tbuckley/cabot-search huggingface dataset:
The Updated Genome Warehouse: Enhancing Data Value, Security, and Usability to Address Data Expansion
Authors: Yingke Ma, Xuetong Zhao, Yaokai Jia, Zhenxian Han, Caixia Yu, Zhuojing Fan, Zhang Zhang, Jingfa Xiao, Wenming Zhao, Yiming Bao, Meili Chen
Journal: Genomics Proteomics & Bioinformatics (2025)

The Genome Warehouse (GWH), accessible at https://ngdc.cncb.ac.cn/gwh, is an extensively utilized public repository dedicated to the deposition, management and sharing of genome assembly sequences, annotations, and metadata. This paper highlights noteworthy enhancements to the GWH since the 2021 version, emphasizing substantial advancements in web interfaces for data submission, database functionality updates, and resource integration. Key updates include the reannotation of released prokaryotic genomes, mirroring of genome resources from National Center for Biotechnology Information (NCBI) GenBank and Reference Sequence Database (RefSeq), integration of Poxviridae sequences, implementation of an online batch submission system, enhancements to the quality control system, advanced search capabilities, and the introduction of a controlled-access mechanism for human genome data. These improvements collectively augment the ease and security of data submission and access as well as genome data value, thereby fostering heightened convenience and utility for researchers in the genomics field.
Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graft-versus-host disease
Authors: Julie R Boiko, Kathleen S. Ensbey, Olivia G Waltner, Isaac C Jenkins, Shruti S Bhise, Kelli PA MacDonald, Bruce R Blazar, Anne Marcie Hall, Ted A Gooley, Simone A Minnie, Stephanie J. Lee, Scott N Furlan, Geoffrey R Hill
Journal: Blood (2025)
Surface pTα expression predicts LCK activation and preclinical synergy of LCK and JAK coinhibition in adult T-ALL
Authors: Lucien Courtois, Antoine Pinton, Aurelie Cabannes-Hamy, Mathieu Simonin, Guillaume P. Andrieu, Mélodie Queri, Charlotte Smith, Guillaume Charbonnier, Marie-Emilie Dourthe, Marianne Courgeon, Grégoire Huré, Nicolas Gaidot, Elizabeth A. Macintyre, Hervé Dombret, André Baruchel, Nicolas Boissel, Aurore Touzart, Ludovic Lhermitte, Philippe Rousselot, Vahid Asnafi
Journal: Blood (2025)
Host-Calibrated Time Tree Caps the Age of Giant Viruses
Authors: Hwee Sze Tee, Chuan Ku
Journal: Molecular Biology and Evolution (2025)

Abstract Viruses are widespread parasites with important impacts on public health, economy, and ecosystems. However, little is known about their origins, ages, and early evolutionary relationships with hosts. Here, we infer the maximum divergence times for eukaryotic giant DNA viruses (phylum Nucleocytoviricota) with dating analyses calibrated by host taxon ages of virus lineages with specific host ranges. The last common ancestor of Nucleocytoviricota existed after 1,000 million years ago, suggesting a much later origin than that of the eukaryotes. The early evolution of Nucleocytoviricota either coincided with or postdated a substantial increase in the oxygen levels on the Earth's surface during the Neoproterozoic Era. The lineage diversification of giant viruses was frequently associated with host shifts, including two major transitions from amoebozoan hosts to animal hosts that eventually led to the emergence of iridoviruses and African swine fever viruses within the last 450 million years. These results outline the evolutionary timescale of a major virus group and are pivotal for further understanding the virus–host interactions and their potential ecological roles in the Earth's history.
Skin mutation burden drives adaptive immunity and response to immunotherapy
Authors: Timothy Looney
Journal: Journal for ImmunoTherapy of Cancer (2025)

Numerous studies over the past century have reported an inverse correlation between lifetime solar ultraviolet radiation (UV) exposure and all-cancer incidence and mortality. For decades, this relationship was hypothesized to reflect the action of photosynthesized vitamin D, though subsequent clinical trials have failed to demonstrate the expected anti-cancer properties. Rather than a consequence of vitamin D, I hypothesize that this inverse correlation reflects the immune stimulatory action of UV-derived skin neoantigens. Over time, such UV-mediated immune education drives immune repertoire diversification and superior adaptive immune responses to infectious disease and cancer. This hypothesis would explain the strong positive selection for light skin pigmentation following the out-of-Africa migration among humans inhabiting northerly latitude regions, and the longstanding racial disparities in cancer and infectious disease observed in North America. It suggests that the skin comprises an important reservoir of anti-cancer T cells that may be harnessed for anti-cancer therapy, and that skin mutation burden (SMB) may serve as a predictive biomarker of immunotherapy response. I propose a novel, non-invasive method for quantifying SMB as a biomarker.
Corticosteroid premedication on anti-tumor effect of immune checkpoint blockade in murine hepatocellular carcinoma models
Authors: Ying-Chun Shen, Nai-Wen Chang, Ching-Ping Yeh, Wan-Ying Lin, Ming-Feng Wei, Da-Liang Ou, Chia-Lang Hsu, Ann-Lii Cheng
Journal: Journal for ImmunoTherapy of Cancer (2025)

