tbuckley/cabot-search huggingface dataset:
CXCL8 secreted by immature granulocytes inhibits WT hematopoiesis in chronic myelomonocytic leukemia
Authors: Paul Deschamps, Margaux Wacheux, Axel Gosseye, Margot Morabito, Arnaud Pagès, Anne-Marie Lyne, Alexia Alfaro, Philippe Rameau, Aygun Imanci, Rabie Chelbi, Valentine Marchand, Aline Renneville, Mrinal M Patnaik, Valerie Lapierre, Bouchra Badaoui, Orianne Wagner-Ballon, Céline Berthon, Thorsten Braun, Christophe Willekens, Raphael Itzykson, Pierre Fenaux, Sylvain Thépot, Gabriel Etienne, Emilie Elvira-Matelot, Francoise Porteu, Nathalie Droin, Leïla Perié, Lucie Laplane, Eric Solary, Dorothée Selimoglu-Buet
Journal: Journal of Clinical Investigation (2024)

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate. Our hypothesis is that therapeutic control of the inflammatory component in CMML could contribute to stepping down disease progression. The present study explored the contribution of immature granulocytes (iGRANs) to CMML progression. iGRANs were detected and quantified in the peripheral blood of patients by spectral and conventional flow cytometry. Their accumulation was a potent and independent poor prognostic factor. These cells belong to the leukemic clone and behaved as myeloid-derived suppressor cells. Bulk and single-cell RNA-Seq revealed a proinflammatory status of iGRAN that secreted multiple cytokines of which CXCL8 was at the highest level. This cytokine inhibited the proliferation of WT but not CMML hematopoietic stem and progenitor cells (HSPCs) in which CXCL8 receptors were downregulated. CXCL8 receptor inhibitors and CXCL8 blockade restored WT HSPC proliferation, suggesting that relieving CXCL8 selective pressure on WT HSPCs is a potential strategy to slow CMML progression and restore some healthy hematopoiesis.
Cell-cycle machinery is critical in regulating uterine steroid hormone for embryo implantation and development
Authors: Francesco J. DeMayo
Journal: Journal of Clinical Investigation (2024)

Proper embryo implantation is necessary for a successful pregnancy. In this issue of the JCI, Aljubran et al. identified the cell cycle regulatory protein cyclin A2 (CCNA2) as a factor in supporting embryo implantation and embryo development. Endometrial stromal cells showed higher levels of CCNA2 in patients undergoing assisted reproductive technology who had successful pregnancies. CCNA2 expression correlated with stromal cell proliferation and the expression of steroid hormone receptors for estrogen (ESR1, also known as ERα) and progesterone (PGR). Notably, loss of Ccna2 in mouse models resulted in infertility. The uteri of these mice were hypoplastic with reduced estrogen sensitivity, resulting in the disruption of stroma cell decidualization and loss of embryo viability after implantation. These findings demonstrate the importance of stroma cell proliferation in preparing the uterus for embryo implantation. They also identify CCNA2 as a coregulator of steroid hormone receptor signaling and suggest that impaired uterine stroma can underly early pregnancy loss.
Early-life Upper Airway Microbiota are Associated with Decreased Lower Respiratory Tract Infections
Authors: Susan Zelasko, Mary Hannah Swaney, Shelby Sandstrom, Kristine E Lee, Jonah Dixon, Colleen Riley, Lauren Watson, Jared J Godfrey, Naomi Ledrowski, Federico Rey, Nasia Safdar, Christine M Seroogy, James E Gern, Lindsay Kalan, Cameron Currie
Journal: Journal of Allergy and Clinical Immunology (2024)

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI - namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.
Cardiogenic shock
Authors: Enzo Lüsebrink, Leonhard Binzenhöfer, Marianna Adamo, Roberto Lorusso, Alexandre Mebazaa, David A Morrow, Susanna Price, Jacob C Jentzer, Daniel Brodie, Alain Combes, Holger Thiele
Journal: The Lancet (2024)

