tbuckley/cabot-search huggingface dataset:
Abstract 13994: Single-Dose Intervention With Rapamycin at Reperfusion Preserves Cardiac Function Through Attenuation of Inflammation and Increased Cardiomyocyte Proliferation in Diabetic Rabbit- Role of Hippo Pathway
Authors: Arun Samidurai, Ramzi A Ockaili, Donatas Kraskauskas, Sean Roh, Rakesh C Kukreja, Anindita Das
Journal: Circulation (2021)

Background: Rapamycin (RAPA, mTOR inhibitor) given at reperfusion protects diabetic rabbit hearts against ischemia/reperfusion (I/R) injury by reducing infarct size and apoptosis. We hypothesized that RAPA administration may preserve post-ischemic cardiac function through decreased inflammation and increased cardiomyocyte proliferation with regulation of YAP- the effector of Hippo pathway). Methods and Results: Diabetes (DM) was induced by administration of alloxan monohydrate (125 mg/kg, i.v.) in New Zealand rabbits (n=12; body weight≈3 kg, 4-month-old). Four weeks after alloxan treatments, conscious diabetic rabbits (maintaining blood glucose&gt;250 mg/dL) were subjected to 45 min of ischemia and 10 days of reperfusion (R) by inflating/deflating previously implanted hydraulic balloon occluder. RAPA (0.25 mg/kg, i.v.) or DMSO (vehicle) was infused 5 min before onset of R. Post-I/R cardiac function in diabetic rabbit, assessed by echocardiography, showed significant improvement of ejection fraction (EF, Fig. A ). Left ventricular fibrosis ( Fig. B , evaluated by picrosirius red staining) was attenuated following treatment of RAPA in diabetic rabbits. Immunofluorescence staining revealed the attenuation of post-I/R inflammasome formation with RAPA treatment as shown by reduced ASC aggregation (apoptosis speck-like protein with a caspase recruitment domain) in cardiomyocytes ( Fig. C ). RAPA suppressed the phosphorylation of YAP in cytosol of cardiomyocytes ( Fig. D ). Proliferation markers, Ki-67 positive and phospho-Aurora B Kinase positive cells indicated cardiomyocytes were in G2-M phase in RAPA-treated diabetic rabbits after I/R injury ( Fig. E ). Conclusion: RAPA treatment at reperfusion preserves cardiac function and improves cardiomyocyte proliferation with attenuation of inflammation and possibly regulation of Hippo pathway following I/R injury in diabetes.
T細胞CD6受容体はT細胞活性化において反対機能をもつマルチタスクシグナロソームを作動させる【JST・京大機械翻訳】
Authors: Mori Daiki, Gregoire Claude, Voisinne Guillaume, Celis-Gutierrez Javier, Aussel Rudy, Girard Laura, Camus Mylene, Marcellin Marlene, Argenty Jeremy, Burlet-Schiltz Odile, Fiore Frederic, Gonzalez de Peredo Anne, Malissen Marie, Roncagalli Romain, Malissen Bernard
Journal: The Journal of Experimental Medicine (2020)
Abstract 11345: Incidence, Characteristics, and Outcomes of Patients Presenting to an Urban Academic Institution with ST-Segment Elevation Myocardial Infarction During the COVID-19 Pandemic
Authors: Eric Taylor, Katrina Bidwell, Peyton Tharp, Daniel Cook, Noah Blaker, Chris Nielsen, VALERIAN Fernandes
Journal: Circulation (2021)

