ICB) therapies, better selection criteria are needed. This study explores how the N-glycosylation of PD-L1 affects its interaction with PD-1 and ICB efficacy, focusing on its four N-linked glycosylation sites: N35, N192, N200, and N219. Methods Human PD-L1 glycosylation mutants—at each individual site or at all four sites together (Nx4)—were tested for their functional interaction with PD-1 using an artificial immune checkpoint reporter assay (IcAR-PD1). The blocking efficacy of anti-PD-L1 and anti-PD-1 antibodies was evaluated using human breast cancer cell lines (MDA-MB231 and MCF7), as well as A375 melanoma and A549 lung carcinoma cells expressing the glycosylation mutants. Results were validated through ex vivo activation and cytotoxicity assays using human CD8+ T cells. Results The binding of the PD-L1 N35A mutant to PD-1 was not effectively blocked by anti-PD-L1 and anti-PD-1 ICBs. In contrast, high blocking efficacy of PD-L1 binding to PD-1 was obtained at minimal ICB concentrations when PD-L1 did not express any glycosylation site (PD-L1 Nx4 mutant). The PD-L1 N35A mutant produced elevated levels of PD-L1 as a soluble (sPD-L1) and extracellular vesicles (EV)-bound molecule; in contrast, the PD-L1 Nx4 mutant had lower sPD-L1 and EV levels. PD-L1 glycosylation status influenced the ability of PD-L1 interactions with PD-1 to down-regulate T-cell activation and cytotoxicity, with the PD-L1 N35A mutant showing the lowest levels of T cell functions and the PD-L1 Nx4 mutant the highest. Conclusions The N-glycosylation of PD-L1 at all four sites interferes with the ability of anti-PD-L1 and anti-PD-1 ICBs to block PD-L1 interactions with PD-1; in contrast, glycosylation at the N35 site enhances ICB blocking efficacy. These effects are connected to the ability of sPD-L1 to compete with ICB binding to PD-L1 or PD-1. Thus, assessing PD-L1 glycosylation, beyond expression levels, could improve patient stratification and outcomes.
EASL Clinical Practice Guidelines on extrahepatic abdominal surgery in patients with cirrhosis and advanced chronic liver disease
Authors: Bobby V.M. Dasari, Dominique Thabut, Manon Allaire, Annalisa Berzigotti, Annabel Blasi, Pål-Dag Line, Mattias Mandorfer, Vincenzo Mazzafero, Virginia Hernandez-Gea
Journal: Journal of Hepatology (2025)
EASL Clinical Practice Guidelines on the management of autoimmune hepatitis
Authors: Nikolaos Gatselis, Joost P. Drenth, Michael Heneghan, Marianne Jørgensen, Ansgar W. Lohse, Maria Londoño, Luigi Muratori, Maria Papp, Marianne Samyn, Dina Tiniakos, Ana Lleo
Journal: Journal of Hepatology (2025)
Scoping review of deep learning research illuminates artificial intelligence chasm in otolaryngology-head and neck surgery
Authors: George S Liu, Soraya Fereydooni, Melissa Chaehyun Lee, Srinidhi Polkampally, Jeffrey Huynh, Sravya Kuchibhotla, Mihir M Shah, Noel F Ayoub, Robson Capasso, Michael T Chang, Philip C Doyle, F Christopher Holsinger, Zara M Patel, Jon-Paul Pepper, C Kwang Sung, Francis X Creighton, Nikolas H Blevins, Konstantina M Stankovic
Journal: npj Digital Medicine (2025)

Abstract Clinical validation studies are important to translate artificial intelligence (AI) technology in healthcare but may be underperformed in Otolaryngology - Head &amp; Neck Surgery (OHNS). This scoping review examined deep learning publications in OHNS between 1996 and 2023. Searches on MEDLINE, EMBASE, and Web of Science databases identified 3236 articles of which 444 met inclusion criteria. Publications increased exponentially from 2012–2022 across 48 countries and were most concentrated in otology and neurotology (28%), most targeted extending health care provider capabilities (56%), and most used image input data (55%) and convolutional neural network models (63%). Strikingly, nearly all studies (99.3%) were in silico, proof of concept early-stage studies. Three (0.7%) studies conducted offline validation and zero (0%) clinical validation, illuminating the “AI chasm” in OHNS. Recommendations to cross this chasm include focusing on low complexity and low risk tasks, adhering to reporting guidelines, and prioritizing clinical translation studies.
