tbuckley/cabot-search huggingface dataset:
A Comprehensive Approach to the Diagnosis and Treatment of Chronic Coronary Syndrome
Authors: Velina Stoyanova
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Coronary artery disease (CAD) is a chronic progressive disease with social significance, result of obstructive or non- obstructive atherosclerotic plaque accumulation in the epicardial arteries. CAD is one of the leading causes for deterioration in quality of life and cardiovascular mortality. CAD has dynamic character and its major clinical presentations are: acute coronary syndromes / STEMI, NSTEMI, UA/ and chronic coronary syndromes. In this case report we present the treatment algorithm in patient with chronic coronary syndrome: from optimal medical therapy, through objective methods of examination leading to the decision for interventional treatment and the importance of regular follow-up
Whole-Genome Sequencing of Common Salivary Gland Carcinomas: Subtype-Restricted and Shared Genetic Alterations
Authors: Tatiana V. Karpinets, Yoshitsugu Mitani, Bin Liu, Jianhua Zhang, Kristen B. Pytynia, Linton D. Sellen, Danice T. Karagiannis, Renata Ferrarotto, Andrew P. Futreal, Adel K. El-Naggar
Journal: Clinical Cancer Research (2021)

Salivary gland carcinomas (SGCs) are pathologically classified into several widely diverse subtypes, of which adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and salivary duct carcinoma (SDC) are the most commonly encountered. A comparative genetic analysis of these subtypes provides detailed information on the genetic alterations that are associated with their tumorigenesis and may lead to the identification of biomarkers to guide tumor-specific clinical trials.Whole-genome sequencing of 58 common SGCs (20 ACCs, 20 SDCs, and 18 MECs) was performed to catalog structural variations, copy number, rearrangements, and driver mutations. Data were bioinformatically analyzed and correlated with clinicopathologic parameters, and selected targets were validated.Novel and recurrent type-specific and shared genetic alterations were identified within and among 3 subtypes. Mutually exclusive canonical fusion and nonfusion genomic alterations were identified in both ACC and MEC. In ACCs, loss of chromosome 12q was dominant in MYB or MYBL1 fusion-positive tumors and mutations of NOTCH pathway were more common in these fusion negatives. In MECs, CRTC1-MAML2 fusion-positive tumors showed frequent BAP1 mutation, and tumors lacking this fusion were enriched with LRFN1 mutation. SDCs displayed considerable genetic instability, lacked recurrent chromosomal rearrangements, and demonstrated nonoverlapping TP53 mutation and ERBB2 amplification in a subset of tumors. Limited genetic alterations, including focal amplifications of 8q21-q23, were shared by all subtypes and were associated with poor survival.This study delineates type-specific and shared genetic alterations that are associated with early phenotypic commitment and the biologic progression of common SGCs. These alterations, upon validation, could serve as biomarkers in tumor-specific clinical trials.
Abstract 16562: Association of County-Level Social Vulnerability Index and Cardiovascular Disease in the United States, 1999-2018
Authors: Quentin R Youmans, Megan E McCabe, Clyde W Yancy, Lucia Petito, Kiarri N Kershaw, Norrina B Allen, Sadiya S Khan
Journal: Circulation (2020)

Introduction: Social determinants of health are multi-dimensional and span various interrelated domains. In order to inform community-engaged clinical and policy efforts, we sought to examine the association between a national social vulnerability index (SVI) and age-adjusted mortality rate (AAMR) of CVD. Hypothesis: Higher county-level SVI or greater vulnerability will be associated with higher AAMR of CVD between 1999-2018 in the United States. Methods: In this serial, cross-sectional analysis, we queried CDC WONDER for age-adjusted mortality rates (AAMRs) per 100,000 population for cardiovascular disease (I00-78) at the county-level between 1999-2018. We quantified the association of county-level SVI and CVD AAMR using Spearman correlation coefficients and examined trends in CVD AAMR stratified by median SVI at the county-level. Finally, we performed geospatial county-level analysis stratified by combined median SVI and CVD AAMR (high/high, high/low, low/high, and low/low). Results: We included data from 2766 counties (representing 95% of counties in the US) with median SVI 0.53 (IQR 0.28, 0.76). Overall SVI and the household and socioeconomic subcomponents were strongly correlated with 2018 CVD AAMR (0.47, 0.50, and 0.56, respectively with p&lt;0.001 for all). CVD mortality declined between 1999-2011 and was stagnant between 2011-2018 with similar patterns in high and low SVI counties (FIGURE). Counties with high SVI and CVD AAMR were clustered in the South and Midwest (n=977, 35%). Conclusion: County-level social vulnerability is associated with higher CVD mortality. High SVI and CVD AAMR coexist in more than 1 in 3 US counties and have persisted over the past 2 decades. Identifying counties that are disproportionately vulnerable may inform targeted and community-based strategies to equitably improve cardiovascular health across the country.
