tbuckley/cabot-search huggingface dataset:
Education Levels and Poststroke Cognitive Trajectories
Authors: Mellanie V. Springer, Rachael T. Whitney, Wen Ye, Emily M. Briceño, Alden L. Gross, Hugo J. Aparicio, Alexa S. Beiser, James F. Burke, Mitchell S. V. Elkind, Rebecca A. Ferber, Bruno Giordani, Rebecca F. Gottesman, Rodney A. Hayward, Virginia J. Howard, Adam S. Kollipara, Silvia Koton, Ronald M. Lazar, W. T. Longstreth, Sarah T. Pendlebury, Jeremy B. Sussman, Evan L. Thacker, Deborah A. Levine
Journal: JAMA Network Open (2025)

Importance Acute stroke is associated with accelerated, years-long cognitive decline. Whether education levels are associated with faster cognitive decline after stroke is unclear. Objective To evaluate the association of education level with poststroke cognitive decline and to determine whether age at stroke modifies the association. Design, Setting, and Participants Individual participant data meta-analysis of 4 US cohort studies (January 1971 to December 2019). Analysis began August 2022 and was completed in January 2024. Exposures Education level (less than high school, completed high school, some college, and college graduate). Main Outcomes and Measures Harmonized cognitive outcomes were global cognition (primary outcome), memory, and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition, with higher score representing better function. Linear mixed-effect models estimated the trajectory of cognitive decline after incident stroke. Results The analysis included 2019 initially dementia-free stroke survivors (1048 female [51.9%]; median [IQR] age at stroke, 74.8 [69.0-80.4] years; 339 with less than a high school education [16.7%]; 613 who completed high school [30.4%]; 484 with some college [24.0%]; 583 with a college degree or higher [28.9%]). Median (IQR) follow-up time after stroke was 4.1 (1.8-7.2) years. Compared with those with less than a high school degree, college graduates had higher initial poststroke performance in global cognition (1.09 points higher; 95% CI, 0.02 to 2.17 points higher), executive function (1.81 points higher; 95%CI, 0.38 to 3.24 points higher), and memory (0.99 points higher; 95% CI, 0.02 to 1.96 points higher). Compared with stroke survivors with less than a high school education, there was a faster decline in executive function among college graduates (−0.44 points/y faster; 95% CI, −0.69 to −0.18 points/y faster) and those with some college education(−0.30 points/y faster; 95% CI, −0.57 to −0.03 points/y faster). Education level was not associated with declines in global cognition or memory. Age did not modify the association of education with cognitive decline. Conclusions and Relevance In this pooled cohort study, the trajectory of cognitive decline after stroke varied by education level and cognitive domain, suggesting that stroke survivors with a higher education level may have greater cognitive reserve but steeper decline in executive function than those with a lower education level.
Author Correction: Combining different CRISPR nucleases for simultaneous knock-in and base editing prevents translocations in multiplex-edited CAR T cells
Authors: Viktor Glaser, Christian Flugel, Jonas Kath, Weijie Du, Vanessa Drosdek, Clemens Franke, Maik Stein, Axel Pruß, Michael Schmueck-Henneresse, Hans-Dieter Volk, Petra Reinke, Dimitrios L. Wagner
Journal: Genome biology (2025)
STRchive: a dynamic resource detailing population-level and locus-specific insights at tandem repeat disease loci
Authors: Laurel Hiatt, Ben Weisburd, Egor Dolzhenko, Vincent Rubinetti, Akshay K. Avvaru, Grace E. VanNoy, Nehir Edibe Kurtas, Heidi L. Rehm, Aaron R. Quinlan, Harriet Dashnow
Journal: Genome Medicine (2025)

Abstract Approximately 8% of the human genome consists of repetitive elements called tandem repeats (TRs): short tandem repeats (STRs) of 1–6 bp motifs and variable number tandem repeats (VNTRs) of 7 + bp motifs. TR variants contribute to several dozen monogenic diseases but remain understudied and enigmatic. It remains comparatively challenging to interpret the clinical significance of TR variants, particularly relative to single nucleotide variants. We present STRchive ( http://strchive.org/ ), a dynamic resource consolidating information on TR disease loci from the research literature, up-to-date clinical resources, and large-scale genomic databases, streamlining TR variant interpretation at disease-associated loci.
The genome and GeneBank genomics of allotetraploid Nicotiana tabacum provide insights into genome evolution and complex trait regulation
Authors: Yanjun Zan, Shuai Chen, Min Ren, Guoxiang Liu, Yutong Liu, Yu Han, Yang Dong, Yao Zhang, Huan Si, Zhengwen Liu, Dan Liu, Xingwei Zhang, Ying Tong, Yuan Li, Caihong Jiang, Liuying Wen, Zhiliang Xiao, Yangyang Sun, Ruimei Geng, Yan Ji, Quanfu Feng, Yuanying Wang, Guoyou Ye, Lingzhao Fang, Yong Chen, Lirui Cheng, Aiguo Yang
Journal: Nature Genetics (2025)

