tbuckley/cabot-search huggingface dataset:
GLOBAL EPIDEMIOLOGY OF PRIMARY BILIARY CHOLANGITIS: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Jarell Jie-Rae Tan, Ambrose Hon Lam Chung, Jing Hong Loo, Joo Wei Ethan Quek, Sagar Sharma, Corrine Lee Singh, Roe Xin Jacqueline Yap, Wei Xuan Tay, Matthew K Smith, Ellina Lytvyak, Andrew Mason, Aldo J Montano-Loza, Yu Jun Wong
Journal: Clinical Gastroenterology and Hepatology (2025)
Transferrin Saturation and Serum Ferritin are Main Predictors of Liver Iron Content in Subjects with Hyperferritinemia
Authors: G I U L I A Risca, S A R A Pelucchi, R A F F A E L L A Mariani, M A R A Botti, G I U L I A Capitoli, F I L I B E R T O DI Gennaro, S T E F A N I A Galimberti, A L B E R T O Piperno
Journal: Clinical Gastroenterology and Hepatology (2025)
Monitoring the Emergence of Resistance With Sotrovimab in Immunocompromised Patients With COVID-19: LUNAR Study
Authors: Judith Breuer, Myriam Drysdale, Jill Walker, Jennifer Han, Alicia Aylott, Melissa K Van Dyke, Helen J Birch, Elizabeth McKie, William Jordan, Kim Gemzoe, Iain A Gillespie, Claire Bethune, Charlotte A Williams, Jonathan Underwood, Anna L Goodman, Michael Brown, Julianne R Brown, Rachel Williams, Luz Marina Martin Bernal, Laura Buggiotti, Effrossyni Gkrania-Klotsas, Clara Green, Ewan Hunter, Charles Miller, Andrew Skingsley, David M Lowe
Journal: Journal of Infection (2025)

To assess outcomes in sotrovimab-treated immunocompromised patients in the United Kingdom. Multicenter, prospective, observational, descriptive study in immunocompromised, non-hospitalized adults infected with SARS-CoV-2 who received intravenous sotrovimab 500mg as standard-of-care (July 1, 2022-June 30, 2023; Omicron predominance). Virology analyses included determination of SARS-CoV-2 viral load, spike sequencing, and determination of amino-acid substitutions in the spike protein and sotrovimab epitope. The proportion of participants (N=217) with undetectable SARS-CoV-2 RNA was 25.1% at day 7, 65.8% at day 14, and 83.5% at day 28. Of 156 participants with paired sequences, 101 (64.7%) and 47 (30.1%) had treatment-emergent substitutions at >50% allelic frequency in the spike protein and sotrovimab epitope, respectively, at any post-baseline timepoint. Ten treatment-emergent substitutions (at positions 337, 340, and 356) were identified in the epitope at >50% allelic frequency. Five of 18 (27.8%) participants with, versus 22/30 (73.3%) of those without, treatment-emergent epitope substitutions at day 14 achieved undetectable SARS-CoV-2 RNA levels at day 28. In this immunocompromised population infected with SARS-CoV-2 who received early treatment with sotrovimab, most participants (83.5%) experienced substantial viral load reductions by day 28. Treatment-emergent substitutions occurred in the sotrovimab epitope, including substitutions known to reduce susceptibility in vitro. Several treatment-emergent substitutions were associated with viral persistence. For requests for access to anonymised subject-level data, please contact the Corresponding Author.
