tbuckley/cabot-search huggingface dataset:
Abstract 247: Cardiac Arrest Management in Rural Prehospital Care
Authors: Gregory A Peters, Alexander Ordoobadi, Rebecca E Cash, Ashish Panchal
Journal: Circulation (2020)

Introduction: Rural prehospital care settings are underrepresented in the out-of-hospital cardiac arrest (OHCA) literature. We analyzed a nationwide database of emergency medical services (EMS) incidents in the US to describe treatment patterns and the odds of return of spontaneous circulation (ROSC) among rural OHCA patients. Methods: Using the 2018 National EMS Informational System dataset, we analyzed OHCA incidents where CPR provided by EMS was documented. We excluded incidents in which trauma was involved, patient age &lt;18 years, transport was not by completed by an advanced life support unit, or response time &gt;60 minutes. The primary outcome was ROSC during the EMS incident. Multivariable logistic regression was performed comparing rural, suburban, and urban settings while controlling for age and gender, incident location type, response time, CPR prior to EMS arrival, arrest witnessed by EMS, initial rhythm, epinephrine administration, mechanical CPR, and advanced airway used. Results: A total of 60,281 OHCA incidents were identified for inclusion, including 5,013 (8.6%) in rural settings. Rural OHCA patients achieved ROSC in 28.8% of cases, compared to 33.0% in urban or suburban settings (p&lt;0.001). Neither age nor gender significantly differed between settings (Table 1). Rural OHCA incidents had greater response times (7.5 vs. 5.9 minutes, p&lt;0.001) and were less likely to receive epinephrine (71.6% vs. 74.9%, p&lt;0.001). Further, EMS were more likely to use mechanical CPR (29.8% vs. 28.1%, p=0.01) and less likely to provide an advanced airway (56.3% vs. 50.5%, p&lt;0.001) for rural OHCA. On multivariable logistic regression, rural OHCA patients had lower odds of achieving ROSC than urban OHCA patients after controlling for other factors (0.80, 95%CI: 0.75-0.86). Conclusion: In this national sample of EMS-treated OHCA, rural patients were less likely to achieve ROSC than patients in urban or suburban settings.
Abstract 15478: In-Hospital and 30-Day Outcomes Following Acute Mechanical Circulatory Support With Impella 5.0®/LD® Device: An Updated Systematic Review and Meta-Analysis
Authors: Rupak Desai, Upenkumar Patel, Sandeep Singh, Tarang Parekh, Muhammad Uzair Lodhi, Kishorbhai Gangani, Rajesh Sachdeva, Gautam Kumar
Journal: Circulation (2019)

Background: Impella 5.0/LD (Abiomed Inc, Danvers, MA) devices are being increasingly used in the management of cardiogenic shock. Considering a varied consensus, we conducted this updated meta-anal...
Fitter, healthier and stronger? Many factors influence elite athletes’ long-term health
Authors: Urho M Kujala
Journal: British Journal of Sports Medicine (2020)

It is now incontrovertible that properly tailored exercise therapy increases physical fitness, reduces depression, lowers cardiometabolic risk factors, reduces pain and improves health-related quality of life in chronically ill patients. Former elite athletes usually exercise more than population controls during their later life. Participating in elite endurance-type sports—an indicator of exceptionally high aerobic fitness—is associated with low risk of premature death, at least before the use of doping became common.1 2 

Athlete mortality statistics are often compared with data from the general population. Finnish male former elite athletes outlived matched controls who were healthy at the age of 20.1 In former endurance athletes, the risk of type 2 diabetes (OR adjusted for age, socioeconomic status, body mass index and smoking 0.24, 95% CI 0.07 to 0.81) and ischaemic heart disease (adjusted OR 0.33, 95% CI 0.18 to 0.61) were dramatically lower than in matched controls. These partly genetically determined1 3 health advantages, combined with a lower rate of smoking, …
Abstract 17239: miRNAs Secreted by Exosomes Derived From Adipose Tissue Mesenchymal Stem Cells Overexpressing GATA-4 Increase Endothelial Cell Survival and Promote Angiogenesis
Authors: Jie Xu, Jiapeng Wang, Min Liu, Yigang Wang, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2020)

