bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR002: Hypoxia-induced epigenetic changes coordinate transcription start site selection and translational control through remodeling of 5’UTRs
Authors: Watt Kathleen , Dauber Bianca , Szkop Krzysztof J , Lee Laura , Jovanovic Predrag , Chen Shan , Masvidal Laia , Tandoc Kristofersson , Palia Ranveer , Topisirovic Ivan , Larsson Ola , Postovit Lynne-Marie 
Published: November 2024

Abstract
Adaptation to hypoxia enhances cancer cell malignancy and negatively impacts patient outcomes. Reprogramming of mRNA translation is an essential component of the hypoxia-adaptive response. During hypoxia, cells undergo a global decrease in protein synthesis. However, translation of subsets of transcripts encoding stress-response, survival and stemness factors is increased. This selective regulation is thought to be governed largely via the interactions between specific mRNA features and remodeling of the translational apparatus. However, our understanding of the mechanisms that govern translational perturbations under hypoxia remains incomplete. Here, we interrogated the effects of hypoxia on global changes in histone methylation and transcription start site (TSS) selection, coupled with monitoring corresponding alterations in total mRNA levels and translation efficiencies on a genome-wide scale in T47D breast cancer cells and H9 human embryonic stem cells. This revealed widespread epigenetic alterations leading to TSS switching and extensive remodeling of 5’UTRs, and allowed us to map the impact of specific 5’UTR features on translation efficiency under hypoxia. Pyruvate Dehydrogenase Kinase 1 (PDK1), a key enzyme in orchestrating metabolic adaption to hypoxia, undergoes TSS switching leading to increased availability of efficiently translated 5’UTR isoforms, and we show that this effect is coordinated at an epigenetic level. Therefore, our findings uncover a mechanism driving translational reprogramming under hypoxia, whereby alterations in translational apparatus are orchestrated with epigenetic perturbations that result in 5’UTR remodeling of the transcriptome.
Citation Format: Kathleen Watt, Bianca Dauber, Krzysztof J Szkop, Laura Lee, Predrag Jovanovic, Shan Chen, Laia Masvidal, Kristofersson Tandoc, Ranveer Palia, Ivan Topisirovic, Ola Larsson, Lynne-Marie Postovit. Hypoxia-induced epigenetic changes coordinate transcription start site selection and translational control through remodeling of 5’UTRs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR002.
Abstract PR013: Identification, therapeutic potential, and regulatory networks of tumor suppressing miRNAs in angiosarcoma
Authors: Liu Bozhi , Murphy Ant , Benton Annaleighh , Gartenhaus Lauren E. , Hanna Jason A 
Published: November 2024

Abstract
Angiosarcoma (AS) is an aggressive cancer of endothelial cells arising in the blood and lymphatic vasculature. Among all the rare soft tissue sarcomas, AS patients have some of the worst outcomes, with an estimated 5-year survival rate of only 30%. In mouse models, we discovered that endothelial loss of miRNAs through the conditional deletion of Dicer1 leads to AS development. Since most cells, and even most cancer cells require some level of miRNA expression for survival, this demonstrates that endothelial cells are uniquely sensitive to miRNA loss mediated transformation. Consistent with this finding we have found that Dgcr8 deletion with aP2-Cre phenocopies Dicer1 loss resulting in AS with 100% penetrance. This implicates miRNAs as critical tumor suppressors in AS. Thus, we tested the repurposing of the antibiotic, enoxacin as an anticancer therapeutic based on its known potential to enhance miRNA processing. Indeed, enoxacin significantly reduces AS cell proliferation and migration. Small RNA-sequencing revealed that several known tumor suppressing miRNAs were increased in abundance following enoxacin treatment. To discover other miRNAs critical in AS, we conducted an unbiased CRISPR-Cas9 screen with a miRNA specific gRNA library and identified several potential candidates. Among these, our preliminary data indicates miR-410 as a potent tumor suppressor. To determine the miRNA and mRNA target interactome of these miRNAs in AS, we are utilizing AgoTRIBE. This method fuses the Ago2 miRNA effector protein to the RNA editing domain of ADAR2 to generate RNA edits on transcripts that are associated with Ago2-miRNAs as determined by RNA-seq. This work will further utilize in vitro and in vivo tools to dissect the underlying biology and role of these tumor suppressing miRNAs in AS. We aim to leverage these findings to develop novel strategies for therapeutic interventions, including miRNA-based approaches that may improve patient outcomes.
Citation Format: Bozhi Liu, Ant Murphy, Annaleighh Benton, Lauren E. Gartenhaus, Jason A Hanna. Identification, therapeutic potential, and regulatory networks of tumor suppressing miRNAs in angiosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR013.
Abstract 4138965: The Triglyceride-Glucose Index and Type 2 Diabetes are Mutually Independent Predictors of Major Cardiovascular Events in Patients With Established Cardiovascular Disease
Authors: Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H 
Published: November 2024

