tbuckley/cabot-search huggingface dataset:
Abstract 13196: The Utility of Silent Myocardial Infarction on Electrocardiogram as an ASCVD Risk Enhancer for Primary Prevention: The Multi-Ethnic Study of Atherosclerosis
Authors: Matthew J Singleton, Charles German, Elsayed Z Soliman, Gregory Burke, Joseph Yeboah
Journal: Circulation (2020)

Introduction: The 2018 AHA/ACC cholesterol guidelines introduced a new list of markers called “risk enhancers” that, if present, confer an increased risk of atherosclerotic cardiovascular disease (ASCVD). Notably absent is silent myocardial infarction (SMI) on electrocardiogram (ECG), even though SMI has been shown to be associated with future ASCVD. Hypothesis: Adding SMI to the pooled cohort equation (PCE) will improve risk discrimination and classification in those with intermediate ASCVD risk (5 - 20% 10-year risk). Methods: SMI was defined as a major Q-wave abnormality or minor Q/QS waves in the setting of major ST-T abnormalities in the absence of history of clinical cardiovascular disease. Incident ASCVD events included myocardial infarction, coronary heart disease death, and fatal and non-fatal stroke. Results: Among 2,278 intermediate-risk MESA participants, 48 (2.1%) had SMI at baseline. Over 32,150 person-years (median 15.8), incident ASCVD events occurred in 297/2,230 (13%) of those without SMI and 13/48 (27%) of those with SMI. In a Cox proportional hazards model that was adjusted for calculated 10-year ASCVD risk based on the PCE, SMI was associated with increased risk of ASCVD (HR 2.22, 95% CI 1.27 - 3.87, p = 0.005). Adding SMI to the PCE did not improve discrimination, with areas under the receiver operating characteristic curves for models without and with SMI of 0.5812 and 0.5874, respectively (p-value for difference 0.22; Figure 1a). The net reclassification improvement for adding SMI as a risk enhancer to reclassify participants from intermediate-risk to high-risk was 0.0242 (95% CI 0.0011 - 0.0472, p = 0.04; Figure 1b). Conclusions: Our findings suggest that the prevalence of SMI is 2.1% among those without known clinical cardiovascular disease considered intermediate-risk by the pooled cohort equation. In our analysis, SMI only modestly improved classification of risk, suggesting that it may not be very useful as an ASCVD risk enhancer.
Abstract 14790: Prospective Evaluation of the Effect of Smartphone Electrocardiogram Usage on Anticoagulant Medication Compliance: Results of the Better Outcomes of Anticoagulation Therapy by Observation of Atrial Rhythm (BOAT OART) Study
Authors: Sanjaya K Gupta, Andy T Tran, Daniel Steinhaus, Omair Yousuf, Michael Giocondo, Brian M Ramza, Alan P Wimmer
Journal: Circulation (2020)

Introduction: Compliance with anticoagulation treatment for atrial fibrillation is variable. Smartphone electrocardiograms that provide accurate arrhythmia diagnosis may allow patients to have greater insight into their arrhythmia burden. Hypothesis: Our hypothesis was that regular use of a smartphone electrocardiogram would improve anticoagulant compliance. Methods: Patients were enrolled if they had atrial fibrillation with a CHA2DS2-VASc score of 2 or more, were eligible for anticoagulation and had a smartphone. Participants were randomly assigned to receive a smartphone electrocardiogram (AliveCor Kardia) or to the control group. All patients received 6 months of anticoagulant (apixaban) dispensed as 1-month pre-loaded pill boxes. Patients returned monthly to assess medication compliance and receive subsequent month medication. Monitor patients were encouraged to record their electrocardiogram 5 times a week. Results: A total of 100 patients were enrolled from July 2017 to August 2019, but 4 patients in the monitor arm withdrew prematurely. The monitor and control groups did not differ in age, gender, CHA2DS2-VASc score, comorbidities or atrial fibrillation burden. Medication compliance was 99.1%, with greater compliance in the monitor group (99.5 ± 0.86%) than the control group (98.8% ± 2.19%; p=0.03). In the monitor group, there was no association between missed doses and use or nonuse of the smartphone monitor on a given day. Overall monitor compliance was 87.0±14% with an average of 4.35 recorded electrocardiograms per week. Monitor group patients with 100% medication compliance had a higher average monitor compliance than those patients who missed doses (90.3±11% vs 83.5±15.8%; p=0.05). There were no major adverse events related to anticoagulation. Conclusions: Despite excellent overall anticoagulant medication compliance, this study indicates that smartphone electrocardiogram usage is associated with higher medication compliance. Greater monitor compliance was also associated with greater medication compliance. Future studies are necessary to determine if smartphone electrocardiograms can be used to maintain anticoagulant compliance long-term or improve compliance at onset of anticoagulation treatment.
Increased detection of pulmonary tuberculosis amongst hospitalised inpatients during the COVID-19 pandemic
Authors: Liang En Wee, Kenneth Choon Meng Goh, Edwin Philip Conceicao, Jamie Bee Xian Tan, Li-Hwei Sng, Indumathi Venkatachalam
Journal: European Respiratory Journal (2021)

