tbuckley/cabot-search huggingface dataset:
Outcomes of Venetoclax and Hypomethylating Agents (HMA) in Adult Patients with KMT2A-Rearranged Leukemias
Authors: Brian Ball, Shukaib Arslan, Paul Koller, Joyce Murata-Collins, Michelle Afkhami, Raju Pillai, Karl Gaal, Amandeep Salhotra, Monzr M. Al Malki, Ahmed Aribi, Haris Ali, Salman Otoukesh, Idoroenyi Amanam, Ryotaro Nakamura, Eileen P. Smith, Forrest Stewart, Guido Marcucci, Vinod A. Pullarkat, Ibrahim Aldoss
Journal: Blood (2021)
PATH-03. FERROPTOSIS-RELATED LONG NON-CODING RNA SIGNATURES PREDICT PROGNOSIS IN PATIENTS WITH GLIOMA
Authors: Donglin Lai, Xiaojia Zuo, Xintong Yang, Yanjun Zheng, Baoyu Duan, Yanfei Li, Guoqing Wan, Changlian Lu, Xuefeng Gu
Journal: Neuro-Oncology (2021)

Abstract Ferroptosis, with iron-dependent and ROS-dependent, is a novel type of cell death in a variety of diseases and some studies confirmed that ferroptosis-related lncRNAs are involved in the occurrence and development of several cancers. However, the ferroptosis-related lncRNA in the role of gliomas is unclear. Here, we constructed a prognostic scoring model of ferroptosis-related lncRNAs in gliomas. Data were downloaded from the Chinese glioma genome atlas (CGGA), the cancer genome atlas, and FerrDb database. In this study, we found 1051 lncRNAs associated with ferroptosis by Spearman's rank correlation analysis in CGGA653, and 547 lncRNAs were related to prognosis in gliomas. Subsequently, we identified 9 ferroptosis-related signatures (AC010729.2, AC062021.1, FAM225B, FAM66C, HOXA-AS2, LINC00662, LINC00665, MIR497HG, and TMEM72-AS1) by least absolute shrinkage and selection operator and Cox proportional hazards model. Next, all glioma patients were divided into high- and low-risk groups based on the median risk score based on these signatures, and the low-risk group had better prognosis significantly than the high-risk group by Kaplan-Meier curve. Moreover, the risk score can predict survival status with high sensitivity and specificity by receiver operating characteristic curve (area under the curve at 1, 3, 5 years: 0.791, 0.84, 0.856, respectively). In addition, some pathways (cell cycle, p53 signaling pathway, apoptosis, and oxidative phosphorylation) significantly enriched in KEGG enrichment pathway, and a nomogram was constructed by integrating some independent prognostic clinicopathological features to predict the overall survival in gliomas (C-index: 0.786). In summary, these 9 ferroptosis-related signatures have potential prognostic value and could be crucial factors for treating malignant gliomas.
Abstract 13576: Retinoic Acid Enhances Phenotypic Characteristics of Alternative Activation in Macrophages
Authors: Ivan Pinos, Jaume Amengual
Journal: Circulation (2021)

Introduction: Macrophages are key players in atherosclerosis, an inflammatory condition that leads to cardiovascular diseases. Classically-activated (M1) macrophages show a pro-inflammatory phenotype, whereas alternatively-activated (M2) are anti-inflammatory. The M1/M2 balance in atherosclerosis determines the fate of the lesions and strategies to increase M2-like macrophages entail promising candidates against atherosclerosis. We have previously shown that vitamin A delays atherosclerosis progression in mice, and others have proposed retinoic acid (RA), the transcriptionally active form of vitamin A, as a modulator of macrophage polarization. Hypothesis: RA modulates macrophage polarization by inducing M2-like responses. Methods: Bone marrow-derived macrophages (BMDM) from three wild type C57BL/6J mice were differentiated (M0) and stimulated with LPS/IFNγ (M1) or IL-4 (M2) for 24h, followed by 6h exposure to 1 μM RA or vehicle (DMSO). RNAseq and gene enrichment analysis was performed on differentially expressed genes. Autophagy flux and the lysosomal protein breakdown rate were analyzed. Results: RNAseq and differential gene expression analysis showed that RA induced changes in 1,485 genes in M2 macrophages, while 821 and 227 genes were significantly regulated in M0 and M1, respectively (FDR&lt;0.05). Arginase 1 , a well-known marker of M2 activation, was significantly upregulated by RA in M0 (FC=3.74; FDR=0.03) and M2 (FC=3.33; FDR=0.03). Autophagy and Lysosome pathways were significantly over-represented in M2 macrophages treated with RA (-log2 P=4.3 and 5.1, respectively). However, autophagy flux and protein breakdown rate were not affected by RA in M2. Conclusions: Transcriptomic data suggest that M0 and M1 macrophages are less responsive to RA in comparison to M2 macrophages. Even though RA seems to modulate the transcriptional machinery to induce the expression of autophagy genes, these changes did not alter autophagy flux or lysosomal degradation under our experimental conditions. Our data suggest that the responsiveness of M2 macrophages to RA might prompt phenotypic differences towards enhancing M2-like phenotype. Future experiments will explore the role of RA on other features of M2 polarization
Estimating the direct and indirect risks of becoming food insecure during the COVID-19 pandemic: a cross-sectional analysis using UK cohort data
Authors: Susanna Mills, Viviana Albani, Heather Brown
Journal: The Lancet (2021)

