tbuckley/cabot-search huggingface dataset:
Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications
Authors: Victoria Gudiño, Raquel Bartolomé-Casado, Azucena Salas
Journal: Gut (2025)

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all intestinal cell types, including immune, epithelial and stromal cells, have been described in these diseases. The study of IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse cell types, limiting insights. Single-cell omic technologies overcome the intrinsic limitations of bulk analysis and reveal the complexity of multicellular tissues at a cell-by-cell resolution. Within healthy and inflamed intestinal tissues, single-cell omics, particularly single-cell RNA sequencing, have contributed to uncovering novel cell types and cell functions linked to disease activity or the development of complications. Collectively, these results help identify therapeutic targets in difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae or inflammation of the pouch. More recently, single-cell omics have gradually been adopted in studies to understand therapeutic responses, identify mechanisms of drug failure and potentially develop predictors with clinical utility. Although these are early days, such studies lay the groundwork for the implementation in clinical practice of new technologies in diagnostics, monitoring and prediction of disease prognosis. With this review, we aim to provide a comprehensive survey of the studies that have applied single-cell omics to the study of UC or CD, and offer our perspective on the main findings these studies contribute. Finally, we discuss the limitations and potential benefits that the integration of single-cell omics into clinical practice and drug development could offer.
Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8<sup>+</sup>T cell exhaustion
Authors: Fangzhi Lou, Li Yan, Shihong Luo, Yunmei Dong, Jingyi Xu, Ning Kang, Haiyang Wang, Yiyun Liu, Juncai Pu, Bing Yang, Richard D Cannon, Peng Xie, Ping Ji, Xin Jin
Journal: Gut (2025)

Background Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown. Objective We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8 + T cells. Design 4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model. Results Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8 + T cells, thereby promoting HNSCC tumourigenesis. Conclusion CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8 + T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.
Carbon footprinting and environmental impact of gastrointestinal endoscopy procedures at a tertiary care institution: a prospective multi-dimensional assessment
Authors: Hardik Rughwani, Rakesh Kalapala, Anudeep Katrevula, Nitin Jagtap, Madhav Desai, Sara Teles de Campos, Mohan Ramchandani, Sundeep Lakhtakia, Rupjyoti Talukdar, Santosh Darisetty, Sana Fatima Memon, Guduru Venkat Rao, Marco Bruno, Prateek Sharma, D Nageshwar Reddy
Journal: Gut (2025)

Background Given the imperative to combat climate change, reducing the healthcare sector’s implications on the environment is crucial. Objective This study aims to offer a comprehensive assessment of the environmental impact of gastrointestinal endoscopy (GIE) procedures, specifically focusing on greenhouse gas (GHG) emissions and waste generation. Design A prospective study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India, from 29 May to 10 June 2023, including all consecutive GIE procedures. Carbon emissions for various variables involved were calculated with specific emission factors using ‘The GHG Protocol’. Results Based on data from 3244 consecutive patients undergoing 3873 procedures, the study revealed a total carbon footprint of 148 947.32 kg CO 2 e or 38.45 kg CO 2 e per procedure. Excluding patient travel, the emissions were 6.50 kg CO 2 e per procedure. The total waste generated was 1952.50 kg, averaging 0.504 kg per procedure, far less than 2–3 kg per procedure in the West. The waste disposal breakdown was 9.5% direct landfilling, 64.8% incineration, then landfilling and 25.7% recycling, which saved 380 kg CO 2 e. India effectively recycles 25.7% of hospital-related waste, which undergoes landfilling in the West. The primary contributors to GHG emissions were patient travel (83.09%), electricity consumption (10.42%), medical gas transport and usage (3.63%) and water consumption (1.86%). Diagnostic procedures generate less waste and lower carbon footprint than therapeutic procedures. Conclusion This study highlights the significant environmental footprint of GIE procedures, emphasising the importance of optimising practices to reduce patient travel and repeat procedures, alongside improving electricity and water management for sustainable healthcare.
Differential Effectiveness of Water, Sanitation, and Handwashing Interventions to Reduce Child Diarrhea in Dry and Rainy Seasons: A Systematic Review and Meta-Analysis of Intervention Trials
Authors: Sydney Hubbard, Jennyfer Wolf, Hemali H. Oza, Benjamin F. Arnold, Matthew C. Freeman, Karen Levy
Journal: Environmental Health Perspectives (2025)

Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric pathogen infections and diarrhea are highly seasonal and climate-sensitive, which could explain heterogeneous findings. Understanding how season influences the effectiveness of WASH interventions is critical for informing intervention approaches that will be resistant under the varying weather conditions that climate change will bring.
‘The right advice’: a qualitative study examining enablers and barriers to recreational running and beliefs about knee health following knee surgery
Authors: James L N Alexander, Allison M Ezzat, Adam G Culvenor, Danilo De Oliveira Silva, Melissa Haberfield, Jean-François Esculier, Christian J Barton
Journal: British Journal of Sports Medicine (2025)

Objectives To examine the experiences, knowledge and beliefs of recreational runners with a history of knee surgery regarding (i) enablers and barriers to running participation, (ii) the association of running and knee joint health, and (iii) perceived benefits and motivations for running. Methods 17 runners (≥3 times/week, ≥10 km/week) with a history of knee surgery (7±7 years post-surgery, 9 women, age 36±8 years) participated in one-on-one semi-structured interviews. Interviews were recorded, transcribed verbatim and analysed using reflexive thematic analysis. Trustworthiness was built by following established qualitative research guidelines and by participant validation of findings in the final analysis stages. Results We identified 9 themes (5 subthemes) for aim (i); 3 themes (10 subthemes) for aim (ii); and 2 themes (4 subthemes) for aim (iii). Positive health professional support including education, exercise rehabilitation and a tailored return-to-run plan enabled participants to return to running following surgery. Effective load management either independently or with coach assistance, and consistent strength training were considered key to maintaining participation. Barriers to running following surgery included unhelpful health professional encounters, persistent knee symptoms and muscle weakness, new running-related injuries, anxiety and fear about reinjury, and difficulty finding time. Participants had varying beliefs about running and knee joint health, although most believed that running benefited long-term knee health. Improved mental health and social connection were the most common motivators to run. Conclusion Our qualitative findings may inform strategies to support adults to commence, or return to, and maintain running participation following knee surgery.
Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma
Authors: Thomas Eigentler, Ioannis Thomas, Igor Samoylenko, Michael Erdmann, Lucie Heinzerling, Sebastian Ochsenreither, Jürgen Krauss, Arjun Oberoi, Caroline Robert, Celeste Lebbe, Juan Martin-Liberal, Lukas Koch, Erika Richtig, Patrick Terheyden, Carsten Weishaupt, Peter Mohr, Yulia Semiletova, Casilda Llacer Perez, Peter Brossart, Franz Georg Bauernfeind, Michael Fluck, Artem Poltoratskiy, Marina Sekacheva, Ainara Soria, Beate Schmitt-Bormann, Marina Gonzalez, Jana Heß, Peter Wengenmayer, Tobias Seibel, Sven D Koch, Gianluca Quintini, Paula Codó, Martin Falk, Oliver Schönborn-Kellenberger, Ulrike Gnad-Vogt
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background CV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-naïve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma. Methods This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor. The preliminary efficacy of the RD was assessed in patients with cMEL in the expansion cohorts. Results Between September 2017 and October 2022, 98 patients were enrolled in monotherapy and combination therapy dose escalation and dose expansion cohorts. Two patients in the CV8102 monotherapy dose escalation cohort experienced relevant toxicities at the 900 µg dose level. One patient had Grade 3 aspartate transaminase/alanine aminotransferase elevation which met dose-limiting toxicity (DLT) criteria. Another patient experienced Grade 3 immune-mediated pneumonitis. No DLTs occurred in the combination therapy dose escalation cohort. The MTD was not formally reached and the RD for expansion was 600 µg. Common treatment-emergent adverse events were fever (57%), chills (37%) and fatigue (25%). In the dose escalation part, objective responses occurred in 3/33 patients treated with CV8102 as monotherapy and in 2/25 patients treated with CV8102 plus a PD-1 inhibitor. In the expansion cohorts in patients with anti-PD-1 therapy-refractory melanoma, 0/10 patients treated with CV8102 as monotherapy and 5/30 patients (17%) treated in combination with a PD-1 inhibitor experienced objective responses. Conclusions IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor. Trial registration number NCT03291002 .
Modulating lipid metabolism improves tumor immunotherapy
Authors: Yu Ping, Qiuqing Fan, Yi Zhang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immunotherapy has progressed significantly in cancer treatment; however, several factors influence its outcomes. Abnormal lipid metabolism, which is frequently observed in cancers, promotes tumor proliferation, invasion, and metastasis. Li et al from the Medical Oncology Department of Chongqing University Cancer Hospital constructed a lipid metabolism scoring system and reported that MK1775 inhibited fatty acid oxidation in tumor-associated macrophages and reduced T-cell infiltration, further enhancing the efficacy of immunotherapy. This study demonstrated the critical role of lipid metabolism scoring system and lipid metabolism in immunotherapy. Currently, the metabolism of lipids, such as fatty acids, phospholipids, and cholesterol, has been reported to affect the tumor microenvironment by regulating immune cells, including T cells, natural killer cells, and macrophages. These metabolic changes can impair the efficacy of immunotherapy, resulting in tumor progression. Consequently, lipid metabolism emerges as an important immune regulator for improving immunotherapeutic outcomes and provides a novel and powerful strategy for tumor combination therapy.
Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis
Authors: Cameron Wood, Liliana Lyniv, James M Isaacs, Jacob M Kaufman, Eziafa I Oduah, Jeff Clarke, Jeffrey Crawford, Thomas Stinchcombe, Betty C Tong, Xiaofei Wang, Lin Gu, Dennis Wigle, Konstantin H Dragnev, Scott J Antonia, Kent Weinhold, Neal Ready
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC. Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers. Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively. Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.
Associations of Prenatal Mercury Exposure and PUFA with Telomere Length and mtDNA Copy Number in 7-Year-Old Children in the Seychelles Child Development Nutrition Cohort 2
Authors: Anja Stajnko, Daniela Pineda, Jonathan K. Klus, Tanzy M. Love, Sally W. Thurston, Maria S. Mulhern, J. J. Strain, Emeir M. McSorley, Gary J. Myers, Gene E. Watson, Emelyn Shroff, Conrad F. Shamlaye, Alison J. Yeates, Edwin van Wijngaarden, Karin Broberg
Journal: Environmental Health Perspectives (2025)

Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life.
Development of RelB-Targeting Small Molecule Inhibitors of Non-canonical NF-κB Signaling with Antitumor Efficacy
Authors: Cuifeng Li, Shuqi Wei, Donglin Sun, Zhuo Yang, Qi Wang, Han Lin, Haohao Zhang, Yiming Hu, Dandan Liu, Deji Ye, Yu Tao, Zhanjie Liu, Zhijian Xu, Bo Li, Lingling Li, Jie Zhang, Xi Chen, Ningxia Xie, Yufang Shi, Sanhong Liu, Yongzhong Liu, Yuhang Jiang, Weiliang Zhu, Xiaoren Zhang
Journal: Molecular Therapy (2025)

Dysfunction of the non-canonical NF-κB signaling pathway has been causally associated with numbers of cancers and autoimmune diseases. However, specific inhibitors for this signaling pathway remain to be developed. Here we showed that structure-based cell-based screening yielded a potent and specific small molecule targeting RelB to inhibit non-canonical NF-κB signaling pathway, while had no inhibitory effect on canonical NF-κB signaling pathway. Mechanistically, the inhibitor directly interacted with RelB protein and disrupted RelB binding to its target DNA, thus repressing RelB transactivity on target genes. Through blocking oncogenic activity of non-canonical NF-κB signaling pathway in colorectal cancer or B lymphoma, the inhibitor efficiently exerted a potent antitumor effect in vitro and in vivo. Thus, our study provided new RelB-targeting inhibitor that inhibited non-canonical NF-κB signaling pathway and facilitated precise therapeutic applications in cancers and possibly other diseases.
5-HT orchestrates Histone Serotonylation and Citrullination to Drive Neutrophil Extracellular Traps and Liver Metastasis
Authors: Kaiyuan Liu, Yingchao Zhang, Genyu Du, Xinyu Chen, Lingling Xiao, Luyao Jiang, Na Jing, Penghui Xu, Chaoxian Zhao, Yiyun Liu, Huifang Zhao, Yujiao Sun, Jinming Wang, Chaping Cheng, Deng Wang, Jiahua Pan, Wei Xue, Pengcheng Zhang, Zhi-Gang Zhang, Wei-Qiang Gao, Shu-Heng Jiang, Kai Zhang, Helen He Zhu
Journal: Journal of Clinical Investigation (2025)

