tbuckley/cabot-search huggingface dataset:
Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study
Authors: Shou-Wu Lee, Sheng-Shun Yang, Pei-Chien Tsai, Chung-Feng Huang, Chi-Yi Chen, Chao-Hung Hung, Chien-Hung Chen, Chi-Ming Tai, Pin-Nan Cheng, Hsing-Tao Kuo, Kuo-Chih Tseng, Lein-Ray Mo, Ching-Chu Lo, Yi-Hsiang Huang, Han-Chieh Lin, Pei-Lun Lee, Ming-Jong Bair, Te-Sheng Chang, Chun-Yen Lin, Szu-Jen Wang, Tsai-Yuan Hsieh, Tzeng-Hue Yang, Cheng-Yuan Peng, Chi-Chieh Yang, Lee-Won Chong, Chien-Wei Huang, Chih-Wen Lin, Cheng-Hsin Chu, Ming-Chang Tsai, Jia-Horng Kao, Chun-Jen Liu, Wan-Long Chuang, Teng-Yu Lee, Ming-Lung Yu
Journal: Clinical and Molecular Hepatology (2025)

The survival benefit of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC), particularly in BCLC stages B/C, remains largely uncertain. We aimed to explore the impact of DAA therapy on overall survival (OS) in HCC patients using a nationwide cohort study. We utilized the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) database to include all adults receiving a DAA therapy for HCV, excluding those with other viral infections, liver transplantation, non-HCC malignancies, and terminal-staged HCC. We respectively analyzed the adjusted odds ratio (aOR) for SVR and adjusted hazard ratio (aHR) for OS. Between December 2013 and December 2020, 2,205 (9.3%) patients with HCC and 21,569 (90.7%) patients without HCC were recruited. The sustained virological response (SVR) rates were 96.6% in the HCC group and 98.8% in the non-HCC group (p < 0.001), with HCC being an independent risk factor affecting SVR (aOR 0.41, 95% CI 0.31-0.54; p < 0.001). In the whole patient cohort, SVR was independently associated with improved OS (aHR 0.46, 95% CI 0.35-0.60; p < 0.001). Among patients with baseline HCC, SVR remained an independent factor related to OS (aHR 0.41, 95% CI 0.28-0.59; p < 0.001). The impact of SVR on OS persisted significantly across BCLC stages 0-A and stages B-C. High SVR rates among HCC patients underscore the importance of DAA therapy in enhancing OS, reaffirming its efficacy across various HCC stages.
Deciphering adenosine signaling in hepatocellular carcinoma: pathways, prognostic models, and therapeutic implications
Authors: Huihai Yang, Martina Mang Leng Lei, Longfei Xie, Yinuo Shou, Terence Kin Wah Lee
Journal: Clinical and Molecular Hepatology (2025)

Hepatocellular carcinoma (HCC) is a highly lethal cancer due to its aggressive nature and poor prognosis. Adenosine, a key metabolic regulator in the tumor microenvironment (TME), plays a crucial role in cancer progression. In this review, we first described adenosine triphosphate (ATP)-adenosine metabolism in the TME and summarize its effects on tumor growth, immune suppression, angiogenesis, and metastasis in HCC. Given the limited number of clinical studies on adenosine signaling in HCC, we conducted Lasso-Cox analysis using the TCGA-LIHC cohort to develop a prognostic risk model composed of eight adenosine signaling-related genes. This model stratified the patients into low- and high-risk groups, with Kaplan‒Meier survival analysis revealing poorer overall survival in the high-risk group. Additionally, differential gene expression analysis between the two groups identified 24 enriched signaling pathways for further investigation. Immune infiltration and single cell RNA-seq analyses revealed a correlation between adenosine and immunosuppressive activity in the TME, with a particularly strong association observed in macrophages, dendritic cells, and monocytes. Finally, we provided an overview of the advancements of antagonists that target adenosine receptors progress in both preclinical research and clinical trials. In conclusion, this review aims to deepen our understanding of the biological role of adenosine and highlights emerging therapeutic strategies that may improve treatment outcomes for HCC.
Baveno VI-SSM was able to stratify the risk of portal hypertension-related events in patients with HBV-related cirrhosis
Authors: Haiyu Wang, Weihao Liang, Ling Zhou, Jiankang Song, Biao Wen, Qiaoping Wu, Yuanjian Zhang, Xiaofeng Zhang, Haoran Ke, Yujun Tang, Fuyuan Zhou, Youfu Zhu, Weiqun Wen, Zhihua Liu, Yali Ji, Qintao Lai, Qinjun He, Wenfan Luo, Tingting Qi, Miaoxia Liu, Xiaoqin Lan, Yongpeng Chen, Ranran Xi, Junting Wan, Lin Dai, Yuan Li, Jinjun Chen
Journal: Clinical and Molecular Hepatology (2025)