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established cardiovascular disease is unclear and is addressed in the present study.
We enrolled 1790 consecutive patients, 1481 with angiographically proven CAD and 309 with sonographically proven PAD. Prospectively, MACE were recorded over a mean follow-up period of 10.7±5.0 years.
At baseline, the TyG index was significantly higher in patients with T2DM (n=586) than in non-diabetic subjects (9.2±0.7 vs. 8.7±0.5; p<0.001). During follow-up, 916 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in non-diabetic subjects (60.2 vs. 47.7%; p<0.001). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.21 [1.12-1.30], p<0.001); HRs in patients without T2DM and in diabetic subjects were 1.08 [0.95-1.25], p=0.272 and 1.16 [1.03-1.31], p=0.013, respectively, with no evidence of an interaction between TyG and T2DM (p=0.093). With T2DM additionally entered into the regression model, TyG in the total study population predicted cardiovascular events independently from the presence of T2DM (HR 1.12 [1.03- 1.23], p=0.008), while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.42 [1.19-1.67]; p<0.001).
From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with CAD.
Abstract 4139432: The Mixing Enigma? Does Interchanging Leads and Generators Still Cause Concern in the MRI? Could this be the Final Device Hurdle for Routine MRI Patients?
Authors: Biederman Robert , WILLIAMS RONALD , Boltralik Mark , Lombardi Richard , Shah Moneal , Doyle Mark 
Published: November 2024

Background:
Over the last two decades substantial efforts have been aimed at improving acceptability of pacemakers and ICD's in the MRI scanner. Many labs have evaluated the construction, safety, efficacy, reproducibility and more recently, clinical impact value in such legacy devices. In conjunction, there has been extensive effort by the major vendors to develop safe MRI compatible devices. We believe that there remain few reasons for hesitation in more universal useage of any PM/ICD in the MRI bore. Yet, mixing vendor leads and generators remain a major hurdle considerably limiting contemporary MRI usage in
nearly
all MRI laboratories. Accordingly, we
Hypothesize:
mixed leads and generators have no distinct safety signal from common devices; whether CIED or non-CIED.

Methods:
We undertook a retrospective DB analysis to determine safety signals in those patients possessing mixed vendor leads and devices. Comparisons of impedance, amplitude, threshold and battery voltage and patient safety etc. were performed.

Results:
Patients from 5/2004 to 5/2024, representing 2008 pts with CIED (78%) and non-CIED (22%) underwent an MRI in a dedicated CMR Lab. The majority of the mixed cohort were obtained from the non-CIED cohort (>98%), having no need for generator replacement.

Accordingly, 12% of these underwent MRI to include: 76% neurologic, 7% orthopedic and 17% cardiac indications.
In safety signals comparisons between standard and mixed lead/generator implants, there were no differences in any implant parameters either pre-MRI or post-interrogation (p=NS). Similarly, there were no peri-MRI pt events reported in the 30d, 180d and 365 day post-MRI scan (p=NS). Importantly, especially for EP considerations, there were no added complications to interrogations.
Moreover, utilizing a similar approach to manipulation of MRI parameters for maximum safety intrinsic to dependent/non-dependent PM status was employed regardless of lead/generator configuration yielding no complications.

