bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns, Potential Teratogenicity, and Associated Factors of Drugs Prescribed to Pregnant Women Attending Antenatal Care Units in Debre Tabor Comprehensive Specialized Hospital, Debre Tabor, Northwest Ethiopia
Authors: Alemu Muluken Adela , Zewdu Woretaw Sisay , Ferede Yared Andargie , Zeleke Mulugeta Molla , Ayele Teklie Mengie , Assefa Abraham Nigussie , Zeleke Tirsit Ketsela , Kassie Achenef Bogale
Published: November 2024

Background: About 80% of pregnant women use at least one medication during their pregnancy period. Many drugs that are not allowed to be used during pregnancy (from FDA Pregnancy Categories D and X) were used. Irrational use of these drugs during pregnancy may result in different birth defects, as explained by thalidomide and diethylstilbestrol’s tragedy. Knowledge of drug utilization and associated factors that affect the pattern is important to enhance rational prescribing. But information about prescription patterns and associated factors among pregnant women is scarce in the Debre Tabor area and generally in Ethiopia.

Objective: This study was aimed at assessing drug prescription patterns, potential teratogenicity, and associated factors among pregnant women attending the antenatal care unit at Debre Tabor Comprehensive Specialized Hospital, Debre Tabor, Northwest Ethiopia.

Methods: A retrospective cross‐sectional study design was performed on 359 pregnant women attending antenatal care units from June 01, 2022, to August 30, 2022, in the hospital. Necessary data were obtained through a questionnaire by reviewing the medical charts of the women. Analysis of the data was performed using SPSS Version 23. The association of the independent variables to medication use was assessed using multivariate logistic regression. A p value of less than 0.05 was considered significant.

Results: Most of the study participants (325/359) were married (90.5%). From a total of 359 participants, 350 (97.5%) were prescribed with drugs. About 64% (385/602) of the prescribed medications were iron and vitamins. The most commonly prescribed medications are iron and folic acid combination (340/602, 56.5%), albendazole (48/602, 8%), mebendazole (37/602, 6.1%), omeprazole (33/602, 5.5%), followed by amoxicillin (32/602, 5.3%). The majority (79.3%) of the drugs were from FDA Pregnancy Categories A and B. Prescribed drug utilization was more probable in women who first visited the facility at their second (AOR = 2.91, 95% CI [1.12–6.64]) and third trimesters (AOR = 4.32, 95% CI [1.37–6.81]), had chronic illness (AOR = 7.54, 95% CI [2.34–14.68]), and live in rural areas (AOR = 2.47, 95% CI [1.56–8.43]).

Conclusion: The study revealed that the prescription pattern in the hospital is in line with the WHO reference. Age, gravidity, number of ANC visits, first visit to the facility, presence of chronic illness, educational status, and residency were significantly associated with prescription drug use in pregnant mothers. But still, some pregnant women received drugs that may have teratogenicity risk (FDA Category C).
A Multimodal Low Complexity Neural Network Approach for Emotion Recognition
Authors: Rodriguez Aguiñaga Adrian , Ramirez Ramirez Margarita , Salgado Soto Maria del Consuelo , Quezada Cisnero Maria de los Angeles
Published: November 2024

This paper introduces a neural network‐based model designed for classifying emotional states by leveraging multimodal physiological signals. The model utilizes data from the AMIGOS and SEED‐V databases. The AMIGOS database integrates inputs from electroencephalogram (EEG), electrocardiogram (ECG), and galvanic skin response (GSR) to analyze emotional responses, while the SEED‐V database continuously updates EEG signals. We implemented a sequential neural network architecture featuring two hidden layers, which underwent substantial hyperparameter tuning to achieve optimal performance. Our model’s effectiveness was tested through binary classification tasks focusing on arousal and valence, as well as a more complex four‐class classification that delineates emotional quadrants for the emotional tags: happy, sad, neutral, and disgust. In these varied scenarios, the model consistently demonstrated accuracy levels ranging from 79% to 86% in the AMIGOS database and up to 97% in SEED‐V. A notable aspect of our approach is the model’s ability to accurately recognize emotions without the need for extensive signal preprocessing, a common challenge in multimodal emotion analysis. This feature enhances the practical applicability of our model in real‐world scenarios where rapid and efficient emotion recognition is essential.
Response of Hot Pepper (Capsicum annuum) to Potassium Nitrate Seed Priming
Authors: Dagne Belay Andarge , Duga Jima Nego , Hirpa Gerba Daba
Published: November 2024

