tbuckley/cabot-search huggingface dataset:
Abstract 12390: Machine Learning Model Predicts One-Week Blood Pressure Average and Trajectory From One Drop Data
Authors: Lindsay Sears, Colin Harvey, Lindsay Sears, Dan Goldner, Jeff Dachis
Journal: Circulation (2021)

Introduction: Self-monitoring of blood pressure (BP) is associated with better BP management. Studies to date have focused on monitoring historic or real-time BP values, which are not inherently informative for prospective health decisions. Having a prediction of next week’s average BP gives both immediate feedback on current activity and an opportunity to take action to prevent a predicted rise in BP. Using BP and other tracking and clinical data from One Drop, an app that integrates digital therapeutics, health predictions and health sensing data, we developed a machine learning model to forecast weekly average systolic and diastolic BP. Method: One Drop has collected over 25 billion data points from people in all 195 countries, including BP, glucose, weight, medication, food, physical activity, heart rate, comorbidities, other behaviors such as sleep, and biographic data such as gender and age. Data through June 2020 were used to train two supervised learning models: 1) a regression model to predict next week’s average BP, and 2) a classification model to predict next week’s BP trend direction: rising, falling, or steady, with steady defined as a change in weekly average of less than 5 mm Hg. The trained models were used to predict hold-out values collected after June 2020 and were evaluated using mean absolute error (MAE) and AUC. Results: This study was based on a sample of 17 million BP measurements over 150,000 person-weeks from 6,600 One Drop members (46.7% male, 16.0% female; 37.3% unreported). The MAE of the regression model was 4.55 mm Hg, 22.2% less than assuming persistence (MAE = 5.85 mm Hg). For the classification model, one-vs-rest AUCs were 88.9% (rising); 80.3% (steady), 89.2% (falling) with a weighted AUC of 84.5%. Conclusion: Machine learning models based on app-collected health and self-care data can provide accurate short-term forecasts of changes in average BP. Timely feedback of this kind may empower people to make healthier choices that prevent predicted rising BP and potentially reduce overall CVD risk.
Abstract 10628: The Role of Hepatic Endoplasmic Reticulum Homeostasis in Liver-Heart Crosstalk in Sepsis
Authors: Mark Li, Qingwen Qian, Zeyuan Zhang, Mikako Harata, Winter Philibert, Biyi Chen, Adam Rauckhorst, Eric B Taylor, Dale Abel, Long-sheng Song, Ling Yang
Journal: Circulation (2021)

The heart demands continuous supply of energy substrates, primarily in the form of lipids, to sustain its contractility and other functions. During episodes of severe stress such as sepsis, an overwhelming pathogen-induced systemic immuno-metabolic response, the heart heavily relies on lipid particles synthesized at the endoplasmic reticulum in the liver. However, it is currently unknown how this lipid-dependent crosstalk supports cardiac function during stress and how it is regulated in the liver. In this study, we employed proteomic, lipidomic, and metabolomic approaches to show that hepatic Inositol-Requiring Enzyme 1 α (IRE1α), a key regulator of ER homeostasis, interacts with and regulates the activity of Fatty Acid Synthase (FAS), a well-known enzyme that synthesizes lipids. Notably, this dynamic physical interaction was disrupted in the setting of experimental sepsis induced by lipopolysaccharide (LPS). Specific deletion of IRE1α in the liver sensitized mice to LPS-associated mortality due to cardiac dysfunction. Mechanistically, we found that loss of IRE1 did not alter hepatic or systemic cytokine response, but suppressed FAS enzymatic activity, compromising the adaptive hepatic lipid metabolic reprogramming in response to the LPS challenge. Notably, IRE1α deletion diminished the LPS-induced lysophosphatidylcholine (LPC) secretion from the liver, a critical lipid species that is positively correlated with survival in septic human patients. In turn, this impaired hepatic ER-mediated lipid reprogramming contributed to cardiac dysfunction in part through reducing cardiac oxygen consumption and promoting neutrophil infiltration in response to sepsis. Together, our study provides the first insight into how adisruption of hepatic ER-mediated lipid metabolic regulation promotes sepsis-associated cardiac immuno-metabolic imbalance. Knowledge gained from this study might speed the development of novel therapeutic targets for hepatic ER homeostasis in sepsis-associated heart dysfunction.
Abstract 13392: Impaired Oxygen Uptake Efficiency Slope (OUES) Predicts Mortality in Wild-Type Transthyretin Amyloid Cardiomyopathy (ATTRwt-CM)
Authors: Michael Fattouh, Akash Patel, Amir Gilad, Brian Smerkers, Anam Waheed, John Berk, Lawreen Connors, Vaishali Sanchorawala, Omar Siddiqi, Frederick Ruberg, Gary J Balady, Deepa M Gopal
Journal: Circulation (2021)