Cost-Effective Yet High-Performance Ionizable Lipids for mRNA-Lipid Nanoparticle Vaccines
Authors: Zhan Gao, Haihong Yang, Zepeng He, Yizi Zhou, Xiaofei Ge, Hong Liu, Zhihong Yan, Haomeng Wang, Lai Wei, Dongdong Qiao, Zhijia Liu, Tao Zhu, Lixin Liu, Yongming Chen
Journal: Biomaterials (2025)
Comparative effectiveness of intravenous versus subcutaneous tocilizumab for refractory uveitis: a retrospective analysis
Authors: Mathilde Leclercq, Robin Jacquot, Camille Charbonnier, Anne-Claire Desbois, Georgina Maalouf, Sara Touhami, Amine Ghembaza, Fanny Domont, Gaëlle Leroux, Thomas Sales de Gauzy, Adélaïde Toutée, Nicolas Girszyn, Paul Goupillou, Marc Muraine, Christine Fardeau, Ygal Benhamou, Laurent Kodjikian, Patrice Cacoub, Pascal Sève, Bahram Bodaghi, David Saadoun, Julie Gueudry
Journal: Ophthalmology (2025)
Microfluidic Captured Patient-derived Circulating Endothelial Cells Identify Novel Targets of Pulmonary Arterial Hypertension
Authors: Riajul Wahab, Ali Keshavarz, Zulfikar Azam, Tamanna Islam, Md Mahedi Hasan, Xiaojun Zhang, Ahmed Alobaida, Muhit Rana, Jeong Uk Choi, Farzana Alam, In-San Kim, Youngro Byun, Joseph H McCarty, Nils Patrick Nickel, Sourav Roy, Taslim A Al-Hilal
Journal: Biomaterials (2025)
Evidence of Greater Immune Aging among Untreated HIV Slow Progressors than Antiretroviral-controlled People Living with HIV
Authors: Anthony Y Y Hsieh, Renying Cai, Nicole F Bernard, Cecile L Tremblay, Hélène C F Côté
Journal: Journal of Infection (2025)

Uncontrolled HIV viremia results in the progression to AIDS, however this can be stopped with antiretroviral therapy (ART). Slow progressors are rare individuals who can prevent or delay HIV disease progression without ART. It is unknown whether they experience immune aging akin to normal progressors on ART. We investigated persons living with HIV (PWH) who were either HIV slow progressors (n=58), PWH on ART with undetectable HIV viremia (n=58), PWH not on ART with detectable viremia (n=56), and 56 controls without HIV. The groups were well matched for age and sex. A panel of T-cell differentiation and immune aging markers were measured, along with T and B cell subset telomere length, adjusting for major confounders. Relative to the ART-suppressed HIV group, slow progressors showed immune aging markers indicative of more advanced aging, including lower CD8 naïve:effector memory ratio (standardized effect size -0.41 [95% CI -0.74,-0.07]), and shorter telomere length in B cells (-0.52 [-0.97,-0.07]), CD4 T cells (-0.58 [-0.94,-0.23]), and proliferative CD8 cells (-0.41 [-0.80,-0.01]). Comparison of slow progressors with the control group without HIV showed the same effects. Further, within the slow progressor group, immune aging patterns for the subgroup of elite controllers were not different. Our findings indicate that despite natural host control of HIV replication, slow progressors show evidence of disproportionately advanced immune aging. This reinforces the potential benefit of ART and emphasizes the need to both diagnose slow progressors, and study their potential age-related comorbidities.
Hydrogen Activates Acod1-Itaconate Pathway to Ameliorate Steroid-Associated Osteonecrosis
Authors: Yuanming An, Lizhen Zheng, Shi'an Zhang, Haozhi Zhang, Yuantao Zhang, Hongwei Shao, Wenxue Tong, Ziyi Chen, Hao Yao, Zhenkang Wen, Shunxiang Xu, Ye Li, Qinyu Tian, Liming Cheng, Wei Sun, Ling Qin, Jiankun Xu
Journal: Biomaterials (2025)
Home‐based urinary sodium monitoring via point‐of‐care testing for personalized diuretic titration in heart failure management: The <scp>EASY</scp>‐<scp>STOP</scp> study