Hot pepper (Capsicum annuum L.) is the most important cash crop in Ethiopia. However, the poor quality of the seed affects germination and seedling performance of hot pepper. Therefore, this study was initiated to investigate the germination and seedling growth response of hot pepper to potassium nitrate (KNO3) seed priming at Jimma, southwest Ethiopia under laboratory conditions. A laboratory experiment was conducted to study the effects of KNO3 concentrations, which consists five levels of KNO3 concentration (0%, 0.5%, 1%, 1.5%, and 2% KNO3), nonprimed seed as a control, and the experiment was laid out in a randomized complete block design (RBCD) with four replications. The results of the study showed that all KNO3 concentrations significantly (p  < 0.05) increase germination percentage, rate, seedling height, dry weight, and seedling vigour‐I and seedling vigour‐II except at 2% KNO3 concentration as compared to control. But at 1% KNO3 concentration, there was more pronounced result on the abovementioned response variables (90 cm, 9.67 cm, 9.01 cm, 2.75 mg, 811.48 mg, and 247.3 mg, respectively). Even though, this treatment resulted the most pronounced effect, KNO3 concentrations at 0.5% KNO3, 0% KNO3 (distilled water only) seed priming had also resulted higher germination percentage, rate, seedling height, dry weight, and seedling vigour‐I and seedling vigour‐II. Correlation analysis of the positive and significant relationship was observed between germination percentage, root length, shoot length, seedling dry weight, seedling fresh weight, seedling vigour index‐I and vigour index‐II, etc. Negative correlation was observed between germination rate and other mentioned parameter in the above. Therefore, we alternatively recommend these two (0.5% and 1%) levels of KNO3 concentration and more promisingly distilled water due to its simple priming protocol and availability for both subsistence and commercial type of farmers.
Supplementary Table 5 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

List of 142 significant positively correlated drug-gene pairs
Figure 5 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

AZD5582 acts on OSCC predominantly via triggering CASP8-dependent apoptosis. A, Western blot showing CASP8 protein expression in wild-type and mutant OSCC (red). B, Dose–response curve on the effect of CASP8 knockout (KO) on AZD5582 sensitivity in ORL-215. C, Dose–response curve on the effect of CASP8 KO on AZD5582 sensitivity in ORL-174. D, Western blot showing the levels of apoptotic and necroptotic markers in CASP8 KO cells. E, Dose–response curve toward AZD5582 upon CASP8 KO and/or RIP3 KO, confirming the involvement of RIP3-dependent necroptosis in mediating the effect of AZD5582. F, Western blot confirming CASP8 and/or RIP3 KO in ORL-174.
Data 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

Abstract
Drug repurposing can accelerate the development of novel therapeutic strategies. Oral squamous cell carcinoma (OSCC) is prevalent in Asians and is associated with poor prognosis. In this study, we integrate newly generated sensitivity data for 339 anticancer drugs with genome-wide CRISPR-Cas9 gene essentiality data for 21 cell lines mostly derived from Asian patients with OSCC to identify drug repurposing candidates. We observe potent activity of AZD5582 (an antagonist of the inhibitor of apoptosis family of proteins) in a subset of OSCC cells, which was associated with dependency on NF-κB pathway genes (RNF31, MAP3K7, and IKBKG). We confirm the on-target specificity and potency of AZD5582 in vitro and its ability to suppress cell growth in xenograft models. Furthermore, we identify TNF as a key mediator of AZD5582 sensitivity in OSCC. Caspase-8–dependent apoptotic and Caspase-8–independent necroptotic cellular programs mediate AZD5582-induced cell death. In summary, through the systematic integration of pharmacologic and CRISPR data, we identified a subset of OSCC with potent sensitivity to AZD5582 mediated through the NF-κB and TNF signaling pathways.
Significance:
Mechanistically guided drug repurposing has been made possible by systematically integrating pharmacologic and CRISPR-Cas9 screen data. Our study discovers the biomarker and cell death mechanisms underpinning sensitivity toward AZD5582, an antagonist of the inhibitor of apoptosis family protein. Our findings have important implications for improving future trial design for patients with OSCC using this emerging drug class.
Barriers to cultural participation by people with disabilities: a qualitative investigation about Lollapalooza Brazil (2022)
Authors: Lacerda Igor , Brennand Jorgiana Melo de Aguiar , Freitas Ricardo Ferreira
Published: November 2024

This study examines the inclusion of people with disabilities at Lollapalooza (2022) based on the perspectives of digital influencers with disabilities. Despite the festival’s professed commitment to inclusivity, it falls short in accommodating these influencers, highlighting mobility and autonomy challenges due to accessibility issues, hindering their full participation. This study emphasizes superficial measures in fostering genuine inclusion and advocates for substantive efforts to ensure the participation and enjoyment of all individuals in public events and spaces.
(Re)conceituando a comunicação pública para enfrentar a desinformação
Authors: Rothberg Danilo
Published: November 2024

La comunicación pública puede proveer una pluralidad de perspectivas e información con una contextualización, precisión y confiabilidad adecuadas. Este artículo tiene como objetivo aplicar la metodología de revisión sistemática de la literatura para reconstituir, de manera original, respuestas a preguntas urgentes en el área. Así, recupera aspectos comunes de la conceptualización específica en Brasil, señala su contribución a la formación de identidades democráticas y al enfrentamiento a la desinformación, y revisa y problematiza sus bases jurídicas, además de sugerir mejoras oportunas.
Comunicação pública e movimentos sociais: práticas para construção da cidadania na pandemia de covid-19
Authors: Luvizotto Caroline Kraus , Volpato Alana Nogueira , Sena Kárita Emanuelle Ribeiro
Published: November 2024

