tbuckley/cabot-search huggingface dataset:
NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmias
Authors: Larry Scott Jr, Anke C Fender, Arnela Saljic, Luge Li, Xiaohui Chen, Xiaolei Wang, Dominik Linz, Jilu Lang, Mathias Hohl, Darragh Twomey, Thuy T Pham, Rodrigo Diaz-Lankenau, Mihail G Chelu, Markus Kamler, Mark L Entman, George E Taffet, Prashanthan Sanders, Dobromir Dobrev, Na Li
Journal: Cardiovascular Research (2021)

Abstract Aims Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the ‘NACHT, LRR, and PYD Domains-containing Protein 3’ (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF. Methods and results Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wild-type (WT) and NLRP3 homozygous knockout (NLRP3−/−) mice were subjected to high-fat-diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3−/− mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3−/−) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice. Conclusion These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation.
A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Intravenous and Subcutaneous Garadacimab (CSL312) in Healthy Subjects
Authors: Andrew McKenzie, Anthony Roberts, Sourabh Malandkar, Henrike Feuersenger, Con Panousis, Dipti Pawaskar
Journal: Journal of Allergy and Clinical Immunology (2021)
Implementation of Virtual Training Visits During the Coronavirus Pandemic: a Nursing Perspective
Authors: Linda Trotto, Christopher Vanname, Timothy Kingas
Journal: Journal of Allergy and Clinical Immunology (2021)

Coronavirus (COVID-19) has created a need for alternative practices to provide safe patient care in home infusions. The use of virtual platforms to conduct patient training in the self-administration of ordered medications will prove to be a viable teaching method. Web-based meetings, social media platforms and educational tools have assisted in cohesive virtual teaching among the organization's nurse educators. Evaluation of nurse educator surveys helped to determine the overall effectiveness and educational experience of the virtual training. March 1, 2020 through June 30, 2020, a total number of 2257 visits were performed. Live visits equaled 1875 (83%) compared to 382 (17%) virtual trainings. There was no difference found in the number of visits to reach self-administration competency between live and virtual visits. Technology utilized consisted of a laptop and the social media platforms of Zoom, Skype, and Facetime. During the National COVID-19 pandemic virtual training helped to decrease risk of exposure between the nurse educator and the patient and family. Cost effectiveness was analyzed by the quantity of visits required to indicate patient competency. Nurse educators were able to successfully teach patients safe and independent administration of ordered medications and minimize the risk of exposure to COVID-19 via virtual training during the pandemic.
Fine Particle Exposure and Clinical Aggravation in Neurodegenerative Diseases in New York State
Authors: Yanelli Nunez, Amelia K. Boehme, Marc G. Weisskopf, Diane B. Re, Ana Navas-Acien, Aaron van Donkelaar, Randall V. Martin, Marianthi-Anna Kioumourtzoglou
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Adult-onset neurodegenerative diseases affect millions and negatively impact health care systems worldwide.Evidence suggests that air pollution may contribute to aggravation of neurodegeneration, but studies have been limited.OBJECTIVE: We examined the potential association between long-term exposure to particulate matter ≤2:5 lm in aerodynamic diameter [fine particulate matter (PM 2:5 )] and disease aggravation in Alzheimer's (AD) and Parkinson's (PD) diseases and amyotrophic lateral sclerosis (ALS), using first hospitalization as a surrogate of clinical aggravation.METHODS: We used data from the New York Department of Health Statewide Planning and Research Cooperative System (SPARCS 2000(SPARCS -2014) ) to construct annual county counts of first hospitalizations with a diagnosis of AD, PD, or ALS (total, urbanicity-, sex-, and age-stratified).We used annual PM 2:5 concentrations estimated by a prediction model at a 1-km 2 resolution, which we aggregated to population-weighted county averages to assign exposure to cases based on county of residence.We used outcome-specific mixed quasi-Poisson models with county-specific random intercepts to estimate rate ratios (RRs) for a 1-y PM 2:5 exposure.We allowed for nonlinear exposure-outcome relationships using penalized splines and accounted for potential confounders.RESULTS: We found a positive nonlinear PM 2:5 -PD association that plateaued above 11 lg=m 3 (RR = 1:09, 95% CI: 1.04, 1.14 for a PM 2:5 increase from 8.1 to 10:4 lg=m 3 ).We also found a linear PM 2:5 -ALS positive association (RR = 1:05, 95% CI: 1.01, 1.09 per 1-lg=m 3 PM 2:5 increase), and suggestive evidence of an association with AD.We found effect modification by age for PD and ALS with a stronger positive association in patients <70 years of age but found insufficient evidence of effect modification by sex or urbanization level for any of the outcomes.CONCLUSION: Our findings suggest that annual increase in county-level PM 2:5 concentrations may contribute to clinical aggravation of PD and ALS.Importantly, the average annual PM 2:5 concentration in our study was 8:1 lg=m 3 , below the current American national standards, suggesting the standards may not adequately protect the aging population.
Abstract 16687: Brain Abnormalities Causing Surgical Postponement in Single Ventricle Patients Throughout Staged Surgical Reconstruction
Authors: Mark A Fogel, David Shore, Tom Pawlowski, Peter Schwab, Matthew Harris, Kevin K Whitehead, Marc Keller, Thomas Spray, William Gaynor, Stephanie Fuller, Susan Nicolson, Lisa Montenegro, Laura Diaz, Arastoo Vossough, Daniel Licht
Journal: Circulation (2012)