BackgroundThe COVID-19 pandemic and associated UK containment measures implemented to reduce viral spread are likely to influence the prevalence of food insecurity. Food insecurity is associated with wide-ranging negative effects on health and wellbeing. Specific containment measures such as closure of schools and hospitality venues might be expected to disproportionately affect some vulnerable groups, including single parents and young people. We aimed to identify sociodemographic and economic factors that increase the likelihood of reporting food insecurity during the COVID-19 pandemic, and to explore the extent to which financial vulnerability and experiencing COVID-19 symptoms explain the likelihood of becoming food insecure.MethodsThis analysis used cross-sectional cohort data from April, July, and September, 2020, of the UK Understanding Society COVID-19 Survey, which involved approximately 17 000 households. Food insecurity was defined as reporting positively to either or both of: "being hungry and not able to eat" or "inability to access sufficient and nutritious food because of lack of money or other resources". Logistic regression was used to identify sociodemographic and economic factors associated with increased risk of food insecurity during the COVID-19 pandemic. A decomposition approach was used to explore the extent to which these associations were explained by financial vulnerability, or experiencing COVID-19 symptoms. Ethics approval for the study was not required.FindingsSingle parents and young people aged 16–30 years were at highest risk of reporting either or both measures of food insecurity. For single parents, financial vulnerability explained 5–20% of the likelihood of being food insecure, and experiencing COVID-19 symptoms explained less than 5%. For young people, financial vulnerability explained 5–25% of the likelihood of being food insecure, and experiencing COVID-19 symptoms explained 5–30%.InterpretationSingle parents and young people may be especially at risk of food insecurity in the context of COVID-19. The wide explanatory ranges identified could be attributable to heterogeneity within groups and differing eligibility for financial support. Targeted funding, including for those self-isolating, could be an effective strategy to avoid or mitigate food insecurity among such vulnerable groups in the UK during the COVID-19 pandemic and other future pandemics.FundingNone.
Abstract 9062: A Rapid and Point-of-Care Device for Real-Time Monitoring of Pulmonary Hypertension Biomarkers
Authors: Tanzila Noushin, Shawana Tabassum
Journal: Circulation (2021)

Introduction: Pulmonary hypertension (PH) is a life-threatening condition that remains undetected at an early stage because diagnosis relies heavily on physiological presentations. The gold standard for biomolecular analysis is a blood test, which is invasive and increases the risk of infections, particularly in rural areas. To narrow this gap, we used a low-cost fabrication method to develop a sensor for real-time and bedside monitoring of a PH biomarker, B-type natriuretic peptide (BNP) in serum. Hypothesis: The sensor will facilitate research on early identification of the risk of PH from dynamic measurements of biomarkers, which will reduce cardiac failures resulting from delayed and missed diagnoses of PH Methods: We used a low-cost screen-printing technique to fabricate a 3 electrode-based electrochemical sensor on a flexible polyimide substrate (Fig. 1a). The working electrode (WE) was functionalized with anti-BNP. The sensor was interfaced with a potentiostat that applied a potential between the WE and reference electrode (RE) and measured the resulting current from the WE to counter electrode (CE). The BNP/anti-BNP binding on the WE resulted in variations in the redox current. Results: The sensor detected BNP in only 50 μl of fetal bovine serum. Fig. 1b shows the current vs. potential scan for BNP concentrations ranging from 0.1 to 500 pg/mL. The amount of current flow between WE and CE was proportional to the serum BNP levels. The sensor exhibited a sensitivity of 0.584 μA (pg/mL) -1 cm 2 (from Fig. 1c) and a response time of 4s. The sensor also showed high selectivity against common interfering species (Fig. 1d) and good repeatability with a response variability of &lt;1% between identical sensors (Fig. 1e). Conclusions: The project will advance the field of bedside monitoring of PH biomarkers. The low-cost and plug-and-play feature of the sensor allows adoption by rural communities. The sensor can be readily reconfigured and expanded to monitor other biomarkers.
Abstract 13373: Cost-Effectiveness of Population-Based Atrial Fibrillation Screening Using Wearable Devices
Authors: Wanyi Chen, Shaan Khurshid, Daniel Singer, Steven Atlas, Jeffrey M Ashburner, Patrick T Ellinor, David D McManus, Jagpreet Chhatwal, Steven A Lubitz
Journal: Circulation (2021)