A pandemia de covid-19 desencadeou crises que extrapolaram a área da saúde, com discursos conflitantes no espaço público. Este artigo pretende explorar como movimentos sociais participaram de processos de comunicação pública, com vistas à construção da cidadania, na pandemia de covid-19, no Brasil. Desenvolvemos análise de conteúdo de postagens relacionadas à pandemia, em páginas do Facebook de três movimentos sociais, durante dois anos. Discutimos como movimentos sociais ampliaram seu escopo de atuação para enfrentar as crises que se desenrolavam no país.
O SUS e a encruzilhada da desinformação sobre saúde: estratégias do contexto pós-pandêmico
Authors: Pinto Pâmela Araujo , Salomão Sarah Lopes , Bezerra André Gonçalves da Silva
Published: November 2024

El objetivo de este artículo es mapear las iniciativas para enfrentar la desinformación sobre salud pública en Brasil a partir de las acciones de las instituciones de salud y de los consejos federales de profesiones de salud. La metodología utilizada fue una revisión bibliográfica, un estudio exploratorio de 13 sitios web y un análisis documental. Los resultados mostraron acciones del Ministerio de Salud, de la Fundación Oswaldo Cruz (Fiocruz), del Instituto Butantan y del Consejo Nacional de Salud dirigidas a ciudadanos y a profesionales, con énfasis en la verificación de la información.
El efecto tabla redonda comunicación y política pública
Authors: Jaramillo López Juan Camilo
Published: November 2024

The construction of public policy, in addition to political action, is communicative action. As a mechanism that complies with and gives dynamism to the principle of publicity and as an exercise in public communication that admits agreements, consensuses and commitments, it organizes and gives character to citizen participation. The “round table” effect uses metaphor to refer to the kind of broad, horizontal and inclusive conversation that this democratic exercise requires, both in public deliberation and in direct spaces of participation.
Diálogo e distorção sobre as tragédias de Mariana e Brumadinho: a comunicação estratégica das organizações responsáveis
Authors: Carnielli Fiorenza Zandonade
Published: November 2024

Este artículo tiene como objetivo identificar las estrategias y las características de comunicación de las organizaciones Samarco, Fundação Renova y Vale a partir de su presentación pública en el evento de las tragedias de Mariana (2015) y Brumadinho (2019). De acuerdo con la traducción dialógica de Bohman para una comunicación exitosa y teniendo en cuenta la propuesta de Mafra y Marques, el diálogo se asume como criterio de evaluación normativa y pragmática de la comunicación de las organizaciones. El análisis de contenido de 14 informes de actividad publicados por las organizaciones entre 2016 y 2020 apoya la creación y reflexión sobre el marco pragmático de la comunicación estratégica. En conclusión, se afirma que la trama del evento formada por las tragedias de Mariana y Brumadinho es reveladora de estrategias comunicativas de las organizaciones que indican una comunicación sistemáticamente distorsionada y permiten caracterizar la comunicación cínica en superposición con la comunicación pública.
“Ao muito alto e excelente senhor...”: um estudo sobre as dedicatórias quinhentistas
Authors: Barbosa Saulo Vinicius Souza
Published: November 2024

Based on printed books' dedications, this paper studies the relations between intellectuals and nobles in the sixteenth-century European Republic of Letters. It is based on thirty-two dedications from works published between 1531 and 1598. The analysis of the material revealed the following results: a) the dedications are part of a 16th century social institution, the literary patronage; b) this institution has at its core an exchange of homage, given by the intellectual, for protection, retributed by the nobleman. The interpretation of these findings led to conclude that the practice of dedicating books was both a device to reinforce the status of the nobles and a strategy for intellectuals to ascend in their careers. All this shows that the sixteenth-century dedication is a privileged document for the social history of ideas and intellectuals in the Cinquecento.
No espelho, o outro: as urgências históricas, acordos da memória e síntese sociológica de Júlio de Mesquita Filho (1954)
Authors: Macêdo Francisco Adriano Leal , Biazo Glauber Cícero Ferreira
Published: November 2024

O texto aborda o livro “Memórias de um revolucionário, notas para um ensaio de sociologia política” (1954), de Júlio Mesquita Filho, para a problematização dos conceitos que o mobiliza, suas adesões e filiações históricas. A abordagem teórica tem como premissa as disputas pelos significados do passado, do trabalho da memória e, finalmente, objetiva produzir a obra em tela como fonte histórica para problematizar as maneiras por meio das quais o memorialista elabora legitimidade política, delineia embates e propõe perspectivas de poder.
O contracinema feminista de Agnès Varda: imagens do desnudamento na reinvenção do amor
Authors: Almeida Fernanda Albuquerque de
Published: November 2024

The text aims to characterize the feminist counter-cinema of Agnès Varda in three fiction films, Cleo from 5 to 7 (1962), One sings, the other doesn’t (1976) and Vagabond (1985), based on an interpretative analysis that outlines three categories of images of nudity: literal, existential-metaphorical and cinematographic. The cine-pamphlet Women reply: our body, our sex (1975) summarizes the common proposal of the films and sheds light on their goal: the reinvention of love. This is an exercise in film analysis and philosophical interpretation, in dialogue with studies in history, theory and criticism of cinema, which seeks to characterize a particular form of feminist counter-cinema.
Abstract 4112926: Echocardiography in Hypertrophic Cardiomyopathy: Virtual Continuing Medical Education Advances Physician Knowledge and Confidence
Authors: Harris Margaret , Stefan Margie , Sendaydiego Anne
Published: November 2024

Purpose:
This study examined whether online CME could improve the knowledge and confidence of cardiologists regarding the use of echocardiography for HCM diagnosis and management.

