tbuckley/cabot-search huggingface dataset:
Abstract 9530: Plaque Rupture, Compared to Plaque Erosion, is Associated With Higher Level of Pan-Coronary Inflammation, Measured by Peri-Coronary Adipose Tissue Attenuation on Coronary Computed Tomography Angiography
Authors: Akihiro Nakajima, Tomoyo Sugiyama, Makoto Araki, Lena M Seegers, Damini Dey, Iris McNulty, Hang Lee, Taishi Yonetsu, Yumi Yasui, Yun Teng, Tatsuhiro Nagamine, Sunao Nakamura, Stephan Achenbach, Tsunekazu Kakuta, Ik-kyung Jang
Journal: Circulation (2021)

Introduction: Vascular inflammation plays a key role in plaque rupture, while the role of inflammation in plaque erosion remains less well defined. Peri-coronary adipose tissue attenuation (PCATA) has emerged as a marker specific for coronary artery inflammation. Direct comparison of the level of vascular inflammation between plaque rupture and plaque erosion has not been reported. Objectives: To compare the level of coronary inflammation between plaque rupture and plaque erosion using PCATA. Methods: Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) who underwent pre-intervention coronary computed tomography angiography and optical coherence tomography (OCT) culprit lesion imaging were enrolled. PCATA was measured in the culprit lesion and in the proximal 40mm segment of the coronary arteries. The relationship between OCT culprit plaque characteristics and PCATA was also examined. Results: Out of 198 patients, plaque rupture was the underlying mechanism in 107 patients (54.0%) and plaque erosion in 91 (46.0%) patients. Plaque rupture had higher PCATA than plaque erosion both at the culprit plaque level (-65.8 ± 7.5 vs. -69.5 ± 11.4 Hounsfield unit [HU], p = 0.010) and at the culprit vessel level (-67.1 ± 7.1 vs. -69.6 ± 8.2 HU, p = 0.024). The mean PCATA of all 3 coronary arteries was also significantly higher in plaque rupture than in plaque erosion indicating a higher level of inflammation (-67.9 ± 5.7 vs. -69.9 ± 6.8 HU, p = 0.030). In the multivariable analysis, plaque rupture was significantly associated with high PCATA at all 3 levels: culprit plaque, culprit vessel, and pan-coronary arteries. Conclusions: PCATA in culprit plaque, culprit vessel, and all 3 coronary arteries was higher in plaque rupture than in plaque erosion. The results indicate pan-coronary inflammation plays a more significant role in plaque rupture than in plaque erosion.
Abstract 9867: Associations of Urinary Isoprostane Levels with Prevalence and Progression of Coronary Artery Calcification and Carotid Plaque in the Multi-Ethnic Study of Atherosclerosis (mesa)
Authors: Ryan Wallace, Di Zhao, Oluseye Ogunmoroti, Eliseo Guallar, Wendy Post, Dhananjay Vaidya, Amir S Heravi, Wendy Ying, Chiadi E Ndumele, Joao A Lima, Pamela Ouyang, Matthew Budoff, Matthew Allison, Ron C Hoogeveen, Erin Michos
Journal: Circulation (2021)

Introduction: Urinary isoprostanes reflect oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) &amp; carotid plaque are markers of subclinical atherosclerosis and prognostic of ASCVD risk. We examined if the urinary isoprostane iPF2α-III and its metabolite iPF2α-III-M were associated with CAC &amp; carotid plaque. Hypothesis: Higher urinary isoprostanes are associated with a greater prevalence, incidence, burden, and progression of CAC &amp; carotid plaque. Methods: 1097 MESA participants free of ASCVD had urinary isoprostanes measured at baseline. All participants underwent cardiac CT at baseline; 1083 underwent repeat CT ~10 yrs later. CAC was measured by Agatston scoring. All participants had carotid ultrasound (US) at baseline; 837 underwent repeat carotid US ~10 yrs later. Carotid plaque score (CPS) was defined as the number of carotid segments containing plaque. Isoprostane levels were divided into tertiles. Relative risk regression and linear mixed effect models determined prevalence/incidence and burden/progression respectively of CAC &amp; CPS. Results: Mean age of participants at baseline was 62.2 (8.3) yrs; 49% were women. There was no association of isoprostanes with CAC at baseline. There was a positive, but not statistically significant association, comparing the highest vs lowest tertiles of iPF2α-III-M and CAC progression over 10 yrs (Fig 1a). There was a statistically significant association comparing the highest vs lowest tertiles of isoprostanes with prevalence and burden of carotid plaque at baseline, but not with CPS incidence/progression (Fig 1b). Conclusions: In this multiethnic cohort, urinary isoprostanes were weakly but positively associated with carotid plaque burden and prevalence in cross sectional analysis and also showed a non-significant trend toward CAC progression, suggesting this measure of oxidative stress may be associated with ASCVD.