Nicotiana tabacum is an allotetraploid hybrid of Nicotiana sylvestris and Nicotiana tomentosiformis and a model organism in genetics. However, features of subgenome evolution, expression coordination, genetic diversity and complex traits regulation of N. tabacum remain unresolved. Here we present chromosome-scale assemblies for all three species, and genotype and phenotypic data for 5,196 N. tabacum germplasms. Chromosome rearrangements and epigenetic modifications are associated with genome evolution and expression coordination following polyploidization. Two subgenomes and genes biased toward one subgenome contributed unevenly to complex trait variation. Using 178 marker–trait associations, a reference genotype-to-phenotype map was built for 39 morphological, developmental and disease resistance traits, and a novel gene regulating leaf width was validated. Signatures of positive and polygenic selection during the process of selective breeding were detected. Our study provides insights into genome evolution, complex traits regulation in allotetraploid N. tabacum and the use of GeneBank-scale resources for advancing genetic and genomic research. Chromosome-level genome assemblies of allotetraploid Nicotiana tabacum and its ancestors, along with their transcriptomes, epigenomes and genotype and phenotype data for 5,196 N. tabacum germplasms, provide insights into genome evolution and complex trait regulation.
Distinct type 1 immune networks underlie the severity of restrictive lung disease after COVID-19
Authors: Glenda Canderan, Lyndsey M. Muehling, Alexandra Kadl, Shay Ladd, Catherine Bonham, Claire E. Cross, Sierra M. Lima, Xihui Yin, Jeffrey M. Sturek, Jeffrey M. Wilson, Behnam Keshavarz, Kyle B. Enfield, Chintan Ramani, Naomi Bryant, Deborah D. Murphy, In Su Cheon, Michael Solga, Patcharin Pramoonjago, Coleen A. McNamara, Jie Sun, Paul J. Utz, Sepideh Dolatshahi, Jonathan M. Irish, Judith A. Woodfolk
Journal: Nature Immunology (2025)
Development of ROBUST-RCT: Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials
Authors: Ying Wang, Sheri Keitz, Matthias Briel, Paul Glasziou, Romina Brignardello-Petersen, Reed A C Siemieniuk, Dena Zeraatkar, Elie A Akl, Susan Armijo-Olivo, Dirk Bassler, Carrol Gamble, Lise Lotte Gluud, Jane Luise Hutton, Luz M Letelier, Philippe Ravaud, Kenneth F Schulz, David J Torgerson, Gordon H Guyatt
Journal: BMJ (2025)

Recent innovations in evidence based medicine methods, in particular instruments assessing risk of bias in randomised trials, have focused on methodological rigour at the expense of simplicity and practicability. Such a focus could lead to challenges in application and loss of reliability of instruments. To deal with these shortcomings, the Risk Of Bias instrument for Use in SysTematic reviews-for Randomised Controlled Trials (ROBUST-RCT) was created—a rigorously developed, simply structured, and user friendly instrument for assessing risk of bias of randomised controlled trials included in systematic reviews. This paper describes the development of ROBUST-RCT and provides associated documents and a manual of instructions.
2025 Canadian guideline for physical activity, sedentary behaviour and sleep throughout the first year post partum
Authors: Margie H Davenport, Stephanie-May Ruchat, Alejandra Jaramillo Garcia, Muhammad Usman Ali, Milena Forte, Nicole Beamish, Karen Fleming, Kristi B Adamo, Émilie Brunet-Pagé, Radha Chari, Kirstin N Lane, Michelle F Mottola, Sarah E Neil-Sztramko
Journal: British Journal of Sports Medicine (2025)

