tbuckley/cabot-search huggingface dataset:
“Dr. Jekyll and Mr. Hyde”: AT2 Cells in Lung Regeneration and Tumor Development
Authors: Xinyuan Tong, Gen Lin, Hongbin Ji
Journal: Cancer Research (2025)

Abstract Alveolar type II (AT2) cells, the primary stem cell population in the distal lung epithelium, are known to be the most common cell of origin for lung adenocarcinoma (LUAD). A recent study published in Cell Stem Cell reveals that KRASG12D mutant AT2 cells hijack lung regeneration programs to initiate lung adenocarcinoma, resembling “Dr. Jekyll and Mr. Hyde” where their “Jekyll” side promotes tissue repair while their “Hyde” side drives tumorigenesis. Sustained NF-κB activation drives lineage infidelity, enabling these mutant cells to bypass normal differentiation, remodel the surrounding microenvironment, and ultimately promote tumorigenesis.
Age-Associated Modulation of TREM1/2-Expressing Macrophages Promotes Melanoma Progression and Metastasis
Authors: Marzia Scortegagna, Rabi Murad, Parinaz Bina, Yongmei Feng, Rebecca A. Porritt, Alexey V. Terskikh, Xiao Tian, Peter D. Adams, Kristiina Vuori, Ze'ev A. Ronai
Journal: Cancer Research (2025)

Abstract Aging is a known risk factor for melanoma, yet mechanisms underlying melanoma progression and metastasis in older populations remain largely unexplored. Aging might alter phenotypes of cells in the melanoma microenvironment, selecting for populations that support metastatic progression. Here, we demonstrated that age engenders the development of an immunosuppressive tumor microenvironment, which is linked to phenotypes associated with melanoma metastasis. Among cellular populations enriched by aging were macrophages with a tolerogenic phenotype expressing TREM2 and dysfunctional CD8+ T cells with an exhausted phenotype, while macrophages with a profibrotic phenotype expressing TREM1 were depleted. Notably, TREM1 inhibition decreased melanoma growth in young but not old mice, whereas TREM2 inhibition prevented lung metastasis in aged mice. These data identify age-related targets associated with melanoma metastasis and may guide aged-dependent immunotherapeutic strategies.
Hypertension and Atrial Fibrillation: A Frontier Review From the AF-SCREEN International Collaboration
Authors: Teemu J. Niiranen, Renate B. Schnabel, Aletta E. Schutte, Yitschak Biton, Giuseppe Boriani, Claire Buckley, Alan C. Cameron, Albertino Damasceno, Søren Z. Diederichsen, Wolfram Doehner, Yutao Guo, F.D. Richard Hobbs, Boyoung Joung, Graeme J. Hankey, Gregory Y.H. Lip, Trudie Lobban, Maja-Lisa Løchen, Georges Mairesse, Amam Mbakwem, Peter A. Noseworthy, George Ntaios, Steven Steinhubl, George Stergiou, Jesper Hastrup Svendsen, Robert G. Tieleman, Jiguang Wang, Neil R. Poulter, Jeff S. Healey, Ben Freedman
Journal: Circulation (2025)

Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in &gt;70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.
Rapid Intracranial Response With Tarlatamab in Patients With Untreated Brain Metastases From SCLC—A Real-World Case Series: Case Report
Authors: Bingnan Zhang, Komal B Shah, Mitchell Parma, Kaiwen Wang, Eric K Singhi, Whitney Lewis, Melvin Rivera, Mehmet Altan, Jenny Pozadzides, Xiuning Le, Natalie Vokes, Frank Fossella, Barbara O'Brien, Chenyang Wang, Martin C Tom, Thomas Beckham, Todd Swanson, Julianna Bronk, Steven H Lin, Maria Franco Vega, Joshua Jacome, Alexa Halliday, Marcelo Negrao, Jianjun Zhang, Don L Gibbons, John V Heymach, Lauren A Byers, Carl M Gay
Journal: Journal of Thoracic Oncology (2025)
Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis
Authors: Matija Zelic, Anna Blazier, Fabrizio Pontarelli, Michael LaMorte, Jeremy Huang, Ozge E Tasdemir-Yilmaz, Yi Ren, Sean K Ryan, Cynthia Shapiro, Caroline Morel, Pavithra Krishnaswami, Mikhail Levit, Disha Sood, Yao Chen, Joseph Gans, Xinyan Tang, Jennifer Hsiao-Nakamoto, Fen Huang, Bailin Zhang, James D Berry, Dinesh S Bangari, Giorgio Gaglia, Dimitry Ofengeim, Timothy R Hammond
Journal: Immunity (2025)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation is prominent in ALS, but the cell state dynamics and pathways driving disease remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords and identified altered glial cell states, including increased expression of inflammatory and glial activation markers. Many of these signals converged on the inflammation and cell death regulator receptor-interacting protein kinase 1 (RIPK1) and the necroptotic cell death pathway. In superoxide dismutase 1 (SOD1)G93A mice, blocking RIPK1 kinase activity delayed symptom onset and motor impairment and modulated glial responses. We used human induced pluripotent stem cell (iPSC)-derived motor neuron, astrocyte, and microglia tri-cultures to identify potential biomarkers that are secreted upon RIPK1 activation in vitro and modulated by RIPK1 inhibition in the cerebrospinal fluid (CSF) of people with ALS. These data reveal ALS-enriched glial populations associated with inflammation and suggest a deleterious role for neuroinflammatory signaling in ALS pathogenesis.
Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins
Authors: Jenna J Guthmiller, Linda Yu-Ling Lan, Lei Li, Yanbin Fu, Sean A Nelson, Carole Henry, Christopher T Stamper, Henry A Utset, Alec W Freyn, Julianna Han, Olivia Stovicek, Jiaolong Wang, Nai-Ying Zheng, Min Huang, Haley L Dugan, Micah E Tepora, Xueyong Zhu, Yao-Qing Chen, Anna-Karin E Palm, Dustin G Shaw, Madhumathi Loganathan, Benjamin F Francis, Jiayi Sun, Jordan Chervin, Chloe Troxell, Philip Meade, Nancy H L Leung, Sophie A Valkenburg, Sarah Cobey, Benjamin J Cowling, Ian A Wilson, Adolfo García-Sastre, Raffael Nachbagauer, Andrew B Ward, Lynda Coughlan, Florian Krammer, Patrick C Wilson
Journal: Immunity (2025)
Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results
Authors: Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hebraud, Cyrille Hulin, Marie-Christine Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jerome Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W.C.J. van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuilleme, Pieter Sonneveld
Journal: Blood (2025)

Previous results from CASSIOPEIA (NCT02541383) demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed multiple myeloma (NDMM). Here, we present long-term MRD status and PFS outcomes after an 80.1-month median follow-up. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were re-randomized to daratumumab maintenance or observation for £2 years. MRD status was assessed at pre-defined timepoints during each study phase. D-VTd improved overall MRD-negativity rates (10-5) post-induction (34.6% vs 23.1%; P&amp;lt;0.0001) and post-consolidation (63.7% vs 43.7%; P&amp;lt;0.0001) and provided PFS benefit, regardless of post-induction MRD status, versus VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation: 10-5, 77.3% vs 70.7% [P=0.0417]; 10-6, 60.7% vs 52.0% [P=0.0365]; VTd/daratumumab vs VTd/observation: 10-5, 70.9% vs 51.2% [P&amp;lt;0.0001]; 10-6, 48.4% vs 30.7% [P&amp;lt;0.0001]), and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or revised International Staging System score. Further, daratumumab maintenance provided PFS benefit versus observation, regardless of induction/consolidation treatment and post-consolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, accumulative, and sustained MRD-negativity rates (10-5 and 10-6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes.
Publisher Correction: EFFECT of daily antiseptic bathing with octenidine on ICU-acquired bacteremia and ICU-acquired multidrug-resistant organisms: a multicenter, cluster-randomized, double-blind, placebo-controlled, cross-over study
Authors: Tiffany Schaumburg, Norbert Köhler, Yasmine Breitenstein, Susanne Kolbe-Busch, Dirk Hasenclever, Iris F. Chaberny
Journal: Intensive Care Medicine (2025)
Immune cell metabolic dysfunction in Parkinson’s disease
Authors: Julian R. Mark, Malú Gámez Tansey
Journal: Molecular Neurodegeneration (2025)