Forward-viewing echoendoscope-guided pancreaticojejunostomy for post-pancreaticoduodenectomy stricture
Authors: Toru Kaneko, Mitsuhiro Kida, Takahiro Kurosu, Yutaro Saito, Shiori Koyama, Tomohiro Betto, Chika Kusano
Journal: Endoscopy (2025)
A novel technique for submucosal tumors in esophagus: mucosal zipper endoscopic resection
Authors: Zhenkai Luo, Jiangping Yu, Hui Zhang, Shaopeng Yang, Jian Li, Jianling Liu, Shi Wang
Journal: Endoscopy (2025)

Background The mucosal zipper endoscopic resection (MZER) technique was developed as a novel approach for treating esophageal submucosal tumors (SMTs). This study aims to introduce the MZER technique and evaluate its feasibility. Methods This retrospective study included 24 patients who underwent MZER between January 2022 and January 2024. Clinical data and treatment outcomes were collected and analyzed. Results Among these patients, the median distance from the incisor teeth to the SMTs was 25 cm (range: 16–38 cm), the median tumor length was 3.0 cm (range: 2.2-7.0 cm) and the median tumor width was 2.2 cm (range: 1.8-4.0 cm). All esophageal SMTs were successfully resected, achieving an en bloc resection rate of 100%. Intra-procedural perforation occurred in 10 patients (41.7%). The median operation time was 50 minutes (range: 30-180 minutes), and the median duration of hospitalization was 3 days (range: 2-6 days). No delayed bleeding or perforation occurred. Conclusion MZER seems to provide an optional treatment for proximal or larger esophageal SMTs. The efficacy and safety profiles need further validation through multicenter studies with larger cohorts, given the current limitations of sample size and single-center design.
Management of bleeding from a left-sided epiphrenic esophageal diverticulum: role of positional adjustment in clot removal
Authors: Kohei Uyama, Yohei Yabuuchi, Yoshiki Morihisa, Soichiro Nagao, Shinsuke Akiyama, Shuko Morita, Tetsuro Inokuma
Journal: Endoscopy (2025)
Emerging Role of Targeted Therapies Combined with Radiotherapy in Inoperable Stage I-III, Non-Small Cell Lung Cancer (NSCLC): A Review from the International Association for the Study of Lung Cancer (IASLC) Advanced Radiation Technology (ART) Subcommittee.
Authors: Sarah Bowen Jones, Clara Chan, Andrea R Filippi, Ken Harada, Alexander V Louie, Colin R Lindsay, Ernest Nadal, Pablo Munoz Schuffenegger, David Woolf, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2025)
Symptom Burden and Post-COVID-19 Syndrome 24 Months Following SARS-CoV-2 Infection: Longitudinal Population-Based Study
Authors: Raphael S Peter, Lisamaria Eble, Alexandra Nieters, Stefan O Brockmann, Siri Göpel, Uta Merle, Jürgen M Steinacker, Hans-Georg Kräusslich, Dietrich Rothenbacher, Winfried V Kern
Journal: Journal of Infection (2025)
Impact of co-infection with SARS-CoV-2 and other respiratory viruses on illness: Pooled analyses of 11 COVID-19 cohorts
Authors: Marieke LA de Hoog, Emma Sem Hauser-van Westrhenen, Angelique Mam Winkel, Menno D de Jong, Marlies A van Houten, Steven Fl van Lelyveld, Dirk Eggink, Sjoerd Euser, Liesbeth Duijts, Joanne G Wildenbeest, Rob Schuurman, Janneke Hhm van de Wijgert, Margareta Ieven, Katherine Loens, Alike W van der Velden, Marc Jm Bonten, Herman Goossens, Patricia Cjl Bruijning-Verhagen
Journal: Journal of Infection (2025)
Peritoneum-inspired adaptive hydrogel sheath orchestrating long-term lubrication and antibacterial properties for drainage tube intubation
Authors: Zhi-Guo Wang, Ming Cai, Xue Xiao, Run-Lin Sun, Xi Liao, Rui Hong, Ju-Xiang Gou, Ka Li, Jia-Zhuang Xu, Zhong-Ming Li
Journal: Biomaterials (2025)
Randomized Non-Inferiority Trial of Direct Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension: GLAUrious
Authors: Gus Gazzard, Nathan Congdon, Augusto Azuara-Blanco, Eytan Z Blumenthal, Ketevan Gomelauri, Monika Zaliniyan, Carlo E Traverso, Zohar Bracha, Ana Dvalishvili, Yoram Solberg, Michael Belkin, Thomas W Samuelson
Journal: Ophthalmology (2025)
The global HIV response at a crossroads: protecting gains and advancing sustainability amid funding disruptions
Authors: Beatrice Matanje, Ruth Laibon Masha, Gallican Rwibasira, Kenneth Ngure, Hidayat B Yahaya, Florence R Anam, Mumbi Chola, Hasina Subedar, Lilian Chunda, Charles B Holmes
Journal: The Lancet HIV (2025)
Medical conditions and the risk of subsequent major depressive disorder: a nationwide, register-based, retrospective cohort study
Authors: Per E Sigvardsen, Emil Fosbøl, Anders Jørgensen, Christian Torp-Pedersen, Lars Køber, Klaus F Kofoed
Journal: The Lancet Public Health (2025)

