bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 15762: Gapdh Interaction With Ape1 Endonuclease Protects Vascular Smooth Muscle Cells Against Apoptosis: Potential Role of These Enzymes in Prevention of Atherosclerotic Plaque Destabilization
Authors: Hou XW. , Yoshida T. , Higashi Y. , Shai SY , Kim C. , Delafontaine P. , Sukhanov S. 
Published: July 2021

We have shown that oxidized lipids (OxLDL) co-localized with apoptotic vascular smooth muscle cells (VSMC) in atherosclerotic plaque and that OxLDL downregulated the major glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cultured VSMC via H2O2-dependent mechanism. We hypothesized that maintenance of sufficient GAPDH levels is critical for cell survival under oxidative stress. H2O2 (220 uM, 12h) decreased GAPDH protein (55±5% decrease) and induced apoptosis (TUNEL assay) in human VSMC. Human VSMC transfection with pCMV-GAPDH increased GAPDH protein (3.5-fold) and prevented H2O2-induced apoptosis (74±4% decrease) vs. pCMV-GFP. We generated rat VSMC with constitutive 2-fold overexpression GAPDH (R3-VSMC). R3-VSMC had increased glycolysis (2.5 folds increase, pyruvate levels), ATP levels (38±2% increase) and reduced oxidative DNA damage (40±2% reduction in number of apurinic/apyrimidinic (AP) sites) and these effects correlated with suppressed H2O2-induced cell apoptosis (>90% reduction, TUNEL assay; 45.7±3.6% reduction, Cell Death ELISA). GAPDH-targeted siRNA reduced GAPDH protein (for 55%) and potentiated H2O2-induced apoptosis (9.4±0.3 folds increase, TUNEL; 8.6±0.4 folds increase, ELISA) in WT-VSMC and blocked anti-apoptotic effect seen in R3-VSMC.
GAPDH known to bind apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a major DNA repair enzyme. We found that GAPDH was co-immunoprecipitated and co-localized with APE1 in cytosolic/nuclear fraction and H2O2 induced further GAPDH-Ape1 co-localization and migration toward nuclei. APE1 specific activity was increased in H2O2-treated R3-VSMC vs. H2O2-treated WT VSMC, suggesting that GAPDH preserved APE1 activity under oxidative stress. APE1-targeted siRNA abrogated the protection of GAPDH overexpression against H2O2-induced apoptosis in VMSC. In summary, GAPDH downregulation mediates oxidant-induced VSMC apoptosis and forced expression of GAPDH protects VSMC from H2O2-induced cell death potentially via activation of APE1-dependent DNA repair. Our data suggest that preservation of GAPDH and APE1 activity in plaque VSMC could be a potential strategy to stabilize plaque and prevent acute coronary events.
Abstract 16005: Highly Efficient Derivation of Human Pacemaker Cells From Pluripotent Stem Cells in Chemically Defined Conditions
Authors: Ghazizadeh Zaniar , Fattahi Seyedeh Faranak , Sharifi-tabar Mehdi , Mirshahvaladi Shahab , Shabani Parisa , Fonoudi Hananeh , Baharvand Hossein , Lee Bong Hee , Aghdami Nasser , Evans Todd , Chen Shuibing , Salekdeh Ghasem H 
Published: July 2021

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. Dysfunction of the cardiac conduction system plays a central role in the pathogenesis of arrhythmia. While much progress has been made understanding cardiomyocyte differentiation, the molecular mechanisms regulating the specification and patterning of cells that form this conductive network is largely unknown.
The LIM-homeodomain transcription factor ISL1 is highly expressed in the secondary heart field (SHF) progenitor population that makes a substantial contribution to the developing heart, comprising most cells in the right ventricle, both atria and pacemaker cells. Pacemaker cells comprise the most proximal component of the cardiac conduction system, which have been proposed as the source of most arrhythmogenic events. Their dominance on other spontaneous beating cell types makes them a suitable target for pharmacologic compounds, making access to this cell lineage necessary for the study of new therapeutic agents.

