bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B050: Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities
Authors: Mueller Christopher R , Parr Keira , Mates Mihaela , Robinson Andrew , Feilotter Harriet , Frosst Keira
Published: November 2024

We have developed a version of our "methylation DETection of Circulating Tumour" DNA (mDETECT) assay that is able to sensitively and quantitatively monitor Non-Small Cell Lung Cancer (NSCLC). We used this assay to frequently assess the tumour burden of a small cohort (17 individuals) of patients undergoing first line monotherapy with pembrolizumab for metastatic disease. Patients were tested weekly or biweekly in the period immediately after initiation of treatment with radiological assessment being done at approximately 3 months. Radiologically non-responding patients showed constant or increased mDETECT levels over the 3 month time frame. Responding patients showed 2 different patterns, with some showing dramatically increasing mDETECT levels for a short period of time followed by a rapid decrease. Other responders showed an immediate decrease within the first few week of treatment. In both responder groups these decreases were associated with a longer term response. Continued monitoring did reveal eventual progression in some of these patients with increasing mDETECT levels being seen 4 to 6 months before radiological changes. In some non-responding patients complex responses were seen, with mDETECT levels varying significantly over time. In one non-responding patient the addition of carboplatin to their treatment regime did produce a temporary improvement in their mDETECT levels. Frequent assessment of tumour burden by a liquid biopsy such as mDETECT offers the opportunity to rapidly determine a patient's response to therapy and potentially modify treatments to improve responses.

Citation Format: Christopher R Mueller, Keira Parr, Mihaela Mates, Andrew Robinson, Harriet Feilotter, Keira Frosst. Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B050.
Abstract B052: Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade
Authors: Wright Samuel J. , Zamora Izabella , Parikh Milan , Yeramosu Deepika , Bi Lynn , Kang Sarah , Rucevic Marijana , Sade-Feldman Moshe , Liu Baolin , Nguyen Ngan , Guess Jamey , Schneider Alexis , Lieb David , Woods Elliot , Michaud William , Lawless Aleigha R. , Sharova Tatyana , Kasumova Gyulnara , Kim Michelle S. , Park Ryan J. , Jenkins Russell W. , Klempner Samuel J. , Sullivan Ryan J. , Flaherty Keith T. , Hacohen Nir , Boland Genevieve M. , Mehta Arnav
Published: November 2024

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR018) of the Conference Program/Proceedings.

Citation Format: Samuel J. Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Lynn Bi, Sarah Kang, Marijana Rucevic, Moshe Sade-Feldman, Baolin Liu, Ngan Nguyen, Jamey Guess, Alexis Schneider, David Lieb, Elliot Woods, William Michaud, Aleigha R. Lawless, Tatyana Sharova, Gyulnara Kasumova, Michelle S. Kim, Ryan J. Park, Russell W. Jenkins, Samuel J. Klempner, Ryan J. Sullivan, Keith T. Flaherty, Nir Hacohen, Genevieve M. Boland, Arnav Mehta. Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B052.
Abstract B074: Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care
Authors: Woldesonbet Zelalem Desalegn , Yohannes Meron , Porsch Martin , Stückrath Kathrin , Anberber Endale , Santos Pablo , Bauer Marcus , Addissie Adamu , Bekuretsion Yonas , Assefa Mathewos , Worku Yasin , Taylor Lesley , Abebe Tamrat , Kantelhardt Eva J , Vetter Martina
Published: November 2024

Objective: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. Patients and methods: Formalin-fixed paraffin- embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. Results: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. Conclusion: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary-level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context.

Citation Format: Zelalem Desalegn Woldesonbet, Meron Yohannes, Martin Porsch, Kathrin Stückrath, Endale Anberber, Pablo Santos, Marcus Bauer, Adamu Addissie, Yonas Bekuretsion, Mathewos Assefa, Yasin Worku, Lesley Taylor, Tamrat Abebe, Eva J Kantelhardt, Martina Vetter. Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B074.
Abstract IA007: Modulating cfDNA biology to enhance liquid biopsies
Authors: Adalsteinsson Viktor
Published: November 2024

Liquid biopsies could transform cancer care but require higher sensitivity to detect early-stage tumors and minimal residual disease (MRD) and to enable tumor molecular profiling and therapy response monitoring for most patients. In this talk, I will focus on the significant biological bottlenecks upstream of cell-free DNA (cfDNA) testing. I will posit that in many circumstances, insufficient circulating tumor DNA (ctDNA) drawn in a blood tube cannot be overcome by assay technology alone, and that in vivo modulation of cfDNA biology may also be required to enhance liquid biopsies. Inspired by widespread use of diagnostic drugs in other areas of medicine, we sought to create the first “priming agents” for liquid biopsies that could be administered before a blood draw to recover more ctDNA. I will describe two such approaches—a monoclonal antibody against double-stranded DNA and a liposome nanoparticle—that briefly attenuate cfDNA clearance by shielding it from nuclease digestion and cellular uptake. These enabled >10x more ctDNA to be collected when administered within 1-2 hours of a blood draw in mice. This improved the analytical limit of detection for ctDNA testing by >10-fold, provided more complete representation of the tumor genome in each blood sample, and increased the sensitivity for detection of small tumors from <10% to >75% in mice. Envisioning a future where liquid biopsies are optionally enhanced with priming, I will also explore a unique potential pairing with our tumor-informed, whole-genome, mutation enrichment sequencing MRD test called MAESTRO, and how it stands to enable routine ctDNA detection below 1 part per million.

