bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4142541: Chronic heart failure associates with activation and clonal expansion of T cells with predicted autoreactive capacity
Authors: Abplanalp Wesley , Merten Maximilian , Rasper Tina , Cremer Sebastian , John David , Speer Thimoteus , Leistner David , Hoffmann Jedrzej , Bonig Halvard , Knosalla Christoph , Potapov Evgenij , Sarapki Tamim , Mustafic Emina , Berkowitsch Alexander , Zeiher Andreas , Dimmeler Stefanie 
Published: November 2024

Background:
Chronic heart failure (HF) is characterized by adverse remodeling and persistent inflammation, leading to impaired heart function and poor prognosis. While the acute immune response post-myocardial infarction (MI) is well-studied, the role of the immune system in chronic HF remains unclear. This study aims to elucidate the response of T cells to HF.

Methods and Results:
In a cohort of 188 HF patients and healthy controls (HC), flow cytometry of peripheral blood revealed an increase in T cell memory/effector cells (HF=65%, HC=53% activated T cells) and a reduction in naïve T cells in HF patients. Additionally, antigen-presenting cells (APCs) displayed a higher immune stimulatory profile (e.g., HLA-DR, ICAM-1, TREM-1). Immune secretome analysis supported the chronic inflammatory state with significantly elevated serum levels of sICAM-1, IL6, and TNFRI in HF patients.

Phenotyping of peripheral blood T cells showed a decline in T central memory cells (TCM) and an increase in CD4+ Th17 and CD8+ T effector memory cells in HF patients compared to healthy controls. This decline in TCM cells and the increased expression of the homing marker CCR5 on T cell subsets were associated with poor prognosis in HF. T cell receptor (TCR) sequencing revealed reduced TCR diversity (p=0.03) and clonal expansion in circulating and cardiac T cells of HF patients. Epitope prediction modeling identified 22 unique human-derived epitopes specific to HF, suggesting potential autoreactivity.
Single-cell RNA sequencing (scRNA-seq) of CD45+ sorted cardiac and circulating cells confirmed clonal TCR expansion in the heart and blood of HF patients. Post-MI mouse models demonstrated an accumulation of pro-inflammatory Th17 T cells in the heart at days 14, 28, and 48, with later time points showing more pronounced pro-inflammatory profiles.

Conclusion:
Chronic HF is associated with persistent T cell activation and clonal expansion, potentially contributing to adverse remodeling and poor prognosis through autoimmune mechanisms. These findings provide insights for therapeutic cardio-immunological interventions targeting T cell responses in HF.
Abstract 4142625: Ultrasonic Evaluated Endothelial Dysfunction Highly Predicts Future Diabetic Evolution And Development Of Fatal Events
Authors: Murakami Tatsuaki 
Published: November 2024

Introduction:
Although diabetes mellitus (DM) and endothelial dysfunction are thought to affect atherogenic processes, we know little about the clinical impact of endothelial dysfunction on evolutional mechanisms of DM.

Hypothesis:
This study assessed hypothesis that endothelial dysfunction accelerates diabetic evolution and adverse clinical events.

Methods:
Endothelial dysfunction was graded by reactive changes in lumen diameter of right brachial artery following transient forearm occlusion (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with stable coronary artery disease using high-resolution ultrasonography.

The enrolled patients were categorized into 3 groups according to the values of FMD, and their glucose tolerance and adverse clinical events were followed-up for 36 months or more. We prospectively followed up diabetic evolution, which was defined as newly diagnosed DM by 75g-OGTT or new administration of an antidiabetic agent.

Results:
For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD<4%; Group-L, n=174), more frequently manifested diabetic evolution [Group-L versus Group-M with mild endothelial dysfunction (4%≤FMD<8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, n=173): 25 (14.4%) versus 12 (7.0%) plus 7(4.0%), p<0.001, by Kaplan-Meier analysis].

The patients in Group-L more frequently resulted in fatal events [Group-L versus Group-M plus Group-H: 15(8.6%) versus 4(2.3%) plus 2(1.2%), p<0.001].
HbA1c significantly elevated in Group-L (5.9±0.6 to 6.2±0.9, p=0.009) but not in Group-M or in Group-H.
Cox proportional hazard model analysis including clinical variables showed that severe endothelial dysfunction was a significant predictor for future diabetic evolution (hazard ratio=2.69, p=0.011) and all-causal death (hazard ratio=5.87, p=0.009).

