tbuckley/cabot-search huggingface dataset:
Targeting the histone reader ZMYND8 inhibits antiandrogen-induced neuroendocrine tumor transdifferentiation of prostate cancer
Authors: Hanling Wang, Sulin Zhang, Qiang Pan, Jiacheng Guo, Ni Li, Lifan Chen, Junyu Xu, Jingyi Zhou, Yongqiang Gu, Xuege Wang, Guoying Zhang, Yannan Lian, Wei Zhang, Naiheng Lin, Zige Jin, Yi Zang, Weihua Lan, Xiaoyan Cheng, Minjia Tan, Fei Xavier Chen, Jun Jiang, Qiuli Liu, Mingyue Zheng, Jun Qin
Journal: Nature Cancer (2025)
Retraction Note: Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer
Authors: Ting Li, Hanqing Guo, Ying Song, Xiaodi Zhao, Yongquan Shi, Yuanyuan Lu, Sijun Hu, Yongzhan Nie, Daiming Fan, Kaichun Wu
Journal: Molecular Cancer (2025)
Nivolumab adjuvant to chemo-radiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT)
Authors: Gliceida M Galarza Fortuna, Daniel Grass, Benjamin L Maughan, Rohit K Jain, Christopher Dechet, Julia Beck, Ekke Schuetz, Alejandro Sanchez, Brock O'Neil, Michael Poch, Roger Li, Shane Lloyd, Jonathan Tward, Tenzin Phunrab, Josiah Lyn Hawks, Umang Swami, Kenneth M Boucher, Neeraj Agarwal, Sumati Gupta
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Muscle-invasive urothelial cancer (UC) has a high risk of recurrence after definitive treatment. Nivolumab adjuvant to radical surgery improves disease-free survival in patients with UC with a high risk of recurrence; however, its role adjuvant to chemoradiation therapy (CRT) is unknown. Methods The NEXT trial is a single-arm, phase-2 study evaluating the efficacy and tolerability of nivolumab adjuvant to CRT in patients with localized or locoregional UC. The primary endpoint is failure-free survival (FFS) at 2 years. Secondary endpoints include patterns of recurrence, toxicity and quality of life (QoL). Plasma cell-free DNA (cfDNA) was subjected to shallow whole-genome sequencing to correlate with outcomes. Results 28 patients were enrolled and received 480 mg of nivolumab intravenously every 4 weeks for up to 12 cycles adjuvant to CRT. The FFS at 2 years was 33.2% (95% CI 18.5% to 59.6%). Nine (32%) patients had localized progression, and eight (29%) had distant progression. 25 (89%) had one or more high-risk features (ie, plasmacytoid differentiation, T4, N+, multiple tumors, tumors &gt;5 cm, residual disease before CRT, carcinoma in situ, and hydronephrosis). Patients with ≤2 high-risk features had a median FFS of 45.2 months (95% CI 14.56 to not reached (NR)) compared with 8.2 months (95% CI 7.1 to NR) in those with three or more risk features (p=0.0024). Nivolumab-associated treatment-related adverse events occurred in 18 (64.3%) patients, only 3 had grade 3 TRAEs, with significant changes in QoL. Plasma cfDNA copy number instability (CNI) scores ≤25 before the first dose of adjuvant nivolumab and at cycle 4 were associated with better overall survival compared with CNI scores ≥26 (49.6 months vs 20.5 months, p=0.0024). Genome copy number changes indicated chromatin remodeling and tyrosine kinase pathways, among others, as oncogenic drivers implicated in progression. Conclusion Nivolumab adjuvant to CRT in localized or locally advanced UC is well tolerated. Stratification by risk factors and correlation with plasma cfDNA analyses generate hypotheses for potential patient selection and putative therapeutic targets for future study. Trial registration number NCT03171025 .
