tbuckley/cabot-search huggingface dataset:
Directly Isolated Allogeneic Virus–Specific T Cells in Progressive Multifocal Leukoencephalopathy
Authors: Nora Möhn, Lea Grote-Levi, Mike P. Wattjes, Agnes Bonifacius, Dennis Holzwart, Franziska Hopfner, Sandra Nay, Sabine Tischer-Zimmermann, Mieke Luise Saßmann, Philipp Schwenkenbecher, Kurt-Wolfram Sühs, Nima Mahmoudi, Clemens Warnke, Julian Zimmermann, David Hagin, Lilia Goudeva, Rainer Blasczyk, Armin Koch, Britta Maecker-Kolhoff, Britta Eiz-Vesper, Günter Höglinger, Thomas Skripuletz
Journal: JAMA Neurology (2024)

Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment.
Opioid Overdose in Patients With Concomitant Use of Tramadol and Clopidogrel vs Alternative Antiplatelet Agents
Authors: Sungho Bea, Krista F Huybrechts, Heba H Edrees, C Andrew Basham, Seanna M Vine, Robert J Glynn, Brian T Bateman, Katsiaryna Bykov
Journal: Journal of the American College of Cardiology (2024)
You have to work twice as hard as a woman to show that you are competent. Experiences, opportunities and workplace gender harassment for Sport and Exercise Medicine practitioners working in elite sport in Australia
Authors: Sallie M Cowan, Michael Girdwood, Melissa Haberfield, Andrea Britt Mosler, Andrea M Bruder, Kate Mahony, Kirsty Forsdike, Nicola McNeil, Kate A Beerworth, Miranda Menaspa, Phillipa Inge, Sue White, Rachel Harris, Adam Castricum, Kay M Crossley
Journal: British Journal of Sports Medicine (2024)

Objective Our aim was to investigate (1) gender representation, (2) opportunities and training and (3) harassment experiences in Sport and Exercise Medicine (SEM) practitioners working in elite sport in Australia. Methods All titled Australian Physiotherapy Association Sport and Exercise Physiotherapists, SEM Physicians and Registrars and doctors and physiotherapists (SEM practitioners) currently/previously/aspiring to work in Australian elite sport were invited to participate in a bespoke online survey and the Gender Experiences Questionnaire. Results For SEM practitioners currently working in elite sport, men worked more paid hours each week (mean difference (MD) 12.2 (95% CI 5.5 to 19.0)) and more paid weeks each year (MD 6.8 (95% CI 1.2 to 12.5)). Women SEM practitioners (both currently and previously) were more likely than men to work with women, rather than men athletes. All women SEM practitioners experienced significantly more gender harassment, infantilisation, work/family policing and gender policing than men. For SEM practitioners (both current and previous), there were no gender differences in how practitioners found out about or were recruited to their elite sports roles. Women were four times more likely than men to report that their gender or sexual orientation influenced their opportunities in elite sport. Most roles were not advertised with direct approach being the most common method of job recruitment. Conclusion Women SEM practitioners currently working in elite sport worked less paid hours per week and less paid weeks per year. All SEM practitioners were appointed to positions without established procedures, and there were significant challenges for women SEM practitioners in the elite sport workplace with women facing considerably more gender harassment than men.
Bivalirudin vs Heparin Anticoagulation in STEMI
Authors: Gregg W Stone, Marco Valgimigli, David Erlinge, Yaling Han, Philippe Gabriel Steg, Rod H Stables, Enrico Frigoli, Stefan K James, Yi Li, Patrick Goldstein, Roxana Mehran, Ghazaleh Mehdipoor, Aaron Crowley, Shmuel Chen, Björn Redfors, Clayton Snyder, Zhipeng Zhou, Behnood Bikdeli
Journal: Journal of the American College of Cardiology (2024)
International Clinical Practice Guideline Recommendations for Acute Pulmonary Embolism
Authors: Marco Zuin, Behnood Bikdeli, Jennifer Ballard-Hernandez, Stefano Barco, Elisabeth M Battinelli, George Giannakoulas, David Jimenez, Frederikus A Klok, Darsiya Krishnathasan, Irene M Lang, Lisa Moores, Katelyn W Sylvester, Jeffrey I Weitz, Gregory Piazza
Journal: Journal of the American College of Cardiology (2024)
Neither seen nor heard: the evidence gap on the effect of covid-19 on mental health in children
Authors: Tamsin Ford, Tamsin Newlove-Delgado, Ann Kannuralil Sabu, Abigail Russell
Journal: BMJ (2024)