Introduction: Cardiopulmonary exercise testing (CPET) is a prognostic tool for advanced heart failure. Whether exercise metrics can provide incremental mortality prediction in ATTRwt-CM has not been well-studied. Hypothesis: We hypothesize CPET metrics improve mortality prediction in ATTRwt-CM. Methods: A retrospective review was conducted in ATTRwt-CM patients evaluated at the BU Amyloidosis Center between 2009-2019 who underwent CPET testing. Baseline demographic, clinical, and mortality data was collected. Continuous and categorical variables were compared using paired t-testing and chi-square testing, respectively. Baseline variable association with mortality was evaluated using logistic regression. Kaplan-Meier curves were used for survival estimation and Hazard ratios (HR) were estimated using Cox proportional hazards regression analysis. Results: A total of 136 patients with ATTRwt-CM were analyzed with median follow-up of 4 years (IQR 2.4, 5.6) with 43% deaths (n=59) during follow-up. Differences in baseline characteristics and metrics between individuals with and without mortality are shown in the table. Peak VO 2 , V E /VCO 2 , ventilatory threshold, heart rate recovery, and OUES were significantly associated with mortality. Using backwards stepwise regression, only OUES remained significantly associated with mortality among CPET variables. Using multivariable Cox survival analysis (adjusting for age, NYHA, eGFR, LVEF, troponin I, and BNP), OUES remained significantly associated with mortality (HR 0.25, 95% CI 0.08 - 0.77; p=0.02). The addition of OUES to troponin I, BNP, GLS, and eGFR increased the Wald chi-square statistic from 22.5 to 26.5 (p=0.01). Conclusions: The addition of OUES in ATTRwt-CM improves mortality prediction when added to current disease staging biomarkers: troponin I, BNP, GLS, and eGFR. This study highlights the incremental strength in outcome prediction using an exercise parameter, OUES, in ATTRwt-CM.
Abstract 10138: Evening Blood Pressure and Heart Rate: An Age-Specific Association of Nocturia in the Japanese at High-Risk of Cardiovascular Disease
Authors: Michiaki Nagai, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2021)

Background: Earlier epidemiologic studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has not been established in relation to heart rate (HR). Hypothesis: We hypothesized that blood pressure (BP), HR, and the class of antihypertensive agent might be associated with severity of nocturia in the Japanese at high-risk of cardiovascular disease. In addition, these associations were hypothesized to be moderated by age. Methods: In the Japan Morning Surge-Home Blood Pressure Study, measurements of home BP as well as HR at evening (mean 11.2 days) were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). A self-administered questionnaire included items on nocturia was used. Results: The mean levels of evening systolic BP (SBP) and HR were 130±15mmHg and 70±9.6bpm, respectively. According to the number of nocturia, we divided into the three groups (no void: n= 2382; one void: n=847; &gt; 2 voids per night: n=1082). In the multinomial logistic regression analysis adjustment for confounders including age, gender, smoking, total cholesterol, fasting blood glucose, HbA1c, log B-type natriuretic peptide, beta-adrenergic blockade use, clinic SBP and clinic HR, the use of diuretics (OR, 1.23, 95%CI, 1.01-1.50, p&lt;0.05) was significantly associated with one nocturnal void, while evening SBP (OR per 1SD, 1.14, 95%CI, 1.05-1.24, p&lt;0.01) and evening HR (OR per 1SD, 1.12, 95%CI: 1.02-1.24, p&lt;0.05) were significantly associated with multiple nocturnal voids. In the lower aged group (&lt;66yrs), only evening HR remained significant (p=0.003), while only evening SBP remained significant for multiple nocturnal voids in the higher aged group (66yrs &lt; ) (p=0.007). A significant interaction was found between age and evening HR for multiple nocturnal voids (p&lt;0.05). Conclusions: In this study, evening SBP and evening HR were significant indicators of multiple nocturnal voids in the high-risk Japanese population. Increased evening HR was specifically associated with severe nocturia in the lower aged group. Age-stratified approach to reduce BP and HR burdens might be important to improve sleep disturbance caused by nocturia.
Abstract 13118: Sex Disparities in Hemodynamics and Outcomes Among Women Undergoing Contemporary Transcatheter Aortic Valve Replacement
Authors: Giorgio A Medranda, Toby Rogers, Brian C Case, Cheng Zhang, Corey Shea, Lowell F Satler, ITSIK Ben-Dor, Ron Waksman
Journal: Circulation (2021)

