bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 4 from High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis
Authors: Chai Annie Wai Yeeng , Tan Yee Hua , Ooi Shiyin , Yee Pei San , Yee Shi Mun , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: November 2024

Gene expression analysis reveals that AZD5582-induced apoptosis is associated with inhibition of the NF-κB pathway and high TNF levels. A, Volcano plots showing the overall transcriptomic changes induced by AZD5582 treatment in sensitive and resistant OSCC cell lines. B, Heatmap of differentially up- or downregulated genes from the RNA-seq analysis of DMSO control and AZD5582-induced transcriptomic changes in sensitive and resistant OSCC cell lines. C, Venn diagram showing the number of differentially up- or downregulated genes upon AZD5582 treatment. D, Correlation plot of TNF expression from RNA-seq data of 21 OSCC cell lines with the natural log of IC50 (lnIC50). of AZD5582. E, Boxplot showing the difference in TNF expression between AZD5582-sensitive and AZD5582-resistant OSCC. F, Western blot showing the TNF protein level in AZD5582-sensitive and AZD5582-resistant OSCC. G, Dose–response curves (DRC) of BICR10 toward AZD5582 upon sensitization to increasing concentrations of recombinant TNF (rTNF).
Figure 2 from High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis
Authors: Chai Annie Wai Yeeng , Tan Yee Hua , Ooi Shiyin , Yee Pei San , Yee Shi Mun , Lightfoot Howard , Barthorpe Syd , Garnett Mathew J. , Cheong Sok Ching
Published: November 2024

Validation of AZD5582 as a potent anticancer drug in a subset of OSCC via on-target degradation of cIAP1/2. A, Gene dependency and characteristics of the 21 OSCC cell lines according to the order of the most sensitive (lowest IC50) to least sensitive (highest IC50) response to AZD5582. B, Boxplots of IC50 values for three IAP inhibitors from the initial discovery screen and the focused screen with six additional IAP inhibitors. C, Similarity matrix of all nine IAP inhibitors tested in the focused screen, as estimated by the pairwise Pearson correlation R score using IC50 values. D, Dose-dependent effect of AZD5582 on OSCC cells as measured by apoptosis assay. Barcharts show the percentage of apoptotic cells after treatment with increasing concentrations of AZD5582. Error bars represent the mean ± SD of two biological repeats, each with technical triplicate. An unpaired Student t test was used with an untreated control (0 nmol/L AZD5582) as the comparator. *, P < 0.05; **, P < 0.01; ***, P < 0.005; ns, not significant. E, Effect of AZD5582 on colony formation in sensitive and resistant OSCC cell lines. F, Baseline expression of AZD5582 putative targets cIAP1, cIAP2, and XIAP. G, Time-dependent effect of 10 nmol/L AZD5582 demonstrating the on-target degradation of IAPs, as measured by Western blotting.
Joint Anatomical, Histological, and Imaging Investigation of the Midbrain Target Region for Superolateral Medial Forebrain Bundle Deep Brain Stimulation
Authors: Coenen Volker Arnd , Zielinski Jana Maxi , Sajonz Bastian Elmar Alexander , Reinacher Peter Christoph , Thierauf-Emberger Annette , Wessolleck Johanna , Frosch Maximilian , Spittau Björn , Schläpfer Thomas Eduard , Baldermann Juan Carlos , Endres Dominique , Lagrèze Wolf , Döbrössy Máté Daniel , Reisert Marco
Published: November 2024

Introduction: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) is currently being researched in clinical trials and open case series as a therapeutic option for treatment-resistant major depressive disorder and treatment-resistant obsessive-compulsive disorder (TR-OCD). There are numerous publications describing stimulation in such proximity to the ventral tegmental area (VTA) and open questions remain concerning the stimulation target and its functional environment. As of right now, we are not aware of any publications that compare the typical electrode placements with the histologically supported tractographic depiction of the target structure. Methods: We used three cadaver midbrain samples with presumed unaltered anatomy. After fixation, staining and slicing, the histological samples were warped to the Montreal Neurological Institute (MNI) big brain environment. Utilizing a tractographic atlas, a qualitative analysis of the typical slMFB stimulation site in the lateral VTA utilizing a subset of clinically implanted DBS electrodes in n = 12 patients, successfully implanted for TR-OCD was performed. Results: A joint qualitative overlay analysis of predominantly tyrosine hydroxylase stained histology at different resolutions in an anatomical common space was achieved. Localization of the DBS lead bodies was found in the typical positions in front of the red nuclei in the lateral VTA. DBS lead tip region positions explained the oculomotor side effects of stimulation related to paranigral or parabrachial pigmented sub-nuclei of the VTA, respectively. The location of active electrode contacts suggests downstream and antidromic effects on the greater VTA related medial forebrain bundle system. Conclusion: This is the first dedicated joint histopathological overlay analysis of DBS electrodes targeting the slMFB and lateral VTA in a common anatomical space. This analysis might serve to better understand the DBS target region for this procedure.
Risk for Second Primary Ovarian Cancer: A Large Population Based on Surveillance, Epidemiology, and End Results Database
Authors: Hu Haiyang , Ren Yangsheng , Li Huixing , Zhang Tishuo , Sun Lin
Published: November 2024

