tbuckley/cabot-search huggingface dataset:
A novel allosteric driver mutation of β‐glucuronidase promotes head and neck squamous cell carcinoma progression through STT3B‐mediated PD‐L1 N‐glycosylation
Authors: Zhonglong Liu, Xiaoyan Meng, Xiao Tang, Jian Zhang, Zhiyuan Zhang, Yue He
Journal: MedComm (2025)

Abstract Head and neck squamous cell carcinoma (HNSCC) develops and advances because of the accumulation of somatic mutations located in orthosteric and allosteric areas. However, the biological effects of allosteric driver mutations during tumorigenesis are mostly unknown. Here, we mapped somatic mutations generated from 10 tumor‐normal matched HNSCC samples into allosteric sites to prioritize the mutated allosteric proteins via whole‐exome sequencing and AlloDriver, identifying the specific mutation H351Q in β‐glucuronidase (GUSB), a lysosomal enzyme, as a novel allosteric driver mutation, which considerably encouraged HNSCC progression both in vitro and in vivo. Mechanistically, the allosteric mutation of H351Q remarkably attenuated protein trafficking from the endoplasmic reticulum (ER) to lysosomes, leading to ER retention, in which GUSB‐H351Q facilitated the aberrant N‐glycosylation of PD‐L1 through increasing protein stability and mRNA transcripts of the STT3 oligosaccharyltransferase complex catalytic subunit B, an oligosaccharyltransferase complex. Moreover, GUSB‐H351Q reshaped a more immunosuppressive microenvironment featuring increased infiltration of exhausted CD8 + T cells and remodeled tumor metabolism, characterized by increased activity of the purine metabolism pathways and pyruvic acid accumulation. This study provides a mechanism‐driven approach to overcoming HNSCC progression and immune evasion and identifies novel druggable targets based on the presence of GUSB allosteric driver mutation.
Targeting farnesoid X receptor as aging intervention therapy
Authors: Lijun Zhang, Jing Yu, Xiaoyan Gao, Yingxuan Yan, Xinyi Wang, Hang Shi, Minglv Fang, Ying Liu, Young-Bum Kim, Huanhu Zhu, Xiaojun Wu, Cheng Huang, Shengjie Fan
Journal: Acta Pharmaceutica Sinica B (2025)

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr -/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.
Dynamic hierarchical ligand anisotropy for competing macrophage regulation in vivo
Authors: Kanghyeon Kim, Sunhong Min, Ramar Thangam, Kyong-Ryol Tag, Hyun-Jeong Lee, Jeongyun Heo, Hwapyung Jung, Thet Thet Swe, Iman Zare, Guosheng Song, Alireza Hassani Najafabadi, Junmin Lee, Hyun-Do Jung, Jong Seung Kim, Sunghoon Hur, Hyun-Cheol Song, Sung-Gyu Park, Kunyu Zhang, Pengchao Zhao, Liming Bian, Se Hoon Kim, Juyoung Yoon, Jae-Pyoung Ahn, Hong-Kyu Kim, Heemin Kang
Journal: Bioactive Materials (2025)
Clinical entity augmented retrieval for clinical information extraction
Authors: Ivan Lopez, Akshay Swaminathan, Karthik Vedula, Sanjana Narayanan, Fateme Nateghi Haredasht, Stephen P. Ma, April S. Liang, Steven Tate, Manoj Maddali, Robert Joseph Gallo, Nigam H. Shah, Jonathan H. Chen
Journal: npj Digital Medicine (2025)

Abstract Large language models (LLMs) with retrieval-augmented generation (RAG) have improved information extraction over previous methods, yet their reliance on embeddings often leads to inefficient retrieval. We introduce CLinical Entity Augmented Retrieval (CLEAR), a RAG pipeline that retrieves information using entities. We compared CLEAR to embedding RAG and full-note approaches for extracting 18 variables using six LLMs across 20,000 clinical notes. Average F1 scores were 0.90, 0.86, and 0.79; inference times were 4.95, 17.41, and 20.08 s per note; average model queries were 1.68, 4.94, and 4.18 per note; and average input tokens were 1.1k, 3.8k, and 6.1k per note for CLEAR, embedding RAG, and full-note approaches, respectively. In conclusion, CLEAR utilizes clinical entities for information retrieval and achieves &gt;70% reduction in token usage and inference time with improved performance compared to modern methods.
Comments on “Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study”
Authors: Jing‐jin Hu, Yang‐yang Lu, Jun‐kang Zhao, Dan Ma, James Cheng‐Chung Wei, Li‐yun Zhang
Journal: Arthritis & Rheumatology (2025)

Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Comparison of oronasal and nasal masks in home mechanical ventilation: an observational cohort and bench study
Authors: Emeline Fresnel, Christian Caillard, Marius Lebret, Léa Razakamanantsoa, Adrien Kerfourn, Johan Dupuis, Jean-François Muir, Elodie Lhuillier, Kinan El Husseini, Thomas Similowski, Antoine Cuvelier, Maxime Patout
Journal: European Respiratory Journal (2025)

Background In patients with chronic respiratory failure, home non-invasive ventilation (NIV) is delivered through oronasal or nasal masks. Masks are a cornerstone for NIV success but can be associated with side-effects. However, the type, frequency and consequences of these side-effects are unknown. Here, we aimed to study the prevalence, nature and impact of mask-related adverse events in a cohort of stable patients. We then investigated differences between oronasal and nasal masks both in our cohort and in a bench study. Methods This was a prospective observational cohort including patients established on long-term NIV admitted for their elective review. Data regarding mask-related side-effects were assessed using a structured questionnaire. Our bench study was performed using a three-dimensional printed head connected to an artificial lung. Results 800 patients were included, of whom 84% had an oronasal mask. Moderate to very severe mask-related side-effects occurred in 47% of patients and severe to very severe side-effects occurred in 18% of patients. Side-effects were associated with poorer daytime arterial partial pressure of carbon dioxide (p=0.005), poorer subjective sleep quality (p=0.003) and poorer quality of life (p&lt;0.001). Mask-related side-effects were more frequently reported with the use of oronasal masks compared to nasal masks (p=0.023). Our bench study showed that nasal masks were more stable than oronasal masks (p&lt;0.001). Conclusions Mask-related side-effects are frequent and associated with poorer outcomes. Our data suggest that nasal masks may have a better tolerance profile and should be used as a first-line interface.
Residual sleepiness and impaired alertness in treated obstructive sleep apnoea: role of hypoxic burden and sleep fragmentation
Authors: Pierre Tankéré, Jacques Tailliard, Thierry PetitJean, Pierre Le-Cam, François Ricordeau, Margaux Blanchard, Jade Vanbuis, Anice Nofal, Renaud Tamisier, Laure Peter-Derex, Emeric Stauffer
Journal: Thorax (2025)

The pathophysiology of residual sleepiness in treated obstructive sleep apnoea (OSA) remains poorly understood. Animal models suggest that it may involve neuronal damage due to intermittent hypoxia and sleep fragmentation. In a cohort of 122 continuous positive airway pressure (CPAP) treated OSA patients referred for maintenance of wakefulness test, we explored the determinants of (objective) alertness and those of (subjective) sleepiness assessed by Epworth Sleepiness Scale. We found that in logistic models, residual hypoxic burden was significatively associated with objective impaired alertness (OR=1.005, 95% CI 1.002 to 1.008), p=0.003), whereas arousal index &gt;25/h was significatively associated with subjective residual sleepiness (OR=1.23, 95% CI 1.05to 1.43, p=0.02). This suggests that hypoxia and sleep fragmentation may be involved in different dimensions of residual hypersomnolence in treated OSA.
Measuring the impact of hospitalisation for infectious diseases on the quality of life of older patients in four European countries: the AEQUI longitudinal matched cohort study (2020-2023)
Authors: Nicola Veronese, Maria Cristina Polidori, Stefania Maggi, Javier Zamora, Gabriel Ruiz-Calvo, Mathieu Bangert, Pierre Bourron, Annika Bausch, Juan Dionisio Avilés-Hernández, Alfonso López-Soto, Daniel Padrón Guillén, Jean-Philippe Lanoix, Alfonso J Cruz-Jentoft, Gaëtan Gavazzi, Abd-El-Rachid Mahmoudi, Marc Paccalin, Saber Touati, Bertrand Fougere, Sarah Laurent Badr, Sarah Boulahrouz, Aymric Kisserli, Soraya Sabeur, Arthur Fourmy, Carole Grand, Elodie Edwige, Pauline Caraux Paz, Sylvain Diamantis, Emmanuel Forestier, Marion Le Marechal, Cyprien Arlaud, Meryl Dodge
Journal: Clinical Microbiology and Infection (2025)