Methods:
The CME intervention comprised of a series of 6 online interviews between 1 moderator and 2 expert faculty. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge, and 1, rated on a Likert-type scale, assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, and a McNemar’s test was conducted at the question level (significance level,
P
< .05). Data were collected August 8-September 8, 2023.

Results:
165 cardiologists answered all assessment questions during the study period. Analysis of pre- vs. post-intervention responses demonstrated a significant improvement in overall knowledge; average correct responses increased from 48% pre-assessment to 74% post-assessment (
P
<.001). Specific areas of improvement include: Knowledge of the quantification of LVOT gradients, MR, and LVEF in the echocardiographic workup of HCM: 21% improved and 62% reinforced; the correct response increased (P<.001) from 65% (pre) to 84% (post). Knowledge of the utility of echocardiography for follow-up and monitoring response to HCM treatment: 48% improved and 35% reinforced; the correct response increase (P<.001) from 39% (pre) to 70% (post).

Post-education, 48% of cardiologists had a measurable increase in their ability to diagnose HCM using echocardiographic parameters, resulting in 43% who were mostly or very confident after education (24% pre vs 43% post; P<.001).

Conclusion:
This study demonstrated the success of online CME at improving the knowledge and confidence of cardiologists related to the use of echocardiography to identify and manage HCM.
Abstract 4112931: The Nature of Collagen Cross-links Differs in Reversibly and Irreversibly Infarcted Myocardium
Authors: Akam-Baxter Eman , Bergemann David , Ridley Sterling , To Samantha , Andrea Brittany , Moon Brianna , Ma Hua , Caravan Peter , Gonzalez-Rosa Juan Manuel , Sosnovik David
Published: November 2024

Background:
Persistent scarring after myocardial infarction (MI) is a major driver of heart failure in mammals. However, unlike mammals, zebrafish exhibit a remarkable ability to resorb scar, which consists predominantly of collagen in both species.

Aims:
We aimed here to develop a toolbox of techniques to characterize the nature of collagen in infarcted mammalian and zebrafish hearts. Specifically, we aimed to characterize the early and late cross-links that form in collagen and determine whether differences in these cross-links exist in zebrafish and mammals.

Methods:
To characterize the initial oxidation and cross-linking of collagen we developed a novel fluorescent probe (TMR-O) that binds to lysine aldehydes on collagen and inform on the degree of collagen cross-linking. Additionally, we used high performance liquid chromatography (HPLC) to quantify degradation-resistant mature collagen cross-links, such as pyridinoline (Pyd), and its precursor, hydroxylysine.

Results:
TMR-O imaging revealed similar overall CCL levels in both zebrafish and mouse infarcts. However, the irreversible cross-link pyridinoline (Pyd) was abundant in mouse infarcts but completely absent in zebrafish (p<0.0001). High Pyd levels in mice were accompanied by a dynamic increase in lysine hydoxylation (>200%), which was not observed in zebrafish (<10%).

Conclusions:
While collagen in mammalian and zebrafish infarcts may appear histologically similar, marked biochemical differences exist. Mature degradation-resistant collagen cross-links, such as Pyd form, in murine but not zebrafish infarcts and likely explains why zebrafish can resorb myocardial scar. Targeting Pyd formation in mammals could pave the way for novel therapeutic strategies to promote scar resolution and improve cardiac function after MI.
Abstract 4112952: Developing culturally informed materials to enhance Native Hawaiians' and Pacific Islanders’ participation in clinical trials
Authors: Ing Claire , Fan Anna , Aweau Kiilaweau , yoshimura sheryl , Kenney Meghan , Kaholokula Joseph
Published: November 2024

Background:
Native Hawaiians and Pacific Islanders (NHPI) suffer disproportionately from cardiometabolic disorders and are underrepresented in related clinical trials, limiting our ability to control these disorders for this population. We identified recruitment and retention barriers (complicated clinical language) and facilitators (relationship-building opportunities). Addressing recruitment and retention barriers and facilitators can increase NHPI representation in clinical trials.

Goal:
To develop culturally informed, educational videos and infographics to improve NHPI trust and attitudes toward research and recruitment and retention in clinical trials.

Methods:
The videos and infographics are based on focus group data with NHPI past clinical trial participants or staff. The videos focus on recruitment. The infographics focus on recruitment and retention. The videos address the complicated clinical language and hesitancy in disclosing information while leveraging trial outcomes relevant to NHPI health concerns and cultural inclusiveness. The infographics build on the video content. Facilitators include relationship-building opportunities, seeking healthier outcomes for future generations, relationship-building opportunities, and sharing and learning opportunities provided in clinical trials.

