tbuckley/cabot-search huggingface dataset:
Abstract 13011: RNA-Seq Analysis Of Human Abdominal Aorta Samples Identifies Putative Markers For Early Stage Atherosclerosis
Authors: Chunhong Mao, James Hixson, Do-Kyun Kim, Fannie Jackson, Richard Vander Heide, Yue Wang, Jennifer E Van Eyk, David M Herrington
Journal: Circulation (2021)

Introduction: Atherosclerosis can be defined as an assembly of hundreds of intra- and extra-cellular expressed genes that jointly alter cellular processes and produce characteristic remodeling of the local tissue environment. To improve early detection, and to interrupt the disease process before clinical consequences occur, it is necessary to recognize and understand the specific patterns of expressed genes that constitute the molecular signature of early atherosclerosis. To study this, we used RNA-Seq to identify expressed genes that are differentially abundant across normal and diseased human aortic tissues. Methods: Pairs of diseased (fatty streak (fs), fibrous plaque (fp), complex fibrous plaque (fc)) and adjacent normal (nl) grossly identified aortic samples were collected from coroner’s autopsies at the Louisiana State University (n=59). Each aortic specimen (100 mg tissue) was homogenized for total RNA extraction and generation of cDNA libraries which were sequenced by the Ion Proton™ System (Life Technology). RNA-Seq reads (avg. read length = 125) were evaluated using FASTQC for sequencing quality and aligned to the human reference genome using HISAT2. The RNA transcripts were assembled and quantified using StringTie. DESeq2 was used to compare expression levels for 16,827 genes passing QC across diseased and non-diseased samples. Results: Diseased samples had a large number of differentially expressed genes (DEGs) (fc:1731&gt; fp:380 &gt; fs:80) when compared with paired nl samples (Benjamin-Hochberg adjusted p-value &lt; 0.05), including 70 genes expressed in mitochondria. GO enrichment analysis of the fs, fp and fc DEGs showed the top enriched biological processes for the advanced lesions (fp, fc) were mostly immune response related pathways while the top enriched processes in fs samples were mainly lipoprotein metabolism. A group of 42 genes were differentially expressed in all the diseased samples compared with their adjacent nl control samples. Conclusions: The differentially expressed genes identified here provide greater resolution concerning molecular dysregulation of lipoprotein and immune function pathways and reinforce emerging data concerning abnormal mitochondrial function in early atherosclerosis.
Abstract 12470: miR-187 Mimic Targets Pro-Inflammatory Cytokynes in Cardiomyocytes Treated With Bacterial Endotoxin
Authors: Amin Ektesabi, James N Tsoporis, Sahil Gupta, Chirag Vaswani, Thomas G Parker, Claudia C dos Santos
Journal: Circulation (2021)

Introduction: 1 in 18 Canadians dies from sepsis, a life-threatening dysfunction caused by a dysregulated host response to infection which can lead to sepsis-induced Cardiac dysfunction. In the past, we have shown that administration of mesenchymal stem cells (MSCs) in the cecal ligation and puncture (CLP) model of polybacterial sepsis leads to the mitigation of sepsis-induced cardiac dysfunction by modulating microRNAs in the septic heart. Differential expression of miRNAs alters mRNA expression profile leading to a change in cellular response. In our CLP model, we identified miR-187 as a host-derived MSC-regulated miRNA. Hypothesis: Here we investigate the broader immunoregulatory of miR-187. Therefore, we tested the hypothesis that miRNA-187 inversely regulates sepsis-induced cardiac dysfunction by attenuating pro-inflammatory gene expression. Methods: Primary cardiomyocytes were isolated from 1-2 days old CD1 neonates. Cultured cells were transfected with miR-187 mimic (25 nM/mL) for 24 hours. Transfected cells were then subsequentially exposed to lipopolysaccharide (LPS, 1 μg/mL) for an additional 24 hours post-transfection. We chose to measure the expression of pro and anti-inflammatory cytokines and some cardiac injury markers via Real-Time Polymerase Chain Reaction (RT-qPCR). Results: Cardiomyocytes treated with bacterial LPS showed a significant decline in expression of miR-187 (n=4, p&lt;0.05) and a significant surge (n=4, p&lt;0.05) in the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα and IL-12 in comparison to untreated cells. Conversely, LPS-stimulated cardiomyocytes transfected with exogenous miR-187 mimic versus non-transfected LPS-stimulated cardiomyocytes demonstrated reduced expression of IL-1β, IL-6, and IL-12 (n=3, p&lt;0.05) and Fasl, S100A4 and S100A9 (n=3, p&lt;0.05). Conclusions: Transfecting neonatal cardiomyocytes with mimic miR-187 in the presence of LPS decreases the production of key inflammatory genes involved in sepsis-induced cardiac dysfunction. Our findings show miR-187 to be a potential therapeutic target to improve cardiac function in a pre-clinical model of sepsis by reducing pro-inflammatory cytokine expression.
Pathophysiology of Takotsubo syndrome: still a puzzle. Letter regarding the article ‘Pathophysiology of Takotsubo syndrome – a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology – Part 2: vascular pathophysiology, gender and sex hormones, genetics, chronic cardiovascular problems and clinical implications’
Authors: John E. Madias
Journal: European Journal of Heart Failure (2021)
TAMI-61. EXAMINING THE ROLE OF HYPOXIA INDUCED GENES CXCR4 AND NXPH4 IN INVASION OF HYPOXIC GLIOBLASTOMA CELLS
Authors: Valerie Marallano, Anirudh Sattiraju, Hongyan Zou, Roland Friedel
Journal: Neuro-Oncology (2021)