Conclusions:
This is the first clinical ultrasonic vascular investigation demonstrating that endothelial dysfunction accelerates diabetic evolution and causes excess of fatal events and strategies based on practical status of endothelial dysfunction are required for metabolic and prognostic management.
Abstract 4144467: Associations between High-density Lipoprotein Cholesterol Efflux and Brain Health
Authors: Giacona John , Wang Jijia , Zhang Rong , Kelley Brendan , Hajjar Ihab , Thomas Binu , Lacritz Laura , Yu Fang , de Lemos James , Rohatgi Anand , Vongpatanasin Wanpen 
Published: November 2024

Previous studies have linked plasma levels of high-density lipoprotein cholesterol (HDL-C) with impaired cognitive function. However, few studies have investigated the associations between plasma HDL functionality and brain structure and function. Thus, our study aimed to elucidate the associations between plasma HDL measures and brain structure/function in a multiethnic cohort of middle-aged adults.
Accordingly, we conducted a cross-sectional study in 1,826 adults (mean age 51.0±9.7 years, 58% female, 47% Black adults) without preexisting cardiovascular disease or stroke who participated in the Dallas Heart Study to determine associations between HDL measures and brain structure/function. Whole brain white matter hyperintensities (WMH) and grey matter volume (GMV) was measured using a 3-T MRI scanner and normalized to total cranial volume (TCV), and the Montreal Cognitive Assessment (MoCA) was used to measure cognition. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages and was expressed in arbitrary units. HDL particle measures were assessed using NMR spectroscopy. Adjusted multivariable linear regression models were performed with standardized beta estimates reported.

Higher HDL-CEC and small HDL particles (HDL-P) were positively associated with GMV/TCV after adjustment for relevant risk factors (β=0.078 [95% CI: 0.029, 0.126],
Figure
, and β=0.063 [95% CI: 0.014, 0.111], respectively, all p<0.05). Conversely, there were no associations between HDL measures and WMH or MoCA after adjustment (all p>0.05). Associations of HDL-CEC and small HDL-P with GMV were not modified by race/ethnicity or ApoE-ε4 status.

In conclusion, higher HDL function and small HDL-P were associated with higher GMV after adjustment for traditional risk factors and were not modified by race/ethnicity or ApoE-ε4 carrier status. As such, these findings suggest that better HDL functionality is linked with larger brain GM volume in middle-aged adults. Since GMV loss has been linked to the development of mild cognitive impairment (MCI) and conversion of MCI to Alzheimer's disease, our study may have implications for prevention of age-related decline in cognitive function.
Abstract 4144537: Recurrent Myocarditis and Ventricular Arrhythmias Associated with Vascular Endothelial Growth Factor Inhibitor Use and Rechallenge
Authors: Roberts Jacob , Garcia Lizette , Yang Eric , Do Duc , Aksoy Olcay , Salavati Ali , Khakpour Houman , Chmielowski Bartosz , Stein-Merlob Ashley 
Published: November 2024

Introduction:
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy has been associated with cardiotoxicity, particularly hypertension. Cardiomyopathy and ventricular arrhythmias (VA) have rarely been reported.

Case Report:
A 51-year-old male with metastatic sarcoma on pazopanib, a VEGFR-TKI, for the past 4 years presented with 1 month of increasing palpitations and lightheadedness leading to a fall. On arrival, telemetry showed paroxysmal AF with RVR rates to 120 bpm followed by incessant runs of NSVT with rates 200-240 bpm. Initial labs included BNP 191 pg/mL and HS troponin-I 6 ng/L (<5 ng/L). Lidocaine infusion, amiodarone infusion, and metoprolol were required to reduce NSVT burden. Initial TTE revealed LVEF of 30-35% from baseline 55-60%. Coronary angiography showed no significant CAD. Cardiac MRI was negative for LGE or metastatic involvement. Cardiac PET-CT revealed moderate diffuse FDG uptake with focal enhancement suggestive of an inflammatory process. Pazopanib was stopped and the patient started on GDMT and prednisone taper for treatment of myocarditis.

