tbuckley/cabot-search huggingface dataset:
Antihypertensive drugs and survival outcomes in oropharyngeal squamous cell carcinoma patients
Authors: Che-Min Lee, Brennan J Wadsworth, Ryan Urban, Meredith A Clark, Rocky Shi, Daegan Sit, Sarah N Hamilton, Kevin L Bennewith
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Radiation therapy is commonly used to treat head and neck cancer patients, and response may be improved by combining radiation with preexisting medications. Based on recent preclinical and retrospective patient data, we hypothesized that antihypertensive drugs may improve radiotherapy outcomes. Methods Retrospective analyses were conducted on 1077 oropharyngeal squamous cell carcinoma and 608 nasopharyngeal carcinoma patients, all of whom received radiation therapy. Univariate and multivariate analyses were conducted to assess overall survival, disease-specific survival, and locoregional control for cancer patients taking angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors, calcium channel blockers, or beta blockers compared with propensity score–matched groups of patients not taking these medications. Results Oropharyngeal squamous cell carcinoma patients taking antihypertensive medications were statistically older and had higher Charlson Comorbidity Indices at diagnosis. However, these patients had statistically significant improved overall survival, disease-specific survival, and locoregional control compared with propensity score–matched oropharyngeal squamous cell carcinoma patients who were not taking antihypertensive medications, with ARB users showing the greatest improvements. Antihypertensive drugs did not affect outcomes in the nasopharyngeal carcinoma patient cohort. Conclusion The use of antihypertensive medications, and particularly ARBs, was associated with improved outcomes in oropharyngeal squamous cell carcinoma patients who had more advanced age and higher Charlson Comorbidity Indices at diagnosis. This study supports future prospective testing of ARBs in conjunction with radiation therapy in this group of higher risk oropharyngeal squamous cell carcinoma patients. Additionally, this study illustrates the need to use propensity score matching to identify patient subgroups that may benefit from a given treatment in retrospective analyses.
The Safety and Efficacy of Endoscopic Intraperitoneal Subserosal Dissection for Gastric Submucosal Tumors with Extraluminal Growth Pattern
Authors: Li-Yun Ma, Keyi Guo, Xin-Yang Liu, Meng-Jiang He, Wei-Feng Chen, Sheng-Li Lin, Yaoyao Gong, Ping-Hong Zhou, Jian-Wei Hu
Journal: Endoscopy (2025)