To identify the signaling pathways that control the differentiation of human embryonic stem cell (hESC)-derived SHF cells into pacemaker cells, we performed RNA sequencing to compare the hESC-derived ISL1
+
population, non-enriched population and undifferentiated hESCs. Furthermore, using a small molecule screen we identified compounds that can improve differentiation of hESCs toward pacemaker cells.

Pathway analysis identified the Wnt pathway as the most significant regulator of SHF specification. Further differentiation of human pluripotent stem cells by stage-specific activation of BMP and WNT signaling pathways resulted in phenotypic pacemaker cells, which display morphological characteristics. More than 80% of these cells stained positively for HCN4, Contactin2(CNTN2) and GATA6, key markers of pacemaker cells. The differentiated cells express pacemaker markers, including
CNTN2, TBX2, TBX3, HCN4, TBX18, GATA6
indicated by qRT-PCR. They show inward potassium currents through HCN channels in patch clamp experiments.

Our data provides a new strategy to obtain human cardiac conduction cells in large scale for disease modeling, drug screening and cell therapy.
Abstract 16186: Hypoxic Pre-conditioning on Human CD34+ Stem Cells Enhances Exosome Therapeutics of Ischemic Tissue Repair Through ETS-1-Regulated Pathway
Authors: Liang Yaxuan , Mathiyalagan Prabhu , Kim David , Losordo Douglas , Hajjar Roger , Sahoo Susmita 
Published: July 2021

Previous studies in our lab have revealed a novel mechanism that therapeutically important human CD34+ stem cells secrete exosomes (Exo) to extracellular milieu that induce angiogenic activity independent of the cells. Further studies demonstrated that CD34+ exosomes (CD34Exo) carry and transfer of proangiogenic miRNAs, such as miR-126, which affect the therapeutic function of the exosomes.
Herein we hypothesized that hypoxic treatment of CD34+ stem cells can modulate the miRNA content and regenerative efficacy of CD34Exo.

Methods and Results:
Exosomes from human CD34+ cells cultured under hypoxia (H-Exo) were more proliferative, anti-apoptotic and angiogenic in vitro, as compared to exosomes from cells under normoxia (N-Exo). In a mouse model of hind limb ischemia, H-Exo treatment significantly enhanced perfusion (ratio: 0.93±0.05 v 0.77±0.02), increased capillary density (1.6±0.2 v 1.1±0.1/HPF) and prevented ischemic limb amputation (0% v 37.5%) as compared to N-Exo (p<0.05; n=7-8). Flow cytometry and confocal microscopy indicated that H-Exo was uptaken by endothelial cells in the ischemic limb. Interestingly, hypoxic treatment did not alter the size and quantity of Exo or expression of major proteins of CD34Exo compared with normoxic treatment. However, hypoxic treatment altered the proangiogenic miRNA expression in H-Exo including miR-210 and miR-126. ETS-1, a transcription factor induced by hypoxia-inducible fator-1 (HIF-1) is known to regulate expression of miR-126. We have examined the protein and RNA expression of HIF-1 and ETS-1 in Sca-1 positive mouse hematopoietic stem cells, and propose that HIF-1/ETS-1 regulatory mechanisms affect the expression of exosomal miR-126 under hypoxia. These results are being confirmed in human CD34+ cells using siRNA silencing and HIF hydroxylase inhibitor dimethyloxalylglycine.