Introduction: This study aims to evaluate the likelihood of developing a second primary ovarian cancer (OC) considering factors including age, race, and the types of initial malignancies encountered. Methods: This study employed a retrospective cohort approach, compiling data on individuals diagnosed with OC from the Surveillance, Epidemiology, and End Results (SEER) program databases spanning the years 1975–2019. The analysis used standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) to determine the likelihood of developing OC. The result was further refined by categorizing the data based on patient age, race background, first primary cancer types, the time elapsed since the second primary cancer diagnosis, and radiotherapy treatment. Results: A total of 1,536,151 patients with second primary cancer being OC were included. The SIR of the second primary OC was observed to be elevated among patients between the ages of 18–64 years (SIR: 1.09, 95% CI: 1.06–1.13). In contrast, for patients who were 65 years of age or older, the SIR for a second primary OC was found to be relatively lower (SIR: 0.87, 95% CI: 0.83–0.91). A lowering, however, not statistically significant, of the SIR of the second primary OC in patients with white race was presented. Within 2 months to 1-year diagnosis interval, the SIR of the second primary OC was highest (SIR: 1.48, 95% CI: 1.37–1.61). Liver, gallbladder, intrahepatic, and other bile ducts (SIR: 2.00, 95% CI: 1.38–2.81), and breast cancer (SIR: 1.20, 95% CI: 1.15–1.25) had higher SIRs of second primary OC. Conclusion: This study identifies age, ethnicity, the time span between the diagnoses, and the types of initial cancers as factors correlated with the occurrence of a second primary OC. Our findings suggest that targeted surveillance should be considered for high-risk groups.
Potential Cognitive Decline Linked to Electronegative L5 in Type 2 Diabetes: A Holo-Hilbert Spectral Analysis
Authors: Chou Ping-Song , Lee Mei-Yueh , Chang Wen-Sheng , Chou Mei-Chuan , Hsu Chung-Yao , Liou Li-Min , Juan Chi-Hung , Lai Chiou-Lian
Published: November 2024

Introduction: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cognitive impairment. In this study, we investigated the effect of L5 – an electronegative subfraction of low-density lipoprotein cholesterol (LDL-C) – on the cognitive function of patients with T2DM. Methods: This cross-sectional study included 68 patients with T2DM: 15 with normal cognitive function, 39 with mild cognitive impairment (MCI), and 14 with Alzheimer disease (AD). Cognitive evaluation was performed using the Cognitive Abilities Screening Instrument. We developed a new method – Holo-Hilbert spectral analysis (HHSA) – for analyzing electroencephalography signals. Using HHSA, we investigated the effects of L5 on patients’ neural activity. Results: Our findings suggested that a higher percentage of L5 in LDL-C (L5%) was independently associated with increased risks of MCI and AD in patients with T2DM. A negative correlation was observed between serum L5% and cognitive performance, particularly in the concentration subdomain, in patients with MCI. HHSA revealed that an elevated serum L5% value was correlated with an increase in low-frequency neural oscillations but a reduction in high-frequency oscillations in patients with MCI. However, no correlation was observed between L5, cognitive performance, and neural activity in patients with normal cognitive function or AD. Conclusion: Our findings demonstrate L5 to be an efficient biomarker and electroencephalography/HHSA to be an innovative approach for assessing cognitive function in patients with T2DM. L5 may affect frontal lobe function, leading to concentration deficits. The correlation between L5 and cognitive impairment appears to vary depending on the stage of neurodegeneration.
Correlation between Fundus Damage and Renal Function Deterioration in Chronic Kidney Disease Patients
Authors: Tang Min , Lin Lizhi , Liu Songtao , Li Zhicheng , Zeng Lingli , Hao Yan
Published: November 2024

Introduction: This study aimed to explore the correlation between the extent of fundus damage and the severity of chronic kidney disease (CKD). Methods: We collected data from 118 CKD patients, including general information, renal function indicators, and fundoscopic examination results. The stages of CKD and degrees of fundus lesions were graded. SPSS 25.0 software facilitated the analysis of correlations using Kendall’s tau-b correlation analysis and ordinal regression analysis. Results: Statistically significant differences were observed among multiple CKD stages in the distribution of age, systolic blood pressure, diastolic blood pressure, hemoglobin, total cholesterol, homocysteine, cystatin C, serum creatinine, blood urea, eGFR, 24-h urine protein, urine microalbumin, urine microalbumin/urine creatinine, and blood β2-microglobulin, complement C3. Notably, the levels of cytokeratin 19 fragment and transforming growth factor β significantly increased in all CKD stages. Kendall’s tau-b correlation analysis revealed a significant positive correlation between CKD stage and fundus lesion grade. Ordinal regression analysis indicated that sex differences, total cholesterol levels, and hemoglobin levels were significant predictors of fundus lesion risk. Compared with patients at stage 5 CKD, the risk of fundus damage is significantly lower in patients in stage 2 and stage 3, further demonstrating a positive correlation between renal function deterioration and increased risk of fundus damage. Conclusions: Routine fundus screening and early intervention for fundus lesions are vital for assessing CKD deterioration, providing new directions for future related research.
Association of Serum Ferritin Levels with Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study
Authors: Sun Jie , Qi Ying , Wang Yan , Wang Wenxin , Meng Pengpeng , Han Changjin , Chen Bing
Published: November 2024

