bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9703: Cardiac β
3
-Adrenergic Receptor Deficiency Mice Protected from Cardiac Aging: Insights into the Cellular and Molecular Mechanism of Myocardial Aging
Authors: Cheng Che Ping , Chen Zhe , Zhou Peng , Liu Yixi , Herrington David M , Zhao David X , Kitzman Dalane W , Cheng Heng-Jie
Published: June 2023

Background:
We have shown previously that aging-caused declines in cardiac function and β-adrenergic reserve were prevented in β
3
-adrenergic receptor (AR) knockout (β
3
KO) aged mice. The cellular and molecular mechanisms are unclear. We hypothesize that reversal of aging-induced downregulations of cardiac SR Ca
2+
-ATPase (SERCA2a) and β
1
-AR may lead to normalization of myocyte [Ca
2+
]
i
regulation, β-AR regulation, and preserving normal myocyte function, thereby preventing aging-induced cardiac dysfunction and eliminating myocardial aging.

Methods:
We compared protein levels of β
1
- and β
3
-AR, and SERCA2a, myocyte contractile, [Ca
2+
]
i
transient ([Ca
2+
]
iT
) and calcium current (I
Ca,L
) responses to isoproterenol (ISO, 10
-8
M) in LV myocytes obtained from 2 young (Y) (~6 m) and 2 aged (A) (~28 m) groups (7/group) of wild-type (WT) and β
3
KO mice, respectively.

Results:
Compared with YWT, AWT myocytes had significantly decreased protein levels of SERCA2a (AWT: 0.24 vs YWT: 0.67), and β
1
-AR (0.35 vs 0.59), but increased β
3
-AR (0.36 vs 0.16) with reduced basal cell contraction (dL/dt
max
) (85.3 vs 126.8μm/s), relaxation (dR/dt
max
) (66.7 vs 102.1 μm/s), [Ca
2+
]
iT
(0.18 vs 0.24), and I
Ca,L
(4.3 vs 7.6 pA/pF). These changes were accompanied by diminished ISO-stimulated inotropic response. In AWT myocytes, ISO caused significantly less increases in dL/dt
max
(34% vs 82%), dR/dt
max
(26% vs 64%), [Ca
2+
]
iT
(16% vs 38%) and I
Ca,L
(15% vs 34%). Versus YWT, Yβ
3
KO did not alter basal myocyte contraction and relaxation and response to ISO stimulation, but had significantly increased protein levels of SERCA2a (1.41 vs 0.61) and unchanged β
1
-AR (0.65 vs 0.62). Aβ
3
KO mice had similar alterations. Importantly, in contrast to AWT, in Aβ
3
KO myocytes, there was increased SERCA2a (1.3) associated with normal basal cell contraction and relaxation, and preserved ISO-stimulated inotropic response. ISO caused similar increases in dL/dt
max
(Aβ
3
KO: 81% vs Yβ
3
KO: 83%), dR/dt
max
(68% vs 62%), [Ca
2+
]
iT
(31% vs 32%) and I
Ca,L
(30% vs 32%).

Conclusions:
β
3
KO prevents aging-caused downregulations of cardiac β
1
-ARs and SERCA2a, leading to the preservation of myocyte function, [Ca
2+
]
iT
, I
Ca,L
and β-adrenergic reserve in aged hearts. Thus, β
3
-AR may provide a new target for cardiac aging.
Abstract 9724: Left Atrial Volume Index as a Predictor of Atrial Fibrillation Recurrence After Cardioversion
Authors: Thangjui Sittinun , yodsuwan ratdanai , Thyagaturu Harshith S , Shrestha Bishesh , Bathini Tarun , Bondi Gayatri , Zoltick Jerel
Published: June 2023

Introduction:
The left atrial volume index (LAVI) is a standard measurement of the left atrium. To date, there is limited data on the risk of AF recurrence with different LAVI cut-point. We aim to determine the association of LAVI as a predictor of AF recurrence after external electrical cardioversion (ECV).

Methods:
We conducted a retrospective cohort study using data from a single tertiary care center from January 2013 to December 2019. Patients diagnosed with AF who underwent successful ECV were included with the final follow-up date of December 2020. The effect of LAVI on AF recurrence was determined by Cox regression analysis adjusted by age, sex, BMI, comorbidities, type of AF, ejection fraction, and medications.

Results:
A total of 296 patients, 61.8% male, with a mean age of 69.2 ± 11.2 years old were included with a mean follow-up time of 1 year. Antiarrhythmic drugs were used in 104 patients after the ECV. LAVI ≤ 34 ml/m2 is associated with a lower risk of AF recurrence with an adjusted hazard ratio (aHR) of 0.31 (95%CI: 0.20-0.40). LAVI > 34 to < 40 ml/m2, did not significantly increased the risk of AF recurrence (aHR 1.67, 95%CI: 0.97-2.87). LAVI of ≥ 40 ml/m2 and ≥ 50 ml/m2 significantly increased the risk of AF recurrence with aHR of 4.30 (95%CI: 2.61 - 7.10) and 4.97 (95%CI: 2.97 - 8.33), respectively.

Conclusions:
Normal LAVI is associated with a lower AF recurrence after ECV and LAVI ≥ 40 ml/m2 is associated with increased AF recurrence. LAVI is a predictor to consider before undergoing rhythm management in a patient with atrial fibrillation.
Abstract 9733: Echocardiography Workshops Are an Effective Learning Tool for Pre-Clerkship Medical Students
Authors: Gharai Ava , Cone Abigail , Wold Kelsey , Proszek David , Jensen Richard , Anderson Charles
Published: June 2023

Introduction:
Point of care ultrasound curriculum is being taught in undergraduate medical education (UME) with greater frequency and demonstrable benefit to students’ learning. While echocardiography (echo) curricula have been implemented in a small number of medical schools, there is limited data on the efficacy of the learning experience.

