bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9485: Hypertension Risk Differs by Ethnicity in Young Asian Women Independent of Cardiometabolic Conditions
Authors: Liu Jerry , Gu Kristine , Chandra Malini , Guo Lynn , Gordon Nancy P , Lo Joan C
Published: April 2022

Introduction:
Prevalence of polycystic ovary syndrome (PCOS) and diabetes (DM), two cardiometabolic conditions (CMCs), vary by ethnicity in Asian women. Hypertension (HTN) also varies by ethnicity, but this has not been well studied in young Asian women with CMCs. We examined whether HTN diagnosis (Dx) in Asians varies by ethnicity, independent of body mass index (BMI), PCOS and DM.

Methods:
We used electronic health record data from a large US health plan to examine prevalence of HTN (≥2 Dx) in a cohort of 19,258 Chinese, 23,213 Filipina, and 19,108 South Asian women aged 21-44 years for whom BMI, PCOS (≥2 Dx) and DM (≥2 Dx + DM treatment) were ascertained. The associations of ethnicity and CMCs with HTN were examined using multivariable logistic regression.

Results:
Prevalence of HTN was 2% among Chinese and South Asian and 8% among Filipina women. Across all ethnic groups, compared to women with no CMCs, HTN prevalence was highest among those with DM and somewhat higher among those with PCOS and obesity. For all CMCs, Filipinas had the highest HTN prevalence (Figure). Adjusting for age, smoking, BMI, CMCs, and ethnicity, the odds of HTN were higher for Filipinas (2.6; CI 2.3-2.9) and slightly lower for South Asians (0.9; CI 0.7-0.98) compared to Chinese women; DM was associated with 4.7-fold higher odds (CI 4.1-5.3) and PCOS 1.4-fold higher odds (CI 1.1-1.8) of HTN.

Conclusion:
In young Asian women, DM, PCOS and obesity are associated with greater HTN burden. Compared to Chinese women, Filipinas have higher odds and South Asian women lower odds of HTN independent of BMI, PCOS, and DM. These data suggest a need for heightened BP surveillance in young Filipina women and Asian women with obesity or CMCs.
Abstract 9501: Duration of Ideal Cardiovascular Health With Risk of Chronic Kidney Disease and Cardiovascular Disease
Authors: Cho So Mi J , Jeon Justin Y , Yoo Tae-Hyun , Lee Hae-young , Lee Yong-ho , Kim Hyeon Chang
Published: April 2022

Introduction:
Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management in the context of primary and secondary prevention. Yet, little is known regarding the exact cardiovascular risks associated with length of favorable cardiometabolic health sustenance in midlife.

Methods:
From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 7,854 middle-aged adults without chronic kidney disease and 7,796 without cardiovascular disease at baseline. Duration of ideal cardiovascular health was the sum of time spent with ideal body mass index, blood pressure, fasting glucose, total cholesterol, non-smoking, alcohol drinking, and physical activity levels. We employed Cox proportional hazards model to assess chronic kidney disease and cardiovascular events risks.

Results:
The median age of the participants was 50.0 years and 47.9% were male. Over a median follow-up of 15.0 years, 1,401 new chronic kidney disease and 493 new cardiovascular disease occurred. With <5 years group as the reference, multivariable-adjusted hazard ratios [95% confidence intervals] for chronic kidney disease were 0.63 [0.39-0.93] with 5 to 10 years and 0.33 [0.15-0.74] with ≥10 years of ideal cardiovascular health (
P
trend, 0.0057). Similarly, participants lived with longer ideal cardiovascular health had significantly lower cardiovascular disease (5 to 10 years, 0.83 [0.54-1.27]; ≥10 years, 0.22 [0.08-0.60]). Subtype-specific analyses indicated negatively graded risks for coronary artery disease (
P
trend, 0.0239) and cerebrovascular disease (
P
trend, 0.0514).

Conclusions:
Our findings confer that maintaining favorable health behaviors and clinical cardiometabolic profile in midlife will improve later-life cardiovascular outcomes.
Abstract 9505: Myocardial Energetic Impairment is the Basis for Reduced Cardiac Reserve and Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction: Insights From Novel Cardiopulmonary Magnetic Resonance Imaging
Authors: Burrage Matthew K , Hundertmark Moritz , Valkovic Ladislav , Watson William D , Rayner Jennifer , Sabharwal Nikant , Ferreira Vanessa , Neubauer Stefan , Miller Jack J , Lewis Andrew J , Rider Oliver J
Published: April 2022

Introduction:
Abnormal cardiac mitochondrial function and energetics may be a unifying feature in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), while transient pulmonary congestion during exercise is an important determinant of reduced exercise capacity and symptoms.

Hypothesis:
We hypothesized that a gradient of myocardial energetic impairment exists across the spectrum of HFpEF and limits cardiac reserve during exercise, leading to transient pulmonary congestion.

Methods:
43 patients across the spectrum of diastolic dysfunction and HFpEF (age-matched controls n=11; type 2 diabetes (T2DM) n=9; HFpEF n=14; severe diastolic dysfunction due to cardiac amyloid n=9) underwent assessment of cardiac energetics (myocardial phosphocreatine to ATP ratio, PCr/ATP) and function using CMR, and lung water using a novel MR proton density mapping sequence. Studies were performed at rest and during exercise (20 W for 6 minutes).

Results:
Paralleling the stepwise decline in diastolic function across the groups (E/e’ ratio p<0.001) was an increase in NT-pro BNP (p<0.001) and a reduction in PCr/ATP (p<0.001). During exercise, lower left ventricular (LV) diastolic filling rates (r 0.58, p<0.001), left atrial (LA) dilatation (r -0.52, p<0.001), lower right ventricular (RV) contractile reserve (ΔRVEF; r 0.57, p<0.001), and right atrial (RA) dilatation (r -0.71, p<0.001) were strongly linked with impaired energetics. The pulmonary proton density sequence provided images that scaled linearly with water content, validated using a water-doped sponge phantom (r 0.98, p<0.0001), and revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4], p=0.002) and amyloid (+6.4% [3.3, 10.0], p=0.004), which was not seen in controls (-0.1% [-1.9, 2.1], p=0.89) or T2DM (+0.8% [-1.7, 1.9], p=0.82). Exercise-induced pulmonary congestion was associated with reduced LV diastolic filling (r -0.33, p=0.03), RVEF augmentation (r-0.50, p<0.001), RA dilatation (r 0.44, p=0.004), and impaired myocardial energetics (r -0.43, p=0.004).

