tbuckley/cabot-search huggingface dataset:
Abstract 17337: The Effect of Digoxin on Hemocompatibility Related Adverse Events in Patients With Durable Left Ventricular Assist Devices
Authors: Isabel Balachandran, Kevin Kennedy, Jose Nunez, Wilson Grandin, Arthur R Garan, Shweta Motiwala, Pablo A Quintero, Lisa Fleming, Marwa Sabe
Journal: Circulation (2020)

Introduction: Hemocompatibility-related adverse events (HRAE) including stroke, pump thrombosis, and gastrointestinal bleeding (GIB), is a major cause of mortality in patients with continuous flow left ventricular assist devices (CF-LVAD). Digoxin (dig) is used in treatment of advanced heart failure, and has been implicated in decreasing angiogenesis via HIF-alpha/TGF inhibition. There is conflicting data regarding the effect of dig on GIB rates in patients with cf-LVADs. We investigated the association of dig use in patients implanted with CF-LVADs with HRAE with both centrifugal and axial flow devices. Methods: 12,002 patients from the INTERMACS registry implanted with cf-LVADs between 2012-2017 and were alive at 1-month were included. The event rates of HRAE at 1-yr post implant were compared in patients with or without dig use at 1-month post implant. Cox proportional hazards modeling was used to assess the independent association of dig use and HRAE. Results: There was no significant difference in age, sex, race, Cr, INR, DM, and AST in those who were prescribed vs. not prescribed dig at 1 month. On univariate analysis, dig was associated with decreased HRAE in patients with CF-LVADs at 1-year post implantation (37% vs 41%, p&lt;0.01) (Fig. 1) however this was primarily driven by decreased neurologic events. There was no association with GIB (p 0.18). On multivariate analysis, dig was not found to be an independent predictor of HRAE (HR 0.95, 95% CI 0.89-1.02, p 0.2) (Figure 2). Conclusions: Despite previous smaller studies which suggested a decreased risk of HRAE and GIB in patients with cf-LVADs, we found that dig was not an independent predictor of HRAE.
Abstract P111: Untargeted Metabolomics Study And Bidirectional Mendelian Randomization Analyses Identified Novel Metabolites Mediating The Effect Of Current Smoking On Body Mass Index
Authors: Ruiyuan Zhang, Tanika N Kelly, Lydia A Bazzano, Wei Chen, Jiang He, Shengxu Li, Changwei Li
Journal: Circulation (2021)