Conclusions:
Developing a similar approach to MRI scanning in those patients with mixed vendor lead/generator configurations yielded no difference in a multitude of safety, interrogation, devices and efficacy parameters implementing a similar device interrogation/programming strategy as in traditional devices. This reassurance derived from a large MRI lab suggests, despite inherent incompatibility concerns between vendors while in the magnetic field, suggests no such fears are truly warranted.
Abstract 4139646: Disparities in Palliative Care Utilization Among Patients With Heart Failure and LVAD implantation: A Nationwide Comparative Analysis
Authors: Haddad Enad , Nugooru Sudeep , Shah Shreeja , Sevella Prerana , Ginnaram Shravya , Samara Kamel , Janga Sai Shilpitha , Watson Robert 
Published: November 2024

Background:
Heart failure (HF) affects 6.7 million Americans and causes 500,000 deaths annually. Despite advancements in treatment, the 1-year mortality in advanced HF is 25-50%. Implantable left ventricular assist devices (LVAD) are critical for bridge-to-transplant or destination therapy, with 1-year and 2-year survival rates of 80% and 70%, respectively. At least 67% of LVAD patients have palliative care (PC) needs. However, PC involvement rates have been variable. The aim of this study is to measure the utilization of PC focusing on demographic disparities.

Methods:
Data was obtained from the National Inpatient Sample (NIS) 2021 database to identify patients with a principal diagnosis of HF (ICD I50.xx), secondary diagnoses of LVAD placement (Z45.2, Z95.811) and utilization of PC during encounter (Z51.5). Analysis was performed using SPSS statistical software.

Results:
Out of 5,688,355 adult hospitalizations in 2021, 1,048,573 patients were hospitalized with a primary diagnosis of HF. About 7.46% of HF patients received PC. Among these, patients over 75 years old, who constituted 44.4% of the cohort, accounted for 62.6% of PC involvement. PC consultation rates were similar between sexes. White patients made up 67.8% of the HF population but represented 73.6% of PC consultations, while other minority groups had a lower proportion of PC consultations.

LVADs were implanted in 0.09% of HF patients, with 69.5% between 50-74 years old. A significant gender disparity was noted; 76.6% of LVAD recipients were male, and 23.4% female.
PC was only involved in the care of 17.2% of LVAD patients. Age distribution of LVAD patients PC mirrored the overall LVAD cohort. Gender disparity persisted, with 80.4% of LVAD patients receiving PC being male, and 19.6% female. Racial disparities were less pronounced in this group.

Conclusion:
Despite proven benefits of PC involvement on the quality of life, psychological well being, and advanced care planning, specific guidelines in LVAD patients are yet to be established. This study underscores the need for more comprehensive guidelines promoting PC integration in the management of LVAD patients, and highlights demographic disparities in PC utilization among HF and LVAD patients.
Abstract 4139762: Structural and Functional Changes in the Left Atrium Following Arteriovenous Fistula Placement
Authors: Daniel Zachary , Leso John , Musumeci John , Hongalgi Krishnakumar , Torosoff Mikhail 
Published: November 2024

Background:
Arteriovenous fistula (AVF) remains the preferred method of vascular access in patients requiring long-term maintenance hemodialysis for end stage renal disease (ESRD). However, the AVF creates an acute left-to-right shunt, with the potential to cause high output heart failure.

RESEARCH QUESTIONS:
In patients with ESRD and AVF placement:

1) What is the effect of AVF on left atrial (LA) anatomy and function in patients with atrial fibrillation/atrial flutter (AF)?
2) What are the longitudinal effects of AVF placement on prevalence of AF?

Methods:
We retrospectively analyzed 179 consecutive ESRD patients who underwent AVF placement from 2008-2022 at a single tertiary academic center. Trans-thoracic or trans-esophageal echocardiograms were compared for each patient pre- and post-AVF placement. The median interval between echocardiograms was 2.3 years.

Results:
AF was noted in 19.0% of patients prior to AVF placement. An additional 11.2% of the overall cohort developed AF during the study period (59% interval increase). Patients with AF were older (p=0.002), had greater body surface area (p=0.037), and were more likely to have a history of diabetes (p=0.01), but otherwise there were no significant differences in baseline comorbidities.