Conclusion:
A gradient of myocardial energetic deficit exists across the spectrum of HFpEF, leading to impaired cardiac functional reserve and transient exercise-induced pulmonary congestion.
Abstract 9516: Comparison of Mortality Rates Among Rate Control Agents in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Trongtorsak Angkawipa , Kewcharoen Jakrin , Saowapa Sakditad , Polpichai Natchaya , Thangjui Sittinun , Navaravong Leenhapong
Published: April 2022

Introduction:
Rate control strategy is an effective treatment strategy for patients with atrial fibrillation (AF). However, data supporting the selection of rate-control medications is still lacking. We conducted a systematic review and meta-analysis to evaluate and compare mortality rate among beta-blocker (BB), calcium channel blocker (CCB), and digoxin for patients with AF undergoing rate control strategy.

Methods:
We searched MEDLINE, and EMBASE databases from inception to May 2021 to identify studies that compared all-cause mortality among patients who received single rate-control medication (BB, CCB, or digoxin). Data from each study were combined using the random-effects model to calculate pooled relative risk (RR) with 95% confidence interval (CI).

Results:
Five studies (2 randomized control trial and 3 retrospective cohort studies) with a total of 105,129 patients (45,910, 19,241, and 39,978 patients were in BB, CCB, and digoxin groups respectively) were included. Patients in digoxin group had higher mortality rates when compared to the BB group (pooled RR=0.55, 95%CI 0.5-0.61, p=<0.001) and the CCB group (pooled RR=0.73, 95%CI 0.56-0.95, p=0.018). There was a trend favoring BB when comparing BB to CCB, but failed to reach statistical significance (pooled RR=0.76, 95%CI 0.57-1, p=0.052).

Conclusions:
Our meta-analysis showed that rate control strategy in AF patients with digoxin was associated with higher mortality rates, but there was no statistical difference of the survival outcome between BB and CCB.
Abstract 9526: Fto Demethylase Mediates Altered N6-methyladenosine (m6a)-rna Modification in Human Failing Heart and Stressed-Induced Rat Cardiomyocytes
Authors: Dubey Praveen K , Dubey Shubham , Patil Mallikarjun , Singh Sarojini , Ahuja Paras , pogwizd Steven , Krishnamurthy Prasanna
Published: April 2022

Background:
N6-methyladenosine (m6A) methylation is one of the important posttranscriptional modification of RNA, which affects RNA splicing, translation and stability. These modifications are dynamically regulated by writers, readers and erasers, and their alteration affects m6A modification and have shown to play key regulatory role in numerous biological processes. Fat mass- and obesity-associated (FTO) gene, known as a nucleic acid demethylase removes the methyl group from RNA and has been shown to be associated with progression of heart diseases. In this study, we determined m6A methylation in human failing heart, and evaluated if FTO regulates m6A-methylation of transcripts related to inflammation in cultured rat cardiomyocytes under various stress conditions.

Methods and Results:
m6A RNA-methylation was increased in human failing hearts as compared to heart samples from non-failing subjects. Interestingly, failing hearts were associated with significant decrease in FTO mRNA and protein expression. Furthermore, cultured rat cardiomyoblasts (H9C2) cells exposed to stressors (hypoxia or isoproterenol) for 24hrs showed significant decrease of FTO and an associated increase in m6A-RNA methylation (dot blot analysis). To further test if stress-induced increase in m6A-RNA modification is mediated through FTO, we knocked-down FTO, treated with isoproterenol for 24hrs and evaluated m6A methylation status of RNA. Interestingly, dot blot analysis showed significant increase in m6A methylation levels and proinflammatory cytokines (IL6 and TNFa) in FTO knockdown cells as compared to scramble, both at basal level and after exposure to stress. Furthermore, we evaluated the effect of FTO on methylation of RNA transcripts that encode inflammatory cytokines. MeRIP assay (Methylated RNA immunoprecipitation using m6A antibody and analysis of m6A-transcript by qRT-PCR) demonstrated that the gene expression of proinflammatory cytokines, IL6 and TNF-alpha was significantly increased in FTO knockdown cells as compared to scramble control cells .

Conclusion:
This data suggests stress-induced loss of FTO in the heart might mediate m6A-RNA methylation and therefore potential leading to upregulation of inflammatory response in the myocardium.
Abstract 9528: Apical Resection in Newborn Pig Hearts Extends the Regenerative Window of Cardiomyocyte
Authors: Nakada Yuji , Zhou Yang , Gong Wuming , Skie Erik , Zhang Eric Y , Nguyen Thanh , Wei Yuhua , Zhao Meng , Chen Wangping , Sun Jiacheng , Chen Jake Y , Walcott Greg P , Garry Daniel J , Zhang Jianyi
Published: April 2022

Background:
The neonatal porcine heart possesses proliferative cardiomyocyte capacity to recover heart function and structure after an acute myocardial injury during two days of birth. In this study, we have extended the myocardial regenerative window to postnatal day 28 (P28) by a double injury pig model (AR
P1
MI
P28
), which performed apical resection at P1 (AR
P1
) followed by LAD ligation at P28 (MI
P28
). However, the molecular mechanism of regenerative window extension is unknown.

Methods:
The AR
P1
MI
P28
hearts showed no visible sign of myocardial damage or malfunction 4 weeks after LAD ligation. The nuclear RNA contents were isolated from hearts that received none, singe, and double injury hearts. They performed single nuclei RNA-seq to characterize the gene-expression profile of the AR
P1
MI
P28
in cardiomyocytes.