Abstract Hypoxia (low oxygen) has been associated with adverse effects in tumor biology by exaggerating the capabilities of invasion, proliferation, and survival of tumor cells within the tumor microenvironment. We engineered glioblastoma (GBM) proneural cells with a novel hypoxia reporter, HRE-UnaG, to study areas of tumor hypoxia and the effects that these hypoxic cells have on tumorigenesis. Single cell RNA-seq analysis from a mouse intracranially injected with our HRE dUnaG GBM cells revealed a shift to a mesenchymal state upon hypoxia (detected by expression of UnaG). Two genes, CXCR4 and NXPH4, were identified as being specifically induced in the hypoxic population. Our studies focus on the hypothesis that these two hypoxia induced genes, CXCR4 and NXPH4, are upregulated in hypoxic GBM cells, which may allow tumor cells to become more aggressive and resistant to conventional forms of therapies. GBM cells will be transduced with lentiviral vectors for Dox inducible shRNA knockdown of CXCR4 or NXPH4 to test specific contribution of these genes to the phenotype of the hypoxic population, with particular focus on the change in invasion and overall tumor burden upon gene silencing.
Diagnosis, prognosis, and treatment of brief psychotic episodes: a review and research agenda
Authors: Paolo Fusar-Poli, Gonzalo Salazar de Pablo, Ravi Philip Rajkumar, Álvaro López-Díaz, Savita Malhotra, Stephan Heckers, Stephen M Lawrie, Frank Pillmann
Journal: The Lancet Psychiatry (2021)
Abstract 11714: Strategies for Recruiting Young African American Men for Research
Authors: Dawn Aycock, Yodit Oliver, Precious Steeples Davis, Dawn M Aycock
Journal: Circulation (2021)

Introduction: African American (AA) men experience the highest rates of premature mortality and disability than other race/ethnic groups. Stroke is the 8th leading cause of death among young AA men and increases to the 3rd leading cause for older AA men. Despite these realities, AA men continue to be underrepresented in research. Purpose: To develop and evaluate a targeted recruitment plan for the Stroke Counseling for Risk Reduction in Men (SCORRE-M) project. Methods: A recruitment plan was developed from the researchers’ prior experiences with this population and a review of the literature to identify successful strategies for recruiting AA men for research. The plan was then implemented to recruit AA men, aged 20-35 years, who lived in Georgia and had at least one modifiable risk factor for stroke, to participate in a focus group study to assess their thoughts about stroke and the SCORRE intervention. The goal was to conduct six virtual focus groups of 6-8 men. Respondents who completed the screening survey were asked how they learned about the study and focus group participants were asked what recommendations they had for recruiting young AA men for research. Results: Recruitment occurred over 6 weeks. The 81 screening survey respondents were reached by word-of-mouth including snowball sampling (42%), social media (28%), flyers (e-mailed, handouts, posted; 20%), and through prior study participation (7%). Of the 81 respondents, 26 were ineligible (e.g., no risk factors, non-GA resident, age), 41 consented and 32 completed a focus group. During the focus groups, participants recommended incentives (e.g., gift cards, extra credit for students) and using social media to recruit young AA men for future research. They also suggested that learning about the study from a friend, colleague or study participant could motivate participation. Conclusion: The recruitment plan was successful in reaching young AA men and enrolling an adequate sample to reach saturation. The findings highlight the importance of social networks and trusted sources for considering research participation. Findings will be used to refine the recruitment plan to implement in a study testing the SCORRE-M intervention in 80 young AA men at risk of stroke.
Risk of Fracture Among Older Adults With Primary Hyperparathyroidism Receiving Parathyroidectomy vs Nonoperative Management
Authors: Carolyn D. Seib, Tong Meng, Insoo Suh, Alex H. S. Harris, Kenneth E. Covinsky, Dolores M. Shoback, Amber W. Trickey, Electron Kebebew, Manjula Kurella Tamura
Journal: JAMA Internal Medicine (2021)