Citation Format: Viktor Adalsteinsson. Modulating cfDNA biology to enhance liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA007.
Abstract IA018: Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection
Authors: Bratman Scott V
Published: November 2024

Head and neck cancer (HNC) is a molecularly heterogenous disease with a variable clinical course. Current treatment decisions rely primarily on pre-treatment prognostic factors without consideration of treatment response. This presentation will introduce liquid biopsy biomarkers that can be repeated in HNC patients for the purpose of dynamic risk stratification, treatment adaptation, and post-treatment surveillance. Novel approaches to measuring circulating tumor DNA (ctDNA) will be described, with particular attention to viral-associated and non-viral- associated subtypes of HNC. Detection of molecular residual disease (MRD) using ctDNA will be discussed. As HNC is often treated by non-surgical means, there is a pressing need for tissue- agnostic methods for ctDNA-based MRD detection. Analysis of tumor-specific genetic and epigenetic aberrations within ctDNA each present distinct opportunities and challenges for tissue-agnostic characterization of ctDNA. Viral ctDNA has emerged as a convenient target for MRD detection in viral-associated HNC, while ctDNA methylome profiling offers a versatile approach for tissue-agnostic MRD detection across HNC subtypes. Future applications of these methods may improve individualized management of HNC patients without requiring access to precious tumor tissue samples.

Citation Format: Scott V Bratman. Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA018.
Table 1 from Genomic Features of Newly Diagnosed Large B-cell Lymphoma with or without Subsequent Disease Progression
Authors: Landsburg Daniel J. , Morrissette Jennifer J.D. , Nasta Sunita D. , Barta Stefan K. , Schuster Stephen J. , Chong Elise A. , Svoboda Jakub , Barlev Ashley , Bagg Adam , Priore Salvatore F.
Published: November 2024

Count of genomic alterations in all patients and by cohort
Figure 1 from Genomic Features of Newly Diagnosed Large B-cell Lymphoma with or without Subsequent Disease Progression
Authors: Landsburg Daniel J. , Morrissette Jennifer J.D. , Nasta Sunita D. , Barta Stefan K. , Schuster Stephen J. , Chong Elise A. , Svoboda Jakub , Barlev Ashley , Bagg Adam , Priore Salvatore F.
Published: November 2024

Case inclusion/exclusion.
Educação climática: guia prático para famílias e educadores
Authors:   Universidade de São Paulo. Instituto de Estudos Avançados, Vianna Daniela , Proença Samantha Graiki ,   Rede Internacional de Pesquisa Resiliência Climática, Ribeiro Livia ,   Escolas pelo Clima, Menezes Mariana
Published: November 2024

A crise climática é o maior desafio deste século e deverá ser enfrentada coletivamente. Os efeitos das mudanças climáticas já estão acontecendo aqui, agora, no nosso quintal. As soluções existem; faltam, ainda, vontade política e medidas efetivas rumo à mudança urgente e necessária. Por isso, cada ação importa. As vozes e ações de movimentos como Famílias pelo Clima, Escolas pelo Clima e Saúde Planetária Brasil (IEA-USP), com o apoio do IEA-USP, do Programa USPSusten (SGA-USP) e da Reconectta são valiosas no processo de transformação necessário para o enfrentamento da emergência climática na sociedade, com a participação de mães, pais, redes de apoio e educadores. Esta obra apresenta um compilado de conteúdos, ferramentas e práticas que apontam alguns caminhos possíveis para a inclusão da agenda climática de forma transformadora, mobilizadora e engajadora no ambiente escolar, sempre com base na melhor ciência disponível. Este guia prático foi viabilizado graças ao apoio do Fundo de Microssubsídios Climáticos Intergeracionais, cuja concessão é fruto de parceria entre o Fundo UMI, o Our Kids Climate7, o Parents for Future (movimento global de Famílias pelo Clima) e o Social Change Nest (SCN).
Glossário Visual de Conservação: Um Guia de Danos Comuns em Papéis e Livros
Authors: Paglione Camila Zanon
Published: November 2024

Elaborado como instrumento de trabalho para o Laboratório de Conservação Preventiva Guita Mindlin da Biblioteca Brasiliana Guita e José Mindlin da USP, este Glossário Visual de Conservação busca, por meio de imagens e definições sintéticas, esclarecer alguns termos básicos usados para descrição de danos comuns em livros e obras em papel.
Translation, cross-cultural adaptation and scale validation to assess professionalism among medical students
Authors: Souza Edvaldo , Saldanha Gabriel , Nóbrega Rodrigo
Published: November 2024