<b>This study shows an increase in the rate of pulmonary tuberculosis (TB) detected amongst hospitalisations during the COVID-19 pandemic, while detection of extrapulmonary TB remained unchanged; due to improved surveillance and chest imaging utilisation</b>https://bit.ly/3fhVaMG
Epigenetic regulation of melanogenesis
Authors: Shihang Zhou, Hongliang Zeng, Jinhua Huang, Li Lei, Xiaoliang Tong, Si Li, Ying Zhou, Haoran Guo, Manal Khan, Liping Luo, Rong Xiao, Jing Chen, Qinghai Zeng
Journal: Ageing Research Reviews (2021)
Abstract 16539: Heart Failure With Mid-Range or Improved Ejection Fraction Improves Cardiovascular Outcomes
Authors: Matthew Cefalu, Jasneet Devgun, Samuel Kennedy, Jeremy Slivnick, Zachary Garrett, Sakima A Smith
Journal: Circulation (2020)

Heart failure with improved ejection fraction (HFiEF) is a unique and developing clinical entity among the heart failure (HF) spectrum. Prior studies suggest the characteristics, therapy, and prognosis of HFiEF are distinctive from HF with reduced ejection fraction (HFrEF) or mid-range ejection fraction (HFmrEF). We hypothesized that patients diagnosed with acute HF who later progressed to HFiEF would have improved cardiovascular outcomes compared to HFrEF. Our retrospective study included 295 adult patients with no prior history of HF at The Ohio State University diagnosed with acute HF. We defined HFrEF as a persistent ejection fraction &lt; 40%, HFmrEF as persistent ejection fraction 40-49%, and HFiEF as improvement from baseline ejection fraction by &gt; 5%. Nearly 74% of patients were found to have HFiEF while 12% and 14% were classified as HFrEF and HFmrEF respectively. Using a log-rank test, the time to first cardiovascular rehospitalization was significantly longer in HFiEF compared to HFrEF or HFmrEF (p=0.0192, Figure 1). Multivariable analysis, controlled for age and gender, indicated HFiEF had a trend towards significance as an independent predictor for time to cardiovascular hospitalization (p=0.053). Notably amyloid HF, valvular HF, and ischemic HF were all significant independent predictors. Survival analysis demonstrated that HFmrEF had significantly longer survival on log-rank test compared to HFrEF (p=0.0367). Multivariable analysis shows significantly lower hazard of mortality for those with HFmrEF (HR 0.57, 95% CI [0.36-0.92], p=0.017). Our exciting data indicates the progression to HFiEF after the diagnosis of acute HF is associated with reduced cardiovascular rehospitalization, and HFmrEF is associated with increased survival. These data have implications in patient surveillance and risk stratification as well as defining the natural history of HFiEF and HFmrEF as unique entities.
ABC of arterial and venous disease: Chronic lower limb ischaemia
Authors: J D Beard
Journal: BMJ (2000)