Introduction: Screening of atrial fibrillation (AF) using contemporary wrist-worn wearable devices may prevent strokes, but false positive diagnoses could also lead to unnecessary bleeding and utilization of healthcare resources. Aim: To assess the cost-effectiveness of contemporary AF screening strategies and identify optimal conditions for the deployment of such strategies. Methods: We developed a microsimulation model to evaluate 8 distinct AF screening strategies, including 6 strategies utilizing wrist-worn wearable devices and 2 strategies utilizing traditional modalities ( Figure ). Within a simulated cohort of 30 million individuals with an age, sex, and comorbidity profile matching the US population aged ≥65 years (i.e., with a guideline-based screening indication), we assessed cost-effectiveness from the healthcare system perspective using incremental cost-effectiveness ratios (ICERs) at a willingness-to-pay of $100,000 per quality-adjusted life-year (QALY). We used scenario analyses to identify conditions under which the cost-effectiveness of screening may be optimized. Results: In the base case analysis, 7/8 strategies were effective (87.5%, range of QALYs gained 14-862 per 100,000 people). All 6 contemporary screening strategies were effective (range of QALYs gained 226-957 per 100,000 people). The most cost-effective strategy was wearable photoplethysmography, followed conditionally by wearable electrocardiogram with patch monitor confirmation (ICER $57,882/QALY, Figure). The cost-effectiveness of screening was consistent across multiple scenarios, including across strata of sex and targeting the US population aged ≥50 years. Conclusions: AF screening utilizing wrist-worn wearable devices appears cost-effective, and merits prioritization by potential payers.
Abstract 12147: Prognostic Impact of Cardiac MRI Derived Left Atrial Volumetric and Functional Parameters in Patients With Advanced Ischemic Cardiomyopathy
Authors: Chris Anthony, Nancy Obuchowski, Zoran B Popovic, Wilson Tang, Brian P Griffin, Scott D Flamm, Deborah H Kwon
Journal: Circulation (2021)

Background: Left atrial (LA) size has been shown to be predictive of adverse outcomes in patients with various cardiac conditions. However, the significance of left atrial function (LAF) is not clearly defined in patients with advanced ischemic cardiomyopathy (ICM). We assess the effect of cardiac magnetic resonance imaging (CMR) based LA ejection fraction (LAEF), LA volume index (LAVi) and total LA strain(Las) on outcomes in patients with ICM. Methods: Patients with ICM, who underwent cardiac magnetic resonance (CMR) between January 2002 and January 2017, were included in our study. Clinical characteristics and CMR parameters were collected and analyzed. Maximum and minimum left atrial volume (LAV) and LAEF were calculated using the biplane area-length method. Multi-variable Cox proportional hazards models were then built to test whether LAEF, LAs, and LAVi predict all-cause mortality or time to transplant. The proportionality assumption test and supremum test for functional form were used to verify the model. Results: LA functional data on 656 patients were analyzed. Patients were followed for a median of 1900 days (5.2 years). There were 336 deaths and 17 transplants. LAEF and Las were significant predictors of outcome: HR=0.98, 95% CI [0.97, 0.99], p&lt;0.001 , HR=0.94, 95% CI [0.91, 0.96], p&lt;0.001) respectively. LAVi was not an independent predictor of survival after adjusting for the medical risk score (p=0.749). Multivariable Cox proportional analysis and ROC analysis for the prediction of death or transplant of the model within two years is shown in Figure 1. Conclusion: Left atrial function is a more powerful predictor of adverse outcome than left atrial size and ischemic mitral regurgitation. Further studies are needed to assess impact of treatment on LA function.
Assessment of Macrophage Inflammatory Biomarkers and Neutrophil Extracellular Traps Associated Proteins in COVID-19 Patients
Authors: Laura Lopez de Frutos, Irene Serrano-Gonzalo, Barbara Menendez-Jandula, Esther Franco-Garcia, Carlos Lahoz, Paz Latre, Ralf Köhler, Pilar Giraldo
Journal: Blood (2021)
Abstract 12525: TEAD1 is a Novel Regulator of NRF2 and Oxidative Stress Response in Cardiomyocytes
Authors: Rajaganapathi Jagannathan, Jeongkyung Lee, Ruya Liu, Evan Devallance, ping yang, Vinny Negi, FENG LI, Patrick J Pagano, Vijay Yechoor, Mousumi Moulik
Journal: Circulation (2021)