Cirrhotic patients with liver stiffness measurement (LSM) <20kPa and platelet count ≥150/ul (Baveno VI criteria), otherwise spleen stiffness measurement (SSM) ≤ 40kPa (Baveno VI-SSM criteria) can avoid endoscopy screening, however, no prospective data for their hepatic outcomes. Compensated cirrhosis with chronic hepatitis B were prospectively enrolled from April 2019 to April 2022 and followed until July 2023. All patients underwent LSM, SSM and esophagogastroduodenoscopy (EGD) assessment. Among 1224 patients enrolled with median follow-up of 30 months (IQR 21-42), the incidence of decompensation was greater in 560 patients with unfavored Baveno-VI criteria (0.5 vs. 20.4 per 1,000 person-years, p=0.0004) than that in 664 patients with favored Baveno-VI-SSM criteria. The Baveno VI-SSM model identified more patients (54.2%) into low-risk for decompensation than Baveno VII-SSM model (single cutoff) (48.4%, p=0.004) and than Baveno VI criteria (34.6%, p<0.0001) did. Patients with high-risk varices diagnosed via endoscopy following Baveno VI-SSM model assessment had greater probability of decompensation compared to those identified by the Baveno VII-SSM model (single cutoff) (42.8 vs. 21.1 per 1,000 person-years, p=0.0088). Additionally, among the 493 patients who underwent endoscopic re-assessment, 242 patients with favored Baveno VI-SSM criteria had much lower incidence of EV progression (2.6 vs. 99.5 per 1,000 person-years, p=0.0004) and lower risk of decompensation compared to 140 patients with unfavored Baveno VI-SSM model (0 vs. 34.2 per 1,000 person-years, p=0.0256). Baveno VI-SSM model could identify chronic hepatitis B-related cirrhosis patients at low risk of decompensation, which was greatly improved upon Baveno VI-SSM reassessment.
Differential Clinical and Immunological Impacts of Anti–T‐Lymphocyte Globulin (<scp>ATLG</scp>) vs. Anti‐Thymocyte Globulin (<scp>ATG</scp>) in Preventing Graft‐Versus‐Host Disease Post‐Allogeneic Hematopoietic Stem Cell Transplantation: A Comparative Study
Authors: Anne Beatrice Notarantonio, Stéphane Morisset, Romain Piucco, Michaël Pérès, Laura Boulangé, Alizée Alitcher, Jordan Brouard, Lucile Monchablon, Arnaud Campidelli, Siham El Ouahabi, Charles Guisnel, Charline Moulin, Céline Kicki, Gabrielle Roth‐Guepin, Pierre Feugier, Marcelo De Carvalho Bittencourt, Alice Aarnink, Maud D'Aveni‐Piney, Sébastien Hergalant, Simona Pagliuca, Marie Thérèse Rubio
Journal: American Journal of Hematology (2025)