Results:
The Co-Principal Investigators, NHPI clinical trial participants, and NHPI researchers and clinicians contributed to the videos. We created a 5-minute and a 10-minute video. The videos provide 1) an overview of clinical research, 2) considerations for participating in clinical trials, and 3) reasons to participate. Researchers present the first 2 topics, while past participants provide testimonials for the third topic. The 8 infographics include 1) an overview of clinical research, 2) the importance of randomization, 3) research benefits from NHPI participation, 4) the importance of a control group, 5) clinical trial outcomes, 6) individual benefits from research participation, 7) community benefits from research participation, and 8) trust in research.

Discussion:
We will test the impact of these materials on trust and attitudes towards research and recruitment and retention among NHPI in a randomized clinical trial (RCT). Half of the participants (n=104) will be recruited using traditional strategies and half (n=104) using our novel strategy. Rigorous qualitative (interviews with participants) and quantitative (retention rates) analysis will be conducted.
Abstract 4119560: Oxidized Phospholipids and Calcific Aortic Valvular Disease
Authors: Bhatia Harpreet , DWECK MARC , Craig Neil , Capoulade Romain , Pibarot Philippe , Trainor Patrick , Whelton Seamus , Rikhi Rishi , Lidani Karita , Post Wendy , Tsai Michael , Criqui Michael , Shapiro Michael , Budoff Matthew , DeFilippis Andrew , Thanassoulis George , Tsimikas Sotirios
Published: November 2024

Introduction:
Oxidized phospholipids (OxPL) are carried by apolipoprotein B-100-containing lipoproteins (OxPL-apoB) including lipoprotein(a) [Lp(a)]. Both OxPL-apoB and Lp(a) have been associated with calcific aortic valve disease (CAVD).

Aims:
We aimed to evaluate the independent associations between OxPL-apoB, Lp(a) and the prevalence, incidence, and progression of CAVD.

Methods:
OxPL-apoB and Lp(a) were evaluated in the Multi-Ethnic Study of Atherosclerosis (MESA) and a participant-level meta-analysis of four randomized trials of participants with established aortic stenosis (AS). In MESA, the association of OxPL-apoB and Lp(a) with aortic valve calcium (AVC) at baseline and 9.5 years was evaluated using multivariable ordinal regression models. In the meta-analysis, the association between OxPL-apoB and Lp(a) with AS progression (annualized change in peak aortic valve jet velocity (V
max
)) was evaluated using multivariable linear regression models.

Results:
In MESA, both OxPL-apoB and Lp(a) were independently associated with prevalent AVC (OR (95% CI) per SD: 1.19 (1.07-1.32) and 1.13 (1.01-1.27), respectively) with a significant interaction between the two (p<0.01). Both OxPL-apoB and Lp(a) were associated with incident AVC at 9.5 years when evaluated independently (interaction p<0.01). The OxPL-apoB*Lp(a) interaction demonstrated higher odds of prevalent and incident AVC for OxPL-apoB with increasing Lp(a) levels. Mediation analyses demonstrated that Lp(a) partially mediated the association between OxPL-apoB and AVC. In a 2x2 analysis, the greatest risk for both prevalent and incident AVC was observed when Lp(a) and OxPL-apoB were both above the 80
th
percentile (
Figure
). In the meta-analysis, when analyzed separately, both OxPL-apoB and Lp(a) were independently associated with faster increase in V
max
, but when evaluated together, only OxPL-apoB remained significant (ß 0.07, 95% CI 0.01-0.12,
Figure
).

Conclusions:
OxPL-apoB is an independent predictor of the presence, incidence and progression of AVC and established AS, particularly in the setting of elevated Lp(a) levels and may represent a novel therapeutic target for CAVD.
Abstract 4120515: Impact of 2022 AHA/ACC/HFSA Heart Failure Guideline Value Statement Publication on Medicare Drug Coverage Policies
Authors: Mukhopadhyay Amrita , Ladino Nathalia , Stokes Tyrel , Adhikari Samrachana , Narendrula Aparna , Katz Stuart , Reynolds Harmony , Squires Allison , Blecker Saul
Published: November 2024

Background:
Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations (PA) and high out of pocket (OOP) costs. To promote better insurance coverage of high value therapies, the AHA/ACC/HFSA added Value Statements to HF guidelines to inform policymakers about medication cost effectiveness. We assessed whether these guidelines influenced Medicare drug coverage policies for two life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI – guideline “high value”) and sodium glucose cotransporter 2 inhibitors (SGLT2i – guideline “intermediate value”).

Methods:
We performed an observational study of Medicare drug plans from 4/2020-4/2023 to assess for changes in ARNI and SGLT2i coverage after Value Statement publication (4/2022), and subsequent Medicare plan online update (10/2022). The primary outcome was any barrier to drug coverage (PA, tier ≥ 3 OOP cost-sharing, step therapy, or no coverage). Analysis utilized interrupted time series and difference-in-difference (DiD) approaches. DiD analyses used direct oral anticoagulants as a control due to similar cost and utilization as ARNI and SGLT2i, but with no Value Statement.

