tbuckley/cabot-search huggingface dataset:
Abstract P132: Potato Consumption And Risk Of Diabetes And Cardiovascular Mortality In The Alpha Omega Cohort
Authors: Esther Cruijsen, Anne W Simon, Indira M Indyk, Maria C Busstra, Johanna M Geleijnse
Journal: Circulation (2021)

Introduction: Higher potatoes intake, especially French fries, was unfavorably associated with cardiometabolic endpoints in population-based studies. Little is known about this in coronary heart disease (CHD) patients. Hypothesis: Boiled potatoes and French fries intake might increase the risk of type 2 diabetes (T2D), cardiovascular disease (CVD) mortality and all-cause mortality after myocardial infarction (MI). Methods: We analyzed 3401 Dutch patients (60-80 y, 78% male) from the Alpha Omega Cohort, free from T2D, with an MI ≤ 10 y before enrolment. Diet was assessed at baseline (2002-2006) using a 203-item validated food frequency questionnaire, including potato preparation methods. T2D incidence (self-reported physician diagnosis and/or prescribed anti-diabetes medication) was monitored during the first 40 months of follow-up and cause-specific mortality through December 2018. Multivariable Cox models were used to obtain Hazard Ratios (HRs) for incident T2D and fatal endpoints in potato categories. Results: Patients had a median potato intake (mainly boiled) of 111 g/d (3.8 weekly servings of 200 g), with 6% consuming &lt;1 serving per week. French fries were consumed by 48% of the patients (median: 6 g/d). Total potato intake was non-linearly associated with T2D risk during early follow-up (186 cases). Compared to 0-2 servings, HRs were 1.52 (0.97, 2.39) for 3-4 servings and 1.78 (1.10, 2.89) for ≥5 servings per week. During &gt;12 y of follow-up (38,987 person-years) 1618 deaths occurred, of which 697 from CVD, 431 from CHD and 128 from stroke. HRs for fatal endpoints were non-significant in categories of total and boiled potatoes (Table). For French fries (consumers vs. non-consumers), HRs were 1.23 (0.89, 1.69) for T2D, 1.03 (0.87, 1.22) for fatal CVD and 0.93 (0.83, 1.04) for all-cause mortality. Conclusion: In Dutch post-MI patients, potatoes (mainly boiled) were neutrally associated with CVD and all-cause mortality. An increased risk of T2D was found for French fries, which warrants further study in CHD patient cohorts.
Extended-Release Buprenorphine and Its Evaluation With Patient-Reported Outcomes
Authors: Wilson M. Compton, Nora D. Volkow
Journal: JAMA Network Open (2021)

Nicholas Lintzeris, MBBS, PhD; Adrian J. Dunlop, MBBS, PhD; Paul S. Haber, MD, FRACP; Dan I. Lubman, MB ChB, PhD; Robert Graham, MBBS; Sarah Hutchinson, MSc; Shalini Arunogiri, MBBS, PhD; Victoria Hayes, MBBS, MPH; Peter Hjelmström, MD, PhD; Agneta Svedberg, MSc; Stefan Peterson, PhD; Fredrik Tiberg, PhD
Abstract 17028: Single Cell Analysis of T Cells Found in Atherosclerotic Plaque
Authors: Patricia K NGUYEN, Roshni R Chowdhury, Jessica D'Addabbo, Koki Sasagawa, Xianxi Huang, David M Louis, Gunsagar S Gulati, Tiffany K Koyano, Robyn Fong, Jinliang Li, Holden T Maecker, Jack Boyd, Yueh-Hsiu Chen, Charles Chan, Mark Davis
Journal: Circulation (2020)