Results:
Gene-expression profiles revealed that regenerating AR
P1
MI
P28
hearts contained different subpopulations of cardiomyocytes early after 2
nd
injury. Louvain clustering identified the six cardiomyocyte clusters (CM1-CM6). The CM6, CM3, and CM2 clusters have mainly comprised fetal (92.4%), CTL-P1 (95.7%), and CTL-P56 (96.2%) cardiomyocytes. In contrast, the CM1 cluster has comprised heterogeneous cardiomyocyte groups from all other animal groups, including less than 1% of fetal and CTL-P1 cardiomyocytes. The CM5 and CM4 clusters have mainly comprised AR
P1
MI
P28
-P35 (double injury hearts harvested at P35) cardiomyocytes, 97.8% and 68.6%, respectively. Sparse modeling analysis revealed that AR and MI injury, both alone and in combination, appeared to extend the regenerative capacity of cardiomyocytes and perturb cardiomyocyte maturation.

Conclusion:
We have demonstrated that the unique CM5 cluster appeared only after the 2
nd
injury of AR
P1
MI
P28
-P35 hearts. This cell cluster was characterized by a highly expressed isoenzyme of the glycolytic enzyme pyruvate kinase M2 (Pkm2) and skeletal muscle filamentous gene Nebulin. Transient expression of the CM5 cluster induces by the AR
P1
might contribute to the sustained remuscularization and myocardial function recovery following an acute MI in large mammals.
Abstract 9551: Presence of Disabilities is Associated With Reproductive Health Counseling, Concerns, and Experiences and Marital History Among Women With Congenital Heart Defects, 2016-2019
Authors: Farr Sherry L , Klewer Scott E , Nembhard Wendy N , Downing Karrie F , Galindo Maureen , Bolin Elijah H , Benavides Argelia , Judge Ashley , Oster Matthew
Published: April 2022

Most females with congenital heart defects (CHD) will reach reproductive age. Our objective was to examine whether presence of disabilities is associated with reproductive health counseling, concerns, and experiences among women with CHD.

Methods:
We used 2016-2019 population-based data from the Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) among women ages 19 to 38 years with CHD born in Arkansas, Arizona, and Atlanta, Georgia. We examined contraceptive and pregnancy counseling, pregnancy concerns and experiences, and marital history by disability status. Disability was based on six validated questions on vision, hearing, mobility, cognition, self-care, and independent living. Multivariable Poisson regression was used to examine adjusted prevalence ratios (aPR) between reporting ≥ 1 disability and each outcome, adjusted for CHD severity, age, race/ethnicity, place of birth, and insurance type.

Results:
Of 783 survey respondents with complete data (88% of all respondents), 41.9% were 25-30 years of age, 66.8% were non-Hispanic White, and 41.5% reported ≥1 disability. Women with CHD and disabilities were more likely than women without disabilities to receive clinician counseling on safe contraceptive methods (aPR=1.3) and on avoiding pregnancy because of their CHD (aPR=2.3). They were also more likely to report concern about their ability to have children (aPR=1.2) and having delayed or avoided pregnancy because of their CHD (aPR=2.2). They were less likely to have ever been pregnant (aPR=0.8) or married (aPR=0.7). Associations held across specific disability types and after excluding 71 women with known chromosomal anomalies.

Conclusions:
Among women with CHD, those with disabilities may be more likely to receive clinician advice to avoid pregnancy and less likely to ever have been pregnant. Evidence-based information may improve services and help women with CHD and disabilities meet their reproductive health goals.
Abstract 9563: Preventive Therapy Changes Following Coronary Computed Tomography Angiography versus Invasive Coronary Angiography in Patients With Nonobstructive Coronary Artery Disease
Authors: Torosyan Nare , Schwartz Brandon , Chen Billy , Ebinger Joseph , Gransar Heidi , Rozanski Alan , Bairey Merz C N , Berman Daniel
Published: April 2022

Introduction:
Coronary computed tomography angiography (CCTA) in SCOT-HEART led to increased preventive therapy for coronary artery disease (CAD). We hypothesized that atherosclerosis on CCTA would lead to greater preventive therapy changes compared to invasive coronary angiography (ICA).

Methods:
We studied 429 consecutive patients with available electronic health records and nonobstructive CAD (1-69% epicardial stenosis) by CCTA for assessment of chest pain or exertional dyspnea (n=143), ICA (n=142), or no CAD on CCTA (n=144). Changes in preventive therapies were assessed at 6 weeks and 6 months. Statin intensification was defined as change to greater LDL-lowering capacity. Intensification of antiplatelet agents, ACEI/ARB, or beta-blockers was defined as increased dose. Pairwise comparisons were made with Bonferroni adjustment.

Results:
There was no difference in age or gender in nonobstructive CAD patients (
Table
). ICA patients had more baseline therapies. Six week statin initiation was more common (p=0.006) in CCTA nonobstructive group, but not statin intensification (p=0.24) (
Table
). Six month LDL lowering was observed in CCTA (114±40 to 94±39 mg/dL, p<0.001), but not ICA (95±41 to 87±36 mg/dL, p=0.10) nonobstructive patients. Younger age (OR 0.96; 95% CI 0.93-0.99, p=0.006), but not modality (CCTA compared to ICA OR 1.12; 95% CI 0.60-2.07, p=0.73) was associated with statin initiation or intensification at 6 weeks in nonobstructive patients. Greater change in therapies was found in nonobstructive patients by both modalities vs normal coronaries (
Table
).