Both anti-T-lymphocyte globulin (ATLG-Grafalon) and anti-thymocyte globulin (ATG-Thymoglobulin) prevent acute and chronic graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite distinct manufacturing and biological characteristics, the two brands of rabbit anti-lymphocyte globulins have never been compared in a prospective way. In this monocentric study, 114 adult patients transplanted with a matched related or unrelated donor after receiving either ATG (n = 50) or ATLG (n = 64) were included to compare their clinical outcomes and broad immune reconstitution parameters. The use of ATLG, compared with ATG, was associated with a 2-fold reduction in Grade II-IV acute GvHD incidence (Cox HR = 0.29; 95% CI 0.14-0.62, p = 0.006), similar relapse incidence, and improved severe GvHD and relapse-free survival (GRFS) (Cox HR = 0.51; 95% CI 0.29-0.91, p = 0.027). Biologically, reduced IL-15 but increased IL-21 serum concentrations and a significant reduction of PD1+ T cells, mainly across all differentiated stages of CD8+ T cells, were observed in the ATLG group. Immunosequencing of vβ T cell receptor (TCR) repertoires showed similar quantitative characteristics in terms of clonality and diversity across the two groups but different qualitative features, with reduced hyper-expanded T cell clones and higher variability in the distribution of complementarity-determining region 3 (CDR3) lengths in the ATLG group. Altogether, these results suggest that ATLG more effectively regulates alloreactive T cell activation, leading to better prevention of acute GvHD while preserving the graft-versus-leukemia response. These findings led us to initiate a multicentric Phase III randomized trial comparing the two anti-lymphocyte globulins. Trial Registration: The biological REAL GREFFE study was registered in clinicaltrial.gov under the number: NCT03357172.
GLP1 alleviates oleic acid-propelled lipocalin-2 generation by tumor-infiltrating CD8+ T cells to reduce polymorphonuclear MDSC recruitment and enhances viral immunotherapy in pancreatic cancer
Authors: Jingyi Wu, Peng Qian, Yifeng Han, Chuning Xu, Mao Xia, Ping Zhan, Jiwu Wei, Jie Dong
Journal: Cellular and Molecular Immunology (2025)
Peroxisome proliferator-activated receptor alpha is an essential factor in enhanced macrophage immune function induced by angiotensin-converting enzyme
Authors: Suguru Saito, Duo-Yao Cao, Ellen A. Bernstein, Tomohiro Shibata, Anthony E. Jones, Amy Rios, Aoi O. Hoshi, Aleksandr B. Stotland, Erika E. Nishi, Jennifer E. Van Eyk, Ajit Divakaruni, Zakir Khan, Kenneth E. Bernstein
Journal: Cellular and Molecular Immunology (2025)
Cell-associated galectin 9 interacts with cytotoxic T cells confers resistance to tumor killing in nasopharyngeal carcinoma through autophagy activation
Authors: Ngar-Woon Kam, Cho Yiu Lau, Jeffrey Yan Ho Lau, Xin Dai, Yusi Liang, Syrus Pak Hei Lai, Michael King Yung Chung, Valen Zhuoyou Yu, Wenting Qiu, Mengsu Yang, Corey Smith, Rajiv Khanna, Kwan Ming Ng, Wei Dai, Chi Ming Che, Victor Ho-Fun Lee, Dora L. W. Kwong
Journal: Cellular and Molecular Immunology (2025)