Background: Despite advances in medical therapy, heart attack and stroke remain leading causes of morbidity and mortality. Biological, epidemiological, and clinical studies have shown that many patients (up to 33% in some trials) still have residual inflammatory risk that is associated with plaque rupture, even in the setting of low LDL. Methods and Results: In this study, we analyzed the T cell landscape of coronary atherosclerotic plaque to determine their role in the development of atherosclerosis and its adverse sequelae. We recruited 17 patients undergoing heart transplantation. From each explanted heart, we obtained plaques from the major coronary arteries, digested them to form a single cell suspension, sorted the arteries for CD4 and CD8 T cells into 96 well plates, and submitted them for single cell genotyping and phenotyping ( Figure 1 ). Although peripheral blood from these patients also contains T cell clones, plaque CD8 T cell clones appear to function differently than blood (e.g., producing more BCL6, TNF-, and interferon gamma) further supporting that this is not a bystander effect. We found CD4 and CD8 T cells with identical TCR sequence across the arteries of the same patient, suggesting CD8T cells are purposely recruited to the plaques. When we analyzed the percent clonality based upon location and disease severity, we find that clonality is not dependent on location and is present at all severity levels, especially, in early disease (e.g., AHA Type I-IV lesions. Conclusion: CD8 T cells are clonally expanded in atherosclerotic plaque and appear to function differently than blood, suggesting these cells are purposefully recruited.
Abstract 15219: Fully Automated Calcification Segmentation in Intravascular Optical Coherence Tomography Images Using a Two-step Deep Learning Approach
Authors: Juhwan Lee, Yazan Gharaibeh, Vladislav N Zimin, Luis A Dallan, Hiram G Bezerra, David Wilson
Journal: Circulation (2020)

Introduction: Major calcifications are of great concern when performing percutaneous coronary intervention as they hinder stent deployment. Calcifications can lead to under-expansion and strut malapposition, with increased risk of thrombosis and in-stent restenosis. Therefore, accurate identification, visualization, and quantification of calcifications are important. Objective: In this study, we developed a 2-step deep learning approach to enable segmentation of major calcifications in a typical 500+ frame intravascular optical coherence tomography (IVOCT) images. Methods: The dataset consisted of a total of 12,551 IVOCT frames across 68 patients with 68 pullbacks. We applied a series of pre-processing steps including guidewire/shadow removal, lumen detection, pixel shifting, and Gaussian filtering. To detect the major calcifications in step 1, we implemented the 3D convolutional neural network consisting of 5 convolutional, 5 max-pooling, and 2 fully-connected layers. In step-2, SegNet deep learning model was used to segment calcified plaques. In both steps, classification errors were reduced using conditional random field. Results: Step-1 reliably identified major calcifications (sensitivity/specificity: 97.7%/87.7%). Semantic segmentation of calcifications following step-2 was typically visually quite good (Fig. 1) with (sensitivity/specificity: 86.2%/96.7%). Our method was superior to a single step approach and showed excellent reproducibility on repetitive IVOCT pullbacks, with very small differences of clinically relevant attributes (maximum angle, maximum thickness, and length) and the exact same IVOCT calcium scores for assessment of stent deployment. Conclusions: We developed the fully-automated method for identifying calcifications in IVOCT images based on a 2-step deep learning approach. Extensive analyses indicate that our method is very informative for both live-time treatment planning and research purposes.
Covid-19: Advocates urge India’s prime minister to remove barriers to vaccine production and access
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A group of 567 prominent figures in India have called on Prime Minister Narendra Modi to tackle inequalities in vaccine supply to ensure vulnerable populations get the protection they need and to ramp up manufacturing to tackle shortages.In an open letter, 1 public health practitioners, doctors, economists, unions, human rights groups, student groups, civil society organisations, and concerned citizens in India called on Modi to outline a time bound and transparent vaccine action plan to speed up rollout and ensure that everyone can access the covid-19 vaccine free of charge.
Abstract P110: Proteomics Identified Novel Proteins Associated With Genetic Risk Of Abdominal Aortic Aneurysm: The Atherosclerosis Risk In Communities Study (ARIC)
Authors: Brian Steffen, James S Pankow, Nathan Pankratz, Pamela L Lutsey, Faye L Norby, Kunihiro Matsushita, Ryan Demmer, Weihong Tang
Journal: Circulation (2021)