Introduction: Many studies identified that smokers had lower body mass index (BMI) than non-smokers, but the underlying mechanisms are not well understood. Hypothesis: An untargeted metabolomics study will identify novel mechanisms underlying smoking associated weight loss. Methods: We performed cross-sectional analyses among all 248 current smokers and 637 never smokers participated in the Bogalusa Heart Study 2016 survey. After stringent quality control and normalization, 1,202 plasma metabolites were assessed for mediation effects on smoking-BMI association after controlling for age, gender, race, education, drinking and physical activity. The collective mediation effects of metabolites were estimated by comparing the smoking-BMI associations before and after controlling for all significant metabolites after Bonferroni correction. Bidirectional Mendelian randomization analyses were then performed on a subset of participants (n=654) to delineate causal directions among smoking, BMI, and significant metabolites. We constructed multi-locus genetic risk scores (GRS) for smoking and BMI based on findings from published GWASs with a sample size of more than 250,000. Multivariable linear regression controlling for the same covariates as in the mediation analyses was used to estimate associations between smoking- and BMI-GRSs and the significant metabolites. Results: Compared to never smokers, current smokers had a 3.31 kg/m 2 (95% confidence interval [CI]: 2.15-4.47) lower BMI after adjusting for all covariables. A total of 40 metabolites significantly mediated and explained 90.7% of the smoking-BMI association. Seven of the significant metabolites were associated with smoking GRS but not BMI GRS, suggesting a true mediation role in the smoking-BMI association. The seven metabolites, including homoarginine (mediation beta=-0.49 kg/m 2 , 95% CI: -0.78 to -0.26), 1-oleoyl-GPE (18:1) (mediation beta=-0.44 kg/m 2 , 95% CI: -0.72 to -0.22), 1-linoleoyl-GPE (18:2)* (mediation beta=-0.59 kg/m 2 , 95% CI: -0.90 to -0.32), beta-cryptoxanthin (mediation beta=0.53 kg/m 2 , 95% CI: 0.27 to 0.83), 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4) (mediation beta=0.39 kg/m 2 , 95% CI: 0.18 to 0.65), sphingomyelin (d18:2/21:0, d16:2/23:0)* (mediation beta=-0.54 kg/m 2 , 95% CI: -0.84 to -0.28), and sphingomyelin (d17:2/16:0, d18:2/15:0)* (mediation beta=-0.92 kg/m 2 , 95% CI: -1.30 to -0.59), mediated 36.3% of the association between current smoking and BMI. We also identified 6 metabolites significantly associated with BMI GRS but not with smoking GRS, and 2 significantly associated with both smoking- and BMI-GRSs. Conclusions: We identified 7 plasma metabolites that mediated a large proportion of the association between smoking and BMI.
춘계학술대회 : 구연 ; 선택적 COX-2 억제제인 NS398의 간암 세포주 성장억제 기전
Authors: 장우임, 백지연, 배시현, 최종영, 윤승규, 조세현, 양진모, 안병민, 이영석, 차상복, 김부성
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: Cyclooxygenase-2 (COX-2)의 간세포암 세포주내에서의 발현과 NS398 투여 후의 억제효과는 여러 문헌들을 통해 기술되었다. 그러나 NS398의 억제 효과와 COX-2의 발현 정도와의 연관성, NS398의 성장억제 기전 등은 보고자에 따라 다양하다. 본 연구에서는 HepG2, HuH-7 세포주에서 COX-2 발현을 확인하고 NS398에 의한 성장억제 유도 기전을 알아보고자 하였다. 대상 및 방법: HepG, HuH-7 세포주
102P Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases: Characteristics and validation of prognostic models in a large real-life database
Authors: M. Carausu, M. Carton, A. Darlix, D. Pasquier, M. Leheurteur, M. Debled, M-A. Mouret-Reynier, A. Gonçalves, F. Dalenc, B. Verret, M. Campone, J-M. Ferrero, C. Levy, J-D. Fumet, C. Lefeuvre-Plesse, T. Petit, C. Jouannaud, L. Larrouquere, M. Chevrot, L. Cabel
Journal: Annals of Oncology (2021)
Abstract 16090: Mitochondrial Fission Related Mirnas Plays a Role in the Etiology of Pulmonary Artery Diseases
Authors: Noriko Iwatani, Kayoko Kubota, Yoshiyuki Ikeda, Sunao Miyanaga, Akihiro Tokushige, Mitsuru Ohishi
Journal: Circulation (2020)