Corticosteroid is effective in alleviating immune-related adverse events (irAEs) of immune checkpoint blockade (ICB). However, prophylactic use of corticosteroid to prevent irAEs is not recommended due to a looming concern that it may attenuate anti-tumor effect of ICB. This study aims to investigate whether corticosteroid premedication may compromise anti-tumor efficacy of dual ICB, a regimen that may cause significant irAEs. Orthotopic BNL 1MEA.7R.1 and subcutaneous Hepa1-6 syngeneic hepatocellular carcinoma (HCC) models were used. Low-dose (LD; 10 µg) or high-dose (HD; 200 µg) dexamethasone (Dexa) was intraperitoneally administered before each dose of anti-CTLA-4 and anti-PD-1. Tumor shrinkage, T cell priming, cytokine quantitation, as well as cytotoxicity and single-cell RNA-sequencing (scRNA-seq) of tumor-infiltrating T cells were assessed. In the orthotopic model, dual immune checkpoint blockade (dICB) plus phosphate buffered saline (PBS) significantly reduced the mean tumor weight (adjusted for SE) (0.73±0.18 g vs 2.45±0.54 g; p=0.03), while neither LD nor HD Dexa premedication affected dICB-induced tumor shrinkage. In the subcutaneous model, dICB plus PBS or LD Dexa yielded a complete tumor response (CR) rate of 100%, while dICB plus HD Dexa yielded a CR rate of 85.7% (p>0.05, comparing to dICB plus PBS). ScRNA-seq analysis demonstrates that Dexa did not affect dICB-induced reduction of major clusters of exhausted CD4+ and CD8+ T cells but halved dICB-induced expansion of effector memory CD8+ T cells. Nevertheless, Dexa premedication, regardless of dosage, did not diminish dICB-induced T cell priming, cytokine production, or cytotoxicity of tumor-infiltrating CD8+ T cells. Corticosteroid premedication does not significantly compromise anti-tumor efficacy of dICB treatment in murine HCC models. These results suggest that clinical investigations of prophylactic corticosteroids to alleviate severe irAEs may be feasible.
Phase I dose-escalation and pharmacodynamic study of STING agonist E7766 in advanced solid tumors
Authors: Jason J Luke, David J Pinato, Dejan Juric, Patricia LoRusso, Peter J Hosein, Anupam M Desai, Robert Haddad, María de Miguel, Andrés Cervantes, Won Seog Kim, Aurélien Marabelle, Yan Zhang, Yuanxin Rong, Xiaobin Yuan, Stéphane Champiat
Journal: Journal for ImmunoTherapy of Cancer (2025)

