tbuckley/cabot-search huggingface dataset:
Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial
Authors: André Lamy, Dmitry A. Sirota, Frederic Jacques, Ahmad Poostizadeh, Nicolas Noiseux, Sergey Efremov, Philippe Demers, Boris Akselrod, Chew Yin Wang, Rakesh C. Arora, Piotr Branny, Shay P. McGuinness, Craig D. Brown, Hugues Jeanmart, Qiang Zhao, Haibo Zhang, Emilie P. Belley-Côté, Richard P. Whitlock, Austin Browne, Ingrid Copland, Jessica Vincent, Rutaba Khatun, Kumar Balasubramanian, Shrikant I. Bangdiwala, Michael H. McGillion, Alison E. Fox-Robichaud, Jessica Spence, Salim Yusuf, P.J. Devereaux
Journal: Circulation (2024)

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, −0.5% [95% CI, −0.9 to 0.03]; P =0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2–11.5]; P =0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4–12.9). CONCLUSIONS: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03954314.
SuperCellCyto: enabling efficient analysis of large scale cytometry datasets
Authors: Givanna H. Putri, George Howitt, Felix Marsh-Wakefield, Thomas M. Ashhurst, Belinda Phipson
Journal: Genome biology (2024)

Abstract Advancements in cytometry technologies have enabled quantification of up to 50 proteins across millions of cells at single cell resolution. Analysis of cytometry data routinely involves tasks such as data integration, clustering, and dimensionality reduction. While numerous tools exist, many require extensive run times when processing large cytometry data containing millions of cells. Existing solutions, such as random subsampling, are inadequate as they risk excluding rare cell subsets. To address this, we propose SuperCellCyto, an R package that builds on the SuperCell tool which groups highly similar cells into supercells. SuperCellCyto is available on GitHub ( https://github.com/phipsonlab/SuperCellCyto ) and Zenodo ( https://doi.org/10.5281/zenodo.10521294 ).
A Technology-Assisted Web Application for Consumer Access to a Nonprescription Statin Medication
Authors: Steven E. Nissen, Howard G. Hutchinson, Kathy Wolski, Karol Watson, Seth S. Martin, Erin D. Michos, William S. Weintraub, Melanie Morris, Leslie Cho, Luke Laffin, Douglas Jacoby, Christie M. Ballantyne, Jan Ekelund, Filip Birve, Venu Menon, Michelle Strzelecki, Paul M. Ridker
Journal: Journal of the American College of Cardiology (2024)

Although statins reduce adverse cardiovascular outcomes, less than half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins. To assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a Technology Assisted Self-Selection (TASS) Web Application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels. A prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, blood pressure and concomitant medications into the Web App, resulting in three possible outcomes- "Do Not Use," "Ask a Doctor" or "OK to Use". The study included 1196 participants, median age 63 (IQR, 57-68), 39.6% women, 79.3% White, 11.7% Black, and 4.1% with limited literacy. Mean LDL-C was 139.6 mg/dL (SD, 28.3) and median calculated 10-year risk of atherosclerotic cardiovascular disease was 10.1% (IQR, 7.3-14.0). Initial Web App self-selection resulted in an outcome concordant with clinician assessment in 90.7% (95% CI, 88.9-92.3) of participants and 98.1% (95% CI, 97.1-98.8) had a concordant final use outcome during treatment. Mean percent change in LDL-C was -35.5% (95% CI, -36.6 to -34.3). Serious adverse events occurred in 27 (2.3%) participants, none related to study drug. In this actual use study, a technology assisted Web App allowed >90% of consumers to correctly self-select for statin use and achieve clinically important LDL-C reductions.
CD19-directed T cell–engaging antibodies for the treatment of autoimmune disease
Authors: Jennifer S. Michaelson, Patrick A. Baeuerle
Journal: The Journal of Experimental Medicine (2024)

Jennifer S. Michaelson, Chief Scientific Officer at Cullinan Oncology, and Patrick A. Baeuerle, scientific advisor to Cullinan Oncology and honorary professor in immunology at Ludwig Maximilians University Munich, discuss the use of CD19-specific T cell–engaging antibody therapies (TCEs) as therapeutics for autoimmune diseases.
scifi-ATAC-seq: massive-scale single-cell chromatin accessibility sequencing using combinatorial fluidic indexing
Authors: Xuan Zhang, Alexandre P. Marand, Haidong Yan, Robert J. Schmitz
Journal: Genome biology (2024)

