bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic Analysis of the Reduction Processes of a Cisplatin Pt(IV) Prodrug by Mesna, Thioglycolic Acid, and Thiolactic Acid
Authors: Xia Yanqing , Tian Hongwu , Li Yanlei , Yang Xinru , Liu Jinming , Liu Chunli , Zhou Li , Zhang Lincai , Li Tiejian , Shi Tiesheng
Published: November 2020

Although Mesna is an FDA-approved chemotherapeutic adjuvant and an antioxidant based largely on its antioxidative properties, kinetic and mechanistic studies of its redox reactions are limited. A kinetic analysis of the reduction processes of cis-diamminetetrachloroplatinum(IV) (cis-[Pt(NH3)2Cl4], a cisplatin Pt(IV) prodrug) by thiol-containing compounds Mesna, thioglycolic acid (TGA), and DL-thiolactic acid (TLA) was carried out in this work at 25.0°C and 1.0 M ionic strength. The reduction processes were followed under pseudo-first-order conditions and were found to strictly obey overall second-order kinetics; the observed second-order rate constant k′ versus pH profiles were established in a wide pH range. A general reaction stoichiometry of Δ[Pt(IV)] : Δ[Thiol]tot = 1 : 2 was revealed for all the thiols; the thiols were oxidized to their corresponding disulfides which were identified by mass spectrometry. Reaction mechanisms are proposed which involves all the prololytic species of the thiols attacking the Pt(IV) prodrug in parallel, designating as the rate-determining steps. Transient species chlorothiol and/or chlorothiolate are formed in these steps; for each particular thiol, these transient species can be trapped rapidly by another thiol molecule which is in excess in the reaction mixture, giving rise to a disulfide as the oxidation product. The rate constants of the rate-determining steps were elucidated, revealing reactivity enhancements of (1.4–8.9) × 105 times when the thiols become thiolates. The species versus pH and reactivity of species versus pH distribution diagrams were constructed, demonstrating that the species ‒SCH2CH2SO3‒ of Mesna largely governs the total reactivity when pH > 5; in contrast, the form of Mesna per se (mainly as HSCH2CH2SO3‒) makes a negligible contribution. In addition, a well-determined dissociation constant for the Mesna thiol group (pKa2 = 8.85 ± 0.05 at 25.0°C and μ = 1.0 M) is offered in this work, which was determined by both kinetic approach and spectrophotometic titration method.
Ring Extensions with Finitely Many Non-Artinian Intermediate Rings
Authors: Jarboui Noômen , Al-Kuleab Naseam , Almallah Omar
Published: November 2020

The commutative ring extensions with exactly two non-Artinian intermediate rings are characterized. An initial step involves the description of the commutative ring extensions with only one non-Artinian intermediate ring.
Identification of Monotonically Differentially Expressed Genes across Pathologic Stages for Cancers
Authors: Tian Suyan , Wang Chi , Tang Mingbo , Li Jialin , Liu Wei
Published: November 2020

Given the fact that cancer is a multistage progression process resulting from genetic sequence mutations, the genes whose expression values increase or decrease monotonically across pathologic stages are potentially involved in tumor progression. This may provide insightful clues about how human cancers advance, thereby facilitating more personalized treatments. By replacing the expression values of genes with their GeneRanks, we propose a procedure capable of identifying monotonically differentially expressed genes (MEGs) as the disease advances. Using three real-world gene expression data that cover three distinct cancer types—colon, esophageal, and lung cancers—the proposed procedure has demonstrated excellent performance in detecting the potential MEGs. To conclude, the proposed procedure can detect MEGs across pathologic stages of cancers very efficiently and is thus highly recommended.
The Protective Effects of the Ethyl Acetate Part of Er MiaoSan on Adjuvant Arthritis Rats by Regulating the Function of Bone Marrow‐Derived Dendritic Cells
Authors: Ding Jiemin , Liu Min , Xuan Zihua , Liu Meng li , Wang Ning , Jia Xiaoyi
Published: November 2020