Introduction: TEAD1, the Hippo pathway-regulated transcription factor, has a critical non-redundant role in cardiomyocyte (CM) homeostasis, and its loss-of-function results in acute lethal dilated cardiomyopathy. However, the functional pathways regulated by TEAD1 in CMs remain unclear. Hypothesis: TEAD1 plays an essential role in CM oxidative stress response (OSR) via the regulation of NRF2, the master regulator of antioxidant response. Methods and Results: Conditional CM-specific TEAD1 deletion in adult mice results in acute heart failure (HF) and altered expression of OSR genes. In silico analysis of publicly available RNA-seq data revealed significant downregulation of TEAD1 in dilated and ischemic cardiomyopathy patient hearts and a positive correlation between TEAD1 and NRF2 expression. ChIP-seq with TEAD1 antibody and ATAC-seq revealed that TEAD1 occupied open promoter/enhancer regions of multiple OSR genes, including NRF2 and its targets in adult mouse hearts. Mosaic deletion of TEAD1 in ~50% CMs, which allowed assessment of TEAD1 LOF in CMs without confounding HF effect, reduced NRF2 expression, and increased myocardial oxidative stress indicated by 8OHdG staining (DNA oxidative damage) and cellROX only in TEAD1-deficient CM, but not in CM with normal TEAD1 expression. Ex vivo and in vitro TEAD1 knockout in primary murine adult and neonatal CMs and H9C2 cells resulted in significantly elevated total cellular (Boronate assay) and mitochondrial (mitoSOX) ROS due to reduced NRF2 expression and promoter activity (ARE reporter assay). TEAD1-deficient CM had a lower tolerance to chemically (Angiotensin II, DMNQ, or AntimycinA)-induced oxidative stress. Furthermore, hTEAD1 overexpression was sufficient to significantly increase NRF2-ARE activity and rescue the elevated ROS production in CMs. Conclusions: TEAD1 is a novel cell-autonomous direct transcriptional regulator of NRF2 and CM oxidative stress response.
Diabetes Status Modifies the Association Between Different Measures of Obesity and Heart Failure Risk Among Older Adults: A Pooled Analysis of Community-Based NHLBI Cohorts
Authors: Kershaw V. Patel, Matthew W. Segar, Carl J. Lavie, Nitin Kondamudi, Ian J. Neeland, Jaime P. Almandoz, Corby K. Martin, Salvatore Carbone, Javed Butler, Tiffany M. Powell-Wiley, Ambarish Pandey
Journal: Circulation (2021)

Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established.Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m2), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes.The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (R2=0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI (P interaction=0.04) and WC (P interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each).Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.
Abstract 11630: Comparing Outcomes Between Robotic Assisted versus Manual Percutaneous Coronary Intervention - A Meta-Analysis of 2,203 Patients
Authors: Rahul Gupta, aaqib malik, Surya K Aedma, Wilbert S Aronow, Apurva Vyas, Sanjay Mehta, William G Combs, Nainesh Patel
Journal: Circulation (2021)

Introduction: Robotics in percutaneous coronary intervention (R-PCI) has been one such area of advancement where potential benefits may include reduction in radiation exposure, improved outcomes and reduced rate of adverse events. Robotic assistance may offer many potential benefits to both the operator and the patient. Limited data exist about the benefits of R-PCI vs. conventional manual PCI (M-PCI). Hypothesis: The aim for our meta-analysis is to evaluate the procedural measures and clinical outcomes between R-PCI and M-PCI. Methods: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant clinical studies. Summary effects were calculated using a DerSimonian and Laird random effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. All studies adhering to the inclusion criteria of direct comparisons between R-PCI and M-PCI were evaluated. Results: Seven studies with a total of 2,230 patients were identified. There was significant decrease in the chest-level operator radiation exposure (OR= -442.32; 95% CI = -675.88 to -208.76), fluoroscopy time (OR = -1.46; 95% CI -2.92 to 0.00) and amount of contrast used (OR= -18.28; 95% CI -24.16 to -12.41) in the robotic group as compared to the manual group. PCI time (OR = 2.41; 95% CI -3.95 to 8.76) and procedural success rate (OR 1.26; CI 0.19-8.22) was not statistically different between the two groups. In terms of clinical outcomes, there was no difference between R-PCI and M-PCI in terms of major adverse cardiac events (OR 0.90; CI 0.45-1.79), all-cause mortality (OR 0.95; CI 0.21-4.30), and myocardial infarction (OR 0.88; CI 0.41-1.89). Conclusions: Robotic PCI is associated with reduced operator radiation exposure, fluoroscopy time and amount of contrast used. While there is a significant reduction in the procedural characteristics with robotic PCI, the clinical outcomes are not different compared to manual PCI. Use of robotics in PCI appears to be safe and potentially favorable to the patients, in addition to its benefits of improved ergonomics. More randomized studies looking at the use of R-PCI, especially in complex lesions, are needed before consideration for widespread implementation.