Authors: Evelyne Meekers, Pieter Martens, Ruben Knevels, Marie Miseur, Athanasius Ezzat, François Croset, Jeroen Dauw, Henri Gruwez, Sebastiaan Dhont, Jonas Erzeel, Marnicq Van Es, Petra Nijst, Frederik H. Verbrugge, Matthias Dupont, Stefan Janssens, Wilfried Mullens
Journal: European Journal of Heart Failure (2025)
A timeline of cognitive costs in decision-making
Authors: Christin Schulze, Ada Aka, Daniel M Bartels, Stefan F Bucher, Jake R Embrey, Todd M Gureckis, Gerald Häubl, Mark K Ho, Ian Krajbich, Alexander K Moore, Gabriele Oettingen, Joan D K Ongchoco, Ryan Oprea, Nicholas Reinholtz, Ben R Newell
Journal: Trends in Cognitive Sciences (2025)
GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice
Authors: Wen Mei, Guangda Xiang, Yixiang Li, Huan Li, Lingwei Xiang, Junyan Lu, Lin Xiang, Jing Dong, Min Liu
Journal: Molecular Therapy (2025)
Re: Invasive Urodynamic Investigations in the Management of Women with Refractory Overactive Bladder Symptoms (FUTURE) in the UK: A Multicentre, Superiority, Parallel, Open-label, Randomised Controlled Trial
Authors: Maurizio Serati, Tufan Tarcan, Benoit Peyronnet, Enrico Finazzi Agrò
Journal: European Urology (2025)
Erectile Dysfunction: Update on Clinical Management
Authors: Paolo Capogrosso, Maarten Albersen, Arthur L Burnett, Onur Omer Cakir, Federico Dehó, Luís Afonso Morgado, John Mulhall, Andrea Salonia, Ahmet Furkan Sarikaya, Maria Satchi, Ege Can Serefoglu, Maj Shabbir, Ioannis Sokolakis, Tet Yap, Fabio Castiglione
Journal: European Urology (2025)
The Role of Prostate-specific Membrane Antigen Positron Emission Tomography for Assessment of Local Recurrence and Distant Metastases in Patients with Biochemical Recurrence of Prostate Cancer After Definitive Treatment: A Systematic Review and Meta-analysis
Authors: Elio Mazzone, Alice Thomson, David C Chen, Donato Cannoletta, Leonardo Quarta, Antony Pellegrino, Giorgio Gandaglia, Daniel Moon, Renu Eapen, Nathan Lawrentschuk, Francesco Montorsi, Shankar Siva, Michael S Hofman, Arturo Chiti, Alberto Briganti, Marlon L Perera, Declan G Murphy
Journal: European Urology (2025)
The effects of cytisinicline for smoking cessation on arterial stiffness, endothelial function and myocardial performance: A pilot study
Authors: Ignatios Ikonomidis, John Thymis, Gavriella Kostelli, Konstantinos Katogiannis, Dimitrios Vlastos, Eleni Gatourtzidou, Kallirhoe Kourea
Journal:  (2025)
Prospects for understanding and exploiting the consequences of hyperactivation lethality
Authors: Katharin Shaw, René Bernards, Kimberly Stegmaier, Harold Varmus, William R Sellers
Journal: Trends in cancer (2025)

Cancer cells optimize oncogenic signaling to maintain a defined range for survival. The success of targeted therapeutic inhibitors is based on suppressing signaling below this optimal fitness zone. Conversely, cancers are also susceptible to a clinically underutilized vulnerability - oncogenic hyperactivation. Cytotoxic hyperactivation is observed across diverse cancers, with direct small-molecule activators and inhibitors of negative regulators inducing lethal pathway activation. Deep characterization of the cancer genome and unbiased screening approaches have yielded multiple targets vulnerable to hyperactivation; however, translation into the clinical setting will require defining signaling thresholds, discovering biomarkers, and developing appropriate trial designs. By exploiting cancer's intrinsic vulnerabilities, activation lethality offers a promising therapeutic strategy to expand the treatment landscape and overcome resistance to targeted inhibition.