Results:
Among 7,396 Medicare drug plans, 94.3%-97.4% had coverage barriers to ARNI and 93.2%-96.6% to SGLT2i. The majority of barriers were due to tier ≥ 3 OOP cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in 4/2022, and declined slightly in 10/2022 (Figure). In DiD analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for ARNI and SGLT2i.

Conclusion:
Coverage barriers to ARNI and SGLT2i were common and did not change much in response to Value Statements in HF Guidelines. Increased consideration for Value Statements by Medicare policy-makers is needed to meaningfully improve access to high value therapies.
Abstract 4120577: Discrimination of Fabry Disease and Cardiac Amyloidosis Using Cardiac MRI and Echocardiography: A Comprehensive Analysis
Authors: Sugiyama Hazuki , Kato Tomoko , Furusawa Yoshi , Takamura Chisato , Terashima Masahiro
Published: November 2024

Background:
Discriminating Fabry disease from cardiac amyloidosis based on conventional imaging techniques can be challenging due to overlapping features. We aimed to investigate the discriminatory ability of cardiac MRI (CMR) and echocardiography imaging, to differentiate between these conditions.

Methods:
Cardiac MRI and echocardiography with SR imaging were performed on patients with suspected Fabry disease (n=39) or cardiac amyloidosis (n=79). Various imaging parameters, including late gadolinium enhancement (LGE) patterns and T1 mapping values derived from CMR, E/e’ and global longitudinal strain (GLS) were analyzed. Discrimination scores were calculated using multivariate analysis, with sensitivity and specificity determined for selected parameters.

Results:
In Fabry patients, LGE patterns predominantly exhibited a subendocardial distribution (66%), whereas amyloidosis patients showed transmural LGE (93%). LV mass index and T1 mapping values were higher (150±20 vs. 90±15 g/m
2
, 1208±104 vs. 822± 210ms both p p<0.001) in cardiac amyloidosis compared to Fabry disease. Echocardiographic parameters demonstrated significantly reduced GLS (-12±2 vs -18±3%, p<0.001), larger LA size (50 ± 5 mm vs. 40 ± 5 mm, p<0.001) and higher E/e' ratio (15 ± 3 vs. 8 ± 2, p<0.001) in cardiac amyloidosis compared to Fabry disease. Multivariate analysis identified LGE patterns and GLS as significant discriminators, and combining both parameters can discriminate Fabry and Amyloidosis with a sensitivity of 80.0%, specificity of 90.0%, and predictive accuracy of 85.0%. Incorporating LA size, LV mass index and E/e’ further improve the predictive accuracy to 92.0%.

Conclusions:
Cardiac MRI and echocardiography demonstrate promising discriminatory ability in distinguishing Fabry disease from cardiac amyloidosis. GLS emerges as a valuable parameter, reflecting myocardial function and aiding in accurate diagnosis. Integration of these imaging modalities into clinical practice could enhance diagnostic accuracy and guide appropriate management strategies.
Abstract 4120583: Long term Safety and Efficacy of Ultrathin Bioabsorbable polymer sirolimus eluting Stents Versus Thin Durable polymer everolimus eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: A systematic review and meta analysis
Authors: Abouelenien Merna , Tanas Yousef , Bassiouny Mennatullah , Mahmoud Rewan , Zidan Abdelrahman
Published: November 2024

Background:
First generation drug eluting stents (DES) with thick polymers may contribute to local vascular inflammation and late stent thrombosis. Thinner-strut DES (ultrathin), particularly those with biodegradable polymers, aim to reduce this risk by minimizing flow disturbance and vascular injury. However, the long-term safety and efficacy of ultrathin biodegradable polymer sirolimus eluting stents (BP-SES) compared to durable polymer everolimus eluting stents (DP-EES) are still uncertain. Thus, we performed a meta analysis to compare outcomes of these two stents.

Methods:
Inclusion criteria comprised randomized controlled trials comparing ultrathin BP SES and thin DP EES in patients undergoing percutaneous coronary interventions with long term follow-up of at least 3 years. We excluded cohort studies, case reports, editorials, conference abstracts, and animal studies. Primary outcomes were target lesion failure (TLF), cardiac death (CD), target-vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (CI-TLR). We systematically searched PubMed, Cochrane CENTRAL, and Scopus. Cochrane’s ROB 2.0 tool assessed trial quality, and RevMan software (5.4) performed the meta-analysis.

Results:
Our analysis included ten RCTs, totaling 16,216 patients, with 9,108 in the BP SES group and 7,108 in the DP EES group. TLF occurred in 905 patients (9.94%) in the BP-SES group and 821 patients (11.55%) in the DP-EES group, with no statistically significant differences between the groups (RR = 0.92, 95% CI = 0.85 to 1.01, p = 0.08). Additionally, there were no significant differences in cardiac death (RR = 1.00, 95% CI = 0.84 to 1.19, p = 1.00), TV-MI (RR = 0.91, 95% CI = 0.78 to 1.05, p = 0.19), and CI-TLR (RR = 0.88, 95% CI = 0.78 to 1.01, p = 0.06) between the two groups.