AVF placement was associated with a significant increase in LA maximum volume in the overall cohort (70.0+/-32.2 mL post-AVF from 52.1+/-21.0 mL pre-AVF, p<0.001). In patients with AF, LA maximum volume was significantly larger post-AVF compared to those without AF (79.7+/-28.7 vs 60.8+/-26.8 mL, p=0.004). LA strain was significantly lower in patients with AF pre-AVF (42.8+/-11.7% vs 52.5+/-13.6%, p<0.001) and post-AVF (39.9+/-13.1% vs 49.9+/-14.4%, p<0.001). Incidence of newly reduced left ventricular ejection fraction post-AVF was 13% in patients with AF (7/54) compared to 6.4% (8/125, p=0.146) in those without.

Conclusion:
Patients who undergo AVF placement for ESRD are at significant risk for subsequent development of AF, with adverse hemodynamic consequences. Close monitoring of cardiac rhythm, anatomy, and function is warranted in the post-AVF cohort. Additional studies to examine optimal management of this vulnerable population are needed.
Abstract 4145955: In An Experimental Type 2 Diabetes Mellitus Model Induced With Streptozotocin, The Combined Use of Finerenone and Exenatide Reduced Inflammation and Oxidative Stress In The Heart and Kidney Tissues and Improved The Health of The Heart
Authors: gunek emirhan , Aydin Elif , Koldemir Gunduz Meliha , Kaymak Gullu , Kocak Ayse 
Published: November 2024

Introduction:
Cardiovascular problems are the primary cause of morbidity and death in people with diabetes mellitus.The whole nature of diabetic cardiomyopathy(DCM) is yet unknown.In order to investigate the pathogenesis of DCM and find possible treatment targets,animal models have proven invaluable.It has been common practice to create experimental models of type 2 diabetes(T2DM) using streptozotocin (STZ).Finerenone(F) is a selective mineralocorticoid receptor antagonist and reduces cardiovascular and adverse renal outcomes in diabetes.Exenatide(E) has been approved by the FDA to improve glycemic control in T2DM.

Aim:
The aim of this study is to investigate the possible cardiorenal protective effects of potential heart failure and chronic kidney injury associated with T2DM and to assess the potential therapeutic roles of Finerenone and Exenatide.To understand the interactions on cardiorenal outcomes of heart failure and diabetes and to effectively manage these two conditions.

Methodology:
Wistar
male rats with streptozotocin-induced T2DM were used.Five different groups were established as 1)Control,2)STZ,3)STZ+F,4)STZ+E,5)STZ+F+E groups.

During the 21-day experiment, blood glucose concentrations were measured in all animal experimental groups.
The kidney, heart tissues, and blood serum were collected. Serum urea and creatinine were exanimated.Total antioxidant status(TAS) and total oxidant status(TOS) were examined from blood serum,kidney,heart tissues by spectrophotometric assays. Kidney, heart tissues and blood IL-6, IL-1β, TNF-α gene expressions were examined by qPCR. Cardiac troponin T(cTnT) and troponin I(cTnI) gene expressions were examined by qPCR.p-STAT3 and p-NRF2 protein expressions in heart tissue were assessed by western blotting.

Results:
Serum urea and creatinine were significantly lower in STZ+E+F group than control group. TAS were significantly higher in STZ+E+F group than control group in serum,heart and kidney tissues.

TOS, IL-1β, IL-6, and TNF-α gene expressions were lower in STZ+E+F groups than control group significantly in serum, heart and kidney tissues.cTnT and cTnI gene expressions and p-STAT3 and p-NRF2 protein expressions were lower in STZ+E+F groups than control group significantly in heart tissues.

Conclusion:
This study demonstrates the potential beneficial effects of Finerenone and Exenatide on cardiorenal complications in T2DM. Evaluation of these drugs in treatment strategies and further clinical trials are recommended.
Abstract 4146225: Stress Perfusion Cardiac Magnetic Resonance Imaging for Pediatric Patients with Repaired Transposition of the Great Arteries
Authors: Chetan Devin , Thomas Subin , Smaili Hanan , Gill Navjot , Tassos VIvian , Lam Christopher , Yoo Shi-Joon , Valverde Israel , Seed Mike 
Published: November 2024

Introduction:
Patients who underwent arterial switch operation (ASO) for d-transposition of the great arteries (TGA) are at increased risk for early myocardial ischemia. Stress perfusion cardiac MR (SPCMR) is used as a non-invasive tool for risk stratification but interpretation is often challenging.