Primary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown.To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management.This was a population-based, longitudinal cohort study of all Medicare beneficiaries with PHPT from 2006 to 2017. Multivariable, inverse probability weighted Cox proportional hazards and Fine-Gray competing risk regression models were constructed to determine the association of parathyroidectomy vs nonoperative management with incident fracture. Data analysis was conducted from February 17, 2021, to September 14, 2021.The primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period.Among the 210 206 Medicare beneficiaries with PHPT (mean [SD] age, 75 [6.8] years; 165 637 [78.8%] women; 183 433 [87.3%] White individuals), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis, and 147 070 (70.0%) were managed nonoperatively. During a mean (SD) follow-up period of 58.5 (35.5) months, the unadjusted incidence of fracture was 10.2% in patients treated with parathyroidectomy. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted incidence of fracture was 13.7% in patients observed nonoperatively. On multivariable analysis, parathyroidectomy was associated with lower adjusted rates of any fracture (hazard ratio [HR], 0.78; 95% CI, 0.76-0.80]) and hip fracture (HR, 0.76; 95% CI, 0.72-0.79). At 2, 5, and 10 years, parathyroidectomy was associated with adjusted absolute fracture risk reduction of 1.2% (95% CI, 1.0-1.4), 2.8% (95% CI, 2.5-3.1), and 5.1% (95% CI, 4.6-5.5), respectively, compared with nonoperative management. On subgroup analysis, there were no significant differences in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or meeting operative guidelines. Fine-Gray competing risk regression confirmed parathyroidectomy was associated with a lower probability of any fracture and hip fracture when accounting for the competing risk of death (HR, 0.84; 95% CI, 0.82-0.85; and HR, 0.83; 95% CI, 0.80-0.85, respectively).This longitudinal cohort study found that parathyroidectomy was associated with a lower risk of any fracture and hip fracture among older adults with PHPT, suggesting a clinically meaningful benefit of operative management in this population.
Zanubrutinib, Lenalidomide Plus R-CHOP (ZR 2-CHOP) As the First-Line Treatment for Diffused Large B-Cell Lymphoma (DLBCL)
Authors: Huayuan Zhu, Yeqin Sha, Wei Wu, Jingyan Qiu, Yilian Yang, Chen Peng, Chongyang Ding, Zhen Wang, Lei Fan, Wei Xu, Jianyong Li
Journal: Blood (2021)
Abstract P380: Common And Distinct Signatures Of Interstitial And Perivascular Fibrosis In Mouse Models Of Hypertensive Heart Disease
Authors: Louise Thisted, Claudia Correia, Karin Jennbacken, Maria Wagberg, Franziska Wichern, Martin Madsen, Chen Zhang, Jacob L Skytte, Henrik H Hansen, Nora E Zois, Niels Vrang, Jacob Jelsing, Urmas Roostalu, Qing Dong Wang
Journal: Circulation Research (2021)