ABSTRACT Background and Aims: Endoscopic intraperitoneal subserosal dissection (EISD) has been reported to be a promising modified tunnel technique for gastric submucosal tumors (SMTs) with predominantly extraluminal growth pattern. Here we aim to evaluate the safety and efficacy of EISD for gastric extraluminal SMTs. Methods: We prospectively enrolled consecutive patients who underwent EISD for gastric extraluminal SMTs between October 2018 and March 2024. Clinicopathologic characteristics and procedure-related parameters were analyzed. Results: Ten patients with 11 gastric extraluminal SMTs were included. The mean longest and shortest diameters of specimens were 2.1 ± 0.9 cm (range, 0.5-4.0) and 1.8 ± 0.7 cm (range, 0.4-3.0), respectively. All SMTs (100.0%) were en-bloc resected, and ten SMTs (90.9%) were en-bloc retrieved. The mean resection time and suture time was 71.3 ± 37.4 min (range, 30-150) and 12.4 ± 10.1 min (range, 3-25). Two patients experienced type I mucosal injury in tumor site, and no major adverse events occurred. The mean postoperative hospital stay was 3.4 ± 0.8 days (range, 3-5). No recurrence or metastasis occurred during a mean follow-up period of 32.1 ± 18.8 months (range, 7-71). Conclusions: EISD appears to be a feasible and safe method for removing gastric extraluminal SMTs in selected patients.
Gene-by-environment interactions modulate the infant gut microbiota in asthma and atopy
Authors: Sara A Stickley, Zhi Yi Fang, Amirthagowri Ambalavanan, Yang Zhang, Amanda M Zacharias, Charisse Petersen, Darlene Dai, Meghan B Azad, Jeffrey R Brook, Piushkumar J Mandhane, Elinor Simons, Theo J Moraes, Michael G Surette, Stuart E Turvey, Padmaja Subbarao, Qingling Duan
Journal: Journal of Allergy and Clinical Immunology (2025)
Correction to: D.J. Jackson, M.E. Wechsler, G. Brusselle, R. Buhl. Targeting the IL‐5 pathway in eosinophilic asthma: A comparison of anti‐IL‐5 versus anti‐IL‐5 receptor agents. <i>Allergy</i> 2024;1–10. https://doi.org/10.1111/all.16346
Journal: Allergy (2025)
ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders
Authors: Christopher M Sande, Stone Chen, Dana V Mitchell, Ping Lin, Diana M Abraham, Jessie M Cheng, Talia Gebhard, Rujul J Deolikar, Colby Freeman, Mary Zhou, Sushant Kumar, Michael Bowman, Robert L Bowman, Shannon Zheng, Bolormaa Munkhbileg, Qijun Chen, Natasha L Stanley, Kathy Guo, Ajibike Lapite, Ryan Hausler, Deanne M Taylor, James Corines, Jennifer Jd Morrissette, David B Lieberman, Guang Yang, Olga Shestova, Saar Gill, Jiayin Zheng, Kelcy Smith-Simmer, Lauren G Banaszak, Kyle N Shoger, Erica F Reinig, Madilynn Peterson, Peter Nicholas, Amanda J Walne, Inderjeet Dokal, Justin P Rosenheck, Karolyn A Oetjen, Daniel C Link, Andrew E Gelman, Christopher R Reilly, Ritika Dutta, R Coleman Lindsley, Karyn J Brundige, Suneet Agarwal, Alison A Bertuch, Jane E Churpek, Laneshia K Tague, F Brad Johnson, Timothy S Olson, Daria V Babushok
Journal: Journal of Clinical Investigation (2025)

Telomere biology disorders (TBD) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. 47.6% of patients (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% of patients, including 20 presumed loss-of-function variants in ATM. Using multimodal approaches, including single-cell sequencing, assays of ATM activation, telomere dysfunction-induced foci analysis, and cell growth assays, we demonstrate telomere dysfunction-induced activation of ATM-dependent DDR pathway with increased senescence and apoptosis in TBD patient cells. Pharmacologic ATM inhibition, modeling the effects of somatic ATM variants, selectively improved TBD cell fitness by allowing cells to bypass DDR-mediated senescence without detectably inducing chromosomal instability. Our results indicate that ATM-dependent DDR induced by telomere dysfunction is a key contributor to TBD pathogenesis and suggest dampening hyperactive ATM-dependent DDR as a potential therapeutic intervention.
Gut microbial metabolite 4-hydroxybenzeneacetic acid drives colorectal cancer progression via accumulation of immunosuppressive PMN-MDSCs
Authors: Qing Liao, Ximing Zhou, Ling Wu, Yuyi Yang, Xiaohui Zhu, Hangyu Liao, Yujie Zhang, Weidong Lian, Feifei Zhang, Hui Wang, Yanqing Ding, Liang Zhao
Journal: Journal of Clinical Investigation (2025)