Conclusion:
Hypoxia induced miR-126 expression in CD34 cell-derived exosomes stimulating exosomes-mediated angiogenesis and therapeutic recovery via ETS-transcriptional pathway. Our work has important clinical implications for therapeutic angiogenesis, especially in diabetic and cardiovascular patients who have stem cells with diminished angiogenic potential.
Abstract 17612: Hypertension Severity is Associated With Impaired Cognitive Performance
Authors: Muela Henrique C , Costa-Hong Valeria A , Machado Michel F , Moraes Natália C , Memória Claudia M , Yassuda Mônica S , Shu Edson B , Nogueira Ricardo C , Massaro Ayrton R , Feitosa Raul R , Merlin Silvia , Trés Eduardo S , Nitrini Ricardo , Mansur Alfredo J , Bortolotto Luiz A 
Published: July 2021

B: Hypertension affects the target-organs diversely. Most evidence on target-organ damage in hypertension is related to kidney and heart. The cerebrovascular and cognitive impairment are less studied.
O: To study the cognitive function changes in patients with hypertension on different stages compared to the control pairs and their correlation with the arterial stiffness properties assessed by non-invasive methods and cerebral circulation assessed by transcranial Doppler.
M: In a cross sectional study 162 patients (42 controls and 120 hypertensive) were comparatively evaluated. Hypertensive patients were divided in three stages according to the blood pressure levels or medication use (HTN-1: BP 140-159/90-99 or use of one antihypertensive drug; HTN-2: BP 160-179/100-109 or use of two drugs and HTN-3: BP ≥180/110 or use of three or more drugs). The following variables were evaluated: pulse wave velocity, intima medial thickness, cerebral blood flow velocities by transcranial Doppler (TD) and cognitive function. Mean velocity of middle cerebral artery was continuously monitored at resting and during the breath holding test (30 seconds) and 3 minutes handgrip maneuver. Cognitive function was assessed by mini mental state examination and Montreal Cognitive Assessment.
R: Compared to control group, HTN-3 group was older, had higher BMI, IMT and PWV and lower educational level and family income (Table 1). Interestingly, the higher the hypertension stage the poorer was the performance in cognitive tests even after age correction. There was no difference among the groups related to TD velocities at rest and the hand-grip maneuver. However, it was noted a lower breath holding index in the hypertensive group (HTN-1=0.94±0.56; HTN-3=0.97±0.59 vs Control=1.5±0.68; p=0.002) which could infer less vasomotor reactivity in these patients.
C: Cognitive impairment was more frequent in patients with hypertension and this frequency was related to hypertension severity.
Abstract 19091: Prognosis of Patients With Out-of-hospital Refractory Cardiac Arrest Referred for Extracorporeal Life Support: An Observational Study
Authors: Ursat Cecile , Tilliette Marie-Ange , Groizard Charles , Cassuto Margot , Ozguler Anna , Baer Michel , Loeb Thomas 
Published: July 2021

Introduction:
In case of no return of spontaneous circulation (ROSC) after conventional cardio-pulmonary resuscitation (CPR), out-of-hospital cardiac arrest (OHCA) patients could be referred for extracorporeal life support (ECLS). Guidelines have been published concerning this specific situation (1). The aim of our study was to describe the prognosis of OHCA patients and verify if referral to ECLS was compliant with these recommendations mainly studying time intervals (no-flow < 5 min, low-flow < 100 min).

Methods:
A prospective survey on OHCA referred to ECLS was implemented from 03/01/12 until 06/11/15 in an Emergency Medical Service (EMS) located in Paris area (France). This survey included 43 patients referred to hospital for ECLS. Variables were given as means and percentages.

Results:
Patients referred to ECLS were more often men (77%), with a mean age of 51 years old. Most of 43 OHCA occurred at home (51%), although 26% occurred on public area and 16% at workplace. In 40% of cases, CPR was performed by a witness and in 33% by a health professional.

A first Basic Life Support ambulance arrived on scene within 7 min 50 sec, whereas EMS ambulance arrived on scene within 18 min 27 sec after OHCA. At EMS arrival on scene, patients were on asystole (44%), ventricular fibrillation (37%), and on spontaneous circulation (12%). The no-flow time interval was 4 min 10 sec on average (6 patients had a no-flow over 5 min) with 43% of patients with no no-flow. Low-flow time-interval was 44 min.
External electric shock was delivered before EMS arrival on 21% of cases, and EMS itself delivered a shock in 40% of cases. Epinephrine was used for all patients, 10.35 mg on average.
No patient survived OHCA after referral to ECLS.