Introduction: ST-segment elevation myocardial infarction (STEMI) is an emergency presentation of an acutely occluded coronary artery. Following the announcement of the COVID-19 pandemic (March 11, 2020), a global decrease in STEMI incidence has been observed. Incidence, characteristics, and outcomes for STEMI activation patients were investigated in the 5 years prior (“reference period”) to and 1 year into the pandemic (“pandemic period”). We assessed the hypothesis that pandemic period STEMI activations will have more severe infarction (elevated troponin I), a higher percentage of true STEMI, and worse outcomes (higher case fatality rate). Methods: STEMI activation incidence was obtained from an institutional database (reference period n = 430; pandemic period n = 31). Patient characteristics and outcomes were obtained retrospectively from electronic health records (EHRs). True STEMI was adjudicated based on chest pain, EKG, troponins, and angiogram. Results: Monthly STEMI activations declined significantly in the first year of the pandemic (2.50 ± .68 vs. 7.17 ± .41, P = &lt;.001). No significant difference in demographic characteristics (age, BMI, and male-to-female ratio) were observed. True STEMI percentage was higher during the pandemic (80.65% vs. 70.93%), but not statistically significant. Peak troponin levels for true STEMI were significantly higher during the pandemic (98.83 ± 25.82 vs. 51.44 ± 4.11, P = .003). There was no significant difference in 30-day and 90-day case fatality rates. Conclusions: STEMI activation incidence declined significantly during the pandemic; interestingly, the proportion of these which were true STEMIs remained consistent. True STEMIs during the pandemic had higher troponin levels suggesting larger infarct, but there was no significant difference in case fatality. In conclusion, fewer patients presented with STEMI while case fatality remained unchanged despite more severe infarct occurrence during the pandemic.
Abstract 10670: Kidney Function, Bone-Mineral Metabolism Markers, and Calcification of Coronary Arteries, Aorta, and Cardiac Valves in Older Adults
Authors: Yejin Mok, Frances Wang, Shoshana Ballew, Steven Menez, Kenneth R Butler, Lynne E Wagenknecht, Pamela L Lutsey, Josef Coresh, Michael J Blaha, Kuni Matsushita
Journal: Circulation (2021)

Background: Kidney function is a crucial determinant of bone-mineral metabolism (BMM); however, the contribution of kidney dysfunction, especially at mild to moderate stages, to vascular calcification remains controversial. Moreover, little is known about whether BMM markers are associated with coronary artery calcification (CAC) and extra-coronary calcification (ECC) beyond kidney function. Methods: In 1935 ARIC participants (age 73-95 years) with no coronary heart disease and data on CAC and ECC at visit 7 (2018-2019), we evaluated estimated glomerular filtration (eGFR) (based on creatinine, cystatin C, and both) and serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) as exposures. The exposures were modeled as weighted averages over ~15 years (visit 1 [1987-89] to visit 5 [2011-13] to allow a lag time for vascular calcification), and the outcome variables were high CAC and ECC (sex-race specific ≥75 th vs. &lt;75 th percentile Agatston score) or any CAC and ECC (Agatston score &gt;0 vs. 0) using multivariable logistic regression. Results: Low eGFR (overall range 30-149 mL/min/1.73m 2 ), regardless of equations, was not robustly associated with high CAC and ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed significant associations with high CAC and ECC, independent of kidney function ( Figure ). Considering presence of any calcification, results were generally consistent, although cystatin C-based eGFR &lt;60 mL/min/1.73m 2 was associated with mitral valve calcification (present in 47%) (odds ratio 1.70 [95% CI 1.13, 2.58]). Conclusion: Cumulative exposure to lower eGFR showed weak associations with vascular calcification in community-dwelling older adults. Among BMM markers, phosphorus was most robustly associated with CAC and ECC beyond kidney function. Our results suggest a potential key role of phosphorus in the pathophysiology of vascular calcification.
Correspondence on ‘Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients’
Authors: Yudong Liu
Journal: Annals of the Rheumatic Diseases (2021)

I read with great interest the article by Trahtemberg et al 1 on the clinical relevance of antiphospholipid antibodies (aPLs), in particular anticardiolipin antibodies (aCLs), in critically ill COVID-19 positive and negative patients. Severe COVID-19 is associated with a hypercoagulable state. Early studies identified the presence of aPLs in critically ill COVID-19 patients,2 which has attracted considerable attention as the presence of aPLs is one of the mechanisms leading to coagulopathy. Substantial efforts then tried to associate the thrombotic events seen in COVID-19 to aPLs status. The results seem negative, but a number of different types of autoantibodies were identified.3 Chang et al recently reported that autoantibodies were present in approximately half of the hospitalised patients with COVID-19 but in less than 15% of healthy controls.4 In addition to aCLs and anti-beta 2 glycoprotein 1 antibodies (aβ2-GP1), they also identified autoantibodies targeting autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes as well as targeting interferons/interleukins and other cytokines.4 These findings suggest that COVID-19, in particular patients with severe/critical …
Abstract 12301: Anticoagulation for Left Ventricular Thrombus: An Updated Meta-Analysis of Stroke or Systemic Embolization Outcomes
Authors: Sumit Sohal, Krishna Prasad Kurpad, Sanjana Nagraj, sheetal vasundara mathai, Sergio Waxman
Journal: Circulation (2021)