Hypothesis:
Echo workshops in UME are feasible and effective as a means of introducing medical students to basic echo skills.

Methods:
24 pre-clerkship medical students volunteered to undergo 4-hour echo workshops. A variety of preparatory learning materials covering basic aspects of echo were provided to students one week prior to the workshop. A short quiz was administered to all students immediately before and after the workshop. Quiz questions were coded as cardiac anatomy (6 questions), basic echo imaging (8 questions), basic ultrasound and Doppler theory (2 questions), and advanced echo imaging techniques (3 questions). During the workshop, each student was provided at least 30 minutes of hands-on imaging while another student acted as the “patient.” Certified echosonographers and pediatric cardiologists served as the instructors during the workshop. Students completed a survey to characterize the quality of the learning experience. Students’ performance on the quiz pre- and post-workshop were compared using student’s t-test.

Results:
The mean overall pre- and post-workshop quiz scores were 6.8/19 and 11.4/19, respectively (p<0.00001). Mean pre- vs post-quiz scores for cardiac anatomy were 2.0 vs 3.8/6 (p=0.0001); for basic echo imaging were 3.5 vs 5.3/8 (p<0.001); for basic ultrasound and Doppler theory were 0.5 vs 1.5/2 (p<0.00001); and for advanced echo imaging were 0.7 vs 0.9/3 (p=0.5), respectively. All students characterized the quality of their learning experience through the workshop as a very effective use of their time.

Conclusions:
Echo workshops targeted to pre-clerkship medical students are feasible, and provide effective learning experiences in cardiac anatomy, basic echo imaging, and basic ultrasound and Doppler theory in the short-term, and are very well-received by students. Providing basic echo curriculum in the pre-clerkship years of medical school should be further explored.
Abstract 9809: Clinical Outcomes of Transcatheter Aortic Valve Replacement vs.surgical Aortic Valve Replacement in Patients With Durable Left Ventricular Assist Device
Authors: Sagheer Shazib , Minhas Abdul , Zaidi Syeda H , Dani Sourbha , Goel Sachin S , alam mahboob , wasty najam
Published: June 2023

Introduction:
Patients with left ventricular assist device (LVAD) often develop aortic insufficiency (AI) requiring an intervention on the aortic valve. We sought to analyze the outcomes of patients with a history of LVAD who underwent either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

Methods:
The Nationwide Readmission Database (NRD) was used to extract relevant patient information from January 1, 2016, to December 31, 2018. The NRD is a nationally representative sample of all-payer discharges from U.S. non-federal hospitals. The primary outcome of interest was in-hospital mortality. Secondary outcomes included length of stay, inpatient outcomes, costs, and 30-day all-cause readmissions. Complex samples multivariable logistic and linear regression models were used to determine the association of procedure type with outcomes.

Results:
Among 148 hospitalizations with a history of LVAD, 87 underwent TAVR, and 61 underwent SAVR. The inpatient mortality in SAVR group was numerically higher compared to the TAVR cohort, however, it did not reach statistical significance. The use of invasive mechanical ventilation, cardiogenic shock, bleeding, and vascular complications were higher in the SAVR cohort compared to the TAVR cohort. The mean length of stay (in days) and costs were higher in the SAVR cohort compared to the TAVR cohort. The 30-day all-cause readmission rate was numerically higher in the SAVR group, however, it was not statistically significant (Table 1).

Conclusions:
TAVR in patients with LVAD is a viable treatment option for AI and potentially leads to better inpatient mortality and inpatient outcomes compared to patients who undergo SAVR.
Abstract 9818: Use of Outpatient Intravenous Diuretic Therapy Among Patients With Heart Failure in the United States
Authors: Greene Stephen J , Goto Daisuke , Wang Dong , Lautsch Dominik , Hilkert Robert J , Fonarow Gregg C
Published: June 2023

Introduction:
Select centers have published local experiences with outpatient (OP) intravenous (IV) diuretic clinics to treat worsening heart failure (HF) and prevent hospitalization. Little is known regarding widespread use of this care strategy in contemporary US practice, including the potential impact of the COVID-19 pandemic.

Methods:
Inpatient (IP) and OP claims from Optum (April 2018-March 2021) were utilized to identify instances where patients with HF with reduced ejection fraction (HFrEF) received ≥1 administration of IV diuretic. Episodes of care were categorized into hierarchical mutually exclusive groups defined by intensity of care setting, including IP hospitalization, critical care (without IP hospitalization), emergency department (without IP hospitalization), observation unit, nursing facility, and outpatient clinic. Analyses were stratified across pre-pandemic (4/2018-3/2019, 4/2019-3/2020) and COVID-19 pandemic periods (4/2020-3/2021).

Results:
Among 302,397 patients with HFrEF, 56,213 (19%) patients received IV diuretic therapy during the study period, accounting for 94,865 total IV diuretic episodes. Of patients receiving IV diuretics, 44% were female and 20% were Black. Among 85,827 (90%) IV diuretic episodes with available data on location of care, 14% were outpatient clinic visits, 60% were IP hospitalizations, and 21% were ED visits. Critical care, observation unit, and nursing facility locations each constituted ~1-2% of IV diuretic episodes. The proportion of outpatient IV diuretic visits and the overall distribution of IV diuretic episodes was similar over time, spanning the pre-pandemic and COVID-19 pandemic periods
(Figure)
.