<h3>Abstract</h3> Alphaviruses are a diverse genus of arboviruses capable of infecting many vertebrates including humans. Human infection is common in equatorial and subtropical regions and is often accompanied by arthralgia or encephalitis depending on viral lineage. No antivirals or vaccines have been approved, and many alphavirus lineages have only recently been discovered and classified. Alphavirus nsP2 protease is an important virulence factor yet is commonly thought to be a simple papain-like protease which only cleaves viral polyproteins. Here, I reveal novel molecular mechanisms of these proteases via sequence and predicted structure alignment and propose novel cellular mechanisms for the pathogenesis of viral arthritis by predicting which human proteins are likely cleaved by these proteases. In addition to the known primary cysteine mechanism in all alphaviruses and a secondary serine mechanism documented in chikungunya virus (CHIKV), I discovered secondary cysteine and threonine mechanisms exist in many other alphaviruses and that these secondary mechanisms coevolve with their viral polyprotein cleavages. As for cleavage prediction, neural networks trained on 93 different putative viral polyprotein cleavages achieved a Matthews correlation coefficient of 0.965, and, when applied to the human proteome, predicted that hundreds of proteins may be vulnerable. Notable pathways likely affected by cleavages include the cytoskeleton and extracellular matrix, antiproteases, protein translation/folding/glycosylation/ubiquitination, cellular differentiation, inflammation, and vesicle trafficking, hinting that this viral protease is a more important virulence factor than previously believed.
Abstract 16118: Extracorporeal Membrane Oxygenation for Children With Myocarditis: An Update From the Elso Registry
Authors: Maria E E Gutierrez, Danielle Guffey, Marc Anders, Susan W Denfield, satish rajagopal, Javier J Lasa
Journal: Circulation (2020)

Introduction: Acute myocarditis causing cardiogenic shock commonly requires mechanical circulatory support. While it has been shown to be associated with survival to discharge in reports comparing indications for ECMO, our understanding of the impact of patient care related factors on outcomes remains limited by single center analyses and lack of consensus on diagnostic criteria. We therefore aimed to describe ECMO utilization and outcomes for pediatric patients requiring ECMO for acute myocarditis by sampling contemporary cohorts from the Extracorporeal Life Support Organization registry. Methods: Data was requested from ELSO database to include all pediatric patients under 19 years of age with a diagnosis of acute myocarditis who received ECMO support between 2007 and 2018. Index cases were utilized while non-VA ECMO runs were excluded. Primary outcome was mortality. Characteristics of the population are compared by mortality using t-test, Wilcoxon rank sum test, or Fisher’s exact test. Univariate analysis was performed. Multivariate logistic regression was used for significant factors in the unadjusted logistic regression. Results: We analyzed 924 ECMO runs after applying exclusion criteria. Overall survival for the cohort was 69%. Patients experiencing cardiac arrest requiring ECMO (ECPR) were less likely to survive compared to non-ECPR patients (61% vs 72%, p&lt;0.01). The time from intubation from ECMO was found to be associated with mortality, with increased time from intubation to ECMO cannulation in survivors of 6hrs [IQR 2-22] vs non-survivors 9.5hrs [IQR 2-33], p&lt;0.01). Conclusions: The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis reveal a lower likelihood of survival when the indication for ECMO cannulation is ECPR. Increased time from intubation to ECMO cannulation may impact outcomes as much as markers of inadequate oxygen delivery. This suggests that earlier ECMO cannulation may improve outcomes for pediatric patients presenting with acute myocarditis. Further investigation into the factors distinguishing ECPR from non-ECPR patients with myocarditis are needed.
Combined PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates
Authors: Jacob T. Martin, Brittany L. Hartwell, Sidath C. Kumarapperuma, Mariane B. Melo, Diane G. Carnathan, Benjamin J. Cossette, Josetta Adams, Siqi Gong, Wei Zhang, Talar Tokatlian, Sergey Menis, Torben Schiffner, Crystal G. Franklin, Beth Goins, Peter T. Fox, Guido Silvestri, William R. Schief, Ruth M. Ruprecht, Darrell J. Irvine
Journal: Biomaterials (2021)

Antigen accumulation in lymph nodes (LNs) is critical for vaccine efficacy, but understanding of vaccine biodistribution in humans or large animals remains limited. Using the rhesus macaque model, we employed a combination of positron emission tomography (PET) and fluorescence imaging to characterize the whole-animal to tissue-level biodistribution of a subunit vaccine comprised of an HIV envelope trimer protein nanoparticle (trimer-NP) and lipid-conjugated CpG adjuvant (amph-CpG). Following immunization in the thigh, PET imaging revealed vaccine uptake primarily in inguinal and iliac LNs, reaching distances up to 17 cm away from the injection site. Within LNs, trimer-NPs exhibited striking accumulation on the periphery of follicular dendritic cell (FDC) networks in B cell follicles. Comparative imaging of soluble Env trimers (not presented on nanoparticles) in naïve or previously-immunized animals revealed diffuse deposition of trimer antigens in LNs following primary immunization, but concentration on FDCs in pre-immunized animals with high levels of trimer-specific IgG. These data demonstrate the capacity of nanoparticle or "albumin hitchhiking" technologies to concentrate vaccines in genitourinary tract-draining LNs, which may be valuable for promoting mucosal immunity.
Abstract 16044: Association of Area Deprivation Index With Recurrent Cardiovascular Outcomes: Does Cardiac Rehabilitation Participation Mitigate Effects?
Authors: Emily N Guhl, Jianhui Zhu, Amber Johnson, Utibe Essien, Floyd W Thoma, Suresh R Mulukutla, Jared W Magnani
Journal: Circulation (2020)