To evaluate the impact of hospitalisation for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries. HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to six months later (M6) in patients aged over 65 years hospitalised for severe acute respiratory or bloodstream infections, and matched controls hospitalised for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion. Between 2020 and 2023, 1,968 patients aged 65 to 100 years (mean: 81) were included; 1,064 (54.1%) were male and 59 (3%) were institutionalised. Of these 1,968 patients, 826 were hospitalised for infectious diseases and 1,142 for non-infectious conditions. At inclusion, EQ-5D-3L (European Quality of life 5 Dimensions and 3 Lines) scores ranged from -0.7 to 1 (full HRQOL), with a median of 0.7 across all visits and groups. Compared to controls, patients hospitalised for infectious diseases had lower scores on the Activities of Daily Living (ADL) scale (median, 4.5 vs 5.0; p=0.020) and the Instrumental Activities of Daily Living (IADL) scale (median, 3.0 vs 4.0; p<0.001). At discharge, IADL scores were lower in patients hospitalised for infectious diseases than in controls (median, 4.0 vs 5.0, p=0.003), indicating reduced functioning. The proportion of frail patients, determined by a Multidimensional Prognostic Index (MPI) score between 0.67 and 1, was significantly higher among patients hospitalised for infectious diseases (n=113/801, 14.1%) than controls (n=108/1,111, 9.7%; p=0.012). At M6, no statistically significant differences were observed between groups in changes from inclusion in HRQOL (EQ-5D-3L, p=0.436), frailty (MPI, p=0.269), and functioning (ADL, p=0.993). Hospitalisation for infectious diseases and non-infectious diseases or conditions had a similar impact on HRQOL in non-institutionalised older adults. Clinical trials: NCT04825132.
Life’s Essential 8 and risks of mortality and cardiovascular morbidity in individuals with PRISm and its associations with transition trajectories of PRISm
Authors: Yang Geng, Yi Ding, Xujia Lu, Yalong Pei, Matthew D Jankowich, Chaofu Ke
Journal: Thorax (2025)

Background Although morbidity and mortality are reportedly increased in individuals with preserved ratio impaired spirometry (PRISm), little is known about how to optimise PRISm-related health. Aims Is Life’s Essential 8 (LE8) associated with mortality and cardiovascular morbidity in individuals with PRISm and with PRISm transition trajectories? Methods Participants with PRISm (n=31 943) with complete data on LE8 and 23 179 individuals with two spirometry measurements were included from the UK Biobank. Eight health components were used to create the LE8 score (0–100). Cox proportional hazards models were used to assess associations of LE8 with cardiovascular morbidity and all-cause, cardiovascular and respiratory mortality. Multinomial logistic regression models were conducted to assess associations between LE8 and transition trajectories of PRISm. Results Among participants with PRISm, 3113 (9.75%), 25 254 (79.06%) and 3576 (11.19%) were categorised as high (LE8≥80), moderate (50≤LE8&lt;80) and low LE8 (LE8&lt;50) score groups, respectively. Compared with the high LE8 group, the low LE8 group demonstrated higher risks of cardiovascular disease (HR: 2.702, 95% CI 2.391 to 3.054) and all-cause (2.496, 2.082 to 2.993), cardiovascular (4.165, 2.672 to 6.493) and respiratory mortality (4.103, 1.866 to 9.020). Individuals with low LE8 score (vs high LE8) had higher odds to transition from normal spirometry to PRISm (OR: 2.238, 95% CI 1.638 to 3.057) and lower odds to transition from PRISm to normal spirometry (OR: 0.506, 95% CI 0.339 to 0.757). Conclusion A lower LE8 score was associated with increased risks of cardiovascular morbidity and all-cause, cardiovascular and respiratory mortality in PRISm. A lower LE8 score was related to higher likelihood of developing PRISm and lower likelihood of PRISm recovery.
A high-performance brain–computer interface for finger decoding and quadcopter game control in an individual with paralysis
Authors: Matthew S. Willsey, Nishal P. Shah, Donald T. Avansino, Nick V. Hahn, Ryan M. Jamiolkowski, Foram B. Kamdar, Leigh R. Hochberg, Francis R. Willett, Jaimie M. Henderson
Journal: Nature Medicine (2025)

