tbuckley/cabot-search huggingface dataset:
<i>Helicobacter pylori</i> CagA elevates FTO to induce gastric cancer progression via a “hit‐and‐run” paradigm
Authors: Bing He, Yiyang Hu, Yuyun Wu, Chao Wang, Limin Gao, Chunli Gong, Zhibin Li, Nannan Gao, Huan Yang, Yufeng Xiao, Shiming Yang
Journal: Cancer Communications (2025)

Abstract Background Helicobacter pylori ( H. pylori ) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of H. pylori ‐host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential role of fat mass and obesity‐associated protein (FTO) in mediating Cytotoxin‐associated gene A (CagA)‐induced GC progression. Methods The effects of H. pylori infection on N 6 ‐methyladenosine (m 6 A) modification were evaluated in both human samples and GC cell lines. The function of FTO in the progression of GC was elucidated through in vitro and in vivo studies. A series of techniques, including methylated RNA immunoprecipitation sequencing, RNA sequencing, RNA binding protein immunoprecipitation, and chromatin immunoprecipitation assays, were utilized to investigate the mechanism by which FTO mediates the capacity of cagA ‐positive H. pylori to promote GC progression. Furthermore, the therapeutic potential of the FTO inhibitor meclofenamic acid (MA) in impeding GC progression was evaluated across GC cells, animal models, and human GC organoids. Results Infection with cagA ‐positive H. pylori upregulated the expression of FTO , which was essential for CagA‐mediated GC metastasis and significantly associated with a poor prognosis in GC patients. Mechanistically, CagA delivered by H. pylori enhanced FTO transcription via Jun proto‐oncogene. Elevated FTO induced demethylation of m 6 A and inhibited the degradation of heparin‐binding EGF‐like growth factor (HBEGF), thereby facilitating the epithelial‐mesenchymal transition (EMT) process in GC cells. Interestingly, eradication of H. pylori did not fully reverse the increases in FTO and HBEGF levels induced by cagA ‐positive H. pylori . However, treatment with a combination of antibiotics and MA substantially inhibited cagA ‐positive H. pylori ‐induced EMT and prevented GC metastasis. Conclusion Our study revealed that FTO mediates the “hit‐and‐run” mechanism of CagA‐induced GC progression, which suggests that the therapeutic targeting of FTO could offer a promising approach to the prevention of CagA‐induced cancer progression.
Purified oat protein can trigger acute symptoms linked to immune activation in coeliac disease patients but not histological deterioration
Authors: Melinda Y Hardy, Amy K Russell, Lee M Henneken, Greg Tanner, Ferenc Bekes, Ian Brown, Allan Motyer, Sam W Z Olechnowicz, Hugh H Reid, Jamie Rossjohn, Jason A Tye-Din
Journal: Gut (2025)

Background Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals. Objective To correlate immune and clinical outcomes to oats, purified avenin and oat feeding studies were performed to examine symptoms, T-cell immunity and intestinal histology in CD. Design 33 treated HLA-DQ2.5+ adult CD patients underwent single-bolus or 6-week oat avenin or 3-month whole oats ingestion. T cell activation after avenin ingestion was measured using serum interleukin 2 (IL-2), a sensitive and specific biomarker of gluten-induced T cell activation and symptoms in CD. Symptom measures, intestinal histology, and immune studies on blood and duodenum were undertaken. Results Among 29 CD participants, avenin induced dose-dependent T-cell activation in 11 (38%) and acute symptoms in 17 (59%). Higher IL-2 levels correlated with more severe symptoms. A single highly symptomatic patient vomited in response to avenin (1/29; 3%) and exhibited a striking pro-inflammatory cytokine profile similar to wheat-induced responses. Avenin increased the frequency of CD38-expressing tetramer+integrin β7+ T effector memory CD4+ T cells in the blood, however symptoms, IL-2 release and tetramer frequency fell following 6-week avenin intake and no enteropathy was observed. Conclusion Gluten-contamination-free oats can trigger acute dose-dependent immune and symptom responses but usually at a level insufficient to cause sustained symptoms or enteropathy. In 1 of 29 (3%) participants, oat avenin triggered a pro-inflammatory wheat-like response, highlighting that a minority of CD patients may need to exclude oats. Informed choice regarding oats ingestion in CD is important.
Reparative immunological consequences of stem cell transplantation as a cellular therapy for refractory Crohn’s disease
Authors: Daniela Guisado, Sayali Talware, Xiaoli Wang, Andrew Davis, Elbek Fozilov, Aaron Etra, Jean-Frederic Colombel, Christoph Schaniel, Christopher Tastad, John E Levine, James L M Ferrara, Chuang Ling-Shiang, Ksenija Sabic, Shishir Singh, Bridget K Marcellino, Ronald Hoffman, Judy Cho, Louis Cohen
Journal: Gut (2025)