Cardiogenic shock is a complex syndrome defined by systemic hypoperfusion and inadequate cardiac output arising from a wide array of underlying causes. Although the understanding of cardiogenic shock epidemiology, specific subphenotypes, haemodynamics, and cardiogenic shock severity staging has evolved, few therapeutic interventions have shown survival benefit. Results from seminal randomised controlled trials support early revascularisation of the culprit vessel in infarct-related cardiogenic shock and provide evidence of improved survival with the use of temporary circulatory support in selected patients. However, numerous questions remain unanswered, including optimal pharmacotherapy regimens, the role of mechanical circulatory support devices, management of secondary organ dysfunction, and best supportive care. This Review summarises current definitions, pathophysiological principles, and management approaches in cardiogenic shock, and highlights key knowledge gaps to advance individualised shock therapy and the evidence-based ethical use of modern technology and resources in cardiogenic shock.
Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial
Authors: Jeremy S Abramson, Matthew Ku, Mark Hertzberg, Hui-Qiang Huang, Christopher P Fox, Huilai Zhang, Dok Hyun Yoon, Won-Seog Kim, Haifaa Abdulhaq, William Townsend, Charles Herbaux, Jan M Zaucha, Qing-Yuan Zhang, Hung Chang, Yanyan Liu, Chan Yoon Cheah, Herve Ghesquieres, Stephen Simko, Victor Orellana-Noia, Richard Ta, James Relf, Mark Dixon, Martine Kallemeijn, Estefania Mulvihill, Huang Huang, Linda Lundberg, Gareth P Gregory
Journal: The Lancet (2024)
Advancing the management of maternal, fetal, and neonatal infection through harnessing digital health innovations
Authors: Damien K Ming, Abi Merriel, David M E Freeman, Carol Kingdon, Yamikani Chimwaza, Mohammad S Islam, Anthony Cass, Benjamin Greenfield, Address Malata, Mahbubul Hoque, Senjuti Saha, Alison H Holmes
Journal: The Lancet Digital Health (2024)

Infections occurring in the mother and neonate exert a substantial health burden worldwide. Optimising infection management is crucial for improving individual outcomes and reducing the incidence of antimicrobial resistance. Digital health technologies, through their accessibility and scalability, hold promise in improving the quality of care across diverse health-care settings. In settings with poor access to laboratory services, innovative uses of existing data, point-of-care diagnostics, and wearables could allow for better recognition of host responses during infection and antimicrobial optimisation. The linkage and connectivity of information can support the coordinated delivery of care between health-care facilities and the community. Continuous real-time monitoring of infection markers in the mother and neonate through biosensing can provide notable opportunities for intervention and improvements in care. However, the development and implementation of these interventions should be respectful, prioritise safety, and emphasise sustainable, locally derived solutions. Addressing existing gender, economic, and health-care disparities will be essential for ensuring equitable implementation.
Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial
Authors: Loren K Mell, Pedro A Torres-Saavedra, Stuart J Wong, Julie A Kish, Steven S Chang, Richard C Jordan, Tian Liu, Minh Tam Truong, Eric W Winquist, Vinita Takiar, Trisha Wise-Draper, Jared R Robbins, Cristina P Rodriguez, Musaddiq J Awan, Beth M Beadle, Christina Henson, Samir Narayan, Sharon A Spencer, Steven Powell, Neal Dunlap, Assuntina G Sacco, Kenneth Shung Hu, Henry S Park, Julie E Bauman, Jonathan Harris, Sue S Yom, Quynh-Thu Le
Journal: The Lancet Oncology (2024)

Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.
Strategies for more equitable engagement for African researchers
Authors: Bamba Gaye, Ngoné Gaye, Gurbinder Singh, Naoufel Madani, Roberta Lamptey, Jamal Eddine Kohen, Abdoulaye Samb, Léon Tshilolo, Pasquale Maffia, Ibrahima Socé Fall, Modou Jobe
Journal: The Lancet Global Health (2024)
Using digital health technologies to optimise antimicrobial use globally
Authors: Timothy M Rawson, Nina Zhu, Ronald Galiwango, Derek Cocker, Mohammad Shahidul Islam, Ashleigh Myall, Vasin Vasikasin, Richard Wilson, Nusrat Shafiq, Shampa Das, Alison H Holmes
Journal: The Lancet Digital Health (2024)