Conclusions:
Nonobstructive CAD on CCTA is associated with greater statin initiation, but not intensification, at 6 weeks and lowering of LDL compared to ICA. Antiplatelet, beta-blocker, or ACEI/ARB prescriptions were not different in nonobstructive CAD by CCTA vs ICA. More preventive therapy changes occurred in nonobstructive CAD by either modality vs normal coronaries.
Abstract 9573: Significant Reduction in Ventricular Tachyarrhythmia After Myocardial Infarction in Cardiovascular Progenitors Transplanted Pig Hearts
Authors: Yap Lynn , Chong Li Yen , Tan Clarissa , Adusumalli Swarnaseetha , Seow Millie , Guo Jing , Cai Zuhua , Loo Sze Jie , Lim Eric , Lath Narayan , Ye Lei , Petretto Enrico , Tryggvason Karl
Published: April 2022

Stem cell therapy could potentially replace damaged heart muscle for regenerative cardiology. We hypothesized that immature cardiovascular progenitors (CVPs) when transplanted into infarcted hearts would electrically synchronized and mature
in vivo
thus avoiding the occurrence of VTs. In this study, we reported the derivation and applications of hESC-derived CVPs using highly reproducible (R
2
> 0.95) laminin-221 differentiation protocol. The infarction model was created on 3 months old Sus scrofa pigs where we permanently ligated the coronary arteries and intramyocardially transplanted 200 million CVPs. A total of 3 sham, 10 medium control and 10 CVP transplanted pigs were monitored at 4- and 12-weeks post-transplantation. We demonstrated using 10X spatial transcriptomic analysis at 1-week following transplantation the engraftment of the human CVPs into the pig heart. The cells remained viable and proliferated to formed human graft in the infarcted region at 4- and 12-weeks as indicated by IVIS imaging and histology staining. Heart function was analyzed by magnetic resonance imaging (MRI) and revealed overall improvement in left ventricular ejection fraction by 21.35 ± 3.3 %, which was accompanied by significant improvements in ventricular wall thickness and wall motion, as well as a reduction in infarction size after CVP transplantation as compared to medium control pigs (P < 0.05). Electrophysiology analyses revealed electrical propagation between transplanted cells and host tissue CMs. Temporary episodes of VT over a period of 25 days were developed in 4 out of 10 CVP transplanted pigs and 1 pig had persistent VT, while the rest (n = 5) remained in normal sinus rhythm. All ten pigs survived the experiment without any VT-related death. Finally, computerized tomography (CT) scans revealed no tumor formation after 12-weeks transplantation indicating the long-term safety of the treatment. In conclusion, we reported the generation of an effective and potent CVPs and a significant reduction (50 %) in graft induced VT as compared to studies transplanted with contracting cardiomyocytes. This method may pave the way for stem cell therapy of myocardial infarction in humans.
Abstract 9577: Resting Energy Expenditure is Important Factor to Predict Cardiac Mortality in Chronic Heart Failure
Authors: Sato Takamasa , Yoshihisa Akiomi , Ishida Takafumi , Takeishi Yasuchika
Published: April 2022

Introduction:
Parameters derived from cardiopulmonary exercise testing (CPX) including peak oxygen consumption (VO
2
) are important prognostic factors in patients with chronic heart failure (CHF). However, all patients with CHF cannot undergo CPX because of such as exercise intolerance. On the other hands, resting parameters derived from respiratory gas analyzer including resting energy expenditure (REE) could be easily measured and clinical significance of these parameters had not been fully elucidated in patients with CHF. We aimed to determine the prognostic impact of REE in patients with CHF.

Methods:
A total of 1185 consecutive CHF patients underwent CPX were enrolled. The subjects of this study were divided into two groups according to median REE and we compered the clinical characteristics between two groups. Also, we examined the value of REE (Weir’ formula: 3.941resting VO
2
+1.106resting VCO
2
) to predict cardiac mortality in CHF patients.

Results:
In all subjects, 966 were males, median age was 63 years. Median resting VO
2
was 236 ml/min, median resting VCO
2
was 222 ml/min and median REE was 1178 kcal/day. Patients with low REE (<1178 kcal/day) were older and had higher prevalence of female and anemia, lower body mass index (BMI), more impaired renal function, lower parameters of nutrition such as serum total protein and albumin, higher levels of plasma type-B natriuretic peptide, lower resting VO
2
and lower resting VCO
2
and lower peak VO
2
than those with high REE (
>
1178 kcal/day). But left ventricular ejection fraction was similar between two groups. Patients with low REE had significantly higher rates of cardiac death, all cause death and composite cardiac events (cardiac death and re-hospitalization due to worsening heart failure) than those with high REE. Furthermore, REE was the independent predictor of cardiac death, all-cause death and composite cardiac events in the Cox proportional hazard analysis after adjusting for cofounding variables including peak VO
2
.

Conclusions:
REE as well as peak VO
2
is important predictor of cardiac mortality in patients with CHF.
Abstract 9578: Cholesterol Embolization Syndrome Among Patients With Acute Coronary Syndrome Post-Percutaneous Coronary Intervention: A National Inpatient Analysis
Authors: Eromosele Oseiwe B , ASEMOTA IRIAGBONSE , SAFIRIYU ISRAEL , Ajibade Ademola , Abib Oluwole S , Idowu Abiodun B , Adebolu Olayinka I , Okoh Nelson C , Lukan Abdulkareem , Fasanmi Oluwafisayo S , Odeyinka Oladipo , Babayale Omofolarin , Abu Hawa O
Published: April 2022

Introduction:
Percutaneous coronary intervention (PCI) is associated with an increased risk of cholesterol embolization syndrome (CES), accounting for approximately 70% of iatrogenic cholesterol embolization. The clinical outcomes of patients with acute coronary syndrome (ACS), who develop CES post-PCI is yet to be explored on a national scale.

Objectives:
To evaluate the length of hospital stay (LOS), cost of hospitalization; proportion of patients with acute kidney injury (AKI), sepsis, cardiogenic shock and in-hospital mortality among those with ACS who develop CES post-PCI.