Discussion:
Although this is a small series of 43 patients, no OHCA patient referred to ECLS survived. These results are mainly due to a non-shockable initial condition or too long no-flow time intervals.

In order to improve the outcome and bring benefit to the proper expected patients through a cost-effective pathway, we released a reminder of the right recommendations in our EMS. (1) Riou B., Adnet F., Baud F et al. A. Recommandation sur les indications de l’assistance circulatoire dans le traitement des arrêts cardiaques réfractaires. Ann Fr Anesth Réanim 2009 ; 28 : 182-6.
Abstract 9778: Establishing Inter Rater Reliability of the National Early Warning Score (NEWS)
Authors: Miller Donna M 
Published: July 2021

A change in patient condition is a dynamic process which can go unrecognized and result in a failure to rescue. Changes in patients’ vital signs can precede adverse events many hours before critical events such as cardiac arrest or emergent transfer to the Intensive Care Unit occurs.
Quantitative assessment tools are used to predict risk and need for additional resources at the bedside. These tools are referred to as Early Warning Scoring Systems. The Royal College of Physicians developed a standardized tool called the National Early Warning Score (NEWS, 2012) that uses a variety of physiologic parameters to assess risk and establish a trigger threshold for summoning additional resources.

Purpose:
Early warning scoring tools have been found to be reliable and accurate in predicting patient decompensation. However, data from instruments are only as reliable and accurate as the caregiver who obtains and documents the parameters. The purpose of this study was to establish inter rater reliability between the RN and PCA using NEWS.

Design, Sample, Setting, Procedures:
This study was conducted on the clinical units of a 104 bed Long Term Acute Care Hospital (LTCH) system. These units accept patients directly from Intensive Care Units who require intense services to maintain their trajectory toward recovery. The NEWS provides a way for early detection of patient decompensation which can prevent readmission to acute care and the subsequent financial implications

The convenience sample consisted of 22 RNs and 6 PCAs. Consented subjects reviewed an unfolding case study that portrayed a typical patient on the LTCH unit. Subjects were asked to circle the parameter ranges on the NEWS tool that corresponded to physiologic values in the scenario.

Findings:
Krippendorff’s alpha was utilized to determine the level of agreement among the raters examining the three scenarios. An alpha value of 0.94 was obtained indicating a high level of agreement among the raters.

Conclusion:
The NEWS can serve as a reliable adjunct to the provision of safe patient care. While it is not the sole source for determining
Abstract P281: Comparing the Impact of Price Change and Mass Media Campaigns in Reducing Cardiovascular Disease Mortality and Disparities in the US
Authors: Pearson-Stuttard Jonathan , Bnadosz Piotr , Rehm Colin D , Afshin Ashkan , Penalvo Jose , Whitsel Laurie , Danaei Goodarz , Micha Renata , Conrad Zach , Gaziano Thomas , Bromley Helen , Lloyd-Williams Ffion , Mozaffarian Dariush , Capewell Simon , O’Flaherty Martin 
Published: July 2021

Introduction:
Cardiovascular disease (CVD) mortality burdens remain large and unequal in the US, and much is attributable to poor diets. However, few data exist regarding the potential population level impact of policies aimed at improving dietary intake, such as the Supplemental Nutrition Assistance Programme (SNAP), and potential effects on disparities.

Aim:
To estimate reductions in CVD mortality and disparities achievable in the US population up to 2030 through food price changes and mass media campaign interventions targeting fruits and vegetables (F&V) and sugar sweetened beverages (SSBs).