Colorectal cancer (CRC) is characterized by an immune-suppressive microenvironment that contributes to tumor progression and immunotherapy resistance. The gut microbiome produces diverse metabolites that feature unique mechanisms of interaction with host targets, yet the role of many metabolites in CRC remains poorly understood. In this study, the microbial metabolite 4-hydroxybenzeneacetic acid (4-HPA) promoted the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment, consequently inhibiting the anti-tumor response of CD8+ T cells and promoting CRC progression in vivo. Mechanistically, 4-HPA activates the JAK2/STAT3 pathway, which upregulates CXCL3 transcription, thereby recruiting PMN-MDSCs to the CRC microenvironment. Selective knockdown of CXCL3 re-sensitized tumors to anti-PD1 immunotherapy in vivo. Chlorogenic acid (CGA) reduces the production of 4-HPA by microbiota, likewise abolishing 4-HPA-mediated immunosuppression. The 4-HPA content in CRC tissues was notably increased in patients with advanced CRC. Overall, the gut microbiome uses 4-HPA as a messenger to control chemokine-dependent accumulation of PMN-MDSC cells and regulate anti-tumor immunity in CRC. Our findings provide a scientific basis for establishing clinical intervention strategies to reverse the tumor immune microenvironment and improve the efficacy of immunotherapy by reducing the interaction between intestinal microbiota, tumor cells and tumor immune cells.
SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction
Authors: Ying Feng, Ningxin Zhu, Karan Bedi, Jinju Li, Chamila Perera, Maranne Green, Naziheh Assarzadegan, Yali Zhai, Qingzhi Liu, Veerabhadran Baladandayuthapani, Jason R Spence, Kathleen R Cho, Eric R Fearon
Journal: Journal of Clinical Investigation (2025)

The Wnt/β-catenin pathway regulates expression of the SOX9 gene, which encodes SRY-box transcription factor 9, a differentiation factor and potential β-catenin regulator. Because APC tumor suppressor defects in ~80% of colorectal cancers (CRCs) activate the Wnt/β-catenin pathway, we studied SOX9 inactivation in CRC biology. Compared to effects of Apc inactivation in mouse colon tumors, combined Apc and Sox9 inactivation instigated more invasive tumors with epithelial-mesenchymal transition (EMT) and SOX2 stem cell factor upregulation. In an independent mouse CRC model with combined Apc, Kras, and Trp53 defects, Sox9 inactivation promoted SOX2 induction and distant metastases. About 20% of 171 human CRCs showed loss of SOX9 protein expression, which correlated with higher tumor grade. In an independent group of 376 CRC patients, low SOX9 gene expression was linked to poor survival, earlier age at diagnosis, and increased lymph node involvement. SOX9 expression reductions in human CRC were linked to promoter methylation. EMT pathway gene expression changes were prominent in human CRCs with low SOX9 expression and in a mouse cancer model with high SOX2 expression. Our results indicate SOX9 has tumor suppressor function in CRC; its loss may promote progression, invasion, and poor prognosis by enhancing EMT and stem cell phenotypes.
Non-canonical small noncoding RNAs in the plasma extracellular vesicles as novel biomarkers in gastric cancer
Authors: Ping Yang, Zhibo Li, Xi Chen, Chiyuan Ma, Yiyuan Han, Xiaoshan Zhang, Xiaodong Wei, Yueyue Lei, Tonghui Ma, Fangfang Jin
Journal: Journal of Hematology & Oncology (2025)

Identifying robust diagnostic biomarkers for gastric cancer (GC) remains a significant challenge. Emerging studies highlight extracellular vesicle (EV)-derived RNAs in cancer biology, but the diagnostic potential of circulating EV-derived small non-coding RNAs (sncRNAs) in GC is poorly understood. Using panoramic RNA display by overcoming RNA modification aborted sequencing (PANDORA-seq), we mapped non-canonical sncRNAs-specifically ribosomal RNA-derived small RNAs (rsRNAs) and transfer RNA-derived small RNAs (tsRNAs)-in plasma EVs. We identified a three-rs/tsRNA signature that discriminates GC patients from healthy individuals with high sensitivity (80.42%) and specificity (87.43%) (143 GC vs 167 controls). For early-stage GC (stage I), sensitivity and specificity were 81.97% and 81.44%, respectively. Furthermore, the three-rs/tsRNA signature was evaluated in two independent cohorts, resulting in AUC values of 0.97 and 0.91 for distinguishing GC from healthy controls. Functional analyses revealed that these rs/tsRNAs regulate the ErbB/Hippo pathways, suggesting them in the underlying pathogenesis and therapeutic potential. This study establishes a novel EV-derived sncRNA signature for early GC detection.
Large-Scale Proteomics Improve Risk Prediction for Type 2 Diabetes
Authors: Ruijie Xie, Tomislav Vlaski, Kira Trares, Christian Herder, Bernd Holleczek, Hermann Brenner, Ben Schöttker
Journal: Diabetes Care (2025)