Comprehensive immunophenotyping of gastric adenocarcinoma identifies an inflamed class of tumors amenable to immunotherapies
Authors: Joel Veas Rodriguez, Miquel Piñol, Maria Alba Sorolla, Eva Parisi, Anabel Sorolla, Maria Santacana, Maria Ruiz, Genís Parra, Mario Bernabeu, Mar Iglesias, Carles Aracil, Alfredo Escartin, Felip Vilardell, Xavier Matias-Guiu, Antonieta Salud, Robert Montal
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Gastric adenocarcinoma (GAC) imposes a considerable global health burden. Molecular profiling of GAC from the tumor microenvironment perspective through a multi-omics approach is eagerly awaited in order to allow a more precise application of novel therapies in the near future. Methods To better understand the tumor-immune interface of GAC, we identified an internal cohort of 82 patients that allowed an integrative molecular analysis including mutational profiling by whole-exome sequencing, RNA gene expression of 770 genes associated with immune response, and multiplex protein expression at spatial resolution of 34 immuno-oncology targets at different compartments (tumorous cells and immune cells). Molecular findings were validated in 595 GAC from the TCGA and ACRG external cohorts with available multiomics data. Prediction of response to immunotherapies of the discovered immunophenotypes was assessed in 1039 patients with cancer from external cohorts with available transcriptome data. Results Unsupervised clustering by gene expression identified a subgroup of GAC that includes 52% of the tumors, the so-called Inflamed class, characterized by high tumor immunogenicity and cytotoxicity, particularly in the tumor center at protein level, with enrichment of PIK3CA and ARID1A mutations and increased presence of exhausted CD8+ T cells as well as co-inhibitory receptors such as PD1 , CTLA4 , LAG3, and TIGIT . The remaining 48% of tumors were called non-inflamed based on the observed exclusion of T cell infiltration, with an overexpression of VEGFA and higher presence of TP53 mutations, resulting in a worse clinical outcome. A 10-gene RNA signature was developed for the identification of tumors belonging to these classes, demonstrating in evaluated datasets comparable clinical utility in predicting response to current immunotherapies when tested against other published gene signatures. Conclusions Comprehensive immunophenotyping of GAC identifies an inflamed class of tumors that complements previously proposed tumor-based molecular clusters. Such findings may provide the rationale for exploring novel immunotherapeutic approaches for biomarker-enriched populations in order to improve GAC patient’s survival.
Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer
Authors: Julio C Tinoco, Harmony I Saunders, Lauryn Rose Werner, Xiaopeng Sun, Eilidh I Chowanec, Amanda Heard, Prabhakar Chalise, Jeffery M Vahrenkamp, Andrea E Wilson, Cong-Xiao Liu, Gangjun Lei, Junping Wei, Hugo Cros, Hisham Mohammed, Melissa Troester, Charles Perou, Mary A Markiewicz, Jason Gertz, Justin M Balko, Zachary Conrad Hartman, Christy R Hagan
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Breast cancer (BC) continues to be a major health concern with 250,000 new cases diagnosed annually in the USA, 75% of which are hormone receptor positive (HR+), expressing estrogen receptor alpha (ER) and/or the progesterone receptor (PR). Although ER-targeted therapies are available, 30% of patients will develop resistance, underscoring the need for new non-ER/estrogen-based treatments. Notably, HR+BCs exhibit poor lymphocyte infiltration and contain an immunosuppressive microenvironment, which contributes to the limited efficacy of immunotherapies in HR+BC. In this study, we demonstrate that PR/progesterone signaling reduces major histocompatibility complex (MHC) Class I expression, facilitating immune evasion and escape from immune-based clearance of PR+tumors. Methods To determine the effect of PR/progesterone on MHC Class I expression, we treated human and mouse mammary tumor cell lines with progesterone and/or interferon (IFN) and measured expression of genes involved in antigen processing and presentation (APP), as well as surface MHC Class I expression. We used the OT-I/SIINFEKL model antigen system to measure the impact of progesterone on immune cell-mediated killing of modified tumor cells. We also analyzed two large BC clinical cohorts to determine how PR expression correlates with APP gene expression and MHC Class I expression in ER-positive tumors. Results In vitro, we show that PR/progesterone signaling reduces APP gene expression and MHC class I expression in human and breast mammary tumor cell lines. PR-mediated attenuation of APP/MHC Class I expression is more pronounced in the presence of IFN. In immune cell killing assays, PR-expressing mammary tumor cells treated with progesterone are protected from immune-mediated cytotoxicity. We demonstrate that PR expression in vivo prevents immune-mediated rejection of xenoantigen-modified mammary tumor cell lines through mechanisms involving MHC Class I expression and CD8 T cells. Data analysis of two large BC cohorts reveals lower APP gene expression and MHC Class I expression in ER/PR-positive tumors compared with ER-positive/PR-negative tumors. These findings show that HR+BCs, specifically PR+tumors, downregulate APP/MHC class I machinery through PR/progesterone signaling. Use of pharmacological PR/progesterone inhibitors may reverse these effects in patients with BC, thereby improving immunosurveillance and response to immunotherapies.