Abstract 15302: Cardiac MRI Assessment of Cardiac Output Agrees With Simultaneous Fick Assessment in Pediatric Heart Transplant Patients
Authors: Jennifer Schramm, Ileen Cronin, Robert McCarter, Russell Cross, joshua kanter, Tacy E Downing, Laura Olivieri
Journal: Circulation (2020)

Introduction: Systemic cardiac output (Qs) and pulmonary blood flow (Qp) can be measured by cardiac magnetic resonance (CMR) and invasive oximetry, with studies showing good agreement between the two modalities. CMR-guided right heart catheterization (MR-RHC) collects simultaneous CMR and oximetry measurements permitting direct comparison. This study assessed agreement between CMR and Fick measurements of cardiac output in the pediatric heart transplant (HT) population. Methods: Twenty-three pediatric HT patients (body surface area range 0.6-2 m 2 ) with 53 MR-RHC between 2014 -2020 were reviewed. One outlier was excluded due to erroneous pulmonary vein saturation, leaving 52 MR-RHC for analysis. Measurements of un-indexed Qs and Qp from both CMR phase contrast and invasive oximetry using Fick were collected. Bland-Altman (BA) statistical and graphical analyses compared CMR versus Fick estimates of Qs and Qp. Results: BA limits of agreement (LOA) and corresponding concordance plot demonstrate good agreement between CMR and Fick (Figure 1). Panels A and B are the BA and concordance plots for Qs, respectively. Panels C and D are the BA and concordance plots for Qp, respectively. The 95% confidence interval LOA are -1.0 to +1.8 for Qs and -1.0 to +1.7 for Qp. Average bias and Lin correlation are similar for Qs and Qp at +0.36 L/min and 0.8, respectively. Conclusions: CMR and Fick measurements of Qs and Qp are similar in pediatric HT patients, with a tendency for slightly higher values by Fick estimates and similar LOA to previously published results. CMR acquired hemodynamics offer a radiation-free modality to reduce overall radiation exposure for pediatric HT patients.