Conclusion:
The use of BP-SES did not result in higher rates of TLF, CD, TV-MI, or CI-TLR compared to DP-DES. These findings suggest that both BP-SES and DP-DES are viable options for PCI procedures, with comparable long-term safety profiles. However, some trials used strut thicknesses exceeding 70µm in cases requiring wider diameters, similar to the strut thickness in the DP-EES group. This makes it challenging to assess whether, in addition to biodegradable polymers, lower strut thickness contributes to reducing target lesion-related events. Further research may be needed to explore other relevant outcomes and to confirm these findings in diverse patient populations.
Abstract 4122307: Longitudinal Changes in Parent-reported Quality of Life in Children with Single Ventricle
Authors: Uzark Karen , Yu Sunkyung , Afton Katherine , Atz Andrew , Floh Alejandro , Kasparian Nadine , Lambert Linda , Morrison Tonia , Pemberton Victoria , Shah Amee , Sood Erica , Suthar Divya , Trachtenberg Felicia , Votava-Smith Jodie , Williams Jason , Newburger Jane , Goldberg Caren
Published: November 2024

Introduction:
Increased knowledge of quality of life (QOL) and the potential impact of the Fontan on QOL is essential to improving outcomes in patients with single ventricle. The primary aim of the Pediatric Heart Network Single Ventricle Reconstruction (SVR) trial II was to investigate outcomes in subjects with SV at age 6 yrs while SVR III characterized outcomes in this cohort at age 10-12 yrs.

Aims:
The purpose of this study was to evaluate changes in health-related QOL from SVR II to SVR III and to identify factors associated with changes in QOL over time.

Methods:
Parents completed proxy-reports for their child using the Pediatric Quality of Life Inventory (PedsQL) generic and cardiac scales at SVR II and SVR III. Within-subject differences in PedsQL scores and proportions scoring in the ‘at-risk’ range for significantly impaired QOL between time points were examined using one-sample t-test and McNemar’s tests, respectively. Factors associated with changes in QOL were evaluated using standard univariate tests.

Results:
A total of 163 patients were included (63% male, 89% Caucasian, 16% Hispanic). PedsQL scores reported by parents decreased across all domains: total score -6.1 ± 17.1, p <.0001; physical -4.0 ± 22.3, p=0.02; psychosocial -7.2 ± 17.4, p<.0001; emotional -6.5 ± 20.7, p=.0001; social -6.6 ± 22.6, p= 0.0003; and school -8.6 ± 22.5, p<.0001, functioning. No significant change in parent-reported heart problems/cardiac symptoms was detected across timepoints (-1.0 ± 20.4, p=0.52). Proportions with impaired QOL increased over time: total 28 to 39%, p=.01, physical 27 to 39%, p=.01, psychosocial 25 to 40%, p=.002, emotional 20 to 34%, p=.001, social 22 to 31%, p=.06, and school 21 to 38%, p=.0001. Only treatment for a psychological or behavioral disorder (n=26) was significantly associated with decline in psychosocial (mean -14.0 vs. -5.9; p=.03) and emotional (mean -17.1 vs. -4.5; p=.004) functioning scores. There was no significant association between socioeconomic status, Vineland adaptive scores at SVR II, or interval complications or procedures and changes in QOL.

Conclusion:
As perceived by their parents, health-related QOL in children with SV decreases over time unrelated to cardiac symptoms and complications. The greatest decline was in school functioning with 1 in 3 children having significantly impaired school QOL at SVR III. Greater attention to assessment of learning and psychosocial needs is essential to improve QOL in patients with SV.
Abstract 4122309: Prognostic implication and hemodynamic characteristics of modified SCAI class in comatose OHCA patients: data from the BOX trial.
Authors: Linde Louise , Beske Rasmus , Meyer Martin , Molstrom Simon , Grand Johannes , Helgestad Ole , Ravn Hanne Berg , Schmidt henrik , Kjaergaard Jesper , Hassager Christian , Moller Jacob
Published: November 2024

Background:
Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high mortality. Transient myocardial stunning seen after out-of-hospital cardiac arrest (OHCA) often presents similar clinical characteristics as CS upon hospital arrival. OHCA involves a sudden cessation of circulation followed by a low-flow period during resuscitation, while CS involves prolonged myocardial dysfunction leading to hypoperfusion. The Society for Cardiovascular Angiography and Interventions (SCAI) proposed five distinct shock stages, further refined by the Cardiogenic Shock Working Group (CSWG). OHCA typically places patients in SCAI stage E, but this study abandoned that automatic classification.

Methods:
This post hoc analysis of the BOX trial data involved comatose OHCA patients with a presumed cardiac cause. Patients were classified using the CSWG-SCAI shock classification upon hospital admission without automatically assigning OHCA patients to stage E. Invasive arterial and pulmonary arterial measurements were taken within the first 72 hours of ICU admission. Cardiac Index (CI), cardiac power output (CPO), and perfusion pressure (mean arterial pressure minus central venous pressure) were calculated.