Aims. The aim of this study was to evaluate the protective effects of Er Miao San (EMS) and the regulative function of bone marrow‐derived dendritic cells (BMDCs) on adjuvant arthritis (AA) in rats. Methods. The ethyl acetate part of EMS (3 g/kg, 1.5 g/kg, and 0.75 g/kg) was orally administered from day 15 after immunization to day 29. The polyarthritis index and paw swelling were measured, the ankle joint pathological changes were observed using hematoxylin‐eosin (HE) staining, and the spleen and thymus index were determined. Moreover, T and B cell proliferation were determined using the CCK‐8 assay. The expression of BMDC surface costimulatory molecules and inflammatory factors were determined using flow cytometry and ELISA kits, respectively. Results. Compared with the AA model rats, the ethyl acetate fraction of EMS obviously reduced paw swelling (from 1.0 to 0.7) and the polyarthritis index (from 12 to 9) (P < 0.01) and improved the severity of histopathology (P < 0.01). The treatment using ethyl acetate fraction of EMS significantly reduced the spleen and thymus index (P < 0.01) and inhibited T and B cell proliferation (P < 0.01). Moreover, EMS significantly modulated the expression of surface costimulatory molecules in BMDCs, including CD40, CD80, CD86, and major histocompatibility complex class II (MHC‐II) (P < 0.01). The results also showed that the ethyl acetate part of EMS significant inhibited the levels of proinflammatory cytokines interleukin‐ (IL‐) 23 tumor necrosis factor‐ (TNF‐) α and inflammatory factor prostaglandin (PG) E2 in the supernatant of BMDCs. However, the level of anti‐inflammatory cytokine IL‐10 was significantly increased (P < 0.01). Conclusion. These results suggest that the ethyl acetate part of EMS has better protective effects on AA rats, probably by regulating the function of BMDCs and modulating the balance of cytokines.
Investigation on Nonlinear Flow Behavior through Rock Rough Fractures Based on Experiments and Proposed 3-Dimensional Numerical Simulation
Authors: Liu Xianshan , Li Man , Zeng Nandou , Li Tao
Published: November 2020

Rock fractures as the main flow channels, their morphological features, and spatial characteristics deeply influence the seepage behavior. Reservoir sandstones as a case study, four splitting groups of fractures with different roughness were scanned to get the geometric features, and then the seepage experiments were taken to analyze the relationship of the pressure gradient

∇
P

and flow rate

Q

, and the critical Reynolds number(

Re

c

) and wall friction factor (

f

) were determined to explain the translation of linear seepage to nonlinear seepage condition. Based on the scanning cloud data of different rough fractures, the fractures were reconstructed and introduced into the COMSOL Multiphysics software; a 3-dimensional seepage model for rough fractures was calibrated and simulated the seepage process and corresponding pressure distribution, and explained the asymmetry of flow velocity. And also, the seepage characteristics were researched considering aperture variation of different sample fractures; the results indicated that increasing aperture for same fracture decreased the relative roughness, the fitting coefficients by Forchheimer formula based on the data

∇
P

~

Q

decreased, and the figures about the coefficients and corresponding aperture described nonlinear condition of the above rough fractures. In addition, the expression of wall friction factor was derived, and relationship of

f

,

Re

, and relative roughness indicated that

f

increased with increasing fracture roughness considering the same aperture, resulting in nonlinear flow more easily, otherwise is not, showing that

f

could be used to describe the seepage condition and corresponding turning point. Finally, it can be seen from the numerical results that the nonlinearity of fluid flow is mainly caused by the formation of eddies at fracture intersections and the critical pressure gradient decreases with increasing angle. And also, analysis about the coefficient

B

in the Forchheimer law corresponding to fracture intersections considering the intersecting angle and surface roughness is proposed to reveal the flow nonlinearity. The above investigations give the theoretical support to understand and reveal the seepage mechanism of the rock rough fractures.
Boundary Effect and Dynamic Response Study for the Penetration of Rigid Projectiles into Thick, Finite-Radius, Metallic Targets
Authors: Wang Juan , Zhao Junhai , Zhou Yuan , Sun Shanshan
Published: November 2020