At 2 months follow up, TTE revealed LVEF improved to 45-50% and ambulatory rhythm monitoring showed rare PVCs and few NSVT episodes. Repeat cardiac PET-CT revealed resolution of myocardial inflammation.
Due to sarcoma progression, the patient started on regorafenib, another VEGFR-TKI, 3 months after initial hospitalization. About 3 weeks later, he presented with frequent NSVT which required lidocaine and amiodarone infusions for arrhythmia control. Repeat cardiac PET demonstrated myocarditis recurrence. He received intravenous pulse dose steroids followed by prednisone taper and was transitioned to oral mexiletine and amiodarone with resolution of VA. Review of ambulatory rhythm monitoring 1 week following regorafenib initiation already showed 20.6% burden of ventricular ectopy and >8000 NSVT episodes.

Discussion:
This patient had an unusual, delayed presentation of VEGFR-TKI induced myocarditis presenting with significant VA. Although TKI induced myocarditis is rare and the mechanism is not well understood, recurrence of myocarditis in this case with an alternative agent indicates a possible medication-class effect.
Abstract 4144964: Low-Dose IL-2 Lowers Arterial Inflammation and Trends Towards Lower MACE in patients with ACS: The results of the IVORY trial and IVORY FINALE study
Authors: Sriranjan Rothwell Rouchelle , Zhao Tian , Hoole Stephen , Bond Simon , Tarkin Jason , hubsch Annette , Helmy Joanna , Bumanlag-Amis Elaine , Jalaludeen Navazh , Templin Heike , Brubert Jacob , Krishnan Unni , O'Brien James , Rudd James , Cheriyan Joseph , Mallat Ziad 
Published: November 2024

Major adverse cardiovascular (CV) events (MACE) occur in a substantioal percentage of individuals following acute coronary syndromes (ACS), primarily driven by residual vascular inflammation. Anti-inflammatory drugs have improved CV outcomes but their use is limited by significant side-effects. Low-dose interleukin 2 (IL2) increases regulatory T (Treg) cells, which are powerful endogenous regulators of the immune response, and could provide a new, targeted anti-inflammatory strategy in high-risk ACS patients. In IVORY, we hypothesised that treatment with low-dose IL2 would reduce arterial inflammation measured by
18
F-fluorodeoxyglucose (
18
F-FDG) positron emission tomography/computed tomography (PET/CT), compared to placebo. In IVORY FINALE we hypothesised that low dose IL2 could reduce MACE compared to placebo at follow up (up to 5 years.)

IVORY was a double-blind, placebo-controlled, Phase IIb trial randomising ACS patients with high-sensitivity CRP levels ≧ 2mg/L to receive either 1.5×10
6
IU IL2 or placebo (1:1). Dosing consisted of a daily induction (5 days) and a weekly maintenance phase (7 weeks).
18
F-FDG-PET/CT imaging of the ascending aorta and carotid arteries was performed before and after treatment. The primary outcome was the difference in the mean maximum target-to-background ratio (TBRmax) in the index vessel on follow-up imaging between the groups.

60 patients (IL2:placebo, n=31:29) completed the trial. Arterial inflammation in the index vessel was lower at the end of treatment in the IL2 group than in placebo (TBRmax = -0.171[-7.7%], 95% CI -0.308 to -0.034, p=0.015)[Fig1]. In more inflamed areas with a mean TBRmax ≧ 2 (active slices), the difference between the groups was greater (-0.185 [-8.3%], P=0.009, 95% CI -0.323 to -0.0478). Overall, the additive treatment effect of low-dose IL2 was greater at higher baseline inflammation [Fig 2]. Low-dose IL2 significantly increased circulating Tregs compared to placebo (p<0.001) [Fig 3]. There was no difference between the groups for changes in effector T cells. It was well-tolerated in ACS. At a median follow-up of 2.5 years, a trend towards lower MACE in the IL2 group (number of events [n]=0), compared to placebo (n= 7; 2 deaths, 2 non-fatal MIs, 3 unplanned revascularisations) was seen.
In summary, in high-risk ACS, immunomodulation with low-dose IL2 produces a safe and significant reduction in arterial inflammation, compared to placebo. Larger trials are needed to confirm its impact on CV outcomes.
Abstract 4144999: Cardiac Magnetic Resonance Imaging in Tetrology of Fallot Patients and Relationship to Obesity
Authors: Dusza Patrick , Tran Andrew , Hor Kan 
Published: November 2024