Ruxolitinib Targets JAK-STAT Signaling to Modulate Neutrophil Activation in Refractory Macrophage Activation Syndrome
Authors: Yuning Ma, Xia Chen, Mengyan Wang, Jianfen Meng, Dehao Zhu, Longfang Chen, Yu Xiao, Da Yi, Hui Shi, Honglei Liu, Xiaobing Cheng, Yutong Su, Junna Ye, Huihui Chi, Zhuochao Zhou, Tingting Liu, Chengde Yang, Jialin Teng, Yue Sun, Jinchao Jia, Qiongyi Hu
Journal: Blood (2025)

Macrophage activation syndrome (MAS) is believed to be the result of inappropriate proliferation and activation of the mononuclear phagocytic system. Adult-onset Still's disease (AOSD) is characterized by neutrophil activation and a cytokine storm, which can lead to its severe and potentially life-threatening complication MAS. RNA sequencing revealed that neutrophils may play a distinct and enhanced role in innate immunity in AOSD patients with MAS (AOSD-MAS). In the CpG-induced secondary hemophagocytic lymphohistiocytosis (HLH) model, depletion of neutrophils significantly reduced cytokine levels, with effects comparable to monocyte depletion. Significant enrichment was observed in the type I/II interferon and JAK-STAT pathways in neutrophils from AOSD-MAS patients. Treatment of 10 refractory AOSD-MAS patients with ruxolitinib led to the resolution of inflammatory parameters and clinical symptoms. RNA sequencing and ex vivo assays confirmed that ruxolitinib suppressed aberrant NETosis and STAT3/STAT5 signaling. In vivo, PAD4 knockout further confirmed the pathogenic role of NETosis in secondary HLH model. Moreover, selective inhibition of STAT3 or STAT5 alleviated systemic inflammation. Ten functional variants were identified in genes related to the JAK-STAT pathway, although their clinical relevance requires further validation. These findings suggest the potential of ruxolitinib in achieving disease remission in refractory AOSD-MAS patients by broadly inhibiting JAK-STAT signaling and modulation of neutrophil activation and NETosis.
Validation of guidelines for genetic investigation of myeloid neoplasms with germline predisposition: results from a prospective cohort study
Authors: Bianca Tesi, Anna Robelius, Berivan Baskin, Vladimir Lazarevic, Stefan Deneberg, Martin Höglund, Linda Fogelstrand, Johanna Ungerstedt, Tatjana Pandzic, Magnus Tobiasson, Hege Gravdahl. Garelius, Ekaterina Kuchinskaya, Fredrik Persson, Helena Ågerstam, Helene Hallböök, Thoas Fioretos, Jessika Nordin, Anna Norberg, Ann-Charlotte Thuresson, Sören Lehmann, Claes Ladenvall, Gisela Barbany, Lovisa Vennström, Elisabeth Ejerblad, Lucia Cavelier, Jörg Cammnega, Martin Jädersten, Eva Hellström-Lindberg, Panagiotis Baliakas
Journal: Clinical Cancer Research (2025)

Abstract Purpose: In a multicenter prospective cohort-study we assessed the diagnostic yield of the Nordic guidelines for germline investigation in myeloid neoplasms (MN) and mapped the spectrum of inherited and somatic variants. Experimental Design: Eighty-five patients (acute myeloid leukemia (AML): n=38; myelodysplastic syndromes (MDS): n=26; thrombocytopenia: n=14; other: n=7) fulfilling the Nordic criteria for germline investigation: (1) medical history (MH) or family history (FH) suggestive of a germline condition; (2), relevant findings from the somatic diagnostic work-up (CytoMol), were recruited. The genetic analysis included enhanced whole-exome sequencing (WES, n=69) or sequencing of specific variants of interest (n=16). Results: Pathogenic or likely pathogenic (P/LP) germline variants were identified in 35% of patients (30/85). The diagnostic yield varied from 6% (1/16) in the FH group to 52% (17/33) in the CytoMol group. Germline DDX41 P/LP variants were the most frequent finding (13/30, 43% of all positive cases), almost exclusively found within the CytoMol group (12/13). Seven variants of unknown significance (VUS) were also detected (TERT n=2; DDX41, RTEL1, ETV6, PARN and SAMD9: n=1). Five patients carried a P/LP variant in genes associated with another hereditary cancer syndrome (BRCA1 n=3; PALB2 n=1; CHEK2; n=1). Survival analysis showed a trend for longer survival among patients with AML and confirmed or suspected germline predisposition that underwent allogeneic stem cells transplantation (allo-HSCT). Conclusions: The implementation of the Nordic guidelines in a prospective Swedish cohort, results in a high overall diagnostic yield (35%), proving the feasibility and utility of these or similar guidelines in a clinical setting.