Background: This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study seeks to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients with SA-AKI. Methods: This retrospective cohort study utilized clinical data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including all patients with SA-AKI admitted to the intensive care unit for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan-Meier curves and Cox regression models were employed to evaluate the association between serum ferritin levels and mortality. Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results indicated that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, patients in the highest quartile of serum ferritin had significantly higher 28-day mortality compared to those in the reference group (the first quartile of ferritin levels). After adjusting for various factors, the fully adjusted hazard ratio was 1.92 (95% CI: 1.24–2.96, p = 0.003). Conclusion: In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.
Avaliação institucional da política de transparência da Assembleia Legislativa do Ceará: percepções dos deputados e servidores
Authors: Barros Antonio Teixeira de , Lima Maria Érica de Oliveira , Nascimento Willber da Silva
Published: November 2024

This study evaluates on the perceptions of parliamentarians and civil servants about the transparency policy of the Legislative Assembly of the state of Ceará. Its methodology consisted of applying an electronic questionnaire with 89.13% of the deputies and 80.21% of the employees. The perception of state deputies shows a predominance a positive view in practically all aspects. The view of the servants also describes a positive evaluation, especially among men and veterans who have worker longer in the communication services of the institution.
Comunicação pública e transparência: questões conceituais para a pesquisa
Authors: Locatelli Carlos , Luz Ana Javes , Pecoraro Caroline
Published: November 2024

Este trabalho discute as interpretações predominantes no Brasil sobre comunicação pública e transparência em busca de regularidades, diferenças e complementaridades. Percebe-se nos autores estudados a tendência de ancorar os conceitos às perspectivas participativo-deliberacionistas de democracia e empoderamento da sociedade civil. Nota-se que, ao escolherem um dos conceitos como centrais à abordagem, tendem a considerar o outro dado. Conclui-se que modelagens teóricas que incorporem uma relação conceitual dual podem responder de forma mais robusta a questões que envolvam transparência e comunicação pública.
Comunicação e ativismo institucional na Amazônia: análise das coordenadorias de gênero e raça em Belém
Authors: Sarmento Rayza
Published: November 2024

Este artigo analisa como a comunicação da Prefeitura de Belém evidencia as dinâmicas de ativismo institucional que ocorrem na gestão atual. A análise foca na comunicação pública das Coordenadorias da Mulher e Antirracista, que têm em seus quadros ativistas dos movimentos feminista e negro. O corpus empírico é composto por 87 notícias sobre os dois órgãos publicadas no portal da prefeitura (Agência Belém) durante o atual mandato, bem como por entrevistas com funcionários(as) das pastas supracitadas.
Políticas de Comunicação Pública em Universidades: UFG e UFSM em análise
Authors: Stasiak Daiana , Kegler Jaqueline Quincozes da Silva
Published: November 2024

Las instituciones públicas de enseñanza superior de Brasil llevan en su misión los presupuestos básicos de la comunicación pública, ya que su foco es formar a ciudadanos para promover la transformación y el desarrollo de la sociedad. Aun así, las universidades federales se encuentran en un escenario en el que cerca del 70% todavía no cuentan con políticas de comunicación aprobadas por sus consejos de educación superior. En este contexto, este artículo hace una reflexión crítica a partir de un estudio comparativo de dos universidades federales y propone ejes temáticos y categorías de contenido pertinentes a las políticas de comunicación.
Abstract 4114705: Clinical Predictors of Stress Induced Cardiomyopathy
Authors: Marwaha Bharat
Published: November 2024

Introduction:
Stress Induced Cardiomyopathy is increasingly becoming more prevalent with increasing awareness about disease condition with annual incidence of 30 cases/100000 per year and an incidence of 1-2% in the patients presenting with acute coronary syndrome.[1] Physical and emotional triggers have been linked with occurrence of Stress induced Cardiomyopathy.

Methods:
We have obtained the National Readmission database for the year of 2020. We have used the ICD 10 code I51.81 for stress induced cardiomyopathy and found 10450 patients in the data base. Total 494 patients had cardiac arrest and 191 patients out of this 494 had died. We have used Binary logistic regression methods to find the odd ratio for physical and emotional risk factors for stress induced cardiomyopathy.

Results:
Grief disorder with an odd ratio of 7.2, followed by female gender with an odd ratio of 4.1, septic shock with an odd ratio of 3.3, Hemorrhagic stroke with an odd ratio of 1.73, ischemic stroke with an odd ratio of 1.72, depression with an odd ratio of 1.5, followed by asthma exacerbation with an odd ratio of 1.35 and seizure disorder with an odd ratio of 1.34 were among the few predictors for stress induced cardiomyopathy. Incidence of Cardiac Arrest was 4.7% and mortality rate of 1.8% was observed in the patients with stress induced Cardiomyopathy.

Discussion:
Extreme emotional and physical triggers like stroke, septic shock are among few significant risk factors for the stress induced cardiomyopathy.
Abstract 4114716: Concurrent Ethanol Infusion with Pulsed Field Ablation Augments Electroporation of Porcine Atria
Authors: Koya Taro , Otsuka Naoto , Tri Jason , ying yang , Sauer William , Asirvatham Samuel , Nguyen Duy
Published: November 2024

Background:
Pulsed field ablation (PFA) is a promising modality for treatment of cardiac arrhythmias. PFA increases cell permeability, thereby promoting cell apoptosis. Although greater PFA energy may produce larger lesions, it also carries risks of side effects such as arcing, hemolysis, and microbubbles. Chemical ablation using ethanol (EtOH), such as with injection of the Vein of Marshall, has been used to treat atrial myocardium for refractory atrial arrhythmias.

Hypothesis:
We hypothesize that PFA in the atria can increase EtOH uptake through PFA-generated pores, thereby augmenting ablation efficacy by utilizing the cell permeability effects of PFA.

