bluuebunny/crossref_metadata_2025 huggingface dataset:
An Oncolytic Virus Expressing IL15/IL15Rα Combined with Off-the-Shelf EGFR-CAR NK Cells Targets Glioblastoma
Authors: Ma Rui , Lu Ting , Li Zhenlong , Teng Kun-Yu , Mansour Anthony G. , Yu Melissa , Tian Lei , Xu Bo , Ma Shoubao , Zhang Jianying , Barr Tasha , Peng Yong , Caligiuri Michael A. , Yu Jianhua
Published: May 2021

IL15 is a pleiotropic cytokine with multiple roles that improve immune responses to tumor cells. Oncolytic viruses (OV) specifically lyse tumors and activate immune responses. Systemic administration of IL15 or its complex with the IL15Rα and chimeric antigen receptor (CAR) natural killer (NK) cells are currently being tested in the clinic. Here, we generated a herpes simplex 1–based OV-expressing human IL15/IL15Rα sushi domain fusion protein (named OV-IL15C), as well as off-the-shelf EGFR-CAR NK cells, and studied their monotherapy and combination efficacy in vitro and in multiple glioblastoma (GBM) mouse models. In vitro, soluble IL15/IL15Rα complex was secreted from OV-IL15C–infected GBM cells, which promoted GBM cytotoxicity and improved survival of NK and CD8+ T cells. Frozen, readily available off-the-shelf EGFR-CAR NK cells showed enhanced killing of tumor cells compared with empty vector–transduced NK cells. In vivo, OV-IL15C significantly inhibited tumor growth and prolonged survival of GBM-bearing mice in the presence of CD8+ T cells compared with parental OV. OV-IL15C plus EGFR-CAR NK cells synergistically suppressed tumor growth and significantly improved survival compared with either monotherapy, correlating with increased intracranial infiltration and activation of NK and CD8+ T cells and elevated persistence of CAR NK cells in an immunocompetent model. Collectively, OV-IL15C and off-the-shelf EGFR-CAR NK cells represent promising therapeutic strategies for GBM treatment to improve the clinical management of this devastating disease.

Significance:

The combination of an oncolytic virus expressing the IL15/IL15Rα complex and frozen, ready-to-use EGFR-CAR NK cells elicits strong antitumor responses in glioblastoma.
Green Tea-Derived Epigallocatechin Gallate Inhibits Acid Production and Promotes the Aggregation of Streptococcus mutans and Non-Mutans Streptococci
Authors: Han Sili , Abiko Yuki , Washio Jumpei , Luo Yufang , Zhang Linglin , Takahashi Nobuhiro
Published: May 2021

It has been suggested that green tea-derived epigallocatechin gallate (EGCG), which has antimicrobial properties, might help prevent dental caries. However, the detailed properties of EGCG remain unclear. In this study, the antimicrobial properties of EGCG were evaluated by examining its bactericidal activity, its inhibitory effects against bacterial growth, acid production, acidic end-product formation, and sugar uptake (phosphoenolpyruvate-dependent phosphotransferase system, PEP-PTS activity), and its effects on bacterial aggregation, using monocultured planktonic cells of Streptococcus mutans and non-mutans streptococci. Coincubating S. mutans with EGCG (1 mg/mL) for 4 h had no bactericidal effects, while it decreased the growth and acid production of S. mutans by inhibiting the activity of the PEP-PTS. EGCG (2 mg/mL) caused rapid bacterial cell aggregation and had reduced the optical density of S. mutans cell suspension by 86.7% at pH 7.0 and 90.7% at pH 5.5 after 2 h. EGCG also reduced the acid production of non-mutans streptococci, including S. sanguinis, S. gordonii, and S. salivarius, and promoted the aggregation of these non-mutans streptococci. Furthermore, these antimicrobial effects of short-term EGCG treatment persisted in the presence of saliva. These results suggest that EGCG might have short-term antibacterial effects on caries-associated streptococci in the oral cavity.
ХРОМАТОГРАФІЧНИЙ АНАЛІЗ ЕФІРНИХ ОЛІЙ ІЗ ТРАВИ МОНАРДИ ЛИМОННОЇ РІЗНИХ ФАЗ ВЕГЕТАЦІЇ
Authors: Shanaida M. I. , Svydenko L. V. , Hvozdyk N. V. , Hudz N. I.
Published: May 2021

Мета роботи. Хроматографічний аналіз ефірних олій монарди лимонної (Monarda citriodora Cerv. ex Lag, родина Lamiaceae Martinov), отриманих із трави рослини в різні фази вегетації.

Матеріали і методи.  Матеріалом для досліджень була трава M. citriodora, яку заготовляли на дослідних ділянках у Херсонській області на початку цвітіння та у період масового цвітіння рослин. Ефірну олію отримували методом гідродистиляції. Аналіз її компонентного складу проводили методом газової хроматографії з мас-спектрометричним детектуванням (ГХ/МС). Для отримання «хроматографічних відбитків» компонентів ефірної олії використовували метод тонкошарової хроматографії (ТШХ).

Результати й обговорення. На основі ГХ/МС аналізу вивчено компонентний склад ефірних олій сировини M. citriodora. Всього в ефірній олії із трави рослини при її заготівлі на початку цвітіння ідентифіковано 28 компонентів, під час масового цвітіння – 27. В обох ефірних оліях домінували ароматичні монотерпеноїди тимол і карвакрол. Проведення заготівлі сировини M. citriodora у фазу масового цвітіння визначено більш перспективним з огляду на вищий сумарний вміст в ефірній олії тимолу й карвакролу (84,07 %) порівняно з початком цвітіння (75,09 %). Запропоновано застосувати ТШХ-аналіз ефірної олії з трави досліджуваної рослини, заготовленої під час масового цвітіння, як експрес-метод її ідентифікації.