Introduction: the professionalism of the physician should be present not only in the technical attributes, such as decision making and clinical reasoning, but also personal and interpersonal attributes, such as empathy, ethics, commitment, sense of social responsibility, altruism, teamwork and confidentiality. However, these attributes should be worked already during the medical course and includes the need to be assessed. Objective: To translate, cross-culturally adapt and validate a scale to assess professionalism in medical students. Method: We conducted a methodological validation study of the Professionalism Assessment Scale for Medical Students developed in Slovenia and authorized by the main author. The study was developed in four phases: translation and retranslation phase; cross-cultural adaptation phase; test and retest phase; and final application phase of the scale. The study population in the final phase consisted of a medical student and the sample was of convenience. The questionnaire was developed through the open LimeSurvey software and available via link in social networks. Data analysis was performed in Epi Info 7.2.4.0 and study approved by the institution’s Research Ethics Committee. Results: 82 students participated, with a mean age of 21 years (SD = 1.8) and predominance of males. Before answering the Professional Assessment Scale (PAS), 73.2% said they knew how to define what professionalism was and 47.3% said they had a medical relative. Participants achieved very high PAS scores, with only 4 participants (4.88%) scoring less than 100. The mean score was 107 on a scale of no more than 110 points. The PAS presented a Cronbach alpha coefficient of 0.7. Conclusion: The study revealed that the students of the educational institution have a high degree of professionalism and the validation of the scale in its final stage reached an acceptable level of reliability and can be used in other studies.
Entre a Jāhilīyyah e a Dīn: as imagens de Khadījah ao advento do mundo islâmico segundo os escritos de al-Ţabarī, al-Bukhārī e ibn Isḥāq
Authors: Motelewski Heloisa
Published: November 2024

Este trabalho tem como objetivo analisar a formação de imagens narrativas sobre Khadījah bint Khuwailid, mulher central para o nascimento e desenvolvimento do Islã. Partindo das reflexões contemporâneas sobre o papel da mulher no mundo islâmico, busca-se refletir sobre a formação de um modelo comportamental feminino nos documentos da medievalidade muçulmana, os quais seguem repercutindo, ainda que não explicitamente, nos debates da atualidade. Sendo assim, a análise toma como base as obras de al-Ţabarī, al-Bukhārī e ibn Isḥāq, nelas objetivando constatar a construção de espectros específicos sobre a figura da comerciante mecana aos séculos VIII e IX E.C.
Do atomismo ao primordialismo: diferenças e aproximações entre Epicuro e Lucrécio
Authors: Prado Cezar
Published: November 2024

Este ensaio pretende estabelecer relações de diferença e de proximidade entre Epicuro e Lucrécio, tendo em vista o problema existente na leitura tradicional que reduz o pensamento lucreciano a uma mera tradução ao latim do pensamento de Epicuro. Se tanto Epicuro quanto Lucrécio chegam a praticamente os mesmos resultados no âmbito da física, como pretendo mostrar, o primeiro trata estes resultados com uma sobriedade austera (porém, não ascética), enquanto o segundo com uma volúpia mística de caráter venusiano. Essa inflexão mística de Lucrécio terá como uma de suas consequências – parcialmente definida – a elaboração de uma ética também distinta daquela de Epicuro, como veremos na terceira parte deste ensaio, assim dividido em três momentos: física, mística e ética.
Existe Verdade na Interpretação? Um modelo de correção do domínio interpretativo a partir da obra de Joseph Raz
Authors: Xavier Caio
Published: November 2024

Este artigo objetiva articular um critério de correção para proposições interpretativas sobre determinado objeto a partir de fundamentos da obra de Joseph Raz sobre teoria da interpretação e filosofia moral. Parte-se de uma situação-problema em que diversos indivíduos contendem sobre a melhor interpretação de um quadro surrealista. Em sequência, são expostas premissas centrais do pensamento raziano e apresentado o modelo de parâmetros para avaliação das interpretações, pautado em um nível mínimo de correspondência com o objeto interpretado e um grau de fomento do valor almejado com aquela modalidade de atividade interpretativa. Ao final, aplica-se o referido modelo para dirimir, fundamentadamente, a contenda descrita inicialmente
As mães solteiras na São Paulo de finais do século XVIII: uma perspectiva de sua inserção socioeconômica através das listas nominativas de 1798
Authors: Silva Giovanna Turato Citron
Published: November 2024

Este artigo tem como objetivo apresentar o perfil demográfico das mulheres livres, acima dos 12 anos de idade, solteiras e mães, na cidade de São Paulo, na última década do século XVIII, a partir de uma análise das listas nominativas de habitantes de 1798. Foi observada não somente a inserção quantitativa desse nicho populacional na demografia paulista, mas, também, a econômica, levando em consideração não apenas a peculiaridade da cidade na economia colonial, mas, especialmente, a questão de gênero, fator de limitação do campo de possibilidades de experiências dessas mulheres.
Dados demográficos da USP: a pesquisa “Mulheres e Homens da USP” e a conceituação de gênero
Authors: Cordeiro Maria Eduarda Martins Mendes
Published: November 2024

O artigo investiga a conceituação de gênero adotada pela Universidade de São Paulo, utilizando como corpus de pesquisa os Anuários Estatísticos da instituição, de 2001 a 2020 (anos de 2000 a 2019). O presente trabalho tem como fundamento o estudo realizado pelo extinto Escritório USP Mulheres, hoje incorporado à Pró-Reitoria de Inclusão e Pertencimento, em que foi realizada a coleta e tratamento dos dados demográficos da população uspiana, compreendendo os vínculos discentes, de docência e servidores técnico-administrativos. O que se revela patente são as ações crescentes de incorporação oficial de pautas vinculadas à equidade e aos direitos humanos, acompanhadas de uma concomitante persistência da concepção binária de gênero e, até o momento analisado, de uma diminuta política de agregação de outros marcadores sociais nos levantamentos demográficos da instituição.
Abstract 4112620: Cardiomyocyte-specific Increases in Forkhead Box M1 (FoxM1) Expression May Promote Cardiomyocyte Proliferation and Improve Recovery from Myocardial Injury in Mice and Pigs
Authors: Wu Yalin , Wang Yongyu , Walcott Gregory , NGUYEN THANH , Nakada Yuji , Tan Huilan , Jiang Yu , Zhao Jianli , liu yanwen , Zhou Yang , Wang Yajing , Zhang Jianyi
Published: November 2024