Obesity is associated with increased cardiovascular risk and adverse cardiac changes such as left ventricular hypertrophy (LVH) and in TOF higher body mass index (BMI) contributed to increase risk. Previous multicenter study concluded that right ventricular (RV) dysfunction contributed to cardiovascular event. Current recommendations for pulmonary valve replacement (PVR) in TOF patients use indexed RV endiastolic volume (RVEDVi) to determine timing of PVR. In the presence of obesity, RVEDVi may underestimate the severity of RV volume load. We sought to determine both diastolic (RVEDV) and systolic (REVSV) volume in obese and non-obese patients and the impact of the volume on right ventricular ejection fraction (RVEF).
We conducted a retrospective study of adult TOF patients > 18 years age in obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) patients with a cardiac magnetic resonance imaging (CMR) prior to PVR for pulmonary regurgitation (PR). CMR database and electronic records were reviewed to compare anthropometric, demographic, and CMR variables between obese and non-obese patients.
Table 1 shows demographic and CMR results between non-obese (n = 57) and obese (n = 32) patients. Indexed ventricular volume were smaller in obese compared to non-obese patients (LVEDVi 78.7±12.1 vs 84.3±14.9 mL/m2, p=0.04; RVEDVi 157.4±21.5 vs 169.4±32.7 mL/m2, p=0.03), in contrast the non-indexed volume were significantly larger (LVEDV, 166.7±32.9 vs 148.8±30.5 mL, p=0.006; RVEDV 333.1±61.3 vs RVEDV 297.6±56.6 mL, p=0.004). There is an association with ventricular volume with lower RVEF. In both groups the mean RVEF was abnormal but not different (43.2±8.7 vs 43.8±8.4%, P=NS). Patients with lower RVEF trended towards a lower LVEF especially in the obese group (Figure 1A-F).
Our study showed that indexed ventricular volume was smaller in obese patients and may lead to false reassurance suggesting underestimation of the volume load from the PR. Our patients have lower RVEF which correlated with larger volume and evidence of ventricular-ventricular interaction with lower LVEF in patients with lower RVEF. When assessing timing of PVR in asymptomatic TOF patients, other parameters beyond indexed volume in those with elevated BMI should be considered including ejection fraction and different methods of indexing RV volume similar to LVM. Future larger and longitudinal studies are needed to determine if delayed repair in obese patients lead worse remodeling and outcomes.
Abstract 4145065: All Things in Moderation: Right Ventricular Moderator Band Induced Ventricular Fibrillation In A Young Male
Authors: Kamran Wali , Pusukur Bharani , Sutton Peter , Rao Yash , DeBoer Rebecca , Al-Mohamad Talal , Cossu Sergio , Patel Kunal 
Published: November 2024