Висновки. Визначено компонентний склад та специфічні особливості ефірних олій M. citriodora вітчизняної заготівлі у дві різні фази вегетації, на основі чого їх віднесено до тимолово-карвакролового хемотипу. У перспективі визначено доцільним вивчення потенціалу фармакологічної активності ефірної олії M. citriodora.
Оцінка стану кровопостачання тиреоїдного залишку за доплерівськими характеристиками після хірургічних втручань на щитоподібній залозі
Authors: Стець М. М. , Антонів В. Р. , Галига Т. М. , Галига Т. М.
Published: May 2021

Мета роботи: вивчити ехоструктуру, стан і особливості судинної перфузії тиреоїдного залишку щитоподібної залози після операції впродовж часу та визначення клінічної значущості кольорового доплерівського картування (КДК) та енергетичної доплерографії ЕД.

У 86 хворих після виконаних органозберігальних операцій на щитоподібній залозі провели дослідження тиреоїдного залишку на 7 день, через 1 місяць та 1 рік після операцій з використанням апарата ультразвукової діагностики Esaote MyLabX6 (Італія) та НDІ 5000 (АТL США) з лінійним широкосмуговим датчиком L12-5 Мгц. Визначали величину та структурні зміни в залишеній тканині. Кровопостачання тканини та її оболонок вивчали шляхом визначень кількісних характеристик – індексу резистентності (RІ), максимальної систолічної швидкості (МСШ), кінцевої діастолічної швидкості (КДШ) та енергетичної доплерографії (ЕД).

Збільшення об’єму частки чи кукси супроводжується зміною їх типу будови, з пласких (без форми) ділянок становляться шароподібними та конусоподібними, а темпи росту складають певний відсоток зміни типу будови у 37 (43 %) хворих на 7 день і вже 66 (77 %) – через 1 рік. КДК вказує, що кровопостачання тиреоїдного залишку проходить в основному по периферії у місцях новостворених сполученнях.

Впровадження ультразвукового доплерівського сканування для дослідження тиреоїдного залишку після операції дає можливість встановити ступінь кровообігу та швидкість компенсованого стану, що прослідковується за рахунок ультразвукових змін та залежить від типу будови залишеної тканини. Максимальний темп приросту тиреоїдної тканини та відновлення структури кровотоку спостерігається через 1 рік. Значення RІ є найбільш інформативним кількісним показником периферичного кровообігу знову створених судинних з’єднань з тканинами.
A escrita do feminino: assédio e feminicídio no conto Venha ver o pôr-do-sol, de Lygia Fagundes Telles
Authors: Moraes Paulo Eduardo Benites de , Souza Maria Alice Sabaini de
Published: May 2021

O presente trabalho pretende analisar a crise de representação da personagem feminina no conto Venha ver o Pôr-do-sol, de Lygia Fagundes Telles, a partir da perspectiva da literatura de autoria feminina e da violência vivenciada pela protagonista. O conto vale-se de razões estéticas bem definidas ao trabalhar com conceitos como gênero, identidade, subjetividade e a maneira como esses conceitos interferem na elaboração e nas ações das personagens. Desde a primeira linha do conto até o seu desfecho há a focalização nas personagens e a valorização do elemento espacial como responsáveis pelo efeito sombrio e misterioso que se evidencia ao longo do texto. O enfoque nesses elementos narrativos e a forma como a escritora trabalha as temáticas pertinentes à literatura de autoria feminina favorecem a possibilidade de se reconhecer que Venha ver o pôr-do-sol é um conto em que Telles se consolida como uma das representantes deste tipo de literatura no Brasil. Esse artigo apresenta, inicialmente, uma revisão referente ao desenvolvimento da literatura de autoria feminina e a relação entre esse momento literário e a escrita de Lygia Fagundes Telles no que diz respeito à luta das mulheres em sua obra para, em seguida, propor uma análise do conto sob o viés da violência contra a mulher, considerando o gênero e a constituição da identidade das personagens.
Três sentidos para a memória na poesia de autoras brasileiras contemporâneas
Authors: Auad Pedro Henrique Trindade Kalil
Published: May 2021

Este presente artigo realiza uma reflexão sobre a relação entre o corpo e a memória na poesia brasileira de autoria feminina contemporânea, partindo de três sentidos que se fazem presentes de forma mais explícita: o gosto, o tato e o olhar. A partir dessa articulação, pretende-se refletir sobre como esses poemas ajudam a alargar o horizonte poético, assim como suas implicações éticas e políticas. São convocadas para a conversa autoras diversas: Adelaine Ivánova, Alice Sant’Anna, Ana Martins Marques, Bruna Beber, Flávia Péret, Marília Garcia, Natasha Tinet, Nina Rizzi, Tatiana Nascimento, Tatiana Pequeno, Viviane Maroca e Yasmin Nigri.
Silêncios prEscritos: Estudos de romances de autoras negras brasileiras (1859-2006)
Authors: Espallargas Teresa
Published: May 2021

O livro Silêncios prEscritos: Estudos de romances de autoras negras brasileiras (1859-2006) (2019) de Fernanda R. Miranda propõe a criação de um corpus de narrativas de autoras negras brasileiras com o intuito de combater o silenciamento imposto as autoras e suas obras, discutindo noções de literatura brasileira e literatura negra, bem como de colonialidade e resistência. A partir do estudo de 8 romances, e de seus paralelos, baseado em extensa bibliografia crítica, o livro de Miranda abre novos caminhos de leitura e análise literária.
Galo de Ouro e Memorial de Maria Moura: Rachel de Queiroz e as contradições do feminino - entre a independência e a conformação
Authors: Oliva Osmar Pereira
Published: May 2021