This study uses the unified strength theory to analyse the elastoplastic stage and plastic stage of a linear strain-hardening target material while considering the effects of the intermediate principal stress and the free lateral boundaries of the target. In this investigation, analytical solutions of the radial stress in the cavity wall are obtained, and a unified penetration model of the target material is built. On this basis, penetration resistance formulas and penetration depth formulas for rigid projectiles with various nose shapes penetrating into thick, finite-radius, metallic targets are deduced, the solutions of which are obtained by utilizing the Simpson method. Accordingly, the proposed method offers a broader scope of application and higher accuracy than previous methods. Through this method, a series of analytical solutions based on different criteria can be obtained, and the penetration depth ranges of targets under different striking velocities can be effectively predicted. Moreover, penetration processes under different conditions are numerically simulated using the software ANSYS/LS-DYNA to study the motion law of the projectiles and the dynamic response of the targets. From the theoretical and numerical approaches, a list of influencing factors for terminal ballistic effects are analysed, including the strength criterion differences, the strength parameter b, the striking velocity

v

0

, the projectile nose shape, and the target radius-to-projectile radius ratio rt/a. The results indicate that, as b changes from 1 to 0, the penetration depth Dmax increases by 22.45%. Additionally, Dmax increases by 40.76% when rt/a changes from 16 to 4; hence, it cannot be calculated as an unlimited-size target anymore when rt/a ≤ 16. In weapons field tests, the radius of the metallic target can be conservatively designed to be greater than 28 times the projectile radius to ignore the effect from the free lateral boundaries of the target.
Exploring HIV-Related Stigma and Discrimination at the Workplace in Southwestern Uganda: Challenges and Solutions
Authors: Twinomugisha Benedict , Ottemöller Fungisai Gwanzura , Daniel Marguerite
Published: November 2020

Globally, the HIV/AIDS pandemic continues to have an enormous impact on affected societies. Despite several health promotion interventions being carried out, HIV/AIDS remains a major cause of deaths in low and middle income countries. At the workplace, the pandemic has brought about reduction in productivity, increased staff turnover, increased production costs, high levels of stigma, etc. HIV stigma is one of the main reasons why the pandemic has continued to devastate a number of societies around the world. HIV stigma presents barriers to HIV prevention in different settings including the workplace. Unlike large enterprises, small-scale enterprises have received less attention in the fight against HIV/AIDS. This study’s purpose was to explore how employers and employees can overcome challenges of HIV-related stigma at the workplace. This study employed a qualitative case study design. Data were collected from eighteen participants in three small-scale enterprises in Kabale. Findings indicate that small-scale enterprises are faced with the fear of HIV testing, status disclosure, staff turnover, suicidal thoughts, gossip, etc. Implementing operative national HIV workplace policies may enable small-scale enterprises to overcome challenges of HIV-related stigma at the workplace.
Palliative Surgical Management of a Metastatic Lesion of the Tibia with Extension into the Popliteal Fossa Using Polytetrafluoroethylene Felt and Bone Cement
Authors: Papavasiliou Kyriakos , Asteriadis Konstantinos , Panagiotidou Sousana , Tsiridis Eleftherios
Published: November 2020

The treatment of metastatic bony lesions with the involvement of adjacent neurovascular structures presents a surgical challenge. We present—to the best of our knowledge—the first case of a patient suffering from a metastatic lytic lesion at the proximal tibia who underwent palliative treatment with the use of a polytetrafluoroethylene (PTFE) felt as a liner in order to preserve the adjacent vasculature and nerves. An 82-year-old female patient was diagnosed with multiple lytic bone metastases from renal cell carcinoma. One of these metastatic lesions was located at the proximal metaphysis of the left tibia. The lesion destructed the proximal metaphyseal part and the posterior cortex, and it was extending into the popliteal fossa. As a result, the patient was unable to bear weight. The patient was not fit to undergo radical operative treatment. As a means of palliative therapy, she underwent intralesional curettage and instillation of Poly-Methyl-Methacrylate (PMMA) bone cement using an alternative novel surgical technique with the use of a PTFE felt as a liner in order to protect the adjacent vasculature and nerves. This technique has proven to be successful in preventing cement leak into the popliteal cavity and efficient in allowing the patient to bear weight and walk independently until she demised 14 months later. The use of a PTFE felt as a liner, when treating lytic lesions, in order to protect the adjacent vasculature and nerves from PMMA leakage, is a helpful novel surgical option in cases when a radical treatment cannot be implemented.
External Iliac Artery Injury and Thrombosis during Laparoscopic Gynecologic Surgery
Authors: Ishikawa Masako , Nakayama Kentaro , Razia Sultana , Yamashita Hitomi , Ishibashi Tomoka , Sato Seiya , Sasamori Hiroki , Sawada Kiyoka , Kurose Sonomi , Ishikawa Noriyoshi , Suehiro Shoichi , Kyo Satoru
Published: November 2020