OBJECTIVE This study evaluated the incremental predictive value of proteomic biomarkers in assessing 10-year type 2 diabetes risk when added to the clinical Cambridge Diabetes Risk Score (CDRS). RESEARCH DESIGN AND METHODS Data from 21,898 UK Biobank participants were used for model derivation and internal validation, and 4,454 Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung (ESTHER) cohort (Germany) participants were used for external validation. Proteomic profiling included the Olink Explore (2,085 proteins) and Olink Target 96 Inflammation panel (73 proteins). RESULTS Adding 15 proteins from Olink Explore or 6 proteins from the Olink Inflammation panel improved the C-index of the CDRS by 0.029 or 0.016 in internal validation with net reclassification of 23.0% and 29.0%, respectively. External validation was only conducted for the six-protein-extended model, and the C-index improved by 0.014. CONCLUSIONS The Olink Explore–based 15-protein model enhanced the CDRS model performance most, and this promising prediction model should be externally validated. Our successful external validation of the Olink Inflammation panel–based six-protein model shows that this is a promising endeavor.
Prospective Randomised Phase-II Trial of Ipilimumab/Nivolumab versus Standard of Care in non-clear cell Renal Cell Cancer - Results of the SUNNIFORECAST Trial
Authors: L Bergmann, L Albiges, M Ahrens, M Gross-Goupil, E Boleti, G Gravis, A Fléchon, M-O Grimm, J Bedke, P Barthélémy, D Castellano, B Mellado, P Ivanyi, S Rottey, A Flörcken, C Suarez, P Maroto, V Grünwald, S F Oosting, J Kopecky, S Zschäbitz, M Boegemann, T Buchler, G Niegisch, P J Goebell, T Waddell, F Joly, F Priou, M Retz, S Siemer, U Zimmermann, D Deckbar, I Burkholder, A Hartmann, J B Haanen
Journal: Annals of Oncology (2025)
Management of <i>EGFR</i>-Variant and <i>ALK</i>-Positive Non–Small Cell Lung Cancer Brain Metastasis
Authors: Luke R. G. Pike, Helena Yu, Chad G. Rusthoven
Journal: JAMA Oncology (2025)

This clinical evidence synopsis summarizes the results of 3 multi-institutional cohort studies that compare tyrosine kinase inhibitors with or without stereotactic radiosurgery in patients with non–small cell lung cancer with brain metastases.
Changes in Oncology Medication Use After Withdrawal of Accelerated Approval
Authors: Catherine S. Hwang, Aaron S. Kesselheim, Amar H. Kelkar, Edward R. Scheffer Cliff, Benjamin N. Rome
Journal: JAMA Oncology (2025)

This cohort study assesses changes in cancer drug use after negative confirmatory trials and removal of accelerated approval indications from US Food and Drug Administration–approved labeling.
Advances in imaging – Elastography
Authors: Elton Dajti, Adrian T. Huber, Giovanna Ferraioli, Annalisa Berzigotti
Journal: Hepatology (2025)