Fibrosis is the hallmark of hypertensive heart disease and heart failure with preserved ejection fraction. Perivascular fibrosis impairs vascular function while interstitial fibrosis leads to compromised cardiac contractility. How these fibrosis types are represented in mouse models of hypertensive heart disease and to what extent the transcriptional signatures of cardiac fibrosis are defined by their location is unknown. Mice were dosed over 4 weeks with angiotensin II (AngII) alone or together with α 1 -adrenergic agonist phenylephrine (PE) and were characterized by echocardiography, light sheet imaging and fibrosis histology. While both groups developed systolic and diastolic dysfunction, hypertrophy and perivascular fibrosis, co-administration of PE resulted in a more severe disease phenotype and prevalent interstitial fibrosis, highlighting the benefits of this model in preclinical research. High-precision spatial transcriptomics based on laser capture microdissected perivascular and interstitial fibrotic areas revealed activation of distinct pro-fibrotic as well as cardioprotective pathways in the AngII+PE infusion model. Perivascular and interstitial fibrosis showed remarkable differences in global gene expression signatures, as demonstrated by high expression of osteochondrogenic genes and markers of secretory fibroblasts in perivascular fibrosis. A limited number of upregulated genes is shared between the fibrosis locations. These data collectively show the suitability of mouse models of hypertensive heart disease to study cardiac fibrosis and demonstrate how progression of fibrosis in mice is closely coupled to deteriorating cardiac dysfunction associated with highly distinct molecular signatures of perivascular and interstitial fibrosis.
Is cardiac involvement prevalent in highly trained athletes after SARS-CoV-2 infection? A cardiac magnetic resonance study using sex-matched and age-matched controls
Authors: Liliána Szabó, Vencel Juhász, Zsófia Dohy, Csenge Fogarasi, Attila Kovács, Bálint Károly Lakatos, Orsolya Kiss, Nóra Sydó, Emese Csulak, Ferenc Imre Suhai, Kristóf Hirschberg, Dávid Becker, Béla Merkely, Hajnalka Vágó
Journal: British Journal of Sports Medicine (2021)

To investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls.
Single-cell RNA sequencing reveals that <i>BMPR2</i> mutation regulates right ventricular function <i>via ID</i> genes
Authors: Mingxia Du, Haibin Jiang, Hongxian Liu, Xin Zhao, Yu Zhou, Fang Zhou, Chunmei Piao, Guoqiang Xu, Feng Ma, Jianan Wang, Frederic Perros, Nicholas W. Morrell, Hong Gu, Jun Yang
Journal: European Respiratory Journal (2021)

Background Mutations in bone morphogenetic protein type II receptor ( BMPR2 ) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). Our study aimed to clarify whether deficient BMPR2 signalling acts through downstream effectors, inhibitors of DNA-binding proteins (IDs) during heart development to contribute to the progress of PAH in CHD patients. Methods To confirm that IDs are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH, we generated cardiomyocyte-specific Id 1/3 knockout mice (Ids cDKO), and 12 out of 25 developed mild PAH with altered haemodynamic indices and pulmonary vascular remodelling. Moreover, we generated ID1 and ID3 double-knockout (IDs KO) human embryonic stem cells that recapitulated the BMPR2 signalling deficiency of CHD-PAH induced pluripotent stem cells (iPSCs). Results Cardiomyocytes differentiated from iPSCs derived from CHD-PAH patients with BMP receptor mutations exhibited dysfunctional cardiac differentiation and reduced calcium (Ca 2+ ) transients, as evidenced by confocal microscopy experiments. Smad1/5 phosphorylation and ID1 and ID3 expression were reduced in CHD-PAH iPSCs and in Bmpr2 +/– rat right ventricles. Moreover, ultrasound revealed that 33% of Ids cDKO mice had detectable defects in their ventricular septum and pulmonary regurgitation. Cardiomyocytes isolated from mouse right ventricles also showed reduced Ca 2+ transients and shortened sarcomeres. Single-cell RNA sequencing analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type cells. Conclusion We found that BMPR2 signals through IDs and USP9X to regulate cardiac differentiation, and the loss of ID1 and ID3 expression contributes to cardiomyocyte dysfunction in CHD-PAH patients with BMPR2 mutations.
Effect of a neck collar on brain turgor: a potential role in preventing concussions?
Authors: Michael Dinsmore, Zakir Hajat, Connor TA Brenna, Joseph Fisher, Lashmi Venkatraghavan
Journal: British Journal of Sports Medicine (2021)