Although vascular injury during laparoscopic surgery is rare, it is occasionally reported. Previously, several physicians have reported cases of compartment syndrome resulting from a thrombus during gynecologic surgery. However, few reports describe thrombosis occurring in artery vessels as a result of applying angiopressure. Herein, we report the case of a 53-year-old woman with endometrioid carcinoma and a vascular injury that resulted in thrombus formation; this is the first such case to be reported. The complication was successfully treated by means of direct anastomosis following partial resection of the injured iliac artery. This is the first report of a case in which applying angiopressure for a vascular injury during laparoscopic pelvic lymphadenectomy led to an intra-arterial thrombus which was found and treated without sequelae.
Prevalence and Antimicrobial Resistance of Escherichia coli Isolated from Various Meat Types in the Tamale Metropolis of Ghana
Authors: Adzitey Frederick , Assoah-Peprah Prince , Teye Gabriel A. , Somboro Anou M. , Kumalo Hezekiel M. , Amoako Daniel G.
Published: November 2020

Meats are important potential sources of foodborne pathogens including Escherichia coli. This study was conducted to determine the prevalence and antimicrobial resistance of Escherichia coli isolated from meats in the Tamale metropolis of Ghana. Isolation of Escherichia coli was done using the procedure according to the USA-FDA Bacteriological Analytical Manual. Antibiotic resistance patterns in the Escherichia coli isolates were determined by the Kirby-Bauer disk diffusion method against 8 antibiotics. The overall prevalence of Escherichia coli in the meat samples was 84.00% (189/225). Mutton (88.89%), guinea fowl (88.89%), beef (86.67%), local chicken (80.00%), and chevon (75.56%) were contaminated by Escherichia coli. The average coliform count was 4.22 cfu/cm2 and was highest in guinea fowl (4.94 log cfu/cm2) and lowest in local chicken (3.23 log cfu/cm2). The Escherichia coli isolates were highly resistant to erythromycin (85.00%), tetracycline (73.33%), and ampicillin (71.67%). The multiple antibiotic resistance (MAR) index ranged from 0.13 to 1. The Escherichia coli isolates exhibited 23 antimicrobial resistance patterns with resistant pattern TeAmpE (tetracycline-ampicillin-erythromycin) being the most common. Multidrug resistance was 68.33% (41/60) among the Escherichia coli isolates. The results showed that Escherichia coli was commonly present in the various meat types and exhibited multidrug resistances, necessitating efficient antibiotic stewardship guidelines to streamline their use in the production industry.
Treatment of Dyspepsia, Heartburn, and Related Symptoms with Gastricumeel Compared to Proton Pump Inhibitors: A Prospective Reference-Controlled Observational Study
Authors: van Haselen Robbert , Cesnulevicius Konstantin
Published: November 2020

Background: Dyspepsia and heartburn are extremely common conditions, thus a search for safe and effective treatment alternatives is justified. Objectives: To demonstrate the noninferiority of Gastricumeel (Ga6) in terms of effectiveness and safety to proton pump inhibitors (PPIs) in the treatment of patients with dyspepsia and/or heartburn. Methods: Prospective, comparative, observational cohort study. Patients with dyspepsia or heartburn were treated either with Ga6 or with PPIs as monotherapy during approximately 6 weeks. The intensity of eight symptoms was assessed as well as overall condition, treatment compliance and tolerability, and any adverse drug reactions. Adjustment for covariates was done via the calculation of propensity scores in logistic regression. Results: A total of 640 patients (447 Ga6, 193 PPIs) from 48 German general practices participated. More than half the patients had suspected acute gastritis and around 40% of patients had heartburn. Adjusted between-treatment difference scores of changes in the intensity of the eight assessed symptoms were within the bounds for noninferiority of Ga6 compared to PPIs. Effectiveness ratings were comparable; compliance and tolerability were rated better in the Ga6 group. Conclusion: It is worth considering Ga6 as a safe and effective treatment option in the management of dyspepsia and heartburn.
Descrevendo o bom-tom: transferência e mediação da moda impressa na França para o Brasil na metade do século XIX
Authors: Barbosa Everton Vieira
Published: November 2020