Major depressive disorder can develop subsequent to medical conditions; however, it is unknown if some individuals are at higher risk than others. We aimed to provide comprehensive estimates for the risk of major depressive disorder subsequent to the onset of various medical conditions. In this nationwide, population-based, retrospective cohort study, individuals living in Denmark between Jan 1, 1995, and Dec 31, 2022, were included. Individuals who already had a medical condition or major depressive disorder within a 5-year washout period were excluded. Information on medical conditions and major depressive disorder was obtained from the National Danish Registries. The exposure was onset of medical conditions, defined as any of nine categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, haematological, cancers, and neurological. The endpoint was major depressive disorder. Hazard ratios (HRs) were estimated with adjusted Cox regression models. Absolute risks were estimated with competing-risk survival analysis. 6 528 353 individuals were followed up for a total of 100 770 621 person-years. 2 114 575 (32·4%) individuals were diagnosed with a medical condition and 1 112 043 (17·0%) individuals were diagnosed with major depressive disorder. Individuals with medical conditions had a higher rate of major depressive disorder than those without (HR 2·26, 95% CI 2·25-2·28). In the first month after onset of a medical condition, the HR for major depressive disorder was 4·62 (95% CI 4·50-4·74). The HR in the first months after onset of a medical condition was further elevated in individuals aged 60 years or older (HR 9·04, 95% CI 8·63-9·47), in patients hospitalised for a medical condition (11·83, 11·25-12·45), and in those with at least two medical conditions (8·92, 8·74-9·11). Musculoskeletal conditions had the highest HR for major depressive disorder (2·50, 2·49-2·51), whereas endocrine conditions had the lowest (1·35, 1·34-1·36). More than 10 years after onset of a medical condition the HR for major depressive disorder was 1·84 (95% CI 1·82-1·86). The absolute risk for major depressive disorder 20 years after onset of a medical condition was 18·9% (18·8-19·0) in men and 24·4% (24·3-24·5) in women compared with 6·9% (6·8-7·0%) in matched men without a medical condition and 10·7% (10·6-10·8%) in matched women without a medical condition. Onset of medical conditions is associated with an elevated risk of major depressive disorder and is further elevated immediately after diagnosis and in specific subgroups. These findings can be used for early detection and to give attention to specific groups in the period after onset of medical conditions. The Research Council of Rigshospitalet.
GPD1L supports glycerol-3-phosphate and triacylglycerol synthesis and promotes tumor progression in hepatocellular carcinoma
Authors: Tiffany Ching-Yun Yu, Luqing Zhao, Karen Man-Fong Sze, Lu Tian, Vanilla Xin Zhang, Eva Lee, Charles Shing Kam, Joyce Man-Fong Lee, Daniel Wai-Hung Ho, Yu-Man Tsui, Lo-Kong Chan, Irene Oi-Lin Ng
Journal: Hepatology (2025)

Background &amp; Aims: Research on metabolic reprogramming in hepatocellular carcinoma (HCC) has increased; however, studies on the metabolism of glycerolipids or interactions between different pathways remain scarce. Enzymes of glycerol phosphate dehydrogenase (GPD) family, which regulate glycerol-3-phosphate shuttle, link the metabolic processes of glycolysis and glycerolipids. Therefore, we aimed to understand the role and regulation of GPDs in HCC. Approach &amp; Results: We performed transcriptomic analysis on clinical HCC samples from in-house and public cohorts and detected upregulation of glycerol-3-phosphate dehydrogenase 1 like (GPD1L) among GPD family genes in HCC. Further analysis showed that high GPD1L expression was associated with more frequent venous invasion and shorter overall survival. Consistent with these clinical findings, GPD1L knockdown suppressed invasiveness of HCC cells, reduced colony- and sphere-forming abilities, and inhibited stemness gene expression in vitro, while also inhibiting tumor growth and metastasis in vivo . On the other hand, we used mass-spectrometry-based metabolomics to confirm that GPD1L facilitated the biogenesis of the glycerolipid precursor glycerol-3-phosphate (G3P) from dihydroxyacetone phosphate (DHAP). Further untargeted lipidomic analysis revealed that GPD1L supported triacylglycerol synthesis. Additionally, our study identified E74 like E-Twenty-Six transcription factor 1 (ELF1) as a direct activator of GPD1L transcription, binding to the GPD1L promoter to boost its transcription while reducing GPD1L expression when ELF1 levels were lowered. Conclusions: GPD1L is overexpressed in human HCCs and associated with worse clinical outcomes. Aberrant GPD1L expression, driven by ELF1, facilitates conversion of DHAP to G3P conversion to support triacylglycerol synthesis in HCC, promoting tumor growth and metastasis.