Methods:
Adults who had a diagnosis of ACS and PCI done who eventually had CES, were identified from the National In-Patient Sample (NIS) dataset between 2016-2018 using ICD10 codes. Weighted multivariable logistic and linear regression models were used as appropriate. Various sociodemographic, clinical and hospital level factors were adjusted for in the analysis.

Results:
Of the 365 patients who had ACS and developed CES post-PCI; 48% were women, 76.7% were non-Hispanic White and the average age was 69.5 years. The mean LOS was 8.2 days and the mean cost of hospitalization was $99,958.02. Overall, 32.9% of the patients developed AKI, 6.8% developed sepsis, 4.1% subsequently had cardiogenic shock and 11% had in-hospital mortality.

Conclusions:
Our study highlights important patient characteristics, resource utilization and clinical outcomes among patients with ACS who develop CES post-PCI, which provides relevant information needed to generate hypothesis linked to this disease condition.
Abstract 9597: One Drop Digital App and Coaching Improves Lifestyle Risks, Glycemic Control and Psychological Well-Being in People With Hypertension and Type 2 Diabetes
Authors: Sears Lindsay E , Goldner Dan , Nagra, PhD Harpreet , Huddleston Brian , Hirsch Ashley , Osborn Chandra Y , Dachis Jeff
Published: April 2022

Background:
Mobile health interventions for reducing CVD risk have mixed effectiveness. One Drop’s (OD) digital solution integrates a mobile application, in-app coaching and connected devices (glucometer, blood pressure cuff, scale) to support management of pre-diabetes, diabetes and hypertension. Secondary analyses of the Fit-One pragmatic RCT evaluated effects of OD on lifestyle, clinical and psychological outcomes for people with CVD risks of hypertension and type 2 diabetes (T2D).

Methods:
Fit-One enrolled adults with diabetes (HbA1c > 7%) who had never used OD. Subjects were randomized to get OD only, OD with fitness tracker or a waitlist control group. Present analyses compared just OD only to control subjects with T2D and hypertension. At baseline and 3-months, subjects completed validated measures of general self-rated health (GSRH), eating behavior problems (PDQ), vigorous, moderate and walking activity (mins in past week), life satisfaction, depression (PHQ-2) and HbA1c tests. MI corrected for missingness. Intent-to-treat (ITT) and per protocol (PP) analyses used ANCOVA and logistic models controlling for baseline outcomes.

Results:
Participants (N=115) tended to be female, white, non-hispanic and had health insurance. Treatment (N = 58) and control (N = 57) did not differ in baseline demographics or outcomes. In ITT models, main effects for general health, moderate activity, life satisfaction and depression and significant interactions for eating behavior problems, walking and A1c indicated benefit to the OD group (p < .05). Vigorous activity was not significant. PP models replicated findings yet moderate activity was not significant (p = .07), likely due to lower power. Within the OD group, moderate activity increased (p = .01).

Conclusions:
Over 3 months, OD users realized 15% higher health ratings (from 2.2); 10% fewer eating behavior problems (from 4.1); 105% more walking, 132% more moderate activity and 55% more vigorous activity (from 77, 67, 35 mins/wk); .72% absolute reduction in A1c and 4.7 times lower risk of depression vs. control (all PP). RCT results support the effectiveness of One Drop’s digital solution in improving lifestyle risks, glycemic control and psychological well-being in people at risk for CVD.
Abstract 9603: Polycomb Group Protein Cbx7 Represses Cardiomyocyte Proliferation via Modulation of the Tardbp/Rbm38 Axis
Authors: Cho Kyuwon , Mark Andrade , Bae SeongHo , Kim Sangsung , Kim Jin Eyun , Jang Er Yearn , Husain Ahsan , Sutliff R L , Calvert John W , Park Changwon , Yoon Young-sup
Published: April 2022

Introduction:
Cardiomyocyte (CM) proliferation notably decreases during the perinatal period. Regulatory mechanisms for this loss of proliferative capacity are poorly understood. CBX7, a polycomb group (PcG) protein, regulates the cell cycle but its role in CM proliferation is unknown.

Methods:
We profiled CBX7 expression in the mouse hearts via qRT-PCR, western blotting, and immunohistochemistry. We overexpressed CBX7 in neonatal mouse CMs via adenoviral transduction. We knocked down CBX7 by using constitutive and inducible conditional knockout mice (Myh6-cre;Cbx7
fl/+
and Myh6-MCM;Cbx7
fl/fl
, respectively). We measured CM proliferation by immunostaining of proliferation markers such as Ki67, phospho-histone 3, and cyclin B1. We examined the mechanism of CBX7-mediated repression of CM proliferation via co-immunoprecipitation, mass spectrometry, and other molecular techniques.

Results:
The mRNA expression of Cbx7 was increased at the perinatal stage and sustained in the postnatal heart (fold increase of adult vs. prenatal: 32.1 ± 3.3, P < 0.01). Overexpression of CBX7 in neonatal mouse CMs reduced CM proliferation (% of Ki67
+
CMs: Ad-Mock, 22.3 ± 1.7 vs. Ad-CBX7, 7.7 ± 0.7, P < 0.001). The haplodeficiency of CBX7 (Tnnt2-Cre;Cbx7
fl/+
) enhanced proliferation of neonatal CMs
in vivo
(% of Ki67
+
CMs: wild-type, 7.9 ± 0.9% vs. mutants, 24.7 ± 1.2%, P < 0.01), leading to increased myocardial wall thickness, cardiomegaly and neonatal lethality. Genetic deletion of CBX7 in CMs (Myh6-MCM;Cbx7
fl/fl
) at P1 resulted in increased CM proliferation (% of Ki67
+
CMs: vehicle, 9.5 ± 1.4% vs. tamoxifen, 18.3 ± 1.8%, P < 0.01), leading to cardiomegaly at 3 months. Mechanistically, CBX7 interacted with TAR DNA-binding protein 43 (TARDBP) and positively regulated its downstream target, RNA Binding Motif Protein 38 (RBM38). Rbm38 was perinatally upregulated in the mouse hearts and overexpression of RBM38 reduced proliferation of neonatal CMs.