Abstract P038: Characterizing Patterns Of Fruits And Vegetables Intake In Adults With And Without Chronic Kidney Disease In The United States
Authors: Shirin Pourafshar, Binu Sharma, Sibylle Kranz, Indika Mallawaarachchi, Elizabeth Kurland, Jennie Ma, Julia Scialla
Journal: Circulation (2021)

Background: Due to concerns about hyperkalemia, the recommendation for patients with chronic kidney disease (CKD) is to limit intakes of foods high in potassium, including certain types of nuts, fruits and vegetables (F&amp;V). Detailed patterns of F&amp;V intake have not been described in patients with CKD, limiting our ability to study higher or lower risk patterns. In this study, we aimed to characterize the patterns of F&amp;V intake in adults with and without CKD in a nationally representative sample of the US. Methods: We included 16,183 adults, with (n= 3,225) and without (n= 12,958) CKD based on eGFR and albuminuria from the Third National Health and Nutrition Examination Survey (NHANES III). We calculated counts of different types of F&amp;V consumed by the participants according to a 24-h recall interview reported in the NHANES III Individual Food File. Based on their phytonutrient and starch content, F&amp;V were then categorized into: rich in polyphenols; rich in carotenoids; rich in glucosinolates, and high in starch. We also categorized consumption of legumes and nuts. Patterns of legumes, nuts, and F&amp;V intake were identified using latent class analysis (LCA; LCCA package, R 3.0.1). We evaluated differences in serum carotenoids, vitamins A, E, and C as objective biomarkers to help validate patterns. Multinomial logistic regression incorporating survey weights was used to adjust association between CKD status and F&amp;V patterns (SAS Institute, V.9.4). Results: LCA analysis classified the food consumption into 3 distinct patterns: low F&amp;V/low starch; moderate F&amp;V/high starch; and high F&amp;V/moderate starch. Consumption of legumes and nuts was low in all three patterns. Pattern of higher F&amp;V consumption had higher serum levels of carotenoids, vitamins A, E, and C (p for difference across patterns &lt;0.0001). Unadjusted patterns of consumption were not different in patients with vs. without CKD (p=0.654). After adjustment for ethnicity, gender, body mass index, waist circumference, diabetes, and hypertension, patients with CKD were more likely to consume moderate F&amp;V/ high starch (OR=1.23, p=0.0316) or low F&amp;V/starch (OR=1.34, p=0.0001) compared to patients without CKD. Conclusions: Utilizing the LCA analysis and regression, we found higher likelihood of consuming low F&amp;V patterns in patients with vs. without CKD in the US. Further studies are needed to evaluate outcomes to understand risks of benefits of F&amp;V patterns for patients with CKD.
Abstract 12606: Meta-analysis of the Normal Ranges of Right Ventricular Strains by Echocardiography in Healthy Adults
Authors: Tom Kai Ming Wang, Richard A Grimm, Leonardo L Rodriguez, Patrick H Collier, Brian P Griffin, Zoran B Popovic
Journal: Circulation (2020)

Background: Right ventricular (RV) systolic strain has been increasingly shown to be prognostic in some cardiovascular diseases. Despite this, the reference range including the lower limit of normal (LLN) and factors associated with RV strain measurements are not well-established. This meta-analysis aimed to determine the means and LLNs of two- (2D) and three-dimensional (3D) right ventricular global (RVGLS), free wall (RVFWLS) and septal wall (RVSWLS) longitudinal strains in healthy individuals and factors affecting strain measurements. Methods: Pubmed, Embase and Cochrane databases were searched until 31 December 2019 for eligible studies reporting RVGLS, RVFWLS and/or RVSWLS in at least 30 healthy subjects. We pooled the means and LLNs of RV strains by two- (2D) and three- (3D) dimensional echocardiography, and performed meta-regression analyses. Results: From 591 articles screened, 37 eligible studies totaling 2970 subjects were analyzed. Pooled means and LLNs (95% confidence intervals) for 2D- strains were RVGLS -23.3% (-24.3%, -22.3%) and -16.2% (-17.2%, -15.1%) in 22 studies; RVFWLS -27.2% (-28.5%, -25.9%) and 18.5% (-20.0%, -17.1%) in 23 studies; RVSWLS -20.4% (-22.0%, -18.9%) and -11.5% (-13.6%, -9.6%) in 10 studies; and similar results for 3D- RV strains (Table). Right ventricular fractional area change and vendor software were associated with 2D-RVGLS and RVFWLS means and LLNs. Conclusion: We reported the pooled means and LLNs of RV systolic strains in healthy subjects, to define thresholds for abnormal, borderline and normal strains. Important factors associated with RV systolic strains include right ventricular fractional area change and vendor software.