Estimation of Dermal Exposure to Volatile Organic Compounds (VOCs) from Feminine Hygiene Products: Integrating Measurement Data and Physiologically Based Toxicokinetic (PBTK) Model
Authors: Nan Lin, Zengwei Li, Ning Ding, Sung Kyun Park, Stuart Batterman, Wei Du, Jiayin Dai, Ying Zhu
Journal: Environmental Health Perspectives (2025)

Increasing studies have informed noteworthy health risks associated with dermal exposure to volatile organic compounds (VOCs) from feminine hygiene products (FHPs). This study is to address the gap in understanding the absorption, distribution, metabolism, and excretion dynamics of dermal exposure to VOCs from FHPs, and to identify chemicals and products that could cause significant body burden. We used measured contents of eight widely present VOCs across five categories of FHPs to estimate dermal exposure, and applied a physiologically based toxicokinetic (PBTK) modeling approach to elucidate VOC toxicokinetics in human body tissues. Inhalation exposure estimates were derived from 20 air samples collected via passive sampling and analyzed using thermal desorption system coupled with gas chromatography-mass spectrometer. Predicted urinary VOC concentrations based on dermal and inhalation exposure were validated against 99 measurements from 25 females. Via skin absorption, the estimated levels of most target VOCs in nearly all tissues, except adipose and the rest of the body, rapidly peaked within an hour of product use. Specifically, p-cymene was estimated to reach approximately 2.23 ng/mL in adipose tissue before decreasing over several hours due to efficient excretion pathways, including liver metabolism and exhalation. The model estimated that while the majority of absorbed VOCs (78.9%) were eliminated via liver metabolism, exhalation, and urine excretion, VOCs with logKow higher than 3.5, such as p-cymene, hexane, and n-nonane, exhibited a potential cumulative trend in adipose tissue. This resulted in the estimated VOC concentrations in adipose tissue being 1 to 4 orders of magnitude higher than those estimated in other tissues. Notably, in certain cases, n-nonane posed a potential non-cancer risk (up to 0.07), and benzene presented a notable cancer risk (up to 1.82 × 10-7), primarily attributed to wash and moisturizer, respectively. These findings reveal potential significant body burden and health risks associated with dermal exposure to VOCs from FHPs, warranting further research and regulatory measures. Comprehensive assessment of internal exposure by integrating with toxicokinetic modeling to elucidate chemical distribution in various tissues is recommended, rather than solely measuring solely one type of biomarkers, to illustrate exposure variances and ensure accurate risk assessment.. https://doi.org/10.1289/EHP15418.
Novel IgG and IgA autoantibodies validated in two independent cohorts are associated with disease activity and determine organ manifestations in systemic lupus erythematosus: implications for anti-LIN28A, anti-HMGN5, anti-IRF5, and anti-TGIF1
Authors: Julius Lindblom, Denis Lagutkin, Natalia Sherina, Helena Idborg, Lorenzo Beretta, Maria Orietta Borghi, Janique M Peyper, Guillermo Barturen, Per-Johan Jakobsson, Marta E Alarcón-Riquelme, Dionysis Nikolopoulos, Ioannis Parodis
Journal: Annals of the Rheumatic Diseases (2025)

This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE). Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery (n = 196 vs n = 110; NTC02890121) and an independent validation cohort (n = 30 vs n = 83; NCT02890134) from the European PRECISESADS project. Validated daAAbs were analysed in relation to global and organ-specific disease activity using linear and logistic regression, along with daAAb target pathway enrichment analysis. We validated 89 IgG and 66 IgA daAAbs. IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with a SLE disease activity index 2000 score of ≥10, negatively associated with lupus low disease activity state, and highly prevalent in subgroups with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cutoff for positivity in 53% of patients with central nervous system (CNS) involvement, a prevalence higher than that observed for anti-double-stranded DNA (20%) and 47% of patients with renal activity. A cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, was linked to CNS involvement. IgA anti-FOSL2 was elevated uniquely in patients with musculoskeletal activity. Enriched pathways involving DNA binding and repair showed considerable overlap across manifestations. Novel IgG and IgA autoantibodies, including IgG anti-LIN28A, IgG anti-HMGN5, IgG and IgA anti-IRF5, and IgG and IgA anti-TGIF1 were associated with SLE disease activity and highly abundant across organ manifestations.