Conclusions:
CBX7 expression is perinatally increased in the mouse hearts and inhibits proliferation of CMs by controlling TARDBP/Rbm38 pathway. This is the first study to demonstrate the role of CBX7 in regulation of CM proliferation and CBX7 could be an important target for cardiac regeneration.
Abstract 9604: Pulmonary Artery Systolic Blood Pressure Predicted From Cardiac MR Image Data Without Requiring Calibration; A Virtual RHC?
Authors: Doyle Mark , Rayarao Geetha , Lacson Roger , Hussain Nasir , Biederman Robert W
Published: April 2022

Introduction:
Despite decades of initiatives, assessment of absolute pulmonary arterial pressures (PAP) by CMR has remained an elusive goal. We introduce a means to predict the PAP from routine image data easily obtained by CMR. The image data is directly used to calculate the impedance between the LV and the aorta (IMP
LV
) and between the RV and the main PA (IMP
RV
) which are combined to predict PAP.

Methods:
Patients (n=33, 82% F), 51 ±12 yrs) with a diagnosis of (PHTN) underwent evaluation by CMR to assess the blood flow through the aorta and PA at the interface to the LV and RV, respectively. Phase velocity mapping flow data at single plane (acquisition time 2min) was used to calculate the previously described and validated impedance for the LV and RV: IMP
LV
and IMP
RV
. IMP was calculated using the formula:IMP = (end systolic ejection time) x (mean blood velocity) / (vessel diameter).

Systolic PAP was measured during a right heart cath examination performed within one week of the CMR. A multiple linear regression model was generated to predict systolic PAP, with parameters retained with a significance <0.05.

Results:
The parameters that best predicted the systolic PAP were IMP
LV
, IMP
RV
and the distance of the measured IMP
LV
from the center position of the data range of IMP
LV
(r = 0.69, p<0.001), Fig 1. The standard major-axis line was fitted to the data (p<0.001).

Conclusions:
This is the first demonstration of the utility of a CMR-measured left and right ventricular impedance value to directly predict systolic PAP. Critically, the correlation coefficient, identical to Echo, holds over a very wide physiologic range, and has never been demonstrated before by CMR. Of central importance is the distinguishing feature that no calibration of the data is required, thus, unlike typical Echo-derived estimates of PAP or newer implanted pressure monitors, no estimate of CVP or RAP is required. Thus, this is the first-in-man CMR demonstration of a virtual RHC.
Abstract 9610: High Levels of Myeloperoxidase Are Similar Across ASCVD Risk Groups and Are Associated with Markers of Liver Fibrosis and Kidney Function in a Workforce Population
Authors: Iakoubova Olga A , Louie Judy , Shiffman Dov , Mcphaul Michael , Penn Marc S
Published: April 2022

Background:
High blood levels of free myeloperoxidase (MPO) identify patients at risk for cardiovascular disease. We investigated levels of MPO according to 10-year ASCVD risk and the association between high MPO and markers of liver fibrosis and kidney disease.

Methods:
The study included participants in employer-sponsored annual health assessment (August 2020 to March 2021, n=33,984, 63% women, median age 47, IQR 36 to 56). Age and sex adjusted logistic models assessed the association between high MPO and non-alcoholic fatty liver disease (NAFLD) fibrosis score, liver Fibrosis-4 (FIB4) score, and estimated glomerular filtration rate (eGFR), stratified by 10-year ASCVD risk groups.

Results:
High MPO (>540 pmol/L) was found in 3% (n =925), 4% (n=184), and 5% (n =63) of the low (<7.5%), intermediate (7.5% to 20%), and high (>20% or prevalent disease) ASCVD risk groups, respectively. High MPO (>540 vs. ≤540 pmol/L) was associated with high NAFLD fibrosis score (>0.676 vs. <-1.455): OR = 4.7, 95%CI 3.5 to 6.2, high FIB4 score (>3.25 vs. ≤3.25): OR =3.4, 95%CI 1.8 to 6.4 and low eGFR (<60 vs. ≥60 mL/min/1.73m
2
): OR =1.8, 95%CI 1.4 to 2.4. The associations varied according to ASCVD risk (Figure). In the high ASCVD risk group, MPO was not associated with either NAFLD fibrosis score, FIB4 score, or eGFR (P ≥0.2 for all) and the risk differed according to ASCVD risk group (>20% vs. ≤20%) for NAFLD fibrosis score (P
int
=0.03) and eGFR (P
int
=0.01).

Conclusion:
The fraction of those with high MPO did not appreciably differ across ASCVD risk groups and most participants with high MPO levels in this workforce population were in the low ASCVD risk group. This observation is consistent with the hypothesis that subjects in the high ASCVD risk group are more likely to be receiving preventive therapies, whereas guidelines dictate that those in moderate and low risk groups may not. Investigating the association of MPO levels in ASCVD risk groups according to preventive therapy intensity is warranted.
Abstract 9678: The Association of Statins Use With Survival of Covid-19 Patients
Authors: So Matsuo , Takahashi Mai , Egorova Natalia , Kuno Toshiki
Published: April 2022

Introduction:
Statins are frequently prescribed for patients with hypertension, dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in COVID-19 patients. Statin’s beneficial effect on mortalities in COVID-19 infection has been reported in several studies, but still inconclusive.

Hypothesis:
The inconclusive study results in association of satin use and COVID-19 can be resulted from variable timing of statins used among the studies. Our aim was to investigate whether consistent use of statins before and during hospitalization was effective to decrease the mortality due to COVID-19.

Methods:
We conducted a retrospective study among 6,095 patients with COVID-19 hospitalized in New York City between March 1st 2020 and May 7th 2021. Patients were stratified into two groups: statins use prior or during hospitalization (N=2,423) versus no statins (N=3,672). We evaluated in-hospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In addition, we compared continuous use of statins (N=1,108) versus no statins.