Conclusions:
In this cohort of US patients with HFrEF, approximately 1 in 7 care episodes involving IV diuretic therapy occurred in outpatient clinic. The relative proportion of outpatient IV diuretic visits did not meaningfully change during the first year of the COVID-19 pandemic.
Abstract 9824: Cardiovascular Complications During Delivery Admissions Associated With Systemic Lupus Erythematosus: A National Inpatient Sample Analysis (2004-2019)
Authors: Zahid Salman , Mohamed Mohamed Salah , wassif heba , Nazir Noreen , Khan Sadiya S , Michos Erin D
Published: June 2023

Introduction:
Persons with systemic lupus erythematosus (SLE) have an increased risk of obstetric-associated complications. However, data on acute cardiovascular (CV) complications during delivery remain limited.

Hypothesis:
SLE is associated with increased acute CV complications at the time of delivery.

Methods:
We used data from the National Inpatient Sample (2004-2019) while utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and a diagnosis of SLE.

Results:
A total of 63,037,442 weighted delivery hospitalizations were identified, of which 0.1% were among persons with SLE (n=77,560). Individuals with SLE were older (median 30 vs. 28 years, p<0.01) and had a higher prevalence of polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), obesity, and dyslipidemia (p<0.01). After adjustment for age, race/ethnicity, comorbidities, insurance, and income, SLE remained an independent predictor of peripartum CV complications including preeclampsia (aOR 2.12 [2.07-2.17]), peripartum cardiomyopathy (aOR 4.42 [3.79-5.13]), heart failure (aOR 4.06 [3.61-4.57]), and cardiac arrhythmias (aOR 2.06 [1.94-2.21]) compared with no SLE. Likewise, the risk of acute kidney injury (AKI), stroke, pulmonary edema and venous thromboembolism (VTE) were higher with SLE. An overall increasing trend of obesity, GDM and PCOS was also observed among individuals with SLE. For resource utilization, length of stay and cost of hospitalization was higher for deliveries among persons with SLE.

Conclusions:
Persons with SLE had a higher risk of preeclampsia, peripartum cardiomyopathy, heart failure, arrhythmias, pulmonary edema, AKI, stroke and VTE during delivery hospitalizations. Furthermore, cardiometabolic risk factors among individuals with SLE are on the rise over this 15 year period.
Abstract 9832: Liver-Heart Crosstalk Mediated by Coagulation Factor XI Protects Against Heart Failure
Authors: Cao Yang , Wang Yuchen , Zhou Zhenqi , Pan Calvin , Jiang Ling , Zhou Zhiqiang , Meng Yonghong , Charugundla Sarada , Li Tao , Allayee Hooman , Seldin Marcus , Lusis Aldons J
Published: June 2023

Introduction:
Tissue-tissue crosstalk by endocrine factors is a vital mechanism to maintain proper physiologic homeostasis. The heart and the liver display multifaceted interactions and it is common to observe heart diseases affecting the liver and vice versa.

Hypothesis:
We hypothesized that the liver-heart interactions may be mediated by novel endocrine factors.

Methods:
Global transcriptomic data from the heart and the liver were generated across all 100 diverse inbred strains of mice, the Hybrid Mouse Diversity Panel (HMDP), and used to detect the correlation structure between secreted proteins from the liver and their downstream effects on the heart. Candidates were validated in a “two-hit” model of heart failure with preserved ejection fraction (HFpEF) and plasma samples from HFpEF patients and controls were used to examine the clinical relevance.

Results:
Using the bioinformatics framework, we predicted that coagulation factor XI (FXI) is a liver-derived protein that influences heart gene expression and diastolic dysfunction, a key trait of HFpEF. In a mouse model of HFpEF, mice overexpressing FXI in the liver showed improved diastolic function and reduced inflammation and fibrosis, whereas FXI knockout mice were sensitized for diastolic dysfunction. FXI overexpression activated the bone morphogenetic protein (BMP)-Smad1/5 pathway in the heart, thus inhibiting genes involved in inflammation and fibrosis. The action of FXI on heart requires proteolytic activity, as point mutations in its catalytic domain eliminated effects on BMP signaling and heart function. BMP7 is secreted as an inactive precursor and our results indicate that it is cleaved by FXI, releasing the active dimer and monomer growth factor from the prodomain that binds to the extracellular matrix. Further, plasma FXI was inversely correlated with E/e’ ratio in all human participants and HFpEF patients.

Conclusions:
Our studies indicate that liver-derived FXI specifically regulates cardiomyocytes through the BMP-Smad1/5 pathway, resulting in attenuation of fibrosis, inflammation, and diastolic dysfunction in the context of a HFpEF model. Our study reveals a protective role of FXI on heart injury, distinct from its role in coagulation.
Abstract 9834: Lysosomal Ca
2+
Release Contribute to Arrhythmia After Myocardial Infarction
Authors: Xie An , Kang Gyeoung-Jin , Liu Hong , Kim Eun Ji , Feng Feng , Dudley Samuel C
Published: June 2023

Introduction:
In heart failure (HF), mitochondria Ca
2+
handling is involved in arrhythmogenesis by modulating diastolic sarcoplasmic reticulum (SR) Ca
2+
release. Recently, it has been reported that lysosomal Ca
2+
release can trigger a SR Ca
2+
release.

Hypothesis:
We investigated whether lysosomal Ca
2+
flux could contribute to ischemic HF arrhythmia in a similar manner to mitochondria.

Methods:
Ischemic HF was induced in wild type FVB/NJ mice by ligated left anterior descending coronary artery. Mice were studied at three weeks after myocardial infarction (MI).