Introduction: Thromboembolic events including stroke or systemic embolization (SSE) are the most dreaded complications in patients who develop left ventricular (LV) thrombus. Vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) have been used in the management of LV thrombus however the efficacy of these treatment strategies have been rarely studied in head-to-head trials. Our aim was to study the differences in embolization outcomes in patients with LV thrombus on either NOACs or VKAs. Methods: A comprehensive search of electronic databases was conducted for studies comparing VKAs and NOACs in patients with LV thrombus. Event level data were extracted from studies for each arm and used to calculate the risk ratio (RR) with 95% confidence intervals (CI) which were pooled for the effect of original treatment allocation on the outcome of SSE. Random effects model was used to calculate the risk ratio. Results: We found a total of 12 studies from which 2281 patients were identified with LV thrombus and were treated with anticoagulation. 596 (26.13%) received NOACs and 1685 (73.87%) received VKAs. Events of SSE occurred in 92 (15.44%) patients on NOACs and 307 (18.22%) patients on VKAs. Overall, patients treated with NOACs had similar rate of SSE events as compared to patients treated with VKAs using random effects model (RR: 1.02 [95% 0.64-1.65], p=0.08, I 2 =39%). Conclusions: This meta-analysis suggests that the use of NOACs is associated similar rate of SSE events in patients with LV thrombus as compared to the use of VKAs. Additional prospective studies are required to determine the most effective anticoagulant strategy for patients with LV thrombus.
Prognostic Value of Baseline PET/CT Imaging in Diffuse Large B-Cell Lymphoma: Does the Largest Distance between Two Lesions Play a Role in Prognosis?
Authors: Carolina Afonso, Sara Duarte, Bárbara Almeida Marques, Carla Barros Lima, Dulcelena Neves, Ana Catarina Lai, Mauro Monteiro, Tiago Saraiva, Adriana Roque, Lenka Ruzickova, José Pedro Carda, Marilia Gomes, Maria José Julião, Gracinda Costa, Ana Espadana
Journal: Blood (2021)
Abstract 9192: Efficacy and Safety of Dabigatran in the Treatment and Secondary Prophylaxis of Children With Congenital Heart Disease
Authors: Manuela Albisetti, Igor Tartakovsky, Jacqueline Halton, Lisa Bomgaars, Elizabeth Chalmers, Lesley Mitchell, Matteo Luciani, Ildar Nurmeev, Kirill Gorbatikov, Eva Kleine, Martina Brueckmann, Leonardo Brandao
Journal: Circulation (2021)

Introduction: Congenital heart disease (CHD) is associated with an increased frequency of thrombotic events in children, particularly in cyanotic conditions (i.e., single ventricles). Phase IIb/III clinical trials in children with venous thromboembolism (VTE) reported the noninferiority of dabigatran etexilate (DE) versus standard of care in treating acute VTE (DIVERSITY, NCT01895777) and a favorable safety profile for VTE prevention (NCT02197416). Aim: To evaluate the efficacy and safety of DE in the treatment and secondary prophylaxis of VTE in children with CHD, including subsets with cyanotic CHD. Methods: The primary composite efficacy endpoint in DIVERSITY was complete thrombus resolution and freedom from VTE recurrence or VTE-related death; safety endpoints included bleeding events (BEs). Primary endpoints in the VTE prevention trial were VTE recurrence and BEs. CHD status was confirmed locally using standard diagnostic modalities. Results: In DIVERSITY, 48/267 (18.0%) children had CHD. DE was noninferior to standard of care in both the CHD and non-CHD groups for the composite primary endpoint ( Table ), irrespective of the presence of cyanotic or noncyanotic CHD ( Table ). BEs (mainly minor) appeared to be lower in the CHD (8.3%) than the non-CHD group (25.7%), regardless of treatment. In the secondary VTE prevention trial, 17/211 (8.1%) children had CHD. Recurrent VTE at 12 months occurred in 0 and 3 (1.5%) children in the CHD and non-CHD groups respectively ( Table ). Conclusions: In children with CHD, DE has an efficacy and safety profile consistent with the overall DIVERSITY trial. Furthermore, our results confirm the safety profile for secondary VTE prevention, suggesting that DE is a viable anticoagulant alternative for this population.
Placing health equity at the heart of the COVID-19 recovery: data analysis from the first Welsh Health Equity Status Report initiative
Authors: James Allen, Andrew Cotter-Roberts, Anna Stielke, Rajendra Kadel, Benjamin Bainham, Kathryn Ashton, Karen Hughes, Mariana Dyakova
Journal: The Lancet (2021)