Exosomes (EXO) secreted from stem cells play a critical role in cell based therapy and appear to have greater salutary therapeutic effects than whole cells. Our previous study showed that EXO produced by GATA-4-overexpressing mesenchymal stem cells (MSCs) significantly promoted angiogenesis and protected cardiomyocytes resulting in improved ischemic myocardial function. In the present studies, we compared the miR expression pattern and determined whether Exo GATA-4 delivered miRs particularly promoted angiogenesis. Methods and Results: EXO were collected from conditioned medium of adipose tissue derived MSCs that were transfected with GATA-4 (Exo GATA-4 ) or with vector-empty (Exo null ) using ultracentrifugation ( Fig A ). Functional analysis showed that Exo GATA-4 significantly increased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs) compared to Exo null . MicroRNA-seq data showed that 7 of the 230 miRs found in EXO, were significantly upregulated in Exo GATA-4 ( Fig B ). To determine the effect of upregulated miRs on Exo GATA-4 mediated angiogenesis, miR-155 and miR-6240 mimic, inhibitor, and negative control were directly transferred into HUVECs. After 48 hours, HUVECs were harvested for measuring endothelial cell behavior. Transfection of miR-6240-mimic significantly increased HUVECs proliferation, tolerance against H 2 O 2 induced injury ( Fig C ), tube-like structure formation ( Fig D ) and cell migration ( Fig E ) compared to those transfected with negative control. Concurrently, no significant differences were found in proliferation, survival, and tube-like structure formation among the cells transfected with miR-155-mimic and negative control, although miR-155-mimic significantly increased cell migration. Conclusion: The upregulated miRs in Exo GATA-4 may variably regulate endothelial cell behavior and the role of various miRs needs to be investigated individually.
Abstract 17115: Age-Related Outcomes for Takotsubo Syndrome Differ by Sex
Authors: Varun Pattisapu, HUA HAO, Trevor Trung Nguyen, Noel B Merz, Susan Cheng
Journal: Circulation (2020)

Background: Takotsubo syndrome (TTS) is an uncommon but increasingly recognized cause of myocardial infarction in both women and men across the age spectrum. Emerging data suggest that outcomes are worse in younger compared to older adults, and the extent to which this trend differs by sex is unclear. Methods: Using the National Inpatient Sample data from years 2006 to 2014, we identified hospitalizations with either a primary or secondary diagnosis of TTS. We analyzed these data stratified by age and sex. Outcomes measured include in-hospital mortality and in-hospital complications of cardiac arrest, cardiogenic shock, any type of shock, vasopressor use, intra-aortic balloon pump use, and mechanical ventilation. Results: We identified a total of N=18,051 TTS cases over the study period, most of which were experienced by women (89%). Despite the majority cases occurring in patients over age 50 years (89%), younger patients hospitalized with TTS were consistently more likely to suffer almost all major types of in-hospital complications except for in-hospital mortality ( Figure ). These apparently paradoxical age-based trends were observed in women more so than in men. Conclusion: Our results demonstrate that while individuals age 50 years and older continue to be more frequently hospitalized with TTS than younger patients, younger patients present with greater complications. This age-based finding is seen predominantly in women and much less so in men, potentially related to sex differences in sympathetic regulation of cardiovascular responses to stress. Further research is needed to validate and investigate the potential mechanisms underlying our findings.
Abstract 17121: Initiation of Anti-Hypertensive Therapy and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) and a History of Hypertension (HTN)
Authors: Poonam Bhyan, Phillip H Lam, cherinne arundel, charles faselis, Prakash Deedwania, Apostolos Tsimploulis, Richard M Allman, Michel White, Wilbert S Aronow, Steven Singh, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2020)

Background: According to the ACC/AHA HF guideline, in patients (pts) with HFpEF and HTN, optimal systolic blood pressure (SBP) target is &lt;130 mm Hg. Although SBP &lt;130 has been shown to be associated with a higher risk of death in HFpEF (PMC5875342), the use of anti-HTN therapy in those with SBP ≥130 has not been well studied. We tested the hypothesis that anti-HTN therapy in pts with HFpEF, HTN and SBP ≥130 would be associated with improved outcomes. Methods: Of the 8873 hospitalized pts with HF w EF ≥50% in Medicare-linked OPTIMIZE-HF, 6781 (76%) had a history of HTN, of whom 3680 (54%) had a discharge SBP ≥130 mmHg. We assembled an inception cohort by excluding 1611 (44%) receiving anti-HTN drugs (HCTZ, hydralazine, or a CCB) before admission. Of the remaining 2069 pts, 430 (21%) received a new discharge prescription for anti-HTN drugs. Propensity scores for anti-HTN drug initiation, estimated for each of the 2069 pts, were used to assemble a cohort of 427 pairs of pts started and not started on anti-HTN therapy, balanced on 60 baseline characteristics including use of ACEI/ARBs and BBs. Results: The 854 matched pts had a mean age of 77 years, mean SBP of 149 mmHg, 67% were women, and 17% African American. 3-year all-cause mortality occurred in 45% and 53% of matched pts started vs. not started on anti-HTN therapy, resp. (HR 0.77; 95% CI, 0.64-0.94; p=0.009; Figure ). There was no association with readmissions. Conclusion: In pts with HFpEF, HTN and SBP ≥130 mm Hg, initiation of anti-HTN therapy is associated with a lower risk of death.
Abstract 13170: Bicuspid Aortic Valve Exacerbates the Ascending Aorta Aortopathy but Not Hypertension in Repaired Coarctation of the Aorta
Authors: Kwannapas Saengsin, Kimberly Gauvreau, Ashwin Prakash
Journal: Circulation (2020)