Methods:
We developed a US IMPACT Food Policy Model to compare four contrasting food policy scenarios targeting dietary intake: A) - national F&V mass media campaign, B) F&V price reductions of 10% universally and C) 30% to SNAP participants, D) - SSB price increase of 10% universally.

Data sources included the National Vital Statistics System, SEER single year population estimates, the US Bureau 2012 National Population projections, and NHANES. We stratified the US population into SNAP participants, SNAP eligible but not participating, and SNAP ineligible.
We modelled cumulative deaths prevented or postponed (DPP) and life years gained (LYG) using best-evidence effect sizes for each policy, existing mortality rates and trends, and F&V and SSB mortality effects. We stratified by age, sex, and CVD subtype from 2015 to 2030. Sensitivity analyses were conducted with Monte Carlo simulation.

Results:
Scenario B (universal 10% price reduction) would yield the greatest national benefits, generating approximately 88,000 DPPs (95% CI: 81,000-94,000) and 1,369,000 LYGs (1,268,000-1,460-000) by 2030. This compares with between 28,000 (26,000-30,000) and 84,000 (79,000-89,000) DPPs in Scenario A, depending on duration of media campaigns; and approximately 27,000 (24,000-30,000) and 29,000 (25,000-33,000) DPPs in scenarios C and D respectively.

Scenario C (30% price reduction to SNAP participants) might reduce CVD disparities by about 18% comparing SNAP participants with the ineligible population. Scenarios A, B and D would have negligible effects on mortality disparities.

Conclusions:
All four dietary policies would be effective in reducing mortality. Reducing fruit and vegetable (F&V) price by 10% to the entire US would save most lives. Reducing F&V price by 30% to SNAP participants would reduce disparities the most, particularly if SNAP program coverage and penetration were improved. These results support population fiscal strategies targeting diet to reduce cardiovascular mortality and disparities in the US.
Abstract 136: Impact of Abnormal Ventricular Conduction on TAVR Outcomes
Authors: Marthy Andrew , Delago Augustin , Elkharbotly Ali , Bulibek Batyrjan , El-Hajjar Mohammad , Torosoff Mikhail 
Published: July 2021

Background and hypothesis:
The association of abnormal ventricular conduction with co-morbidities and effect of conduction abnormalities on TAVR outcomes have not been well investigated.

Methods:
A retrospective chart review was conducted in 200 consecutive TAVR patients. ECG data was collected and stratified into normal conduction (WNL, n=138), LBBB (n=25), RBBB (n=20), and intra-ventricular conduction delay (IVCD, n=17). Outcomes were adjudicated according to the PARTNER trial definitions (NEJM 2010; 363: 1597-1607). Analyses of variation, correlation, chi-square, and logistic regression were used. The study was approved by the institutional IRB.

Results:
There was no association between any conduction delay and history of CVA, PVD, chronic renal disease, smoking, hyperlipidemia, hypertension, or COPD.

Conduction delays were associated with decreased ejection fraction (LBBB 45.4+/-2.2, RBBB 50.3+/-1.5, IVCD 48.0+/-3.2 vs. 50.7+/-10.9 in WNL conduction, p= 0.03) and lower aortic valve gradient (LBBB 35.0+/- 3.2 mm Hg, RBBB 42.2+/- 2.9, IVCD 40.5 +/- 5.0 vs. 46.2+/-1.5 in WNL conduction, p= 0.022). Standard error was used as the measure of dispersion.
Despite the decreased ejection fraction and lower aortic valve gradient, conduction delays were not associated with an increased incidence of post-TAVR death, re-hospitalizations, stroke, or acute renal failure.

Conclusion:
Despite association with decreased ejection fraction and lower aortic valve gradient, electrocardiographic conduction delays do not lead to inferior TAVR outcomes.
Abstract 270: Reduction in 30-day Heart Failure Readmissions
Authors: Kravitz Kathleen A , Khot Umesh N 
Published: July 2021

Heart failure (HF) 30-day readmission after hospitalization continues to have a significant clinical and economic burden and hospitals are seeking methods to prevent these readmissions.
We tried many projects to reduce heart failure readmissions without much success. After much analysis we found that preventable readmissions occur early. Our hypothesis was that the “defect” is in-hospital or in transition at discharge. This idea led to a pilot study to reduce HF readmissions.