Mild internal jugular vein (IJV) compression, aimed at increasing intracranial fluid volume to prevent motion of the brain relative to the skull, has reduced brain injury markers in athletes suffering repeated traumatic brain injuries. However, an increase in intracranial volume with IJV compression has not been well demonstrated. This study used transorbital ultrasound to identify changes in optic nerve sheath diameter (ONSD) as a direct marker of accompanying changes in intracranial volume.Nineteen young, healthy adult volunteers (13 males and 6 females) underwent IJV compression of 20 cm H2O low in the neck, while in upright posture. IJV cross-sectional area at the level of the cricoid cartilage, and the change in right ONSD 3 mm behind the papillary segment of the optic nerve, were measured by ultrasound. Statistical analysis was performed using a paired t-test with Bonferroni correction.Mean (SD) cross-sectional area for the right IJV before and after IJV compression was 0.10 (0.05) cm2 and 0.57 (0.37) cm2, respectively (p=0.001). ONSD before and after IJV compression was 4.6 (0.5) mm and 4.9 (0.5) mm, respectively (p=0.001).These data verify increased cerebral volume following IJV compression, supporting the potential for reduced brain 'slosh' as a mechanism connecting IJV compression to possibly reducing traumatic brain injury following head trauma.
Abstract 10686: Lack of Normal Blood Pressure Awareness Among Cardiology Clinic Patients
Authors: Mohammed Mahdi, Arshdeep Nagra
Journal: Circulation (2021)

Introduction: Hypertension is a condition of elevated blood pressure associated with significant morbidity and mortality. Normal blood pressure is defined as systolic blood pressure of &lt;120 mm Hg and diastolic blood pressure of &lt;80 mm Hg. Uncontrolled hypertension and patient awareness of hypertension remain large public health challenges. Hypothesis: We hypothesized that a significant number of patients have poor awareness of what is normal blood pressure. Patient’s unawareness of this definition could be a significant contributor to poorly controlled hypertension. Thus, we set out to assess the awareness level for normal blood pressure readings amongst patients visiting a cardiology clinic. Methods: This is an observational study of randomly recruited patients from a cardiology clinic located in Trenton, New Jersey. After patient consent, a questionnaire written in both English and Spanish was given to each patient. The questionnaire was in the form of a multiple-choice question with options to identify normal blood pressure reading as less than either 170/90, 140/90, 160/100, or 120/80 mmHg. Results: A total of 252 patients were recruited. The sample was made up of 57% women and 40% men, with a mean age of 62.7 years. Patients’ primary spoken language was English among 81% of the sample, Spanish among 13%, and other languages among 6%. The race/ethnicity of patients surveyed were Black/African American in 50% of the sample, White/Caucasian in 24%, Hispanic in 16%, Asian in 4%, and other in 6%. Among those surveyed, 35% of patients were unable to identify the normal blood pressure values, with 22% identifying “normal” blood pressure as 140/90 mm Hg, 7% identifying 160/100 mm Hg, and 6% identifying 170/90 mm Hg. Conclusions: Health illiteracy is common among patients with at least one cardiac problem and might be associated with poor outcome. Mass education regarding normal blood pressure values could aid in better hypertension awareness and management.
Abstract 11657: Cannabis Use is Associated With Abnormal P-wave Axis
Authors: Nikhil Patel, Travis Skipina, Bharathi Upadhya, Elsayed Soliman
Journal: Circulation (2021)

Introduction: Cannabis use has been linked to incident ischemic cerebrovascular disease (CVA) and atrial arrhythmias in various case series and population studies. Hypothesis: Cannabis is independently associated with abnormal p-wave axis (aPWA), a marker of atrial myopathy. Methods: This analysis included 3,600 (age 48.2 ± 5.9 years, 47.6% male, 69.1% whites) participants from the Third National Health and Nutrition Examination Survey. Cannabis use was defined by self-report. aPWA was defined as p-wave axis outside of 0-75 degrees. Multivariable logistic regression was used to examine the association between cannabis use and aPWA. The consistency of this association was tested among subgroups stratified by demographic and comorbid covariates. Results: About 24.3% (n = 875) of participants were ever-cannabis users and 20.4% (n = 735) had aPWA. In multivariable and logistic regression analysis, ever- and former cannabis users had increased odds of aPWA compared to never users [OR (95% CI): 1.27 (1.03-1.56) and 1.28 (1.03-1.59), respectively]. Those reporting ≥10 lifetime uses had 40% increased odds of aPWA [OR (95% CI): 1.40 (1.07-1.84)]. This effect was stronger among ever-users with a history of cardiovascular (CV) disease versus those without [OR (95% CI): 4.11, 95% CI: 1.35 - 12.52, interaction p-value 0.03]. Conclusion: Cannabis use is associated with atrial myopathy reflected as aPWA. This association is stronger among participants with a history of CV disease. These findings underscore a potential mechanism by which cannabis use increases the risk for ischemic CVA/atrial arrhythmias and highlights the need for personalized cannabis risk assessment.