tbuckley/cabot-search huggingface dataset:
Anticoagulant Therapy for 6 Weeks vs 3 Months and Recurrence and Bleeding in Patients Younger Than 21 Years With Provoked Venous Thromboembolism
Authors: Ahmed Abdelmonem, Dhruvil Prajapati, Jigar Patel
Journal: JAMA (2022)

To the Editor We have several comments about the recent study1 investigating the effect of anticoagulant therapy for 6 weeks vs 3 months on recurrence and bleeding in patients younger than 21 years old with provoked venous thromboembolism.
JAMA Internal Medicine
Authors: Thomas Easley, Brian Shields, Karen Adams-Taylor, Paul Gee, Monica Smith, Jeff Ery, J Bonistalli, Kathy Russell, Mirna Monal, Stacey Mchugh, Tim Melroy, Marketing Thornbury, Tricia Castellano, Anna Coordinator, Meghan Thue, Sade Deramus-Townsend, Thalia Recruitment, Samantha Bauer, Hank Eurich, Marsha Fogler, Rachel Sisholtz, Saskia Bolore, Gretchen Linder, Brian Mccartney, Christine Hearne, Natasha Staff, Henry Aguillon, David Baum, Ron Marketing, Rick Bell, Elizabeth Solaro, Sara Zimmerman, Geoff Rey, Lindsay Dawson, Ellen Gibson, Craig Mccaff Rey, Michael Mcgraw, Daniel Pickhardt, Romando Rossini, Sarah Subramanian, Stacy Tucker, Walsh Business, Analyst Sirisha, Alluri Staff, Millette Jackson-Bates, Tom Miller, Jacob Mishkin, Morgan Business, Karl Elvin, Nancy Essex, Jaye Mize, Sean O'donnell, Sue Managers, David Antos, Anthony Bautista, Chris Borden, Debbie Camp, Jennifer Carney, Lydia Cruz, Scott Curl, Diane Darnell, Nanette Diaz, Jordynn Farrar, Allison Hughes, Colleen Kelly, John Lash, Chris Meyer, Annemarie Neff, J Neff, Sean Ohlson, Phil O'leary, Bill Pedone, Susan Price, Jaynam Shah, Erin Spencer, Denise Steinhauser, Joe Advertising, Production Services, Ahmed Avendano, Kim Boler, Rhonda Brown, Fin Carter, Michael Deegan, Euwanaha Joiner-Smith, Joshua Lane, Cindy Rendlen, Janis Trinchere, Annissa Zak, Circulation Services, Julie Burton, Ronna Hewitt, Mary Sieck, Geneine Someren, Jamaal Vargas, Content Systems, Mike Bujewski, Nathan Mitre, Digital Production, Regina Brownlee, Amanda Camino, Brenda Chandler-Grayer, Emily Dunn, Amy Evers, Maleeka Holden, Teri Hutchison, Dan Knowles, Joshua Lampinen, Natalie Marsh, Patricia Panek, Marla Seidell, La Son Diggs-Sledge, Julian Graphics, Joe Amft, Jonathan Chala, James Collver, Maria Duda, Fred Furtner, Carolyn Hall, Maria Kowalkowski, Proofreading Carol, Joy Farrell, Maria Giannini, Sasha Grossman, Kate Lander, Judith Literskis, Teresa Omiotek, Michael Ryder, James Madara, Terri Carter, Fellows Mithi, Del Rosario, Vinay Guduguntla, Anand Habib, Audrey Han, Natalie Richmond, Eric Ward, Zachary Goldberger, Nora Goldschlager, San Francisco, Elsayed Soliman, Winston-Salem North, Fiona Clement, Rita Redberg, Deborah Grady, Michael Incze, Salt City, Tanner Caverly, Ann Arbor, Brandon Combs, Sanket Dhruva
Journal: JAMA Internal Medicine (2022)

Mission Statement: To promote the art and science of medicine and the betterment of public health by publishing manuscripts of interest and relevance to internists practicing as generalists or as medical subspecialists.
Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma
Authors: Xiaofei Song, Shiun Chang, Lucia Seminario-Vidal, Alvaro de Mingo Pulido, Leticia Tordesillas, Xingzhi Song, Rhianna A. Reed, Andrea Harkins, Shannen Whiddon, Jonathan V. Nguyen, Carlos Moran Segura, Chaomei Zhang, Sean Yoder, Zena Sayegh, Yun Zhao, Jane L. Messina, Carly M. Harro, Xiaohui Zhang, José R. Conejo-Garcia, Anders Berglund, Lubomir Sokol, Jianhua Zhang, Paulo C. Rodriguez, James J. Mulé, Andrew P. Futreal, Kenneth Y. Tsai, Pei-Ling Chen
Journal: Cancer Discovery (2022)

Abstract Cutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosystem using integrative multiomics spanning whole-exome sequencing (WES), single-cell RNA sequencing, and immune profiling in a unique cohort of 56 patients. WES of 70 skin biopsies showed high tumor mutation burden, UV signatures that are prognostic for survival, exome-based driver events, and most recurrently mutated pathways in tCTCL. Single-cell profiling of 16 tCTCL skin biopsies identified a core oncogenic program with metabolic reprogramming toward oxidative phosphorylation (OXPHOS), cellular plasticity, upregulation of MYC and E2F activities, and downregulation of MHC I suggestive of immune escape. Pharmacologic perturbation using OXPHOS and MYC inhibitors demonstrated potent antitumor activities, whereas immune profiling provided in situ evidence of intercellular communications between malignant T cells expressing macrophage migration inhibitory factor and macrophages and B cells expressing CD74. Significance: Our study contributes a key resource to the community with the largest collection of tCTCL biopsies that are difficult to obtain. The multiomics data herein provide the first comprehensive compendium of genomic alterations in tCTCL and identify potential prognostic signatures and novel therapeutic targets for an incurable T-cell lymphoma. This article is highlighted in the In This Issue feature, p. 1171
Effect of Structured, Moderate Exercise on Kidney Function Decline in Sedentary Older Adults
Authors: Michael G. Shlipak, Anoop Sheshadri, Fang-Chi Hsu, Shyh-Huei Chen, Vasantha Jotwani, Gregory Tranah, Roger A. Fielding, Christine K. Liu, Joachim Ix, Steven G. Coca, Marco Pahor, Jack M Guralnik, Christina Leeuwenburgh, Connie Caudle, Lauren Crump, Latonia Holmes, Jocelyn Leeuwenburgh, Ching-ju Lu, Michael E Miller, Mark A Espeland, Walter T Ambrosius, William Applegate, Daniel P Beavers, Robert P Byington, Delilah Cook, Curt D Furberg, Lea N Harvin, Leora Henkin, John Hepler, Fang-Chi Hsu, Laura Lovato, Wesley Roberson, Julia Rushing, Scott Rushing, Cynthia L Stowe, Michael P Walkup, Don Hire, W Jack Rejeski, Jeffrey A Katula, Peter H Brubaker, Shannon L Mihalko, Janine M Jennings, Evan C Hadley, Sergi Romashkan, Kushang V Patel, Denise Bonds, Mary M McDermott, Bonnie Spring, Joshua Hauser, Diana Kerwin, Kathryn Domanchuk, Rex Graff, Alvito Rego, Timothy S Church, Steven N Blair, Valerie H Myers, Ron Monce, Nathan E Britt, Melissa Harris, Ami McGucken, Ruben Rodarte, Heidi K Millet, Catrine Tudor-Locke, Ben P Butitta, Sheletta Donatto, Shannon H Cocreham, Abby C King, Cynthia M Castro, William L Haskell, Randall S Stafford, Leslie A Pruitt, Kathy Berra, Veronica Yank, Roger A Fielding, Miriam E Nelson, Sara C Folta, Edward M Phillips, Christine K Liu, Erica C McDavitt, Kieran F Reid, Dylan R Kirn, Evan P Pasha, Won S Kim, Vince E Beard, Eleni X Tsiroyannis, Cynthia Hau, Todd M Manini, Stephen D Anton, Susan Nayfield, Thomas W Buford, Michael Marsiske, Bhanuprasad D Sandesara, Jeffrey D Knaggs, Megan S Lorow, William C Marena, Irina Korytov, Holly L Morris, Margo Fitch, Floris F Singletary, Jackie Causer, Katie A Radcliff, Anne B Newman, Stephanie A Studenski, Bret H Goodpaster, Nancy W Glynn, Oscar Lopez, Neelesh K Nadkarni, Kathy Williams, Mark A Newman, Geroge Grove, Janet T Bonk, Jennifer Rushing, Piera Kost, Diane G Ives, Stephen B Kritchevsky, Anthony P Marsh, Tina E Brinkley, Jamehl S Demons, Kaycee M Sink, Kimberly Kennedy, Rachel Shertzer-Skinner, Abbie Wrights, Rose Fries, Deborah Barr, Thomas M Gill, Robert S Axtell, Susan S Kashaf, Nathalie de Rekeneire, Joanne M McGloin, Karen C Wu, Denise M Shepard, Barbara Fennelly, Lynne P Iannone, Raeleen Mautner, Theresa Sweeney Barnett, Sean N Halpin, Matthew J Brennan, Julie A Bugaj, Maria A Zenoni, Bridget M Mignosa, Jeff Williamson, Hugh C Hendrie, Stephen R Rapp, Joe Verghese, Nancy Woolard, Mark Espeland, Janine Jennings, Valerie K Wilson, Carl J Pepine, Mario Ariet, Eileen Handberg, Daniel Deluca, James Hill, Anita Szady, Geoffrey L Chupp, Gail M Flynn, John L Hankinson, Carlos A Vaz Fragoso, Erik J Groessl, Robert M Kaplan
Journal: JAMA Internal Medicine (2022)

Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults.
Evolution of associating liver partition and portal vein ligation for staged hepatectomy from 2012 to 2021: A bibliometric analysis. Review
Authors: Junwei Zhang, Xiaobo Yang, Jinyu Fang, Quan-Cheng Cheng, Hui-Ru Ding, Yan-Rong Sun, Man Li, Jing-Lin Zhang, Lei Zhang, Haitao Zhao, Xinting Sang, Yi-Yao Xu, Wei-Guang Zhang, Xin Lu
Journal: International Journal of Surgery (2022)
Sustaining Antimicrobial Stewardship in a High–Antibiotic Resistance Setting
Authors: Tat Ming Ng, Shi Thong Heng, Boon Hou Chua, Li Wei Ang, Sock Hoon Tan, Hui Lin Tay, Min Yi Yap, Jason Quek, Christine B. Teng, Barnaby E. Young, Ray Lin, Brenda Ang, Tau Hong Lee, David C. Lye
Journal: JAMA Network Open (2022)

There is a lack of studies comparing the intended and unintended consequences of prospective review and feedback (PRF) with computerized decision support systems (CDSS), especially in the longer term in antimicrobial stewardship.To examine the outcomes associated with the sequential implementation of PRF and CDSS and changes to these interventions with long-term use of antibiotics for and incidence of multidrug resistant organisms (MDROs) and other unintended outcomes.This cohort study used an interrupted time series with segmented regression analysis of data from January 2007 to December 2018. Data were extracted from the electronic medical records of patients admitted at a large university teaching hospital with high rates of antibiotic resistance in Singapore. Data were analyzed from June 2019 to June 2020.PRF of piperacillin-tazobactam and carbapenems (intervention 1, April 2009), with the addition of hospital-wide CDSS (intervention 2, April 2011), and lifting of CDSS for half of the hospital wards for 6 months (intervention 3, March 2017).Monthly antimicrobial use was measured in defined daily doses (DDDs) per 1000 patient-days. The monthly incidence of MDROs was calculated as number of clinical isolates detected per 1000 inpatient-days over a 6-month period. Unintended outcomes examined included in-hospital mortality and age-adjusted length of stay (LOS).The number of inpatients increased from 56 263 in 2007 to 63 572 in 2018. During the same period, the mean monthly patient days increased from 33 929 in 2007 to 45 603 in 2018, and the proportion of patients older than 65 years increased from 45.5% in 2007 to 56.6% in 2018. After intervention 1, there were 0.33 (95% CI, 0.18 to 0.48) more DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -11.05 (95% CI, -15.55 to -6.55) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 2, there were -0.22 (95% CI, -0.33 to -0.10) fewer DDDs per 1000 patient-days per month of piperacillin-tazobactam and carbapenems and -2.10 (95% CI, -3.13 to -1.07) fewer DDDs per 1000 patient-days per month for other broad-spectrum antibiotics. After intervention 3, use of piperacillin-tazobactam and carbapenem increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1000 patient-days per month. After intervention 2, incidence of Clostridioides difficile decreased (estimate, -0.02 [95% CI, -0.03 to -0.01] cases per 1000 patient-days per month).In this cohort study, concurrent PRF and CDSS were associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other antibiotics.
Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice
Authors: Jinxi Wang, Qian Shi, Yihui Wang, Logan W. Dawson, Grace Ciampa, Weiyang Zhao, Guangqin Zhang, Biyi Chen, Robert M. Weiss, Chad E. Grueter, Duane D. Hall, Long-Sheng Song
Journal: Circulation Research (2022)

Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby JP2 (junctophilin-2), an essential component of the excitation-contraction coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT [N-terminal fragment of JP2]) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes. This study aims to determine whether JP2NT can be leveraged by gene therapy techniques for attenuating HF progression in a preclinical pressure overload model.
Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment
Authors: Talia Salzman, Yanina Sarquis-Adamson, Surim Son, Manuel Montero-Odasso, Sarah Fraser
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Older adults with mild cognitive impairment (MCI) have the highest risk of progressing to dementia. Evidence suggests that nonpharmacological, single-domain interventions can prevent or delay progressive declines, but it is unclear whether greater cognitive benefits arise from multidomain interventions. <h3>Objective</h3> To determine whether multidomain interventions, composed of 2 or more interventions, are associated with greater improvements in cognition among older adults with MCI than a single intervention on its own. <h3>Data Sources</h3> MEDLINE, Embase, PsycInfo, AgeLine, CINAHL, and Cochrane Central Register of Controlled Trials were systematically searched from database inception to December 20, 2021. <h3>Study Selection</h3> Included studies contained (1) an MCI diagnosis; (2) nonpharmacological, multidomain interventions that were compared with a single active control; (3) older adults aged 65 years and older; and (4) randomized clinical trials. <h3>Data Extraction and Synthesis</h3> Data were screened and extracted by 3 independent reviewers. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, random-effects meta-analyses were used to calculate effect sizes from the standardized mean difference (SMD) and 95% CIs. <h3>Main Outcomes and Measures</h3> Postintervention cognitive test scores in 7 cognitive domains were compared between single-domain and multidomain groups. Exposure to the intervention was analyzed. <h3>Results</h3> A total of 28 studies published between 2011 and 2021, including 2711 older adults with MCI, reported greater effect sizes in the multidomain group for global cognition (SMD, 0.41; 95% CI, 0.23-0.59;<i>P</i> &lt; .001), executive function (SMD, 0.20; 95% CI, 0.04-0.36;<i>P</i> = .01), memory (SMD, 0.29; 95% CI, 0.14-0.45;<i>P</i> &lt; .001), and verbal fluency (SMD, 0.30; 95% CI, 0.12-0.49;<i>P</i> = .001). The Mini-Mental State Examination (SMD, 0.40; 95% CI, 0.17-0.64;<i>P</i> &lt; .001), category verbal fluency test (SMD, 0.34; 95% CI, 0.13-0.56;<i>P</i> = .002), Trail Making Test–B (SMD, 0.46; 95% CI, 0.13-0.80;<i>P</i> = .007), and Wechsler Memory Scale–Logical Memory I (SMD, 0.47; 95% CI, 0.15-0.80;<i>P</i> &lt; .001) and II (SMD, 0.26; 95% CI, 0.07-0.45;<i>P</i> &lt; .001) favored the multidomain group. Exposure to the intervention varied between studies: the mean (SD) duration was 71.3 (36.0) minutes for 19.8 (14.6) weeks with sessions taking place 2.5 (1.1) times per week, and all interventions lasted less than 1 year. <h3>Conclusions and Relevance</h3> In this study, short-term multidomain interventions (&lt;1 year) were associated with improvements in global cognition, executive function, memory, and verbal fluency compared with single interventions in older adults with MCI.
Bias Reduction through Analysis of Competing Events (BRACE) Correction to Address Cancer Treatment Selection Bias in Observational Data
Authors: Casey W. Williamson, Tyler J. Nelson, Caroline A. Thompson, Lucas K. Vitzthum, Kaveh Zakeri, Paul J. Riviere, Alex K. Bryant, Andrew B. Sharabi, Jingjing Zou, Loren K. Mell
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Cancer treatments can paradoxically appear to reduce the risk of noncancer mortality in observational studies, due to residual confounding. Here we introduce a method, Bias Reduction through Analysis of Competing Events (BRACE), to reduce bias in the presence of residual confounding. Experimental Design: BRACE is a novel method for adjusting for bias from residual confounding in proportional hazards models. Using standard simulation methods, we compared BRACE with Cox proportional hazards regression in the presence of an unmeasured confounder. We examined estimator distributions, bias, mean squared error (MSE), and coverage probability. We then estimated treatment effects of high versus low intensity treatments in 36,630 prostate cancer, 4,069 lung cancer, and 7,117 head/neck cancer patients, using the Veterans Affairs database. We analyzed treatment effects on cancer-specific mortality (CSM), noncancer mortality (NCM), and overall survival (OS), using conventional multivariable Cox and propensity score (adjusted using inverse probability weighting) models, versus BRACE-adjusted estimates. Results: In simulations with residual confounding, BRACE uniformly reduced both bias and MSE. In the absence of bias, BRACE introduced bias toward the null, albeit with lower MSE. BRACE markedly improved coverage probability, but with a tendency toward overcorrection for effective but nontoxic treatments. For each clinical cohort, more intensive treatments were associated with significantly reduced hazards for CSM, NCM, and OS. BRACE attenuated OS estimates, yielding results more consistent with findings from randomized trials and meta-analyses. Conclusions: BRACE reduces bias and MSE when residual confounding is present and represents a novel approach to improve treatment effect estimation in nonrandomized studies.
Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
Authors: Chuang Guo, Mingming Wu, Beibei Huang, Rui Zhao, Linlin Jin, Binqing Fu, Ping Wang, Dongyao Wang, Meijuan Zheng, Jingwen Fang, Haiming Wei, Kun Qu, Fang Ni
Journal: Genome Medicine (2022)