Abstract Immune effector cells, including cytotoxic T lymphocytes (CTLs) play essential roles in eliminating cancer cells. However, their functionality is often compromised, even when they infiltrate the tumor microenvironment (TME) or are transferred to cancer patients adoptively. In this study, we focused on galectin 9 (G9), an inhibitory ligand that we observed to be predominately positioned on the plasma membrane and readily interacts with CD8 + CTL in the TME of nasopharyngeal carcinoma (NPC). We discovered that cell-cell contact between activated effector CTLs and target tumor cells (TarTC) with G9 overexpression led to cellular death defects. Despite the formation of CTL–TarTC conjugates, there is no impact on the cell number nor viability of CTL, and the release of cytolytic content and associated activity were not completely abrogated. Instead, this interaction promoted autophagy and restricted necrosis in the TarTC. Furthermore, reducing G9 expression in tumor cells enhanced the suppressive effect on tumor growth upon adoptive transfer of activated effector CTL. Additionally, inhibiting autophagy effectively controlled tumor growth in cases of G9 overexpression. Therefore, we highlight the contribution of G9 in facilitating the resistance of NPC to CTL-mediated killing by inducing a selection-cell death state in tumor cells, characterized by increased autophagy and decreased necrosis.
Six Injections of Modified Adjuvanted <scp>PQ</scp> Grass Is Effective and Well‐Tolerated in a Pivotal Phase <scp>III</scp> Trial
Authors: Stefan Zielen, Jonathan A. Bernstein, Gunter J. Sturm, Marek Jutel, Oliver Pfaar, Mohamed H. Shamji, Ralph Mösges, Markus Berger, Uwe E. Berger, Lawrence DuBuske, Janice A. Layhadi, Ludger Klimek, Markus Ollert, Murray A. Skinner, Matthias F. Kramer, Pieter‐Jan de Kam
Journal: Allergy (2025)

ABSTRACT Background PQ Grass 27600 SU (PQ Grass) cumulative dose is a pre‐seasonal, six‐injection, aluminium‐free, modified subcutaneous immunotherapy product under development for the treatment of allergic rhinitis (AR). A pivotal Phase III randomised double‐blind, placebo‐controlled clinical trial was performed to evaluate the efficacy and safety of PQ Grass in subjects with seasonal AR. Methods An adaptive group sequential trial PQGrass306 (G306) with one pre‐defined interim analysis was designed, using 2 parallel groups applying a 1:1 active versus placebo randomisation of patients aged 18–65. The primary efficacy endpoint was the EAACI (European Academy of Allergy and Clinical Immunology) Combined Symptom and Medication Score (EAACI‐CSMS 0–6 ) averaged over the peak grass pollen season (GPS). Results 858 subjects were screened and 555 subjects were randomised. Based on the results of the pre‐defined interim analysis, the trial was stopped for success showing superiority in favour of PQ Grass. The primary endpoint EAACI‐CSMS 0–6 (peak GPS) demonstrated a highly significant and clinically meaningful point difference of PQ Grass over placebo of −0.27 points (95% CI: −0.42 to −0.12), corresponding to a relative difference of −20.3% ( p = 0.0005). Highly consistent and beneficial results were obtained for PQ Grass for all key secondary endpoints. Significant induction of blocking IgG4 and IgA antibody subclasses occurred. PQ Grass was well tolerated, and no unexpected safety signals occurred. Conclusions This pivotal Phase III trial demonstrated a significant and clinically meaningful effect on the primary endpoint as well as highly consistent secondary endpoint results and a supportive safety profile.
Epigenome‐Wide Association Study of Asthma Exacerbations in Europeans
Authors: Elena Martin‐Gonzalez, Javier Perez‐Garcia, Esther Herrera‐Luis, Mario Martin‐Almeida, Simon Kebede‐Merid, Natalia Hernandez‐Pacheco, Fabian Lorenzo‐Diaz, Ruperto González‐Pérez, Olaia Sardón, José M. Hernández‐Pérez, Paloma Poza‐Guedes, Inmaculada Sánchez‐Machín, Elena Mederos‐Luis, Paula Corcuera, Leyre López‐Fernández, Berta Román‐Bernal, Antoaneta A. Toncheva, Susanne Harner, Christine Wolff, Susanne Brandstetter, Mahmoud Ibrahim Abdel‐Aziz, Simone Hashimoto, Susanne J. H. Vijverberg, Aletta D. Kraneveld, Uroš Potočnik, Michael Kabesch, Anke H. Maitland‐van der Zee, Jesús Villar, Erik Melén, Maria Pino‐Yanes
Journal: Allergy (2025)