Background: Single ventricle (SV) pts undergoing staged surgical reconstruction experience a high rate of brain injury & structural brain abnormalities. Much research has documented the occurrence ...
Use of fibrinolytics and deoxyribonuclease in adult patients with pleural empyema: a consensus statement
Authors: Udit Chaddha, Abhinav Agrawal, David Feller-Kopman, Viren Kaul, Samira Shojaee, Fabien Maldonado, Mark K Ferguson, Kevin G Blyth, Horiana B Grosu, John P Corcoran, Ashutosh Sachdeva, Alex West, Eihab O Bedawi, Adnan Majid, Ravindra M Mehta, Erik Folch, Moishe Liberman, Momen M Wahidi, Sidhu P Gangadharan, Mark E Roberts, Malcolm M DeCamp, Najib M Rahman
Journal: The Lancet Respiratory Medicine (2021)
Abstract 19305: Higher Levels of Beta-2 Microglobulin Predict Incident Hypertension
Authors: Shih-Jen Hwang, George Chen, Chen Yao, Chunyu Liu, Ci Song, Tianxiao Huan, Michael Mendelson, Asya Lyass, Paul Courchesne, Andrew D Johnson, Daniel Levy
Journal: Circulation (2016)

Background and significance: Beta-2-microglobulin (β2M) is a subunit of the histocompatibility class I (MHC I) molecule and a biomarker of renal dysfunction. Prior studies have shown associations o...
Corrigendum to: Recycling drug screen repurposes hydroxyurea as a sensitizer of glioblastomas to temozolomide targeting de novo DNA synthesis, irrespective of molecular subtype
Authors: Jian Teng, Seyedali Hejazi, Lotte Hiddingh, Litia Carvalho, Mark de Gooijer, Hiroaki Wakimoto, Marco Barazas, Marie Tannous, Andrew S Chi, David P Noske, Pieter Wesseling, Thomas Wurdinger, Tracy T Batchelor, Bakhos A Tannous
Journal: Neuro-Oncology (2020)

The authors wish to correct a mistake in Figure 1, Panel A: the label for cell SNZ308, SNZ308r1, and SNZ308r2 should be LNZ308, LNZ308r1, and LNZ308r2, respectively (Volume 20, Issue 5, doi:10.1093/neuonc/nox198).
Adenoma detection by Endocuff-assisted versus standard colonoscopy in an organized screening program: the “ItaVision” randomized controlled trial
Authors: Manuel Zorzi, Cesare Hassan, Jessica Battagello, Giulio Antonelli, Maurizio Pantalena, Gianmarco Bulighin, Saverio Alicante, Tamara Meggiato, Erik Rosa-Rizzotto, Federico Iacopini, Carmelo Luigiano, Fabio Monica, Arrigo Arrigoni, Bastianello Germanà, Flavio Valiante, Beatrice Mallardi, Carlo Senore, Grazia Grazzini, Paola Mantellini
Journal: Endoscopy (2021)