Idiopathic ventricular fibrillation (VF) arrest can be a challenging diagnosis, especially when the etiology is unclear. We present a case of a young male who was found to have VF originating from the right ventricular (RV) moderator band (MB).
A 19-year-old male with a history of idiopathic VF arrest with ICD placement presented with a complaint of sudden dizziness and lightheadedness. Upon device interrogation, he was found to have 17 seconds of fine-VF terminated by one out-of-hospital ICD shock. He reported non-adherence to daily nadolol. He was also noted to have a high burden of unifocal premature ventricular contractions (PVC) on telemetry. On EKG the morphology of PVCs was of a LBBB with a superior axis, suggesting origin from the MB. The patient then underwent an electrophysiological (EP) study, where it was felt that earliest site of activation was identified at the mid-inferior RV along a muscle band extending from mid inferior free wall, superiorly to the interventricular septum. He then had successful radiofrequency ablation at this site, with no post-ablation PVCs or ICD discharge, and was subsequently restarted on his home nadolol.
Idiopathic VF is defined as VF in the absence of clinical cause. Our patient’s PVCs and fine-VF were highly suspicious for RV MB origination. We proceeded with EP mapping and identified the earliest site of PVC activation at the MB. Pace mapping revealed 95% matching at this site. Following ablation, no further PVCs were induced even with isoproterenol. Though not fully understood, the MB is becoming increasingly noted as a source for Purkinje-mediated ventricular arrhythmias. Possible mechanisms of arrhythmogenesis include fibrosis, stretching of fibers, and ion channel variations. Arrythmias from the MB are potentially responsive to catheter ablation.
Early recognition of typical PVC morphology from the RV MB as the source of VF can provide an opportunity for timely intervention. Younger patients, especially, can be treated with catheter ablation to reduce their risk of sudden cardiac death.
Abstract Su403: Iterative Simulation to Optimize Mechanical CPR Device Application
Authors: Lauer Caroline , Wilhelm Kelsey , Leon Elizabeth , Howard Kim , Cook Shane , Schlesinger Shira 
Published: November 2024

Mechanical chest compression devices (MCDs) are commonly used for in-hospital and emergency department (ED) cardiac arrest resuscitation. Manufacturer guidelines and educational materials demonstrate that in the prehospital setting, MCDs can be deployed with an interruption in CPR of less than 15 seconds. No similar materials exist for the in-hospital environment, where observational studies have noted median CPR interruptions of up to 40 seconds for MCD deployment. With the integration of extracorporeal CPR (eCPR) into OHCA systems of care, the need to transfer patients with ongoing CPR to MCDs in the ED is growing.
To develop a hospital-specific procedure for receiving a patient in cardiac arrest and deploying the MCD with minimal no-flow time.
We used an iterative participatory design process to develop a procedure for receiving patients in cardiac arrest from Emergency Medical Services (EMS). Tasks included transferring a patient, replacing defibrillator pads, and deploying the hospital MCD with minimal no-flow time. Participants including ED physicians, nurses, and respiratory therapists performed a series of simulations using a high-fidelity manikin, resuscitation equipment, and an MCD. Simulations were followed by focused debriefings, participant-directed modification of the working procedure, and repeat simulation until participants expressed satisfaction with the procedure. Participant roles were shuffled after each round. The primary outcome was the duration of CPR interruption required to deploy the MCD; change in this time over successive iterations was assessed using a Wilcoxon signed-rank test. The final procedure described a sequence of steps and responsibilities that participants deemed efficient and reproducible.
Through seven simulation-debriefing cycles, CPR interruption associated with MCD deployment decreased from 19 to 10 seconds (p = 0.033). The most common failure modes that participants corrected during modifications involved needed equipment that was out of reach, obstructed provider positioning, and poorly defined roles. On subsequent days, two additional groups of on-shift ED providers deployed the MCD in less than 15 seconds following the developed procedure.
Using an iterative design process, we created an MCD deployment procedure that minimized CPR interruptions and was acceptable to hospital staff. This represents an effective, low-cost methodology to design a process for transfer of care during CPR and MCD deployment.
Understanding Indo-Canadian Sikh Women’s Challenges after Covid-19
Authors: Morve Roshan K. , Bose Neilesh 
Published: November 2024

Abstract
This paper focuses on Indo-Canadian Sikh women’s issues after Covid-19 and their challenges of diasporic consciousness. It is based on a study conducted with face-to-face interviews in Victoria, Canada, to assess these women’s post-Covid-19 challenges in healthcare and employment and their diasporic dual identity crisis. The research addressed questions like: What are the challenges of Indo-Canadian Sikh women in Canada after Covid-19 and the impact of current political affairs? What are women’s integration challenges (perhaps insecurity, discrimination, etc.)? This research is significant for understanding the difficulties of Indo-Canadian Sikh women as a vulnerable group in terms of diasporic dual consciousness, racial discrimination and post-Covid experiences. Discussions on identity incorporate a diasporic theoretical understanding of the dual identity crisis and elaborate on Canadian multicultural policy from a political perspective.