Background:
The cardiomyocytes (CMs) can not regenerate after myocardial infarction (MI) in adult mammals. FoxM1 is essential for cell proliferation. Targeted deletion of the Foxm1 in mice leads to serious cardiac proliferation defects and embryo death. The primary aim of this study was to demonstrate that the Specific Modified mRNA Translation System (SMRTs) can specifically overexpress FoxM1 in CMs and observe the benefits of overexpressing FoxM1 on myocardial repair in mice and pigs with myocardial injury.

Methods:
The FoxM1-CM SMRTs is composed of two modRNA constructs: one encoding L7Ae regulates the specific expression of FoxM1 on the other coding chain in CMs and inhibits its expression in non-cardiomyocytes through he CM-specific microRNAs miR-1 and miR-208 on L7Ae coding chain. Myocardial-specific expression of FoxM1-CM SMRTs and its proliferation-promoting effect were detected in hiPSC-CM (human-induced pluripotent stem cell-derived cardiomyocyte), mouse and pig models (days 3 after FoxM1-CM SMRTs treatment). In vivo experiments were conducted in both mouse and pigs with LAD (left anterior descending) ligation. The effects of FoxM1-CM SMRTs on cardiac function, MI size and hypertrophy in mice and pig models were detected after 4 weeks of FoxM1-CM SMRTs treatment.

Results:
FoxM1 was abundantly expressed in postmitotic CMs after transfection with the FoxM1-CM SMRTs, accompanied by activation of cell-cycle and proliferation markers (Ki67, PH3 and Aurora B kinase) and an increase in cell number. When the GFP-CM SMRTs was injected into mouse hearts with MI, GFP was only expressed in CMs, but not in non-CMs. Compared with the MI group, FoxM1-CM SMRTs significantly increased CM proliferation (days 3 after treatment administration in mice and pigs), improved left-ventricular ejection fractions (days 10 and 28 in both species) and hypertrophy, and reduced MI size (days 28 in both species).

Conclusion:
Intramyocardial injections of the FoxM1-CM SMRTs promoted CM proliferation, reduced MI size, and improved cardiac function in small and large mammals with acute myocardial infarction.
Abstract 4112639: A Rare Case of Atypical Sarcoidosis Presenting as an Intra-Atrial Septal Mass
Authors: Dod Rohan , Tushak Zackary
Published: November 2024

Introduction:
Sarcoidosis is a granulomatous disease that can affect multiple organ systems, including the heart. Cardiac Sarcoidosis (CS) is one of the most severe manifestations. It is characterized by a dysregulated T-cell driven immune response which generates non-necrotic inflammatory granulomas with myocardial infiltration. CS has a range of clinical syndromes: impaired conduction, arrhythmias, heart failure, and sudden cardiac death. We discuss a rare presentation of CS as an intra-atrial septal mass.

Case Description:
A 27-year-old Caucasian female with history of depression on citalopram presented with a one-month history of palpitations, fatigue, and dyspnea with exertion. An EKG demonstrated sinus rhythm with first-degree AV block. A cardiac monitor revealed intermittent 2-1 AV block and high degree AV block occurring mostly during sleep. An echocardiogram revealed normal biventricular function and morphology. Due to the concern for infiltrative cardiomyopathy, she underwent a cMRI which revealed a focal mass centered along the intra-atrial septum extending from the fossa ovalis to the septal AV junction, measuring 4.5 cm in size. She underwent pacemaker implantation with mild improvement of symptoms. PET scan demonstrated hypermetabolic activity of the intra-atrial region. She underwent surgical resection of the cardiac mass. Pathology was significant for fibrotic tissue with non-caseating granuloma and multinucleated giant cells consistent with an extremely rare presentation of CS. She was started on immunosuppressive medications. Subsequent cMRI and PET demonstrated resolution of the mass and hypermetabolic activity.

Discussion:
CS is a severe condition that most commonly presents with symptoms of heart failure, conduction abnormalities, and cardiac morphological changes of hypertrophy or thinning. However, it is often missed as a diagnosis, even in patients with extracardiac sarcoidosis. It is rare for CS to present as an isolated cardiac mass, especially in a younger patient as in this case. Advances in imaging techniques such as echocardiography, MRI, and PET have improved the ability to diagnosis CS and provide timely specialized treatment. This case highlights the need to include CS as an important diagnosis on the differential for a patient presenting with conduction abnormalities, heart block, and dyspnea. It also accentuates the critical role of multimodality imaging in working up this disease.
Abstract 4112869: Development of a Sitosterolemia Risk Prediction Scale (SRPS): A Screening Tool
Authors: Tawde Poonam , Mohammad Salim
Published: November 2024

Introduction:
Sitosterolemia, a hereditary disorder marked by elevated plant sterol levels, presents diagnostic challenges due to its similarity to other lipid disorders. The development of the Sitosterolemia Risk Prediction Scale (SRPS) aims to address this by synthesising genetic, clinical, and dietary data into a coherent risk assessment model.