Background Treatment strategies for Crohn’s disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown. Objective The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs). Design Adults with CD with active clinical and endoscopic disease who failed available medical therapies were enrolled in a phase II study of SCT for refractory CD (n=19). Blood and intestinal samples were collected longitudinally and analysed using CyTOF and scRNA-seq. Stem cell autografts were functionally assayed in mouse xenograft models. Results scRNA-seq and CyTOF analyses reveal that SCT predominantly affected the intestinal myeloid lineage with loss of inflammatory populations and return of macrophages capable of supporting mucosal healing. Xenograft models using patient HSCs suggested that HSCs support the early reconstitution of the myeloid lineage and reveal an impairment of short and long-term HSC engraftment that may determine SCT outcomes. Conclusions This study suggests SCT functions as a myeloid-directed cellular therapy reinforcing the critical role of macrophages in refractory CD pathophysiology and as a target for cellular therapies. Furthermore, we report an unrecognised functional heterogeneity among HSC subpopulations in CD that may be relevant to our understanding of CD treatment and pathophysiology.
Gut microbiota-related neuroinflammation at the crossroad of food reward alterations: implications for eating disorders
Authors: Sabrina J P Huwart, Nuria Morales-Puerto, Amandine Everard
Journal: Gut (2025)

The link between gut microbiome and eating behaviours, especially palatable food intake, is a growing focus of scientific investigation. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function and neurobehavioural signalling. This review explores the role of neuroinflammation in dysregulations of food-induced reward signalling and the potential causal role of the gut microbiota on these proinflammatory processes. Particular attention is given to eating disorders (ED, specifically anorexia nervosa, binge eating disorder and bulimia nervosa) and potential links with the gut microbiota, food reward alterations and neuroinflammation. Finally, we propose gut microbiota modulation as a promising therapeutic strategy in food reward alterations and ED.
Risk of metachronous advanced neoplasia in patients with serrated lesions depending on follow-up schedule
Authors: Juliette Labelle, Roupen Djinbachian, Heiko Pohl, Douglas K Rex, Edgard Medawar, Benoit Panzini, Mickael Bouin, Edmond-Jean Bernard, Daniel von Renteln
Journal: Gut (2025)
Increasing the number of minor salivary glands from patients with Sjögren's disease improves the diagnostic and measurement precision of the histological focus score
Authors: Konstantinos Tryposkiadis, Saba Nayar, Valentina Pucino, Charlotte G Smith, Rachel M Brown, Timothy Bates, Simon J Bowman, Alice Sitch, Malcolm Price, Francesca Barone, Jon Deeks, Benjamin A Fisher
Journal: Annals of the Rheumatic Diseases (2025)

Minor salivary gland (MSG) biopsy has an important role in Sjögren's disease diagnosis and research. MSGs show within-patient variation in number of lymphocytic foci per unit area, but the optimal number of MSGs required to balance reproducibility and clinical acceptability has not been determined. Monte Carlo simulations were performed to investigate impact of MSG number on (i) diagnosis based on focus score (FS) ≥1; (ii) reproducibility, defined as the extent to which 2 FS measurements obtained from 2 within-patient biopsies are the same, assuming no systematic differences have occurred in between biopsies; and (iii) smallest sample size required to detect a clinically meaningful difference in FS. Data simulation was repeated for different MSG numbers (range, 2-7). Higher reproducibility was noted for every unit increase in MSG number, with the median absolute difference between 2 within-patient FS measurements decreasing from 1.05 (SD = 0.25) with 2 glands to 0.52 (SD = 0.12) with 7 glands. MSG number influenced the probability of a simulated patient receiving a FS ≥1, increasing from a median of 0.67 with 2 glands to 0.77 with ≥5 glands. MSG number influenced clinical trial sample sizes. For example, 80% statistical power to detect a 40% FS reduction required a sample size per group of 62 with 2 glands and 25 with 7 glands. For a diagnostic threshold of FS ≥1, a minimum of 5 glands should ideally be targeted. For continuous FS values, a larger number of MSGs (eg, 6) will increase reproducibility further and reduce clinical trial sample size requirements.
Do newly approved drugs have a worse observed safety profile than once established? A study on time trends in risks of key safety outcomes with immunomodulatory drugs against rheumatoid arthritis
Authors: Viktor Molander, Hannah Bower, Thomas Frisell, Johan Askling
Journal: Annals of the Rheumatic Diseases (2025)