Introduction: Coarctation of the aorta (COA) is a generalized vascular disease, associated with reduced aortic distensibility and a higher prevalence of systemic hypertension. 60-85% of COA patients have a bicuspid aortic valve (BAV). BAV is independently associated with lower aortic distensibility, but not hypertension (HTN). It is not known if the presence of a BAV accentuates the aortopathy and hypertension in CoA patients. Hypothesis: COA patients with a BAV have a stiffer aorta than those with a tricuspid aortic valve (TAV). Methods: We retrospectively identified COA patients with and without BAV in whom the cardiac MRI (CMR) data was available from 2005-2019 and calculated aortic distensibility at the ascending (AAO) and descending aorta (DAO). Patients with residual COA were excluded. Results: Among 215 COA patients (median age 25.3 years, 56% male), 67% of patients had a BAV. BAV and TAV groups were similar to the current age, gender, and modality of COA treatment. As expected, BAV patients had larger AAO size (median diameter z -score 1.4 versus 0.1, p&lt;0.001). Median AAO distensibility z-score was significantly lower in the BAV group (-1.2 versus -0.7; p=0.014) but DAO distensibility was similar in BAV and TAV patients. The prevalence of HTN was not different between BAV (32%) and TAV groups (36%, p = 0.56). On multivariable analysis, HTN was not associated with BAV or AAO distensibility but was associated with lower DAO distensibility (p=0.01). Conclusions: In young adults with adequately treated COA, the BAV group had lower AAO distensibility and a larger AAO compared with the TAV group. However, DAO distensibility and the prevalence of hypertension were similar in BAV and TAV patients. These results suggest that although the presence of a BAV in COA exacerbates the AAO aortopathy in a localized fashion, it does not exacerbate the more generalized vascular dysfunction and associated HTN.
Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis
Authors: Yinu Wang, Guangyuan Zhao, Salvatore Condello, Hao Huang, Horacio Cardenas, Edward J. Tanner, JianJun Wei, Yanrong Ji, Junjie Li, Yuying Tan, Ramana V. Davuluri, Marcus E. Peter, Ji-Xin Cheng, Daniela Matei
Journal: Cancer Research (2020)

Abstract Defining traits of platinum-tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum-tolerant cells and tumors were identified using in vitro and in vivo ovarian cancer models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were enriched in ALDH+ cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared with parental cells. Additionally, platinum-tolerant cells and tumors exhibited expression of the Wnt receptor Frizzled-7 (FZD7). Knockdown of FZD7 improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7+ from FZD7− cells included epithelial-to-mesenchymal (EMT), stemness, and oxidative phosphorylation-enriched gene sets. Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7+ platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. FZD7, Tp63, and glutathione metabolism gene sets were strongly correlated in the ovarian cancer Tumor Cancer Genome Atlas (TCGA) database and in residual human ovarian cancer specimens after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial cancer stem cell features, characterized by FZD7 expression and dependent on the FZD7–β-catenin–Tp63–GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum-tolerant cancer cells and provide new insight into a potential “persister cancer cell” phenotype. Significance: Frizzled-7 marks platinum-tolerant cancer cells harboring stemness features and altered glutathione metabolism that depend on GPX4 for survival and are highly susceptible to ferroptosis.
Over-expression of Sec61-gamma fosters glioblastoma growth and survival in culture
Authors: Anjan Misra, Ivan Smirnov, Colin Morrow, Madhusudan, Burt Feuerstein
Journal: Cancer Research (2008)