This consensus aims to provide guidance for postpartum women and people, healthcare providers and exercise professionals on physical activity, sedentary behaviour and sleep throughout the first year postpartum. The development of this guideline followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and the Appraisal of Guidelines for Research and Evaluation II instrument. The Guideline Consensus Panel consisted of representatives from key professional groups, researchers and methodological experts. Literature was retrieved through searches of 12 online databases, and articles on maternal physical activity, sedentary behaviour or sleep in the first year after childbirth were eligible for inclusion if they reported on any of 21 maternal or infant health outcomes, which were prioritised considering the preferences and values of postpartum individuals. There was no restriction on language, and all study designs were eligible except for case studies. The certainty of evidence was rated using GRADE. This evidence review produced seven systematic reviews, which informed this consensus statement. A Delphi process was conducted to identify relative contraindications to postpartum moderate-intensity to vigorous-intensity physical activity, which informed the development of the Get Active Questionnaire for Postpartum. Evidence to decision tables were developed, and feedback on the recommendations was solicited from end users (healthcare providers, exercise professionals, researchers, policy organisations and postpartum women and people). Adhering to these consensus recommendations for postpartum women and people is likely to result in large improvements in psychological well-being, as well as pelvic, musculoskeletal and cardiometabolic health, and reduced fatigue, while not experiencing adverse events (moderate certainty evidence). Most end users indicated that following these recommendations would be feasible, acceptable and equitable, and likely to require minimal resources from individual and health systems perspectives. PROSPERO registration number CRD42022359282.
Inhibition of 6-phosphogluconate dehydrogenase suppresses esophageal squamous cell carcinoma growth and enhances the anti-tumor effects of metformin via the AMPK/mTOR pathway
Authors: Bei Wang, Zixuan Wang, Zini Zhou, Gui Liu, Zhenyuan Jiang, Mingyue Zheng, Wei Geng
Journal: Molecular Cancer (2025)

Metabolic reprogramming plays a pivotal role in the development and progression of tumors. Tumor cells rely on glycolysis as their primary energy production pathway and effectively utilize biomolecules generated by the pentose phosphate pathway (PPP) for efficient biosynthesis. However, the role of 6-phosphogluconate dehydrogenase (6PGD), a crucial enzyme in the PPP, remains unexplored in esophageal squamous cell carcinoma (ESCC). In this study, we observed a significant upregulation of 6PGD expression in ESCC tissues, which correlated with an unfavorable prognosis among patients. The experiments demonstrated that knockdown of 6PGD induces oxidative stress and suppresses ESCC cell proliferation. Mechanistically, this is achieved through AMPK activation and subsequent inhibition of downstream mTOR phosphorylation. Moreover, physcion has been found to inhibit 6PGD activity and exert its anti-ESCC effect via the AMPK/mTOR pathway. Subsequently, we conducted both in vitro and in vivo experiments to validate the anticancer efficacy of combining metformin, an AMPK activator, with physcion. The results demonstrated a significantly enhanced inhibition of ESCC growth. This study elucidates the impact of 6PGD on ESCC cell proliferation along with its underlying molecular mechanisms, highlighting its potential as a therapeutic target for ESCC. Furthermore, we investigated a novel approach for improved anti-tumor therapy involving physcion and metformin. These findings will contribute new insights to clinical treatment strategies for ESCC while providing a theoretical foundation for developing molecular targeted therapies.
Immunomodulatory gene networks predict treatment response and survival to de-escalated, anthracycline-free neoadjuvant chemotherapy in triple-negative breast cancer in the WSG-ADAPT-TN trial
Authors: Darren Korbie, Clare Stirzaker, Oleg Gluz, Christine zu Eulenburg, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun, Mathias Warm, John Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Rachel Wuerstlein, Enrico Pelz, Hans Heinrich Kreipe, Susan J. Clark, Matt Trau, Monika Graeser, Nadia Harbeck
Journal: Molecular Cancer (2025)