Este trabalho pretende discutir os romances Galo de ouro e Memorial de Maria Moura, de Rachel de Queiroz, na perspectiva de gênero, ressaltando as representações do feminino, entre a independência e a conformação ao lar. Em sua maioria, as personagens femininas criadas pela autora cearense lutam por igualdade social, reivindicam liberdade de pensamento e poder de decisão nas relações afetivas e procuram resistir à subordinação ao masculino, ao mesmo tempo em que sentem a falta de uma companhia masculina, gerando a aparente contradição.
A insurreição da imagem ou quando o cinema visita Raoul Ubac
Authors: Scansani Andréa C.
Published: May 2021

A história das imagens no cinema e na fotografia é inscrita sobre uma base material comum coordenada pelos instrumentos de criação da fotografia. Mesmo compartilhando substratos equivalentes, seus processos artísticos não poderiam ser mais dessemelhantes. Neste artigo, colocaremos em evidência algumas iniciativas de cineastas-artesãs que estreitam a distância entre os diferentes métodos e nos fazem pensar a materialidade do cinema. Para tanto, percorreremos o período em que o artista Raoul Ubac subverte o caráter figurativo da fotografia e, com o apoio de Georges Bataille, Rosalind Krauss e Agostinho de Hipona, nos dedicaremos a refletir sobre o informe tanto nas obras fotográficas de Ubac quanto em três filmes manufaturados nos ateliers L’Etna e L’Abominable na França.
Pensar a transparência, refletir a opacidade: Tautologia e transitividade na série Hoppe, de Mariano Klautau Filho
Authors: Reis Lucas Manuel Mazuquieri
Published: May 2021

Este artigo busca pensar o duplo paradigma da transparência e da opacidade com as fotografias da série Hoppe, de Mariano Klautau Filho. Apresentam-se aqui alguns dos sentidos disseminais desses conceitos, para então se analisar, com base neles, a qualidade reflexiva dos enquadramentos das fotografias da série (sua aparente recusa em deixar transparecer, a implicação do olhar em sua materialidade) e a espessura temporal intrínseca às suas imagens (mobilizando aqui os conceitos de entre-imagens e de montagem de tempos).
Função-historiador: o projeto Grupo Atlas como modelo contemporâneo de autoria artística
Authors: Santos Vivian Braga dos
Published: May 2021

O artigo apresenta o conceito “função-historiador” como modelo possível de autoria de uma arte da memória. Elaborado por meio de uma modulação da função-artista, de Peter Osborne, e da análise do projeto Grupo Atlas, prática artística de Walid Raad sobre as guerras civis libanesas, o termo é desenvolvido como contraposição ao modelo crítico de artista-testemunha, predominantemente utilizado nas mediações de práticas artísticas sobre conflitos políticos recentes. O enfrentamento entre essas propostas se faz a partir do distanciamento entre o sujeito-artista e uma posição de autoria artística. Essa separação permite investigar outros formatos de apresentação do artista como parte de sua produção e verificar novas abordagens dos vínculos autobiográficos e identitários nas produções artísticas contemporâneas.
Abstract 002: Assessing Profiles Of Cardiometabolic Risk Among South Asians Living In The United States Using A Syndemic Framework And Acculturation
Authors: Montiel Ishino Francisco A , Canenguez Katia M , Cohen Jeffrey H , Needham Belinda , Kandula Namratha , Williams Faustine , Shields Alexandra E , Kanaya Alka M
Published: May 2021

Background:
South Asians (SA) are the second largest US immigrant group and have excess cardiometabolic (CM) disease. While acculturation is associated with increased CM risk among immigrants and refugees, the role of acculturation on SA CM risk is relatively unknown. CM disease presents as a syndemic or synergistic epidemic involving multiple disease clusters as well as the biological, social, and psychological interactions from the acculturative process to worsen morbidity within subgroups.

Methods:
We used latent class analysis to identify SA CM risk based on acculturation subgroups using data from adults aged 40-84 in the Mediators of Atherosclerosis in South Asians Living in America study (N=771). The distal outcome of CM risk was constructed using hypertension, type 2 diabetes, and body mass index. Proxies of acculturation included years lived in the US, English proficiency, cuisine eaten at home, cultural traditions, ethnicity of friends, social and neighborhood support, and experienced discrimination; as well as mental health indicators, which included depression, trait anxiety, anger, and positive and negative spiritual coping. Covariates included demographic characteristics, family income, education, study site, exercise, smoking, alcohol use, religiosity and spirituality.

Results:
Four CM risk profiles and acculturation subgroups were identified: 1) lowest risk [73.8%] were the most integrated with both SA and US culture; 2) intermediate-low risk [13.4%] had high mental health distress and discrimination and separated from SA and US culture; 3) intermediate-high risk [8.9%] were more assimilated with US culture; and 4) highest risk [3.9%] were more assimilated with US culture [Figure].

Conclusion:
Our approach identified distinct nuanced profiles of syndemic CM risk to understand how acculturation and sociocultural factors cluster with health in US South Asians. Our syndemic framework will further understanding of CM risk among SA to best design tailored prevention and intervention programs.
Abstract 014: Posttraumatic Stress Disorder, Mental Stress-induced Myocardial Ischemia And Cardiovascular Outcomes In Patients With CAD
Authors: Almuwaqqat Zakaria , young an , Garcia Mariana , Sullivan Samaah , Lima Bruno B , Kim Jeong Hwan , alkhalaf mhmtJamil , Moazzami Kasra , Driggers Emily , Ko Yi-an , Lewis Tene T , Shah Amit J , Garcia Ernest V , Bremner J Douglas , Quyyumi Arshed A , Vaccarino Viola
Published: May 2021

Introduction:
Mental stress-induced myocardial ischemia (MSI) is a risk marker for adverse outcomes among coronary artery disease (CAD) that is more prevalent among patients with posttraumatic stress disorder (PTSD).