Chronic liver disease (CLD) affects over a billion people worldwide. Liver fibrosis is the key driver of liver-related complications and mortality. Elastography has been a transformative tool in hepatology allowing diagnosing and staging liver fibrosis non-invasively, and is evolving beyond these purposes into a prognostication tool. By measuring tissue stiffness, elastography techniques such as shear-wave and magnetic resonance elastography (MRE) offer critical insights into liver fibrosis, portal hypertension, and the progression of disease. MRE stands out for its reliability across fibrosis stages and robustness in obese patients affected by metabolic liver disease. Spleen stiffness measurement (SSM) complements liver assessments, enhancing the identification of portal hypertension and refining patient risk stratification. This review covers current clinical applications but also anticipates future innovations such as artificial intelligence based algorithms that could expand elastography’s clinical impact so improving patient outcomes.
Erratum: Reciprocal regulation of microRNA-122 and c-Myc in hepatocellular cancer: Role of E2F1 and transcription factor dimerization partner 2
Authors: Bo Wang, Shu-hao Hsu, Xinmei Wang, Huban Kutay, Hemant Kumar Bid, Jianhua Yu, Ramesh K. Ganju, Samson T. Jacob, Mariia Yuneva, Kalpana Ghoshal
Journal: Hepatology (2025)
Deporting Immigrants May Further Shrink the Health Care Workforce
Authors: Lenore S. Azaroff, Steffie Woolhandler, Sharon Touw, David Bor, David U. Himmelstein
Journal: JAMA (2025)

This study explores the potential for health care staffing shortages in the US by estimating the number of immigrants employed in health care who could be affected by deportation or immigration restrictions.
Cell therapies and liver organogenesis technologies: Promising strategies for end-stage liver disease
Authors: Shaoyang Qin, Xiaochen Bo, Hongyuan Liu, Zhishuo Zhang, Zhicong Zhao, Qiang Xia
Journal: Hepatology (2025)

End-stage liver disease (ESLD) represents a critical hepatic condition with high mortality, for which liver transplantation remains the only effective treatment. However, the scarcity of suitable donors results in numerous patients dying while awaiting transplantation. Novel strategies, including cell therapies and technologies mimicking liver organogenesis, offer promising alternatives for treating ESLD by potentially providing new sources of liver grafts. Recently, significant progress has been made in this field, including stem cell transplantation, hepatocyte transplantation, in vitro liver tissue generation, and liver replacement technologies. Several clinical studies have demonstrated that stem cell transplantation and hepatocyte transplantation can prolong patient survival and serve as a bridge to liver transplantation. Furthermore, in vitro liver tissue generation technologies, such as liver organoids and three-dimensional bioprinting, can generate hepatic tissues with sophisticated structures and functions, making them promising transplantation materials. Notably, liver replacement technologies hold considerable potential for producing biologically functional and transplantable liver grafts. In this review, we discuss the fundamental principles and recent advancements in cell therapies and liver organogenesis technologies while also addressing the challenges and future prospects in this rapidly evolving field.
Renin-angiotensin-aldosterone system inhibitor use improves clinical outcomes in patients with metabolic dysfunction-associated steatotic liver diseases: Target trial emulation using real-world data
Authors: Wee Han Ng, Yee Hui Yeo, Hyunseok Kim, Ekihiro Seki, Jonathan Rees, Kevin Sheng-Kai Ma, Cynthia A. Moylan, Luz María Rodriquez, Manal Abdelmalek, Augusto Villanueva, Mazen Noureddin, Ju Dong Yang
Journal: Hepatology (2025)