Desde os primórdios da publicação de periódicos femininos sobre moda no Brasil Oitocentista, a França se destacava como uma referência cultural. As constatações desta afirmação aparecem nos diversos artigos de moda, assim como na inserção de estampas litografadas, representando vestidos e padrões de bordados, a fim de instruir suas leitoras sobre as distintas indumentárias que poderiam ser usadas em determinados espaços de sociabilidade públicos e privados, na perspectiva de uma pedagogia do olhar. O surgimento do periódico feminino O Jornal das Senhoras (1852-1855), considerado um dos primeiros impressos dirigidos por mulheres no Brasil, reforça a ideia da pedagogia do olhar, na medida em que quase 80% das edições publicadas tiveram a inserção de uma estampa ilustrando vestidos ou padrões de bordado. Grande parte destas ilustrações eram extraídas do periódico de moda francês Le Moniteur de la Mode (1843-1913), assim como a descrição da estampa, traduzida para o português. Neste sentido, propomos compreender as trocas existentes entre os mediadores culturais envolvidos neste processo, e os meios utilizados na transferência cultural da moda francesa para o Brasil.
O Brasil no Mercure de France e o Mercure de France no Brasil (Séculos XIX E XX)
Authors: López Camila Soares
Published: November 2020

No fim do século XIX, o Simbolismo estabeleceu-se no campo literário francês e, para garantir a difusão de suas obras, seus representantes fundaram as petites revues. Nas páginas dessas publicações, não figuraram apenas as contribuições de autores franceses, mas, também, de outras nacionalidades. O Mercure de France, cuja série moderne data de 1890, foi uma petite revue que circulou em Paris e aportou em outros locais, a exemplo do Brasil. Neste artigo, discutiremos a chegada do Mercure entre nossos escritores e redações de periódicos, bem como discorreremos sobre as rubricas “Lettres Portugaises” e “Lettres Brésiliennes”. Ademais, consideraremos a representatividade de Xavier de Carvalho, Philéas Lebesgue, Figueiredo Pimentel e dos jornais O Paiz e Gazeta de Notícias nesse diálogo entre França e Brasil.
Nonada ou travessia: reflexões sobre o sertão de Guimarães Rosa e do Brasil
Authors: Pelissaro Suelen Rosa
Published: November 2020

Trata a relação entre a geografia e a literatura de João Guimarães Rosa. A partir da leitura de seus contos, confrontados com estudos de materialismo histórico que abordam criticamente a territorialização do País, discute-se como a concepção do autor sobre o sertão pode contribuir para um debate geográfico de viés crítico, de maneira a enquadrá-lo entre os pensadores intérpretes do Brasil e seu sentido de formação. Como resultado, compreende-se que sua literatura não só aproximou as duas esferas de conhecimento, como também apresentou as visões de Brasil e de sua constituição dentro dos impasses contextuais de se projetar o país. A contribuição de João Guimarães Rosa para se pensar o sertão como território imbuído de contradições seria um dos grandes legados de todo o conjunto da obra do autor.
Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex
Authors: Sheu Wayne Huey-Herng , Lin Keng-Hung , Wang Jun-Sing , Lai De-Wei , Lee Wen-Jane , Lin Fu-Yu , Chen Po-Hsun , Chen Cheng-Hsu , Yeh Hsiang-Yu , Wu Sheng-Mao , Shen Chin-Chang , Lee Maw-Rong , Liu Shing-Hwa , Sheu Meei-Ling
Published: November 2020

Objective:

Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear.

Approach and Results:

Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. N
ε
-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography–tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model.