BackgroundThe Welsh Health Equity Status Report initiative (WHESRi) applies an innovative WHO framework to map the wider impacts of COVID-19 on health equity. The framework is a mechanism to promote policy action and commitment for health equity and identifies five essential conditions needed to live a healthy life; namely, health services, income security, living conditions, social and human capital, and working conditions. We used the framework to assess the immediate health equity impacts of COVID-19 in Wales.MethodsTen relevant variables from Public Health Wales' public engagement survey on health and wellbeing during COVID-19 (captured April 3–July 25, 2020) were mapped to each of the five essential conditions, as defined by the European Health Equity Status Report initiative. Variables were chosen based on alignment to the essential conditions, research objectives and data quality. Estimated marginal means were disaggregated by sociodemographic factors on a nationally representative study sample ranging from 862 to 4747 participants (dependent on duration for which question was asked). Ethical approval was not required as per guidance from the National Health Service Health Research Association ethics decision tool.FindingsThe WHESRi framework allowed the assessment and quantification of the immediate impacts of COVID-19 on the wider determinants of health through the lens of the five essential conditions. For example, in relation to income security, a significantly higher proportion (181 [50·6%] of 358; p<0·05) of survey respondents aged 18–24 years reported being worried about losing their job, or not being able to find one, than any other age group. Of those respondents aged 18–24 years, 54·4% (p<0·05) of men (equivalent to 78 000) reported being worried, compared with 44·3% (p<0·05) of women (equivalent to 72 000), a difference of 10·1%.InterpretationApplication of the WHESRi framework allowed us to draw a holistic picture of health and its determinants at the population level. This application has highlighted quantifiable differences in impacts between population groups, and encouraged the dialogue around policy action. A priority moving forward is to apply the framework to vulnerable population groups and population health priorities to assess the health equity impacts according to factors such as rurality, disability, and ethnicity. Our findings resulting from the application of this WHO framework can be used to enable an equitable and sustainable recovery from the pandemic; they form part of a European initiative for health equity and provide learning to other countries from Wales' role as an innovation site.FundingNone.
Abstract P310: Mitochondrial Electron Transport Chain Dysfunction Is Associated With Mg Deficiency Induced Diastolic Dysfunction
Authors: Man Liu, Hong Liu, Richard T Clements, Feng Feng, Jin O-Uchi, Samuel C Dudley
Journal: Circulation Research (2021)

Introduction: The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, although there is no specific treatment for HFpEF yet because of poor understanding of the underlying pathophysiology. Our previous studies show that hypomagnesemia contributes to diastolic dysfunction and HFpEF by regulation of mitochondrial function and that Mg supplementation improves diastolic function. In this study, we investigated how mitochondria were affected by Mg deficiency. Methods: C57BL/6J mice were fed with a low-Mg diet (HypoMg mice, 15-30 mg/kg Mg) or a normal Mg diet (control mice, 600 mg/kg Mg) for 6 weeks. Mg repletion was achieved by feeding HypoMg mice with normal diet for another 6 weeks. Results: HypoMg mice showed significantly decreased serum Mg (0.38±0.03 mM vs. 1.14±0.03 mM of control, P&lt;0.0001), diastolic dysfunction (E/e’=21.1±1.1 vs. 15.4±0.4 of control, P=0.011), increased mitochondrial ROS (1.9±0.2-fold of control, P&lt;0.0001), decreased total mitochondrial Mg content (3.6±1.8 vs. 18.3±4.7 μM total Mg/mg mitochondrial protein of control, P=0.019), decreased ATP production in hearts (1.2±0.2 vs. 2.7±0.2 μmol/g heart tissue of control, P=0.0002), decreased complex I activity (ΔOCR NADH-rotenone =0.27±0.10 vs. 1.02±0.04 of control, P=0.0004 measured with Seahorse), and decreased complex I protein levels (50.2% reduction compared with control mice, P=0.009). Mg repletion reversed all these changes. Conclusion: HypoMg-induced diastolic dysfunction likely results from HypoMg-induced electron transport chain dysfunction resulting from a decrease in mitochondrial Mg content. Mg repletion reverses these changes, reinforcing the known correlation of increased Mg intake and reduced heart failure symptoms. In deficiency states, Mg supplementation may represent a novel treatment for diastolic heart failure by improving mitochondrial function.
Abstract 9815: Role for Btg1 and Btg2 in Postnatal Cardiomyocyte Cell Cycle Arrest and Maturation
Authors: Nivedhitha Velayutham, Frank N van Leeuwen, Blanca Scheijen, Katherine E Yutzey
Journal: Circulation (2021)