Background/Aim: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) prevent fibrosis progression in a preclinical model of steatotic liver disease. Our objective was to assess the impact of ACEi/ARB use on clinical outcomes in patients with metabolic dysfunction-associated steatotic liver diseases (MASLD). Approaches and Results: Using TriNetX, a nationwide database, we identified all patients with MASLD from 01/01/2011 to 12/31/2019. Using a target trial emulation framework, ACEi/ARB users were matched with calcium channel blocker (CCB) users using propensity score matching (PSM). Patients were followed up to 10 years after the index date. Cox regression was used to determine the risk of mortality, major adverse liver outcomes (MALO), major adverse cardiac events (MACE), and incident cancers. Of the 35988 eligible patients, 28423 were ACEi/ARB users and 7565 were CCB users. After PSM, 7238 pairs were well-balanced. ACEi/ARB use was associated with a significantly decreased mortality risk (Hazard Ratio (HR) 0.59, 95% confidence interval [CI]: 0.51–0.68). ACEi/ARB was associated with a significantly reduced risk of developing MALO (HR 0.70, 95% CI: 0.61–0.80), including ascites (HR 0.78, 95% CI: 0.63–0.98) and hepatic encephalopathy (HR 0.67, 95% CI: 0.57–0.78). ACEi/ARB use was also associated with a lower risk of MACE (HR 0.82, 95% CI: 0.76–0.90) but not incident cancer (HR 0.97, 95% CI: 0.86-1.10) compared to CCB. Conclusions: ACEi/ARB use in patients with MASLD was associated with a reduced risk of mortality, MALO, and MACE compared to CCB use. A large prospective study is needed for external validation.
Broth microdilution susceptibility testing reveals underestimation of resistance to penicillin and high levels of resistance to ampicillin of Streptococcus pneumoniae clinical isolates in Sweden.
Authors: Alexandros Petropoulos, Eva Morfeldt, Kerstin Nyrén, Karin Blomqvist, Birgitta Henriques-Normark
Journal: Clinical Microbiology and Infection (2025)
<i>Notes from the Field</i>: Response to a Case of Travel-Associated Lassa Fever — Iowa, October–November 2024
Authors: Diana L. Von Stein, Alexandra Barger, Andrew Hennenfent, Robert Ramaekers, Amanda Mandi, Kenzie Teno, Karen Brust, Jonathan Simmons, Nicholas Mohr, Lisa Veach, Sudhir Kumar, Aneesa Afroze, Emily McCutchen, Amanda Bartling, Michael Pentella, Megan Nelson, Jennifer Craft, Rikki Hetzler, Amy Thoreson, Alicia Coppedge, Sam Jarvis, Jennifer Miller, Alison M. Todres, Jessica L. Wickline, Sheena Tarrant, Leanna Sayyad, Inna Krapiunaya, Amy Schuh, Amy Whitesell, Gerard C. Kuotu, Kiara McNamara, Nancy Cornish, Shelly Schwedhelm, Angela Vasa, Angela Hewlett, Shantyl Galloway, Aaron D. Kofman, Katrin S. Sadigh, Robert Kruse, Barbara Knust, Matthew Donahue
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Human Metapneumovirus Seasonality and Co-Circulation with Respiratory Syncytial Virus — United States, 2014<b>–</b>2024
Authors: Ndey Bassin Jobe, Erica Rose, Amber K. Winn, Leah Goldstein, Zachary D. Schneider, Benjamin J. Silk
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Human metapneumovirus (hMPV) infections cause acute respiratory illness and lower respiratory tract disease. Respiratory syncytial virus (RSV) is a closely related virus within the Pneumoviridae family, and hMPV and RSV infections are associated with similar clinical manifestations. Although no specific antiviral therapies or vaccines exist for hMPV, vaccines and monoclonal antibody products are available to protect against severe RSV disease. This report summarizes hMPV circulation relative to the timing of RSV epidemics before, during, and after the COVID-19 pandemic. Polymerase chain reaction testing results reported to the National Respiratory and Enteric Virus Surveillance System during July 2014-June 2024, were analyzed. Before the COVID-19 pandemic, the median hMPV season onset, peak, and offset occurred in early January, late March, and early June, respectively (median duration = 21 weeks). The 2021-22 season was atypically long (35 weeks); seasonality reverted to more typical patterns during the 2022-23 and 2023-24 seasons. In the two COVID-19 pandemic seasons (2021-22 and 2022-23) and one postpandemic season (2023-24), RSV offsets occurred earlier in January (2021-22 and 2022-23) or March (2023-24) than before the pandemic, when the median offsets occurred in April. The annual interval from peak RSV to peak hMPV circulation increased from a prepandemic median of 11.5 weeks (range = 2-17 weeks) to 19 weeks (range = 19-20 weeks) during and after the pandemic. Fewer than 5 weeks of cocirculation of RSV and hMPV occurred in most regions during the 2022-23 and 2023-24 seasons. Real-time surveillance of RSV and hMPV co-circulation patterns can help guide clinician-directed testing and supportive care, optimize the use of prevention products, prompt detection of and response to outbreaks, and help ensure health care system preparedness for seasonal increases in illnesses.