Abstract People with paralysis express unmet needs for peer support, leisure activities and sporting activities. Many within the general population rely on social media and massively multiplayer video games to address these needs. We developed a high-performance, finger-based brain–computer-interface system allowing continuous control of three independent finger groups, of which the thumb can be controlled in two dimensions, yielding a total of four degrees of freedom. The system was tested in a human research participant with tetraplegia due to spinal cord injury over sequential trials requiring fingers to reach and hold on targets, with an average acquisition rate of 76 targets per minute and completion time of 1.58 ± 0.06 seconds—comparing favorably to prior animal studies despite a twofold increase in the decoded degrees of freedom. More importantly, finger positions were then used to control a virtual quadcopter—the number-one restorative priority for the participant—using a brain-to-finger-to-computer interface to allow dexterous navigation around fixed- and random-ringed obstacle courses. The participant expressed or demonstrated a sense of enablement, recreation and social connectedness that addresses many of the unmet needs of people with paralysis.
NO-releasing double-crosslinked responsive hydrogels accelerate the treatment and repair of ischemic stroke
Authors: Wen Guo, Cheng Hu, Yue Wang, Wen Zhang, Shaomin Zhang, Jin Peng, Yunbing Wang, Jinhui Wu
Journal: Acta Pharmaceutica Sinica B (2025)

Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction of blood vessels at the lesion site. Here, a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke, including anti-inflammation, anti-oxidant, and promotion of angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide (NO) and ISO-1 (inhibitor of macrophage migration inhibitory factor, MIF). The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), and MIF. In a mouse stroke model, hydrogels, when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release, would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect. Concurrently, NO was sustained release to facilitate angiogenesis and provide neuroprotective effects. Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score, rotarod test, and open field test. These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.
Longitudinal Changes of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer in Highly Myopic Glaucoma: A 3-year Cohort Study
Authors: Jingwen Jiang, Kangjie Kong, Fengbin Lin, Fengqi Zhou, Yunhe Song, Xiaoyi Liu, Zige Fang, Dilimulati Xiaokaiti, Ling Jin, Meiling Chen, Jost B Jonas, Dennis S C Lam, Linda M Zangwill, Xiaodong Sun, Robert N Weinreb, Fei Li, Xiulan Zhang
Journal: Ophthalmology (2025)
Engineered antigen-specific T regulatory cells suppress autoreactivity to the anti-glomerular basement membrane disease antigen.
Authors: Peter J Eggenhuizen, Boaz H Ng, Cecilia Lo, Janet Chang, Sarah L Snelgrove, Rachel My Cheong, Chanjuan Shen, Steven Lim, Yong Zhong, Poh-Yi Gan, Joshua D Ooi
Journal: Kidney International (2025)
Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial
Authors: Melanie J Davies, Peter van der Meer, Subodh Verma, Shachi Patel, Khaja M Chinnakondepalli, Barry A Borlaug, Javed Butler, Dalane W Kitzman, Sanjiv J Shah, Signe Harring, Afshin Salsali, Søren Rasmussen, Dirk von Lewinski, Walter Abhayaratna, Mark C Petrie, Mikhail N Kosiborod
Journal: The Lancet Diabetes & Endocrinology (2025)
Vaccine-derived poliovirus type 3 emergence in Guinea, 2024
Authors: Martin Faye, Ndack Ndiaye, Etienne Kouame Kouadjo, Seydou Albert Camara, Sekou Solano, Ousmane Kébé, Niouma Nestor, Balkissa Modibo, Daman Keita, Bangaly Diakité, Kankou Sidibé, Moctar Kandé, Dadja Essoya Landoh, Mohamed Sylla, Sadou Sow, Annick Dosseh, Julius Ebua Chia, Ousmane Diop, Abdourahmane Sow, Ndongo Dia, Amadou Alpha Sall, Gassim Cissé, Ousmane Faye, Kfuthwah Anfumbom, Jean Marie Kipela
Journal: The Lancet Infectious Diseases (2025)
Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
Authors: Yaqiang Li, Xiaowei Xun, Liang Duan, Erji Gao, Jiaxin Li, Lei Lin, Xinping Li, Aijuan He, Haiyong Ao, Yong Xu, Huitang Xia
Journal: Bioactive Materials (2025)
Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial
Authors: Susan van der Lei, Robbert S Puijk, Madelon Dijkstra, Hannah H Schulz, Danielle J W Vos, Jan J J De Vries, Hester J Scheffer, Birgit I Lissenberg-Witte, Luca Aldrighetti, Mark Arntz, Maarten W Barentsz, Marc G Besselink, Bart Bracke, Rutger C G Bruijnen, Tineke E Buffart, Mark C Burgmans, Thierry Chapelle, Marielle M E Coolsen, Sanne W de Boer, Francesco de Cobelli, Koert de Jong, Johannes H W de Wilt, Arjen L Diederik, Anniek M C Dooper, Werner A Draaisma, Hasan H Eker, Joris I Erdmann, Jurgen J Futterer, Bart Geboers, Gerie M C Groot, Jeroen Hagendoorn, Henk H Hartgrink, Karin Horsthuis, Rob Hurks, Sjoerd F M Jenniskens, Matthijs Kater, Geert Kazemier, Jakob W Kist, Joost M Klaase, Robrecht R M M Knapen, Johan W H Kruimer, Armand B G N Lamers, Wouter K G Leclercq, Gerrit-Jan Liefers, Eric R Manusama, Mark A J Meier, Marleen C A M Melenhorst, J Sven D Mieog, Quintus I Molenaar, Karin Nielsen, Maarten W Nijkamp, Vincent B Nieuwenhuijs, Irene M G C Nota, Bart Op de Beeck, Christiaan G Overduin, Gijs A Patijn, Fons H Potters, Francesca Ratti, Floris J Rietema, Simeon J S Ruiter, Evelien A C Schouten, Wilhelmina H Schreurs, Gianpiero Serafino, Colin Sietses, Gerrit D Slooter, Maarten L J Smits, Ezgi A Soykan, Gert-Jan Spaargaren, Martijn W J Stommel, Florentine E F Timmer, Laurens J van Baardewijk, Ronald M van Dam, Otto M van Delden, Bente A T van den Bemd, Janneke E van den Bergh, Peter B van den Boezem, Christiaan van der Leij, Rutger W van der Meer, Bram B M van der Meijs, Augustinus P T van der Ploeg, Jeroen J van der Reijden, Peter van Duijvendijk, Arian R van Erkel, Anne M van Geel, N Tjarda Van Heek, Christiaan J van Manen, Carla S P van Rijswijk, Jan Hein T M van Waesberghe, Kathelijn S Versteeg, Ted Vink, Ijsbrand A J Zijlstra, Barbara M Zonderhuis, Rutger-Jan Swijnenburg, M Petrousjka van den Tol, Martijn R Meijerink
Journal: The Lancet Oncology (2025)
Respiratory syncytial virus vaccine effectiveness among US veterans, September, 2023 to March, 2024: a target trial emulation study
Authors: Kristina L Bajema, Lei Yan, Yuli Li, Stephanie Argraves, Nallakkandi Rajeevan, Alexandra Fox, Robert Vergun, Kristin Berry, David Bui, Yuan Huang, Hung-Mo Lin, Denise M Hynes, Cynthia Lucero-Obusan, Patricia Schirmer, Francesca Cunningham, Grant D Huang, Mihaela Aslan, George N Ioannou
Journal: The Lancet Infectious Diseases (2025)