Results:
The lysosomal-restricted transient receptor potential mucolipin 1 (TRPML1) Ca
2+
release channel, but not the two-pore channel 2, was significantly upregulated by 84.8% in cardiac border zone and 55.4% in a remote zone after MI, and cardiomyocyte TRPML1 was significantly increased in human patients with ischemic or nonischemic cardiomyopathy. As expected, TRPML1 co-localized with the lysosome marker, LAMP1. The master transcriptional lysosomal regulator, dephosphorylated TFEB (i.e., active TFEB) and LAMP1 labelled lysosomes increased after MI. Lysosomal Ca
2+
release directly as indicated by GCaMP7-TRPML1, a fluorescent Ca
2+
sensor coupled to TRPML1, was upregulated in MI mouse CMs. TRPML1 specific agonist, ML-SA1, could evoke Ca
2+
sparks in the CMs isolated from MI mice, and these sparks were inhibited by a specific antagonist, ML-SI1. Furthermore, thapsigargin or high concentration ryanodine, inhibited Ca
2+
loading and release from the SR respectively and prevented TRPML1-dependent Ca
2+
sparks in the MI CMs. TRPML1-dependent sparks were not affected by S107, a drug which specifically inhibits Ca
2+
leak, however. Blocking TRPML1depressed early and delayed afterdepolarizations (EADs and DADs) in CMs isolated from MI mice while increasing TRPML1 activity enhanced triggered activity. The inhibition of TRPML1 had no effect on the APs recorded from sham mouse CMs, however. ML-SA1 could increase induced ventricular fibrillation episodes in MI mice while ML-SI1 could reduce arrhythmia by optical mapping and pacing.

Conclusions:
Lysosomes contribute to arrhythmic risk in MI by releasing Ca
2+
during diastole causing SR diastolic Ca
2+
release and triggered activity.
Abstract 9838: Safety and Feasibility of Staged or Concomitant Transcatheter Edge-to-Edge Mitral Valve Repair After Transcatheter Aortic Valve Replacement
Authors: Zahid Salman , Hashem Anas , Khan Muhammad Z , balla sudarshan
Published: June 2023

Introduction:
The data on safety and feasibility of performing concomitant or staged Transcatheter Edge-to-Edge Repair (TEER) of the mitral valve with Transcatheter Aortic Valve Replacement (TAVR) remains limited.
Hypothesis:

Methods:
The Nationwide Readmission Database (NRD) was utilized to identify TEER and TAVR procedures from 2015, to 2019, using ICD-10-CM administrative claim codes.

Results:
A total of 28,180 weighted cases of TEER were included in the analysis. Of the included cases 27,562 underwent TEER as a separate procedure and were compared with TEER cases performed concomitantly with TAVR (n=174) or performed as a staged procedure (n=453). In terms of crude outcomes, in-hospital mortality (4.4% vs 2.1%, p<0.01) and associated complications including cardiogenic shock (8.5% vs 4.5%, p<0.01), acute kidney injury (27.7% vs 15.2%, p<0.01) and pacemaker implantation rates (3.7% vs 0.6%, p<0.01) were higher for concomitant or staged procedures. However, in the propensity matched group there was no difference between the two groups in terms of in-hospital mortality (4.4% vs 6.2%, p0.13) and associated complications. Furthermore, in the matched group there was no difference in terms of hospital length of stay (3 days vs 3 days, p0.21) and hospitalization cost (USD 49,356 vs USD 49,037, p0.46) for TEER alone compared with concomitant or staged TEER procedures.

Conclusions:
TEER performed in the same admission as TAVR or as a staged procedure maybe safe and a feasible treatment option for patients with concomitant mitral regurgitation and severe aortic stenosis compared with TEER alone.
Abstract 9841: Outcomes Following Biventricular Repair of Atrioventricular Septal Defect With a Single Left Ventricular Papillary Muscle
Authors: Woodrick Scarlet , Kleeman Kellianne , Yu Sunkyung , Lowery Ray , Romano Jennifer , Fifer Carlen G
Published: June 2023

Introduction:
In patients with atrioventricular septal defect (AVSD) with single papillary muscle attachments in the left ventricle (LV), the left AV valve (LAVV) is at risk for suboptimal repair. This study aimed to evaluate outcomes following repair of AVSD with single LV papillary muscle attachments and to identify preoperative predictors of postoperative LAVV outcomes.

Methods:
All patients with AVSD and anatomically or functionally single LV papillary muscle who underwent biventricular repair at our institution from 07/01/2000 - 07/01/2020 were retrospectively reviewed. Univariate analysis was used to identify associations between patient demographics, preoperative echocardiographic measures, and surgical characteristics with the degree of LAVV stenosis or regurgitation postoperatively and the need for reintervention on the LAVV.

Results:
Of 38 patients included, nearly all (97%) were repaired with no or partial closure of the LAVV cleft. Freedom from LAVV reintervention was 91% and 84% at 1 and 3 years. Five patients (13%) required reintervention on the LAVV with a median time to reintervention of 3.3 months post-AVSD repair; indication was LAVV regurgitation for four of the five patients. Preoperative LAVV regurgitation > mild was associated with an increased risk for LAVV reintervention (p= 0.02). At discharge, 63% of patients had > mild LAVV regurgitation and 5% had > mild LAVV stenosis. At most recent follow-up, 32% had > mild LAVV regurgitation and 12% had > mild LAVV stenosis. Patients with younger age at repair and preoperative AV valve index <0.67 had significantly increased risk of > mild LAVV regurgitation at discharge (p=0.01 and p=0.04, respectively), however this did not persist at most recent follow-up. More pronounced unbalance of the AVSD was not associated with postoperative LAVV stenosis.