E7766 is a novel stimulator of interferon genes (STING) agonist, capable of potent activation of immune cells and generating strong antitumor response in preclinical murine tumor models. Here we present the safety, efficacy, and biomarker results of the first-in-human phase I/Ib study of intratumoral E7766 in patients with advanced solid tumors. Eligible patients with relapsing/refractory cancers (n=24) were enrolled in dose-escalating cohorts to receive intratumoral injections of E7766 from 75 to 1000 µg. The most frequent treatment-related treatment-emergent adverse events were chills (50.0%; 85.7%), fever (40.0%; 85.7%), and fatigue (30.0%; 35.7%) in patients who received non-visceral and visceral injections, respectively. Eight patients (33.3%) achieved stable disease as their best response per modified Response Evaluation Criteria In Solid Tumors version 1.1 with variability between injected and non-injected lesions. Plasma levels of IFN-α, IFN-β, IFN-γ, TNF-α, IL-6, IP-10, MCP1, and MIP1b transiently increased in all evaluable patients within 10 hours postinjection, then dropped to baseline levels. Levels of blood and tumor gene expression increased in most interferon-related and STING genes tested. Further increases in programmed death ligand 1 and cluster of differentiation 8 expression at both the RNA and protein levels were also observed in some patients across dose levels. In total, E7766 generated on-target pharmacodynamic effects in patients with solid tumors. Further exploration in a homogeneous patient population is necessary to assess efficacy.
Ethanol inhibits the growth and metastasis of hepatocellular carcinoma by inducing immunogenic cell death
Authors: Yu-Chen Hsu, Meng-Chuan Wu, Meng Tzu Weng, Ying-Te Lee, Huei-Chi Chou, Hsuan-Shu Lee, Li-Fang Wang, Jin-Chuan Sheu, Chien-Hung Chen
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immunogenic cell death (ICD) can elicit an adaptive immune response with significant antitumor effects. Percutaneous ethanol injection therapy has been applied as tumor ablation for small hepatocellular carcinoma (HCC). However, it was not clear whether ethanol can elicit ICD. The aim of this study is to investigate the role of ethanol as an ICD inducer. HCC cell lines were treated with low-concentration ethanol and ICD markers, such as calreticulin, high-mobility group box 1, and ATP were assayed. The mouse vaccination-rechallenge assay was used to further confirm ethanol as an ICD inducer. Western blot and real-time PCR were used to investigate ICD-related endoplasmic reticulum (ER) stress and signaling pathways. The genes with differential expression levels between primary and distant tumors were analyzed by nCounter gene expression. Intratumoral injection of ethanol was done to investigate the abscopal effect. The low-concentration ethanol could induce ICD in HCC cell lines through unfolded protein responses initiated by ER stress and multiple cell-death pathways. Intratumoral injections of low-concentration ethanol had significantly direct and abscopal antitumor effects in mouse models of both subcutaneous and orthotopic HCC. nCounter gene expression analysis in primary and distant tumors revealed the activation of various immune-response pathways, notably those mediated by CD8 T cells and the interferon pathway. Vaccinating mice with low-concentration ethanol-treated HCC cells successfully inhibited metastasis in both intravenous and intrasplenic metastasis models. Our results suggest that low-concentration ethanol could serve as an inducer of ICD. Low-concentration ethanol could potentially improve therapeutic antitumor immunity by inducing substantial ICD.
The association between sleep quality and telomere attrition: a systematic review and meta-analysis comprising 400,212 participants
Authors: Arina Jocelyn Fostitsch, Guido Schwarzer, Maria Buchgeister, Werner Surbeck, Claas Lahmann, Kai Spiegelhalder, Lukas Frase, Derek Spieler
Journal: Sleep Medicine Reviews (2025)

Psychosocial stressors accelerate telomere attrition, a biomarker of cell aging, whereas good sleep is hypothesized to be a mitigating factor. However, methodological aspects - particularly underpowered studies, inconsistent findings, and multiple approaches to assessing sleep - demonstrate the need for a meta-analysis. After PROSPERO registration, we conducted a systematical search of the following databases until June 2024 to identify studies examining the relationship between sleep quality and telomere length in adult humans: CINAHL, Cochrane Library, MEDLINE, PsychINFO, PubMed, Web of Science, and Google Scholar. In total, 29 studies met inclusion criteria for the systematic review according to the preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA), 19 of which provided data that was appropriate for meta-analytic calculations. We identified the Pittsburgh sleep quality index (PSQI) global score (odds ratio (OR) 1.24, CI 95 % [1.03; 1.50], p = 0.02), sleep-related daytime impairments (OR 1.01 [1.00; 1.02], p = 0.04), and wake after sleep onset (WASO) time (OR 1.28 [1.12; 1.47], p < 0.01) as to be significantly associated with telomere attrition. Thus, the subtle telomere attrition-mitigating role of sleep has been demonstrated based on a sufficiently large body of data and defined aspects of sleep quality.
Biomarkers, Omics and Artificial Intelligence for Early Detection of Pancreatic Cancer.
Authors: Kate Murray, Lucy Oldfield, Irena Stefanova, Manuel Gentiluomo, Paolo Aretini, Rachel O'Sullivan, William Greenhalf, Salvatore Paiella, Mateus N Aoki, Aldo Pastore, James Birch-Ford, Bhavana Hemantha Rao, Pinar Uysal-Onganer, Caoimhe M Walsh, George B Hanna, Jagriti Narang, Pradakshina Sharma, Daniele Campa, Cosmeri Rizzato, Andrei Turtoi, Elif Arik Sever, Alessio Felici, Ceren Sucularli, Giulia Peduzzi, Elif Öz, Osman Uğur Sezerman, Robert Van der Meer, Nathan Thompson, Eithne Costello
Journal: Seminars in Cancer Biology (2025)
Quantifying the relative intensity of free-living physical activity: differences across age, association with mortality and clinical interpretation—an observational study
Authors: Alex V Rowlands, Mark W Orme, Benjamin D Maylor, Andrew P Kingsnorth, Joe Henson, Jonathan Goldney, Melanie Davies, Cameron Razieh, Kamlesh Khunti, Francesco Zaccardi, Thomas Yates
Journal: British Journal of Sports Medicine (2025)