Abstract 11404: Disparities in Anticoagulation for Atrial Fibrillation: A Systematic Review of Recent Literature
Authors: Danielle Daly, Jason Wasfy
Journal: Circulation (2021)

Atrial fibrillation (AF) causes 1 in 7 strokes as it is the most prevalent arrhythmia in the United States. 1 Previous work has shown that even with significant recurring AF and high CHA 2 DS 2 VASc scores, there are various disparities that occur within the prescription, type, and quality of anticoagulation control. One previous systematic review published in 2018 discusses disparities within anticoagulation for AF. Given the importance of health equity for this highly efficacious intervention, we aimed to review recent data on disparities with respect to anticoagulation for AF published after 12/31/17. This systematic review used the PubMed database to identify 19 articles that discuss disparities within anticoagulation for AF. We limited our search to articles published after 12/31/17. The search string consisted of 7 phrases that combined AF, anticoagulation, and disparities involving sex, race, ethnicity, income, socioeconomic (SE) status, etc. Articles were excluded if they focused on anticoagulation for conditions other than AF, if they did not discuss anticoagulation as a treatment for AF, and/or lack of inclusion of data referring to disparity as defined above. We found 7 articles on race and anticoagulation, 6 articles on anticoagulation and sex/gender, 3 articles that discussed SE status and anticoagulation, and 5 articles that discuss other types of disparity related to anticoagulation. Results showed that black populations were much less likely to be given anticoagulation than other patients. Black patients were more likely to be given warfarin over DOACs. Women were less anticoagulated than men even when their stroke risk was higher. Some studies in this review found that there were not statistically meaningful differences in anticoagulation use in women and men. Lower income and less educated patients were less likely to receive DOAC compared to warfarin. Compared to a prior systematic review, focusing on articles after 2017 revealed much more information about DOAC use. Disparities first noted in the warfarin era have persisted with DOACs. Given that we have identified disparities in anticoagulation with respect to race, sex, and SE status, more work is needed to identify mechanisms of these disparities and identify potential solutions.