Introduction: Abdominal aortic aneurysm (AAA) is a condition characterized by a weakened dilated vessel wall with the potential for lethal rupture. A recent genome-wide association study identified and replicated nine AAA-related variants (rs602633, rs4129267, rs3827066, rs1795061, rs10757274, rs10985349, rs9316871, rs6511720, and rs2836411), but pathways through which these loci may influence disease have not been elucidated. Hypothesis: AAA risk variants were hypothesized to be associated with plasma proteins with numerous roles including, but not limited to, inflammation and extracellular matrix remodeling. Methods: Data from participants of the community-based ARIC Study were used. Genomic DNA from whole blood was genotyped using the Affymetrix Genome-Wide Human SNP array 6.0. Concentrations of 4,870 proteins were determined using the SomaLogic aptamer-based capture array in plasma collected at visit 3 (1993-95). Outliers that were 6 standard deviations from the means were excluded. Race-specific multiple linear regression analysis evaluated associations between genetic variants and log base 2 transformed protein levels, with adjustment for age, sex, estimated glomerular filtration rate, field center, and ten principal components of ancestry. Identified proteins in whites (N=7,241) were then examined for replication in Black participants (N=1,671). Cox regression was used to evaluate the associations between identified proteins and incident AAA (n=454) over a median 21.2-year follow-up in all 11,064 participants. Results: In white participants twenty-six protein associations were identified for rs602633 ( PSRC1-CELSR2-SORT1 ), rs4129267 ( IL6R ), and rs3827066 ( PCIF1-ZNF335-MMP9 ) following Bonferroni correction ( p ≤5.13x10 -6 ). Associations were observed between rs4129267 and soluble interleukin-6 receptor subunit alpha (β=-0.339; p&lt;1.0E-200) and CRP (β=0.093; p=2.24E-7); rs602633 and granulin (β=0.184; p&lt;1.0E-200), complement C1q TNF-related protein-1 (β=0.115; p=2.17E-184), and neogenin (β=-0.031; p=5.60E-13); and rs3827066 and kit ligand (β=-0.045; p=2.41E-08). Five associations were replicated in Black participants ( p ≤1.9x10 -3 ). In the whole cohort, top quintiles of CRP (HR: 1.68; 95% CI: 1.22, 2.31), kit ligand (HR: 0.56; 95% CI: 0.40, 0.78) and neogenin (HR: 0.57 95% CI: 0.42, 0.78) were significantly related to incident AAA risk compared to corresponding bottom quintiles. Conclusions: Three of the nine AAA risk variants were associated with plasma protein concentrations, with the strongest associations for those involved in inflammation, endothelial dysfunction, and extracellular matrix remodeling. Granulin, complement C1q tumor necrosis factor-related protein-1, kit ligand, and neogenin represent novel targets for genetic risk of AAA and may link genetic susceptibility to disease pathogenesis.
Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study
Authors: Santiago Romero-Brufau, Ayush Chopra, Alex J Ryu, Esma Gel, Ramesh Raskar, Walter Kremers, Karen S Anderson, Jayakumar Subramanian, Balaji Krishnamurthy, Abhishek Singh, Kalyan Pasupathy, Yue Dong, John C O’Horo, Walter R Wilson, Oscar Mitchell, Thomas C Kingsley
Journal: BMJ (2021)

To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination.Simulation agent based modeling study.Simulated population based on real world US county.The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions.Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine); and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated.Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid-19 over 180 days.Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested.A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.
Abstract 12199: Diagnostic Utility And Pathogenic Role of Circulating Micrornas in Vasospastic Angina
Authors: Chan Soon Park, Inho Kim, Gyu Chul Oh, Jung-Kyu Han, Han-Mo Yang, Kyung Woo Park, Hyun-Jai Cho, Hyun-Jae Kang, Bon-Kwon Koo, Woo-Young Chung, Seil Oh, Hae-Young Lee
Journal: Circulation (2019)

Introduction: Vasospastic angina (VA) is often overlooked and difficult to diagnose non-invasively. Furthermore, though endothelial dysfunction and smooth muscle hyperactivity are suggested as main...
Abstract 16027: Reporting of Neoplasms Following Angiotensin Receptor Blocker Recalls Using the FDA Adverse Event Reporting System Database
Authors: Robert Cohen Sedgh, Jungyeon Moon, Cynthia JACKEVICIUS
Journal: Circulation (2020)