Conclusions:
Despite concern for repair in patients with AVSD and single papillary muscle attachments, surgical outcomes are favorable with low risk for reintervention. Risk of LAVV stenosis is low when repair of LAVV cleft is modified. Preoperative LAVV regurgitation, younger age at repair, and more pronounced unbalance of the AVSD predicted early postoperative LAVV regurgitation, with improvement over time.
Abstract 9893: The Associations Between Layer-Specific Global Circumferential Strain Parameters and Incident Heart Failure: The Copenhagen City Heart Study
Authors: Skaarup Kristoffer G , Lassen Mats H , Johansen Niklas D , Jensen Gorm B , Schnohr Peter , Mogelvang Rasmus , Biering-Srensen Tor
Published: June 2023

Introduction:
Global circumferential strain (GCS) has been demonstrated to be sensitive marker of early cardiac pathology compared to conventional echocardiographic measurements. Improvement in speckle tracking echocardiography has introduced layer-specific quantification of GCS. This study investigated the differences in the prognostic value of endomyocardial (GCS
Endo
) and epimyocardial (GCS
Epi
) GCS regarding incident HF (heart failure) in the general population.

Methods:
The prospective cohort study included randomly invited individuals from the general population. All participants were examined with echocardiography. Exclusion criteria were prevalent HF at baseline, non-sinus rhythm during echocardiography and inadequate image quality for speckle tracking analysis. Cox proportional hazard regression models were utilized to assess associations between GCS
Endo
and GCS
Epi
with incident HF. A multivariable model was created, which included left ventricular (LV) ejection fraction, LV mass index, and the variables from the ARIC HF risk score.

Results:
A total of 2874 individuals were included in the study sample. Mean age was 53 years ± 18 years and 40% were males. Mean GCS
Endo
and GCS
Epi
were 31.9 ± 5.3% and 14.3 ± 4.0% respectively. During a follow-up period of 5.4 years (IQR: 4.5; 6.3) 52 suffered incident HF. The cumulative incidence of HF according to the medians of layer-specific GCS is illustrated in
Figure 1.
In multivariable Cox regressions, GCS
Endo
remained significantly associated with HF (HR = 1.06 95%CI: [1.00; 1.12], per 1 % decrease), while GCS
Epi
did not (HR = 1.01 95%CI: [0.94; 1.10], per 1 % decrease). The same pattern was observed when only adjusting for age and sex. Additionally, GCS
Endo
provided significantly higher Harrel’s C-statistics as compared to GCS
Epi
(0.68 95%CI[0.58; 0.77] vs 0.60 95%CI[0.50; 0.69]).

Conclusions:
In the general population, GCS
Endo
is independently associated with incident HF while GCS
Epi
is not.
Abstract 9972: Sex-Related Differences and the Influence of Pregnancy on Cardiac Outcomes in Adults With a Systemic Right Ventricle and Biventricular Physiology
Authors: Mahdi Naima-Ayane , guerma lea , Mongeon Francois P , Dore Annie , Mondesert Blandine , Khairy Paul , Leduc Line , Codsi Elisabeth , Chaix Marie
Published: June 2023

Introduction:
Transposition of the great arteries (TGA) with a systemic right ventricle (sRV) and biventricular physiology is associated with increased morbidity and mortality. There is a paucity of data regarding sex-related differences in outcomes in the context of a sRV. Moreover, pregnancy has been associated with deterioration of sRV function in short-term post-partum follow-up, but the long-term impact remains largely unknown.

Methods and Results:
A retrospective cohort study was conducted on 214 adults, age 44.7±12.3 years, with a sRV and biventricular physiology followed for a median of 13 years at an adult congenital heart disease center. No sex-related difference was identified in the prevalence of atrial or ventricular arrhythmias, permanent pacemaker implantation, hospitalization for heart failure, systemic atrio-ventricular valve intervention, heart transplant, or cardiac death. Among the 82 (38.3%) women, age 44.0±12.5 years, 43 (52.4%) had at least one full-term pregnancy. Women had a lower prevalence of moderate to severe sRV dysfunction than men (21% vs 42.6%, p=0.001) despite similar ages. Beta-blockers (p=0.008), furosemide (p=0.012), and mineralocorticoid receptor antagonists (p=0.028) were less frequently prescribed to women than men. Women had fewer implantable cardioverter-defibrillators (ICDs) for primary prevention than men (3.7% vs 13.6%, p=0.016), with no difference in the prevalence of secondary prevention ICDs (1.2% vs 2.3%, p=1). The four women with a prohibitive maternal mortality risk (modified WHO class IV) complied with recommendations to avoid pregnancy. After excluding these 4 women, no differences regarding frequency of adverse cardiac events, age at the time of event, and proportion with moderate or severe sRV dysfunction were observed in women with (N=43) and without (N=35) pregnancies during 14 years of follow-up.

Conclusions:
Women with TGA and a sRV had a lower prevalence of moderate to severe systemic ventricular dysfunction than men, along with a lower proportion of primary prevention ICDs. Following risk assessment and counselling with contraindication of pregnancy in the highest risk subgroup, pregnancy had no impact on long-term cardiac outcomes.
Abstract 9990: Hypertension Risk Differs by Asian Ethnicity Across the Adult Lifespan
Authors: Lien Irvin , Macko Christopher A , Rana Jamal S , Lo Joan C , Gordon Nancy P
Published: June 2023

Introduction:
Hypertension risk increases with higher age and body mass index (BMI). We previously found that the prevalence of diagnosed hypertension among Filipino adults is similar to Black adults and higher than White, Chinese, and South Asian adults aged 45-84y. Among young women, the difference between Filipina and Chinese adults was >2-fold. We now examine disparities in hypertension prevalence across the adult lifespan, accounting for differences in weight status.