Tamsin Ford and colleagues say better evidence on how children's mental health is affected by health shocks is essential to inform policy responses The impact of health shocks, such as pandemics and human made and natural disasters, on children and young people is too often under-researched, meaning evidence informed responses are inadequate. The original terms of reference of the UK Covid-19 Inquiry omitted children, for example, as did much of the global pandemic response. Yet data indicate that the pandemic had a disproportionate impact on their mental health.1 This was entirely predictable, given that pandemic restrictions resulted in social isolation and disrupted routines and sleep, as well as financial and academic stress, all of which undermine mental health, in addition to fears about loss of educational opportunities and family members becoming ill (box 1).2 Box 1 ### Young person's perspective, by Ann Kannuralil Sabu I am 17 and in full time education. Over the past few years, I have collaborated with the Cambridge Children's Hospital (CCH) youth forum. To elicit views about the effects of the pandemic that needed researching, in August 2023 we sent a survey to about 600 people linked to the CCH youth forum, as well as the linked parents and carers forum, and about 20 third sector organisations that work with children and families in the east of England. We also shared it through social media. We received 38 responses. The following are typical of the comments received.RETURN TO TEXT
Research across multiple disciplines to respond to health shocks
Authors: Amitava Banerjee, Angela Coulter, Shifalika Goenka, Aidan Hollis, Azeem Majeed
Journal: BMJ (2024)

Research that spans clinical specialties and research disciplines beyond health and healthcare is a priority for planning equitable responses to manage future health shocks, argue <b>Amitava Banerjee and colleagues</b>
Building public trust in preparation for future health shocks: a research agenda
Authors: Heidi J Larson, Rachel L Eagan, Anne Pordes Bowers, Ieva Smilingyte, Alex de Figueiredo, Angela Coulter
Journal: BMJ (2024)

Trust is fundamental to cooperation, essential in times of crisis. Researching and understanding trust networks and perceptions of trustworthiness is therefore crucial in preparing for future health shocks, write <b>Heidi Larson and colleagues</b>
None of us are prepared unless all of us are prepared: research for the next health shock must be inclusive and equitable
Authors: Ebere Okereke, Spring Gombe, Ouma Onyango
Journal: BMJ (2024)

Rich countries like the UK will need to match rhetoric with investment and action at home and internationally to ensure global health security and resilience to health shocks, write <b>Ebere Okereke and colleagues</b>
Workforce research priorities for resilience to future health shocks—and the workforce crisis
Authors: Kieran Walshe, Judith Smith, Tara Lamont, Alison Leary
Journal: BMJ (2024)

More and better research is needed now to develop an evidence base that informs policy to maximise workforce effectiveness and wellbeing to respond to both the next health shock and the ongoing shock of the workforce crisis, write <b>Kieran Walshe and colleagues</b>
A call to action to scale up research and clinical genomic data sharing
Authors: Zornitza Stark, David Glazer, Oliver Hofmann, Augusto Rendon, Christian R. Marshall, Geoffrey S. Ginsburg, Chris Lunt, Naomi Allen, Mark Effingham, Jillian Hastings Ward, Sue L. Hill, Raghib Ali, Peter Goodhand, Angela Page, Heidi L. Rehm, Kathryn N. North, Richard H. Scott
Journal: Nature Reviews Genetics (2024)
Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer
Authors: Vamsi Mangena, Rony Chanoch-Myers, Rafaela Sartore, Bruna Paulsen, Simon Gritsch, Hannah Weisman, Toshiro Hara, Xandra O. Breakefield, Koen Breyne, Aviv Regev, Kwanghun Chung, Paola Arlotta, Itay Tirosh, Mario L. Suva
Journal: Cancer Discovery (2024)

Glioblastoma (GBM) is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. In this study, we model this ecosystem by growing GBM into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA sequencing analysis suggests that, compared with matched gliomasphere models, GBM cortical organoids more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of GBM transcripts and GFP to nonmalignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased toward defined GBM cell states and astroglia cell types. These results extend previous GBM organoid modeling efforts and suggest widespread intercellular transfer in the GBM neuroglial microenvironment. Significance: Models that recapitulate intercellular communications in GBM are limited. In this study, we leverage GBM cortical organoids to characterize widespread mRNA and GFP transfer from malignant to nonmalignant cells in the GBM neuroglial microenvironment. This transfer involves extracellular vesicles, may contribute to reprogramming the microenvironment, and may extend to other cancer types. See related commentary by Shakya et al., p. 261.
Comparative analysis of the duodenojejunal microbiome with the oral and fecal microbiomes reveals its stronger association with obesity and nutrition
Authors: Emilie Steinbach, Eugeni Belda, Rohia Alili, Solia Adriouch, Charlène J. G. Dauriat, Gianfranco Donatelli, Jean-Loup Dumont, Filippo Pacini, Thierry Tuszynski, Véronique Pelloux, Flavien Jacques, Laura Creusot, Emavieve Coles, Paul Taillandier, Marta Vazquez Gomez, Davide Masi, Véronique Mateo, Sébastien André, Melissa Kordahi, Christine Rouault, Jean-Daniel Zucker, Harry Sokol, Laurent Genser, Benoit Chassaing, Tiphaine Le Roy, Karine Clément
Journal: Gut Microbes (2024)