Digital health technology (DHT) describes tools and devices that generate or process health data. The application of DHTs could improve the diagnosis, treatment, and surveillance of bacterial infection and the prevention of antimicrobial resistance (AMR). DHTs to optimise antimicrobial use are rapidly being developed. To support the global adoption of DHTs and the opportunities offered to optimise antimicrobial use consensus is needed on what data are required to support antimicrobial decision making. This Series paper will explore bacterial AMR in humans and the need to optimise antimicrobial use in response to this global threat. It will also describe state-of-the-art DHTs to optimise antimicrobial prescribing in high-income and low-income and middle-income countries, and consider what fundamental data are ideally required for and from such technologies to support optimised antimicrobial use.
Effectiveness and safety of immune checkpoint inhibitors in Black patients versus White patients in a US national health system: a retrospective cohort study
Authors: Sean Miller, Ralph Jiang, Matthew Schipper, Lars G Fritsche, Garth Strohbehn, Beth Wallace, Daria Brinzevich, Virginia Falvello, Benjamin H McMahon, Rafael Zamora-Resendiz, Nithya Ramnath, Xin Dai, Kamya Sankar, Donna M Edwards, Steven G Allen, Shinjae Yoo, Silvia Crivelli, Michael D Green, Alex K Bryant
Journal: The Lancet Oncology (2024)
Innovative diagnostic technologies: navigating regulatory frameworks through advances, challenges, and future prospects
Authors: Jesus Rodriguez-Manzano, Sumithra Subramaniam, Chibuzor Uchea, Katarzyna M Szostak-Lipowicz, Jane Freeman, Marcus Rauch, Halidou Tinto, Heather J Zar, Umberto D'Alessandro, Alison H Holmes, Gordon A Awandare
Journal: The Lancet Digital Health (2024)

Diagnostic tools are key to guiding patient management and informing public health policies to control infectious diseases. However, many diseases still do not have effective diagnostics and much of the global population faces restricted access to reliable, affordable testing. This limitation underscores the urgent need for innovation to enhance diagnostic availability and effectiveness. Developing diagnostics presents distinct challenges, especially for innovators and regulators. Unlike medicines, regulatory pathways for diagnostics are often less defined and more complex due to their diverse risk profiles and wide range of products. These challenges are amplified in low-income and middle-income countries, which often do not have regulatory frameworks for this specific purpose. In the UK, initiatives aim to support innovation by providing clearer regulatory pathways and ensuring that diagnostics are safe and effective. Regulators are also collaborating internationally to expedite diagnostics for high-need regions. Harmonised standards, regulatory frameworks, and approval processes are essential to ensure consistent quality and safety across regions and facilitate faster development and global access. This Series paper explores the regulatory challenges in infectious disease and antimicrobial resistance diagnostics, focusing on the UK's response and the broader global efforts to address these issues.
Adjunctive ivermectin mass drug administration for malaria control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a quadruple-blinded, cluster-randomised, placebo-controlled trial
Authors: Harry Hutchins, Elizabeth Pretorius, John Bradley, Eunice Teixeira da Silva, Hristina Vasileva, Mamadou Ousmane Ndiath, Robert T Jones, Harouna Dit Massire Soumare, Haddy Nyang, Aurelia Prom, Sarata Sambou, Fatima Ceesay, Sainey Ceesay, Sophie Moss, David Mabey, Paulo Djata, Jose Ernesto Nante, Cesario Martins, James G Logan, Hannah Slater, Kevin Tetteh, Chris Drakeley, Umberto D'Alessandro, Amabelia Rodrigues, Anna Last
Journal: The Lancet Infectious Diseases (2024)