Hypothesis:
CAD patients with PTSD who develop MSI experience a higher risk of adverse cardiovascular events compared with those who do not develop MSI.

Methods:
We studied 995 individuals with stable CAD who participated in two contemporary cohort studies with similar protocols, the Mental Stress Ischemia Prognosis Study (MIPS), and the Myocardial Infarction and Mental Stress Study (MIMS). Provocation of myocardial ischemia with a standardized mental stress test (speech task) was assessed with single-photon emission computed tomography. PTSD was assessed with the structured clinical interviews for DSM-IV. Participants were categorized into four groups based on their MSI and PTSD status. The primary endpoint was a composite outcome of cardiovascular death or nonfatal myocardial infarction (MI), stroke, or heart failure hospitalization. Cox regression models were used to investigate the interaction of PTSD and MSI on the study endpoint in the two samples pooled with meta-analysis.

Results:
In total, 603 participants in MIPS and 392 in MIMS were included. MSI occurred in 16% of the patients in MIPS and 17% in MIMS. Over a 5-year median follow-up, there were 126 outcome events in MIPS and 117 in MIMS. In Cox regression models with adjustment for demographic and clinical risk factors, participants with both MSI and PTSD had a higher risk for the study endpoint, compared to those with neither. In contrast, participants with PTSD or MSI but not both were not at a higher risk (
p
interaction=0.01). Separate analyses in the two studies were consistent.

Conclusions:
There is a synergistic association of PTSD and MSI on adverse outcomes in CAD patients. These findings support the confluence of chronic mental health vulnerability with acute stress responses in defining elevated risk in CAD patients.patients.
Abstract 015: Geographic Variation In Pre-pregnancy Cardiometabolic Health In The United States, 2016-2018
Authors: Cameron Natalie A , Freaney Priya M , Wang Michael C , Perak Amanda M , Dolan Brigid M , O'Brien Matthew J , Grobman William A , Allen Norrina B , Greenland Philip , Lloyd-Jones Donald M , Khan Sadiya S
Published: May 2021

Introduction:
Poor cardiometabolic health is a major contributor to growing rates of maternal morbidity and mortality. Given known state-level variation in maternal outcomes, we sought to describe the geographic distribution of pre-pregnancy cardiometabolic health as it could inform policy changes to optimize maternal and offspring outcomes.

Hypothesis:
We hypothesized that pre-pregnancy cardiometabolic health has declined over time and varies by state.

Methods:
We conducted a nationwide, serial cross-sectional analysis using maternal birth record data from the CDC Natality Files 2016-2018, which include all live births in the US. We included all live births to women aged 20-44 years (N= 10,693,708). Pre-pregnancy cardiometabolic health was quantified by number of pre-pregnancy risk factors: overweight or obesity (body mass index > 25 kg/m
2
), diabetes, and/or hypertension. We calculated annual age-standardized prevalence of favorable (no risk factors), suboptimal (any single risk factor), or poor ( > 2 risk factors) pre-pregnancy cardiometabolic health and quantified percentage change between 2016-2018 by state.

Results:
From 2016-2018, the percentage of live births to women with favorable cardiometabolic health decreased from 43.5% (43.4, 43.6) to 41.3% (41.2, 41.3), suboptimal health increased from 51.1% (51.1, 51.2) to 53.3% (53.3, 53.4), and poor health increased from 2.1% (2.1, 2.1) to 2.4% (2.4, 2.4). All states experienced declines in favorable cardiometabolic health. There was significant geographic variation with prevalence of favorable pre-pregnancy cardiometabolic health ranging from 32.7% (32.2, 33.3) in Mississippi to 48.2% (47.7, 48.6) in Utah in 2018
(FIGURE)
; poor health ranged from 1.3% (1.3, 1.4) in California to 4.6% (4.4, 4.8) in Louisiana in 2018.

Conclusions:
Less than half of women had favorable pre-pregnancy cardiometabolic health between 2016-2018, with significant geographic heterogeneity. Public health efforts to improve pre-conception cardiometabolic health are needed.
Abstract 017: Meal Intervals And Weight Trajectories In Adults Using The Daily24 Mobile Application: A Prospective Cohort Study
Authors: Zhao Di , Woolf Thomas , Martin Lindsay , Guallar Eliseo , Lehmann Harold , Coughlin Janelle , Song Shanshan , Holzhauer Katherine , Clark Jeanne , McTigue Kathleen M , Lent Michelle , Bennett Wendy L
Published: May 2021

Background:
Small pilot and randomized controlled studies suggest that time-restricted feeding may decrease body weight. However, the role of meal timing and intervals, measured using mobile applications, has not been examined in larger population-based studies. The objective of this study is to evaluate the association between meal intervals and weight trajectories among adults from a population-based clinical cohort.

Methods:
Multi-site prospective cohort study of adults recruited from three health systems. Over the 6-month study period, 547 participants downloaded and used the Daily24 mobile application to record the timing of meals and sleep for at least one day. Intervals were calculated as the average of all available daily entries for each participant. We obtained information on weight and comorbidities at each outpatient visit from electronic health records available for up to 10 years prior to until 10 months after baseline. We used mixed linear regression to model weight trajectories.

Results:
The mean (SD) baseline (at consent) age was 51.1 (15.0) years and body mass index (BMI) 30.8 (7.8) kg/m
2
; 77.9% were women and 77.5% were White. Average time in the cohort was 5.9 years prior to and 0.3 years after baseline. The mean interval from first to last meal was 11.5 (2.3) hours. The associations between meal intervals and weight trajectories are shown in the
Table
. The number of meals per day was positively associated with weight change before baseline, and number of snacks and drinks per day was inversely associated with weight change after baseline. Each additional occasion of snacks and drinks was associated with a 3.20 kg weight decrease (95% CI 1.41 to 4.99). None of the other associations were statistically significant.