Abstract Background The Endocuff Vision device (Arc Medical Design Ltd., Leeds, UK) has been shown to increase mucosal exposure, and consequently adenoma detection rate (ADR), during colonoscopy. This nationwide multicenter study assessed possible benefits and harms of using Endocuff Vision in a fecal immunochemical test (FIT)-based screening program. Methods Patients undergoing colonoscopy after a FIT-positive test were randomized 1:1 to undergo Endocuff-assisted colonoscopy or standard colonoscopy, stratified by sex, age, and screening history. Primary outcome was ADR. Secondary outcomes were ADR stratified by endoscopists’ ADR, advanced ADR (AADR), adenomas per colonoscopy (APC), withdrawal time, and adverse events. Results 1866 patients were enrolled across 13 centers. After exclusions, 1813 (mean age 60.1 years; male 53.8 %) were randomized (908 Endocuff Vision, 905 standard colonoscopy). ADR was significantly higher in the Endocuff Vision arm (47.8 % vs. 40.8 %; relative risk [RR] 1.17, 95 % confidence interval [CI] 1.06–1.30), with no differences between arms regarding size or morphology. When stratifying for endoscopists’ ADR, only low detectors (ADR &lt; 33.3 %) showed a statistically significant ADR increase (Endocuff Vision 41.1 % [95 %CI 35.7–46.7] vs. standard colonoscopy 26.0 % [95 %CI 21.3–31.4]). AADR (24.8 % vs. 20.5 %, RR 1.21, 95 %CI 1.02–1.43) and APC (0.94 vs. 0.77; P = 0.001) were higher in the Endocuff Vision arm. Withdrawal time and adverse events were similar between arms. Conclusion Endocuff Vision increased ADR in a FIT-based screening program by improving examination of the whole colonic mucosa. Utility was highest among endoscopists with a low ADR.
Effect of Wearing a Novel Electronic Wearable Device on Hand Hygiene Compliance Among Health Care Workers
Authors: Daniela Pires, Angele Gayet-Ageron, Chloe Guitart, Yves-Alain Robert, Carolina Fankhauser, Ermira Tartari, Alexandra Peters, Funda Tymurkaynak, Simon Fourquier, Herve Soule, Rene Beuchat, Fernando Bellissimo-Rodrigues, Yves Martin, Walter Zingg, Didier Pittet
Journal: JAMA Network Open (2021)

Hand hygiene (HH) is essential to prevent hospital-acquired infections.To determine whether providing real-time feedback on a simplified HH action improves compliance with the World Health Organization's "5 Moments" and the quality of the HH action.This open-label, cluster randomized, stepped-wedge clinical trial was conducted between June 1, 2017, and January 6, 2018 (with a follow-up in March 2018), in a geriatric hospital of the University of Geneva Hospitals, Switzerland. All 12 wards and 97 of 306 eligible health care workers (HCWs) volunteered to wear a novel electronic wearable device that delivered real-time feedback on duration of hand rubbing and application of a hand-sized customized volume of alcohol-based handrub (ABHR).This study had 3 sequential periods: baseline (no device), transition (device monitoring without feedback), and intervention (device monitoring and feedback). The start of the transition period was randomly allocated based on a computer-generated block randomization.The primary outcome was HH compliance, according to the direct observation method during intervention as compared with baseline. Secondary outcomes included the volume of ABHR and duration of hand rubbing measured by the device during intervention as compared with transition.All wards and respective HCWs were evenly assigned to group 1 (26 participants), 2 (22 participants), 3 (25 participants), or 4 (24 participants). Twelve HCWs did not fully complete the intervention but were included in the analysis. During 759 observation sessions, 6878 HH opportunities were observed. HH compliance at intervention (62.9%; 95% CI, 61.1%-64.7%) was lower than at baseline (66.6%; 95% CI, 64.8%-68.4%). After adjusting for covariates, HH compliance was not different between periods (odds ratio, 1.03; 95% CI, 0.75-1.42; P = .85). Days since study onset (OR, 0.997; 95% CI, 0.994-0.998; P < .001), older age (OR, 0.97; 95% CI, 0.95-0.99; P = .015), and workload (OR, 0.29; 95% CI, 0.20-0.41; P < .001) were independently associated with reduced HH compliance. The median (interquartile range) volume of ABHR and duration of hand rubbing in transition and intervention increased from 1.12 (0.76-1.68) mL to 1.71 (1.01-2.76) mL and from 6.5 (4.5-10.5) seconds to 8 (4.5-15.5) seconds, respectively. There were no serious adverse events.The use of this device did not change HH compliance, but increased the duration of hand rubbing and volume of ABHR used by HCWs.isrctn.org Identifier: ISRCTN25430066.
Clinical and genetic characteristics of children with acute lymphoblastic leukemia and Li–Fraumeni syndrome
Authors: Greta Winter, Renate Kirschner-Schwabe, Stefanie Groeneveld-Krentz, Gabriele Escherich, Anja Möricke, Arend von Stackelberg, Martin Stanulla, Simon Bailey, Lisa Richter, Doris Steinemann, Tim Ripperger, Adela Escudero, Roula Farah, Olli Lohi, Karin Wadt, Marjolijn Jongmans, Nienke van Engelen, Cornelia Eckert, Christian Peter Kratz
Journal: Leukemia (2021)