A paper based checklist was created, utilizing a patient-centered approach to the delivery of care to optimize clinical outcomes. This checklist included in-hospital care metrics which were reinforced at various times throughout the patient’s hospital stay to ensure discharge readiness. A multi-disciplinary team: nursing, physician/LIP, pharmacy, nutrition and care management were responsible to address the following measures:

Medication reconciliation

Diet compliance

Importance of follow up care

Standard physician care

Addressing quality metrics

We implemented this pilot study on one nursing unit and limited the use of the checklist to two physician/LIP service groups. We used an intention-to-treat analysis approach and included concurrent and historical data to determine effectiveness of the HF discharge checklist.
Data for the pilot study was from the index discharge date starting April 1, 2013 to June 22, 2013. The HF readmissions for 2013 were compared to the heart failure readmissions for 2012, using the same time period April 1 to June 22. We also filtered to the physician service group in the previous year (2012) for comparison.
Heart failure readmission rates in all primary and secondary HF diagnosis patient population using the checklist were very positive with results at 14.6% (12 of 82). This was compared to the previous year (2012) using the selected physician group and found the readmission rate was 26.5% (18 of 68). Heart failure readmission rates for the hospital population were 18.7% (67 of 358) in 2013, compared to 24.5% (83 of 339) in 2012. Heart failure readmission rates on the selected nursing unit, including both patient populations with and without the checklist, were 20% (29 of 145) in 2013 vs. 25.2%927 of 107) in 2012.
The use of the paper based checklist was a success to reduce heart failure 30 day readmissions.
Abstract 204: Echocardiographic Evidence for Systemic Atherosclerosis, Atrial Fibrillation, and Long-Term Prognosis in Stroke Patients
Authors: Pieper Justin , Ashamalla Michael , Yager Neil , Sedhom Daniel , Gate Khetan , Nguyen Veronica , Shkolnik Boris , Torosoff Mikhael 
Published: July 2021

Background:
Echocardiography is routinely performed for evaluation of cardiac embolic causes in stroke patients. We sought to examine the association of echocardiographic evidence of atherosclerosis with atrial fibrillation and long-term outcomes.

Materials and methods:
Retrospective chart review was performed in 756 consecutive patients treated for non-hemorrhagic stroke at a single academic medical center. Transthoracic echocardiograms were reviewed for presence of mitral annular calcifications, aortic valve sclerosis, or aortic atherosclerosis. Admission ECG and telemetry recordings were evaluated for documented dysrhythmias. Mean follow up length was 46+/- 20 months.

Results:
A significant number (57.7%) of patients with non-hemorrhagic stroke diagnosed with atrial fibrillation had evidence of cardiac and systemic atherosclerosis on transthoracic echocardiogram, which was less likely in patients with normal sinus rhythm (35.4%) or non-sinus non-atrial fibrillation rhythms (37.1%, p<0.05).

Findings of cardiac and systemic atherosclerosis were more common in older patients (75+/- 11 vs 60+/- 16 years old, p<.001), with lower BMI (27.4+/- 6.0 vs. 29+/- 6.5, p<.001), and hypertension (71.9% vs. 59.2 %, p=.002).
Patients with findings of cardiac and systemic atherosclerosis were more likely to die during follow-up (56.1% vs. 43.9%, p<.001).

Conclusion:
In patients with non-hemorrhagic stroke, cardiac and systemic evidence of atherosclerosis was strongly associated with atrial fibrillation and portended poor long-term prognosis. In stroke patients with cardiac and systemic evidence of atherosclerosis and rhythms other than atrial fibrillation, extended ECG monitoring may be warranted.