Conclusions:
Number of daily meals was positively associated with weight change in previous periods, while the number of daily snacks and drinks was inversely associated with weight trajectory. The intervals from first to last meal was not associated with weight change.
Abstract 023: Effects Of Sodium Reduction And The Dash Diet On Subclinical Cardiac Damage: Results From The Dash-Sodium Trial
Authors: Juraschek Stephen P , Kovell Lara , Appel Lawrence J , Miller Edgar R , Sacks Frank M , Chang Alex R , Christenson Robert H , Rebuck Heather , Mukamal Kenneth J
Published: May 2021

Background:
We recently documented that the DASH diet has beneficial effects on cardiac biomarkers. The effects of sodium reduction, alone or combined with the DASH diet, are unknown.

Objective:
To determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.

Methods:
DASH-Sodium was a controlled, feeding study in adults with pre- or stage 1 hypertension, who were randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. The three sodium levels were low (50 mmol/d), medium (100 mmol/d), and high (150 mmol/d). Outcomes were 3 biomarkers representing distinct pathways of cardiac damage: high-sensitivity cardiac troponin I (hs-cTnI, measure of cardiac injury), N-terminal b-type pro natriuretic peptide (NT-proBNP, measure of strain), and high-sensitivity C-reactive protein (hs-CRP, measure of inflammation), collected at baseline and at the end of each feeding period.

Results:
Of the original 412 participants, mean age was 48 yr; 56% were women, and 56% black. Mean baseline SBP/DBP was 135/86 mm Hg. Lower sodium reduced NT-proBNP independent of diet (overall %-difference of -19%; 95% CI: -24, -14), but not hs-cTnI or hs-CRP (
Figure
). In contrast, DASH (vs control) reduced hs-cTnI by 18% (95% CI: -27, -7) and hs-CRP by 13% (95% CI: -24, -1), but not NT-proBNP. Combining both sodium reduction with DASH reduced hs-cTnI by 20% (95% CI: -31%, -7%), NT-proBNP by 23% (95% CI: -32%, -12%), and hs-CRP by 7% (95% CI: -22%, 9%) compared to the high sodium, control diet.

Conclusions:
Combining sodium reduction with a DASH dietary pattern represents an efficacious strategy to lower three distinct mechanisms of subclinical cardiac damage: injury, strain, and to a lesser extent inflammation.
Abstract 024: Effects Of Diet On 10-year Atherosclerotic Cardiovascular Disease Risk Using The Pooled Cohort Equations Risk Calculator: Results From The Dash Trial
Authors: Jeong Sun Young , Kovell Lara , Plante Timothy B , Wee Christina C , Miller Edgar R , Appel Lawrence J , Mukamal Kenneth J , Juraschek Stephen P
Published: May 2021

Background:
The Dietary Approaches to Stop Hypertension (DASH) diet is known to reduce cardiovascular disease (CVD) risk factors, but its effects on 10-year CVD risk based on the pooled cohort estimating equation has not been reported.

Objective:
To determine the effects of adopting the DASH diet on 10-year atherosclerotic cardiovascular disease (ASCVD) risk compared to a typical American (control) diet or a diet rich fruit and vegetables (F/V), but otherwise similar to control.

Methods:
The DASH trial was a 3-arm, parallel-group, randomized controlled feeding trial of 459 adults aged 22 to 75 years without CVD and not taking anti-hypertensive or diabetes medications. These participants were randomized to a control diet, a F/V diet, or the DASH diet for 8 weeks. Weight was kept constant. Blood pressure (BP) and lipids were measured at baseline and at 8-weeks to compare 10-year ASCVD risk scores across dietary assignments. Comparisons were performed via linear regression adjusted for baseline ASCVD risk score.

Results:
The mean age of participants was 45 years; 49% were women, 60% were black, and 10% were current smokers. Mean systolic BP was 131.3±10.8 mm Hg, mean LDL cholesterol was 121±32 mg/dL, and mean HDL cholesterol was 48±14 mg/dL. Both DASH and F/V diets shifted the distribution of ASCVD risk scores downward compared to the control diet (
Figure, Panel A
). Compared to the control diet, the DASH and F/V diets reduced 10-year ASCVD risk by 10.0% (95% CI: -17.7, -1.5;
P
= 0.02) and 11.7% (95% CI: -19.3, -3.3;
P
= 0.007) respectively (
Figure, Panel B
). There was no difference between the DASH and F/V diets (-1.9%; 95% CI: -10.3, 7.4;
P
= 0.68).

Conclusions:
Compared to the control diet, the DASH and F/V diets reduced 10-year ASCVD risk, while the DASH and F/V had similar effects.
Abstract 028: Biomarkers Of Kidney Function And Cognitive Ability: A Mendelian Randomization Study
Authors: Richard Erin , McEvoy Linda , Cao Steven , Lacroix Andrea Z , Salem Rany
Published: May 2021

Background:
Estimated glomerular filtration rate (eGFR), albuminuria and serum uric acid (SUA) are markers of kidney function that have been associated with cognitive ability. However, whether these associations are causal is unclear.

Methods:
We performed one-sample Mendelian randomization (MR) to estimate the effects of kidney function markers on cognitive performance using data from 357,590 participants from the UK Biobank. Polygenic scores for serum uric acid (SUA), urine albumin to creatinine ratio (ACR), estimated glomerular filtration rate based on serum creatinine (eGFRcre) and serum cystatin-c (eGFRcys) were used as instruments, and cognitive function outcomes included a test of verbal-numeric reasoning and reaction time. Sensitivity analyses were carried out to address potential pleiotropy using MR-Egger and weighted median regression.