Results:
Statins use prior or during hospitalization group were older (70.8±12.7 versus 59.2±18.2, P<0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in in-hospital mortality between patients with statins versus those without (28.9% versus 31.0%, P=0.19, odds ratio (OR) [95% confidence interval (CI)]: 0.91 [0.79-1.05]). This result was confirmed using IPTW analysis (OR [95% CI]: 0.96 [0.81-1.12], P=0.53). As the additional analysis comparing continuous use of statins versus no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group (26.3% versus 34.5%, P<0.001, OR [95% CI]: 0.68 [0.55-0.82]) after matching by propensity score (944 pairs). IPTW analysis showed the similar result (OR [95% CI]: 0.77 [0.64-0.94], P=0.009).

Conclusions:
Use of statins prior or during hospitalization was not associated with a decreased risk of in-hospital mortality, however, continuous use of statins might have potential benefit of a decreased risk of in-hospital mortality due to COVID-19.
Abstract 9695:
RASA3
as a Novel Candidate Gene in Sickle Cell Disease-associated Pulmonary Hypertension and Pulmonary Arterial Hypertension
Authors: Prohaska Clare C , Zhang Xu , Schwantes-An Tae-Hwi , Stearman Robert , Aldred Micheala A , Lutz Katie , Pauciulo Michael , Nichols Bill , Desai Ankit A , Gordeuk Victor , MacHado Roberto F
Published: April 2022

Introduction:
Sickle cell disease (SCD)-associated PH is associated with increased mortality when tricuspid regurgitant jet velocity (TRV) is ≥2.5m/s and mPAP is ≥25mmHg on right heart catheterization. RASA3, a ubiquitously expressed GTPase-activating protein, is integral to angiogenesis and maintenance of endothelial barrier function.

Hypothesis:
Loss of RASA3 leads to the development of PH in patients with SCD-associated PH and PAH.

Methods:
Cis-eQTLs were queried for
RASA3
using whole genome genotype arrays and gene expression profiles from PBMCs of subjects with SCD from 3 cohorts. Genome-wide SNPs near or in the
RASA3
gene that may associate with lung RASA3 expression were identified using data from the Genotype-Tissue Expression project, reduced to 9 tagging SNPs for RASA3 and associated with TRV≥2.5m/s and RHC hemodynamics. Associations between the top RASA3 SNP and RHC hemodynamics were tested using whole genome genotype data from subjects in the PAH Biobank. PAECs collected from explanted lungs from patients with IPAH or control lungs were cultured with RASA3 expression evaluated on Western blot.

Results:
PBMC-derived RASA3 expression was significantly lower in patients with SCD-associated PH using TRV≥2.5m/s and RHC hemodynamics, with significantly higher mortality (Figure 1). The risk allele (T) at rs9525228, an eQTL for RASA3, correlated with PH risk, higher TRV and higher PVR among PBMCs associated with decreased RASA3 expression in patients with SCD-associated PH. The T allele at rs9525228 was significantly associated with increased mPAP (p=0.014), PVR (p=0.041) and mean right atrial pressure (p=0.04) in patients from the PAH Biobank. RASA3 expression was significantly lower in PAECs from patients with IPAH compared to control.

Conclusions:
RASA3
is a novel candidate gene in SCD-associated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.
Medicine and Religion at the Early Modern Deathbed: How Can We Reframe the Narrative?
Authors: Donato Maria Pia
Published: April 2022

Since the 1960s, at a time when medicine was transforming Western conceptions of, and approaches to, the end of life, historians, historians of medicine, and specialists of religious studies have delved into death from a historical perspective. In the wake of historiens de la mentalité like Philippe Ariès and Michel Vovelle, studies commonly emphasise the limited autonomy of medicine vis-à-vis religion in conceptualising death and care for the dying. Only in the late eighteenth century, with Enlightenment culture and the secularization of society, were physicians supposedly encouraged to adopt a more active stance on the end of life. The aim of this paper is to survey recent scholarship that revisits the interaction of medicine and religion at the deathbed. In doing so, it presents an alternative to the rather dichotomous interpretation of the rise of medicine going hand in hand with the downfall of religion. It points to problems and sources that might be reconsidered in order to gain a more nuanced understanding of the interaction and reciprocal developments of medicine and religion in early modern Europe.
A brief report on the Palaeocene insects from the Sanshui Basin of Guangdong, South China
Authors: ZHANG ZHI-JUN , WANG XI , LIU ZHENG , ZHANG XIAN-QIU
Published: April 2022

More than two hundred and seventy specimens belonging to seven neopteran orders were collected, primarily from the upper part of the Xinzhuangcun Formation. Hemiptera, Hymenoptera, and Diptera have become more diverse groups in the Early Paleocene. The environment and climate in this period are putatively reconstructed.
Xenoastrosphaeriella aquatica sp. nov. from freshwater habitat in Yunnan Province, China
Authors: LUO ZONG-LONG , BAO DAN-FENG , LI LONG-LI , LUAN SHA , SU HONG-YAN
Published: April 2022

Xenoastrosphaeriella aquatica sp. nov. was discovered during an investigation of lignicolous freshwater fungi in northwestern Yunnan Province, China. Evidence of morphological characters and sequence data indicated that the new collection has affiliation to Xenoastrosphaeriella. Phylogenetic analysis of combined LSU, SSU and tef1-α sequence data was carried out to determine the phylogenetic placement of this species, which showed that X. aquatica clustered with X. tornata and X. trochus, but these three species are phylogenetically distinct. Xenoastrosphaeriella aquatica differs from other species in having dark olive to brown and larger ascospores. A detailed description and illustration of the new species are provided, as well as the comparisons with similar taxa.
Two new species of the genus Rhopalopsole (Plecoptera: Leuctridae) from China
Authors: CHEN JING , WANG HONGLIANG , LI WEIHAI
Published: April 2022