Introduction: Several studies have demonstrated worse outcomes following transcatheter aortic valve replacement (TAVR) in women compared to men using early transcatheter heart valves (THV). Different THV designs impact hemodynamics in patients with small annuli and women constitute the majority of these patients. Hypothesis: We hypothesized that women represent the majority of patients with small annuli resulting in worse hemodynamics. Methods: We examined patients with symptomatic severe aortic stenosis who underwent TAVR using contemporary THVs across all surgical risk categories. We compared baseline characteristics, procedural details, in-hospital outcomes, and hemodynamics (30-day) according to sex. We then performed a secondary analysis focusing on the female patients, dichotomizing them based on aortic annular area above or below 430mm 2 . Results: Included were a total of 869 patients who underwent TAVR using a contemporary THV. The majority of patients with an annular area &lt;430mm 2 were female (82.5%) and most with an annular area &gt;430mm 2 were male (76.8%). Females saw a trend towards higher 30-day (1.5% vs. 0.6%; p=0.313) and 1-year (4.1% vs. 2.7%; p=0.265) mortality. Females with an annular area &lt;430mm 2 who received an self-expanding THV saw lower mean gradients at 30 days compared to those who received a balloon-expandable THV (8.0mmHg vs. 13.8mmHg; p&lt;0.001) which resulted in lower rates of moderate patient prosthesis mismatch (PPM) (21.2% vs. 73.6%; p&lt;0.001). A similar trend was seen in females with an annular area &gt;430mm 2 who received a self-expanding THV (9.3mmHg vs. 11.5mmHg; p&lt;0.001) which resulted in lower rates of moderate PPM as well (24.5% vs. 59.2%; p&lt;0.001). Conversely, female patients who received a self-expanding THV saw higher rates of permanent pacemaker implantation regardless of annular size. Conclusions: Female patients undergoing contemporary TAVR saw numerically higher short-term mortality which could be, a result of higher rates of PPM. These findings were more pronounced in the subset of females with small aortic annuli, where those who received a self-expanding THV demonstrated superior hemodynamics but at the cost of increased rates of permanent pacemaker implantation.
EPCO-14. MULTIFACETED TRANSCRIPTOMIC AND PROTEOMIC ANALYSES IDENTIFIED PUTATIVE ALTERNATIVE SPLICING-DERIVED CELL SURFACE ANTIGENS IN GLIOMA
Authors: Takahide Nejo, Darwin Kwok, Kevin Leung, Lin Wang, Albert Wang, Payal Watchmaker, David Diebold, Hannah Driks, Jim Wells, Aaron Diaz, Joseph Costello, Hideho Okada
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND To develop effective immunotherapy for gliomas, it is crucial to expand the repertoire of targetable antigens. Recent studies have suggested that alternative splicing (AS), or its deriving tumor-specific junctions (“neojunctions”), could generate cryptic amino acid sequences that can be a source of neoantigens. In this study, we investigated neojunctions based on multifaceted transcriptomic and proteomic analyses, seeking the potential cell surface antigens that may be targeted by CAR. METHODS For screening, we analyzed bulk RNA-sequencing data of TCGA-GBM/LGG with high tumor purity (n = 429) and GTEx normal tissues (n = 9,166). Cohorts of spatially mapped intratumoral samples and longitudinally collected tumors were used to determine clonality and stability of the candidate neojunctions. Nanopore long-read amplicon sequencing was deployed to confirm the full-length transcript sequence. Their protein-level expression was explored by analyzing the Clinical Proteomic Tumor Analysis Consortium (CPTAC)-GBM proteomics dataset. RESULTS In the screening analysis comparing TCGA and GTEx datasets, we identified 218 neojunctions with adequate expression, prevalence, and tumor-specificity. Of these, 12 were predicted to be cell-surface antigens. Eight of the 12, such as BCAN, DLL3, and PTPRZ1, were also observed in multiple cases of another validation dataset. In the analysis of tumors with spatially mapped intratumoral samples, 7 of the 12 were recurrently detected in no less than 50% of the samples in multiple cases. In addition, 5 of the 12 were found to be conserved in primary and recurrent pairs of tumors in multiple cases. Full-length transcript sequencing corroborated our predictions based on short reads, and also demonstrated more complex AS patterns. Finally, CPTAC-GBM proteomics analysis identified one cryptic peptide that substantiated the corresponding transcriptome-based prediction. CONCLUSION: We identified neojunctions with the potential to generate cell-surface antigens. These multifaceted transcriptomic and proteomic analyses provide the rationale to pursue the development of immunotherapy targeting neojunction-derived antigens.
Abstract MP241: Roflumilast-mediated Phosphodiesterase 4d Inhibition Reverses Diabetes-associated Cardiac Dysfunction And Remodeling: Effects Beyond Glucose Lowering
Authors: Rui Xu, Jing Fu, Qin Fu
Journal: Circulation Research (2021)