The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While most research focuses on the fecal microbiota due to its easier accessibility, the small intestine, as a major site for nutrient sensing and absorption, warrants further investigation to determine its microbiota composition and functions. Here, we conducted a clinical research project in 30 age- and sex-matched participants with (
Gut microbiota genome features associated with brain injury in extremely premature infants
Authors: David Seki, Rasmus Kirkegaard, Jay Osvatic, Bela Hausmann, Joana Séneca, Petra Pjevac, Angelika Berger, Lindsay J Hall, Lukas Wisgrill, David Berry
Journal: Gut Microbes (2024)

Severe brain damage is common among premature infants, and the gut microbiota has been implicated in its pathology. Although the order of colonizing bacteria is well described, the mechanisms underlying aberrant assembly of the gut microbiota remain elusive. Here, we employed long-read nanopore sequencing to assess abundances of microbial species and their functional genomic potential in stool samples from a cohort of 30 extremely premature infants. We identify several key microbial traits significantly associated with severe brain damage, such as the genomic potential for nitrate respiration and iron scavenging. Members of the
Genome-wide association testing beyond SNPs
Authors: Laura Harris, Ellen M. McDonagh, Xiaolei Zhang, Katherine Fawcett, Amy Foreman, Petr Daneck, Panagiotis I. Sergouniotis, Helen Parkinson, Francesco Mazzarotto, Michael Inouye, Edward J. Hollox, Ewan Birney, Tomas Fitzgerald
Journal: Nature Reviews Genetics (2024)
Mpox genomics in outbreak control: challenges and limitations
Authors: Kathryn Edenborough, Ammar Aziz, Nicola Sexton-Oates, Ivana Savic, Eike Steinig, Brendan Quinn, Mihaela Ivan, Alicia Arnott, Leon Caly, Chuan Kok Lim
Journal: The Lancet Microbe (2024)
Blood‐Brain Barrier‐Penetrating Metal‐Organic Framework Antioxidant Nanozymes for Targeted Ischemic Stroke Therapy
Authors: Qing Chen, Jin Wang, Xiaoxing Xiong, Junyang Chen, Bo Wang, Haixia Yang, Jianliang Zhou, Hongping Deng, Lijuan Gu, Jian Tian
Journal: Advanced Healthcare Materials (2024)

Abstract Overproduction of reactive oxygen species (ROS) during reperfusion in ischemic stroke (IS) severely impedes neuronal survival and results in high rates of morbidity and disability. The effective blood‐brain barrier (BBB) penetration and brain delivery of antioxidative agents remain the biggest challenge in treating ischemic reperfusion‐induced cerebrovascular and neural injury. In this study, a metal‐organic framework (MOF) nanozyme (MIL‐101‐NH 2 (Fe/Cu)) with ROS scavenging activities to encapsulate neuroprotective agent rapamycin is fabricated and decorating the exterior with BBB‐targeting protein ligands (transferrin), thereby realizing enhanced drug retention and controlled release within ischemic lesions for the synergistic treatment of IS. Through the receptor‐mediated transcellular pathway, the transferrin‐coated MOF nanoparticles achieved efficient transport across the BBB and targeted accumulation at the cerebral ischemic injury site of mice with middle cerebral artery occlusion/reperfusion (MCAO/R), wherein the nanocarrier exhibited catalytic activities of ROS decomposition into O 2 and H 2 O 2 ‐responsive rapamycin release. By its BBB‐targeting, antioxidative, anti‐inflammatory, and antiapoptotic properties, the MOF nanosystem addressed multiple pathological factors of IS and realized remarkable neuroprotective effects, leading to the substantial reduction of cerebral infarction volume and accelerated recovery of nerve functions in the MCAO/R mouse model. This MOF‐based nanomedicine provides valuable design principles for effective IS therapy with multi‐mechanism synergies.
High density genomic surveillance and risk profiling of clinical Listeria monocytogenes subtypes in Germany
Authors: Sven Halbedel, Sabrina Wamp, Raskit Lachmann, Alexandra Holzer, Ariane Pietzka, Werner Ruppitsch, Hendrik Wilking, Antje Flieger
Journal: Genome Medicine (2024)