Research Question:
We propose that a structured risk scale, integrating diverse factors known to affect sitosterolemia, can significantly improve the accuracy of predicting the disorder. The SRPS is hypothesised to facilitate early detection and inform targeted interventions.

Aim:
The primary aim is to conceptualise and outline the SRPS, which categorises individuals into risk categories based on a point system reflecting genetic predispositions, clinical symptoms, dietary habits, and response to treatments. This scale seeks to enhance the clinical identification of sitosterolemia, promoting timely and personalised management strategies.

Methods:
A detailed table was generated to present the SRPS, categorising risk factors into genetic, clinical, dietary, and response to treatment. This innovative method allowed for the efficient synthesis and visualisation of complex data.

Results:
The SRPS table methodically organizes risk factors into low (0-2 points), moderate (3-5 points), and high (6+ points) categories. This stratification guides further diagnostic actions, ranging from exploring alternative causes of hyperlipidemia to necessitating comprehensive genetic and lipid analyses.

Conclusion:
The SRPS represents an innovative framework for assessing sitosterolemia risk, highlighting the potential benefits of integrating genetic, clinical, and dietary information. It further underscores the importance of a multifactorial approach in the early detection and management of sitosterolemia.
Abstract 4113411: Long Term Outcomes of Hypertension and Antihypertensive Drugs in Young Healthy Adults: A Nationwide Population-based Prospective Cohort Study in Korea
Authors: Moon In Tae , Park Yung Ki
Published: November 2024

Background:
Long term follow-up data on elevated blood pressure (BP) or antihypertensive drugs in young adults are scarce. The effect of hypertension (HTN) and antihypertensive medications on the cardiovascular disease incidence in young healthy adults (20~45 years) was analyzed using a large-scale population medical use database in Korea.

Methods:
In total, 4,590,597 young Korean adults without comorbidities who underwent regular health examination were included in this study. They were stratified into four groups according to their BP (optimal BP, normal BP, high normal BP, and HTN). The primary outcome was a composite of the incidence of myocardial infarction and ischemic and hemorrhagic stroke, obtained by tracking the medical use data of the first-ever ICD-10 codes. Subgroup analysis was conducted by categorizing the HTN group into two subgroups according to the prescription ratios of the antihypertensive drugs during the follow-up period.

Results:
The average age was 33.8 years and median follow-up duration was 15.9 years. HTN elevated the incidence risk of major cardiovascular disease by 2.16 times compared to that of the optimal BP group. Dyslipidemia and HTN were the most dominant risk factors for myocardial infarction and stroke, respectively. In the subgroup analysis, antihypertensive medications decreased the incidence of cardiovascular disease by 70% in all diseases.

Conclusions:
Cardiovascular risk factors, including HTN, contribute to major cardiovascular disease incidence in young adults. The antihypertensive medications decreased the major cardiovascular disease incidence estimates.
Abstract 4113475: Association of Age at Diabetes Diagnosis and All-cause and Cardiovascular Mortality among 600,000 US Adults
Authors: Thomson Blake , Bragg Fiona , CLARKE Shoa , Herrington William , Assimes Themistocles , Emberson Jonathan , Geldsetzer Pascal
Published: November 2024

Introduction:
Diabetes is a leading cause of morbidity and mortality in the United States, causing an estimated 440,000 deaths among US adults in 2019. Establishing the relevance of diabetes diagnosis at various ages to mortality in the contemporary US population, both overall and among major demographic subgroups, may inform public health policy and strategy.

Methods:
We aimed to quantify the association between age at diabetes diagnosis and all-cause and cardiovascular mortality among US adults using publicly-available data from the National Health Interview Survey 1997-2018, linked to the National Death Index through 2019. We used Cox regression adjusted for age, sex, race and ethnicity, educational attainment, smoking status, body-mass index, physical activity, and insurance coverage to estimate all-cause and cardiovascular mortality rate ratios overall, by sex, and by race and ethnicity.

Results:
Among 601,467 included adults (56% female, 16% Hispanic and 14% non-Hispanic Black) there were 75,122 deaths during 6.6 million person-years of follow-up. Overall, the all-cause mortality rate ratio associated with diabetes diagnosed at ages 20-29, 30-39, 40-49, 50-59, 60-69, or 70-79 years were 3.87 (95% CI 3.47-4.32), 2.87 (2.68-3.07), 2.26 (2.16-2.36), 1.72 (1.65-1.79), 1.47 (1.41-1.53), and 1.26 (1.19-1.33), respectively. The corresponding cardiovascular mortality rate ratios were 5.02 (4.09-6.16), 3.37 (2.99-3.78), 2.88 (2.65-3.13), 1.94 (1.81-2.09), 1.53 (1.43-1.65), and 1.27 (1.15-1.40), respectively. Although these associations were similar by sex and by race and ethnicity, the age-specific prevalence of diabetes was greatest among non-White participants. Among individuals with diabetes diagnosed at ages 20-29, 30-39, 40-49, 50-59, 60-69, or 70-79 years, an estimated 74%, 65%, 56%, 42%, 32%, or 20% of deaths from any cause were attributable to diabetes.