Corrigendum to ‘Direct 3D bioprinting of perfusable vascular constructs using a blend bioink’ [Biomaterials Volume 106, (2016) Pages 58–68]
Authors: Weitao Jia, P Selcan Gungor-Ozkerim, Yu Shrike Zhang, Kan Yue, Kai Zhu, Wanjun Liu, Qingment Pi, Batzaya Byambaa, Mehmet Remzi Dokmeci, Su Ryon Shin, Ali Khademhosseini
Journal: Biomaterials (2025)
Time-independent disease state identification defines distinct trajectories determined by localised vs systemic inflammation in patients with early rheumatoid arthritis
Authors: Nils Steinz, Tjardo D Maarseveen, Erik B van den Akker, Andrew P Cope, John D Isaacs, Aaron R Winkler, Tom W J Huizinga, Yann Abraham, Rachel Knevel
Journal: Annals of the Rheumatic Diseases (2025)

Patients with rheumatoid arthritis (RA) display different trajectories towards improvement of disease. We aimed to disentangle the heterogeneity of RA disease trajectories from the first clinical visit onwards using graph-based pseudotime analysis. We studied early patients with RA over 1.5 years in 2 data sets: Leiden (Netherlands), n = 1237, with 5017 visits, and Towards a Cure for Early Rheumatoid Arthritis (TACERA) (United Kingdom), n = 243, with 750 visits. We created a pipeline for time-independent clustering of clinical and haematologic features to identify disease states. Sequence analyses of these states defined the trajectories. We studied the predictability of the trajectories with baseline features. Clustering identified 8 disease states with localised inflammation (joints) and systemic inflammation (erythrocyte sedimentation rate [ESR] or leucocytes) as the main discriminating factors. The disease state sequences consisted of 4 trajectories, which we independently replicated in TACERA: A, high ESR; B, rapid progression from many inflamed joints towards remission; C, high leucocytes; and D, many inflamed joints with poor prognosis. Systemic vs local inflammation patterns showed moderate predictability at baseline (sensitivity of 71% and precision of 0.73 for trajectory A, although lower precision of 0.52 for trajectory B), while other trajectories were less predictable. Trajectories C and D had strong resemblance with B at baseline but deteriorated into less favourable trajectories. Patients in trajectory A were more often female and on average older. The trajectories were not explained by time till disease-modifying antirheumatic drug, baseline disease activity, or symptom duration. The suboptimal trajectories coincided with worse patient-reported outcomes, even when the inflammation was mainly systemic. We identified 4 distinct trajectories in early RA, differentiating RA into localised vs systemic inflammation. Our results highlight potential differences in disease pathology and opportunities for further targeted treatment. Inevitably, patterns without linkage to our selected features could not be detected.
Usability testing a web application to support evidence-based commissioning decisions for implementing mobile stroke units
Authors: Lisa Moseley, Anna Laws, Michael Allen, Gary A Ford, Martin James, Stephen McCarthy, Graham McClelland, Laura J Park, Kerry Pearn, Daniel Phillips, Christopher Price, Lisa Shaw, Phil White, David Wilson, Peter McMeekin, Jason Scott
Journal: npj Digital Medicine (2025)

Abstract Commissioning of innovations in healthcare is a complex socio-technical process, ideally informed by high quality evidence. However, evidence is not always prepared and presented in a format usable for commissioning decisions. Agile methodology, combined with qualitative co-design, were used to develop a digital web application incorporating machine learning models of stroke outcomes to inform commissioning decisions for the implementation of mobile stroke units (MSUs) in England, followed by usability testing using think aloud methodology. Sixteen stakeholders involved in developing consensus on model parameters and pathways participated with data thematically analysed. Required improvements to the web application were identified and novel insights into the complexity of context-specific commissioning decisions were generated, which also informed participants’ views on the viability of MSUs. This study provides empirical evidence in support of developing innovative and accessible digital dissemination methods to engage with commissioning processes and prospectively understand commissioning challenges.
Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements
Authors: Alex Bataller, Hannah E Goulart, Ghayas C Issa, Courtney D DiNardo, Naval Daver, Tapan Kadia, Alexandre Bazinet, Ian M Bouligny, Jayastu Senapati, Fadi G Haddad, Gautam Borthakur, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Guillermo Montalban-Bravo, Guiling Tang, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Elias Jabbour
Journal: Leukemia (2025)