Aim:
The aim of this study is to investigate the effects of local EtOH infusion after PFA on lesion size in porcine atria.

Methods:
The atria of five porcine subjects were ablated
in vivo
with low PFA power settings (250V, at 20μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared electrogram voltage amplitude reduction and ablation lesion parameters before and after PFA.

Results:
A total of 14 control lesions and 14 EtOH lesions were analyzed. There was significant difference in voltage reduction between two groups (
Figure 1A-B
). On gross pathology, there were significant differences in ablation lesion maximum surface diameter, lesion depth, and volume between the 2 lesion sets (
Figure 1C
).

Conclusion:
Concurrent EtOH infusion after PFA enhanced acute efficacy of electroporation in porcine atria. Adjuvant therapy has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Further studies to assess chronic efficacy are warranted.
Abstract 4119535: Aspirin Use and Cardiovascular Disease Incidence in Adults with High Lipoprotein(a): A Multi-Cohort Study
Authors: Colantonio Lisandro , Wang Zhixin , Ghazi Lama , Alanaeme Chibuike , Christenson Ashley , Dubal Medha , Malick Waqas , Levitan Emily , Rosenson Robert , Bittner Vera
Published: November 2024

Introduction:
There is an active debate about who may benefit from taking aspirin to reduce their incidence of cardiovascular disease (CVD). Some prior cohort studies with small sample size suggest that aspirin use may be associated with a lower incidence of CVD or coronary heart disease (CHD) in adults with Lp(a) ≥50 mg/dL but not in those with Lp(a) <50 mg/dL, a hypothesis that needs confirmation.

Research question:
Does the association of aspirin use with incident CVD or CHD vary by Lp(a) among US adults?

Methods:
We analyzed publicly available data from adults without CVD at baseline in the ARIC (n=13,085, mean age 54 years), CHS (n=3,956, mean age 72 years), and MESA (n=6,324, mean age 62 years) studies. Lp(a) ≥50 mg/dL was defined as high. Participants were followed for incident CVD (myocardial infarction, stroke, or CVD death) and CHD (myocardial infarction or CHD death; median follow-up: ARIC 26 years, CHS 12 years, MESA 14 years). Hazard ratios associated with aspirin use were calculated after propensity score matching (primary analysis) and in all participants using multivariable adjustment (secondary analysis). Mixed-effects models were used to obtain pooled hazard ratios.

Results:
Aspirin use was 25.1% in ARIC, 29.6% in CHS, and 19.9% in MESA. In MESA, adults taking aspirin were older, had higher blood pressure, and were more likely to have diabetes and a low estimated glomerular filtration rate and to be taking antihypertensive medication and a statin versus those not taking aspirin. These differences were attenuated or not present in ARIC and CHS. The CVD incidence rate per 1,000 person-years (95%CI) was higher in adults with versus without high Lp(a): 16.3 (15.3-17.4) and 12.5 (12.1-13.0), respectively, in ARIC, 35.8 (31.5-40.1) and 32.3 (30.6-34.0) in CHS, and 10.8 (9.1-12.4) and 8.2 (7.5-8.9) in MESA. Aspirin use was not associated with CVD or CHD incidence in adults with or without high Lp(a) in the primary analysis (
Figure
). No association between aspirin use and CVD or CHD incidence was present in the secondary analysis using multivariable adjustment (data not shown).

Conclusion:
The association of aspirin use with CVD and CHD incidence did not differ by Lp(a) in this multi-cohort study.
Abstract 4119595: Impact of Environmental Noise and Sleep Health on Pediatric Hypertension Incidence: The ABCD Study
Authors: Ferreira De Moraes Augusto Cesar , Nascimento-Ferreira Marcus , Ma Martin Y. , Hoelscher Deanna
Published: November 2024

Background:
Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored.

Research Question:
How does the interaction between neighborhood environmental noise and sleep health affect the incidence of pediatric hypertension?

Aims:
To estimate the incidence of hypertension in American adolescents and to investigate the individual and joint effects of exposure to neighborhood environmental noise and sleep health on its incidence.

Methods:
Our analysis involved 3,320 individuals from the Adolescent Brain Cognitive Development (ABCD) study across 21 US cities, followed prospectively from 2018-2020 (T0) to 2020-2022 (T1). We included only those with complete data: Fitbit-tracked sleep, blood pressure, height, neighborhood noise, and relevant covariates (biological sex, ethnicity, pubertal stage, waist circumference). Hypertension was defined as average blood pressure at or above the 95th percentile for age, sex, and height, based on American Academy of Pediatrics guidelines. Sleep health was classified based on daily duration into three categories: healthy (9-12 hours), moderately healthy (1 hour below or above optimal), and low (more than 1-hour deviation). Neighborhood noise exposure was quantified using median anthropogenic noise levels at night, linked to participants’ zip codes. We estimated hypertension incidence and its relative risks (RR, 95% CI), examining the effect (individual and joint) of sleep health and environmental noise on hypertension risk.

Results:
At Time 1 (T1), the mean age was 13.9 years; 47.6% were girls, and 52.9% were White. Hypertension prevalence in 2018-2020 was 1.7% (CI95% 1.4; 2.1), and the incidence after two years was 2.9% (CI95% 2.4; 3.6). Night noise was 58.4 decibels, 29.9% healthy sleep time (T0); 20.3% healthy sleep time (T1). Adolescents with more favorable healthy sleep showed a lower risk of developing hypertension RR= 0.63 (CI 95% 0.25 to 0.82). We found no association between noisy neighborhoods and no joint effects (neighborhood noise + sleep health) with hypertension incidence.