Abstract Background Foodborne infections such as listeriosis caused by the bacterium Listeria monocytogenes represent a significant public health concern, particularly when outbreaks affect many individuals over prolonged time. Systematic collection of pathogen isolates from infected patients, whole genome sequencing (WGS) and phylogenetic analyses allow recognition and termination of outbreaks after source identification and risk profiling of abundant lineages. Methods We here present a multi-dimensional analysis of &gt; 1800 genome sequences from clinical L. monocytogenes isolates collected in Germany between 2018 and 2021. Different WGS-based subtyping methods were used to determine the population structure with its main phylogenetic sublineages as well as for identification of disease clusters. Clinical frequencies of materno-foetal and brain infections and in vitro infection experiments were used for risk profiling of the most abundant sublineages. These sublineages and large disease clusters were further characterised in terms of their genetic and epidemiological properties. Results The collected isolates covered 62% of all notified cases and belonged to 188 infection clusters. Forty-two percent of these clusters were active for &gt; 12 months, 60% generated cases cross-regionally, including 11 multinational clusters. Thirty-seven percent of the clusters were caused by sequence type (ST) ST6, ST8 and ST1 clones. ST1 was identified as hyper- and ST8, ST14, ST29 as well as ST155 as hypovirulent, while ST6 had average virulence potential. Inactivating mutations were found in several virulence and house-keeping genes, particularly in hypovirulent STs. Conclusions Our work presents an in-depth analysis of the genomic characteristics of L. monocytogenes isolates that cause disease in Germany. It supports prioritisation of disease clusters for epidemiological investigations and reinforces the need to analyse the mechanisms underlying hyper- and hypovirulence.
Author Correction: Sepsis-trained macrophages promote antitumoral tissue-resident T cells
Authors: Alexis Broquet, Victor Gourain, Thomas Goronflot, Virginie Le Mabecque, Debajyoti Sinha, Mitra Ashayeripanah, Cédric Jacqueline, Pierre Martin, Marion Davieau, Lea Boutin, Cecile Poulain, Florian P. Martin, Cynthia Fourgeux, Melanie Petrier, Manon Cannevet, Thomas Leclercq, Maeva Guillonneau, Tanguy Chaumette, Thomas Laurent, Christelle Harly, Emmanuel Scotet, Laurent Legentil, Vincent Ferrières, Stephanie Corgnac, Fathia Mami-Chouaib, Jean Francois Mosnier, Nicolas Mauduit, Hamish E. G. McWilliam, Jose A. Villadangos, Pierre Antoine Gourraud, Karim Asehnoune, Jeremie Poschmann, Antoine Roquilly
Journal: Nature Immunology (2024)
Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)
Authors: Benjamin A. Derman, Ajay Major, Jennifer Cooperrider, Ken Jiang, Aubrianna Ramsland, Theodore Karrison, Tadeusz Kubicki, Andrzej J. Jakubowiak
Journal: Blood Cancer Journal (2024)

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10
Biohybrid Micro/Nanorobots: Pioneering the Next Generation of Medical Technology
Authors: Atefeh Zarepour, Arezoo Khosravi, Siavash Iravani, Ali Zarrabi
Journal: Advanced Healthcare Materials (2024)

Abstract Biohybrid micro/nanorobots hold a great potential for advancing biomedical research. These tiny structures, designed to mimic biological organisms, offer a promising method for targeted drug delivery, tissue engineering, biosensing/imaging, and cancer therapy, among other applications. The integration of biology and robotics opens new possibilities for minimally invasive surgeries and personalized healthcare solutions. The key challenges in the development of biohybrid micro/nanorobots include ensuring biocompatibility, addressing manufacturing scalability, enhancing navigation and localization capabilities, maintaining stability in dynamic biological environments, navigating regulatory hurdles, and successfully translating these innovative technologies into clinical applications. Herein, the recent advancements, challenges, and future perspectives related to the biomedical applications of biohybrid micro/nanorobots are described. Indeed, this review sheds light on the cutting‐edge developments in this field, providing researchers with an updated overview of the current potential of biohybrid micro/nanorobots in the realm of biomedical applications, and offering insights into their practical applications. Furthermore, it delves into recent advancements in the field of biohybrid micro/nanorobotics, providing a comprehensive analysis of the current state‐of‐the‐art technologies and their future applications in the biomedical field.
EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma
Authors: Lynnette Wei Hsien Koh, Qing You Pang, Wisna Novera, See Wee Lim, Yuk Kien Chong, Jinyue Liu, Samantha Ya Lyn Ang, Ron Weng Yee Loh, Huilin Shao, Jianhong Ching, Yulan Wang, Stephen Yip, Patrick Tan, Shang Li, David Chyi Yeu Low, Anne Phelan, Gabriel Rosser, Nguan Soon Tan, Carol Tang, Beng Ti Ang
Journal: Neuro-Oncology (2024)