Arthropod vectors feeding on the blood of individuals treated with ivermectin have substantially increased mortality. Whether this effect will translate into a useful tool for reducing malaria burden at scale is not clear. Our trial aimed to assess whether using ivermectin as an adjunct to mass drug administration (MDA) with dihydroartemisinin-piperaquine would further reduce malaria prevalence.
Fast-tracking ERCP learning with the Boškoski–Costamagna Trainer: results of a multicenter randomized clinical trial
Authors: Sara Teles de Campos, Ivo Boškoski, Theodor Voiosu, Maurine Salmon, Guido Costamagna, Alexandra Langers, Jeanin E. van Hooft, Geoffroy Vanbiervliet, Cécile Gomercic, Arnaud Lemmers, Paul Fockens, Rogier P. Voermans, Marc Barthet, Jean-Michel Gonzalez, Wim Laleman, Ilaria Tarantino, Jan Werner Poley, Rogier de Ridder, José M. Conchillo, Marco J. Bruno, Pieter J.F. de Jonge, Jacques Devière, Marianna Arvanitakis
Journal: Endoscopy (2024)

Achieving competence in endoscopic retrograde cholangiopancreatography (ERCP) requires extensive training. Recognizing the potential of simulator-based education for safe and effective skill development, we aimed to assess whether initial training with the Boškoski-Costamagna ERCP Trainer (BCT) is beneficial compared with conventional training alone (i.e. predictive validity).
Physical activity and life expectancy: a life-table analysis
Authors: Lennert Veerman, Jakob Tarp, Ruth Wijaya, Mary Njeri Wanjau, Holger Möller, Fiona Haigh, Peta Lucas, Andrew Milat
Journal: British Journal of Sports Medicine (2024)

Low physical activity (PA) levels are associated with increased mortality. Improved measurement has resulted in stronger proven associations between PA and mortality, but this has not yet translated to improved estimates of the disease burden attributable to low PA. This study estimated how much low PA reduces life expectancy, and how much life expectancy could be improved by increasing PA levels for both populations and individuals.
Self-Propelling Intelligent Nanomotor: A Dual-Action Photothermal and Starvation Strategy for Targeted Deep Tumor Destruction
Authors: Ling Mei, Qihang Ding, Yuxin Xie, Haowei Liu, Hongping Li, Eunji Kim, Xue Shen, Yibin Zhang, Shuai Zhang, Jong Seung Kim
Journal: Biomaterials (2024)
Expert Perspective: Diagnostic Approach to Differentiating Juvenile Dermatomyositis from Muscular Dystrophy
Authors: Jacqueline A. Madison, Sean P. Ferris, Marianne Kerski, Grace Hile, Sophia Matossian, Cara Komisar, Peter J. Strouse, Elizabeth Ames, Erin Neil Knierbein, Jessica L. Turnier
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Do we need distinct paediatric classification criteria for rheumatic diseases that affect both children and adults?
Authors: Coziana Ciurtin, Marija Jelusic, Seza Ozen
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Genetic study of intrahepatic cholestasis of pregnancy in Chinese women unveils East Asian etiology linked to historic HBV epidemic
Authors: Yanhong Liu, Yuandan Wei, Xiaohang Chen, Shujia Huang, Yuqin Gu, Zijing Yang, Xinxin Guo, Hao Zheng, Hanxiao Feng, Mingxi Huang, Shangliang Chen, Tiantian Xiao, Liang Hu, Quanfu Zhang, Yang Zhang, Guo-Bo Chen, Xiu Qiu, Fengxiang Wei, Jianxin Zhen, Siyang Liu
Journal: Journal of Hepatology (2024)
A Roadmap of Peptide‐Based Materials in Neural Regeneration
Authors: Yu‐Liang Tsai, Jialei Song, Rachel Shi, Bernd Knöll, Christopher V. Synatschke
Journal: Advanced Healthcare Materials (2024)