Background: Mitochondria play a crucial role in developing cardiovascular diseases through reactive oxygen species production. Mitochondria are dynamic organelles that undergo fission and fusion and mitochondrial fission is reported to cause pulmonary artery diseases (PH). This study examined whether and how mitochondrial fission-related miRNA are involved in the etiology of PH. Methods: We enrolled 41 patients with PH (mean age: 61.2±13.4, 31 female) and 30 control patients (mean age: 67.4±12.0, 14 female). PH patients were then categorized as group 1 (n=12), group 3(n=7) and group 4 (n=22). We isolated total RNAs from blood samples and measured circulating miR-140 regulating mitochondrial dynamics to fission and miR-30, miR-485 and miR-499 which induce mitochondrial fusion by real-time PCR. Results: The circulating miRNA levels of miR-140-3p was higher and that of miR-485-3p and miR-485-5p were lower in PH compared to Ctr, whereas miR-30 and miR-499 did not change between the two groups. Among PH patients, circulating levels of miR-140 was highest in patients with group1, and that of miR-485was lowest in patients with group3. These results suggest that circulating miRNA which regulate mitochondrial dynamics to fission is related to PH. Moreover, the levels of miR-140 was co-related to SvO2 (p=0.0065) and the change in cardiac index in PH(p=0.0385), indicating that circulating miR-140 may play a crucial role in the etiology and severity of PH. Conclusion: Circulating miRNA which regulate mitochondrial dynamics to fission may Plays a crucial role in developing PH.
Author Correction: Trained immunity, tolerance, priming and differentiation: distinct immunological processes
Authors: Maziar Divangahi, Peter Aaby, Shabaana Abdul Khader, Luis B. Barreiro, Siroon Bekkering, Triantafyllos Chavakis, Reinout van Crevel, Nigel Curtis, Andrew R. DiNardo, Jorge Dominguez-Andres, Raphael Duivenvoorden, Stephanie Fanucchi, Zahi Fayad, Elaine Fuchs, Melanie Hamon, Kate L. Jeffrey, Nargis Khan, Leo A. B. Joosten, Eva Kaufmann, Eicke Latz, Giuseppe Matarese, Jos W. M. van der Meer, Musa Mhlanga, Simone J. C. F. M. Moorlag, Willem J. M. Mulder, Shruti Naik, Boris Novakovic, Luke O’Neill, Jordi Ochando, Keiko Ozato, Niels P. Riksen, Robert Sauerwein, Edward R. Sherwood, Andreas Schlitzer, Joachim L. Schultze, Michael H. Sieweke, Christine Stabell Benn, Henk Stunnenberg, Joseph Sun, Frank L. van de Veerdonk, Sebastian Weis, David L. Williams, Ramnik Xavier, Mihai G. Netea
Journal: Nature Immunology (2021)
A global database of COVID-19 vaccinations
Authors: Edouard Mathieu, Hannah Ritchie, Esteban Ortiz-Ospina, Max Roser, Joe Hasell, Cameron Appel, Charlie Giattino, Lucas Rodés-Guirao
Journal: Nature Human Behaviour (2021)

An effective rollout of vaccinations against COVID-19 offers the most promising prospect of bringing the pandemic to an end. We present the Our World in Data COVID-19 vaccination dataset, a global public dataset that tracks the scale and rate of the vaccine rollout across the world. This dataset is updated regularly and includes data on the total number of vaccinations administered, first and second doses administered, daily vaccination rates and population-adjusted coverage for all countries for which data are available (169 countries as of 7 April 2021). It will be maintained as the global vaccination campaign continues to progress. This resource aids policymakers and researchers in understanding the rate of current and potential vaccine rollout; the interactions with non-vaccination policy responses; the potential impact of vaccinations on pandemic outcomes such as transmission, morbidity and mortality; and global inequalities in vaccine access. The Our World in Data COVID-19 vaccination tracker charts the scale and rate of global vaccinations against COVID-19, making the data available to scientists, policymakers and the general public
I <i>SPI1</i> something needed for B cells
Authors: Lara Wahlster, Vijay G. Sankaran
Journal: The Journal of Experimental Medicine (2021)

In this issue, Le Coz et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201750) describe a novel immunodeficiency syndrome caused by mutations in SPI1. Through a series of in-depth studies, the authors provide insights into how SPI1 affects blood lineage specification, highlighting the important role of master transcription factors as cellular fate determinants.
β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice
Authors: Nicolas Panayotis, Philip A. Freund, Letizia Marvaldi, Tali Shalit, Alexander Brandis, Tevie Mehlman, Michael M. Tsoory, Mike Fainzilber
Journal: Cell Reports Medicine (2021)

Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-induced gene-expression profiles with the hippocampal transcriptome of an importin α5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent β-sitosterol as a promising candidate. β-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. β-sitosterol injection reduces the effects of restraint stress, contextual fear memory, and c-Fos activation in the prefrontal cortex and dentate gyrus. Moreover, synergistic anxiolysis is observed when combining sub-efficacious doses of β-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of β-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs.
Abstract 046: Characteristics And Outcomes Of In-Hospital Cardiac Arrest Among Patients Diagnosed With COVID-19: A Systematic Review
Authors: Jooyoung Moon, Hanna Moon
Journal: Circulation (2021)