Conclusion:
Age at diabetes diagnosis was associated with all-cause and cardiovascular mortality in a dose-dependent and approximately log-linear manner. Although associations were similar across diverse demographic groups, age-specific diabetes prevalence was greatest among non-White individuals, leading to greater mortality burden. If these associations were interpreted as largely causal, diabetes accounted for more than half of all deaths among those diagnosed before age 50 years. Preventing, delaying, and appropriately managing diabetes could prevent substantial excess mortality among US adults.
Abstract 4113486: Cardiovascular Benefits of Sotagliflozin in Diabetic Populations: A Meta-Analysis
Authors: Menon Tushar , Mistry Ameera , Bhagwagar Shahin
Published: November 2024

Background:
Sotagliflozin, an inhibitor of both SGLT1 and SGLT2, is under investigation for potential cardioprotective effects in diabetic patients.

Aims:
This study assesses the efficacy and cardiovascular benefits of sotagliflozin in patients with type 1 or type 2 diabetes at high cardiovascular risk or with diagnosed heart failure.

Methods:
We systematically searched digital databases including ClinicalTrials.gov, PubMed, Google Scholar, Cochrane, Medline, and Embase, using a PICOS-based strategy and the PRISMA framework for data reporting. Randomized controlled trials comparing sotagliflozin against placebo over a minimum duration of eight weeks were analyzed using Review Manager (RevMan) 5.4.1.

Results:
Our meta-analysis included 7 studies with 16,315 participants with all studies comparing either 200 or 400 mg sotagliflozin to placebo. The meta analaysis revealed significant improvements in reduction the total number of cardiovascular deaths [OR= 0.70 (95% CI (0.51- 0.95)), p = 0.02]; reduction in Non-fatal MI [OR=0.76 (95% CI (0.70- 0.84)), p < 0.00001]; reduction in the incidence of hospitalizations due to HF [OR=0.54 (95% CI (0.44, 0.66)), p < 0.00001]; reduction In urgent hospitalizations [OR=0.66 (95% CI (0.53, 0.83)), p=0.0004]; improvement in LVEF>50% [ OR= 0.41 (95%CI (0.34, 0.51)), p<0.0001] and reduction in systolic blood pressure mean reduction of -0.81 (95% CI (1.36, -0.25)), p=0.005]. However there was no statistically significant reduction in all cause mortality [0.73 (95% CI (0.42, 1.26)), p=0.26] .

Conclusion:
Sotagliflozin significantly reduces the incidence of cardiovascular deaths, adverse events, and hospitalizations in diabetic patients at high risk of cardiovascular complications.
Abstract 4113617: Single-cell Analysis Reveals Endothelial Cell CD45 Deficiency Prevents Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis
Authors: Peng Qianman , Arulsamy Kulandai Samy , Lu Yao Wei , Zhu Bo , Li Kathryn , Singh Bandana , Wu Hao , Cui Kui , EISA-BEYGI SHAHRAM , Nasim Sana , Wylie-Sears Jill , Malovichko Marina , Sun Liang , Wong Scot , Cowan Douglas , Srivastava Sanjay , Wang Da-Zhi , Chen Kaifu , Bischoff Joyce , Chen Hong
Published: November 2024

Introduction:
Protein-tyrosine-phosphatase CD45 is exclusively expressed in all nucleated cells of the hematopoietic system but is rarely expressed in endothelial cells (ECs). However, a recent study indicated that activation of the endogenous CD45 promoter in human endothelial colony forming cells induced expression of EndMT marker genes. Also, the CD45 phosphatase inhibitor blocked EndMT activities in TGFβ1-treated ovine mitral valve endothelial cells. EndMT contributes to atherosclerotic pathobiology and is associated with more complex plaques. We identified CD45-positive ECs undergoing EndMT in atherosclerotic ApoE-deficient (ApoE
-/-
) mice. Here, we aim to investigate whether endothelial CD45-specific deletion can prevent EndMT in a mouse model of atherosclerosis.

Methods and Results:
We generated a tamoxifen-inducible EC-specific CD45-deficient mouse strain (EC-iCD45KO) on an ApoE
-/-
background (C57BL/6) and fed these mice a Western diet for 16 weeks. We isolated and enriched mouse aortic endothelial cells with CD31 beads to perform single-cell RNA-seq. Cells populated 15 major clusters after integrating the single-cell transcriptomic profiles. In the EC-iCD45KO group, the population of endothelial, resident macrophage, and mesenchymal-endothelial transition cells increased while vascular smooth muscle, EndMT, and fibroblast cells decreased. In EndMT cells, EC markers (Cdh5, Cldn5, Pecam1) increased, but SMC markers (Acta2) and EndMT markers (Col1a2 and Col3a1）decreased. In addition, we characterized EndMT cells into two sub-clusters: 1 and 2. EC-specific CD45 deletions reduced the cell numbers in the EndMT2 sub-cluster in atherosclerotic mice but had less impact on the EndMT1 sub-cluster. FGFR pathways were potentiated while TGFβ1 and Tgfbr2 decreased in EndMT1 sub-cluster， and the genes controlling endothelial cell development were upregulated but the genes controlling actin cytoskeleton organization were downregulated in both EndMT1 and 2 sub-clusters.