Abstract Single-cell ATAC-seq has emerged as a powerful approach for revealing candidate cis-regulatory elements genome-wide at cell-type resolution. However, current single-cell methods suffer from limited throughput and high costs. Here, we present a novel technique called scifi-ATAC-seq, single-cell combinatorial fluidic indexing ATAC-sequencing, which combines a barcoded Tn5 pre-indexing step with droplet-based single-cell ATAC-seq using the 10X Genomics platform. With scifi-ATAC-seq, up to 200,000 nuclei across multiple samples can be indexed in a single emulsion reaction, representing an approximately 20-fold increase in throughput compared to the standard 10X Genomics workflow.
Sex Differences in Heart Failure With Improved Ejection Fraction
Authors: Maria A. Pabón, Xiaowen Wang, Carolyn S.P. Lam, Eileen O’Meara, Muthiah Vaduganathan, Brian L. Claggett, Alberto Foà, Henri Lu, Anna Maria Langkilde, Rudolf A. De Boer, Akshay S. Desai, Adrian F. Hernandez, Silvio E. Inzucchi, Pardeep S. Jhund, Mikhail N. Kosiborod, Felipe A. Martinez, Sanjiv J. Shah, Magnus Petersson, John J.V. McMurray, Scott D. Solomon, Orly Vardeny
Journal: JACC Heart Failure (2024)
Preventive allergen immunotherapy with inhalant allergens in children
Authors: Varsha Dwivedi, Sonja Kopanja, Klara Schmidthaler, Justyna Sieber, Christina Bannert, Zsolt Szépfalusi
Journal: Allergy (2024)

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.
Trajectories of Health Care Contact Days for Patients With Stage IV Non–Small Cell Lung Cancer
Authors: Arjun Gupta, Paul Nguyen, Danielle Kain, Andrew G. Robinson, Amit A. Kulkarni, David H. Johnson, Carolyn J. Presley, Anne H. Blaes, Gabrielle B. Rocque, Ishani Ganguli, Christopher M. Booth, Timothy P. Hanna
Journal: JAMA Network Open (2024)

Importance Patients with stage IV non–small cell lung cancer (NSCLC) experience substantial morbidity and mortality. Contact days (ie, the number of days with health care contact outside the home) measure how much of a person’s life is consumed by health care, yet little is known about patterns of contact days for patients with NSCLC. Objective To describe the trajectories of contact days in patients with stage IV NSCLC and how trajectories vary by receipt of cancer-directed treatment in routine practice. Design, Setting, and Participants A retrospective, population-based decedent cohort study was conducted in Ontario, Canada. Participants included adults aged 20 years or older who were diagnosed with stage IV NSCLC (January 1, 2014, to December 31, 2017) and died (January 1, 2014, to December 31, 2019); there was a maximum 2-year follow-up. Data analysis was conducted from February 22 to August 16, 2023. Exposure Systemic cancer-directed therapy (yes or no) and type of therapy (chemotherapy vs immunotherapy vs targeted therapy). Main Outcomes and Measures Contact days (days with health care contact, outpatient or institution-based, outside the home) were identified through administrative data. The weekly percentage of contact days and fitted models with cubic splines were quantified to describe trajectories from diagnosis until death. Results A total of 5785 decedents with stage IV NSCLC were included (median age, 70 [IQR 62-77] years; 3108 [53.7%] were male, and 1985 [34.3%] received systemic therapy). The median overall survival was 108 (IQR, 49-426) days, median contact days were 36 (IQR, 21-62), and the median percentage that were contact days was 33.3%. A median of 5 (IQR, 2-10) days were spent with specialty palliative care. Patients who did not receive systemic therapy had a median overall survival of 66 (IQR, 34-130) days and median contact days of 28 (IQR, 17-44), of which a median of 5 (IQR, 2-9) days were spent with specialty palliative care. Overall and for subgroups, normalized trajectories followed a U-shaped distribution: contact days were most frequent immediately after diagnosis and before death. Patients who received targeted therapy had the lowest contact day rate during the trough (10.6%; vs immunotherapy, 15.4%; vs chemotherapy, 17.7%). Conclusions and Relevance In this cohort study, decedents with stage IV NSCLC had a median survival in the order of 3.5 months and spent 1 in every 3 days alive interacting with the health care system outside the home. These results highlight the need to better support patients and care partners, benchmark appropriateness, and improve care delivery.
Universal Newborn Screening for Spinal Muscular Atrophy
Authors: Maryam Oskoui, Tamara Dangouloff, Laurent Servais
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Vitamin C Supplementation Among Pregnant Smokers and Airway Function Trajectory in Offspring
Authors: Cindy T. McEvoy, Lyndsey E. Shorey-Kendrick, Kelvin D. MacDonald, Byung S. Park, Eliot R. Spindel, Cynthia D. Morris, Robert S. Tepper
Journal: JAMA Pediatrics (2024)