Methods:
This cross-sectional study used electronic health record data for 1,018,159 non-Hispanic White (White), 146,517 Black, 348,715 Hispanic, 128,124 Filipino, 126,321 Chinese, and 80,723 South Asian adults aged 30-79 who were members of a Northern California health plan in 2016. Hypertension prevalence (ICD 9/10 diagnosis in 2016) was examined by race/ethnicity and sex for ages 30-39, 40-49, 50-59, 60-69, 70-79y. Poisson regression was used to estimate prevalence ratios (aPRs) for hypertension compared to White adults in each age decade, adjusting for age, English language, current smoking, and BMI category (underweight, healthy weight, overweight, obesity class 1, 2, 3). Lower BMI thresholds were used for Asian adults.

Results:
Across all age decades, Filipino adults had a prevalence of hypertension similar to Black adults and higher than White, Chinese, and South Asian adults. In each age decade, the Filipino:White aPRs approached or exceeded the Black:White aPRs and were much higher than South Asian:White and Chinese:White aPRs (Figure). Differences in hypertension risk were greatest for those aged 30-59y.

Conclusions:
Filipino adults, similar to Black adults, had earlier onset and higher prevalence of hypertension than White, Chinese, and South Asian adults across 5 age decades, a disparity that persisted after adjusting for weight status, smoking, and language. These results support the need for earlier and more aggressive blood pressure screening in high-risk populations.
iPSC-Based Modeling of Variable Clinical Presentation in Hypertrophic Cardiomyopathy
Authors: Escribá Rubén , Larrañaga-Moreira José M. , Richaud-Patin Yvonne , Pourchet Léa , Lazis Ioannis , Jiménez-Delgado Senda , Morillas-García Alba , Ortiz-Genga Martín , Ochoa Juan Pablo , Carreras David , Pérez Guillermo Javier , de la Pompa José Luis , Brugada Ramón , Monserrat Lorenzo , Barriales-Villa Roberto , Raya Angel
Published: June 2023

Background:

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here, we set out to investigate genotype-phenotype relationships in 2 siblings with an extensive family history of HCM, both carrying a pathogenic truncating variant in the
MYBPC3
gene (p.Lys600Asnfs*2), but who exhibited highly divergent clinical manifestations.

Methods:

We used a combination of induced pluripotent stem cell (iPSC)-based disease modeling and CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9)-mediated genome editing to generate patient-specific cardiomyocytes (iPSC-CMs) and isogenic controls lacking the pathogenic
MYBPC3
variant.

Results:

Mutant iPSC-CMs developed impaired mitochondrial bioenergetics, which was dependent on the presence of the mutation. Moreover, we could detect altered excitation-contraction coupling in iPSC-CMs from the severely affected individual. The pathogenic
MYBPC3
variant was found to be necessary, but not sufficient, to induce iPSC-CM hyperexcitability, suggesting the presence of additional genetic modifiers. Whole-exome sequencing of the mutant carriers identified a variant of unknown significance in the
MYH7
gene (p.Ile1927Phe) uniquely present in the individual with severe HCM. We finally assessed the pathogenicity of this variant of unknown significance by functionally evaluating iPSC-CMs after editing the variant.

Conclusions:

Our results indicate that the p.Ile1927Phe variant of unknown significance in
MYH7
can be considered as a modifier of HCM expressivity when found in combination with truncating variants in
MYBPC3
. Overall, our studies show that iPSC-based modeling of clinically discordant subjects provides a unique platform to functionally assess the effect of genetic modifiers.
The Semantics of Eucharistic Miracles
Authors: Wierzbicka Anna
Published: June 2023

The term “Eucharistic miracles” refers to some seemingly inexplicable phenomena which have been observed at many times in Catholic churches in various countries. (“Eucharist” is the central element of Christian worship in general and Catholic worship in particular). According to Wikipedia, “reported Eucharistic miracles usually consist of unexplainable phenomena such as consecrated hosts visibly transforming into myocardium [heart] tissue”.

From a believer’s point of view, a “Eucharistic miracle” can be read as a message – a message which doesn’t force belief but which does “want to be believed”; and which, first of all, “wants to be understood”. As such, these phenomena present a task for a semanticist: what meaning can be plausibly attributed to them by people open to faith and how can this message be best articulated?

In this paper, the author, a semanticist with a special interest in the semantics of religion (Wierzbicka, 2001, 2019) takes a look at “Eucharistic miracles” from a semantic point of view. Her goal is to explore these phenomena through Minimal English anchored in universal human concepts (Wierzbicka, 1996, 2014; Goddard and Wierzbicka, 2014; Goddard, 2018, 2021).
Flying, Floating, Hurtling – a Corpus-Assisted Study of astromotion Verbs in American English
Authors: Törmä Kajsa
Published: June 2023

This paper establishes and explores the lexical field of astromotion (motion in outer space) from a Cognitive Linguistic perspective by investigating verb collocates of space, outer space and deep space from the Corpus of Contemporary American English (coca). The primary focus is on the moving figure and the manner of motion involved. The paper accounts for prototypical uses of the verbs and puts the results in dialogue with previous research into motion events on earth. The main findings are that (1) astromotion is primarily lexicalized by general motion verbs or relexicalizations from other domains of motion; (2) transitive verb constructions are more common than in previously studied domains of motion and; (3) control and speed are important disambiguating properties. The paper also illustrates how the lexical field has been influenced by our empirical knowledge, imagination, and embodied experiences.
Saponins modulates fatty alcohol oxidase to reduce myocardial remodeling and control heart failure by regulating cGMP-PKG signaling pathway
Authors: Lin Yan , Bai Yang , Huang Jiliang , Huang Jinlong , Gao Peng , Dan Hanliang
Published: June 2023

