tbuckley/cabot-search huggingface dataset:
From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy
Authors: Anqi Lin, Aimin Jiang, Lihaoyun Huang, Yu Li, Chunyanx Zhang, Lingxuan Zhu, Weiming Mou, Zaoqu Liu, Jian Zhang, Quan Cheng, Ting Wei, Peng Luo
Journal: Gut Microbes (2025)

The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.
Low-dose aspirin versus placebo in postpartum venous thromboembolism: a multi-national, pilot, randomised, placebo-controlled trial
Authors: Leslie Skeith, A Kinga Malinowski, Darine El-Chaâr, Wee-Shian Chan, Jennifer Donnelly, Céline Chauleur, Wessel Ganzevoort, Stephen Wood, Suzanne Dubois, Claire McCarthy, Andrea Buchmuller, Hanke Wiegers, Paul S Gibson, Fionnuala Ní Áinle, Saskia Middeldorp, Lisa Duffett, Shannon M Bates, Alexandra Garven, Jill Baxter, Brendan Cord Lethebe, Marc A Rodger
Journal: The Lancet Haematology (2025)
Performance of the pooled cohort equations and D:A:D risk scores among individuals with HIV in a global cardiovascular disease prevention trial: a cohort study leveraging data from REPRIEVE
Authors: Steven K Grinspoon, Markella V Zanni, Virginia A Triant, Amy Kantor, Triin Umbleja, Marissa R Diggs, Sarah M Chu, Kathleen V Fitch, Judith S Currier, Gerald S Bloomfield, José L Casado, Mireia de la Peña, Lori E Fantry, Edward Gardner, Judith A Aberg, Carlos D Malvestutto, Carl J Fichtenbaum, Michael T Lu, Heather J Ribaudo, Pamela S Douglas
Journal: The Lancet HIV (2025)
Antibiotic treatment versus appendicectomy for acute appendicitis in adults: an individual patient data meta-analysis
Authors: Jochem C G Scheijmans, Jussi Haijanen, David R Flum, Wouter J Bom, Giana H Davidson, Corinne Vons, Arnold D Hill, Luca Ansaloni, David A Talan, Stefan T van Dijk, Sarah E Monsell, Saija Hurme, Suvi Sippola, Caroline Barry, Sorcha O'Grady, Marco Ceresoli, Ramon R Gorter, Gerjon Hannink, Marcel G Dijkgraaf, Paulina Salminen, Marja A Boermeester
Journal: The Lancet. Gastroenterology & hepatology (2025)
Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications
Authors: Pharaoh Fellow Mwale, Cheng-Ta Hsieh, Ting-Lin Yen, Jing-Shiun Jan, Rajeev Taliyan, Chih-Hao Yang, Wen-Bin Yang
Journal: Molecular Neurodegeneration (2025)

Abstract Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors. This review explores the role of CHI3L1 in the pathogenesis of these disorders, with a focus on its contributions to neuroinflammation, immune cell infiltration, and neuronal degeneration. As a key regulator of neuroinflammation, CHI3L1 modulates microglia and astrocyte activity, driving the release of proinflammatory cytokines that exacerbate disease progression. In addition to its role in disease pathology, CHI3L1 has emerged as a promising biomarker for the diagnosis and monitoring of brain disorders. Elevated cerebrospinal fluid (CSF) levels of CHI3L1 have been linked to disease severity and cognitive decline, particularly in AD and MS, highlighting its potential for clinical diagnostics. Furthermore, therapeutic strategies targeting CHI3L1, such as small-molecule inhibitors and neutralizing antibodies, have shown promise in preclinical studies, demonstrating reduced neuroinflammation, amyloid plaque accumulation, and improved neuronal survival. Despite its therapeutic potential, challenges remain in developing selective and safe CHI3L1-targeted therapies, particularly in ensuring effective delivery across the blood–brain barrier and mitigating off-target effects. This review addresses the complexities of targeting CHI3L1, highlights its potential in precision medicine, and outlines future research directions aimed at unlocking its full therapeutic potential in treating neurodegenerative diseases and brain pathologies.
Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity
Authors: Liming Gui, Kaiwen Chen, Jingjing Yan, Ping Chen, Wei-Qiang Gao, Bin Ma
Journal: Cell Reports Medicine (2025)