Approximately 10% of cases of childhood cancer arise in the context of a cancer predisposition syndrome (CPS) [1].Among the rare CPS, Li-Fraumeni syndrome (LFS, MIM#151623) is relatively common and estimated to account for >1% of cases of childhood cancer [2].LFS is a dominantly inherited condition caused by pathogenic germline variants in the TP53 tumor suppressor gene [3,4].Children with LFS are predisposed to a range of neoplasms such as osteosarcoma, adrenocortical carcinoma, medulloblastoma, choroid plexus carcinoma, anaplastic rhabdomyosarcoma, and (frequently hypodiploid) acute lymphoblastic leukemia (LFS-ALL) [5,6].Notably,
Endothelial Cell Receptors in Tissue Lipid Uptake and Metabolism
Authors: Nada A. Abumrad, Ainara G. Cabodevilla, Dmitri Samovski, Terri Pietka, Debapriya Basu, Ira J. Goldberg
Journal: Circulation Research (2021)

Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids (FAs), excess lipid accumulation can cause cardiomyopathy. Similarly, high delivery of cholesterol can initiate coronary artery atherosclerosis. Hearts and arteries-unlike liver and adrenals-have nonfenestrated capillaries and lipid accumulation in both health and disease requires lipid movement from the circulation across the endothelial barrier. This review summarizes recent in vitro and in vivo findings on the importance of endothelial cell receptors and uptake pathways in regulating FAs and cholesterol uptake in normal physiology and cardiovascular disease. We highlight clinical and experimental data on the roles of ECs in lipid supply to tissues, heart, and arterial wall in particular, and how this affects organ metabolism and function. Models of FA uptake into ECs suggest that receptor-mediated uptake predominates at low FA concentrations, such as during fasting, whereas FA uptake during lipolysis of chylomicrons may involve paracellular movement. Similarly, in the setting of an intact arterial endothelial layer, recent and historic data support a role for receptor-mediated processes in the movement of lipoproteins into the subarterial space. We conclude with thoughts on the need to better understand endothelial lipid transfer for fuller comprehension of the pathophysiology of hyperlipidemia, and lipotoxic diseases such as some forms of cardiomyopathy and atherosclerosis.
Identification of theranostic factors for patients developing metastasis after surgery for early-stage lung adenocarcinoma
Authors: Wei-Chung Cheng, Chun-Yu Chang, Chia-Chien Lo, Chih-Ying Hsieh, Ting-Ting Kuo, Guan-Chin Tseng, Sze-Ching Wong, Shu-Fen Chiang, Kevin Chih-Yang Huang, Liang-Chuan Lai, Tzu-Pin Lu, K.S. Clifford Chao, Yuh-Pyng Sher
Journal: Theranostics (2021)