Anthracycline-containing neoadjuvant chemotherapy (NACT) is the standard treatment for early triple-negative breast cancer (eTNBC); however, it is associated with substantial toxicity. We performed whole transcriptome profiling of baseline tumor biopsies to identify gene networks predictive and prognostic for pathological complete response (pCR) and survival after de-escalated, anthracycline-free NACT in the WSG-ADAPT-TN trial (NCT01815242). eTNBC patients (cT1c-cT4c, cN +) were randomized to 12 weeks of nab-paclitaxel + gemcitabine (n = 182) or nab-paclitaxel + carboplatin (n = 154). The primary endpoint was pCR (ypT0/is, ypN0), and the secondary endpoints included survival and translational research. AmpliSeq RNA sequencing, allowing simultaneous analysis of the expression of > 20,000 genes, was performed in 135 patients. Differentially expressed genes were evaluated in training (n = 67) and validation (n = 68) sets, and a polygenic score (PS) for prediction of pCR (PS:pCR) and a PS for prediction of invasive disease-free survival (PS:iDFS) were found. 49/135 (36.3%) patients had pCR; 30 iDFS events occurred during 60-month median follow-up. Immune recruitment and viral defense gene networks were strongly associated with pCR, while metabolic pathways were associated with survival. PS:pCR and PS:iDFS predominantly included immune-related genes. Diagnostic accuracy (ROC AUC) in the validation cohort was 83% for PS:pCR and 64% for PS:iDFS. At optimized cut-off, PS:pCR identified a group with a 67.7% pCR rate (vs. 10.8%; p < .0001), and PS:iDFS detected a group with 79.5% (95%CI 64.1%, 88.8%) 5-year iDFS rate (vs. 55.0%, 95%CI 29.8%, 74.5%; p = .04). Polygenic scores incorporating immunoregulatory genes can predict pCR and survival and represent an opportunity to select patients for de-escalated, anthracycline-free NACT. This transcriptome network analysis also identifies potential new targets for personalized medicine approaches in patients without response to NACT. NCT01815242.
Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells
Authors: Xin Wang, Kun Wang, Weixing Zhang, Zhongjie Tang, Hao Zhang, Yuying Cheng, Da Zhou, Chao Zhang, Wen-Zhao Zhong, Qing Ma, Jin Xu, Zheng Hu
Journal: Genome biology (2025)

Mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, but their efficacy as reliable lineage markers are hindered by the complex dynamics of mtDNA in somatic tissues. Here, we use computational modeling and single-cell genomics to thoroughly interrogate the origin and clonal dynamics of mtDNA variants across various biological settings. Our findings reveal that the majority of mtDNA variants which are specifically present in a cell subpopulation, termed subpopulation-specific variants, are pre-existing heteroplasmies in the first cell instead of de novo somatic mutations during divisions. Moreover, subpopulation-specific variants demonstrate limited discriminatory power among different genuine lineages under weak clonal expansion; however, certain subpopulation-specific variants with consistently high frequencies among a subpopulation are capable of faithfully labeling cell lineages in scenarios of stringent clonal expansion, such as strongly expanded T cell populations in diseased conditions and clonal hematopoiesis in aged individuals. Inspired by our simulations, we introduce a lineage informative score, facilitating the identification of reliable mitochondrial lineage tracing markers across different modalities of single-cell genomic data. Combining computational modeling and single-cell sequencing, our study reveals that the performance of mitochondrial lineage tracing is highly dependent on the extent of clonal expansion, which thus should be considered when applying mitochondrial lineage tracing.
Re: Andreas Josefsson, Marianne Månsson, Kimia Kohestani, et al. Performance of 4Kscore as a Reflex Test to Prostate-specific Antigen in the GÖTEBORG-2 Prostate Cancer Screening Trial. Eur Urol 2024;86:223–9
Authors: Francesco Montorsi, Giorgio Gandaglia, Francesco Barletta, Alberto Briganti
Journal: European Urology (2025)
Three-dose immunogenicity of the type 2 novel oral poliovirus vaccine in a campaign setting in Tajikistan: a follow-up study
Authors: Azamdzhon Mirzoev, Grace Macklin, Giovanna Sifontes, Bernardo A Mainou, Umeda Sadykova, Shahin Huseynov, Murodali Ruziev, Faizali Saidzoda, Mahtob Bobokhonova, Rocio Lopez Cavestany, Ondrej Mach
Journal: The Lancet Global Health (2025)
Evaluation of a decentralised model of care on case isolation and patient outcomes during the 2018–20 Ebola outbreak in the Democratic Republic of the Congo: a retrospective observational study
Authors: Patrick M Barks, Anton Camacho, Trish Newport, Filipe Ribeiro, Steve Ahuka-Mundeke, Richard Kitenge, Justus Nsio, Rebecca M Coulborn, Emmanuel Grellety
Journal: The Lancet Global Health (2025)
Current surveillance strategy is less effective for detecting early-stage hepatocellular carcinoma in patients with non-viral and non-cirrhotic liver disease
Authors: Jessica Spiers, Wenhao Li, Aloysious D Aravinthan, Ayman Bannaga, Katharine Caddick, Emma L Culver, Rosemary E Faulkes, Victoria Gordon, Yaqza Hussain, Hamish Miller, Jenny Merry, Muhammad Saad, Abhishek Sheth, Tahir Shah, Shishir Shetty, Ankur Srivastava, Mohsan Subhani, Muhammad Nauman Tahir, Nwe Ni Than, Esther Unitt, William Alazawi
Journal: Liver Cancer (2025)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Current international guidelines recommend 6-monthly ultrasound surveillance in all patients with cirrhosis and those with hepatitis B virus-related risk factors to detect early-stage HCC. However, it is unknown whether the benefits of surveillance are comparable across patient groups and underlying disease-related factors. We aimed to evaluate patient- and disease-related factors associated with HCC stage at diagnosis and survival in an ethnically diverse UK population. This was a multicentre retrospective observational study including patients with newly diagnosed HCC between 2007 and 2020 from six UK centres. Cox proportional-hazards regression and multivariate logistic regression models were used. Overall, 1,780 HCC patients comprising 20.9% with ArLD, 29.7% with NAFLD, and 31.0% with viral hepatitis were analysed. Surveillance was associated with improved survival in patients with viral hepatitis but not in patients with ArLD and NAFLD. Surveillance was also associated with early-stage disease (BCLC stage 0 or A) at presentation in viral hepatitis but not in patients with ArLD. Females with ArLD were 2.5-fold more likely to present with early-stage HCC than males. Patients with NAFLD were more likely to develop HCC in the absence of cirrhosis. Type 2 diabetes was not associated with mortality, but metformin use did show survival benefit. Patients of white ethnicity had improved survival and were less likely to present with late-stage HCC compared to other ethnicities. HCC surveillance as currently delivered was less effective for detecting early-stage HCC in patients with non-viral and non-cirrhotic liver disease. Gender and ethnicity influences stage at presentation and outcomes. HCC surveillance strategies are needed to refine risk stratification particularly in patients with NAFLD or without cirrhosis.
Metallophilic marginal zone macrophages cross-prime CD8+ T cell-mediated protective immunity against blood-borne tumors
Authors: François-Xavier Mauvais, Yamina Hamel, Aymeric Silvin, Kevin Mulder, Kai Hildner, Ramazan Akyol, Marc Dalod, Despoina Koumantou, Loredana Saveanu, Meriem Garfa, Nicolas Cagnard, Barbara Bertocci, Florent Ginhoux, Peter van Endert
Journal: Immunity (2025)
XPO1-dependency of DEK::NUP214 leukemia
Authors: Fiorella Charles Cano, Arnold Kloos, Rucha Y. Hebalkar, Thomas Plenge, Robert Geffers, Hanna Kirchhoff, Nadine Kattre, Kerstin Görlich, Guntram Büsche, Halyna R. Shcherbata, Michaela Scherr, Konstanze Döhner, Razif Gabdoulline, Michael Heuser
Journal: Leukemia (2025)

Abstract The nuclear export protein XPO1 interacts with nucleoporin 214 (NUP214) and has been implicated in the pathogenesis of SET::NUP214 acute myeloid leukemia (AML). We evaluated DEK::NUP214 (DN), characterizing a distinct AML entity, for its dependency on XPO1 in human AML models. Deletion of XPO1 in DN-positive FKH-1 cells revealed a strong dependency on XPO1. Pharmacologic inhibition of XPO1 by the second-generation selective inhibitor of nuclear export, eltanexor, in primary human and FKH-1 cells reduced XPO1 expression, disrupted co-localization of XPO1 and DN, and induced apoptosis and cell cycle arrest. Functionally, XPO1 and DN co-localized at chromatin, and this co-localization was strongly reduced by XPO1 inhibition. Loss of chromatin binding resulted in downregulation of DN target genes and pathways related to cell cycle and self-renewal. Eltanexor treatment of a patient-derived DN-AML xenograft model disrupted leukemia development, showing molecular clearance in bone marrow after a median of 377 days in eltanexor-treated mice, while control mice succumbed after a median of 244 days. In summary, XPO1 stabilizes DN at chromatin to allow the activation of its oncogenic gene signature, while targeting XPO1 treats leukemia successfully in vivo. These findings establish XPO1 as a molecular target in DEK::NUP214 AML.