Conclusion:
Our single-cell analysis indicates that the loss of endothelial CD45 protects against EndMT-driven atherosclerosis, inhibiting TGFβ and EndoMT marker expression while stimulating FGFR pathways. Consistently, EC-iCD45KO/ApoE
-/-
mice showed reduced plaque macrophages, expression of cell adhesion molecules, foam cell formation, and lesion development when compared to ApoE
-/-
controls. Thus, targeting endothelial CD45 may be a novel therapeutic strategy for EndMT and atherosclerosis.
Abstract 4113854: Outcomes Of Atrial Fibrillation Ablation In Elderly: A Retrospective Cohort Study
Authors: Thakkar Aditya , Gupta Soumya , Sanku Koushik , KOMMINENI SAI KARTHIK , Namburu Lalith , Kumar Dilpat , ramu vijay
Published: November 2024

Introduction:
Atrial fibrillation (Afib) is a common cardiac arrhythmia that increases in prevalence with age. Ablation has been widely used for managing Afib, but its outcomes in octogenarians have been less thoroughly investigated.

Research Question:
This study aims to assess the in-hospital outcomes of Afib ablation in patients aged above 80 compared to those below 80 years old.

Methods:
Data was obtained from the Nationwide Inpatient Sample database from January 2016 to December 2020. The study included all adult patients with a primary discharge diagnosis of Afib who underwent catheter ablation during their hospitalization. These patients were then categorized into two groups based on age: below 80 and above 80 years. In-hospital outcomes for these groups were then looked at. The primary outcome was inpatient mortality. Secondary outcomes were the length of stay, cost of hospitalization, cardiac arrest, cardiac tamponade, arrhythmias, acute respiratory failure, acute renal failure, procedural complications as well as the need for dialysis, transfusions, pressors, ventilators, and tracheostomy.

Results:
Out of about 35 million admissions screened, 403,247 patients had Afib as their primary discharge diagnosis, of these, 17,927 patients underwent catheter ablations during their hospitalization. Amongst them, 3,051(17%) were above the age of 80 years. The in-hospital mortality was slightly higher in the elderly compared to the younger cohort (1.1% vs 0.5%, aOR: 1.87; 95% CI: 1.20-2.92, p=0.006). They had a longer hospital stay (5.14 days vs. 3.72 days, p<0.001) and lower hospitalization costs (USD 138,091 vs. USD 162,788, p<0.001). Complications such as acute respiratory failure and acute renal failure were more frequent in the older age group, while no significant differences were observed in cardiac arrest, cardiac tamponade, ventricular arrhythmias, and most device-related complications. The need for new dialysis, mechanical ventilation, and pressor use was significantly less in the above-80 group.

Conclusion:
Afib ablation in older adults, results in slightly higher in-hospital mortality and longer hospital stays compared to younger patients. Despite these differences, the overall complication rates are comparable, suggesting that age alone should not deter the selection of patients for Afib ablation. Further studies are needed to validate these findings and optimize management strategies for the elderly population.
Abstract 4114505: Cardiovascular Adverse Events After Anti-BCMA CAR-T (Ide-Cel and Cilta-Cel) for Relapsed/ Refractory Multiple Myeloma
Authors: Palfi Stefanie , Koelmeyer Himara , Alsina Melissa , Baz Rachid , Blue Brandon , Corallo Salvatore , De Avila Gabriel , Freeman Ciara , Grajales-Cruz Ariel , Harvey Kristy , Liu Hien , Nishihori Taiga , Oliveira Guilherme , Oswald Laura , Castaneda Puglianini Omar , Shain Kenneth , Wettenstein Zachary , Jain Michael , Locke Frederick , Alomar Mohammed , Hansen Doris , Lee Dae Hyun
Published: November 2024

Introduction:
Idecabtagene vicleucel (Ide-Cel) and ciltacabtagene autoleucel (Cilta-cel) are novel CAR-T therapies targeting B-cell maturation antigen (BCMA) and approved for relapsed and refractory multiple myeloma (RRMM). While cardiovascular adverse events (CVAE) are relatively common with CD-19 CAR-T, the incidence of CVAE in the real-world setting for anti-BCMA CAR-T in RRMM is largely unknown. This study aims to determine the incidence of CVAE and its associated risk factors in patients treated with ide-cel and cilta-cel.

Method:
This single-center retrospective cohort study evaluated RRMM patients treated with ide-cel and cilta-cel from May 2021 to December 2023. We assessed baseline cardiac and oncologic characteristics and clinical outcomes post-CAR-T. Cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome (ICANS) grading followed ASTCT consensus guidelines.

Result:
A total of 164 RRMM patients treated with ide-cel (N=109) or cilta-cel (N=55) with at least 6 months follow-up were included. The average age was 63 years, and 57% were male. Advanced RRMM stage (R-ISS III) was present in 17% with a median of 6 prior lines of therapy. CRS grade equal or greater than 2 occurred in 22%, and ICANS grade equal or greater than 3 in 6.7%. Twenty patients (12.2%) experienced CVAE, including atrial fibrillation (7.9%), non-sustained ventricular arrhythmia (3.0%), heart failure (3.7%), and cardiovascular death (0.6%). R-ISS III was associated with increased CVAE (52.9% vs. 11.5%; P=0.001). Patients with CVAE had higher baseline ferritin and CRP levels and a higher incidence of CRS grade ≥ 2 (60% vs. 16.7%; P<0.001) and ICANS grade ≥ 3 (20% vs 4.9%; P=0.001). Treatment with tocilizumab, steroids, or anakinra was more common in patients with CVAE.