Results:
The results demonstrated that 31.6% of the 789 included patients were classified as SCAI class B/C, 29.9% as SCAI class D, and 38.5% as SCAI class E. One-year mortality for SCAI classes was as follows: B/C (21.3%), D (34.3%), and E (48.4%), with a p-value of <0.001 (Figure 1). There was no difference in CI and CPO within the first 72 hours of the ICU stay between SCAI classes. The first recorded perfusion pressure differed between SCAI class B/C and E (63.4±14.3 mmHg vs. 60±14.1 mmHg and 60.9±14.2 mmHg, respectively, p=0.008). This difference was only found at the first measurement. As lactate levels are a variable of SCAI classification, it was anticipated that there would be a significant difference in lactate at arrival. This difference in lactate remained at 36 hours after admission (1.3±0.7 mmol/L vs. 1.6±0.8 mmol/L and 1.9±1.1 mmol/L, respectively, p<0.001), but not thereafter. A higher proportion of patients developed acute kidney injury (AKI) as the SCAI classification increased (20%, 31% and 48%, respectively, p<0.001).

Conclusion:
One-year mortality increased with increasing SCAI classes but hemodynamic parameters within the first 72 hours of treatment did not differ between groups.
Abstract 4123630: MRPL44 Plays an Important Role in Cardiac Hypertrophy and Function
Authors: Okamoto Ryuji , Ye Zhe , Ito Rie , Moriwaki Keishi , Ito Hiromasa , Kimena Lupiya , Ida Mizuki , Dohi Kaoru
Published: November 2024

Background:
Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. However, it remains unknown how MRPL44 contributes to cardiac function and hypertrophy.

Aims:
Our aim is to investigate the effect of MRPL44 haploinsufficiency in mice.

Methods:
MRPL44 haploinsufficient (MRPL44
+/-
) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44
+/-
and wild-type (WT, MRPL44
+/+
) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44
+/-
and MRPL44
+/+
mice.

Results:
MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44
+/+
mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44
+/+
mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria.

Conclusion:
MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.
Abstract 4123674: The role of CD34+ PI16+ fibroblast progenitor cells in transplant arteriosclerosis
Authors: Xu Xiaodong
Published: November 2024

Background:
Transplantation arteriosclerosis is one of the major complications for the mid- and long-term survival of recipients with organ transplantation. Although previous studies suggest that CD34 stem/progenitor cells are involved in this process, the heterogeneity and potential adverse effects of CD34
+
SPCs have not been fully determined.

Methods and Results:
A mouse model of transplant arteriosclerosis was established by using Balb/c, C57BL/6J, CD34-CreERT2, R26-tdTomato, Rosa26-iDTR, CD34-Dre, PI16-CreERT2, CAG-LSL-RSR-tdTomato-2A-DTR mice. Using single-cell RNA-seq and the innovative application of genetic lineage tracing with dual recombinases, we identified a subpopulation of fibroblast progenitor cells marked by high CD34 and PI16 expression. Interestingly, this progenitor cell group gave rise to a distinct chemotactic fibroblast subset. Based on chemokine antibody microarray assay and transcriptome analysis, the subgroup with increased CD34 expression and decreased PI16 expression promoted intimal hyperplasia, acting through the paracrine release of a specific chemokine CCL11 (eotaxin-1). Moreover, the binding of CCL11 to its receptor CCR3 triggered the PI3K-AKT signaling pathway in smooth muscle cells, promoting their proliferation and migration to form neointimal lesions. Overexpression of CCL11 by adeno-associated virus can promote neointimal hyperplasia in vivo, while neutralization of CCL11 or inhibition of receptor CCR3 can alleviate neointimal lesions.

Conclusion:
Our findings identified CD34
+
/PI16
+
fibroblast progenitors able to differentiate into specific chemotactic fibroblasts that release chemokines pivotal for neointima formation, implicating a therapeutic potential targeting the chemotactic behavior of these cells.
Abstract 4131228: Where Adults with Advanced Heart Failure Die: Insights from the CDC-WONDER Database
Authors: Ali Farman , Ahmad Shaaf , Raja Adarsh , Azeem Bazil , Maniya Muhammad Talha , Siddiqi Ahmed , Alam Ahsan , Mattumpuram Jishant , Janjua Hamza , Siddiqi Tariq Jamal , Hall Michael
Published: November 2024

Background:
Adults with heart failure (HF) are becoming more and more prevalent. The location of death and related disparities in these patients are poorly understood.

Aim:
The purpose of the study was to look at the locations of adult deaths from HF and identify any age, race, or ethnicity-related variations over a 25-year period.

Methods:
The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Database provided death certificate data and the National Center for Health Statistics provided individual-level mortality data for the trend-level analysis of adults aged (20-64 and 65+ years) conducted from 1999-2023. Hospital, home, hospice and nursing home/long-term care were the categories for the places of death.

Results:
Between 1999 and 2023, a total of 7,644,759 adult deaths from HF were recorded (87.9% White, 53.4% female). HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities.

Conclusion:
Prioritize end-of-life planning for HF patients with poor prognosis, regardless of age, to improve quality of life and death.