Abstract 10163: Ca <sup>2+</sup> Within the Mitochondria Can Affect the Occurrence of Triggered Arrhythmias in Rats with Right Ventricular Hypertrophy
Authors: Kazunori Kumasaka, Haruka Sato, Wakako Satoh, Chiyohiko Shindoh, Masahito Miura
Journal: Circulation (2021)

Background: Ca 2+ within the sarcoplasmic reticulum affects the propagation of intracellular Ca 2+ (Ca i ) waves, and the velocity of Ca i waves play important roles in the occurrence of triggered arrhythmias. It is still unknown, however, whether Ca 2+ within the mitochondria (Ca m ) affects the velocity of Ca i wave and the occurrence of arrhythmias in right ventricular (RV) hypertrophy. Objective: To know the roles of Ca m in the velocity of Ca i waves and the occurrence of triggered arrhythmias in rats with RV hypertrophy. Methods: Rats were subcutaneously injected with 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). Four weeks after the injection, trabeculae were dissected from the RVs. The force was measured using a silicon strain gauge, Ca m using rhod-2, Ca i using microinjected fura-2 and a CCD camera, and production of reactive oxygen species (ROS) from the slope DCF fluorescence during electrical stimulation. Ca 2+ waves and arrhythmias were induced by electrical stimulation (24°C). Results: MCT-rats showed a higher RV pressure, a larger weight ratio of RV free wall to left ventricle (RV/LV), and faster and larger Ca i waves than Ctr-rats (p&lt;0.01). Among MCT-rats, Ru360 (10 μM), a mitochondrial calcium uniporter (MCU) inhibitor, decreased the occurrence of arrhythmias in trabeculae from rats with a higher RV pressure and a larger RV/LV (n=19). Ru360 decreased rhod-2 signal within trabeculae depending on the RV/LV (r=-0.85, p&lt;0.01, n=10) without changes in Ca i transients, suggesting that inhibition of MCU decreases Ca m in MCT-rats with more severe RV hypertrophy. In addition, Ru360 decreased the velocity of Ca i waves depending on systolic RV pressure (r=-0.60, n=6) and the RV/LV (r=-0.64, n= 7), suggesting that inhibition of MCU decreased the velocity of Ca i waves in MCT-rats with higher RV pressure and more severe RV hypertrophy. Ru360 decreased the slope of DCF fluorescence (p&lt;0.01, n=13). Conclusions: In the hearts with severe RV hypertrophy, inhibition of MCU can cause larger reduction of Ca m , decrease ROS production, and decrease the velocity of Ca i waves and arrhythmias. Thus, in the hearts with severe RV hypertrophy, more Ca 2+ may enter the mitochondria through the MCU, and higher Ca m may be involved in the occurrence of arrhythmias.
Thrombocytosis in COVID-19 patients without myeloproliferative neoplasms is associated with better prognosis but higher rate of venous thromboembolism
Authors: Marko Lucijanic, Ivan Krecak, Ena Soric, Martina Sedinic, Anica Sabljic, Lovorka Derek, Ozren Jaksic, Rajko Kusec
Journal: Blood Cancer Journal (2021)

Thrombocytosis in COVID-19 patients without myeloproliferative neoplasms is associated with better prognosis but higher rate of venous thromboembolism
Abstract 9669: Association of Pathogenic DNA Variants for Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality
Authors: Aniruddh P Patel, Minxian Wang, James Pirruccello, Jacqueline S Dron, Kenney Ng, Pradeep Natarajan, Matthew Lebo, Patrick T Ellinor, Krishna Aragam, Amit V Khera
Journal: Circulation (2021)

Introduction: Pathogenic DNA variants associated with inherited cardiomyopathies are recognized as clinically important and actionable when identified, leading some clinicians to recommend population-wide genomic screening. The prevalence and clinical importance of such variants within the context of contemporary clinical care warrant further study. Methods: Using whole exome sequencing data from participants in Atherosclerosis Risk in Communities (ARIC) and the UK Biobank (UKBB), observed DNA sequence variants in any of 12 genes ( ACTC1, GLA, LMNA, MYBPC3, MYH7, MYL2, MYL3, PRKAG2, TNNI3, TNNT2, TPM1, and TTN ) known to be causative of inherited cardiomyopathies with accepted preventative or therapeutic interventions were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status per recommendations from the American College of Medical Genetics. The relationship of carrier status to risk of death or cardiovascular disease was assessed. Results: Among 9,667 ARIC participants (mean [SD] age 54 [5.7] years; 43.8% female) and 49,744 UKBB participants (mean [SD] age 57.1 [8.0] years; 54.6% female), 68 (0.70%) and 362 (0.73%) harbored an actionable pathogenic or likely pathogenic variant associated with cardiomyopathy, respectively. Carriers of these variants were not reliably identifiable by imaging or electrocardiography signatures. Presence of these variants was associated with 1.7- to 1.8-fold increased risk of heart failure, 2.1- to 2.9-fold increased risk of atrial fibrillation, and 1.6- to 1.8-fold increased risk of all-cause mortality across studies. Conclusions: The findings suggest that approximately 0.7% of middle-aged adult population in ARIC and the UKBB harbored a pathogenic variant associated with cardiomyopathy. Carriers of these variants would be difficult to identify within routine clinical practice but suffer from increased risk of cardiovascular disease and all-cause mortality.