Conclusion:
CVAE occurred relatively frequently following BCMA CAR-T therapy, with high-grade CRS identified as a consistent risk factor. Most CVAEs were manageable with appropriate supportive care, including careful observation and active treatment of CRS.
Abstract 4114994: Nursing Management Practice Variations related to Externalized Ventricular and Lumbar Drains
Authors: Hepburn Millie
Published: November 2024

Introduction/Background:
Nursing management of neurologic patients may include placement of externalized ventricular drains (EVDs) or lumbar drains (LDs) to monitor/drain cerebrospinal fluid (CSF), but knowledge and practice related to EVD management varies widely, despite a high potential for life-threatening complications. Limited data exists relative to the relationship between intracranial pressure (ICP) and CSF drainage. These gaps may undermine patient safety.

Research Question:
What are the nursing practices and perspectives regarding management of EVDs and LDs?
Methods/Approach:
A 16-question multiple-choice/text entry survey was distributed electronically to nurses and advanced practice nurses who were members of the American Association of Neuroscience Nurses. Data analysis included chi-square test for multiple choice responses, and qualitative data was analyzed using a six-step thematic analysis and an inductive approach.

Results/Data:
Of 219 participants, 42.8% reported roles as Neuroscience ICU nurses, and 39.2% managed an EVD at least 75% of the time. Neuro ICU nurses were most likely to have a patient with an EVD (
p
=.002). Approximately 63% of respondents reported consulting with colleagues about EVDs nearly every time they cared for a patient with an EVD. Nurses reported a very high care burden, including re-leveling the transducer 4 or more times per shift (n=76), and re-zeroing every 8 hours (n=72) to assure accurate calibration. Of these 82.2% reported that they re-zeroed the EVD more often to obtain an accurate reading. Approximately 25% reported accidental over-drainage, some with negative outcomes. Many (79.3%) reported caring for patients with LDs, 47.4% to diagnose normal pressure hydrocephalus. The nursing care workload was described as 30-120 minutes each shift.

Conclusion:
A wide heterogeneity of nursing practices was revealed in EVD and LD management. No standardized nursing care practices have been adopted by nurses for the management of CSF. The complications of these practice variations have been shown to result in untoward patient outcomes. Increased patient morbidity and mortality are linked to catheter infection and over/under drainage of CSF and may be directly related nursing practice. This reveals critical need for improved, standardized care nursing practices in the management of EVDs and LDs, and an empiric understanding of the relationship between intracranial pressure and the volume and rate of CSF drainage.
Abstract 4115222: Distinct Demographic, Cognitive, and Psychosocial Factors Associated with Different Types of Self-Care in Patients with Type 1 Diabetes and in Patients with Type 2 Diabetes
Authors: Heo Seongkum , Barbe Tammy , Kim JinShil
Published: November 2024

Background:
Poor self-care in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) leads to increased diabetes complications and health costs. While the goal of self-management for patients with T1DM and T2DM is to maintain normal blood glucose levels, the major methods for achieving this differ (exogenous insulin delivery vs. a combination of self-care techniques, respectively). This implies that factors associated with self-care in the two groups may differ.

Hypothesis:
Distinct demographic, cognitive, and psychosocial factors are associated with overall self-care, diet, exercise, blood glucose testing, foot care, and smoking in patients with T1DM and T2DM, in separate models.

Methods:
In this cross-sectional, correlational study, data were collected from 148 patients with T1DM (n = 64, mean age: 51.3 years) or T2DM (n = 84, mean age: 62.5) using REDCap during 2023. The participants were recruited from various organizations, institutions, and ResearchMatch in the United States. Several multiple regression analyses were done to test the hypothesis.

Results:
Patients with T1DM had better self-care, including overall diabetes self-care, exercise, and blood glucose testing than the T2DM group. Older age (p = .003), lower body mass index (BMI) (p = .040), and stronger knowledge (p = .028) in the T1DM group (F[10,53]= 2.290, p = .026, R
2
= .302), while lower BMI (p = .045) and higher levels of self-efficacy (p < .001) in the T2DM group were associated with better overall diabetes self-care (F[10,73] = 3.219, p = .002, R
2
= .306). Older age, lower BMI, stronger knowledge, stronger resilience, and lower self-esteem were associated with better self-care in diet, blood glucose testing, and/or foot care in the T1DM group, while lower BMI, stronger knowledge, higher levels of self-efficacy, and less severe depressive symptoms were associated with better self-care in diet, exercise, and/or blood glucose testing in the T2DM group. None were associated with smoking in both groups. Diabetes distress, self-compassion, and social support were not associated with any types of self-care.

Conclusions:
Factors associated with self-care differed based on types of self-care and types of diabetes, thus, supporting the hypothesis. When healthcare providers provide interventions to improve diabetes self-care in individual patients with diabetes, they need to consider types of diabetes, types of self-care, and distinct factors associated with each type of self-care.