Introduction: Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. Our recent studies reveal that hyperinsulinemia attenuates cardiac contractility by inducing expression of phosphodiesterase 4D (PDE4D) that increases cAMP degradation. Furthermore, there is growing evidence that PDE4 dysregulation is of pathophysiological importance in metabolic disorders. Hypothesis: We propose that inhibition of PDE4D might ameliorate diabetes-associated cardiac dysfunction, in addition to lowering glucose. Methods: Male C57BL/6J mice fed with high-fat diet (HFD) were treated with PDE4 inhibitor roflumilast (currently used to treat chronic obstructive pulmonary disease, COPD). Myocardial structure, contractile function and remodeling were evaluated. For mechanistic studies, specific silencing of cardiac PDE4D and overexpression of miR-1 were administrated in mice undergoing high-fat feeding. These studies were complemented by in vitro analysis in primary cultured rat cardiomyocytes and cardiac fibroblasts. Results: Mice on HFD developed greater body weight compared to normal chow diet-fed mice, manifesting hyperglycemia, hyperinsulinemia, cardiac contractile dysfunction and remodeling, and cardiac PDE4D5 upregulation by 24 weeks. The expression of PDE4D5 was also elevated in human hearts with diabetes. In comparison with vehicle-treated HFD controls, PDE4 inhibitor roflumilast (1mg/kg/day) can prevent and even reverse hyperglycemia and cardiac dysfunction, accompanied by the decrease of cardiac PDE4D expression. In addition, cardiac miR-1 level was reduced in HFD mice, which was restored by PDE4 inhibitor roflumilast treatment. Either cardiac specific PDE4D5 knockdown or miR-1 overexpression significantly reversed cardiac dysfunction in HFD-mice, despite persistence of hyperglycemia and glucose intolerance. Gain- and loss-of-function studies of PDE4D in cardiomyocytes implicated that suppression of PDE4D protected cardiac hypertrophy via SERCA2a-mediated miR-1 restoration. Moreover, inhibition of PDE4D prevented insulin-activated TGF-β1 signaling which promotes miR-1 reduction in cardiac fibroblasts and subsequent fibrosis. Conclusions: These studies elucidate a novel mechanism by which PDE4D contributes to HFD-induced heart failure through reducing miR-1 expression in both cardiomyocytes and cardiac fibroblasts and suggest a therapeutic potential of PDE4 inhibitor roflumilast in preventing or treating cardiac dysfunction associated with diabetes.
Influence of Bisphosphonates or Recombinant Human Parathyroid Hormone on <i>in Vitro</i> Chemotherapy Sensitivity in Acute Lymphoblastic Leukemia Cells
Authors: Demi T.C. de Winter, Jenneke E. van Atteveld, Jessica G.C.A.M. Buijs-Gladdines, Rob Pieters, Sebastian J.C.M.M. Neggers, Jules P.P. Meijerink, Marry M. van den Heuvel-Eibrink
Journal: Blood (2021)
Abstract 14390: Regional Variations in Atrial Fibrillation Hospitalizations
Authors: Olukayode A Busari, Emmanuel Akuna, Michael Fatuyi, Jennifer Asotibe
Journal: Circulation (2021)