Conclusions:
Adequate sleep is associated with a lower risk of hypertension in adolescents. However, no significant link was found between neighborhood noise and pediatric hypertension. This highlights the need for public health efforts to improve sleep quality in youth.
Abstract 4120573: Abrupt cardiac rupture of the patient with ATTR amyloidosis
Authors: Tagata Kento , Yutaro Nomoto , Tao Koji , Kataoka Tetsuro , Ohishi Mitsuru
Published: November 2024

A Japanese male in his 80s was admitted to our emergency department with chest pain. His prior history was syncope and ventricular tachycardia. Transthoracic echocardiography (TTE) revealed thickening of the basal part of the antero-septal wall and thinning of the basal part of the inferior wall. Coronary angiography (CAG), cardiac MRI and blood test revealed no specific abnormalities. The day before his emergency admission, he visited the cardiology outpatient department for a periodic examination of cardiac hypertrophy. ECG, chest X-ray, and TTE were unchanged from his prior examination. However, that night, he experienced chest pain and was transferred to our hospital. On arrival, his vital signs were critical, with a blood pressure of 70/59 mmHg. ECG indicated ST elevation in antero-lateral leads. TTE detected pericardial effusion, and contrast-enhanced CT identified two focal areas of non-enhancement in the myocardium and pericardial effusion without signs of aortic dissection. CAG revealed no significant stenosis or obstructive lesion. During coronary angiography, the patient deteriorated to asystole. Cardiopulmonary resuscitation and percutaneous pericardial drainage were initiated. Hemorrhagic pericardial effusion was aspirated. Immediate surgical hemostasis was undergone, revealing about 2 cm lacerations and hematoma in the anterior and inferior wall. After surgery, he complained of abdominal discomfort. Esophageal gastrointestinal endoscopy was undergone to investigate the abdominal discomfort, and he was diagnosed with early gastric cancer. Endoscopic submucosal dissection (ESD) was undergone, and histopathological examination revealed adenocarcinoma and eosinophilic amorphous materials deposited in the submucosal vessels. Congo red staining of the submucosal vessels revealed orange-red areas. A technetium-99m pyrophosphatase scintigraphy showed Grade 2 uptake in the heart. Transthyretin (TTR) staining was positive in the specimen from ESD, leading to a diagnosis of TTR amyloidosis. Genetic test for TTR was negative, which led to a diagnosis of wild-type TTR amyloidosis and tafamidis was started. In cases of acute pericardial effusion and/or cardiac rupture, it is imperative to consider cardiac amyloidosis as a potential etiology, in addition to myocardial infarction and aortic dissection, especially in patients with left ventricular wall thickening, neuropathy, or abnormal ECG, also known as “red flag”.
Abstract 4122348: APOL1 Risk Variants and Risk of Incident Atrial Fibrillation in Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Ahmad Muhammad , Kazibwe Richard , Mostafa Mohamed , Naeem Rimsha , Singh Sanjay , Bansal Nisha , Soliman Elsayed
Published: November 2024

Background:
Apolipoprotein L1 gene (APOL1) G1 and G2 risk variants (RVs) have been associated with the progression of chronic kidney disease in individuals of recent African descent. However, the association of APOL1 RVs with atrial fibrillation (AF) is unknown and may help identify individuals at risk.

Aim:
To examine the association of APOL1 RVs with incident AF in the Systolic Blood Pressure Intervention Trial (SPRINT).

Methods:
This post-hoc analysis included SPRINT participants free of AF at baseline who had baseline APOL1 and follow-up AF data. Cox proportional hazard regression models were used to examine the risk of AF for Black individuals with high-risk APOL1 (2 RVs) compared with low-risk (0-1 RVs) (reference). Additionally, three analyses were performed: a comparison of the risk of AF between all Black and White participants, Black participants with low-risk APOL1 RVs and White participants, and Black participants with high-risk APOL1 RVs and White participants.

Results:
2,254 Black and 4694 White participants were included in the analysis. During a median follow-up of 2 years, there were 16 and 134 cases of incident AF among Blacks and Whites, respectively. In a multivariable-adjusted model, compared with Black individuals with low-risk APOL1 RVs, high-risk APOL1 RVs were associated with approximately 3.5 times greater risk of AF. This association was stronger among participants without chronic kidney disease (CKD) compared to those with CKD (hazard ratio (HR) (95% confidence interval (CI)), 6.01 (1.44-25.0) vs. 2.98 (0.21-41.7), respectively, interaction
p
-value=0.11). Compared to White participants, all Black and Black participants with low-risk APOL1 RVs had a significantly lower risk of AF. In contrast, Black individuals with high-risk APOL1 RVs had a similar risk of AF compared to White participants (
Table
).

Conclusions:
In hypertensive, non-diabetic Black participants, high-risk APOL1 RVs are associated with a higher risk of AF, and these individuals had an AF risk comparable to White participants. These hypothesis-generating findings underlie the need for future investigation to confirm this association and whether APOL1 status can explain racial differences in the risk of AF.
Abstract 4123631: Significance of collagen triple helix repeat-containing protein 1 as a right ventricular biomarker in pulmonary hypertension
Authors: Nishiura Kazuto , Yokokawa Tetsuro , Katahira Masataka , Miura Shunsuke , Sato Akihiko , Shimizu Takeshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Yoshihisa Akiomi , Sugimoto Koichi , Fukushima Kenji , Nakazato Kazuhiko , Takeishi Yasuchika
Published: November 2024

Background:
Right ventricular failure is a major prognostic determinant of pulmonary hypertension and progresses with myocardial fibrosis. Extracellular matrix proteins play a major role in myocardial fibrosis. Right ventricular biomarkers for right ventricular function and fibrosis are poorly examined in pulmonary hypertension. This study investigated the significance of collagen triple helix repeat-containing protein 1 (CTHRC1), one of the extracellular matrix proteins, as a right ventricular biomarker.