Conclusions:

The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.
Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor
Authors: Barreto Joaquim , Karathanasis Sotirios K. , Remaley Alan , Sposito Andrei C.
Published: November 2020

Atherosclerosis, the underlying cause of cardiovascular disease (CVD), is a worldwide cause of morbidity and mortality. Reducing ApoB-containing lipoproteins—chiefly, LDL (low-density lipoprotein)—has been the main strategy for reducing CVD risk. Although supported by large randomized clinical trials, the persistence of residual cardiovascular risk after effective LDL reduction has sparked an intense search for other novel CVD biomarkers and therapeutic targets. Recently, Lox-1 (lectin-type oxidized LDL receptor 1), an innate immune scavenger receptor, has emerged as a promising target for early diagnosis and cardiovascular risk prediction and is also being considered as a treatment target. Lox-1 was first described as a 50 kDa transmembrane protein in endothelial cells responsible for oxLDL (oxidized LDL) recognition, triggering downstream pathways that intensify atherosclerosis via endothelial dysfunction, oxLDL uptake, and apoptosis. Lox-1 is also expressed in platelets, where it enhances platelet activation, adhesion to endothelial cells, and ADP-mediated aggregation, thereby favoring thrombus formation. Lox-1 was also identified in cardiomyocytes, where it was implicated in the development of cardiac fibrosis and myocyte apoptosis, the main determinants of cardiac recovery following an ischemic insult. Together, these findings have revealed that Lox-1 is implicated in all the main steps of atherosclerosis and has encouraged the development of immunoassays for measurement of sLox-1 (serum levels of soluble Lox-1) to be used as a potential CVD biomarker. Finally, the recent development of synthetic Lox-1 inhibitors and neutralizing antibodies with promising results in animal models has made Lox-1 a target for drug development. In this review, we discuss the main findings regarding the role of Lox-1 in the development, diagnosis, and therapeutic strategies for CVD prevention and treatment.
Abstract 12717: Enhance Negative Modulation of Beta
3
-Adrenergic Stimulation on Cardiomyocyte Functional Performance, [Ca
2+
]
i
Regulation and β-Adrenergic Reserve in Rats Expressing Human Angiotensinogen Gene
Authors: Cao Jing , Sun Xiaoqiang , Cheng Heng Jie , Li Tiankai , Liu Yixi , VonCannon Jessica L , Ferrario Carlos M , Cheng Che
Published: November 2020

Background:
Transgenic rats expressing the human angiotensinogen gene [TGR (hAogen) 1623] (hAogen) exhibit sustained hypertension and systolic dysfunction associated with altered cardiac renin-angiotensin system and β- adrenergic receptor (AR) signal transduction systems. We have shown previously, in contrast to β
1
- and β
2
-ARs, β
3
-ARs are linked to G
i
proteins, and stimulation of β
3
-ARs inhibits cardiac contraction and relaxation. Hypertension is associated with increased cardiac expression of G
i
proteins. This may alter β
3
-AR stimulation and play an important role in the cardiac functional impairment of this humanized model of hypertension. However, the alteration and functional effect of β
3
-AR activation in this model are unknown. We tested the hypothesis that high cardiac tissue Ang II content in hAogen may cause an up-regulation of cardiac β
3
-AR, which exacerbates myocyte dysfunction and impairs calcium regulation, thereby directly contributing to the cardiac dysfunction.

Methods:
We compared LV myocyte β
3
-AR expression and myocyte functional and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to β- and β
3
-AR stimulation in myocytes obtained from 8 Sprague Dawley (SD) control and 8 hAogen male adult rats.

Results:
Versus SD, in hAGT rats, basal myocyte contraction (dL/dt
max
, 107.1 vs 138.8 μm/s), relaxation (dR/dt
max
, 94.0 vs 103.9 μm/s) and [Ca
2+
]
iT
(0.15 vs 0.21) were depressed. A non-selective β-AR agonist, isoproterenol (ISO) (10
-8
M) produced significantly smaller increases in dL/dt
max
, (42% vs. 61%), dR / dtmax (35% vs. 51%), and [Ca
2+
]
iT
(20% vs. 30%). Moreover, versus SD, in hAogen rats, LV myocyte β
3
-AR protein level increased by 32% (0.29 vs 0.22) with resulted significantly altered myocyte functional response to β
3
-AR stimulation. Compared with the changes in SD myocytes, in hAogen myocytes, BRL (10
-8
M) produced a significantly greater decreases in dL/dt
max
, (27% vs 12%), dR/dt
max
(28% vs 11%), and [Ca
2+
]
iT
(17% vs 10%).