This secondary analysis of a randomized clinical trial analyzes the association of vitamin C supplementation in women who smoked during pregnancy with airway function trajectory in their offspring at 4 to 6 years of age.
Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma
Authors: Samantha Guinn, Benedict Kinny-Köster, Joseph A. Tandurella, Jacob T. Mitchell, Dimitrios N. Sidiropoulos, Melanie Loth, Melissa R. Lyman, Alexandra B. Pucsek, Daniel J. Zabransky, Jae W. Lee, Emma Kartalia, Mili Ramani, Toni T. Seppälä, Christopher Cherry, Reecha Suri, Haley Zlomke, Jignasha Patel, Jin He, Christopher L. Wolfgang, Jun Yu, Lei Zheng, David P. Ryan, David T. Ting, Alec Kimmelman, Anuj Gupta, Ludmila Danilova, Jennifer H. Elisseeff, Laura D. Wood, Genevieve Stein-O'Brien, Luciane T. Kagohara, Elizabeth M. Jaffee, Richard A. Burkhart, Elana J. Fertig, Jacquelyn W. Zimmerman
Journal: Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial–mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell–cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation. Significance: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.
Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial
Authors: Seung-Jung Park, Jung-Min Ahn, Do-Yoon Kang, Sung-Cheol Yun, Young-Keun Ahn, Won-Jang Kim, Chang-Wook Nam, Jin-Ok Jeong, In-Ho Chae, Hiroki Shiomi, Hsien-Li Kao, Joo-Yong Hahn, Sung-Ho Her, Bong-Ki Lee, Tae Hoon Ahn, Ki-Yuk Chang, Jei Keon Chae, David Smyth, Gary S Mintz, Gregg W Stone, Duk-Woo Park, Seung-Jung Park, Jung-Min Ahn, Do-Yoon Kang, Sung-Cheol Yun, Young-Keun Ahn, Won-Jang Kim, Chang-Wook Nam Nam, Jin-Ok Jeong, In-Ho Chae, Hiroki Shiomi Shiomi, Hsien-Li Kao, Joo-Yong Hahn, Sung-Ho Her, Bong-Ki Lee, Tae Hoon Ahn, Ki-Yuk Chang, Jei-Keon Chae, David Smyth, Gary Mintz, Gregg Stone, Duk-Woo Park
Journal: The Lancet (2024)
Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals
Authors: Joshua T. B. Williams, Kate Kurlandsky, Kristin Breslin, M. Joshua Durfee, Amy Stein, Laura Hurley, Jo Ann Shoup, Liza M. Reifler, Matthew F. Daley, Bruno J. Lewin, Kristin Goddard, Michelle L. Henninger, Jennifer C. Nelson, Gabriela Vazquez-Benitez, Kayla E. Hanson, Candace C. Fuller, Eric S. Weintraub, Michael M. McNeil, Simon J. Hambidge
Journal: JAMA Network Open (2024)

Importance Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures Self-reported or electronic health record (EHR)–derived race, ethnicity, and preferred language. Main Outcomes and Measures Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ 2 1 = 7.8; P &amp;amp;lt; .001), non-Hispanic White respondents (72% vs 43%; χ 2 1 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ 2 1 = 22.8; P = .002). Conclusions and Relevance Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.
Oncogene-Driven Non–Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations
Authors: Chen-Yang Huang, Nanhai Jiang, Meixin Shen, Gillianne G. Lai, Aaron C. Tan, Amit Jain, Stephanie P. Saw, Mei Kim Ang, Quan Sing Ng, Darren W. Lim, Ravindran Kanesvaran, Eng Huat Tan, Wan Ling Tan, Boon-Hean Ong, Kevin L. Chua, Devanand Anantham, Angela M. Takano, Kiat Hon Lim, Wai Leong Tam, Ngak Leng Sim, Anders J. Skanderup, Daniel S. Tan, Steven G. Rozen
Journal: Cancer Research (2024)

Abstract Non–small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these “nonsmoking-related oncogenes” (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations. Significance: Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic.
Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: a prospective cohort study
Authors: Natalia Maldonado, Inmaculada López-Hernández, Luis Eduardo López-Cortés, Pedro María Martínez Pérez-Crespo, Pilar Retamar-Gentil, Andrea García-Montaner, Sandra De la Rosa Riestra, Adrián Sousa-Domínguez, Josune Goikoetxea, Ángeles Pulido-Navazo, María Del Valle Ortíz, Clara Natera-Kindelán, Alfredo Jover-Sáenz, Alfonso del Arco-Jiménez, Carlos Armiñanzas-Castillo, Ana Isabel Aller-García, Jonathan Fernández-Suárez, Teresa Marrodán-Ciordia, Lucía Boix-Palop, Alejandro Smithson-Amat, José María Reguera-Iglesias, Fátima Galán-Sánchez, Alberto Bahamonde, Juan Manuel Sánchez-Calvo, Isabel Gea-Lázaro, Inés Pérez-Camacho, Armando Reyes-Bertos, Berta Becerril-Carral, Álvaro Pascual, Jesús Rodríguez-Baño
Journal: Clinical Microbiology and Infection (2024)

This study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock).