tbuckley/cabot-search huggingface dataset:
Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis
Authors: Jaxaira Maggi, Montserrat Carrascal, Lilian Soto, Oscar Neira, María C Cuéllar, Octavio Aravena, Eddie A James, Joaquin Abian, Dolores Jaraquemada, Diego Catalan, Juan C Aguillón
Journal: Annals of the Rheumatic Diseases (2022)

Objective Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA. Methods HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry. Results We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity. Conclusions We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.
Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease
Authors: Nathalia Gonzalez-Jaramillo, Matthias Wilhelm, Ana María Arango-Rivas, Valentina Gonzalez-Jaramillo, Cristina Mesa-Vieira, Beatrice Minder, Oscar H. Franco, Arjola Bano
Journal: Journal of the American College of Cardiology (2022)

The role of lifestyle physical activity (PA) trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear.The purpose of this study was to determine the association of longitudinal PA trajectories with all-cause and cardiovascular disease (CVD) mortality in patients with CHD.Longitudinal cohorts reporting the association of PA trajectories with mortality in patients with CHD were identified in April 2021 by searching 5 databases without language restrictions. Published HRs and 95% CIs were pooled using random effects models and bias assessed by Egger regression.A total of 9 prospective cohorts included 33,576 patients. The mean age was 62.5 years. The maximum follow-up was 15.7 years. All of the studies assessed PA through validated questionnaires, and mortality was well documented. Changes in PA defined 4 nominal PA trajectories. Compared with always-inactive patients, the risk of all-cause mortality was 50% lower in those who remained active (HR: 0.50; 95% CI: 0.39-0.63); 45% lower in those who were inactive but became active (HR: 0.55; 95% CI: 0.44-0.7); and 20% lower in those who were active but became inactive (HR: 0.80; 95% CI: 0.64-0.99). Similar results were observed for CVD mortality, except for the category of decreased activity (HR: 0.91; 95% CI: 0.67-1.24). The overall risk of bias was low. No evidence of publication bias was found. Multiple sensitivity analyses provided consistent results.This study illustrates how patients with CHD may benefit by preserving or adopting an active lifestyle. The observation that the benefits of past activity can be weakened or lost if PA is not maintained may be confounded by disease progression.
Survival Following Alcohol Septal Ablation or Septal Myectomy for Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Hao Cui, Hartzell V. Schaff, Shuiyun Wang, Brian D. Lahr, Ethan J. Rowin, Hassan Rastegar, Shengshou Hu, Mackram F. Eleid, Joseph A. Dearani, Carey Kimmelstiel, Barry J. Maron, Rick A. Nishimura, Steve R. Ommen, Martin S. Maron
Journal: Journal of the American College of Cardiology (2022)

There is little information regarding long-term mortality comparing the 2 most common procedures for septal reduction for obstructive hypertrophic cardiomyopathy (HCM), alcohol septal ablation (ASA), and septal myectomy.This study sought to compare the long-term mortality of patients with obstructive HCM following septal myectomy or ASA.We evaluated outcomes of 3,859 patients who underwent ASA or septal myectomy in 3 specialized HCM centers. All-cause mortality was the primary endpoint of the study.In the study cohort, 585 (15.2%) patients underwent ASA, and 3,274 (84.8%) underwent septal myectomy. Patients undergoing ASA were significantly older (median age: 63.0 years [IQR: 52.7-72.8 years] vs 53.7 years [IQR: 44.9-62.8 years]; P < 0.001) and had smaller septal thickness (19.0 mm [IQR: 17.0-22.0 mm] vs 20.0 mm [IQR: 17.0-23.0 mm]; P = 0.007). Patients undergoing ASA also had more comorbidities, including renal failure, diabetes, hypertension, and coronary artery disease. There were 4 (0.7%) early deaths in the ASA group and 9 (0.3%) in the myectomy group. Over a median follow-up of 6.4 years (IQR: 3.6-10.2 years), the 10-year all-cause mortality rate was 26.1% in the ASA group and 8.2% in the myectomy group. After adjustment for age, sex, and comorbidities, the mortality remained greater in patients having septal reduction by ASA (HR: 1.68; 95% CI: 1.29-2.19; P < 0.001).In patients with obstructive hypertrophic cardiomyopathy, ASA is associated with increased long-term all-cause mortality compared with septal myectomy. This impact on survival is independent of other known factors but may be influenced by unmeasured confounding patient characteristics.
Assessment of Frequency of Rosacea Subtypes in Patients With Rosacea
Authors: Yousef A. Barakji, Amalie Thorsti Møller Rønnstad, Maria O. Christensen, Claus Zachariae, Nita K. F. Wienholtz, Anne-Sofie Halling, Julia-Tatjana Maul, Simon F. Thomsen, Alexander Egeberg, Jacob P. Thyssen
Journal: JAMA Dermatology (2022)

Four distinct rosacea subtypes have traditionally been recognized, but the frequency of these subtypes among patients with rosacea remains unknown.To assess the frequency of 4 rosacea subtypes.This systemic review and meta-analysis included a search of 2 databases, PubMed and Embase, from inception of the databases to November 2, 2021. The search was filtered to include only studies of human participants published in English, French, and German.Studies were screened independently by 2 of the authors and were included if they were original with a sample size of 25 or more patients and reported absolute numbers or frequency of patients affected by rosacea subtypes. Studies that did not report sufficient data to calculate the proportions of subtypes were excluded.Data extraction was performed independently and in duplicate by 2 of the authors, using the search term rosacea, according to the Preferred Reporting items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search term, objectives, and study protocol methods were defined before the study was initiated. A total of 292 studies were included for full-text assessment. Owing to the heterogeneity of the included studies, a random-effects model was used.The main outcome was the proportion of patients with rosacea in each of the 4 major subtype groups defined by the 2002 National Rosacea Society classification system. Measures were absolute numbers or frequency of patients affected by each of the 4 rosacea subtypes.A total of 39 studies examining 9190 patients with rosacea were included. The pooled proportion of erythematotelangiectatic rosacea was 56.7% (95% CI, 51.4%-62.0%), of papulopustular rosacea was 43.2% (95% CI, 38.8%-47.6%), of phymatous rosacea was 7.4% (95% CI, 6.1%-8.9%), and of ocular rosacea was 11.1% (95% CI, 6.7%-16.3%). Subtype distribution occurred equally among men and women except for phymatous rosacea, which was more prevalent in men. Studies from Africa showed the lowest proportion of erythematotelangiectatic rosacea. Differences in frequency of subtypes were observed when stratification by publication year was performed.In this systematic review and meta-analysis, differences were found in rosacea subtypes by patient sex and by continent of origin and publication year of included studies. Erythematotelangiectatic and papulopustular rosacea were the most prevalent subtypes, but data should be interpreted with caution. Future studies should use the phenotype-based rosacea approach.
Evaluation of the Prevalence and Incidence of Pediatric Alopecia Areata Using Electronic Health Record Data
Authors: Paige L. McKenzie, Mitchell Maltenfort, Anna L. Bruckner, Deepti Gupta, Katya L. Harfmann, Patrice Hyde, Christopher B. Forrest, Leslie Castelo-Soccio
Journal: JAMA Dermatology (2022)

Pediatric alopecia areata (AA) prevalence and incidence data are key to understanding the natural history of this medical disease.To determine the prevalence and incidence of AA in a pediatric population across time, age, sex, race and ethnicity, and geographic areas within the US.In this multicenter cohort study conducted among 5 children's hospitals, data (January 2009 to November 2020) were collected from a standardized electronic health record (PEDSnet database, version 4.0) to evaluate the incidence and prevalence of pediatric AA. The study cohort included patients younger than 18 years with at least 2 physician visits during which a diagnosis code for AA was recorded, or 1 dermatologist specialty visit for which AA was recorded.The prevalence denominator population comprised 5 409 919 patients. The incidence denominator population was 2 896 241. We identified 5801 children for inclusion in the AA cohort, and 2398 (41.3%) had 12 months or more of follow-up and were included in the incidence analysis.Of 5801 patients in the AA cohort, the mean (SD) age was 9.0 (4.5) years, 3259 (56.2%) were female, 359 (6.2) were Asian, 1094 (18.9%) were Black, 1348 (23.2%) were Hispanic, and 2362 (40.7%) were White. The overall prevalence of pediatric AA was 0.11%, and the participants in the AA cohort were more often older, female, and members of a racial and ethnic minority group than the full PEDSnet population. The 11-year overall incidence rate of pediatric AA between 2009 and 2020 was 13.6 cases per 100 000 person-years (95% CI, 13.1-14.2). The incidence rate by age was normally distributed and peaked at age 6 years. Rates were 22.8% higher in female patients than male patients (15.1 cases per 100 000 person-years for females vs 12.3 cases per 100 000 person-years for males). Additionally, incidence rates were highest among Hispanic children (31.5 cases per 100 000 person-years).This cohort study examined the prevalence and incidence rates of pediatric AA in the US across time, age, sex, race and ethnicity, and region from 2009 to 2020, finding a prevalence of 0.11% (doubling during the last decade) and incidence rate of 13.6 cases per 100 000 person-years. Additionally, the results identified Asian and Hispanic children as high-risk demographic subgroups who were shown to be 2 and 3 times more likely, respectively, to receive a diagnosis of AA.
Antibiotic Prescriptions Associated With COVID-19 Outpatient Visits Among Medicare Beneficiaries, April 2020 to April 2021
Authors: Sharon V. Tsay, Monina Bartoces, Katryna Gouin, Sarah Kabbani, Lauri A. Hicks
Journal: JAMA (2022)

This study of Medicare claims data examines the prescribing of antibiotics to older US patients who had outpatient visits for COVID-19 in an effort to address unnecessary antibiotic use for viral infections.
ONC201 and ONC206: Metabolically ClipPing the wings of diffuse midline glioma
Authors: Benjamin Purow
Journal: Neuro-Oncology (2022)

Journal Article ONC201 and ONC206: Metabolically ClipPing the wings of diffuse midline glioma Get access Benjamin Purow Benjamin Purow Department of Neurology, University of Virginia, Charlottesville, Virginia, USA Corresponding Author: Benjamin Purow, MD, Neuro-Oncology Division, Neurology Department, West Complex Room 6230, University of Virginia, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA (bwp5g@virginia.edu). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 9, September 2022, Pages 1452–1453, https://doi.org/10.1093/neuonc/noac103 Published: 23 April 2022 Article history Published: 23 April 2022 Corrected and typeset: 03 May 2022
Errors in Byline and Abstract
Authors: Amelia Scott, Louise Sharpe, Ben Colagiuri
Journal: JAMA Psychiatry (2022)

Adam R. Teed, PhD; Justin S. Feinstein, PhD; Maria Puhl, PhD; Rachel C. Lapidus, PhD; Valerie Upshaw, BSN, NP; Rayus T. Kuplicki, PhD; Jerzy Bodurka, PhD; Olujimi A. Ajijola, MD, PhD; Walter H. Kaye, MD; Wesley K. Thompson, PhD; Martin P. Paulus, MD; Sahib S. Khalsa, MD, PhD
Intestinal peroxisome proliferator‐activated receptor α‐fatty acid‐binding protein 1 axis modulates nonalcoholic steatohepatitis
Authors: Tingting Yan, Yuhong Luo, Nana Yan, Keisuke Hamada, Nan Zhao, Yangliu Xia, Ping Wang, Changdong Zhao, Dan Qi, Shoumei Yang, Lulu Sun, Jie Cai, Qiong Wang, Changtao Jiang, Oksana Gavrilova, Kristopher W. Krausz, Daxesh P. Patel, Xiaoting Yu, Xuan Wu, Haiping Hao, Weiwei Liu, Aijuan Qu, Frank J. Gonzalez
Journal: Hepatology (2022)