This study analyzed mechanism of saponins regulating fatty alcohol oxidase (FAO) to reduce myocardial remodeling and control heart failure. 30 Sprague-Dawley (SD) rats were randomly and equally assigned into control group, model group, and saponin group, followed by analysis of myocardial
tissue pathology, cyclic guanosine monophosphate (cGMP), Recombinant Human Protein (PKG), Peroxisome proliferator-activated receptors (PPAR-α) expression levels, and cell apoptosis. Compared to control group, cGMP, PKG, PPAR-α, uncoupling protein 3 (UCP3), and cluster
of differentiation 36 (CD36) mRNA levels in the model group were significantly decreased (P <0.001) and elevated in the saponin group (P <0.05). Oxidation rates of adenosine triphosphate (ATP), phosphocreatine/ATP, and palmitic acid in the model group were significantly
decreased (P <0.001) and elevated in the saponin group (P <0.05). Apoptosis and level of Cleaved caspase-3 were significantly reduced in the model group (P <0.001) and increased in the saponin group (P <0.05). Levels of cGMP, PKG, PPAR-α,
UCP3 and CD36 in the model group decreased (P <0.001) and increased in the saponin group (P <0.001), but lower than in the control group. Relative to the model group, Brain Natriuretic Peptide (BNP) level was significantly increased in the inhibitor group and decreased
in the agonist group (P <0.001). Saponins activate cGMP-PKG signaling pathway, up-regulating cGMP and PKG, promoting PPAR-α expression, inhibiting myocardial cell necroptosis, thereby reducing inflammatory infiltration of myocardial cells, improving connective tissue
hyperplasia, and reducing myocardial injury and myocardial remodeling, thus play an anti-heart failure role.
Perinatal mental health and the justice delivery system in India
Authors: Behl Ritika , Nemane Vivek
Published: June 2023

On 20 April 2022 the Sessions Court of Greater Mumbai sentenced a postpartum depressed woman to lifetime imprisonment for abandoning and murdering her twin girl child ( In re: The State of Maharashtra). In the absence of a diagnosis or treatment for postpartum depression at the time when the crime was committed, a plea of insanity was denied. This article considers how the absence of services for perinatal mental health in India may challenge the delivery of criminal justice in cases of infanticide.
‘The Spirit of Jesus’ in Acts 16.7: An Ethnographic Reading
Authors: Christopher Dany
Published: June 2023

‘The spirit of Jesus’ (τὸ πνεῦμα Ἰησοῦ) is an uncommon phrase found only in Acts 16.7. Most scholars presume it to be a variant description of the Holy Spirit without any special significance. Garnering insight from ethnographic studies on spirit possession, this article seeks to overturn this presumption. In particular, the notion of the traveling spirit suggests that τὸ πνεῦμα Ἰησοῦ deliberately emphasizes the expansion of the ‘presentness’ of Jesus to a new geographical area, namely Macedonia. The significance of the coming into the presence of Jesus in Macedonia is also shown by the account of the divine direction of Paul and his companions to pass by other areas on their way to Macedonia, as well as an allusion to Alexander the Great, the conversion of Lydia, and the clash with another specific spirit that wishes to announce its presence—the python spirit.
The regulation of and through information technology: Towards a conceptual ontology for IS research
Authors: Butler Tom , Gozman Daniel , Lyytinen Kalle
Published: June 2023

This special issue addresses a largely neglected area of Information Systems (IS) research – the regulation of and through Information Technology (IT). As with other human technologies, IT artefacts present risks and can harm individuals, groups, organisations, economies, and society: However, this remains a largely unexplored topic in IS research. Nevertheless, regulators, social commentators, the media, and the public have voiced their concerns about such risks, particularly those related to artificial intelligence (AI), cybersecurity, privacy, digital assets (e.g. cryptocurrencies), and the market dominance of digital platforms. Accordingly, regulations have been instituted or proposed to regulate IT artefacts in and across several business sectors. Additionally, in response to the informational challenges posed by a complex web of laws and regulations, regulators and business organisations have implemented IT artefacts to transform regulatory and supervisory processes or to enhance organisational risk management and compliance reporting capabilities. This special issue addresses the research challenges related to emergent issues surrounding the regulation of and through IT. In this editorial, we take stock of where the field currently stands. We advance a conceptual ontology of IT regulation to guide future research by specifying several taken-for-granted core concepts. By rendering the concepts, categories, and their relationships explicit, the model and its related research questions provide a firm foundation to generate a cumulative body of research on the regulation of and through IT.
PPAR-alpha/gamma agonists, glucagon-like peptide-1 receptor agonists and metformin for non-alcoholic fatty liver disease: A network meta-analysis
Authors: Zhang Zhuo-Ya , Yan Qi , Wu Wen-Hao , Zhao Yuan , Zhang Hua , Li Jin
Published: June 2023

Objective

To undertake a network meta-analysis to compare the relative efficacy of a dual peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonist, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin in patients with non-alcoholic fatty liver disease (NAFLD).

Methods

Electronic databases, including Embase®, PubMed® and The Cochrane Library, were searched systematically for eligible studies from inception to 20 July 2022. Randomized controlled trials (RCTs) that investigated aspartate aminotransferase, alanine aminotransferase (ALT) and triglyceride levels were considered for inclusion. Data were extracted using a standardized data collection table. A network meta-analysis was performed. Relative risk and 95% confidence interval were calculated for continuous data and I2 was used to assess the heterogeneity of studies.