ABSTRACT Background Asthma exacerbations (AEs) represent the major contributor to the global asthma burden. Although genetic and environmental factors have been associated with AEs, the role of epigenetics remains uncovered. Objective This study aimed to identify whole blood DNA methylation (DNAm) markers associated with AEs in Europeans. Methods DNAm was assessed in 406 blood samples from Spanish individuals using the Infinium MethylationEPIC microarray (Illumina). An epigenome‐wide association study was conducted to test the association of DNAm with AEs at differentially methylated positions, regions, and epigenetic modules. CpGs suggestively associated with AEs (false discovery rate [FDR] &lt; 0.1) were followed up for replication in 222 European individuals, and the genome‐wide significance ( p &lt; 9 × 10 −8 ) was declared after meta‐analyzing the discovery and replication samples. Additional assessment was performed using nasal tissue DNAm data from 155 Spanish individuals. The effects of genetic variation on DNAm were assessed through cis‐methylation quantitative trait loci (meQTL) analysis. Enrichment analyses of previous EWAS signals were conducted. Results Four CpGs were associated with AEs, and two were replicated and reached genomic significance in the meta‐analysis (annotated to ZBTB16 and BAIAP2 ). Of those, CpG cg25345365 ( ZBTB16 ) was cross‐tissue validated in nasal epithelium ( p = 0.003) and associated with five independent meQTLs (FDR &lt; 0.05). Additionally, four differentially methylated regions and one module were significantly associated with AEs. Enrichment analyses revealed an overrepresentation of prior epigenetic associations with prenatal and environmental exposures, immune‐mediated diseases, and mortality. Conclusions DNAm in whole blood and nasal samples may contribute to AEs in Europeans, capturing genetic and environmental risk factors.
Optimizing Pemphigus Management With Rituximab and Short-Term Relapse Predictors
Authors: Vivien Hébert, Sami Hamwi, Emmanuelle Tancrède-Bohin, Gaelle Quéreux, Anne Pham-Ledard, Frédéric Caux, Billal Tedbirt, Alexis Lefebvre, Nadège Cordel, Marina Alexandre, Manuelle Viguier, Géraldine Jeudy, Michel D’Incan, Sébastien Debarbieux, Alexis Brue, Sophie Duvert-Lehembre, Marion Fenot, Vannina Seta, Saskia Ingen-Housz-Oro, Clémence Lepelletier, Pascal Joly
Journal: JAMA Dermatology (2025)