Methods and Results:
A monocrotaline-induced pulmonary hypertension rat model was used in this study. CTHRC1 expression in the right ventricle was higher in rats with monocrotaline-induced pulmonary hypertension than in controls. CTHRC1 was associated with fibrosis in the rat's right ventricle. Next, human circulating CTHRC1 levels were evaluated in controls (n = 20), pulmonary arterial hypertension (PAH, n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64). Human circulating CTHRC1 levels were higher in PAH (P = 0.006) and CTEPH patients (P = 0.011) than in controls (Figure). Human circulating CTHRC levels were correlated with tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), right ventricular fractional area change (R = -0.225, P = 0.017), and right ventricular global longitudinal strain evaluated by magnetic resonance imaging (R = 0.429, P = 0.009). In addition, human circulating CTHRC1 levels were decreased after balloon pulmonary angioplasty (P < 0.001) in CTEPH patients.

Conclusions:
CTHRC1 could be a novel biomarker associated with right ventricular failure and fibrosis in pulmonary hypertension patients.
Abstract 4123637: Prevalence of Invasively Diagnosed Coronary Endothelial Dysfunction in Patients with Chest Pain and Normal Coronary Flow Reserve: The Systematically Missed Diagnosis on Non-invasive Testing
Authors: Srinivasan Sharanyah , altamirano alvaro , Bhogadi sai , Kubba Saad , Corban Michel
Published: November 2024

Background:
Invasive coronary reactivity testing (CRT) is the gold standard for comprehensive assessment of coronary endothelial and microvascular dysfunction in patients with angina and non-obstructive CAD (ANOCA). Non-invasive imaging modalities (PET and CMR) have emerged as potential alternatives. However, due to the inability to systemically administer acetylcholine, patients with normal coronary flow reserve (CFR) but abnormal endothelial function on invasive Ach testing are systemically missed on non-invasive testing. We aimed to assess the prevalence of coronary endothelial dysfunction in ANOCA patients with normal CFR.

Methods:
Consecutive patients undergoing CRT at our institution were included. Those with normal adenosine-based CFR (>2.5), were further stratified as having normal coronary endothelial function (NEF, <20% epicardial coronary diameter constriction and >50% increase in coronary blood flow in response to ACh) vs abnormal endothelial function (AEF, >20% epicardial coronary diameter constriction and/or <50% increase in coronary blood flow in response to Ach). We then assessed the proportion of AEF patients who would have been otherwise diagnosed with normal coronary physiology based on CFR alone on non-invasive testing.

Results:
37 patients underwent CRT. Mean age was 55 years ± 25, 68% were females. 25 out of 37 patients (68%) had normal CFR. Of those patients, 17 (68%) patients had AEF. Distribution of coronary epicardial vs microvascular endothelial dysfunction is represented in Fig. 1.

Conclusion:
68% of ANOCA patients with normal CFR had coronary epicardial and/or microvascular endothelial dysfunction and would have otherwise been labeled as ‘normal coronary physiology’ by non-invasive microvascular function testing. Our findings re-enforce the need for comprehensive invasive CRT for accurate comprehensive diagnosis of patients with ANOCA.
Abstract 4123653: Association of Inflammatory Bowel Disease with the Risk of Atrial Fibrillation: A Meta-Analysis
Authors: Goyal Aman , MAHALWAR GAURANGA , Jain Hritvik , Kanagala Sai Gautham , Locke John
Published: November 2024

Background:
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a prevalent condition associated with chronic noninfectious inflammation of the gastrointestinal tract. It has been hypothesized that chronic inflammation can predispose patients to atrial fibrillation (AF), with proposed mechanisms being structural remodeling of atrial tissue, autonomic dysfunction, and oxidative stress; however, no clear evidence exists to support this.

Aims:
Our meta-analysis aims to pool all existing data to determine if there is an increased risk of AF in patients with IBD, providing more robust evidence on the matter.

Methods:
A systematic literature search was conducted using major databases (PubMed, EMBASE, and SCOPUS) aimed at studies focusing on AF development in patients with IBD. Further subgroup analyses were performed for ulcerative colitis (UC) and crohn’s disease (CD). Risk ratios (RR) with their corresponding 95% confidence intervals (CI) were pooled using a random-effects model in the Review Manager Software. Statistical significance was set at p < 0.05.

Results:
Seven studies with 88,893,407 patients were included (1,002,719 and 87, 890, 688 patients in the IBD and non-IBD groups, respectively). IBD patients were at an increased risk of developing AF [RR: 1.52; 95% CI: 1.19-1.95; p=0.0009] compared to the non-IBD group. In subgroup analyses, patients with UC were at an increased risk of developing AF [RR: 1.29; 95% CI: 1.08-1.53; p=0.004], as were CD patients [RR: 1.30; 95% CI: 1.07-1.58; p=0.008] compared to the non-UC and non-CD groups, respectively (Figure 1).