Abstract Background Enhancer of zeste homolog 2 (EZH2), well known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied noncanonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratification remain relatively unexplored. Current enzymatic EZH2 inhibitors (EZH2inh) targeting its canonical su(var)3–9, enhancer-of-zeste and trithorax domain show limited efficacy and lack durable response, suggesting that underlying differences in the noncanonical pathway may yield new knowledge. Here, we unveiled dual roles of the EZH2 CXC domain in therapeutically distinct, reactive oxygen species (ROS)-stratified tumors. Methods We analyzed differentially expressed genes between ROS classes by examining cis-regulatory elements as well as clustering of activities and pathways to identify EZH2 as the key mediator in ROS-stratified cohorts. Pull-down assays and CRISPR knockout of EZH2 domains were used to dissect the distinct functions of EZH2 in ROS-stratified GBM cells. The efficacy of NF-κB-inducing kinase inhibitor (NIKinh) and standard-of-care temozolomide was evaluated using orthotopic patient-derived GBM xenografts. Results In ROS(+) tumors, CXC-mediated co-interaction with RelB drives constitutive activation of noncanonical NF-κB2 signaling, sustaining the ROS(+) chemoresistant phenotype. In contrast, in ROS(−) subtypes, Polycomb Repressive Complex 2 methyltransferase activity represses canonical NF-κB. Addressing the lack of EZH2inh targeting its nonmethyltransferase roles, we utilized a brain-penetrant NIKinh that disrupts EZH2-RelB binding, consequently prolonging survival in orthotopic ROS(+)-implanted mice. Conclusions Our findings highlight the functional dichotomy of the EZH2 CXC domain in governing ROS-stratified therapeutic resistance, thereby advocating for the development of therapeutic approaches targeting its noncanonical activities and underscoring the significance of patient stratification methodologies.
Histone lactylation drives CD8+ T cell metabolism and function
Authors: Deblina Raychaudhuri, Pratishtha Singh, Bidisha Chakraborty, Mercedes Hennessey, Aminah J. Tannir, Shrinidhi Byregowda, Seanu Meena Natarajan, Abel Trujillo-Ocampo, Jin Seon Im, Sangeeta Goswami
Journal: Nature Immunology (2024)
Optimization of the Irf8 +32-kb enhancer disrupts dendritic cell lineage segregation
Authors: Feiya Ou, Tian-Tian Liu, Pritesh Desai, Stephen T. Ferris, Sunkyung Kim, Haolin Shen, Ray A. Ohara, Suin Jo, Jing Chen, J. Luke Postoak, Siling Du, Michael S. Diamond, Theresa L. Murphy, Kenneth M. Murphy
Journal: Nature Immunology (2024)
Genetic architecture reconciles linkage and association studies of complex traits
Authors: Julia Sidorenko, Baptiste Couvy-Duchesne, Kathryn E. Kemper, Gunn-Helen Moen, Laxmi Bhatta, Bjørn Olav Åsvold, Reedik Mägi, Alireza Ani, Rujia Wang, Ilja M. Nolte, Ilja M. Nolte, Scott Gordon, Caroline Hayward, Archie Campbell, Daniel J. Benjamin, David Cesarini, David M. Evans, Michael E. Goddard, Chris S. Haley, David Porteous, Sarah E. Medland, Nicholas G. Martin, Harold Snieder, Andres Metspalu, Kristian Hveem, Ben Brumpton, Peter M. Visscher, Loic Yengo
Journal: Nature Genetics (2024)
APC mutations dysregulate alternative polyadenylation in cancer
Authors: Austin M. Gabel, Andrea E. Belleville, James D. Thomas, Jose Mario Bello Pineda, Robert K. Bradley
Journal: Genome biology (2024)

Alternative polyadenylation (APA) affects most human genes and is recurrently dysregulated in all studied cancers. However, the mechanistic origins of this dysregulation are incompletely understood.