Introduction: Neighborhood location impacts access to health-promoting resources and outcomes. Cardiac rehabilitation (CR) provides a multidisciplinary approach that improves cardiovascular outcomes. We evaluated the association of Area Deprivation Index (ADI) and cardiovascular events in individuals with incident Heart Failure (HF) or myocardial infarction (MI) and the modifying effect of CR. Methods: We identified an observational cohort admitted with primary diagnosis of 1) MI with percutaneous coronary intervention or 2) a primary diagnosis of incident HF from 2010-2018 at a multi-site regional center. We derived ADI from patient home address and then categorized into quartiles. Demographics, clinical covariates, and CR participation post-hospitalization were obtained from the electronic medical record. We compared rates of readmission for a cardiovascular primary diagnosis and mortality across ADI quartiles. Analyses were then stratified by CR participation. Results: In a cohort of 6957 (38.2% women, 88.7% white) with adjustment for covariates, increasing ADI was significantly associated with higher rates of cardiovascular rehospitalization (p&lt;0.01), Acute Coronary Syndrome (ACS) rehospitalization (p=0.01), HF rehospitalization (p&lt;0.01), and all-cause mortality (p=0.04), Table. When we stratified across CR participation, those with participation had significantly lower rehospitalizations (p&lt;0.01) and mortality (p&lt;0.01) when compared to the no CR group. There was no significant effect of ADI on outcomes in the CR group. Discussion: We found increased ADI was adversely associated with mortality and rehospitalizations in cardiac patients. For those participating in CR, there was 1) no significant effect of ADI and 2) decreased incidence of adverse outcomes vs. those who did not participate in CR. Given the benefit of CR participation on ADI’s adverse effect on outcomes, future interventions should focus on increasing CR participation.
A synthetic consortium of 100 gut commensals modulates the composition and function in a colon model of the microbiome of elderly subjects
Authors: Marta Perez, Alexandra Ntemiri, Huizi Tan, Hugh M. B. Harris, Henrik M. Roager, Céline Ribière, Paul W. O’Toole
Journal: Gut Microbes (2021)

Administration of cultured gut isolates holds promise for modulating the altered composition and function of the microbiota in older subjects, and for promoting their health. From among 692 initial isolates, we selected 100 gut commensal strains (MCC100) based on emulating the gut microbiota of healthy subjects, and retaining strain diversity within selected species. MCC100 susceptibility to seven antibiotics was determined, and their genomes were screened for virulence factor, antimicrobial resistance and bacteriocin genes. Supplementation of healthy and frail elderly microbiota types with the MCC100 in an in vitro colon model increased alpha-diversity, raised relative abundance of taxa including Blautia luti, Bacteroides fragilis, and Sutterella wadsworthensis; and introduced taxa such as Bifidobacterium spp. Microbiota changes correlated with higher levels of branched chain amino acids, which are health-associated in elderly. The study establishes that the MCC100 consortium can modulate older subjects' microbiota composition and associated metabolome in vitro, paving the way for pre-clinical and human trials.
Abstract 17393: Sex Differences in COVID-19 Hospitalization and Mortality in Chicagoland
Authors: Joanne Michelle D Gomez, Jeanne M Du-Fay-de-Lavallaz, Setri Fugar, J. Alan Simmons, Alexandra Sarau, Brian Clark, Rami Doukky, Rupa Sanghani, Neelum Aggarwal, Kim A Williams, Annabelle S Volgman
Journal: Circulation (2020)