Conclusion:
Patients with IBD are at nearly 1.5 times the risk of developing AF compared to the non-IBD population. Our meta-analysis was limited by heterogeneity among the studies, highlighting the importance of further large-scale prospective studies to establish more robust evidence and determine the real-world clinical significance of our findings. Furthermore, future research should explore the impact of confounding variables such as disease severity, medication usage, and lifestyle factors on the observed association between IBD and AF.
Abstract 4128491: Dietary N-3 Very-Long-Chain Polyunsaturated Fatty Acids Improve Retinal Function And Reduce Aortic Atherosclerosis In ApoE-Deficient Mice
Authors: Yang Zhihong , Kun Julia , Pryor Milton , Brock Daniel , Mondal Anupam , Lydic Todd , Sato Seizo , Yamazaki Isao , Yamaguchi Hideaki , Rojulpote Krishna Vamsi , Tang Jingrong , Xie Hairui , Shi Zhen-Dan , Swenson Rolf , Swaroop Anand , Remaley Alan
Published: November 2024

Introduction:
N-3 very-long-chain polyunsaturated fatty acids (VLCPUFA; C≥24), which are found primarily in retina and a few other select tissues, are known to play critical roles in specific biological systems. Although n-3 PUFA, such as eicosapentanoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), may confer cardiovascular benefits, they did not improve age-related macular degeneration (AMD), a leading cause of blindness worldwide, in clinical trials. The activity of ELOVL fatty acid elongase 2 (ELOVL2), an enzyme that converts EPA into tetracosapentaenoic acid (TPA, C24:5 n-3), is known to decrease in the retina with age due to promoter methylation.

Hypothesis:
We hypothesized that dietary VLCPUFA may delay or prevent AMD, by bypassing the ELOVL2-mediated lipid elongation step. We also hypothesize that VLCPUFA may benefit cardiometabolic health like shorter-chain n-3 PUFA through similar mechanisms.

Aims:
We aimed to investigate the effect of dietary VLCPUFA on retinal function and cardiometabolic risk factors in mice.

Methods:
We have produced a new fish oil that contains ~40% (w/w) of C24-C28-rich VLCPUFA. We fed 9-month-old ApoE -/- mice with normal or VLCPUFA fortified diet (1% or 3% (w/w)) for 8 weeks, and age-matched C57BL/6J mice were used as control. We conducted electroretinography (ERG) and cognitive ability tests at the end of feeding period. In
in vitro
studies, we performed PPAR reporter assay and investigated the anti-inflammatory effects of TPA in lipopolysaccharide-stimulated RAW264.7 cells.

Results:
Supplementation of VLCPUFA showed a significant and dose-dependent improvement in ERG response. Like EPA and DHA, we also observed favorable cardiometabolic changes and decreased atherosclerotic plaque area due to dietary VLCPUFA. Intriguingly, VLCPUFA supplemented aging mice exhibit better cognitive performance compared with control. Transcriptome analysis revealed that VLCPUFA-enriched fish oil favorably regulated genes involved in nuclear receptor signaling pathways, lipid metabolism and inflammation. Furthermore, purified TPA potently activates PPARs, and suppressed inflammation in macrophage cells.

Conclusions:
Overall, our studies revealed for the first time several potential health benefits for our new VLCPUFA-enriched fish oil in several age-related diseases and support its future development as a new dietary supplement.
Abstract 4133846: Even Mild Increase in Pulmonary Arterial Pressure Following Kidney Transplantation is Associated with Increased Mortality
Authors: Zeder Katarina , Kundu Suman , siew edward , Birdwell Kelly , Freiberg Matthew , Kovacs Gabor , Brittain Evan , Maron Brad
Published: November 2024

Background:
In end-stage renal disease (ESRD), elevated systolic pulmonary artery pressure (sPAP) is common, attributed to post-capillary pulmonary hypertension (PH) and associated with adverse outcomes. Kidney transplantation (KT) may mitigate ESRD-PH. We aimed to profile sPAP trajectory in a national cohort of ESRD patients pre- and post-KT, and link findings to clinical outcome.

Methods:
We analyzed retrospectively all patients within the Veterans Affairs Healthcare System undergoing KT between 2000-2019 with sPAP recorded pre- and post-KT by echocardiography. PH was defined by >35mmHg. Patients were assigned to one of the following groups: Never PH, New PH post-KT, Resolved PH post-KT, and Persistent PH. Spline curve and Kaplan-Meier analyses were used to test the association of sPAP or PH group with all-cause mortality, adjusted for age and sex.

Results:
From 631 patients (median 62 [IQR 58-65]yr; 97% male), there were 231 (36.6%), 184 (29.2%), 133 (21.1%), and 83 (13.1%) patients in the Persistent PH, Never PH, Resolved PH, and New PH groups, respectively. Never PH, Resolved PH and New PH had, overall, similar cardiopulmonary comorbidities (
Tab. 1
). By contrast, Persistent PH had the highest rate of congestive heart failure, atrial fibrillation, and impaired diastolic relaxation assessed by E/E’. Creatinine post-KT, indicative for graft function, was stable in Never PH, Resolved PH and Persistent PH, but significantly increased in New PH. Of all groups, Resolved PH was associated with the most favorable survival rate (HR 0.73 [95%CI 0.51-1.05], p=0.087). New PH and Persistent PH were associated with a 51% (HR=1.51 [95%CI 1.06-2.15], p=0.023) and 37% (HR=1.37 [95%CI 1.03-1.82], p=0.029; referent group for all: Never PH) increase in adjusted mortality risk post-KT (
Fig. 1a
). Overall, we observed 21% (HR=1.21 [95%CI 1.11-1.31], p<0.001) increase in mortality hazard adjusted for age, sex and baseline sPAP, per 10mmHg increment increase in sPAP from pre-KT to post-KT whereas a 10mmHg sPAP decrease was associated a 17% decrease in mortality (HR=0.83 [95%CI 0.76-0.90], p<0.001) (
Fig. 1b
).