Two new species of the genus Rhopalopsole (Plecoptera: Leuctridae) are described from China: Rhopalopsole liui Chen, Wang & Li, sp. nov. from from Municipality of Chongqing (former Sichuan Province) and Rhopalopsole yadonga Chen, Wang & Li, sp. nov. from from the Tibet Autonomous Region. The new species are compared to similar congeners in the R. shaanxiensis and R. magnicerca groups, respectively.
Tumor Microenvironment-Responsive Nanodrug for Clear-Cell Renal Cell Carcinoma Therapy via Triggering Waterfall-Like Cascade Ferroptosis
Authors: Ni Wenjun , Li Yongxiang , Liang Lingxia , Yang Shuyue , Zhan Meixiao , Lu Cuixia , Lu Ligong , Wen Liewei
Published: April 2022

The most common type of kidney tumor, clear-cell renal cell carcinoma (ccRCC) with relatively insidious development and easily metastatic characteristics is generally insensitive to cytotoxic chemotherapy. The abundant polyunsaturated fatty acids (PUFAs) content in advanced ccRCC allows
it to be intrinsically vulnerable to ferroptosis-based therapeutic strategies. Nevertheless, the strategy to cause the “iron overload” by administration with iron-based nanomaterials has limited therapeutic efficacy. And the classic ferroptosis agonist (RSL3) with low specificity
for tumors, short half-life in the blood, poor water solubility and deficient accumulation at the tumor site prevents its reliable application in vivo. In this study, iron-based metal–organic framework nanoparticles (MIL-101(Fe) NPs) delivered RSL3 to ccRCC tumors, and then released
the iron ions and RSL3 accompanied by the degradation of MIL-101(Fe) NPs in the acidic tumor microenvironment. The MIL-101(Fe)@RSL3 as a pH-responsive nanodrug causes cellular iron overload and promotes the hydroxyl radical (•OH) generation by Fenton reaction to attack PUFAs,
leading to the aberrant accumulation of lipid peroxides (L–OOH). Additionally, RSL3 directly inhibits glutathione peroxidase 4 (GPX4) to detoxify L–OOH, and ferrous ions further catalyze the irreversible conversion of highly reactive lipid alkoxyl radicals (L–O•)
from L–OOH to triggering waterfall-like cascade ferroptosis. In contrast to the limited antitumor efficiency of free RSL3, MIL-101(Fe)@RSL3 with high encapsulation efficiency (88.7%) shows a significant ccRCC-specific antitumor effect and negligible side effects. Taken together, MIL-101(Fe)@RSL3
could aggravate ferroptosis and be expected to be a promising nanodrug for ccRCC systemic therapy due to the targeted delivery and responsive release of RSL3 and iron ions.
Gold-Nanoparticle-Conjugated Citrate Inhibits Tumor Necrosis Factor-α Expression via Suppression of Nuclear Factor Kappa B (NF-κB) Activation in Breast Cancer Cells
Authors: Aljohani Abdullah S. M. , Abdellatif Ahmed A. H. , Rasheed Zafar , Abdulmonem Waleed Al
Published: April 2022

One of the leading causes of death worldwide is cancer. Excessive production of tumor necrosis factor (TNF)-α is known to activate nuclear transcription factor (NF)-κB, which plays a lethal role in the onset of multiple disorders including cancer. In this study,
we aimed to determine the therapeutic role of novel gold nanoparticles conjugated with citrate (AuNPs-CIT) on the elevated expression of TNF-α in breast cancer cells. AuNPs-CIT were synthesized by the citrate-reduction method and were characterized by UV-VIS spectroscopic analysis,
zeta-potential analysis, and size analysis. The potential of these newly generated AuNPs-CIT particles was tested on phorbol 12-myristate 13-acetate (PMA)-stimulated cancer cells. Our data showed that the AuNPs-CIT were spherical, with a mean size of 21.3±0.65 nm and a stabilized zetapotential
at −41.4±0.98 mV. These newly generated AuNPs-CIT nanoparticles inhibited PMA-induced activation and nuclear translocation of NF-κB p65 in MCF-7 cells. They also have the tendency to block TNF-α expression in stimulated cancer cells. In conclusion, AuNPs-CIT
inhibits PMA-induced TNF-α mRNA and protein expression via deactivation of NF-κB signaling in breast cancer cells. These findings suggest that AuNPs-CIT might be useful in cancer treatment.
New Insights into Hemolytic Anemias: Ultrastructural and Nanomechanical Investigation of Red Blood Cells Showed Early Morphological Changes
Authors: Amorim Maria do Socorro do N. , Batista Jerias A. , Junior Francisco Maia , Fontes Adriana , Santos-Oliveira Ralph , Rebelo Alencar Luciana M.
Published: April 2022

Several diseases are characterized by changes in the mechanical properties of erythrocytes. Hemolytic anemias are an example of these diseases. Among the hemolytic anemias, Sickle Cell Disease and Thalassemia are the most common, characterized by alterations in the structure of their
hemoglobin. Sickle cell disease has a pathological origin in synthesizing abnormal hemoglobin, HbS. In contrast, thalassemia results in extinction or decreased synthesis of α and β hemoglobin chains. This work presents a detailed study of biophysical and ultrastructural
early erythrocytes membrane alterations at the nanoscale using Atomic Force Microscopy (AFM). Cells from individuals with sickle cell anemia and thalassemia mutations were studied. The analysis methodology in the AFM was given by blood smear and exposure of the inner membrane for ghost analysis.
A robust statistic was used with 65,536 force curves for each map, ten cells of each type, with three individuals for each sample group. The results showed significant differences in cell rigidity, adhesion, volume, and roughness at early morphological alterations, bringing new perspectives
for understanding pathogenesis. The sickle cell trait (HbAS) results stand out. Significant alterations were observed in the membrane properties, bringing new perspectives for the knowledge of this mutation. This work presents ultrastructural and biomechanical signatures of sickle cell anemia
and thalassemia genotypes, which may help determine a more accurate biophysical description and clinical prognosis for these diseases.