Background and Aims Peroxisome proliferator‐activated receptor α (PPARα) regulates fatty acid transport and catabolism in liver. However, the role of intestinal PPARα in lipid homeostasis is largely unknown. Here, intestinal PPARα was examined for its modulation of obesity and NASH. Approach and Results Intestinal PPARα was activated and fatty acid‐binding protein 1 (FABP1) up‐regulated in humans with obesity and high‐fat diet (HFD)–fed mice as revealed by using human intestine specimens or HFD/high‐fat, high‐cholesterol, and high‐fructose diet (HFCFD)‐fed C57BL/6N mice and PPARA ‐humanized, peroxisome proliferator response element–luciferase mice. Intestine‐specific Ppara or Fabp1 disruption in mice fed a HFD or HFCFD decreased obesity‐associated metabolic disorders and NASH. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with fatty acid uptake assays in primary intestinal organoids revealed that intestinal PPARα induced the expression of FABP1 that in turn mediated the effects of intestinal PPARα in modulating fatty acid uptake. The PPARα antagonist GW6471 improved obesity and NASH, dependent on intestinal PPARα or FABP1. Double‐knockout ( Ppara/Fabp1 ΔIE ) mice demonstrated that intestinal Ppara disruption failed to further decrease obesity and NASH in the absence of intestinal FABP1. Translationally, GW6471 reduced human PPARA‐driven intestinal fatty acid uptake and improved obesity‐related metabolic dysfunctions in PPARA ‐humanized, but not Ppara ‐null, mice. Conclusions Intestinal PPARα signaling promotes NASH progression through regulating dietary fatty acid uptake through modulation of FABP1, which provides a compelling therapeutic target for NASH treatment.
The obesity paradox is mostly driven by decreased noncardiovascular disease mortality in the oldest old in China: a 20-year prospective cohort study
Authors: Yuebin Lv, Chen Mao, Xiang Gao, John S. Ji, Virginia Byers Kraus, Zhaoxue Yin, Jinqiu Yuan, Huashuai Chen, Jiesi Luo, Jinhui Zhou, Zhihao Li, Jun Duan, Qingyang Zhu, Yi Zeng, Wentao Wang, Jiaonan Wang, Xiaoming Shi
Journal: Nature Aging (2022)
Firearm Violence Following the Implementation of California’s Gun Violence Restraining Order Law
Authors: Veronica A. Pear, Garen J. Wintemute, Nicholas P. Jewell, Jennifer Ahern
Journal: JAMA Network Open (2022)

<h3>Importance</h3> California's gun violence restraining order (GVRO) law, implemented beginning in 2016, allows for people at high risk of harming themselves or others with a firearm to be temporarily disarmed and prevented from purchasing firearms for 3 weeks to 1 year; many states have recently enacted similar laws. The research to date is on older and more limited risk-warrant laws. <h3>Objective</h3> To determine whether implementation of the California GVRO law was associated with decreased rates of firearm assault or firearm self-harm in a large metropolitan county between 2016 and 2019. <h3>Design, Setting, and Participants</h3> This serial cross-sectional study including data from 28 counties used the synthetic control method to evaluate differences in firearm violence between San Diego County and its synthetic control following implementation of the California law from 2016 to 2019. San Diego County was used as the treated unit because it issued substantially more GVROs than any other county in California during the study period. A total of 27 California counties that issued no or very few gun violence restraining orders from 2016 to 2019 and that had stable rates of firearm violence between 2005 and 2015 were included in the control pool. Data were analyzed from February 2021 to July 2021. <h3>Exposures</h3> Implementation of the statewide GVRO law in 2016 in San Diego County. <h3>Main Outcomes and Measures</h3> Annual rates of fatal and nonfatal firearm assault injuries and firearm self-harm injuries per 100 000 people. <h3>Results</h3> In the study period, there were 355 GVROs in San Diego county, and a median (IQR) total of 8 (3-20) GVROs per donor county. The mean difference between the observed rate in San Diego County and the estimated rate in the synthetic San Diego County, 2016-2019, was −0.74 firearm assaults per 100 000 (−13% difference) and 0.13 firearm self-harm injuries per 100 000 (3% difference). Results from in-space placebo tests suggested that these differences cannot be distinguished from variation due to chance (pseudo-<i>P</i>values from a 1-sided test:<i>P </i>for assault = .35,<i>P </i>for self-harm = .67). <h3>Conclusions and Relevance</h3> To our knowledge, this study was the first to analyze the association between GVRO implementation and firearm violence in California and the first to evaluate the association between risk-based firearm removal laws and firearm assault in any state. GVROs were not associated with reduced population-level rates of firearm violence in San Diego County, but this may change as the number of orders increases over time; the association between GVROs and firearm violence at the individual level cannot be inferred from our findings and should be the subject of future studies.
Author Correction: Federated deep learning for detecting COVID-19 lung abnormalities in CT: a privacy-preserving multinational validation study
Authors: Qi Dou, Tiffany Y. So, Meirui Jiang, Quande Liu, Varut Vardhanabhuti, Georgios Kaissis, Zeju Li, Weixin Si, Heather H. C. Lee, Kevin Yu, Zuxin Feng, Li Dong, Egon Burian, Friederike Jungmann, Rickmer Braren, Marcus Makowski, Bernhard Kainz, Daniel Rueckert, Ben Glocker, Simon C. H. Yu, Pheng Ann Heng
Journal: npj Digital Medicine (2022)
Assessment of Clinical Response Following Atezolizumab and Bevacizumab Treatment in Patients With Neuroendocrine Tumors
Authors: Daniel M. Halperin, Suyu Liu, Arvind Dasari, David Fogelman, Priya Bhosale, Armeen Mahvash, Jeannelyn S. Estrella, Laura Rubin, Ajaykumar C. Morani, Mark Knafl, Tim A. Overeem, Szu-Chin Fu, Luisa M. Solis, Edwin Parra Cuentas, Anuj Verma, Hong-Lei Chen, Swati Gite, Priya Subashchandrabose, Shannon Dervin, Katja Schulze, Walter C. Darbonne, Cindy Yun, Ignacio I. Wistuba, P. Andrew Futreal, Scott E. Woodman, James C. Yao
Journal: JAMA Oncology (2022)

Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.This single-arm, open-label nonrandomized clinical study in patients with rare cancers included 40 patients with advanced, progressive grade 1 to 2 NETs (20 with pancreatic NETs [pNETs] and 20 with extrapancreatic NETs [epNETs]) treated at a tertiary care referral cancer center between March 31, 2017, and February 19, 2019. Data were analyzed from June to September 2021.Patients received intravenous bevacizumab and atezolizumab at standard doses every 3 weeks until progression, death, or withdrawal.The primary end point was objective radiographic response using Response Evaluation Criteria in Solid Tumors, version 1.1, with progression-free survival (PFS) as a key secondary end point.Following treatment of the 40 study patients with bevacizumab and atezolizumab, objective response was observed in 4 patients with pNETs (20%; 95% CI, 5.7%-43.7%) and 3 patients with epNETs (15%; 95% CI, 3.2%-37.9%). The PFS was 14.9 (95% CI, 4.4-32.0) months and 14.2 (95% CI, 10.2-19.6) months in these cohorts, respectively.In this nonrandomized clinical trial, findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies.ClinicalTrials.gov Identifier: NCT03074513.
Neutralization of SARS-CoV-2 Omicron sub-lineages BA.1, BA.1.1, and BA.2
Authors: John P. Evans, Cong Zeng, Panke Qu, Julia Faraone, Yi-Min Zheng, Claire Carlin, Joseph S. Bednash, Tongqing Zhou, Gerard Lozanski, Rama Mallampalli, Linda J. Saif, Eugene M. Oltz, Peter J. Mohler, Kai Xu, Richard J. Gumina, Shan-Lu Liu
Journal: Cell Host & Microbe (2022)

Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- and infection-induced immunity. We examine the sensitivity of these sub-lineages and other major variants to neutralizing antibodies from mRNA-vaccinated and boosted individuals, as well as recovered COVID-19 patients, including those infected with Omicron. We find that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit substantial immune escape that is largely overcome by mRNA vaccine booster doses. While Omicron BA.1.1 escapes almost completely from neutralization by early-pandemic COVID-19 patient sera and to a lesser extent from sera of Delta-infected patients, BA.1.1 is sensitive to Omicron-infected patient sera. Critically, all Omicron sub-lineages, including BA.2, are comparably neutralized by Omicron patient sera. These results highlight the importance of booster vaccine doses for protection against all Omicron variants and provide insight into the immunity from natural infection against Omicron sub-lineages.
Can “domino” therapy effectively treat the infection around the prosthesis after the limb salvage surgery of bone tumor? - A study of sequential therapy
Authors: Haochen Mou, Hao Qu, Binghao Li, Shengdong Wang, Hengyuan Li, Xiumao Li, Wenkan Zhang, Wangsiyuan Teng, Zengjie Zhang, Keyi Wang, Fangqian Wang, Hangxiang Sun, Liang Chen, Jiahao Zhang, Xiaoqiang Jin, Cong Wang, Xin Huang, Nong Lin, Zhaoming Ye
Journal: International Journal of Surgery (2022)
Alcohol predisposes obese mice to acute pancreatitis via adipose triglyceride lipase-dependent visceral adipocyte lipolysis
Authors: Xinmin Yang, Linbo Yao, Lei Dai, Mei Yuan, Wenhua He, Tingting Liu, Xianghui Fu, Jing Xue, Robert Sutton, Qing Xia, Wei Huang
Journal: Gut (2022)