The induction of immunogenic cell death (ICD) impedes tumor progression via both tumor cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored and optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as a potential target. The ICD-provoking effect of NUAK1 inhibition depends on the production of reactive oxygen species (ROS), consequent to the downregulation of nuclear factor erythroid 2-related factor 2 (NRF2)-mediated antioxidant gene expression. Moreover, the mevalonate pathway/cholesterol biosynthesis, activated by spliced form of X-box binding protein 1 (XBP1s) downstream of ICD-induced endoplasmic reticulum (ER) stress, functions as a negative feedback mechanism. Targeting the mevalonate pathway with CRISPR knockout or the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor simvastatin amplifies NUAK1 inhibition-mediated ICD and antitumor activity, while cholesterol dampens ROS and ICD, and therefore also dampens tumor suppression. The combination of NUAK1 inhibitor and statin enhances the efficacy of anti-PD-1 therapy. Collectively, our study unveils the promise of blocking the mevalonate-cholesterol pathway in conjunction with ICD-targeted immunotherapy.
Assessment of MpoxPlex, a high-throughput and multiplexed immunoassay: a diagnostic accuracy study
Authors: Scott Jones, Bethany Hicks, Helen Callaby, Daniel Bailey, N Claire Gordon, Tommy Rampling, Catherine Houlihan, Rachael Jones, Marcus Pond, Ravi Mehta, Deborah Wright, Clarissa Oeser, Simon Tonge, Ezra Linley, Cathy Rowe, Bassam Hallis, Ashley Otter
Journal: The Lancet Microbe (2025)