Introduction: Atrial fibrillation is a common diagnosis that affects several millions of Americans yearly. Our goal is to criticize if and why geographical location could affect the outcome of a-fib management. We hope to determine if a region holds superiority in the management and outcome of A-fib patients and to understand why. Analysis with the National Inpatient Sample divided the United States into four groups the Northwest, Mid-west, South, and West. We analyzed and compared the regions in terms of the overall outcome. Methods: Data obtained from the Nationwide Inpatient Sample database from 2016 and 2017. We included data on all adult patients (aged 18 and above) hospitalized with a principal diagnosis of A-fib using ICD-10 codes. The primary outcome was inpatient mortality. Secondary outcomes had total death, length of hospital stay, total hospital charges, cost of hospitalization. Multivariate regression analysis was used to adjust for patients’ sociodemographic factors, Charleston comorbidity index, and hospital characteristics as confounders. Results: A total of 821,629.5 hospitalizations were for Atrial fibrillation. The Northeast (NE) region had 165,695 patients, the Midwest (MW) had 198,324.9, the South had 333,849.8, and the West had 123,759.8 of the total Atrial fibrillation hospitalizations. A-fib was higher in females overall (51.06%). There was significant racial variation across regions, with the South having the highest proportion of Blacks (10.36%) while the West had the highest proportion of Hispanics (12,84%). Inpatient mortality for A-fib was 0.09%. There was no significant difference in the adjusted odds ratio for mortality across the regions. Compared to the NE, the MW and W had decreased mean LOS (-0.29, 95% CI: -0.35 - [-0.22], p=0.000 and -0.42, 95% CI: -0.51 - [-0.33], p=0.000 respectively) in days. Conclusions: In conclusion, although A-fib outcomes across all US regions are relatively uniform, local regional differing effects may play a role in the delivery of care to patients. For example, we noticed that the mortality rate was much more significant in the West when compared to the other three regions. This study aims to identify and explain the varying outcomes in management to decrease all round mortality in all regions.
Abstract 11251: Warfarin versus Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus; A Multicenter Retrospective Observational Study
Authors: Abdullah Al-abcha, Shannon Clay, Ling Wang, Rohan M Prasad, Mohammad F Salam, Shaurya Srivastava, manel boumegouas, george Abela, Essa M M Essa
Journal: Circulation (2021)

Introduction: Left Ventricular (LV) thrombus formation is seen in some patients with severely reduced ejection fraction. Current guidelines recommend the use of warfarin in patients with LV thrombus. However, safe and effective warfarin use is often inconvenient and burdensome to some patients. Hypothesis: Direct oral anticoagulants (DOACs) are as effective as warfarin in the treatment of LV thrombus. Methods: We performed a multicenter retrospective analysis of adults admitted between January 2015 and December 2021 and diagnosed with LV thrombus. The primary outcome was thrombus resolution. Secondary outcomes included all-cause mortality, bleeding events and stroke or systemic embolism (SSE). Chi-square test was used to compare categorical variables. T-test was used for continuous variables comparison. Logistic regression was used to evaluate primary and secondary outcomes to control confounding factors such as demographic and comorbidity information. Results: A total of 194 patients were included, 48 (24.7%) of whom were treated with DOACs. The mean age was 61.6 ±13.3 years and 46 (23.7%) of the population were females. The two arms had no significant differences in age, sex, BMI, CHA2DS2-VASc score, history of DM, HTN, atrial fibrillation or ischemic cardiomyopathy. The rate of thrombus resolution (DOACs 58.3% vs warfarin 66.4%, p=0.309) and bleeding events (DOACs 14.6% vs warfarin 13.7%, p=0.878) were similar in both arms. The rate of SSE was numerically lower in the DOACs arm without statistical significance (DOACs 8.3% vs warfarin 15.07%, p=0.309). All-cause mortality was significantly higher in the DOACs arm (DOACs 22.9% vs warfarin 10.3%, p=0.026). In multivariate analysis, there was no significant effect of using warfarin on thrombus resolution, all-cause mortality, bleeding evens, and SSE (Figure). Conclusions: In our retrospective analysis, DOACs had similar efficacy and safety when compared to warfarin in the treatment of LV thrombus.
The dangers in policy and practice of following the consensus
Authors: Kamran Abbasi
Journal: BMJ (2021)

What is the consensus? How is it that women carry out 11 billion hours a day of unpaid work, yet society pays little heed to their wellbeing (doi:10.1136/bmj.n1972)?1 What is the explanation for the unexpected differences in life expectancy between ethnic groups (doi:10.1136/bmj-2021-068537)?2 Why is it so hard to tackle the racism that health professionals from ethnic minority groups experience daily and persistently (doi:10.1136/bmj.n2832)?3 What is the role of health professionals in preventing and tackling abuse of elderly people (doi:10.1136/bmj.n2828)?4

Does consensus even matter when it’s the evidence that should matter? Take the evidence on covid vaccines, for example. However sceptical you might be about the efficacy trials and their lack of transparency, the real world research, a good deal of which The …