Nasal biocompatible powder of Geraniol oil complexed with cyclodextrins for neurodegenerative diseases: physicochemical characterization and in vivo evidences of nose to brain delivery
Authors: Eleonora Truzzi, Cecilia Rustichelli, Edilson Ribeiro de Oliveira Junior, Luca Ferraro, Eleonora Maretti, Daniel Graziani, Giada Botti, Sarah Beggiato, Valentina Iannuccelli, Eliana Martins Lima, Alessandro Dalpiaz, Eliana Leo
Journal: Journal of Controlled Release (2021)
Bacteria as a treasure house of secondary metabolites with anticancer potential
Authors: Chakrabhavi Dhananjaya Mohan, Shobith Rangappa, S. Chandra Nayak, Ragi Jadimurthy, Lingzhi Wang, Gautam Sethi, Manoj Garg, Kanchugarakoppal S. Rangappa
Journal: Seminars in Cancer Biology (2021)
Abstract 15612: Force, Power, and Temperature Settings in Slow Pathway Modification Utilizing an Irrigated Force Sensing Ablation Catheter
Authors: Amit Blumfield, Jay Chudow, John D Fisher, Luigi DiBiase, Kevin J Ferrick, andrew krumerman
Journal: Circulation (2020)

Introduction: Atrioventricular node reentry tachycardia (AVNRT) ablation is typically performed with solid tip catheters set to temperature control (TC) mode. Radiofrequency (RF) output, tip temperature (T), and junctional rhythm response (JRR) during RF application have been well defined. JRR in an intermittent burst, sinus-junction-junction, or sinus-junction-sinus pattern is associated with successful modification of the AV nodal slow pathway (SP). Irrigated force-sensing catheters (IFSC) are often utilized for mapping and ablation of the SP. Despite this, parameters for IFSC used in TC mode resulting in JRR have not been well described. Hypothesis: Parameters predicting JRR and successful SP modification with IFSC include power (P), force (F), impedance drop (I), and target temperature (T). Methods: Consecutive patients that underwent electrophysiologic study and successful ablation of typical AVNRT with an IFSC were studied. Lesion parameters including P, T, F, time and I change were analyzed. Lesions producing JRR were considered efficacious. Independent T-Test and ANOVA were used to determine significance between the two groups (efficacious and non-efficacious lesions). Results: 296 lesions in 39 patients (age 52+/-14) were analyzed. All patients had successful SP modification without complication. Average F producing JRR was 8g, average T producing JRR was 41 o C, average I drop producing JRR was 9 Ohms, and average P producing JRR was 28W. Only RF lesion time was a significant predictor of JRR (p=0.009). (Table 1). Conclusions: Successful SP modification with IFSC was accomplished with catheter contact force as low as 2g. Lower average tip T, and lower average P settings compared to parameters typically used with solid tip catheters were observed. Parameters including P, F, T, and I change were not predictive of JRR. Additional studies controlling for catheter location while varying parameters are indicated.
Abstract P156: Association Of Blood Pressure Responses To Submaximal Exercise With Incident Atrial Fibrillation: The Framingham Offspring Study
Authors: Joowon Lee, Tara Shrout, Emelia J Benjamin, Vasan S Ramachandran, Vanessa Xanthakis
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and a leading cause of stroke. Blood pressure (BP) responses to submaximal exercise are associated with incident cardiovascular disease and mortality. The association of BP responses to submaximal exercise with incident AF in the community is unknown. Hypothesis: We hypothesized that higher BP during and slower BP recovery after submaximal exercise are associated with a higher risk of incident AF. Methods: We evaluated Framingham Offspring Study participants who attended examination cycle 7, were free of AF, and underwent submaximal treadmill exercise testing. Systolic BP (SBP) and diastolic BP (DBP) were obtained pre-exercise (standing), during exercise (second stage, 2.5 mph at 12% grade), and 3-minutes post-exercise (supine). ΔBP during exercise was defined as exercise BP minus pre-exercise BP. ΔBP during recovery was defined as peak exercise BP minus 3-minutes post-exercise BP. We related exercise BP variables to risk of AF using Cox proportional hazards regression, adjusting for age, sex, height, weight, resting heart rate, resting SBP, resting DBP, use of antihypertensive medication, current smoking status, and diabetes. Results: We studied 2,002 participants (mean age 58 years; 53% women). During a median follow-up of 15 years, 236 participants (39% women) developed AF. We observed a positive association of exercise DBP and ΔDBP during exercise with risk of AF (Hazards Ratio [HR] per standard deviation [SD] increase 1.28, 95% CI 1.12-1.47 and HR 1.22, 95% CI 1.07-1.39, respectively). There was also a positive association between 3 minutes post-exercise SBP and AF risk (HR per SD-increase 1.31, 95% CI 1.07-1.60) and an inverse relation between ΔSBP during recovery and AF risk (HR per SD-increase 0.79, 95% CI 0.66-0.94, Table ) Conclusions: BP responses to submaximal exercise during midlife may serve as a marker for AF risk in later life.