To investigate rates of key safety outcomes in patients with rheumatoid arthritis (RA) initiating biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and in reference cohorts, presented over time since the market entry of each b/tsDMARD class and over calendar period at treatment start. This was a nationwide register-based cohort study conducted from 2006 to 2022. From the Swedish Rheumatology Quality Register and national registers, we identified treatment initiators of b/tsDMARDs (n = 33,550 initiations), an early bionaive RA cohort (n = 16,011), and a matched general population cohort (n = 111,074). The main outcome was first of either major adverse cardiovascular event, venous thromboembolism, cancer, or serious infection. We stratified rates by time since market entry of each b/tsDMARD class at treatment start, and by calendar year of treatment start. We calculated incidence rates (IRs) and hazard ratios (HRs) using Cox regression and adjusted for patient characteristics. Overall, 5862 events were observed in the b/tsDMARD initiator cohort. b/tsDMARD treatments initiated >5 (vs <2) years since market entry of that class were associated with lower outcome rates (unadjusted HR = 0.74; 95% CI = 0.67-0.81). This association was attenuated once adjusting for patient characteristics (adjusted HR = 0.93; 95% CI = 0.84-1.03). By contrast, during our study period, adjusted rates declined (adjusted HR = 0.74 and 95% CI = 0.69-0.80 for b/tsDMARDs initiated 2016-2021 vs 2006-2010), despite a constant rate in the background population. Modest channelling makes the safety profile of b/tsDMARDs appear worse when new on the market. Declining incidences of typical RA comorbidities in b/tsDMARD initiators during recent years suggest that the bar defining an "acceptable" safety profile for new b/tsDMARDs for use in RA should be lower(ed).
Substituted Judgment and The Paradigm Case Mistake
Authors: Daniel Brudney
Journal: The American Journal of Bioethics (2025)

Substituted judgment is widely used at the bedside, but the moral value that underpins its use needs examination. I argue that this value is the value of leading an authentic life. I then argue that an authentic life has multiple axes and that patients (like all human beings) vary widely in how they score on these axes. This entails that the moral weight of the value of authenticity in bedside decision-making also varies widely. And that means that, at the bedside, substituted judgment should not be seen as a moral trump. Put differently, when a surrogate must make a bedside decision, the answer to the "What would the patient choose?" question should not be morally decisive for that decision. The answer to that question should be a part, but only a part, of a more complex decision-making process.
Reducing global inequities in medical oxygen access: the Lancet Global Health Commission on medical oxygen security
Authors: Hamish R Graham, Carina King, Ahmed Ehsanur Rahman, Freddy Eric Kitutu, Leith Greenslade, Masooma Aqeel, Tim Baker, Lucio Flavio de Magalhães Brito, Harry Campbell, Karen Czischke, Mike English, Adegoke G Falade, Patricia J Garcia, Mireia Gil, Stephen M Graham, Amy Z Gray, Stephen R C Howie, Niranjan Kissoon, Ramanan Laxminarayan, Inês Li Lin, Michael S Lipnick, Dianne B Lowe, David Lowrance, Eric D McCollum, Tisungane Mvalo, Jacquie Oliwa, Stefan Swartling Peterson, Rediet Shimeles Workneh, Heather J Zar, Shams El Arifeen, Freddie Ssengooba
Journal: The Lancet Global Health (2025)
Cost-utility of a new psychosocial goal-setting and manualised support intervention for independence in dementia (NIDUS-Family) versus goal setting and routine care: an economic evaluation embedded within a randomised controlled trial
Authors: Abdinasir Isaaq, Claudia Cooper, Victoria Vickerstaff, Julie A Barber, Kate Walters, Iain A Lang, Penny Rapaport, Vasiliki Orgeta, Kenneth Rockwood, Laurie T Butler, Kathryn Lord, Gill Livingston, Sube Banerjee, Jill Manthorpe, Helen C Kales, Jessica Budgett, Rachael Hunter
Journal: The Lancet Healthy Longevity (2025)