To describe age-related differences in the absolute and relative intensity of physical activity (PA) and associations with mortality. UK Biobank participants with accelerometer-assessed PA (mg) and fitness data (N=11 463; age: 43-76 years) were included. The intensity distribution of PA was expressed in absolute and relative terms. The outcome was mortality. PA volume (average acceleration) and absolute intensity were lower with increasing age (~-0.03 to -0.04 SD of mean value across all ages per year; p<0.001) but differences in relative intensity by age were markedly smaller in women (-0.003 SD; p<0.184) and men (-0.012 SD; p<0.001). Absolute intensity was higher in men, but relative intensity higher in women (p<0.001). Over a median (IQR) follow-up of 8.1 (7.5-8.6) years, 121 (2.4 per 1000-person-years) deaths occurred in women and 203 (5.0 per 1000-person-years) in men. Lower risk of mortality was observed for increasing absolute or relative intensity in women, but for absolute intensity only in men. In men, the lowest risk (HR 0.62, 95% CI 0.43, 0.91) was observed in those with high absolute intensity (80th centile), but low relative intensity (20th centile). Conversely, in women, the lowest risk was associated with high levels (80th centile) of both absolute and relative intensity (HR 0.59, 95% CI 0.41, 0.86). Absolute PA intensity dropped with age, while relative intensity was fairly stable. Associations between PA intensity and mortality suggest that prescribing intensity in absolute terms appears appropriate for men, while either absolute or relative terms may be appropriate for women.
Depression, reduced physical activity and the risk of heart disease: a prospective cohort of European middle-aged and older adults
Authors: Miguel Peralta, Marcelo Nascimento, Gerson Ferrari, Élvio R Gouveia, Adilson Marques
Journal: British Journal of Sports Medicine (2025)

To assess the impact of depression and physical activity (PA) of different intensities on the incidence of heart disease. A prospective cohort study with 20 645 European middle-aged and older adults (mean baseline age 63 years; 55.1% women; median follow-up 9.5 years) was conducted using data from the Survey of Health, Ageing and Retirement in Europe. The EURO-D 12-item scale assessed depression. Moderate-intensity and vigorous-intensity PA and heart disease diagnoses were self-reported. We classified participants into the following four groups: (1) depression plus low PA, (2) no depression plus low PA, (3) depression plus moderate/high PA, (4) no depression plus moderate/high PA. Hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazards models adjusted for confounders. Compared with having depression and low PA levels, adjusted HR for heart disease similarly decreased for participants with depression and moderate/high PA (moderate-intensity PA: HR=0.63, 95% CI=0.50, 0.78; vigorous-intensity PA: HR=0.69, 95% CI=0.53, 0.89) and participants without depression and low PA (moderate-intensity PA: HR=0.64, 95% CI=0.50, 0.82; vigorous-intensity PA: HR=0.68, 95% CI=0.58, 0.80). The greatest risk reduction was found in participants without depression and moderate/high PA (moderate-intensity PA: HR=0.46, 95% CI=0.37, 0.55; vigorous-intensity PA: HR=0.48, 95% CI=0.40, 0.58). Moderate-intensity and vigorous-intensity PA seems to counteract the increased risk for heart disease associated with depression. This highlights the importance of PA as a possible intervention strategy aiming to manage the risk of heart disease among people with depression.
Reaffirming the JAMA Network Commitment to the Health of Patients and the Public
Authors: Kirsten Bibbins-Domingo, Robert O. Bonow, Neil M. Bressler, Linda Brubaker, Dimitri Christakis, Stacy L. Christiansen, Gregory Curfman, Mary L. (Nora) Disis, Annette Flanagin, Sandro Galea, Sharon K. Inouye, S. Andrew Josephson, Melina R. Kibbe, Tracy A. Lieu, Preeti N. Malani, Mary M. McDermott, Christopher C. Muth, Dost Öngür, Hannah Park, Jay F. Piccirillo, Eli N. Perencevich, Joseph S. Ross, Kanade Shinkai, Kristin L. Walter
Journal: JAMA (2025)
Author Correction: Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells
Authors: Dorsa Toghani, Sanika Gupte, Sharon Zeng, Elmir Mahammadov, Edie I. Crosse, Negar Seyedhassantehrani, Christian Burns, David Gravano, Stefan Radtke, Hans-Peter Kiem, Sonia Rodriguez, Nadia Carlesso, Amogh Pradeep, Alexis Georgiades, Fabienne Lucas, Nicola K. Wilson, Sarah J. Kinston, Berthold Göttgens, Le Zong, Isabel Beerman, Bongsoo Park, Derek H. Janssens, Daniel Jones, Ali Toghani, Claus Nerlov, Eric M. Pietras, Marion Mesnieres, Christa Maes, Atsushi Kumanogoh, Thomas Worzfeld, Jin-Gyu Cheong, Steven Z. Josefowicz, Peter Kharchenko, David T. Scadden, Antonio Scialdone, Joel A. Spencer, Lev Silberstein
Journal: Nature Aging (2025)
METTL3-catalyzed m6A methylation facilitates the contribution of vascular smooth muscle cells to atherosclerosis
Authors: Zhigang Dong, Yourong Jin, Yicong Shen, Jiaqi Huang, Jiaai Tan, Qianqian Feng, Ze Gong, Shirong Zhu, Huiyue Chen, Fang Yu, Wei Li, Yiting Jia, Wei Kong, Yi Fu
Journal: Cardiovascular Research (2025)