Background: In-hospital cardiac arrest (IHCA) is difficult to manage, especially so in severe COVID-19 patients. The aim of this study was to investigate the characteristics and prognosis of IHCA in patients who were diagnosed with COVID-19. Methods: We performed a systematic review using the PubMed, Embase, Google Scholar, and MedRxiv databases from December 1, 2019 to October 1, 2020. Two independent investigators reviewed studies reporting information on IHCA in COVID-19 patients. Results: Twelve studies and case reports met our inclusion criteria, including a total of 7,134 COVID-19 patients from six countries. IHCA occurred in 956 patients, and of these, CPR documentation was available in 634. The number of males were almost double that of females (65.9% vs. 34.1%), and the mean age ranged from 42 to 69. The initial cardiac rhythm at the time of CPR in descending order of frequency was pulseless electrical activity (43.2%), asystole (37.1%), ventricular fibrillation/pulseless ventricular tachycardia (9.9%), and other/unknown (9.8%). Common comorbidities included hypertension, diabetes, hyperlipidemia, heart disease, and chronic kidney disease. Rate of survival to discharge was 8.8% (56/634), and lower rates were associated with increasing age. Among those who survived, 44.2% (23/52) had moderate to severe neurological dysfunction, defined by cerebral performance category score of 3 or 4. Conclusions: IHCA in COVID-19 patients carry a poor prognosis. Risks are higher in those with comorbidities and the probability of survival is lower in older adults. Even after successful resuscitation, the risk of neurological complications is high. Further studies are needed to stratify risks and optimally manage IHCA in patients with COVID-19.
Abstract 15214: Food Insecurity and Cardiovascular Disease in NHANES (National Health and Nutrition Examination Survey) 2011-2016
Authors: MONICA M DELSON, Janice F Bell, Tequila S Porter, Julie T Bidwell
Journal: Circulation (2020)

Background: Adherence to a heart-healthy diet is foundational for the prevention, management, and treatment of cardiovascular disease (CVD). Despite the fact that adhering to dietary guidelines may be challenging in the context of food insecurity, little is known about the likelihood of food insecurity in persons with CVD. Hypothesis: We hypothesized that persons with CVD (hypertension, coronary artery disease, heart failure, or stroke) would have significantly higher odds of food insecurity. Methods: This was an analysis of data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional study of health in the United States. All adults aged 19 years or older with food insecurity data were included across 3 cycles of NHANES (2011-2016). Food insecurity was measured using the 10-item Food Security Scale. CVD diagnosis was measured by self-report. Risk for food insecurity by CVD diagnosis was examined using multivariable logistic regression models, incorporating NHANES sample and person weights, and controlling for common sociodemographic confounders (age, gender, race/ethnicity, education, marital status). Results: The sample consisted of 17,175 persons (weighted study N =229,247,659). Slightly more than half were male (51.9%), and most were non-Hispanic white (65.1%). Just under half (45.6%) were in early adulthood (19-44 years), 35.3% were in middle adulthood (45-64 years), and 18.6% were in late adulthood (≥65 years). One quarter (25.9%) were food insecure. Consistent with our hypothesis, diagnosis of any CVD (stroke, heart failure, coronary artery disease, or hypertension) was significantly associated with higher likelihood for food insecurity (stroke: OR=2.18; 95% CI 1.83-2.60; p&lt;0.001; heart failure OR=1.94, 95% CI 1.46-2.57, p&lt;0.001; coronary artery disease: OR=1.90, 95% CI 1.49-2.43, p&lt;0.001; and hypertension: OR=1.25, 95% CI 1.10-1.42, p=0.001). Conclusions: Diagnoses of hypertension, stroke, coronary artery disease, and heart failure were all significantly associated with higher risk for food insecurity. Given the necessity of dietary modification in CVD, further efforts to study food insecurity in CVD alongside other social determinants of health are urgently needed.
Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma
Authors: Lisa H. Y. Kim, Carol Saleh, Anna Whalen-Browne, Paul M. O’Byrne, Derek K. Chu
Journal: JAMA (2021)

The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.
Abstract 15702: Chronic Use of Electronic or Tobacco Cigarettes Alters Circulating Polyunsaturated Fatty Acids, Oxidation Status and Cardiovascular Risk in Healthy Young Adults
Authors: Rajat Gupta, Yan Lin, Karla Luna, Anjali Logue, Alexander Yoon, Kacey Haptonstall, Roya Moheimani, Yasmine Choroomi, Kevin Nguyen, Elizabeth Tran, Yifang Zhu, Kym Faull, Jeffrey Gornbein, Holly Middlekauff, Jesus A Araujo
Journal: Circulation (2020)