Results:
We found no evidence of a causal effect of genetically determined SUA, eGFRcre or eGFRcys on either cognitive function outcomes. There was no association between a polygenic score for ACR and verbal-numeric reasoning. However, there was suggestive evidence of a relationship between genetically increased ACR and slower reaction time (β (95% confidence interval [CI])) for 1 standard deviation log ACR = 4.93 (1.60 to 8.26), p=0.004). Pleiotropy adjusted estimates were directionally consistent with those of the principal analysis but overlapped with the null.

Conclusions:
This MR study does not support causal effects of SUA, eGFRcre or eGFRcys on cognitive performance. Genetically-increased ACR was associated with lower processing speed, but results need confirmation in independent samples.
Abstract 046: Characteristics And Outcomes Of In-Hospital Cardiac Arrest Among Patients Diagnosed With COVID-19: A Systematic Review
Authors: Moon Jooyoung , Moon Hanna
Published: May 2021

Background:
In-hospital cardiac arrest (IHCA) is difficult to manage, especially so in severe COVID-19 patients. The aim of this study was to investigate the characteristics and prognosis of IHCA in patients who were diagnosed with COVID-19.

Methods:
We performed a systematic review using the PubMed, Embase, Google Scholar, and MedRxiv databases from December 1, 2019 to October 1, 2020. Two independent investigators reviewed studies reporting information on IHCA in COVID-19 patients.

Results:
Twelve studies and case reports met our inclusion criteria, including a total of 7,134 COVID-19 patients from six countries. IHCA occurred in 956 patients, and of these, CPR documentation was available in 634. The number of males were almost double that of females (65.9% vs. 34.1%), and the mean age ranged from 42 to 69. The initial cardiac rhythm at the time of CPR in descending order of frequency was pulseless electrical activity (43.2%), asystole (37.1%), ventricular fibrillation/pulseless ventricular tachycardia (9.9%), and other/unknown (9.8%). Common comorbidities included hypertension, diabetes, hyperlipidemia, heart disease, and chronic kidney disease. Rate of survival to discharge was 8.8% (56/634), and lower rates were associated with increasing age. Among those who survived, 44.2% (23/52) had moderate to severe neurological dysfunction, defined by cerebral performance category score of 3 or 4.

Conclusions:
IHCA in COVID-19 patients carry a poor prognosis. Risks are higher in those with comorbidities and the probability of survival is lower in older adults. Even after successful resuscitation, the risk of neurological complications is high. Further studies are needed to stratify risks and optimally manage IHCA in patients with COVID-19.
Abstract 052: Hypertensive Diseases In Pregnancy And Hemodynamic Stress Later In Life
Authors: Oshunbade Adebamike A , Lirette Seth , Kamimura Daisuke , Hamid Arsalan , Mathews Lena , Fox Ervin R , Kerut Edmund K , Granger Joey P , Butler Javed , Butler Kenneth R , Mosley Thomas , Hall Michael E
Published: May 2021

Background:
Hypertensive diseases in pregnancy have been associated with cardiovascular diseases later in life. However, less is known about the relationship between hypertensive diseases in pregnancy and hemodynamic stress later in life. We evaluated the relationship between hypertensive diseases in pregnancy and plasma levels of biomarkers of hemodynamic stress later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

Methods and Results:
We investigated 1605 women from the GENOA study (mean age 61±10 years, 57.1% African American).Women were classified as self-reported as nulliparous women (n=140), a history of normotensive pregnancies (n=1,195), a history of a hypertensive pregnancy (n= 229), or a history of preeclampsia (n= 41). We compared adjusted associations among this groups with 4 biomarkers of hemodynamic stress using generalized estimating equations to account for familial clustering. After adjusting for age, race, level of education, smoking history, hypertension, body mass index (BMI), history of coronary artery disease, and diabetes, women with a history of preeclampsia had higher levels of C-terminal proendothelin (CT-proET) compared to women with a history of normotensive pregnancies (Table, p=0.01). There were no significant differences in the levels of midregional proatrial natriuretic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), and C-Terminal proarginine vasopressin (CT-proAVP) in this groups.

Conclusions:
Elevated levels of CT-proET (a precursor to the potent vasoconstrictor Endothelin 1) demonstrates a strong relationship among those with a history of preeclampsia. Future studies are warranted to further explore the relationship between CT-proET in the pathogenesis of preeclampsia as well as subsequent changes in cardiovascular structure and function associated with a history of preeclampsia later in life.
Abstract 062: Global Patterns Of Mean Systolic Blood Pressure Over Three Decades: Results From The Global Burden Of Disease 2019 Study
Authors: Shakil Saate S , Johnson Catherine O , Roth Gregory A , Razo Christian A
Published: May 2021

Background:
Atherosclerotic cardiovascular disease and its risk factors are increasing globally. We estimated global and regional mean levels of systolic blood pressure (SBP) for the Global Burden of Disease (GBD) 2019 study.

Methods:
Mean SBP in mm Hg was estimated by age (adults >25 years), sex, location and year using all available population-based health surveys and studies that systematically measured brachial blood pressure. Estimates were produced using a Bayesian statistical model, spatiotemporal Gaussian process regression, which produces a smoothed time series from 1990 to 2019, borrowing strength over space and time, then aggregates to GBD regions. Each point in the figure represents age- and sex-specific mean SBP for one of 21 GBD regions, color coded by the 7 GBD super regions; black triangles denote global mean SBP. We report 95% uncertainty intervals in brackets.