Conclusion:
These data suggest that PH is common post-KT and includes a sizeable group of patients without PH pre-KT. Increased PAP or failure for PH to resolve post-KT were independently associated with mortality. Overall, these data warrant prospective studies in sex-balanced cohorts that use PH to stratify KT candidacy and PAP as a longitudinal biomarker of graft function post-KT.
Abstract 4134305: Intraoperative indicators depending on QRS morphology are required to narrow QRS width during CRT implantation
Authors: Mine Takanao , Terao Soichiro , Sugitani Miho , Kogame Takehiro , Ishihara Masaharu
Published: November 2024

Introduction:
Various indicators to detect the most delayed electrical or mechanical activation site of left ventricular (LV) have been studied using intracardiac electrocardiogram or speckle tracking echocardiogram to narrow QRS width in patients with cardiac resynchronization therapy (CRT).

Hypothesis:
Unusual intraoperative indicators are required to narrow QRS width in patients with non-LBBB (left bundle branch block) during CRT implantation.

Methods:
Nineteen patients (14 men, 71±12yrs, 7 with left bundle branch block: LBBB / 10 non-LBBB / 2 pacing-depend, 6 ischemic cardiomyopathy, LVEF 29.6±8.9%, QRS 152±28ms) underwent CRT implantation. Q-LV (an interval from QRS onset to LV potential), RV-LV (from RV to LV), RVp-LV (from RV pacing to LV), and S-QRS (from LV pacing stimulation to QRS onset) were measured in multi-sites of coronary sinus (CS) veins using a 5 mm spacing 2Fr 8-polar catheters. Q-peak strain (an interval from QRS onset to peak radial strain) was evaluated by speckle tracking echocardiogram in each LV segment during sinus rhythm (SR) and RVp. QRS narrowing was defined as the difference between the QRS interval during SR (or RVp) and the QRS interval with biventricular pacing.

Results:
Parameters were evaluated in 17±7 (8-32) sites of 1.9±0.9 (1-4) CS branches in each patient. In LBBB patients, longer Q-LV during SR, extended RV-LV during SR, and lengthy Q-peak strain during SR were associated with QRS narrowing. Shorter S-QRS during LVP and longer RVP-LV during RVP were related to QRS narrowing in non-LBBB patients. (Table)

Conclusion:
Suitable indicators depending on QRS morphology are required for QRS narrowing in CRT implantation. The parameters using speckle tracking echocardiogram to detect mechanical LV delay sites might not be useful in patients with non-LBBB.
Abstract 4134309: From Heartache to Headache: Cryptococcal Meningitis Post-Heart Transplant in a Chronic Hepatitis B and Sarcoidosis Patient
Authors: Kingma Tyler , Singh Kerry , Feingold Andrew , Scatola Andrew
Published: November 2024

Introduction:
We report the case of a heart transplant patient on chronic immunosuppression diagnosed with cryptococcal meningitis. Up to 5% of solid organ transplant patients develop cryptococcosis, carrying a 50% mortality rate in central nervous system involvement.

Case Presentation:
This is a 57-year-old male with a past medical history of heart failure with reduced ejection fraction (HFrEF) status post orthotopic heart transplantation (on prednisone 7.5 mg daily, mycophenolate, tacrolimus and sirolimus), pulmonary sarcoid, and chronic hepatitis B (on tenofovir and entecavir) who presented with headache, nausea, vomiting and seizure-like activity. The patient’s heart rate was 129 beats per minute, blood pressure 188/92 mmHg, but was afebrile. He eventually underwent a lumbar puncture with the cerebrospinal fluid (CSF) positive for cryptococcal antigen (1:2560). The patient was started on liposomal amphotericin B and flucytosine. Mycophenolate and sirolimus were held in the setting of his infection. The patient’s hospital course was complicated by acute kidney injury likely secondary to elevated tacrolimus levels while on fluconazole. He was ultimately discharged with plans to repeat CSF studies as an outpatient.

Discussion:
Here we report a case of cryptococcal meningitis in a heart transplant patient in the context of pulmonary sarcoidosis, chronic hepatitis B and quadruple immunosuppression. Of note, as part of rejection surveillance, the patient undertook serial AlloSure and AlloMap testing. Sirolimus was added to his regimen due to persistently elevated AlloSure scores. Indeed, immunosuppressive agents are the leading risk factor for cryptococcosis in organ transplant patients. Our patient also has two important risk factors for cryptococcal infection. Firstly, sarcoidosis is associated with T-cell dysregulation, compromising cell-mediated immunity. Additionally, hepatitis B carriers have an increased predisposition for cryptococcal infections, notwithstanding that our patient had been on dual antiviral therapy.

Conclusion:
Quadruple immunosuppression in heart transplant patients, especially in the context of risk factors such as sarcoidosis and hepatitis B infection, can result in cryptococcal meningitis and should be considered in patients with suggestive symptoms. Effective prophylactic regimens for such higher risk patients may be a potential area for further investigation.