<i>Nedd9</i> Restrains Autophagy to Limit Growth of Early Stage Non–Small Cell Lung Cancer
Authors: Alexander Y. Deneka, Meghan C. Kopp, Anna S. Nikonova, Anna V. Gaponova, Anna A. Kiseleva, Harvey H. Hensley, Douglas B. Flieder, Ilya G. Serebriiskii, Erica A. Golemis
Journal: Cancer Research (2021)

Abstract Non–small cell lung cancer (NSCLC) is the most common cancer worldwide. With overall 5-year survival estimated at &amp;lt;17%, it is critical to identify factors that regulate NSCLC disease prognosis. NSCLC is commonly driven by mutations in KRAS and TP53, with activation of additional kinases such as SRC promoting tumor invasion. In this study, we investigated the role of NEDD9, a SRC activator and scaffolding protein, in NSCLC tumorigenesis. In an inducible model of NSCLC dependent on Kras mutation and Trp53 loss (KP mice), deletion of Nedd9 (KPN mice) led to the emergence of larger tumors characterized by accelerated rates of tumor growth and elevated proliferation. Orthotopic injection of KP and KPN tumors into the lungs of Nedd9-wild-type and -null mice indicated the effect of Nedd9 loss was cell-autonomous. Tumors in KPN mice displayed reduced activation of SRC and AKT, indicating that activation of these pathways did not mediate enhanced growth of KPN tumors. NSCLC tumor growth has been shown to require active autophagy, a process dependent on activation of the kinases LKB1 and AMPK. KPN tumors contained high levels of active LKB1 and AMPK and increased autophagy compared with KP tumors. Treatment with the autophagy inhibitor chloroquine completely eliminated the growth advantage of KPN tumors. These data for the first time identify NEDD9 as a negative regulator of LKB1/AMPK–dependent autophagy during early NSCLC tumor growth. Significance: This study demonstrates a novel role for the scaffolding protein NEDD9 in regulating LKB1-AMPK signaling in early stage non–small cell lung cancer, suppressing autophagy and tumor growth.
Abstract 13013: Grk4-mediated Adiponectin Receptor-1 Phosphorylative Desensitization as a Novel Mechanism of Reduced Renal Sodium Excretion in Hypertension
Authors: Yan Zhang, Chunyu Zeng, Pedro A Jose
Journal: Circulation (2020)

Introduction: Hypertensive patients have impaired sodium excretion. However, the mechanisms are incompletely understood. There is interaction between kidney and adipose tissue. Whether and how adiponectin, one of adipokines, contributes to impaired sodium excretion in hypertension has not been previously investigated. Hypothesis: Adiponectin promotes natriuresis and diuresis and their impairment is involved in hypertension. Methods: We used Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs), GRK4g142A&gt;V transgenic mice to test the natriuresis-effect of adiponectin through intrarenal arterial infusion. Renal proximal tubule (RPT) cells, adiponectin knock out (Adipo-/-) mice, mutant plasmid were used. Results: We demonstrate that sodium excretion was reduced in Adipo-/- mice. The intrarenal arterial infusion of adiponectin induced natriuresis and diuresis in WKY rats, which was impaired in SHRs. Adiponectin inhibited Na+-K+-ATPase activity in RPT cells from WKY rats but not from SHRs. Increased adiponectin receptor phosphorylation and subsequent uncoupling from Gai, rather than altered adiponectin receptor expression, were responsible for the loss of adiponectin-mediated inhibition of RPT Na+-K+-ATPase activity, impaired natriuresis and diuresis in SHRs. Mutation of the AdipoR1 phosphorylation site restored its linkage to Gai and the adiponectin-mediated inhibition of Na+-K+-ATPase activity in RPT cells from SHRs. Finally, we identified G protein-coupled receptor kinase 4 (GRK4) as the cause of adiponectin receptor hyper-phosphorylation. GRK4g142A&gt;V transgenic mice replicated the abnormal adiponectin function in SHRs, whereas down-regulation of GRK4 by renal-ultrasound directed siRNA restored the adiponectin-mediated sodium excretion and reduced the blood pressure in SHRs. Conclusions: The stimulatory effect of adiponectin on sodium excretion is impaired in hypertension, which is attributable to increased renal GRK4 expression and subsequent adiponectin receptor hyper-phosphorylation. Targeting GRK4/adiponectin receptor/Gai may restore the impaired adiponectin-mediated sodium excretion in hypertension, thus representing a novel strategy against hypertension.