4246  Sec61-gamma (Sec61G) is a subunit of the mammalian endoplasmic reticulum (ER) translocon, an evolutionarily conserved transmembrane protein that moves newly synthesized proteins across the ER. Crystal structures of the bacterial and yeast Sec61 translocon suggest that Sec61 a,b and g subunits form a complex to transport protein from the ribosome into golgi, plasma membrane or cytoplasm. Sec61g is located on the short arm of chromosome 7, next to the epidermal growth factor receptor (EGFR). Since EGFR is frequently amplified in GBM, with a large amplicon encompassing megabases, Sec61g is likely amplified and over-expressed in most of GBM with EGFR amplification. The effect of SEC61g over-expression on GBM behavior is unknown. We used 3 sets of published Affymatrix GBM gene expression data from the University of California, San Francisco (Nigro et al, 2005), M.D.Anderson Cancer Center (Phillips et al, 2006) and the University of California, Los Angeles (Freije et al, 2004), and an array of traditional and novel statistical methods, bioinformatics, structural modeling, and biological assays to investigate effects of Sec61g overexpression. There was extremely high correlation between Sec61g expression and EGFR expression (p=2.2e-16) in this set of 195 GBM. Almost all EGFR amplification cases had Sec61g amplification and overexpression. Sec61g was over-expressed in the poorly surviving mesenchymal and proliferative subgroups (Phillips et al, 2006), but not in the longer surviving proneural subgroup. Furthermore, Sec61g was associated with poor survival (p=0.005), and was a strong negative predictor of >1 year survival (p=7.6e-6). Structural modeling of the human SEC61 complex indicates similarity to lower species. Human Sec61g is composed of two alpha helices of unequal length forming a structure that resembles the number “7” with an evolutionarily conserved proline residue at the junction of the arms. Over-expression of Sec61g in U251NCI cells in culture increased growth rate (p
Abstract 13531: Coronary Artery Disease Predicts Venous Occlusion in Patients Undergoing Lead Extraction
Authors: Kris Kumar, Stacey Howell, Saket Sanghai, George Giraud, Peter Jessel, Charles A Henrikson
Journal: Circulation (2020)

Introduction: Pacemaker and ICD lead failure or vascular occlusion can require lead extraction. Predictors of a need for lead extraction due to venous occlusion are not well characterized. Hypothesis: Coronary artery disease (CAD) is an independent predictor of lead extraction due to venous occlusion. Methods: We performed a retrospective study of consecutive patients in a prospectively collected registry at a single center undergoing lead extraction due to either venous occlusion or lead failure from 10/2011 to 02/2020. Patients requiring lead extraction due to infection were excluded. Continuous variables are reported as mean ± standard deviation or total number reported as a percentage (%). Chi square test and logistic regression were used to estimate difference in rates and Odds Ratio. Statistically significant findings were identified with a p valve &lt; 0.05. Results: Of 384 procedures included in the database, 131 patients met inclusion criteria for venous occlusion (17%) or lead failure (83%) (Table 1). Average age of the cohort was 55.1 ± 16.4 years and 51% were female. Baseline ejection fraction was 44.6 ± 15.5% and 19.7% of patients had NYHA class III or IV symptoms. 29.7% had a history of CAD. Average number of leads extracted was 1.3 ± 0.57 compared to 2.1 ± 0.82 leads in situ. Patients with CAD had a statistically significant increased risk for extraction as a result of venous occlusion Odds Ratio of 6.80, 95% CI 2.47-18.6, p = 0.0001. Conclusions: Identification of predictors of venous occlusion and risk stratification of these patients is an important component of procedural planning and shared decision making. CAD is a predictor of venous occlusion in patients undergoing lead extraction and should be assessed as a risk factor for complex lead management decisions. Further study is warranted to identify mechanisms by which this relationship can be used to predict need for extraction due to vascular occlusion.
Abstract 17050: Pulmonary Vein Isolation Leads to Decreased Stability of Rotational Activities in Atrial Regions Remote From the Site of Ablation - A New Mechanism by Which Pulmonary Vein Isolation Leads to Beneficial Remodeling in the Atria
Authors: Markus Rottmann, Shin Yoo, Anna Pfenniger, David Johnson, Gail Elizabeth Geist, Suman Mandava, Amy Burrell, Andrew Wasserstrom, Bradley P Knight, Rod S Passman, Rishi Arora
Journal: Circulation (2020)