Rationale: Lung adenocarcinoma (LUAD) is an aggressive disease with high propensity of metastasis. Among patients with early-stage disease, more than 30% of them may relapse or develop metastasis. There is an unmet medical need to stratify patients with early-stage LUAD according to their risk of relapse/metastasis to guide preventive or therapeutic approaches. In this study, we identified 4 genes that can serve both therapeutic and diagnostic (theranostic) purposes. Methods: Three independent datasets (GEO, TCGA, and KMPlotter) were used to evaluate gene expression profile of patients with LUAD by unbiased screening approach. Upon significant genes uncovered, functional enrichment analysis was carried out. The predictive power of their expression on patient prognosis were evaluated. Once confirmed their theranostic roles by integrated bioinformatics, we further conducted in vitro and in vivo validation. Results: We found that four genes (ADAM9, MTHFD2, RRM2, and SLC2A1) were associated with poor patient outcomes with an increased hazard ratio in LUAD. Knockdown of them, both separately and simultaneously, suppressed lung cancer cell proliferation and migration ability in vitro and prolonged survival time in metastatic tumor mouse models. Moreover, these four biomarkers were found to be overexpressed in tumor tissues from LUAD patients, and the total immunohistochemical staining scores correlated with poor prognosis. Conclusions: These results suggest that these four identified genes could be theranostic biomarkers for stratifying high-risk patients who develop relapse/metastasis in early-stage LUAD. Developing therapeutic approaches for the four biomarkers may benefit early-stage LUAD patients after surgery.
Definitions and Clinical Trial Design Principles for Coronary Artery Chronic Total Occlusion Therapies: CTO-ARC Consensus Recommendations
Authors: Luiz F. Ybarra, Stéphane Rinfret, Emmanouil S. Brilakis, Dimitri Karmpaliotis, Lorenzo Azzalini, J. Aaron Grantham, David E. Kandzari, Kambis Mashayekhi, James C. Spratt, Harindra C. Wijeysundera, Ziad A. Ali, Christopher E. Buller, Mauro Carlino, David J. Cohen, Donald E. Cutlip, Tony De Martini, Carlo Di Mario, Andrew Farb, Aloke V. Finn, Alfredo R. Galassi, C. Michael Gibson, Colm Hanratty, Jonathan M. Hill, Farouc A. Jaffer, Mitchell W. Krucoff, William L. Lombardi, Akiko Maehara, P.F. Adrian Magee, Roxana Mehran, Jeffrey W. Moses, William J. Nicholson, Yoshinobu Onuma, Georgios Sianos, Satoru Sumitsuji, Etsuo Tsuchikane, Renu Virmani, Simon J. Walsh, Gerald S. Werner, Masahisa Yamane, Gregg W. Stone, Stéphane Rinfret, Gregg W. Stone
Journal: Circulation (2021)

Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.
LKB1/<i>STK11</i> Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms
Authors: Christian Marinaccio, Praveen Suraneni, Hamza Celik, Andrew Volk, Qiang Jeremy Wen, Te Ling, Marinka Bulic, Terra Lasho, Richard P. Koche, Christopher A. Famulare, Noushin Farnoud, Brady Stein, Michael Schieber, Sandeep Gurbuxani, David E. Root, Scott T. Younger, Ronald Hoffman, Naseema Gangat, Panagiotis Ntziachristos, Navdeep S. Chandel, Ross L. Levine, Raajit K. Rampal, Grant A. Challen, Ayalew Tefferi, John D. Crispino
Journal: Cancer Discovery (2021)

The myeloproliferative neoplasms (MPN) frequently progress to blast phase disease, an aggressive form of acute myeloid leukemia. To identify genes that suppress disease progression, we performed a focused CRISPR/Cas9 screen and discovered that depletion of LKB1/Stk11 led to enhanced in vitro self-renewal of murine MPN cells. Deletion of Stk11 in a mouse MPN model caused rapid lethality with enhanced fibrosis, osteosclerosis, and an accumulation of immature cells in the bone marrow, as well as enhanced engraftment of primary human MPN cells in vivo. LKB1 loss was associated with increased mitochondrial reactive oxygen species and stabilization of HIF1α, and downregulation of LKB1 and increased levels of HIF1α were observed in human blast phase MPN specimens. Of note, we observed strong concordance of pathways that were enriched in murine MPN cells with LKB1 loss with those enriched in blast phase MPN patient specimens, supporting the conclusion that STK11 is a tumor suppressor in the MPNs. SIGNIFICANCE: Progression of the myeloproliferative neoplasms to acute myeloid leukemia occurs in a substantial number of cases, but the genetic basis has been unclear. We discovered that loss of LKB1/STK11 leads to stabilization of HIF1a and promotes disease progression. This observation provides a potential therapeutic avenue for targeting progression.This article is highlighted in the In This Issue feature, p. 1307.