Introduction: The novel coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. Higher COVID-19 mortality in men compared to women seen in many countries is not yet explained. We analyzed sex differences in COVID-19 outcomes in a large Illinois-based cohort. Methods: This is a multicenter retrospective cohort study of confirmed COVID-19 infections from March 1–June 3, 2020 in Rush University System. We compared men and women with COVID-19 infection for the rates of hospitalization, intensive care unit (ICU) admission, vasopressor use, endotracheal intubation, and death. A multivariable model correcting for age, race, and sum of comorbidities (obesity, hypertension, diabetes, coronary artery disease, heart failure, end-stage renal disease, asthma, chronic obstructive pulmonary disease, active smoking) was used to determine independent association with outcomes. Results: Of the 8,086 patients who tested positive, 4,267 (53%) were females, while 3,819 (47%) were males. Males had a higher rate of hospitalization (19% vs. 14%; p&lt;0.001), ICU transfer (8% vs. 4%; p&lt;0.001), vasopressor support (4% vs. 2%; p&lt;0.001), or endotracheal intubation (5% vs. 2%; p&lt;0.001). Of the 132 patients who died (10% of hospitalized patients), 76 were males, while 56 were females (2% vs. 1%; p=0.018). The prevalence of active smoking, coronary artery disease, end-stage renal disease, and HIV were higher in males, while hypertension and asthma were more common in females. Multivariable model correcting for age, race, and sum of comorbidities showed a significant association between male sex and in-hospital mortality (OR 1.78; 95% CI 1.23-2.58; p=0.002). Conclusions: There were more women who tested positive for COVID-19 disease. Male sex was independently associated with higher rates of death, hospitalization, ICU admissions, need for vasopressors or endotracheal intubation, after correction for important covariates. The interplay of biological and and behavioral factors is likely responsible for the worse outcomes observed in men with COVID-19 infection. Further investigations into the pathophysiology of sex differences in COVID-19 outcomes responses are needed.
Mounting evidence for immunizing previously infected subjects with a single dose of SARS-CoV-2 vaccine
Authors: Gonzalo Perez Marc, Damian Alvarez-Paggi, Fernando P. Polack
Journal: Journal of Clinical Investigation (2021)

Efforts to best protect the world from SARS-CoV-2 as variants emerge and despite limited vaccine supply are ongoing. One strategy that may maximize vaccine coverage and expedite immunization campaigns involves providing single mRNA vaccine doses to individuals with previous COVID-19. In this issue of the JCI, two independent studies, one by Levi and Azzolini et al. and another by Mazzoni and Di Lauria et al., explored vaccine responses in individuals previously infected with the virus. Levi and Azzolini and colleagues used multilinear regression models to correlate exposure and symptoms with antibody response to the vaccine. Mazzoni and Di Lauria and colleagues characterized B cell and T cell kinetics in whole blood after one and two doses of vaccine in health care workers with and without previous infection. Both studies indicated that one vaccine dose may sufficiently protect individuals who have recovered from COVID-19. Implementing a single-dose mRNA vaccine protocol in previously symptomatic individuals may facilitate and expedite immunization campaigns.
Self-assembled FeS-based cascade bioreactor with enhanced tumor penetration and synergistic treatments to trigger robust cancer immunotherapy
Authors: Hao Ren, Jiahui Yong, Qingqing Yang, Zhen Yang, Zhangya Liu, Yan Xu, Hao Wang, Xing Jiang, Wenjun Miao, Xueming Li
Journal: Acta Pharmaceutica Sinica B (2021)

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP) via hydrophobic interaction. After accumulated at tumor sites, FGP disassembles to smaller FeS-GOx for enhanced deep tumor penetration. GOx maintains high enzymatic activity to catalyze glucose with assistant of oxygen to generate hydrogen peroxide (H2O2) as starvation therapy. Fenton reaction involving the regenerated H2O2 in turn produced more hydroxyl radicals for enhanced CDT. Following near-infrared laser at 808 nm, FGPs displayed pronounced tumor inhibition in vitro and in vivo by the combination therapy. The consequent increased exposure to calreticulin amplified ICD and promoted dendritic cells maturation. In combination with anti-CTLA4 checkpoint blockade, FGP can absolutely eliminate primary tumor and avidly inhibit distant tumors due to the enhanced intratumoral infiltration of cytotoxic T lymphocytes. Our work presents a promising strategy for primary tumor and metastasis inhibition.