Serotonin (5-HT) is a neurotransmitter that has been linked to tumorigenesis. Whether and how 5-HT modulates cells in the microenvironment to regulate tumor metastasis remains to be largely unknown. Here, we demonstrate that 5-HT is secreted by neuroendocrine prostate cancer (NEPC) cells to communicate with neutrophils and to induce neutrophil extracellular traps (NETs) in the liver, which in turn facilitates the recruitment of disseminated cancer cells and promotes liver metastasis. 5-HT induces histone serotonylation (H3Q5ser) and orchestrates histone citrullination (H3cit) in neutrophils to trigger chromatin decondensation and facilitate the formation of NETs. Interestingly, we uncover in this process a reciprocally reinforcing effect between H3Q5ser and H3cit and a crosstalk between the respective writers TGM2 and PAD4. Genetic ablation or pharmacological targeting of TGM2, or inhibiting 5-HT transporter (SERT) with the FDA-approved antidepressant drug fluoxetine reduces H3Q5ser and H3cit modifications, suppresses NETs formation, and effectively inhibits NEPC, small cell lung cancer, and thyroid medullary cancer liver metastasis. Collectively, the 5-HT-triggered NETs production highlights a new targetable neurotransmitter-immune axis in driving liver metastasis of neuroendocrine cancers.
Why Is C5a Inflammatory Complement Inhibition Not Enough to Improve C3 Glomerulopathy?
Authors: Peter F. Zipfel, Christine Skerka
Journal: Journal of the American Society of Nephrology (2025)

Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany Correspondence: Prof. Dr. Peter F. Zipfel, email: [email protected] See related article, "Safety and Efficacy of Avacopan in Patients with Complement 3 Glomerulopathy: Randomized, Double-Blind Clinical Trial," on pages XXX–XXX.
Increasing the Removal of Large Solutes by Kidney Replacement Therapy
Authors: Timothy W. Meyer
Journal: Journal of the American Society of Nephrology (2025)

Abstract Solutes that accumulate when the kidneys fail range in size from about 40 to 40,000 Da. Their dialytic clearance tends to decrease as their size increases. Disproportionate accumulation of large solutes has therefore long been considered a potential contributor to residual illness in dialysis patients. Early efforts focused on the removal of "middle molecules" with mass from 300 to 2000 Da. The identification of amyloidosis caused by ß 2 microglobulin (ß 2 M) with mass 12,000 Da shifted the focus to low molecular weight proteins. High-flux dialysis and hemodiafiltration increase the clearance of these larger solutes. However non-kidney clearance and solute compartmentalization limit the extent to which their plasma levels can be lowered by increasing their clearance during treatments of standard duration. Clinical benefits of high-volume hemodiafiltration thus cannot readily be accounted for by a reduction in the levels of known large solutes. The accumulation of peptides in the original middle molecular range and the clearance of larger solutes by peritoneal dialysis has been largely neglected. There is new interest in increasing the clearance of solutes even larger than ß 2 M by "extended dialysis." Ongoing clinical trials will extend our knowledge of the effects of extended dialysis and hemodiafiltration. In the future we might more effectively reduce plasma large solute levels by manipulating their non-kidney clearance, which is now poorly understood. ß 2 M is the only large solute whose accumulation in kidney failure has been shown to have specific ill effects. Identification of the ill effects of other large solutes might prompt the development of more targeted therapies.