Abstract 12806: Anatomic Correlates of Systolic Anterior Motion in D-looped Transposition of the Great Arteries Post Atrial Switch
Authors: Norman Aiad, Mark Sherrid, Jodi Feinberg, Leon AXEL, Ralph S Mosca, TK Kumar, Michael Argilla, Dan Halpern
Journal: Circulation (2020)

Introduction: A paucity of data exists of the anatomic-physiological mechanisms for sub-pulmonic systolic anterior motion (SAM) of the mitral valve (MV) in d-looped transposition of the great arteries post atrial switch (d-TGA/AtS). Hypothesis: The development of SAM may be inherent to the anatomy of the MV or affected by external factors such as a dilated systemic right ventricle (RV) or pectus deformity. Methods: Clinical and cardio-imaging analysis of 18 adult patients with d-TGA/AtS (Age 42±6 years old, 56% Male) between 2015-2019 was performed. Echocardiography data included mitral apparatus anatomy (Figure) and CT/MRI data included biventricular dimensions, function, and Haller index (HI). Results: Patients with leaflet SAM (n=5) compared to patients without SAM (n=13) had significantly higher MV protrusion height (2.1 ± 0.4 vs 1.5 ± 0.4 cm p ≤0.01, respectively, Table) and longer anterior MV leaflet length (3.0 ± 0.24 vs 2.6 ± 0.34 cm p ≤0.05, respectively, Table) when compared to those without. CT/MRI showed higher sub-pulmonic left ventricular ejection fraction (LVEF) in the SAM group relative to No SAM (68 ± 5 vs 54 ± 7 % p ≤0.005, respectively, Table). RV size and function, chest deformity (HI&gt;3.5), presence of a ventricular lead pacemaker, and septal thickness did not play a role in development of SAM (Table). Conclusions: An elongated mitral apparatus is associated with the development of SAM in d-TGA/AtS and the development of LVOT obstruction. Increased sub-pulmonic LVEF contributes to SAM, whereas the systemic RV dimensions, septal thickness, and degree of chest deformity do not correlate with SAM.
Therapy-Related ALL Has Distinct Clinical and Pathologic Features Compared to De Novo ALL
Authors: Ibrahim Aldoss, Nicole Tsai, Joo Y. Song, Thai Cao, Amandeep Salhotra, Samer Khaled, Ahmed Aribi, Monzr M. Al Malki, Matthew Mei, Haris Ali, Ricardo Spielberger, Margaret R. O'Donnell, Amrita Krishnan, David S. Snyder, Joycelynne M. Palmer, Ryotaro Nakamura, Anthony S. Stein, Stephen J. Forman, Guido Marcucci, Vinod Pullarkat
Journal: Blood (2017)
Enhancement of clot visualization and ultrasound thrombolysis using microbubbles targeted to activated platelet
Authors: K Hagisawa, Toshihiko Nishioka, Shin-ichiro Umemura, Bompei Takase, Takemi Matsui, Nobuo Yoshimoto, Tumitaka Ohsuzu, Akira Kurita, Makoto Kikuchi
Journal: Circulation (2003)