Introduction: Pulmonary vein isolation (PVI) is thought to be efficacious in patients with paroxysmal and persistent atrial fibrillation (AF). However, the underlying mechanisms by which PVI leads to beneficial atrial remodeling are not clear. Hypothesis: We hypothesized that PVI leads to beneficial atrial remodeling by affecting electrophysiological characteristics at sites ‘remote’ from the site of ablation. We examined the effect of PVI on stability of rotational activity throughout both atria. Methods: AF was induced in 12 dogs by rapid atrial pacing for 3-6 weeks. PVI was performed in 3 dogs, 9 dogs were used as controls. Epicardial high-density mapping was performed (117 electrodes, inter-elec. distance 2.5mm) before and after PVI. The AF characteristics were analyzed in 6 regions in the left (LA) and right atrium (RA): Cycle length (CL), stability, number of observed rotational activities based on local activation time (LAT) maps. Results: Multiple interacting rotational activities were detected in all regions with highest stability in the appendages (Figure A). PVI led to a significant increase in CL (range: 2.26 %-14.1%) in all regions (Figure B). Stability of rotational activity decreased (baseline vs after PVI) in all atrial regions: LAA (594±344ms, median 525ms vs 354±126ms, median 300ms), PLA (564±491ms, median 360ms vs 180±25ms, median 180ms), LAFW (323±248ms, median 240ms vs 240±70ms, median 240ms), in PRA (260±1167ms, median 210ms vs 239±75ms, median 240ms), RAA (1521±1301ms, median 975ms vs 457±251ms, median 450ms), P&lt;=0.05 for all comparisons, RAFW (1521±1301ms, median 975ms vs 457±251ms, median 450ms, P=0.46) (Figure C). PVI reduced number of observed rotational activities by 25.76% in all regions (P&gt;0.5). Conclusions: PVI significantly reduces the stability of rotational drivers in atrial regions remote from the site of ablation. We believe we have discovered a new mechanism by which PVI leads to beneficial remodeling in both the LA and RA.
3D Bioprinting of Neural Tissues
Authors: Melissa Cadena, Liqun Ning, Alexia King, Boeun Hwang, Linqi Jin, Vahid Serpooshan, Steven A. Sloan
Journal: Advanced Healthcare Materials (2020)

Abstract The human nervous system is a remarkably complex physiological network that is inherently challenging to study because of obstacles to acquiring primary samples. Animal models offer powerful alternatives to study nervous system development, diseases, and regenerative processes, however, they are unable to address some species‐specific features of the human nervous system. In vitro models of the human nervous system have expanded in prevalence and sophistication, but still require further advances to better recapitulate microenvironmental and cellular features. The field of neural tissue engineering (TE) is rapidly adopting new technologies that enable scientists to precisely control in vitro culture conditions and to better model nervous system formation, function, and repair. 3D bioprinting is one of the major TE technologies that utilizes biocompatible hydrogels to create precisely patterned scaffolds, designed to enhance cellular responses. This review focuses on the applications of 3D bioprinting in the field of neural TE. Important design parameters are considered when bioprinting neural stem cells are discussed. The emergence of various bioprinted in vitro platforms are also reviewed for developmental and disease modeling and drug screening applications within the central and peripheral nervous systems, as well as their use as implants for in vivo regenerative therapies.
Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production
Authors: Heejung Chun, Hyeonjoo Im, You Jung Kang, Yunha Kim, Jin Hee Shin, Woojin Won, Jiwoon Lim, Yeonha Ju, Yongmin Mason Park, Sunpil Kim, Seung Eun Lee, Jaekwang Lee, Junsung Woo, Yujin Hwang, Hyesun Cho, Seonmi Jo, Jong-Hyun Park, Daesoo Kim, Doo Yeon Kim, Jeong-Sun Seo, Byoung Joo Gwag, Young Soo Kim, Ki Duk Park, Bong-Kiun Kaang, Hansang Cho, Hoon Ryu, C. Justin Lee
Journal: Nature Neuroscience (2020)
Pathway information extracted from 25 years of pathway figures
Authors: Kristina Hanspers, Anders Riutta, Martina Summer-Kutmon, Alexander R. Pico
Journal: Genome biology (2020)

Abstract Thousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual curation, we identified 64,643 pathway figures published between 1995 and 2019 and extracted 1,112,551 instances of human genes, comprising 13,464 unique NCBI genes, participating in a wide variety of biological processes. This collection represents an order of magnitude more genes than found in the text of the same papers, and thousands of genes missing from other pathway databases, thus presenting new opportunities for discovery and research.