<i>Akkermansia muciniphila</i> reverses neuronal atrophy in <i>Negr1</i> knockout mice with depression-like phenotypes
Authors: Hee-Gon Hwang, Ji-Woo Park, Hyo-Jin Lee, Moon Yi Ko, Minhan Ka, Yun Kyung Lee, Jaeyoon Choi, Su-A In, Ye-Eun Lee, Soojin Lee, Min-Soo Kim, Jeong-Yoon Kim
Journal: Gut Microbes (2025)

Genetic predispositions can shape the gut microbiome, which in turn modulates host gene expression and impacts host physiology. The complex interplay between host genetics and the gut microbiome likely contributes to the development of neuropsychiatric disorders, yet the mechanisms behind these interactions remain largely unexplored. In this study, we investigated the gut microbiota in Negr1 knockout (KO) mice, which exhibit anxiety- and depression-like behaviors, as NEGR1 (neuronal growth regulator 1) is a cell adhesion molecule linked to neuronal development and neuropsychiatric disorders. Our findings show significant early-life alterations in the gut microbiota composition of Negr1 KO mice, most notably a marked reduction in Akkermansia spp. along with reduced dendritic arborization and spine density in the nucleus accumbens (NAc) and the dentate gyrus (DG) of the hippocampus. Remarkably, daily administration of an Akkermansia strain isolated from wild-type mice reversed the neuronal structural abnormalities and ameliorated anxiety- and depression-like behaviors in Negr1 KO mice. Transcriptomic profiling revealed upregulation of mitochondrial genome-encoded genes in the NAc and hippocampus of Negr1 KO mice, along with a predisposition toward a pro-inflammatory state in the colon of Negr1 KO mice. The Akkermansia supplementation downregulated these mitochondrial genes in the NAc and hippocampus and upregulated genes involved in T cell activation and immune homeostasis in the colon. These findings demonstrate a novel gene-microbiome interaction in the pathophysiology of Negr1 KO mice, positioning Akkermansia spp. as a key mediator that improves neuronal atrophy and modulates anxiety- and depression-like behaviors. Our study provides compelling evidence for bidirectional interactions between host genetics and the gut microbiome in modulating neuropsychiatric phenotypes, offering new insights for addressing genetically influenced mental disorders.
Inhibition of terminal complement complex formation alleviates murine antibody-mediated TRALI
Authors: Dawei Chen, Huaqin Liang, Xiuzhang Xu, Wenjie Xia, Xin Ye, Yalin Luo, Jiansen He, Yaori Xu, Jing Liu, Hui Ren, Shengxue Luo, Trent M. Woodruff, Wioleta M. Zelek, Bryan Paul Morgan, Rick Kapur, Sentot Santoso, Yongshui Fu
Journal: Blood (2025)

Transfusion-related acute lung injury (TRALI) is a leading cause of blood transfusion triggered mortality. Recently, we demonstrated the critical role of Fc-dependent complement activation in anti-CD36-mediated murine TRALI. In this study, we found that C5−/− mice were protected and administration of anti-C5 rescued wild-type mice from anti-CD36-mediated TRALI. However, C5aR1−/− mice were not protected against anti-CD36-mediated TRALI, implying a possible role of C5b-9 (membrane attack complex [MAC]). Accordingly, elevated levels of MAC were detected in bronchoalveolar lavage fluid and lung tissue of mice with anti-CD36 induced TRALI. Inhibition of MAC formation by administration of anti-C7 blocking monoclonal antibody (mAb) alleviated TRALI in mice, suggesting the critical role of the MAC in the pathology of anti-CD36-mediated TRALI. Furthermore, anti-C7 treatment also led to favorable outcome in anti-MHC I-induced murine TRALI, indicating the potential broader applicability of MAC inhibitors in the treatment of antibody-mediated TRALI. Therefore, this approach may be promising to further explore for the treatment of TRALI patients.