Results:
Globally, mean SBP increased with age, peaking at 75-84 years, followed by a plateau and slight decline amongst oldest adults. In adults >60 in 1990 and >70 in 2019, females had higher SBP than males globally; this difference declined over time. In 1990, mean SBP was highest among females in Central Europe aged 60-64 (150 [147- 154]) and High-income Asia Pacific aged 80-84 (150 [147 - 152]), and in males aged 80-84 in Western Europe (150 [147-152]) and High-income Asia Pacific (148 [146 - 150]). By 2019, mean SBP was highest among adults aged 80-84 in Western and Southern Sub-Saharan Africa for both females (150 [136 - 164]; 149 [142 - 156], respectively), and males (145 [140 - 150]; 144 [136 - 153], respectively).

Conclusions:
SBP increased globally with age and was higher in older women than men. The 5-year age group with highest estimated SBP shifted over time from parts of Europe and High-income Asia Pacific to parts of Sub-Saharan Africa. Elevated SBP remains a major health risk for the world’s population, suggesting a need for increased investments in understanding its etiologies and how to treat and eventually prevent it as a cause of disease.
Abstract 077:
In Utero
Exposure To Metal Mixtures And Offspring Blood Pressure: An Analysis Of The Boston Birth Cohort Using Bayesian Kernel Machine Regression
Authors: Zhang Mingyu , Liu Tiange , Wang Guoying , Buckley Jessie P , Guallar Eliseo , Hong Xiumei , Wang Mei Cheng , Wills-Karp Marsha , Appel Lawrence J , Wang Xiaobin , Mueller Noel T
Published: May 2021

Background:
In utero
exposure to metals lead (Pb), cadmium (Cd), and mercury (Hg) may be associated with higher childhood systolic blood pressure (SBP), while trace elements manganese (Mn) and selenium (Se) may have protective, antioxidant effects that modify metal-SBP associations. No study has examined how
in utero
co-exposure to these metals affect offspring SBP.

Objectives:
To examine the individual and joint effects of
in utero
exposure to Cd, Pb, Hg, Mn, and Se on offspring SBP.

Methods:
We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured metals in maternal red blood cells collected 24-72 hours after delivery. We calculated child age-, sex-, and height-specific SBP percentile per 2017 American Academy of Pediatrics guidelines. We used linear regression models to estimate associations of each metal, and Bayesian kernel machine regression (BKMR) to examine metal co-exposures, with child SBP between 3 to 15 years of age.

Results:
Our analytic sample comprised 1194 mother-child pairs (61% Black, 20% Hispanic). Hg and Pb were not associated with child SBP. Se and Mn were inversely associated with child SBP: each log2(Se) and log2(Mn) increment was associated with a 6.23 (95% CI: 0.96-11.51) and a 2.62 (95% CI: 0.04-5.20) percentile lower child SBP, respectively. BKMR models showed similar results (
Panel A
). While Cd was not overall associated with child SBP, there was an antagonistic interaction between Cd and Mn (P-interaction = 0.036): the association of Mn and lower child SBP was stronger with higher levels of Cd (
Panel B
). Consistent with this finding,
in utero
exposure to cigarette smoke (a major source of Cd) modified the association of Mn and child SBP: among children born mothers who smoked cigarette in pregnancy, each log2(Mn) increment was associated with a 10.09 (95% CI: 2.15-18.03) percentile lower SBP (
Panel C
).

Conclusion:
Optimizing
in utero
Se levels, as well as Mn levels in pregnant women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood.
Abstract 078: Total Brachial Artery Reactivity And Incident Heart Failure And Heart Failure Sub-types: Multi-ethnic Study Of Atherosclerosis
Authors: Charry Daniela
Published: May 2021

Introduction:
Endothelial dysfunction may be a phenotypic expression of heart failure (HF). Total brachial artery reactivity (TBAR) is a non-invasive measurement of endothelial function that has been associated with increased risk of cardiovascular outcomes. Limited information is currently available on the impact of TBAR on incident HF and its subtypes. The aim of this study was to evaluate whether TBAR is associated with incident HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF) in a community-based study.

Hypothesis:
We hypothesized that TBAR would be inversely related with incident HF and both HF subtypes.

Methods:
Sample included 5,499 participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. Brachial artery ultrasound was performed after five minutes of cuff occlusion at the right forearm. TBAR was calculated as the difference between maximum and minimum brachial artery diameters following cuff release, divided by the minimum diameter multiplied by 100%. A dichotomous TBAR variable was created based on the median value (below or above 7.9%). Participants with EF ≤ 40% were considered HFrEF and those with EF ≥ 50% were considered HFpEF. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals.

Results:
Over a mean follow-up period of 12.5 years, incident HF was diagnosed in 250 participants; 106 classified as HFpEF, 98 as HFrEF, and 46 with unknown or borderline EF (41-49%). Crude analysis revealed that those with TBAR below the median have significantly higher risk of HF (HR 1.46; 95% CI 1.13-1.88, p<0.01) and HFrEF (HR 1.61; 95% CI 1.07-2.43, p<0.05). Following adjustment for known HF risk factors (e.g. age, gender, race, blood pressure, others), these relationships were no longer statistically significant. Borderline significant results were revealed in those with HFpEF (HR 1.43; 95% CI 0.97-2.12, p=0.06). Kaplan-Meier curves suggest significantly lower risks of developing HF and HFrEF in those with TBAR above the median (log-rank p<0.05 for both). When examined as a continuous variable, with a cut point of 50% for EF, every 1-standard deviation (9.7%) increase in TBAR resulted in a 19% and 29% decrease in risk of HF (p<0.05) and HFrEF (p=0.05), respectively.