Hypothesis:
There is significant interobserver variability in SPCMR image interpretation in patients with repaired TGA.

Aims:

1. Determine incidence and severity of adverse effects of stress agents.
2. Evaluate incidence of positive SPCMR.
3. Assess agreement amongst reviewers in image interpretation.

Methods:
Patients with repaired TGA with SPCMR imaging from 2013 to 2024 were reviewed. Three patients with previous coronary intervention and one with severe chest pain after adenosine, unable to complete SPCMR, were excluded. 61 studies were performed in 56 patients. Images were independently reviewed by two investigators blinded to initial interpretation and clinical outcome. Perfusion defects were displayed on a circumferential polar plot using standard LV segmentation.

Results:
Median (IQR) age was 15 (11-17) years, weight 55 (36-68) kg, and BSA 1.6 (1.2-1.8) m2. Max heart rate was 110 (100-125) and systolic BP 127 (116-138). Eleven (20%) patients had cardiac symptoms, chest pain in 9 (16%), syncope in 1 (2%), pallor and distress in 1 (2%) infant. Adverse effects from SPCMR in 8/52 (15%) adenosine, 2/4 (50%) dobutamine, and 0/6 (0%) regadenoson were minor and resolved on stress completion. Six (10%) studies were initially interpreted as suspicious (n=5) or definitive (n=1) perfusion defect (Figure). No LGE was detected. Original interpretation did not match blinded reviews for 6 cases (Figure). Blinded reviewers agreed on 3 negative cases but interpretation differed in the other 3 cases (Figure).

Conclusions:
SPCMR is safe and feasible. Significant interobserver variability highlights the challenges in qualitative SPCMR interpretation for TGA. Quantitative perfusion may reduce interobserver variability. Larger multicenter studies would be helpful in further elucidating the risk profile of patient characteristics and coronary artery arrangements to determine whether routine use of SPCMR is warranted for TGA patients.
Abstract 4147769: Outcomes of Elevated Homocysteine in Heart Failure Hospitalizations. A Propensity Matched Retrospective Analysis
Authors: Evbayekha Endurance , Nelson Favour , Okorare Ovie , Palumbo Rachel , Ebong Imoh , Shamaki Garba Rimamskep , Bob-Manuel Tamunoinemi 
Published: November 2024

Introduction:
Elevated homocysteine (HC) predisposes individuals to a prothrombotic state and may increase the risk of poor outcomes, including strokes and deep venous thrombosis (DVT). Previous studies did not find any mortality benefit after normalizing serum homocysteine levels. However, studies on the impact of HC on outcomes such as peripheral vascular disease (PVD) and chronic limb ischemia (CLI) in heart failure (HF) are lacking. We aimed to address this gap.

Methods:
We examined the 2016 to 2021 Nationwide Inpatient Sample database and used the ICD-10 codes to identify the population with HF. We then stratified them into HC and non-HC groups. HC was defined as a composite of homocystinuria and methyltetrahydrofolate deficiency. Chi-square and Student T-test were used to compare continuous and categorical variables. A greedy neighbor 1:1 propensity score matching (PSM) followed by multivariable logistic regression models accounted for confounders and predicted the outcomes. Our primary outcomes were PVD and CLI, while secondary outcomes were ischemic stroke, pulmonary embolism (PE), and DVT.

Results:
There were 3,415 HF hospitalizations with HC, with a mean age of 66.6 + 14.8, and 55.9% (1,910) were females.

After PSM, 1,420 HC hospitalizations were matched to 1,420 no-HC hospitalizations.
Compared to the non-HC group, there was no difference in PVD 1.15 (0.96-1.37) and CLI 0.66 (0.28-1.51), each p> 0.05.
However, ischemic stroke 3.3 (2.30-4.69), PE 6.3 (3.46-11.51), and DVT 3.6 (2.26-5.8) were significantly associated with the HC group, p<0.005, each.

Conclusions:
Among the hospitalized population with heart failure, those with elevated homocysteine showed a higher association with ischemic stroke, DVT, and PE but no difference in peripheral vascular disease or chronic limb ischemia.