Abstract 14444: A Novel Role for the Hypothalamic Paraventricular Nucleus in Resuscitation From Opioid-Induced Respiratory Depression by Fentanyl in the Rat
Authors: Allison D Brackley, Tamara Truong, Jorge Contreras, Mary Ann Andrade, Glenn M Toney
Journal: Circulation (2021)

Introduction: Opioid receptor antagonists, like naloxone, reverses opioid-induced respiratory depression (OIRD). We recently found that systemic oxytocin reverses fentanyl OIRD in rats. Naloxone triggers a surge in oxytocin release from the hypothalamic paraventricular nucleus (PVN) in anesthetized rats. Hypothesis: Given that naloxone induces PVN oxytocin release, we hypothesized that the PVN, an unrecognized brain region for opioid overdose reversal, is capable of respiratory resuscitation following fentanyl OIRD. Methods: Naloxone (5 mg/kg, i.v.) was given to conscious rats with indwelling venous cannulae. Blood samples were extracted at 5 min post-naloxone to measure plasma oxytocin by ELISA. Under anesthesia, phrenic nerve activity was recorded in vagotomized, paralyzed, and artificially ventilated rats to quantify inspiratory drive following fentanyl (60 nmol/kg, i.v.) and assess OIRD reversal potential following unilateral PVN nanoinjection of naloxone (3 nmol/kg, 50 nL) or vehicle (50 nL). In spontaneously breathing mice with channelrhodopsin expressed exclusively in oxytocin neurons, expired CO 2 was used to monitor rhythmic ventilation and to quantify bradypnea during OIRD. Following fentanyl, blue light (473 nm, 12 mW) pulses (10 ms, 20 Hz) or dummy pulses were delivered to the PVN using a 5 s On/1 s Off pattern for 3 min. Results: Systemic naloxone resulted in a surge in plasma oxytocin compared to vehicle in the conscious rat. Naloxone in PVN both reversed and prevented OIRD by systemic fentanyl in the rat. Photostimulation of PVN oxytocin neurons prevented lethal effects of fentanyl OIRD, whereas dummy pulses failed to prevent lethal respiratory arrest in the mouse. Conclusions: Here, we confirm that naloxone stimulates oxytocin neurons of the PVN and results in a surge of plasma oxytocin. PVN opioid receptor antagonism and photoactivation of PVN oxytocin neurons are individually capable of reversing OIRD. Findings also indicate that PVN oxytocin neurons, previously unrecognized in reversal of OIRD, are a novel target for resuscitation agents.