Vascular smooth muscle cells (VSMCs) are involved in the etiology of atherosclerosis, but whether methyltransferase-like 3 (METTL3)-catalyzed N6-methyladenosine (m6A) modulates the contribution of VSMCs to atherosclerosis remains elusive. We generated tamoxifen-inducible VSMC-specific METTL3 knockout mice with VSMC lineage tracing, and found that VSMC-specific METTL3 deficiency substantially attenuated atherosclerosis and reduced the proportion of VSMCs in plaques, due to the inhibition of VSMC atheroprone phenotype as characterized by macrophage-like and inflammatory features as well as high migratory and proliferative capacity. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with polysome profiling analysis mechanistically displayed METTL3 catalyzed m6A methylation of myocardin-related transcription factor A (MRTFA) mRNA, and further enhanced YTH N6-methyladenosine RNA binding protein F3 (YTHDF3)-dependent MRTFA mRNA translation. Conversely, adenovirus or adeno-associated virus-mediated VSMC-specific MRTFA overexpression abolished METTL3 deficiency-mediated alleviation of VSMC atheroprone phenotypic switching and atherosclerotic progression both in vitro and in vivo. METTL3 facilitated the contribution of VSMCs to atherosclerosis through the m6A-YTHDF3-dependent MRTFA mRNA translation enhancement.
Author Correction: Pangenome graphs and their applications in biodiversity genomics
Authors: Simona Secomandi, Guido Roberto Gallo, Riccardo Rossi, Carlos Rodríguez Fernandes, Erich D. Jarvis, Andrea Bonisoli-Alquati, Luca Gianfranceschi, Giulio Formenti
Journal: Nature Genetics (2025)
Strategies to Prevent Hemodialysis Catheter Dysfunction
Authors: Benjamin Lazarus, Charmaine E. Lok, Louise Moist, Kevan R. Polkinghorne
Journal: Journal of the American Society of Nephrology (2025)

Millions of patients with kidney failure rely on hemodialysis (HD) central venous catheters (CVC) for their life-sustaining dialysis treatments. CVC dysfunction necessitates removal of up to 20% of CVCs and is an important problem for patients with kidney failure. Thrombosis and fibrin sheath formation are the most common mechanisms of CVC dysfunction beyond the first week after insertion. Factors such as female sex, left-sided CVC placement and prior CVC dysfunction increase the risk of dysfunction. Patient specific factors contribute substantially to variation in the number of CVC dysfunction events. Weekly thrombolytic locks have been shown to improve CVC blood flow rates, prevent infection and reduce dysfunction requiring removal. However, routine administration may not be cost-effective in HD units with low infection rates, and targeted use among patients with established CVC dysfunction has not been studied. Concentrated heparin lock (e.g., 5000 vs. 1000 IU/ml) have been associated with lower requirements for therapeutic CVC thrombolysis but increased systemic bleeding risks and costs. Citrate 4% was non-inferior to standard heparin locks to prevent thrombosis, may cause less bleeding, and is less costly in some countries. Tunneled CVCs with a symmetrical tip have been associated with a lower risk of CVC dysfunction compared to those with a step tip. Multifaceted CVC care interventions can reduce the incidence of dysfunctional CVCs by 33% compared to usual care. Future research to identify patients at high risk of CVC dysfunction will inform individualized vascular access plans, targeted use of preventive strategies, and enrolment criteria for future clinical trials.