Nivolumab and Relatlimab for the treatment of patients with unresectable or metastatic mismatch repair proficient colorectal cancer
Authors: Eric S. Christenson, Won Jin Ho, Daniel Shu, Jennifer N. Durham, Madelena Brancati, Heather Davis Bruning, Susan Petrie, Hao Wang, Jiayun Lu, Katherine M. Bever, Daniel Laheru, Ana De Jesus-Acosta, Ilene Browner, Ross Donehower, Michael J. Pishvaian, Nilofer Azad, Qingfeng Zhu, Alens Valentin, Jayalaxmi Suresh Babu, Alexei Hernandez, George Apostol, Yiyang Gao, Nicolas Llosa, Franck Housseau, Drew Pardoll, Elizabeth M. Jaffee, Robert Anders, Dung T. Le
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Combined inhibition of lymphocyte-activation gene 3 (LAG-3) and programmed cell death protein 1 (PD-1) improves outcomes in patients with melanoma. Increased LAG-3 expression in colorectal cancer (CRC) correlates with reduced survival. Higher mucin and PD-L1 expression in the mismatch repair proficient (pMMR) CRC tumor microenvironment (TME) was associated with increased LAG-3 and retrospectively with prolonged progression-free survival upon PD-1 blockade. This led to the hypothesis that LAG-3/PD-1 inhibition would improve clinical outcomes in this pMMR CRC subset. Patients and Methods: NCT03642067 was a phase 2 study evaluating combining relatlimab (LAG-3 inhibitor) and nivolumab (PD-1 inhibitor) in patients with previously treated metastatic pMMR CRC. Patients were enrolled onto one of three cohorts, A: mucin/PD-L1 high, B: mucin/PD-L1 low, or C: mucin/PD-L1 unselected. The primary endpoint for each cohort was overall response rate. Results: We enrolled 59 evaluable patients; best treatment responses were partial response: 3, stable disease: 6, progressive disease: 50. Response rates did not differ significantly between cohorts. Subgroup analyses demonstrated 2 of 5 patients with lung-only metastases had a partial response. Comparison of liver and lung metastases identified higher baseline dendritic cell densities in lung lesions. Nivolumab/relatlimab resulted in increased intratumoral cytotoxic T cells. Lower baseline intratumoral Tregs and ADAM10+ cancer cells correlated with clinical response. Conclusions: This investigation did not reach its primary endpoint for any of the three treatment cohorts, but does provide critical insight into the effects of combining nivolumab/relatlimab on the CRC TME and identifies subgroups that may derive greater benefit from this combination.
Concordance between tumor tissue and plasma DNA genotyping in the NCI-MATCH trial (EAY131)
Authors: Mohamed A. Gouda, Filip Janku, Ying Yuan, Leylah M. Drusbosky, Alice P. Chen, Xiaofeng Zheng, Keyur Patel, Stanley R. Hamilton, Mark Routbort, James V. Tricoli, P. Mickey Williams, A. John Iafrate, Jeffrey Sklar, Brent Coffey, Richard F. Little, Carlos L. Arteaga, Peter J. O'Dwyer, Keith T. Flaherty, Lyndsay N. Harris, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Liquid biopsies with circulating tumor DNA (ctDNA) analysis are increasingly being utilized as a non-invasive approach to identify actionable genomic alterations in advanced/metastatic cancers. Herein, we report the correlation between ctDNA analysis of plasma samples collected from patients enrolled in the NCI-MATCH trial and tumor tissue-based sequencing. Patients and Methods: We analyzed plasma samples collected from patients enrolled on 16 subprotocols of NCI-MATCH who had plasma samples collected within 90 days before starting treatment. Concordance was defined as the detection of the same gene alteration leading to patient enrollment in NCI-MATCH in both tissue and plasma. Results: We included 300 patients who were enrolled in NCI-MATCH. Most patients (81%, n=243) were enrolled based on central tissue testing and had contemporaneous tissue and plasma samples. The tissue alteration of interest was detected in the plasma of 81.1% (n=197) of patients. Lower rates of detection of the tissue alteration of interest were observed in samples from 57 patients who were enrolled based on outside designated laboratory testing (56.1%, n=32) and had non-contemporaneous tissue and plasma samples. Variations in concordance rates were observed with different alteration types, by maximum plasma variant allelic frequency, and based on tumor biopsy site. Conclusions: The tumor tissue alteration of interest was detected in the plasma of 81% of patients who were enrolled in the NCI-MATCH trial based on central tissue testing and had contemporaneous tissue and plasma samples. This suggests a potential role for liquid biopsy in patients’ enrollment in trials evaluating biomarker-driven anticancer therapies.