NIDUS-Family is a psychosocial and behavioural intervention comprising six to eight sessions, delivered by non-clinical facilitators, and tailored to goals set by dyads of people with dementia and their unpaid or family carers. The intervention has been shown to be effective for attainment of personalised client goals. The current study aimed to determine whether the intervention is cost-effective. In this cost-utility and cost-effectiveness analysis within a two-armed, single-masked, multisite, superiority randomised controlled trial, we recruited 302 people with dementia living in their own homes and their family carers from National Health Service community settings and social and print media across England. Participants were randomly allocated (2:1) to the NIDUS-Family intervention group or control (goal setting and routine care) group. Randomisation was blocked and site-stratified, with allocation by a remote web-based system. We calculated the probability that NIDUS-Family is cost-effective for a client with dementia based on quality-adjusted life-years from a health and social care perspective and from a societal perspective (additionally including family carer time and out-of-pocket costs), at £20 000-30 000 decision thresholds for additional quality-adjusted life-years compared with usual care over 12 months. Analyses were done using the intention-to-treat population. This study is registered with ISRCTN, ISRCTN11425138, and is completed. Between April 30, 2020, and May 9, 2022, we randomly allocated 204 participants (109 [53%] women and 95 [47%] men) to the intervention group and 98 (60 [61%] women and 38 [39%] men) to the control group. 218 (72%) participants at 6 months and 178 (59%) at 12 months provided cost data. At both a £20 000 and £30 000 decision threshold, there was an 89% probability that NIDUS-Family was cost-effective compared with usual care from a health and social care perspective, and an 87% probability from a societal perspective. Intervention participants accrued on average £8934 (37%) less in costs than control participants (95% CI -£59 460 to £41 592). NIDUS-Family is the first personalised care and support intervention to show both cost-effectiveness from the perspective of the quality of life of people with dementia as well as clinical effectiveness and should therefore be part of routine dementia care. Alzheimer's Society.
Investing in local capacity and grassroots innovation to bridge gaps in medical oxygen access and security
Authors: Millicent Alooh, Gerald Paul Douglas, Tadesse Waktola Gamessa, Phoebe Nelima Khagame, June Kazira Madete, Varun Manhas, Timothy Mayamiko Mtonga, Shri Lak Nanjan Chandran, Zerihun Ketema Tadesse
Journal: The Lancet Global Health (2025)
Palbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): overall survival analysis of a randomised, open-label, phase 2 study
Authors: Hee Kyung Ahn, Ji-Yeon Kim, Kyung-Hun Lee, Gun Min Kim, Seok Yun Kang, Keun Seok Lee, Jee Hyun Kim, Kyong Eun Lee, Moon Hee Lee, Hee-Jun Kim, Han Jo Kim, Su-Jin Koh, In Hae Park, Joohyuk Sohn, Sung-Bae Kim, Jin Seok Ahn, Seonwoo Kim, Hyun Cho, Kyung Hae Jung, Seock-Ah Im, Yeon Hee Park
Journal: The Lancet Oncology (2025)
Europe needs a sustainably funded influenza research and response network
Authors: Florian Krammer, Wendy S Barclay, Martin Beer, Ian H Brown, Rebecca Jane Cox, Menno D de Jong, Ervin Fodor, Ron A M Fouchier, Gülsah Gabriel, Adolfo García-Sastre, Raquel Guiomar, Peter Horby, Marion Koopmans, Nicola S Lewis, Stefania Maggi, Isabella Monne, Nadia Naffakh, Hanna Nohynek, Albert Osterhaus, Katarina Prosenc, Roman Prymula, Rino Rappuoli, Monika Redlberger-Fritz, Guus F Rimmelzwaan, Colin A Russell, Xavier Saelens, Martin Schwemmle, Derek J Smith, Silke Stertz, Paula A Tähtinen, Calogero Terregino, Charlotte Thålin
Journal: The Lancet Infectious Diseases (2025)
Realigning diabetes regimens in older adults: a 4S Pathway to guide simplification and deprescribing strategies
Authors: Medha Munshi, Anna R Kahkoska, Joshua J Neumiller, Anastasia-Stefania Alexopoulos, Nancy A Allen, Tali Cukierman-Yaffe, Elbert S Huang, Sei J Lee, Kasia J Lipska, Lisa M McCarthy, Graydon S Meneilly, Naushira Pandya, Richard E Pratley, Leocadio Rodriguez-Mañas, Alan J Sinclair, Sarah L Sy, Elena Toschi, Ruth S Weinstock
Journal: The Lancet Diabetes & Endocrinology (2025)
Dynamic mortality prediction in critically Ill children during interhospital transports to PICUs using explainable AI
Authors: Zhiqiang Huo, John Booth, Thomas Monks, Philip Knight, Liam Watson, Mark Peters, Christina Pagel, Padmanabhan Ramnarayan, Kezhi Li
Journal: npj Digital Medicine (2025)