In May, 2022, the first global outbreak of mpox (formerly known as monkeypox) occurred. In response, public health agencies in the UK have made smallpox vaccines available to individuals at the highest risk of infection. With mpox cases still being detected globally, novel tools are required to aid with diagnosis, serosurveillance, and the evaluation of immune responses following infection and immunisation with current and new vaccine candidates. Here, we describe the development of a multiplexed immunoassay, MpoxPlex, able to measure IgG responses to 12 Orthopoxvirus antigens concurrently and distinguish between responses to infection and vaccination. Using the Luminex (DiaSorin, Saluggia, Italy) platform, antibody responses to vaccinia virus (VACV) antigens B5, A27, and A33 and monkeypox virus (MPXV) antigens E8, B6, B2, M1, A27, A35, H3, A29, and A5 were assessed in serum from individuals after MPXV infection (n=24) and after vaccination (n=75) with modified VACV Ankara-Bavarian Nordic. Assay characteristics and cutoffs were calculated by fitting receiver operating characteristic curves to the median fluorescence intensities of these positive samples and negative samples that were run alongside (n=435). P values were calculated using non-parametric Mann-Whitney, Kruskal-Wallis, and Dunn's multiple comparisons tests. Using the results from a combination of eight antigens, we were able to distinguish samples as either post-vaccination or post-infection from negative samples with a sensitivity of 98% and a specificity of 95%. IgG responses to MPXV antigen A27 were able to distinguish post-MPXV infection with a sensitivity of 88% and a specificity of 97%. VACV antigen A27 and MPXV antigens A29 and A5 provided little diagnostic advantage. With additional benefits over current serological assays, we believe this assay will provide substantial insight into the current global outbreak of mpox. MpoxPlex shows use for both serosurveillance and immunological studies of vaccination and infection. Grant-in-aid funding to the Emerging Pathogen Serology Group at Porton Down, UK Health Security Agency.
Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24–59 months in The Gambia: a phase 4, open-label, randomised controlled trial
Authors: Chikondi Peno, Ya Jankey Jagne, Melanie Clerc, Carlos Balcazar Lopez, Edwin P Armitage, Hadijatou Sallah, Sainabou Drammeh, Elina Senghore, Gabriel Goderski, Sophie van Tol, Adam Meijer, Alicia Ruiz-Rodriguez, Wouter de Steenhuijsen Piters, Emma de Koff, Sheikh Jarju, Benjamin B Lindsey, Janko Camara, Sulayman Bah, Nuredin I Mohammed, Beate Kampmann, Ed Clarke, David H Dockrell, Thushan I de Silva, Debby Bogaert
Journal: The Lancet Microbe (2025)
Prevalence, misclassification, and clinical consequences of the heteroresistant phenotype in Escherichia coli bloodstream infections in patients in Uppsala, Sweden: a retrospective cohort study
Authors: Gabriel Heyman, Sofia Jonsson, Nikos Fatsis-Kavalopolous, Karin Hjort, Hervé Nicoloff, Mia Furebring, Dan I Andersson
Journal: The Lancet Microbe (2025)
Tuberculous Pericarditis: Diagnostic, Therapeutic, and Prognostic Aspects in a Cardiology Department in Dakar – Senegal
Authors: Aliou Alassane Ngaide
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Introduction: The objectives of this study were to determine the frequency of tuberculous pericarditis and to describe its diagnostic, therapeutic, and prognostic aspects. Methodology: We conducted a retrospective descriptive and analytical study over five years from January 1, 2015, to December 31, 2019, at the General Hospital Idrissa POUYE in Dakar. The study focused on patients aged over 18 years who were hospitalized for tuberculous pericarditis, with or without effusion, and treated with antituberculous drugs according to the protocol established by the National Tuberculosis Control Program (PNLT) of Senegal. This work was carried out in collaboration with the hospital management after obtaining approval from the cardiology department by signing the access form to patient records. Data were entered using Sphinx software version 5.1.0.2 and analyzed with SPSS (Statistical Package for Social Sciences) software version 18. Results: We identified 108 cases of pericarditis from all causes, representing a hospital prevalence of 1.95%. Among these, 42 were of tuberculous origin, with a hospital prevalence of 0.76% and 38.89% of all pericarditis cases, with a male predominance (sex ratio of 1.33). The mean age was 28.6 ± 10 years, with a predominance in the 20-29 age group (57.1%). More than half of the patients (57.1%) had a low socio-economic status, and 42.85% had a history of contact with tuberculosis. Symptoms were mainly dyspnea and chest pain (78.57% each). Tachycardia (85.7%) and pericardial friction rub (42.9%) were frequently observed. The pericardial puncture fluid was sero-hematic in 66.7%, and the study showed a positive Rivalta test with lymphocytic predominance. The adenosine deaminase (ADA) level in the pericardial puncture fluid, performed in 12.5% of patients, was positive. HIV serology was positive in 10% of cases. Cardiac ultrasound showed effusion in all patients, with a large amount in 64.29% of cases. All patients received antituberculous treatment, with 35.7% also receiving corticosteroids. The average hospital stay was 11 days, with complication rates of pericardial constriction (14.3%) and deaths (7.1%). Conclusion: Tuberculous pericarditis remains a significant health issue, particularly among patients of low socio-economic status and those with a history of contact with tuberculosis. Despite the availability of treatments, complication and mortality rates remain considerable, highlighting the need for early diagnosis and comprehensive management.
Comprehensive plasma cytokine profiling reveals a distinct endotype of Type 2 Inflammation in Chronic Pruritus of Unknown Origin
Authors: Jaya Manjunath, Aaron Bao, Wilce Gonzalez, Elizabeth Vojvoda, Anjali J D'Amiano, Shivam Patel, Viviane Liao, Darshan Sivaloganathan, Shrey Bhatt, Michael Ahmadi, Shawn G Kwatra
Journal: Journal of the American Academy of Dermatology (2025)
Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer
Authors: Subhamoy Chakraborty, Utsav Sen, Kedwin Ventura, Vrinda Jethalia, Charles Coleman, Subhasree Sridhar, Avisek Banerjee, Hilal Ozakinci, Yazhini Mahendravarman, Konrad Snioch, Elisa de Stanchina, Misty D. Shields, Lewis E. Tomalin, Deniz Demircioglu, Theresa A. Boyle, Anna Tocheva, Dan Hasson, Triparna Sen
Journal: Cell Reports Medicine (2025)
P2Y14R activation facilitates liver regeneration via CREB/DNMT3b/Dact-2/β-Catenin signals in acute liver failure
Authors: Mengze Zhou, Yehong Li, Jialong Qian, Xinli Dong, Yanshuo Guo, Li Yin, Chunxiao Liu, Kun Hao, Qinghua Hu
Journal: Acta Pharmaceutica Sinica B (2025)

Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y14R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y14R axis in ALF. In this study, hepatic P2Y14R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y14R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y14R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y14R (P2Y14R flox/flox Alb cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y14R (P2Y14R flox/flox Lrat cre/+ ) mice. Mechanistically, P2Y14R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y14R in ALF and provide an effective adjuvant strategy for treatment of ALF.
Epidemiology of bacterial biofilms on polyps and normal tissues in a screening colonoscopy cohort
Authors: Julia L. Drewes, Samara B. Rifkin, Madison McMann, Sara Glass, Emma Spence, Caroline R. Wensel, Abby L. Geis, Courtney Stevens, Joell J. Gills, Hao Wang, Linda M. Hylind, Gerard Mullin, David Kafonek, David Cromwell, Louis La Luna, Francis M. Giardiello, Cynthia L. Sears, Marshall Bedine, Eduardo Gonzalez-Velez, Hazel Marie Galon Veloso, Pamela Marrero, Stacy Gerhart, Amy Schiller, Karin Donato, John Altomare, Nirav Shah, Christopher Ibrahim, Ravi Ghanta, Brent Tabisz, Louis Levine
Journal: Gut Microbes (2025)

Invasive bacterial biofilms are implicated in colorectal cancer. However, their prevalence on histologically normal tissues and polyps is not well established, and risk factors of biofilms have not been previously investigated. Here we evaluated potential procedural and demographic risk factors associated with biofilm status using a cross-sectional observational cohort. Histologically normal colonic biopsies from 2,051 individuals undergoing screening colonoscopy were evaluated for biofilm status using fluorescence in situ hybridization with oligonucleotide probes targeting bacterial 16S rRNA. Polyp tissues from 21 individuals were also examined. Procedural, demographic, and lifestyle predictors of bacterial scores were evaluated using multivariable proportional odds regression models. Procedural variables that negatively impacted bacterial scores and biofilm detection included smaller biopsy forcep size, physician, bowel preparation type, and shorter times from bowel preparation completion to colonoscopy. Lifestyle variables including greater alcohol and cigarette usage were associated with higher bacterial scores, while vigorous physical activity and diabetes mellitus were associated with lower bacterial scores. Bacterial scores on normal tissues were significantly higher in individuals with colorectal cancer but not polyps compared to dysplasia-free individuals. Direct examination of polyp tissues demonstrated similar bacterial burden and taxonomic composition compared to paired normal tissues, but polyps displayed enhanced bacterial invasion into crypts. Additionally, bacterial scores significantly correlated with increasing polyp size, suggesting co-evolution of polyps with bacterial invasion and biofilm status. Colonic biofilms are highly dynamic ecosystems that associate with several other known risk factors for colorectal cancer. However, biofilm detection is impacted by multiple procedural factors.
Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives
Authors: Deshuang Zhang, Dongke Xie, Yi Qu, Dezhi Mu, Shaopu Wang
Journal: Gut Microbes (2025)