Background: Adult mammalian cardiomyocytes (CM) are predominantly post-mitotic and cannot proliferatively repair the heart following myocardial infarction (MI). Overexpression of the transcription factor Tbx20 in adult mouse CMs promotes proliferative cardiac repair post-MI, via mechanisms including direct repression of anti-proliferative genes p21 , Meis1 , and Btg2 . Btg2 (B-cell translocation gene 2), a tumor suppressor and transcriptional co-regulator, exhibits high structural and functional similarity with Btg1. However, both Btg1 and Btg2 (Btg1/2) are virtually uncharacterized in the heart. Here, we investigate the role of Btg1/2 in postnatal cardiac maturation. Methods and Results: By immunostaining in embryonic, neonatal, and adult C57BL/6 mouse hearts, the highest expression of Btg1/2 was observed in late fetal and early neonatal ventricles, concurrent with upregulation of other CM cell cycle inhibitors. In neonatal mouse CMs in vitro, siRNA-mediated loss of Btg2 leads to increased CM proliferation. In vivo , Btg1/2 constitutive single- and double- knockout (SKO and DKO respectively) mice exhibit normal heart weight-to-body weight ratios compared to age-matched wildtype (WT) controls, at postnatal day (P)7, P30, and 1 year after birth. Interestingly, at P7, DKO mice have significantly higher CM mitotic activity, as indicated by pHH3 staining, compared to WT. In addition, DKO mice also exhibit significantly smaller CM cross-sectional area at P7 compared to WT. However, by P15, CM mitotic activity and cell size are comparable between WT and Btg1/2 KO mice. Currently, siRNA-mediated knockdown of Btg1/2 in neonatal rat ventricular cardiomyocyte cultures and RNAseq studies are being performed, to assess the transcriptional regulatory roles of Btg1/2 in rodent CMs. Conclusions: Here, we highlight two novel regulators of postnatal CM maturation, Btg1 and Btg2, which are upregulated coincident with CM mitotic arrest in mice. Similar to p21 and Meis1, Btg1/2 depletion in mice induces a brief period of increased CM proliferative activity before onset of CM cell cycle arrest. Our results provide evidence for Btg1/2 working in tandem with other cardiac transcription factors and cell cycle regulators, to control CM mitotic arrest after birth.
Abstract 9191: Association of Cumulative Social Risk Score With Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis
Authors: Aziz Hammoud, Haiying Chen, Alexander Ivanov, Joseph Yeboah, Miguel Cainzos-Achirica, Khurram Nasir, Alain G Bertoni, Safi U Khan, Michael J Blaha, David M Herrington, Michael D Shapiro
Journal: Circulation (2021)

Introduction: Although the importance of social determinants of health is well-established in atherosclerotic cardiovascular disease (ASCVD), there is a need for a validated polysocial risk construct in the current paradigm of ASCVD prevention and management. Methods: Data from the Multi-Ethnic Study of Atherosclerosis study were used to create an index of baseline Cumulative Social Risk (CSR) to explore its association with incident ASCVD (fatal/non-fatal myocardial infarction, stroke, definite angina, probable angina if followed by revascularization, or resuscitated cardiac arrest). CSR score was defined by assigning a point for the presence of each of 4 social factors: i) educational attainment less than a high school diploma, ii) household income less than the federal poverty level, iii) minority race/ethnicity (Black, Hispanic, or Asian), and iv) single-living status as a proxy for limited social support. Kaplan-Meier survival curves and log-rank tests were used to examine the univariate association between CSR score and ASCVD. Cox proportional hazards models were used to examine the association between CSR score and time-to-ASCVD with and without adjustment for traditional cardiovascular risk factors. Results: A total of 6,529 participants had available CSR scores (0, 24.3%; 1, 35.5%; 2, 25.5%; ≥3, 14.7%). In total, 947 ASCVD events over a median follow-up of 15.6 years were observed. There was a statistically significant difference between the survival curves according to CSR scores (overall log-rank p&lt;0.01). CSR score was crudely associated with increased risk of incident ASCVD in a graded manner (Table 1); however, this association was attenuated in the fully adjusted models. Conclusion: CSR score was associated with incident ASCVD even after adjusting for age and sex; however, this association was attenuated after also adjusting for traditional cardiovascular risk factors, whose role as potential mediators should be explored in future work.