Abstract 14296: Agatston Aortic Valve Calcium Score and the Prediction of Transcatheter Aortic Valve Replacement Complications: A Systematic Review and Meta-Analysis
Authors: Yehia Saleh, Abdullah Al-abcha, Yehia Saleh, Nadeen N Faza, Stephen H Little, Su Min Chang
Journal: Circulation (2021)

Introduction: Aortic valve calcium score (AVCS) is used to determine aortic stenosis severity, but whether it affects transcatheter aortic valve replacement (TAVR) complications is not well studied. Methods: We conducted a literature search in PubMed using the key words “Aortic valve”, “Calcium score”, “Aortic stenosis”, “Computed tomography”,” Calcification”, “Calcium”, “TAVR”, “TAVI”, “Outcomes”, “Complications” up to December, 31 st , 2020. Several studies assessed the different factors affecting TAVR outcomes, of these, AVCS was usually found to be one of them. Only a few studies investigated the effect of AVCS on TAVR outcomes. We included studies classifying their patient cohort into high and low AVCS. These studies used the Agatston AVCS derived from non-contrast computed tomography (CT) in patients with native aortic valves and they investigated the TAVR outcomes in both groups. Results: Three studies were included in our meta-analysis with a total number of 1839 patients. Our pooled analysis showed a similar risk of 30-day mortality (low AVCS 2% vs high AVCS 2.5%, P=0.63), Permanent pacemaker implantation (low AVCS 13.3 % vs high AVCS 11.9 %, P=0.73), Stroke (low AVCS 2.54% vs high AVCS 2.3%, P=0.69), and Major vascular complications (low AVCS 7.3% vs high AVCS 5.5%, P=0.60). Conclusion: The severity of Aortic valve calcification calculated by the Agatston AVCS had no impact on 30-day mortality, stroke, major vascular complications, or the need for a permanent pacemaker after TAVR is performed.
Opportunistic Infections in Patients Receiving Daratumumab Regimens for Multiple Myeloma (MM)
Authors: Ethan A. Burns, Joe E. Ensor, Kartik Anand, Cesar Gentille, Carlo Guerrero, Ryan B. Kieser, Godsfavor Umoru, Shilpan S. Shah, Jenny H. Petkova, Siddhartha Ganguly, Lawrence Rice, Sai Ravi Kiran Pingali
Journal: Blood (2021)
Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis
Authors: Finn Hinrichsen, Jacob Hamm, Magdalena Westermann, Lena Schröder, Kensuke Shima, Neha Mishra, Alesia Walker, Nina Sommer, Kenneth Klischies, Daniela Prasse, Johannes Zimmermann, Sina Kaiser, Dora Bordoni, Antonella Fazio, Georgios Marinos, Georg Laue, Simon Imm, Valentina Tremaroli, Marijana Basic, Robert Häsler, Ruth A Schmitz, Stefan Krautwald, Andrea Wolf, Bärbel Stecher, Philippe Schmitt-Kopplin, Christoph Kaleta, Jan Rupp, Fredrik Bäckhed, Philip Rosenstiel, Felix Sommer
Journal: Cell Metabolism (2021)
Abstract 11296: Short-Term Low-Saturated Fat Diet Compared to High-Saturated Fat Diet in Patients with Hypertriglyceridemia: Lipids and Lipoproteins Associated with Monocyte Phenotypic Changes
Authors: zeqin lian, Xiaoyuan Perrard, Antu Antony, Xiaoyuan Perrard, Anum Saeed, Xiaoming Jia, Aliza Hussain, Ron C Hoogeveen, Christie M Ballantyne, Huaizhu Wu, Veronica OBrien, Lu Xu, Bingqian Zhang
Journal: Circulation (2021)

Background: Monocyte phenotypic changes play a pivotal role in atherogenesis and can be induced by plasma lipids. We analyzed associations of monocyte phenotypes with lipid profiles and the potential of predicting monocyte phenotypes by lipid variables in subjects with hypertriglyceridemia (HTG) after short-term intake of low-saturated fat diet (LSFD) and high-saturated fat diet (HSFD). Method: Subjects with HTG (n=19, 10 men and 9 women, aged 53.9±13.7 years) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) and a test meal on day 5, separated by a 4- to 6-week washout period. Blood was taken on day 1 fasting before the diets and on day 5 fasting and 4 and 6 hours after the test meal to examine lipoprotein profile by enzymatic assay, fatty acids by nuclear magnetic resonance spectroscopy, and monocyte phenotypes by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression models were built to identify influential lipid variables for key monocyte markers that responded differently to the two diets. Results: LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride (TG), VLDL-TG, and LDL-TG and fasting and postprandial total cholesterol and LDL-cholesterol and altered fatty acid composition, with reduced saturated fatty acids (SFAs) but increased polyunsaturated fatty acids (PUFAs). Compared to HSFD, LSFD reduced monocyte lipid accumulation and levels of several surface markers involved in monocyte adhesion and migration including CD11c, a β2 integrin, on intermediate monocytes. Using the LASSO regression models, we identified that total cholesterol, LDL-TG, and apoB were positively correlated and n-3 PUFAs negatively correlated with lipid accumulation in intermediate monocytes and that total TG, LDL-TG, and apoCIII were positively correlated with CD11c levels on intermediate monocytes. Conclusions: In subjects with HTG, short-term LSFD compared to HSFD improves lipid profiles and monocyte phenotypes. We also identified specific plasma lipid parameters that may be reliable predictors for and contribute to specific monocyte phenotypic changes in HTG.
Inhibition of benzo(a)pyrene induced DNA strand breaks by organosulfur compounds (diallyl sulfide, diallyl disulfide and dially trisulfide) in MCF-10A cells
Authors: Selina F. Darling-Reed, Yasmeen M. Barnes-Nkrumah, Alicia Tucker, Ayoola A. Aboyade-Cole, Ronald D. Thomas
Journal: Cancer Research (2006)

809  Polycyclic aromatic hydrocarbons, such as Benzo(a)pyrene (BAP), are known mammary carcinogens in animal models and may be involved in the etiology of human breast cancer. BaP is primarily generated from the combustion of fossil fuels from vehicle exhausts, industrial power generation and incinerators. Upon inhalation, BaP is metabolized to reactive intermediates including reactive oxygen species which lead to DNA strand breaks. These genetic perturbations are associated with cancer formation. Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are naturally occurring organosulfur compounds found in garlic which has been shown to prevent cancer in several animal models via metabolic modulation. In this study, we hypothesize that DAS and DADS will prevent the production of DNA strand breaks. To test this hypothesis, breast epithelial cells (MCF-10A) were treated with BaP (5μM) alone or in combination with DAS (1μM and 10μM), DADS (1 μM and 10 μM) or DATS (1μM and 10 μM) for 3 hours. Cells were also treated with DMSO as a vehicle control and hydrogen peroxide (H2O2) as a positive control. The Comet assay was used to determine the level of DNA damage using the mean olive tail moment as an indicator of DNA strand breaks. BaP (5μM) produced strand breaks with a mean olive tail moment of 20. Increasing concentrations of DAS (1μM and 10μM) decreased the mean olive tail moments to 15 and 10. DADS (1μM and 10μM) also decreased the BaP induced strand breaks in a dose dependent manner resulting in a decrease of the mean olive tail moments to 12 and 5, respectively. In addition, DATS concentrations of 1 μM and 10 μM decreased the mean olive tail moments to 4 and 5, respectively. We have demonstrated that DAS, DADS, and DATS inhibit the production of DNA strand breaks induced by BaP. DATS is most effective in preventing DNA strand breaks. To determine the mechanism of these organosulfur compound induced DNA strand breaks lipid peroxidation studies were performed. These studies demonstrated that there were no effects on the amount of lipid peroxide produced in response to BaP or the organosulfur compounds when compared to the vehicle control. Therefore, we conclude that these organosulfur compounds do not prevent BaP induced strand breaks by alterations in lipid peroxidation. Therefore, DAS, DADS, and DATS may modulate the production of BaP induced strand breaks by some other mechanisms such as direct prevention of the metabolism of BaP or the alterations in gene expression of metabolizing enzymes. This research was supported by NIH/RCMI Grant #RR3020
Establishment of Stable Cell Lines Representing Juvenile Myelomonocytic Leukemia with SHP2 Mutations
Authors: Yuming Zhao, Yao Guo, Chunxiao He, Dengyang Zhang, Han Zhong Pei, Ming Yang, Zhiguang Chang, Liuting Yu, Junbin Huang, Hongman Xue, Chun Chen, Zhizhuang Joe Zhao, Yun Chen
Journal: Blood (2021)