Necrotizing Enterocolitis (NEC) is a severe, life-threatening inflammatory condition of the gastrointestinal tract, especially affecting preterm infants. This review consolidates evidence from various biomedical disciplines to elucidate the complex pathogenesis of NEC, integrating insights from clinical, microbial, and molecular perspectives. It emphasizes the modulation of NEC-associated inflammatory pathways by probiotics and novel biologics, highlighting their therapeutic potential. We further critically examine dysbiotic alterations within the gut microbiota, with a particular focus on imbalances in bacterial and viral communities, which may contribute to the onset of NEC. The intricate interactions among toll-like receptor 4 (TLR4), microvascular integrity, immune activation, and the inflammatory milieu are meticulously summarized, offering a sophisticated understanding of NEC pathophysiology. This academic review aims to enhance the etiological comprehension of NEC, promote the development of targeted therapeutic interventions, and impart the significant impact of perinatal factors on the formulation of preventive and curative strategies for the disease.
Efficacy and safety of KN026 and docetaxel for HER2‐positive breast cancer: a phase II clinical trial
Authors: Jianli Ma, Jingxuan Wang, Ting Xu, Quchang Ouyang, Xiaojia Wang, Jingfen Wang, Lu Gan, Zhong Ouyang, Daren Lin, Tao Sun, Changping Shan, Herui Yao, Baochun Zhang, Zhengguang Li, Zhixiang Zhuang, Ying Lu, Hongwei Yang, Jian Huang, Xingwang Yang, Hongmei Sun, Qingyuan Zhang
Journal: Cancer Communications (2025)

Abstract Background The standard first‐line treatment for human epidermal growth factor receptor 2 (HER2)‐positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel. This study aimed to evaluate the effectiveness of KN026, an anti‐HER2 bispecific antibody, plus docetaxel in first‐line treatment of HER2‐positive recurrent/metastatic breast cancer. Methods This open‐label, single‐arm, phase II study enrolled patients with HER2‐positive recurrent/metastatic breast cancer in 19 centers across China from December 30, 2019 to May 27, 2021. Patients were administered KN026 (30 mg/kg) plus docetaxel (75 mg/m 2 ) in 21‐day cycles. Primary endpoints included the objective response rate (ORR) and duration of response (DOR). In addition, overall survival (OS), progression‐free survival (PFS), clinical benefit rate (CBR) and safety profile were examined. Results A total of 57 patients were included. In the efficacy analysis set of 55 patients, the ORR was 76.4% (95% confidence interval [CI], 63.0%‐86.8%), and the CBR was 85.5% (95% CI, 73.3%‐93.5%). The median DOR was not reached (95% CI, 20.7 months‐not reached). In the safety set of 57 patients, the median PFS was 27.7 months (95% CI, 18.0 months‐not reached). The median OS was not reached, with OS rates at 12, 24 and 30 months of 93.0%, 84.1% and 78.5%, respectively. Grade ≥3 treatment‐emergent adverse events (AEs) were detected in 36 (63.2%) patients. No deaths were attributed to KN026 or docetaxel. Conclusion KN026 plus docetaxel showed promising efficacy and a manageable safety profile in first‐line treatment of HER2‐positive recurrent/metastatic breast cancer.
A pathway from fragmentation to interoperability through standards-based enterprise architecture to enhance patient safety
Authors: Zoie Shui-Yee Wong, Yang Gong, Shin Ushiro
Journal: npj Digital Medicine (2025)

Abstract Creating an ontology is the essential step in natural language processing (NLP). To improve patient safety in this era of generative AI, it is crucial to develop a standards-driven, ontology-based architecture for patient safety that can seamlessly integrate with health systems, thereby facilitating effective detection and monitoring potentially preventable harms in healthcare. This visionary, whole-system approach to patient safety addresses a significant gap in establishing resilient safety systems within the healthcare sector.