Results

A total of 22 RCTs involving 1698 patients were eligible for inclusion in the analysis. Both direct analysis and indirect analysis showed that saroglitazar was significantly superior to GLP-1RAs in improving ALT levels. Metformin improved ALT levels, but the effect was not as good as saroglitazar.

Conclusion

Saroglizatar was the most effective drug for improving NAFLD. INPLASY registration number: INPLASY202340066
Street Renaming as a Means of Symbolic Insult and a Diplomatic Slap in International Relations
Authors: Birnbaum Enav
Published: June 2023

This article finds that states can use street renaming as an act of retaliation against other international actors (states and international organizations). Specifically, it shows how states can employ street renaming to symbolically insult and thus diminish their opponent’s sense of self. After situating the practice of retaliatory street renaming within the study of emotions in international relations (IR), and symbolic insults in diplomacy, in particular, the article surveys a multitude of cases in which states used street renaming to humiliate and defy other international actors. To further substantiate this thesis, the article then delves into one illustrative case: Israel’s 1975 decision to rename all streets carrying the name of the United Nations ‘Zionism Street’ in response to UN General Assembly Resolution 3379, which determined that ‘Zionism is a form of racism and racial discrimination’. The article concludes by calling for more scholarly attention to street renaming and other symbolic acts in IR.

La dénomination des rues comme insulte symbolique et gifle diplomatique en relations internationales
Big-Data Driven Framework to Estimate Vehicle Volume Based on Mobile Device Location Data
Authors: Yang Mofeng , Luo Weiyu , Ashoori Mohammad , Mahmoudi Jina , Xiong Chenfeng , Lu Jiawei , Zhao Guangchen , Saleh Namadi Saeed , Hu Songhua , Kabiri Aliakbar , Ji Ya
Published: June 2023

Vehicle volume serves as a critical metric and the fundamental basis for traffic signal control, transportation project prioritization, road maintenance planning, and more. Traditional methods of quantifying vehicle volume rely on manual counting, video cameras, and loop detectors at a limited number of locations. These efforts require significant labor and cost for expansions. Researchers and private sector companies have also explored alternative solutions, such as probe vehicle data, although this still suffers from a low penetration rate. In recent years, along with the technological advancement in mobile sensors and mobile networks, the quantity of mobile device location data (MDLD) has been growing dramatically in spatiotemporal coverage of the population and its mobility. This paper presents a big-data driven framework that can ingest terabytes of MDLD and estimate vehicle volume over a larger geographical area with a larger sample size. The proposed framework first employs a series of cloud-based computational algorithms to extract multimodal trajectories and trip rosters. A scalable map matching and routing algorithm is then applied to snap and route vehicle trajectories to the roadway network. The observed vehicle counts on each roadway segment are weighted and calibrated against ground truth control totals, that is, annual vehicle-miles traveled and annual average daily traffic. The proposed framework is implemented on the all-street network in the State of Maryland using MDLD for the entire year of 2019. The results demonstrate that our proposed framework produces reliable vehicle volume and also its transferability and generalization ability.
Artificial Intelligence Aided Crowd Analytics in Rail Transit Station
Authors: Zhu Yadi , Ni Ke , Li Xiaohong , Zaman Asim , Liu Xiang , Bai Yun
Published: June 2023

Crowd analysis and management is a key area of study for transit agencies seeking to optimize their operations and to facilitate safety risk management activities. Key features of crowd analytics include passenger flow volume, crowd density, and walking speed. This study proposes a generalized artificial intelligence (AI)-based crowd analytics model framework for rail transit stations, by analyzing and visualizing crowd analysis data from video records of high-density crowds. Specifically, we propose a generalized AI-aided methodological framework (AI-Crowd) for calculating flow volume, crowd density, and walking speed. You Only Look Once (YOLO) and Deep SORT are integrated into the model framework to detect and track each individual’s dynamic position. Camera calibration is utilized to transform detected trajectories into a real-world coordinate system. Methods for calculating crowd dynamic metrics are formulated based on the data. To validate the model framework, several video records from a platform scenario at a major rail transit station are used. The model’s pedestrian counting accuracy can reach 95% and the fundamental diagrams of density–speed are shown to be consistent with empirical studies. Further crowd analysis of a stair scenario and a transferring passage scenario using the proposed model framework shows some differentiations in walking behavior. The methodology has further practical applications, such as monitoring social distancing.
Development and Evaluation of a MASH TL-3 Modified Single Wood-Post Skid-Mounted Sign Support System
Authors: Schulz Nathan , Bligh Roger
Published: June 2023

Previous crash testing determined that the conventional Texas Department of Transportation, U.S., single wood-post, skid-mounted temporary sign support system did not satisfy guidelines included in the American Association of State Highway and Transportation Officials Manual for Assessing Safety Hardware (MASH). Modifications were made to the system to improve impact performance and meet MASH requirements. The modifications included increasing the mounting height of the sign, installing weakening holes in the wood support post at a prescribed height, and adding a wire rope loop around the weakening holes to act as a hinge mechanism when sections of the wood sign support fracture during vehicle impact. Crash tests were performed on the modified system in accordance with the MASH Test Level 3 (TL-3) matrix for work-zone traffic control devices. The modified single wood-post, skid-mounted temporary sign support system with a 90 in. sign mounting height, weakening holes, and tether cable met the performance criteria for MASH TL-3 work-zone traffic control devices.