Conclusions:
TGR (hAogen) 1623, this humanized model of hypertension is associated with an up-regulation of LV myocyte β
3
-AR, which enhances β
3
-AR-caused inhibition of myocyte contractile, relaxation and [Ca
2+
]
iT
and exacerbates β-AR desensitization, thereby directly contributing to the cardiac dysfunction.
Abstract 12725: Smokers Are Aware of Their Health Risk
Authors: Tsuji Hisako , Oishi Yohei , Akita Yuzo , Shiojima Ichiro
Published: November 2020

Background:
Health checkup results, even if 12-lead ECG and chest X-ray are included, usually do not reflect risk of smoking and it may lead smokers to continue smoking. Therefore, to show specific risk amount of smoking, 10-year cardiovascular (CV) risks were calculated with and without smoking at the same level of other risk factors and the information was sent to the smokers. Smoking cessation rate was compared between smokers with and without the information.

Methods:
In subjects who had the annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2018, the brochure which included the 2 values of 10-year CV risks calculated by the Framingham risk score (2008) based on the results of the health checkup was sent to male smokers aged 40 between 74 with no history of CV disease and the 10-year CV risk between 10% and 40%. Male smokers with the same condition were extracted from subjects who had the annual health checkup in 2017 as the control subjects. Smoking cessation was evaluated at the health checkup next year.

Results:
The brochure was sent to 499 smokers in 2018 and 344 of those received the health checkup in 2019. The 10-year CV risk of smokers was 1.80±0.05 times higher than that of non-smokers at the same level of other risk factors. As the control subjects, 568 smokers were extracted from 2017 checkup and 407 of those received the health checkup in 2018. Clinical characteristics of the 2018 checkup (n=344) and the 2017 checkup (n=407) groups were similar in terms of age, clinical risk factors, duration of smoking and number of cigarettes smoked per day. Smoking cessation rate of the 2018 checkup group next year was 7.0% while that of the 2017 checkup group was 7.1%. By the logistic regression analysis adjusted for age, duration of smoking and number of cigarettes smoked per day, smoking cessation rate of the 2018 checkup group was not higher than that of the 2017 checkup group (odds ratio=0.97, 95% confidence interval=0.55 to 1.71, p=0.9131).

Conclusions:
Showing specific amount of risk by smoking was not helpful for smoking cessation. Most smokers seem to be aware of the risk. To promote smoking cessation, interventions such as increased price of cigarette and/or limitation of smoking area may be more practical than emphasizing health hazards of smoking.
Abstract 12881: Noninvasive
In Vivo
Assessment of Cardiac Metabolism in Dobutamine-stressed Ischemic Rat Hearts Using Hyperpolarized
13
C MRI
Authors: Sharma Gaurav , Funk Alexander , Wen Xiaodong , Harrison Crystal , Maptue Nesmine , Sherry A. Dean , Khemtong Chalermchai , Malloy Craig R
Published: November 2020

Introduction and Hypothesis:
Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP)
13
C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1-
13
C]pyruvate.

Methods:
Metabolism of HP[1-
13
C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner.
13
C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned
1
H/
13
C linear volume coil. Anatomical
1
H images were acquired for slice planning and positioning.
13
C intensity maps were generated and displayed as overlays on grayscale
1
H images. In separate experiments,
in vivo
HP-
13
C-MRS data acquisition was initiated immediately after the pyruvate injection.

Results:
The HP signals from [1-
13
C]lactate, [1-
13
C]alanine, and
13
C-bicarbonate were detected in real-time
13
C spectra from hearts following injection of HP[1-
13
C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation.

Conclusions:
Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.
Abstract 12894: Suppressed Local Coagulative Response After Newer-generation Ultrathin Strut SES Implantation Compared to Older-generation SES Implantation
Authors: Yamaguchi Koji , Wakatsuki Tetsuzo , Takahashi Tomonori , Kadota Muneyuki , Kawabata Yutaka , Matsuura Tomomi , Ise Takayuki , Kusunose Kenya , Tobiume Takeshi , Yagi Shusuke , Yamada Hirotsugu , Soeki Takeshi , Sata Masataka
Published: November 2020

Background:
We have previously demonstrated local persistent hypercoagulation after durable polymer (DP)-sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment 1+2 (F1+2) levels. The aim of this study is to evaluate local coagulative response after newer-generation ultrathin strut SES implantation.