Lactate accumulation induces H4K12la to activate super-enhancer-driven RAD23A expression and promote niraparib resistance in ovarian cancer
Authors: Bingfeng Lu, Shuo Chen, Xue Guan, Xi Chen, Yuping Du, Jing Yuan, Jielin Wang, Qinghua Wu, Lingfeng Zhou, Xiangchun Huang, Yang Zhao
Journal: Molecular Cancer (2025)

Ovarian cancer is a gynecological malignancy with the highest recurrence and mortality rates. Although niraparib can effectively affect its progression, the challenge of drug resistance remains. Herein, niraparib-resistant ovarian cancer cell lines were constructed to identify the abnormally activated enhancers and associated target genes via RNA in situ conformation sequencing. Notably, the target gene RAD23A was markedly upregulated in niraparib-resistant cells, and inhibiting RAD23A restored their sensitivity. Additionally, abnormal activation of glycolysis in niraparib-resistant cells induced lactate accumulation, which promoted the lactylation of histone H4K12 lysine residues. Correlation analysis showed that key glycolysis enzymes such as pyruvate kinase M and lactate dehydrogenase A were significantly positively correlated with RAD23A expression in ovarian cancer. Additionally, H4K12la activated the super-enhancer (SE) of niraparib and RAD23A expression via MYC transcription factor, thereby enhancing the DNA damage repair ability and promoting the drug resistance of ovarian cancer cells. Overall, the findings of this study indicate that lactic acid accumulation leads to lactylation of histone H4K12la, thereby upregulating SE-mediated abnormal RAD23A expression and promoting niraparib resistance in ovarian cancer cells, suggesting RAD23A as a potential therapeutic target for niraparib-resistant ovarian cancer.
Sleep and Male (In)Fertility: A Comprehensive Overview
Authors: Catarina Cavalhas-Almeida, Maria Inês Cristo, Cláudia Cavadas, João Ramalho-Santos, Ana Rita Álvaro, Sandra Amaral
Journal: Sleep Medicine Reviews (2025)

Infertility affects millions of couples globally, with male factors contributing up to 50 % of cases. Despite the existing Assisted Reproduction Technologies (ART), decreased sperm quality and male infertility persist. Evidence suggests that sleep is crucial for normal reproductive function, and the noticeable increase in infertility rates aligns with the growing prevalence of sleep deprivation, suggesting a connection between both conditions. This literature review explores the possible links between sleep disturbances, with a special emphasis on insomnia, the most prevalent sleep disorder, and male reproductive health. It delves into the latest findings regarding factors such as sperm quality, hormone levels, and overall reproductive function from studies in mammals, both rodents and humans. Through a concise synthesis of these findings, we unveil potential mechanisms and provide crucial insights for clinicians and researchers in the field of reproductive health.
Immunomodulatory Bioadhesive Technologies
Authors: Xiaoyi Lan, Evan Johnston, Tianqin Ning, Guojun Chen, Lisbet Haglund, Jianyu Li
Journal: Biomaterials (2025)

Bioadhesives have found significant use in medicine and engineering, particularly for wound care, tissue engineering, and surgical applications. Compared to traditional wound closure methods such as sutures and staples, bioadhesives offer advantages, including reduced tissue damage, enhanced healing, and ease of implementation. Recent progress highlights the synergy of bioadhesives and immunoengineering strategies, leading to immunomodulatory bioadhesives capable of modulating immune responses at local sites where bioadhesives are applied. They foster favorable therapeutic outcomes such as reduced inflammation in wounds and implants or enhanced local immune responses to improve cancer therapy efficacy. The dual functionalities of bioadhesion and immunomodulation benefit wound management, tissue regeneration, implantable medical devices, and post-surgical cancer management. This review delves into the interplay between bioadhesion and immunomodulation, highlighting the mechanobiological coupling involved. Key areas of focus include the modulation of immune responses through chemical and physical strategies, as well as the application of these bioadhesives in wound healing and cancer treatment. Discussed are remaining challenges such as achieving long-term stability and effectiveness, necessitating further research to fully harness the clinical potential of immunomodulatory bioadhesives.
Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery
Authors: Martin Kaňa, Alena Braunová, Daniil Starenko, Markéta Frejková, Jan Bouček, Blanka Říhová, Marek Kovář, Tomáš Etrych, Milada Šírová
Journal: Journal of Controlled Release (2025)
Cold snare polypectomy versus hot endoscopic mucosal resection for large non-pedunculated colorectal polyps: a systematic review and meta-analysis of randomized controlled trials
Authors: Andrea Sorge, Michele Montori, Maria Eva Argenziano, Pieter Jan Poortmans, Daniele Balducci, Gian Eugenio Tontini, Sander Smeets, Tamas Tornai, Massimo Del Fabbro, Sandro Sferrazza, Lobke Desomer, Gabriele Gallo Afflitto, David James Tate
Journal: Endoscopy (2025)

Background: This meta-analysis of randomized controlled trials (RCTs) aimed to compare the risk of recurrence and adverse events between cold snare polypectomy (CSP) and hot-endoscopic mucosal resection (H-EMR) for large non-pedunculated colorectal polyps (LNPCPs). Methods: A systematic search of Medline, Embase and Cochrane Library databases was performed through August 2024 for studies comparing recurrence, bleeding and perforation rates between CSP and H-EMR for LNPCPs ≥15mm (PROSPERO ID: CRD42024568272). RCTs were included in the quantitative analysis. A random-effects meta-analysis, with heterogeneity measured with I2, was conducted to generate pooled risk ratios (RR) with 95% confidence intervals. Results: Four RCTs comprising 1516 LNPCPs (766 CSP and 750 H-EMR) in 1442 patients were included in the quantitative analysis. CSP demonstrated a higher recurrence risk at first surveillance colonoscopy than H-EMR in the pooled analysis (22.6% vs. 10.8%; RR=1.98; 95% CI: 1.22–3.21; p=0.02; moderate-certainty evidence), corresponding to a number needed to harm of 9. Regarding adverse events, CSP demonstrated a 67% reduced risk of delayed bleeding (1.2% vs. 3.9%; RR=0.33; 95% CI: 0.12-0.89; p=0.03; high-certainty evidence), corresponding to a number needed to treat of 37. Although CSP appeared to reduce the risk of intraprocedural bleeding (10.0% vs. 19.8%; RR=0.30, 95% CI: 0-52256.34, p=0.42), the wide confidence interval from the random-effects model included 1. There were no intraprocedural or delayed perforations in the CSP group. Conclusion: CSP has nearly double the recurrence risk of H-EMR for LNPCPs. However, its superior safety profile may make it a preferable option for patients where procedural safety is prioritized over radicality, such as those with extensive comorbidities.
Prolonged increase in glutamate whole body and intracellular production in older adults with COPD and healthy controls post-resistance exercise
Authors: Robert H Mbilinyi, Nicolaas E P Deutz, Clayton L Cruthirds, Laura E Ruebush, Tarun Sontam, Gabriella A M Ten Have, John J Thaden, Mariëlle P K J Engelen
Journal: Metabolism (2025)
Positive airway pressure therapy and all‐cause and cardiovascular mortality in people with obstructive sleep apnoea: a systematic review and meta-analysis of randomised controlled trials and confounder-adjusted, non-randomised controlled studies
Authors: Adam V Benjafield, Jean-Louis Pepin, Peter A Cistulli, Alison Wimms, Florent Lavergne, Fatima H Sert Kuniyoshi, Sibyl H Munson, Brendan Schuler, Shrikar Reddy Badikol, Kelly C Wolfe, Leslee Willes, Colleen Kelly, Tetyana Kendzerska, Dayna A Johnson, Raphael Heinzer, Chi-Hang Lee, Atul Malhotra
Journal: The Lancet Respiratory Medicine (2025)
Safety and effectiveness of MVA-BN vaccination against mpox in at-risk individuals in Germany (SEMVAc and TEMVAc): a combined prospective and retrospective cohort study
Authors: David Hillus, Ngoc Han Le, Pinkus Tober-Lau, Anne-Katrin Fietz, Christian Hoffmann, Regina Stegherr, Leu Huang, Axel Baumgarten, Florian Voit, Markus Bickel, Gal Goldstein, Christoph Wyen, Hartmut Stocker, Thomas Wünsche, Marcel Lee, Hubert Schulbin, Mathias Vallée, Ulrich Bohr, Anja Potthoff, Christiane Cordes, Caroline Isner, Bethany Knox, Antonio Carmona, Nicole Stobäus, Ran Balicer, Florian Kurth, Leif Erik Sander
Journal: The Lancet Infectious Diseases (2025)
Cell Type–Specific Studies of Human Tissue for Investigation of the Molecular Cell Biology of Late-Onset Neurodegenerative Disease
Authors: Kert Mätlik, Christina Pressl, Nathaniel Heintz
Journal: Annual Review of Neuroscience (2025)

Decades of research into human neurodegenerative diseases have revealed important similarities as well as dissimilarities between diseases. While investigations of specific mechanistic aspects of diseases have been aided by cell and animal models, true advances in the understanding of neurodegeneration require that we deal with the daunting complexities of the human brain. In this review, we discuss novel molecular profiling methods that have been applied to human postmortem brain tissue during the last decade and highlight insights into cell type–specific molecular characteristics and disease-associated changes in both vulnerable and resilient cell types in Huntington's disease, Parkinson's disease, and Alzheimer's disease. We also illustrate how these approaches can complement human genetic analyses and studies of animal models to advance our understanding of human neurodegeneration.