Importance Rituximab is approved for the treatment of moderate to severe pemphigus. However, 20% of patients in the RITUX 3 trial relapsed within the first year of treatment. Objective To assess the outcome of an additional rituximab infusion at month 6 in patients with pemphigus who were in complete remission (CR) after rituximab regimen but had 1 or more predictors of relapse at month 3. Design, Settings, and Participants This multicenter cohort study was conducted in France from September 2018 to June 2023 to assess patients with newly diagnosed pemphigus who were in CR after treatment with the RITUX 3 regimen but had predictors of relapse at month 3. Relapse factors were a Pemphigus Disease Area Index (PDAI) score of 45 or higher, desmoglein 1 (DSG1) antibodies greater than 20 IU/mL, and/or DSG3 antibodies greater than 130 IU/mL. Exposure Patients in CR at month 6 with at least 1 predictor of relapse were treated with an additional rituximab infusion at month 6. Main Outcomes and Measures Primary end point was the rate of CR without corticosteroid therapy for 2 months at month 12. Secondary end points were the rate of relapse, number of patients needing to be re-treated (NNT) with rituximab to avoid a relapse, and safety. Results The study population comprised 87 patients (44 females [50.6%] and 43 [49.4%] males), with a mean (SD [range]) age of 55.3 (15.2 [24-92]) years at pemphigus diagnosis. Of these, 64 patients (73.6%) had pemphigus vulgaris and 23 (26.4%) had pemphigus foliaceus. At month 6, CR had been achieved by 77 patients (88.5%), and 10 (11.5%) had persistent disease activity. Of the 77 patients in CR, 30 (39.0%) had at least 1 predictor of relapse and received an additional infusion of rituximab; 47 patients (61.0%) without a predictor did not. Two patients without a predictor and no patients with a predictor experienced relapse—an overall relapse rate of 2.6% and an NNT of 3.6 (95% CI, 1.6-46.5). The 10 patients (11.5%) with persistent disease activity at month 6 were re-treated with rituximab, 1000 mg. At month 12, the rate of CR without corticosteroid therapy for a minimum of 2 months was 72 of 77 (93.5%) among patients who had achieved CR at month 6, and 72 of 87 (82.7%) for the whole study population. Eight serious adverse effects were reported among 5 patients; there were no deaths. Conclusion and Relevance This multicenter cohort study indicates that using predictors such as baseline PDAI score, anti-DSG1 antibodies, and/or anti-DSG3 antibodies to initiate preemptive treatment with additional rituximab may reduce the rate of short-term relapse.
UV Stabilizer BTMPS in the Illicit Fentanyl Supply in 9 US Locations
Authors: Chelsea L. Shover, Morgan E. Godvin, Meghan Appley, Elise M. Pyfrom, Fernando Montero Castrillo, Karli Hochstatter, Talia Nadel, Neil Garg, Adam Koncsol, Joseph R. Friedman, Caitlin A. Molina, Ruby Romero, Brendan Harshberger, Jordan A. M. Gonzalez, Jordan Spoliansky, Sarah Laurel, Elham Jalayer, Juan Ruelas, John Gonzales, Soma Snakeoil, Sonya Guerra, Oscar Arellano, Candace Winstead, Margaret Rybak, Joanna Champney, Brent Waninger, Rafael Torruella, Edward Sisco
Journal: JAMA (2025)

This study characterizes the presence of bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate (BTMPS) in the illicit fentanyl supply in 9 US locations.
Recognition of the Large Ambulatory C2D Stage of Advanced Heart Failure—A Call to Action
Authors: Shannon M. Dunlay, Sean P. Pinney, Anuradha Lala, Garrick C. Stewart, Colleen McIlvennan, Renee P. Wong, Alanna A. Morris, Francis D. Pagani, Larry A. Allen, Khadijah Breathett, Rebecca Cogswell, Monica M. Colvin, Jennifer A. Cowger, Stavros G. Drakos, Laura P. Gelfman, Manreet K. Kanwar, Michael S. Kiernan, Michelle M. Kittleson, Eldrin F. Lewis, Nader Moazami, Modele O. Ogunniyi, Ambarish Pandey, Joseph G. Rogers, Kurt R. Schumacher, Mark S. Slaughter, Ryan J. Tedford, Jeffrey Teuteberg, Hannah A. Valantine, Ersilia M. DeFilippis, Debra D. Dixon, Jessica R. Golbus, Gaurav Gulati, Thomas C. Hanff, Stephanie Hsiao, Sabra C. Lewsey, Amanda D. McCormick, Aditi Nayak, Kathleen N. Fenton, Lisa Schwartz Longacre, Sujata M. Shanbhag, Wendy C. Taddei-Peters, Lynne Warner Stevenson
Journal: JAMA Cardiology (2025)

Importance The advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood. Observations In December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D . This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies. Conclusions and Relevance Ten key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.
Eliminating the Medicare Coverage Gap for Intranasal Naloxone and Nicotine Replacement Therapy
Authors: Robert A. Kleinman, Brian S. Barnett
Journal: JAMA (2025)

This Viewpoint explores how FDA approval of intranasal naloxone and nicotine replacement therapy as over-the-counter drugs adversely affects Medicare patients because the treatments are no longer covered and urges policymakers to address this coverage gap.