Abstract Parkinson’s disease (PD) is a multi-system disorder characterized histopathologically by degeneration of dopaminergic neurons in the substantia nigra pars compacta . While the etiology of PD remains multifactorial and complex, growing evidence suggests that cellular metabolic dysfunction is a critical driver of neuronal death. Defects in cellular metabolism related to energy production, oxidative stress, metabolic organelle health, and protein homeostasis have been reported in both neurons and immune cells in PD. We propose that these factors act synergistically in immune cells to drive aberrant inflammation in both the CNS and the periphery in PD, contributing to a hostile inflammatory environment which renders certain subsets of neurons vulnerable to degeneration. This review highlights the overlap between established neuronal metabolic deficits in PD with emerging findings in central and peripheral immune cells. By discussing the rapidly expanding literature on immunometabolic dysfunction in PD, we aim to draw attention to potential biomarkers and facilitate future development of immunomodulatory strategies to prevent or delay the progression of PD.
2024 American Thoracic Society BEAR Cage Winning Proposal: Endothelial-targeted mRNA Lipid Nanoparticles for Acute Respiratory Distress Syndrome
Authors: Eno-Obong I. Essien
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"2024 American Thoracic Society BEAR Cage Winning Proposal: Endothelial-targeted mRNA Lipid Nanoparticles for Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Reversible reduction in brain myelin content upon marathon running
Authors: Pedro Ramos-Cabrer, Alberto Cabrera-Zubizarreta, Daniel Padro, Mario Matute-González, Alfredo Rodríguez-Antigüedad, Carlos Matute
Journal: Nature Metabolism (2025)

Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that the signal for myelin water fraction—a surrogate of myelin content—is substantially reduced upon marathon running in specific brain regions involved in motor coordination and sensory and emotional integration, but recovers within two months. These findings suggest that brain myelin content is temporarily and reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies that suggest that myelin lipids may act as glial energy reserves in extreme metabolic conditions. Using magnetic resonance imaging on marathon runners, Ramos-Cabrer, Cabrera-Zubizarreta et al. report that the signal detected as a surrogate of myelin content is significantly reduced after exercise, but fully recovered within two months.
GULP1, A Multifaceted Diagnostic Biomarker and Potential Therapeutic Target in Hepatocellular Carcinoma: Editorial on “GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma”
Authors: Yuhao Xie, Lu-Qi Cao, John Wurpel, Zhe-Sheng Chen
Journal: Clinical and Molecular Hepatology (2025)

GULP1, A Multifaceted Diagnostic Biomarker and Potential Therapeutic Target in Hepatocellular Carcinoma: Editorial on "GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma"
Prediction and Prognostication of Acute Graft‐Versus‐Host Disease by <scp>MAGIC</scp> Biomarkers
Authors: John E. Levine
Journal: American Journal of Hematology (2025)

ABSTRACT Recent advancements in prophylaxis for acute graft‐versus‐host disease (GVHD) have successfully reduced the incidence of severe cases; however, overall survival rates have not significantly improved, and GVHD continues to be a major cause of mortality. The severity of gastrointestinal (GI) damage is especially critical, as it strongly correlates with treatment failure and non‐relapse mortality, but clinical symptoms do not reliably predict peak severity in its early stages. Biomarker‐based algorithms, such as the Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm, leverage serum levels of GI GVHD biomarkers (ST2 and REG3α) to quantify intestinal crypt damage, providing more accurate predictions of GVHD outcomes compared to clinical assessments. Clinical trials have investigated the use of biomarkers as entry criteria for treatment, with notable success in guiding treatment de‐escalation, which is increasingly important as the presentation of GVHD shifts towards milder forms. The recently developed MAGIC composite scores further enhance prediction accuracy by integrating clinical symptom severity with biomarker assessments. Future clinical trials that employ these composite scores or similar algorithms are anticipated to be more efficient by identifying patients who are most likely to benefit from specific therapies and ultimately improving the management of GVHD.
Deciphering the spatial tumor microenvironment in intrahepatic cholangiocarcinoma
Authors: Rocio I.R. Macias, Stephanie Roessler, Monique M.A. Verstegen
Journal: Hepatology (2025)