The role of multicriteria decision analysis in the development of candidate classification criteria for antisynthetase syndrome: analysis from the CLASS project
Authors: Giovanni Zanframundo, Eduardo Dourado, Iazsmin Bauer-Ventura, Sara Faghihi-Kashani, Akira Yoshida, Aravinthan Loganathan, Daphne Rivero-Gallegos, Darosa Lim, Francisca Bozán, Gianluca Sambataro, Sangmee Sharon Bae, Yasuhiko Yamano, Francesco Bonella, Tamera J Corte, Tracy Jennifer Doyle, David Fiorentino, Miguel Angel Gonzalez-Gay, Marie Hudson, Masataka Kuwana, Ingrid E Lundberg, Andrew Mammen, Neil McHugh, Frederick W Miller, Carlomaurizio Montecucco, Chester V Oddis, Jorge Rojas-Serrano, Jens Schmidt, Albert Selva-O'Callaghan, Victoria P Werth, Paul Hansen, Davide Rozza, Carlo A Scirè, Garifallia Sakellariou, Yuko Kaneko, Konstantinos Triantafyllias, Santos Castañeda, Maria Laura Alberti, Martín Gerardo Greco Merino, Christopher Fiehn, Yair Molad, Marcello Govoni, Ran Nakashima, Erkan Alpsoy, Margherita Giannini, Hector Chinoy, Laure Gallay, Esther Ebstein, Julien Campagne, André Pinto Saraiva, Edoardo Conticini, Gian Domenico Sebastiani, Laura Nuño-Nuño, Salvatore Scarpato, Elena Schiopu, Matthew Parker, Massimiliano Limonta, Lorenzo Cavagna, Rohit Aggarwal
Journal: Annals of the Rheumatic Diseases (2025)

To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD). A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD. Experts' answers were analysed using the Potentially All Pairwise RanKings of all possible Alternatives method to determine the weights of the key variables to formulate the MCDA-based classification criteria. Clinical vignettes scored by the experts as consensus cases or controls and real-world data collected in participating centres were used to test the performance of candidate classification criteria using receiver operating characteristic curves and diagnostic accuracy metrics. Positivity for antisynthetase antibodies had the highest weight for ASSD classification. The highest-ranked clinical manifestation was ILD, followed by myositis, mechanic's hands, joint involvement, inflammatory rashes, Raynaud phenomenon, fever, and pulmonary hypertension. The candidate classification criteria achieved high areas under the curve when applied to the consensus cases and controls and real-world patient data. Sensitivities, specificities, and positive and negative predictive values were >80%. The MCDA-driven candidate classification criteria were consistent with published ASSD literature and yielded high accuracy and validity.
Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance
Authors: Tongxuan Shang, Ziqi Jia, Jiayi Li, Heng Cao, Hengyi Xu, Lin Cong, Dongxu Ma, Xiang Wang, Jiaqi Liu
Journal: Journal of Hematology & Oncology (2025)

In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature of solid tumors and is strongly associated with poor prognosis in cancer patients. Another significant portion of the development of acquired drug resistance is attributed to tumor stemness. Cancer stem cells (CSCs), a small tumor cell subset with self-renewal and proliferative abilities, are crucial for tumor initiation, metastasis, and intra-tumoral heterogeneity. Studies have shown a significant association between hypoxia and CSCs in the context of tumor resistance. Recent studies reveal a strong link between hypoxia and tumor stemness, which together promote tumor survival and progression during treatment. This review elucidates the interplay between hypoxia and CSCs, as well as their correlation with resistance to therapeutic drugs. Targeting pivotal genes associated with hypoxia and stemness holds promise for the development of novel therapeutics to combat tumor resistance.