Abstract Injuries to the nervous system lead to irreversible damage and limited functional recovery. The peripheral nervous system (PNS) can self‐regenerate to some extent for short nerve gaps. In contrast, the central nervous system (CNS) has an intrinsic limitation to self‐repair owing to its convoluted neural microenvironment and inhibitory response. The primary phase of CNS injury, happening within 48 h, results from external impacts like mechanical stress. Afterward, the secondary phase of the injury occurs, originating from neuronal excitotoxicity, mitochondrial dysfunction, and neuroinflammation. No golden standard to treat injured neurons exists, and conventional medicine serves only as a protective approach to alleviating the symptoms of chronic injury. Synthetic peptides provide a promising approach for neural repair, either as soluble drugs or by using their intrinsic self‐assembly propensity to serve as an extracellular matrix (ECM) mimic for cell adhesion and to incorporate bioactive epitopes. In this review, an overview of nerve injury models, common in vitro models, and peptide‐based therapeutics such as ECM mimics is provided. Due to the complexity of treating neuronal injuries, a multidisciplinary collaboration between biologists, physicians, and material scientists is paramount. Together, scientists with complementary expertise will be required to formulate future therapeutic approaches for clinical use.
Unipolar Voltage Mapping to Predict Recovery of Left Ventricular Ejection Fraction in Patients With Recent-Onset Nonischemic Cardiomyopathy
Authors: Corentin Chaumont, Eliot Peyster, Konstantinos C. Siontis, Daniele Muser, Suraj Kapa, Timothy M. Markman, Rajeev K. Pathak, Alireza Oraii, Oriol Rodriguez-Queralto, Frederic Anselme, Kenneth B. Margulies, Francis E. Marchlinski, David S. Frankel
Journal: Circulation (2024)

BACKGROUND: The ability to predict recovery of left ventricular ejection fraction (LVEF) in response to guideline-directed therapy among patients with nonischemic cardiomyopathy is desired. We sought to determine whether left ventricular endocardial unipolar voltage measured during invasive electroanatomic mapping could be used to predict LVEF recovery among those with recent-onset nonischemic cardiomyopathy. METHODS: We analyzed the left ventricular voltage maps of patients included in the eMAP trial (Electrogram-Guided Myocardial Advanced Phenotyping; NCT03293381), a prospective, nonrandomized, interventional trial conducted at 2 institutions between 2017 and 2020. Patients had recent-onset nonischemic cardiomyopathy defined by LVEF ≤45% and development of symptoms or signs of heart failure within the past 6 months. Detailed voltage maps of the left ventricular endocardium were generated using the CARTO electroanatomic mapping system. Abnormal unipolar amplitude was defined as &lt;8.27 mV. The primary end point was recovery of LVEF (Recovery) defined by a 1-year LVEF ≥50% or ≥45% with ≥10% increase from baseline. RESULTS: Of the 29 enrolled patients (median age, 49 years [25th percentile, 39; 75th percentile, 59], 8 females [27.6%]), LVEF recovered in 13 (44.8%) by 1-year follow-up. The percentage of total endocardial surface area with unipolar voltage abnormality (AUA) was significantly lower among Recovery patients than No Recovery patients (18.2% [6.4, 22.4] versus 80.0% [29.5, 90.9]; P =0.004). Percent AUA was associated with lower likelihood of Recovery (odds ratio, 0.64 per 10% increase in AUA; 95% CI, 0.47–0.88; P =0.006). A 28% cutoff value for percent AUA was 92% sensitive and 75% specific with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.63–0.99; P =0.001) for predicting recovery versus no recovery. The majority of patients (12 of 13; 92.3%) with a percent AUA &gt;28% did not recover. CONCLUSIONS: Left ventricular unipolar voltage abnormality is a potent predictor of LVEF recovery among patients recently diagnosed with nonischemic cardiomyopathy. Detailed left ventricular unipolar voltage mapping could therefore be used as a valuable prognostic tool in guiding treatment decisions.
2024 American Heart Association and American Red Cross Guidelines for First Aid
Authors: Elizabeth K. Hewett Brumberg, Matthew J. Douma, Kostas Alibertis, Nathan P. Charlton, Michael P. Goldman, Katrina Harper-Kirksey, Seth C. Hawkins, Amber V. Hoover, Amy Kule, Stefan Leichtle, Sarah Frances McClure, George Sam Wang, Mark Whelchel, Lynn White, Eric J. Lavonas
Journal: Circulation (2024)

Codeveloped by the American Heart Association and the American Red Cross, these guidelines represent the first comprehensive update of first aid treatment recommendations since 2010. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines cover first aid treatment for critical and common medical, traumatic, environmental, and toxicological conditions. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include opioid overdose, bleeding control, open chest wounds, spinal motion restriction, hypothermia, frostbite, presyncope, anaphylaxis, snakebite, oxygen administration, and the use of pulse oximetry in first aid, with the inclusion of pediatric-specific guidance as warranted.