Conclusions:
Lower TBAR values were associated with higher rates of incident HF and HFrEF, suggesting a possible role of endothelial dysfunction in HF pathogenesis. The impact of other known HF risk factors may mediate this relationship, thus further research is warranted.
Abstract 079: Nebivolol Associated With Reduced Incident Cardiovascular Events In Hypertensive Patients Compared With Non-vasodilatory Beta Blockers
Authors: Huck Daniel M , Rosenberg Michael A , Bristow Michael R , Stauffer Brian L
Published: May 2021

Introduction:
Beta blockers are not guideline-recommended first-line agents for hypertension, based on evidence that older generation beta blockers such as atenolol are associated with inferior reduction of some cardiovascular events compared to other antihypertensive classes. Vasodilatory beta blockers such as nebivolol have been found to have beneficial effects on peripheral vasculature through nitric oxide, endothelin-1, and tissue plasminogen activator pathways. The objective of this study is to compare longitudinal cardiovascular outcomes of hypertensive patients taking the vasodilatory beta blocker nebivolol with hypertensive patients taking the non-vasodilatory beta blockers atenolol and metoprolol.

Hypothesis:
Nebivolol will be associated with a reduction in odds of adverse cardiovascular outcomes compared with non-vasodilatory beta blockers.

Methods:
The study is a retrospective cohort analysis of de-identified data from adults in the University of Colorado health system with hypertension and on the vasodilatory beta blocker nebivolol or the non-vasodilatory beta blockers atenolol or metoprolol, without preceding diagnosis of cardiovascular or cerebrovascular disease. The primary outcome is incident cardiovascular hospitalization or diagnosis of cardiovascular event including heart failure, stroke, myocardial infarction, angina pectoris, or coronary revascularization based on diagnosis or procedure codes. Nearest-available propensity matching logistic regression was used, with each patient taking nebivolol matched to two control patients taking a non-vasodilatory beta blocker. Propensity matching variables included baseline demographics, cardiovascular risk factors, Charlson comorbidity index, other cardiovascular medications, and duration of follow-up.

Results:
There were 1395 patients taking nebivolol, and 20208 patients taking atenolol or metoprolol. Patients were predominantly female (54%, 11681 of 21603) and non-Hispanic white (75%, 16185 of 21603), with mean age of 60. The primary outcome occurred in 19% (259 of 1395) of those taking nebivolol, 29% (1891 of 6527) of those taking atenolol, and 40% (5500 of 13681) of those taking metoprolol. In propensity matched logistic regression, nebivolol is associated with reduced odds of incident cardiovascular events when compared to the non-vasodilatory beta blockers atenolol and metoprolol (OR 0.33, 95% CI 0.28 to 0.40). This association was also found with individual comparison with atenolol (OR 0.47, 95% CI 0.39 to 0.57) and metoprolol (OR 0.26, 95% CI 0.21 to 0.32).

Conclusions:
The vasodilatory beta blocker nebivolol is associated with reduced odds of incident cardiovascular events compared to non-vasodilatory beta blockers. Additional study of other beta blockers is necessary to determine if this is a vasodilatory beta blocker class effect, or is specific to nebivolol.
Abstract MP06: Healthy Diet Quality Is Associated With Epigenetic Age Deceleration
Authors: Kim Youjin , Ma Jiantao , Levy Daniel
Published: May 2021

Introduction:
Epigenetic age is a marker of healthy lifespan. Diet quality is known to be associated with the risk of developing chronic diseases; however, the relation between diet quality and epigenetic age remains to be investigated.

Hypothesis:
We tested the hypothesis that healthy diet quality is associated with favorable epigenetic age.

Methods:
Participants were drawn from the eighth examination of the Framingham Heart Study Offspring cohort (
n
=1,995; mean age 67 years; 55% women). Diet quality was estimated using Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS) derived from food frequency questionnaire. A second generation of epigenetic age, DNA methylation GrimAge, was calculated. Epigenetic age acceleration (GrimAA) was derived as residual after adjustment for chronological age using linear regression model.

Results and Conclusions:
Higher AHEI and MDS (i.e., healthier diet) were associated with decreased GrimAA after adjusting for age, sex, body mass index, smoking, physical activity, alcohol consumption, and energy intake (
P
< 0.001). We observed that the association of diet quality with GrimAA was stronger in ever-smokers (i.e., former and current smokers) compared to that in never-smokers (
P
interaction
< 0.001 for both scores). In ever-smokers, adjusted mean Grim AA was 3.95 years (95%CI: 3.47, 4.43) and 0.65 years (95%CI: 0.11, 1.19) in the lowest and highest AHEI quartile category, respectively, or GrimAA was reduced by 1.15 years (95%CI: 0.82, 1.48) per standard deviation (SD) increase in AHEI,
P
< 0.001. In never-smokers, adjusted mean GrimAA was -1.73 years (95%CI: -2.19, -1.26) and -2.37 years (95%CI: -2.80, 1.94) in the lowest and highest AHEI quartile category, respectively, or GrimAA was reduced by 0.23 years (95%CI: 0.05, 0.40) per SD increase in AHEI,
P
= 0.01. Similarly, for one SD increase in MDS, the GrimAA was reduced by 0.92 years (95%CI: 0.56, 1.27;
P
< 0.001) in ever-smokers, but by 0.19 years (95%CI: 0.01, 0.38;
P
= 0.04) in never-smokers. GrimAA significantly mediated the association between diet quality and all-cause mortality with the mean proportion of 37.0% for AHEI (
P
mediation
< 0.001) and 25.5% for MDS (
P
mediation
= 0.001). The mediation effect of GrimAA was more prominent in ever-smokers, which was twice the proportion found in never-smokers for both AHEI and MDS. In conclusion, higher diet quality is associated with decelerated epigenetic aging, which partially explains the beneficial relation of diet quality and healthy lifespan. These results also suggest that better diet quality could be more beneficial in ever-smokers.