Introduction: A worldwide recall of valsartan due to the potential carcinogen N-nitrosodimethylamine in July 2018 received extensive public attention. This was followed by more FDA recalls of other contaminated angiotensin receptor blocker (ARB) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Methods: Data was retrospectively collected from the FAERS database for reports from 1/2015-12/2019. Reporting odds ratios (ROR) were estimated to detect signals for association between ARBs (valsartan, losartan, and irbesartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. Chi-square test was used to compare categorical variables. Results: A total of 2,181,524 AEs, including 19,287 neoplasm AEs were analyzed. 1-year post-recall reported neoplasm AEs were higher for valsartan than losartan ( p &lt;0.0001) and irbesartan ( p &lt;0.0001). Monthly ROR (95% CI) of valsartan-associated neoplasms vs. controls (ROR * : valsartan/negative exposure; ROR † : valsartan/omeprazole; ROR † : valsartan/ranitidine) showed the highest numerical signals post-recall in 7/2018 [7.64 (4.78-12.19) * ; 4.77 (3.36-6.79) † ; 4.13 (2.50-6.84) † ] and 8/2018 [(7.87 (5.19-11.94) * ; 5.65 (4.12-7.75) † ; 7.20 (4.46-11.63) † ]. In contrast, the highest post-recall cancer signals for irbesartan and losartan detected in 3/2019 (4.80 * ; 4.06 † ; 3.38 † ) and 4/2019 (3.63 * ; 3.69 † ; 2.52 † ) respectively, were lower. Conclusion: Significantly more post-recall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with losartan and irbesartan, even though they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals.
Abstract 15583: Cardiovascular Computed Tomography Aortic Valve Calcification, Myocardial Fibrosis and Adverse Outcome Following Transcatheter Aortic Valve Replacement
Authors: Ruben Evertz, Sebastian Hub, Bo E Beuthner, Soeren Jan Backhaus, Torben Lange, Rodi Topci, Miriam Puls, Elisabeth Zeisberg, Joachim Lotz, Gerd Hasenfuss, Andreas Schuster
Journal: Circulation (2020)

Introduction: There is evidence to suggest that subtype of aortic stenosis (AS), degree of myocardial fibrosis (MF) and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Since little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as association with adverse cardiac events. Methods: 100 consecutive patients with severe AS and indication for transfemoral transcatheter aortic valve replacement (TAVR) were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multi detector computed tomography (MDCT) and left ventricular endomyocardial biopsy at the time of TAVR. Results: The final study cohort consisted of 92 patients with completed study protocol comprising of 39 (42.4 %) normal ejection fraction high gradient (NEFHG), 13 (14.1 %) low EF high gradient (LEFHG), 25 (27.2 %) low EF (flow) low gradient (LEFLG) and 15 (16.3 %) paradoxical low flow low gradient (PLFLG) AS. The high gradient phenotype (NEFHG and LEFHG) showed the largest amount of AVC (807 ± 421; 813 ± 281 mm 3 respectively) as compared to the low gradient phenotype (LEFLG and PLFLG; 503 ± 326; 555 ± 594 mm 3 respectively, p&lt;0.05). Conversely, MF was most prevalent in low output phenotypes (LEFLG&gt;LEFHG&gt;PLFLG&gt;HEFHG, p&lt;0.05). This was paralleled by larger cardiovascular mortality within 400 days post TAVR (LEFLG n=7&gt;PLFLG n=4&gt;LEFHG n=2&gt;NEFHG n=1). Within LEFLG AS, patients with larger AVC (&gt;476.8 mm 3 ) had larger MF (40.2%) and higher cardiovascular mortality (n=5) as compared to patients with less AVC (≤476.8 mm 3 , 17.1% MF, p=0.027, cardiovascular mortality n=2). Conclusion: MF is associated with adverse cardiovascular outcome following TAVR which is most prevalent in low ejection fraction situations. Within the low ejection fraction low gradient subtype large AVC was associated with high amounts of MF and adverse cardiovascular outcome.
Abstract 15506: Inhibition of Angiotensin II Type I Receptor Induces Dual Modification of Mitochondrial Dynamics and Mitophagy via Inactivation of Ras/raf/mek Pathway and Contributes Vascular Anti-senescence
Authors: Yoshihiro Uchikado, Yoshiyuki Ikeda, Yuichi Sasaki, Yuichi Akasaki, Mitsuru Ohishi
Journal: Circulation (2020)