Critically ill children who require inter-hospital transfers to paediatric intensive care units are sicker than other admissions and have higher mortality rates. Current transport practice primarily relies on early clinical assessments within the initial hours of transport. Real-time mortality risk during transport is lacking due to the absence of data-driven assessment tools. Addressing this gap, our research introduces the PROMPT (Patient-centred Real-time Outcome monitoring and Mortality PredicTion), an explainable end-to-end machine learning pipeline to forecast 30-day mortality risks. The PROMPT integrates continuous time-series vital signs and medical records with episode-specific transport data to provide real-time mortality prediction. The results demonstrated that with PROMPT, both the random forest and logistic regression models achieved the best performance with AUROC 0.83 (95% CI: 0.79-0.86) and 0.81 (95% CI: 0.76-0.85), respectively. The proposed model has demonstrated proof-of-principle in predicting mortality risk in transported children and providing individual-level model interpretability during inter-hospital transports.
Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study
Authors: Georgina V Long, Victoria Atkinson, Serigne N Lo, Alexander D Guminski, Shahneen K Sandhu, Michael P Brown, Maria Gonzalez, Grant A McArthur, Alexander M Menzies
Journal: The Lancet Oncology (2025)
Cancer vaccines: current status and future directions
Authors: Yingqiong Zhou, Yuquan Wei, Xiaohe Tian, Xiawei Wei
Journal: Journal of Hematology & Oncology (2025)

Cancer continues to be a major global health burden, with high morbidity and mortality. Building on the success of immune checkpoint inhibitors and adoptive cellular therapy, cancer vaccines have garnered significant interest, but their clinical success remains modest. Benefiting from advancements in technology, many meticulously designed cancer vaccines have shown promise, warranting further investigations to reach their full potential. Cancer vaccines hold unique benefits, particularly for patients resistant to other therapies, and they offer the ability to initiate broad and durable T cell responses. In this review, we highlight the antigen selection for cancer vaccines, introduce the immune responses induced by vaccines, and propose strategies to enhance vaccine immunogenicity. Furthermore, we summarize key features and notable clinical advances of various vaccine platforms. Lastly, we delve into the mechanisms of tumor resistance and explore the potential benefits of combining cancer vaccines with standard treatments and other immunomodulatory approaches to improve vaccine efficacy.
A Di-Aptamer-functionalized scaffold promotes bone regeneration by facilitating the selective retention of MSCs and EPCs and then promoting crosstalk between osteogenesis and angiogenesis
Authors: Qiandong Yang, Jiangling Zhou, Ming Yang, Jiayi Wei, Yingtao Gui, Fan Yang, Sihao He, Juan Cai, Bo Yu, Qijie Dai, Zhenzhen Tang, Tianyong Hou
Journal: Biomaterials (2025)
Clinical trials informed framework for real world clinical implementation and deployment of artificial intelligence applications
Authors: Jacqueline G. You, Tina Hernandez-Boussard, Michael A. Pfeffer, Adam Landman, Rebecca G. Mishuris
Journal: npj Digital Medicine (2025)

With rapidly evolving artificial intelligence solutions, healthcare organizations need an implementation roadmap. A "clinical trials" informed approach can promote safe and impactful implementation of artificial intelligence. This framework includes four phases: (1) Safety; (2) Efficacy; (3) Effectiveness and comparison to an existing standard; and (4) Monitoring. Combined with inter-institutional collaboration and national funding support, this approach will advance safe, usable, effective, and equitable deployments of artificial intelligence in healthcare.