Abstract Background Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. Methods We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. Results We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52 + NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. Conclusions We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system.
Social conformism and confidence in systems as additional psychological antecedents of vaccination: a survey to explain intention for COVID-19 vaccination among healthcare and welfare sector workers, France, December 2020 to February 2021
Authors: Simi Moirangthem, Cyril Olivier, Amandine Gagneux-Brunon, Gérard Péllissier, Dominique Abiteboul, Isabelle Bonmarin, Elisabeth Rouveix, Elisabeth Botelho-Nevers, Judith E. Mueller
Journal: Eurosurveillance (2022)

BackgroundThe start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.AimWe explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.MethodsWe developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.ResultsAmong 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51-29.67) and a positive perception of employer's encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36-12.22). The strongest association of a knowledge item was identifying the statement '
Opioid and Naloxone Prescribing Following Insertion of Prompts in the Electronic Health Record to Encourage Compliance With California State Opioid Law
Authors: Lewei Duan, Ming-Sum Lee, John L. Adams, Adam L. Sharp, Jason N. Doctor
Journal: JAMA Network Open (2022)

Opioid addiction or dependency is a serious crisis in the US that affects public health as well as social and economic welfare. The State of California passed Assembly Bill (AB) 2760 in 2018 that mandates the coprescription of naloxone and opioids for patients with a high overdose risk.
Mindfulness-Based Therapy Reduces Chronic Pain and Opioid Misuse
Authors: Anita Slomski
Journal: JAMA (2022)

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