Introduction: Angiotensin II (Ang II) causes vascular senescence by damaging mitochondria that undergo quality control by mitochondrial dynamics and mitophagy. We examined whether and how AngII type I receptor (AT1R) signal regulates mitochondrial dynamics and mitophagy in the etiology of vascular senescence. Methods: We used vascular smooth muscle cells (VSMC) and C57BL6 (WT), apolipoprotein E deficient (ApoE KO) and the double knockout of ApoE and AT1R mice. Results: Administration of Ang II to VSMC forced mitochondria to fission and induced cellular senescence and mitochondrial dysfunction, which were restored by inhibition of fission by use of Mdivi-1. Treatment of ox-LDL also induced cellular senescence accompanied by excessive mitochondrial fission through phosphorylation of Drp1 at Ser616 and mitochondrial dysfunction. These alterations were ameliorated by inhibition of AT1R signal, suggesting that AT1R signal inhibition may contribute anti-cellular senescence by modification of mitochondrial dynamics. AT1R signal inhibition also induced mitophagy assessed by electron microscopy and immunohistochemistry of LAMP2 and TOMM20. AT1R inhibition-induced mitophagy was not affected by Atg7 Knockdown, whereas it was diminished by Rab9 knockdown. Immunohistochemistry showed TOMM20 dots were co-localized to LAMP2 and Rab9 but not LC3. These results suggest that AT1R signal induces mitophagy derived from Rab9-dependent alternative autophagy. Treatment of ox-LDL activated Ras, Raf and MEK, and AT1R inhibition inactivated them. Inhibition of Ras/Raf/MEK decreased excessive mitochondrial fission and induced mitophagy, suggesting that AT1R signal followed by Ras/Raf/MEK pathway modulates both mitochondrial dynamics and mitophagy. The degree of arterial senescence and atherosclerosis, Drp1 expression in mitochondrial fraction and oxidative stress in artery were higher and the number of mitophagy, fused mitochondria and its function were lower in ApoE KO than those of WT mice. AT1R KO to ApoE KO attenuated these adverse effects of ApoE KO. Conclusions: Inhibition of AT1R signal contributes vascular senescence through modification of mitochondrial dynamics and mitophagy by inactivation of Ras/Raf/MEK pathway.
Roles for the gut microbiota in regulating neuronal feeding circuits
Authors: Kristie B. Yu, Elaine Y. Hsiao
Journal: Journal of Clinical Investigation (2021)

The gut microbiota has the capacity to affect host appetite via intestinal satiety pathways, as well as complex feeding behaviors. In this Review, we highlight recent evidence that the gut microbiota can modulate food preference across model organisms. We discuss effects of the gut microbiota on the vagus nerve and brain regions including the hypothalamus, mesolimbic system, and prefrontal cortex, which play key roles in regulating feeding behavior. Crosstalk between commensal bacteria and the central and peripheral nervous systems is associated with alterations in signaling of neurotransmitters and neuropeptides such as dopamine, brain-derived neurotrophic factor (BDNF), and glucagon-like peptide-1 (GLP-1). We further consider areas for future research on mechanisms by which gut microbes may influence feeding behavior involving these neural pathways. Understanding roles for the gut microbiota in feeding regulation will be important for informing therapeutic strategies to treat metabolic and eating disorders.
IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial
Authors: Paul M Ridker, Matt Devalaraja, Florian M M Baeres, Mads D M Engelmann, G Kees Hovingh, Milana Ivkovic, Larry Lo, Douglas Kling, Pablo Pergola, Dominic Raj, Peter Libby, Michael Davidson
Journal: The Lancet (2021)
Abstract 11463: Epidemiological Trends and Outcomes of Acute Myocarditis in the National Health Service of England
Authors: Amrit S Lota, Brian Halliday, Upasana Tayal, Sara Salmi, Rameen Shakur, Daniel Hammersley, Richard Jones, Piers Daubeney, James S Ware, John G Cleland, Stuart A Cook, Dudley J Pennell, Sanjay K Prasad
Journal: Circulation (2019)

Introduction: Epidemiological data on the incidence of symptomatic myocarditis other than that identified by autopsy are lacking. We sought to evaluate the real world clinical burden of acute hospi...