1Laboratory of Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, National Institute for the Study of Liver and Gastrointestinal Diseases (CIBEREHD), IBSAL, Salamanca, Spain 2Institute of Pathology, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany 3Department of Surgery, Erasmus MC Transplantation Institute, University Medical Center Rotterdam, Rotterdam, Netherlands Abbreviations: CAF, cancer associated fibroblast; CK, cytokeratin; FFPE, formalin-fixed paraffin-embedded; HAIC, hepatic arterial infusion chemotherapy; HBV; hepatitis B virus; iCCA, intrahepatic cholangiocarcinoma; ICIs, immune checkpoint inhibitors; TLS, tertiary lymphoid structures; TME, tumor microenvironment. Correspondence Rocio I.R. Macias, Campus M. Unamuno, Edificio Departamental, Lab. B-17 University of Salamanca, 37007, Salamanca, Spain. Email: [email protected]
Erratum: HDV RNA assays: Performance characteristics, clinical utility, and challenges
Authors: Heiner Wedemeyer, Mitchell Leus, Thomas R. Battersby, Jeffrey Glenn, Emmanuel Gordien, Saleem Kamili, Hema Kapoor, Harald H. Kessler, Oliver Lenz, Marc Lütgehetmann, Tonya Mixson-Hayden, Christian O. Simon, Michael Thomson, Gabriel Westman, Veronica Miller, Norah Terrault, Pietro Lampertico
Journal: Hepatology (2025)
SLC3A2-Mediated Lysine Uptake by Cancer Cells Restricts T cell Activity in Hepatocellular Carcinoma
Authors: Yating Chang, Naizhen Wang, Shaopeng Li, Jiaqi Zhang, Yipeng Rao, Zilong Xu, Lu Li, Hongning Wu, Jun Chen, Yanhua Lin, Xiaoxuan Huang, Pingguo Liu, Jun Zhang, Yueting Liao, Chaolong Lin, Chenghao Huang, Ningshao Xia
Journal: Cancer Research (2025)

Abstract Abnormal amino acid metabolism supports cancer cell proliferation, invasion, and immune evasion in hepatocellular carcinoma (HCC). Previous research exploring amino acid metabolism in HCC has primarily focused on how metabolic reprogramming impacts tumor cells. Here, we focused on the role of amino acid metabolism dysregulation in the crosstalk between HCC and T cells. HCC cells disrupted lysine uptake in T cells, leading to impaired T cell immunity. Lysine deprivation decreased STAT3 levels in T cells, inhibiting T cell proliferation and effector function and ultimately promoting tumor progression. Mechanistically, HCC cells outcompeted T cells for lysine by expressing high levels of the lysine transporter SLC3A2. Clinically, elevated SLC3A2 expression correlated with poor survival and was linked to dysregulated T cell functional gene signatures in HCC patients. Furthermore, the multikinase inhibitor lenvatinib induced a c-Myc-SLC3A2 regulatory axis that limited the efficacy of lenvatinib treatment. Lysine supplementation enhanced tumor sensitivity to combined treatment with lenvatinib and anti-PD-1 immunotherapy. These findings suggest that lysine supplementation is a potential therapeutic strategy for treating HCC and enhancing the sensitivity of HCC to tyrosine kinase inhibitors and immune checkpoint blockade.
An Anti-EGFR Antibody-Drug Radioconjugate Labeled with Actinium-225 Elicits Durable Anti-Tumor Responses in KRAS and BRAF Mutant Colorectal Cancer
Authors: Anjong Florence Tikum, Nikita W. Henning, Jessica Pougoue Ketchemen, Alireza Doroudi, Hanan Babeker, Fabrice Ngoh Njotu, Emmanuel Nwangele, Alissar Monzer, Bridget Gray, Emina Torlakovic, Maruti Uppalapati, Humphrey Fonge
Journal: Cancer Research (2025)

Abstract Epidermal growth factor receptor (EGFR) is expressed in approximately 80-85% of colorectal cancer (CRC). While anti-EGFR antibodies benefit some CRC patients, tumors with kirsten rat sarcoma (KRAS) or B-rapidly accelerated fibrosarcoma (BRAF), a proto-oncogene serine/threonine protein kinase mutations are resistant. Here, we developed a theranostic approach that uses an anti-EGFR antibody-drug conjugate labeled with either [225Ac]Ac or [89Zr]Zr and evaluated the strategy against KRAS and BRAF mutant EGFR-positive CRC models. The antibody-drug radioconjugate [225Ac]Ac-macropa-nimotuzumab-PEG6-DM1 showed enhanced in vitro cytotoxicity compared to the unlabeled antibody-drug conjugate nimotuzumab-PEG6-DM1. [225Ac]Ac-macropa-nimotuzumab-PEG6-DM1 extended the survival of mice bearing all tested xenografts compared to untreated and nimotuzumab-PEG6-DM1 treated controls. For the BRAFV600E mutant xenograft, the median survival was not reached following treatment with [225Ac]Ac-macropa-nimotuzumab-PEG6-DM1, while it was 24.5 and 39 days for the saline and nimotuzumab-PEG6-DM1 treated groups, respectively. PET imaging using the non-overlapping anti-EGFR radioimmunoconjugate [89Zr]Zr-DFO-matuzumab before and after treatment of orthotopic CRC xenografts showed that 1/5 mice from the treatment group had complete remission while metastatic spread was prevented in the other mice (4/5). These results show that treatment with [225Ac]Ac-macropa-nimotuzumab-PEG6-DM1 is a potential therapeutic approach for KRAS mutant and BRAFV600E mutant metastatic CRC.
A Genome-Wide Synthetic Lethal Screen Identifies Spermidine Synthase as a Target to Enhance Erdafitinib Efficacy in FGFR-Mutant Bladder Cancer
Authors: Yanchao Yu, Xincheng Gao, Huayuan Zhao, Jiayin Sun, Miao Wang, Xing Xiong, Junping Li, Chao Huang, Hui Zhang, Guosong Jiang, Xingyuan Xiao
Journal: Cancer Research (2025)

Abstract Mutations of the fibroblast growth factor receptor (FGFR) family members are frequently observed in metastatic bladder cancer. The development of erdafitinib, a pan-FGFR inhibitor, provided a significant therapeutic advance in bladder cancer, but resistance still limits its efficacy. In this study, we performed an unbiased whole-genome CRISPR-Cas9 synthetic lethal screen on FGFR-mutant bladder cancer cell lines treated with erdafitinib and identified spermidine synthase (SRM) as a critical contributor to erdafitinib resistance. Moreover, hypusinated eIF5A, catalyzed by SRM-mediated spermidine production, facilitated the efficient translation of HMGA2, which in turn promoted the expression of EGFR. Notably, pharmacologic inhibition of SRM enhanced the efficacy of erdafitinib both in vitro and in vivo. Together, these results offer evidence that targeting SRM could attenuate the translation of HMGA2 and subsequently reduce EGFR transcription, thus enhancing the sensitivity of FGFR-mutant bladder cancer cells to erdafitinib treatment.
Poly-lysine-modified recombinant protein nanocages for effective delivery of small activating RNA
Authors: Lixing Xu, Shanshan Li, Shen Wan, Zhikuan Liu, Yuxin Zhong, Xiaoyang Qian, Jiayi Qin, Liangliang Cai, Haiqin Huang
Journal: Journal of Controlled Release (2025)
Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging
Authors: Wenchuan Zhang, Chenxuan Huang, Haiyang Yao, Shangzhi Yang, Zeyidan Jiapaer, Juan Song, Xianli Wang
Journal: Translational Neurodegeneration (2025)

Abstract Neurological disorders present considerable challenges in diagnosis and treatment due to their complex and diverse etiology. Retrotransposons are a type of mobile genetic element that are increasingly revealed to play a role in these diseases. This review provides a detailed overview of recent developments in the study of retrotransposons in neurodevelopment, neuroaging, and neurological diseases. Retrotransposons, including long interspersed nuclear elements-1, Alu, SINE-VNTR-Alu, and endogenous retrovirus, play important regulatory roles in the development and aging of the nervous system. They have also been implicated in the pathological processes of several neurological diseases, including Alzheimer's disease, X-linked dystonia-parkinsonism, amyotrophic lateral sclerosis, autism spectrum disorder, and schizophrenia. Retrotransposons provide a new perspective for understanding the molecular mechanisms underlying neurological diseases and provide insights into diagnostic and therapeutic strategies of these diseases.