Introduction: Electronic cigarettes (EC) have recently gained unprecedented popularity with over 5 million users in the United States. However, it is not known whether chronic EC use induces cardiovascular health effects in healthy young adults. Hypothesis: We hypothesized that chronic EC use ≥1 year affects lipid peroxidation and/or antioxidant defense in the circulating blood, as compared to chronic tobacco cigarette (TC) smokers. Methods: We enrolled EC-users (n=32), TC-smokers (n=29) and non-users (n=45) with mean ages of 28.3, 27.8 and 27.4 years, respectively. Plasma concentrations of polyunsaturated fatty acids and oxidized metabolites were assessed by liquid chromatography coupled to ion trap mass spectrometry. Total antioxidant capacity (TAC), heme oxygenase-1 (HO-1) and functional activity of paraoxonase1 (PON1) and arylesterase were determined by colorimetric and enzymatic assays in the plasma. Multivariable analysis was performed using classification models aimed at segregating subjects based on biomarker profiles. Results: As shown in table 1, EC-users and TC-smokers exhibited significant alterations in oxidized linoleic acid (LA) metabolites (9- and 13-hydroxyoctadecadienoic acid (HODE)), arachidonic acid (AA), LA, TAC and HO-1. Multivariable analysis identified a set of 5 biomarkers (13-HODE, LA, 9-HODE, 12-hydroxyeicosatetraenoic acid (HETE), and AA) that discriminated EC-users from TC-smokers and non-users with an overall accuracy of 73.4%. Conclusions: Chronic use of EC induces both common (i.e. reduced 9- and 13-HODEs, and increased TAC) as well as differential effects (i.e. altered concentrations of AA and LA) to those induced by TC, along with intermediate plasma HO-1 concentrations, suggesting that EC, likewise TC smoke, could impact cardiovascular risk.
Abstract P017: Sex Differences Of Longitudinal Changes Of Cognitive Function Over 9 Years Among Older Adults: Findings From Tanushimaru Cohort Study
Authors: Nagisa Morikawa, Hisashi Adachi, David R. Jacobs, Mika Enomoto, Ako Fukami, Akiko Sakaue, Kenta Toyomasu, Maki Yamamoto, Yoshihiro Fukumoto
Journal: Circulation (2021)

Introduction: Mild cognitive impairment (MCI) is often a precursor to dementia and is therefore of increasing interest. Some previous studies showed MCI progresses to dementia faster in women than in men. However, sex differences in the progression of cognitive decline requires additional study. Hypothesis: Correlates of changing patterns of cognitive function differ between the sexes. Methods: We recruited 2653 participants (mean age: 59.2±12.0 years, male 41.6%) as a population-based sample of Tanushimaru, Japan in 2009 and conducted a longitudinal study with a follow-up examination in 2018. Mini-Mental State Examination (MMSE) was a 30-point test used to assess cognitive function. We classified cognitive function as dementia, MCI and normal using MMSE cutpoints ≤23, 24-27, and ≥28, respectively. We performed analysis of covariance (ANCOVA) to examine the correlates of change in MMSE scores in 973 people who attended in both 2009 and 2018. Results: Mean MMSE scores in 2009 were 27.7±2.5 (men:27.4±2.8, women:27.8±2.3, p=0.0016) and in 2018 were 28.3±2.3 (men:28.3±2.2, women:28.4±2.5). Changes in MMSE scores were 0.47±3.04 in men and 0.26±3.13 in women. Cognition status progressed from normal to MCI or from MCI to dementia over 9 years in 26.3% (men:24.9%, women:27.2%) and 2.6%(men:2.8%, women:2.5%), respectively. On the other hand, 72.0% of MCI (men:69.7%, women:73.4%) reverted to normal cognitive status. Cognitive improvement for 9 years was associated with higher high-density lipoprotein (HDL) cholesterol, lower log-transformed serum insulin in 2009 in men(p=0.0198, p=0.008),and higher estimated glomerular filtration rate (eGFR) in 2009 in women (p=0.058). Lower serum magnesium levels in 2009 were marginally associated with the progression from MCI to dementia in both sexes. (Figure 1). Conclusions: Cognitive status function was better in women and improved in both sexes during 9 years. A sex-stratified approach for describing correlates of cognitive status may be useful.