Method:
Forty-five patients who were treated about 6-12 months earlier with coronary stenting, with no evidence of restenosis, were studied [DP-SES (Cypher): 26pts, biodegradable polymer (BP)-SES (older BP-SES, Ultimaster): 12pts and ultrathin strut BP-SES (newer BP-SES, Orsiro): 7pts]. We measured plasma levels of F1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Δ) was defined as CS level minus V level.

Results:
No significant difference was observed in the percent diameter stenosis among DP-SES, older BP-SES, and newer BP-SES groups (10.1 ± 16.5 vs 13.1 ± 12.9 vs 12.1 ± 11.9 %). The ΔF1+2 was significantly lower in the BP-SES groups than in the DP-SES group (8.9 ± 10.1 vs 23.4 ± 21.1 pmol/l, p<0.05). The ΔF1+2 was lower in the newer BP-SES group than in the older BP-SES group, however, significant difference was not observed (7.0 ± 7.0 vs 9.7 ± 12.3 pmol/l).

Conclusion:
Suppressed local coagulative response after newer-generation ultrathin strut SES implantation was observed. These findings might indicate that lower strut thickness is more important factor than faster polymer resorption in the newer-generation DES era.
Abstract 12897: Coenzyme Q10 in the Treatment of Heart Failure With Preserved Ejection Fraction: A Prospective, Randomized, Double-blind Trial
Authors: Samuel Tal Y , Hasin Tal , Gotsman Israel , Weitsman Tanya , Ben Ivgi Fanny , Dadon Ziv , Asher Elad , Alcalai Ronny , Leibowitz David
Published: November 2020

Background:
Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in the elderly and is increasing in prevalence. No specific treatment for this condition appears to be effective. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production and reduced levels have been noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF in particular in the elderly.

Aim:
To evaluate the effect of CoQ10 supplementation on diastolic function in patients with HFpEF.

Methods:
A prospective, randomized, double-blind, placebo-controlled trial. Inclusion criteria were age > 50 years, New York Heart Association class II-IV, ejection fraction > 50%, and evidence of impaired diastolic function defined as lateral e' < 0.09 cm/sec, average E/e' > 13 or average E/e' > 8 with additional markers of impaired diastolic function such as delayed relaxation (E/A < 0.5), elevated left atrial volume index (> 40ml / m
2
) elevated left ventricular mass index ( > 122 gr/ m
2
♀ or 149 gr/ m
2
♂) or pulmonary hypertension. Patients with other forms of cardiomyopathies or treated with chronic renal replacement therapy were excluded. Echocardiographic studies and levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) were completed at baseline and following 4 months of CoQ10 (300 mg daily) or placebo supplementation.

Results:
A total of 39 patients were enrolled, 19 patients in the CoQ10 and 20 patients in the placebo group. Groups were similar in baseline clinical characteristics. Compliance was high and similar between groups (average 208 ± 108 mg/day for the CoQ10 versus 212 ± 95 mg/day for the placebo group). No significant effect was observed on indices of diastolic function or NT-proBNP levels following 4 months of CoQ10 use.

Conclusions:
Treatment with CoQ10 did not affect indices of diastolic function or NT-proBNP levels in patients with HFpEF. Our study does not support the routine use of CoQ10 in patients with HFpEF.
Abstract 13218: Machine Learning Can Identify Cardiology Patients With High Future Healthcare Utilization in a Large Regional Health System
Authors: Jing Linyuan , Challa Rameswara S , Ulloa Alvaro , Cauthorn William C , Hartzel Dustin , Leader Joseph , Rocha Daniel B , Haggerty Christopher M , Fornwalt Brandon
Published: November 2020

Introduction:
Healthcare cost has increased drastically in the last decade, and over 50% of the cost can be attributed to a small portion (5-10%) of the population. Certain clinical programs, such as home-based care, aim to reduce this utilization but need methods to identify the most appropriate patients to enroll. We hypothesized that machine learning can predict patients with high future utilization with good accuracy.

Methods:
683,160 cardiology patients (defined broadly as those with an ECG, echocardiogram or cardiology visit) with ~17 million clinical episodes since 2004 were identified from Geisinger’s electronic health records. Utilization was estimated as total cost of care for outpatient, inpatient and emergency department visits. Patients with the highest 10% utilization in a given year were defined as high utilizers. Machine learning models were used to predict high utilization over the next 3, 6 and 12 months. Input variables (n=191) included age, sex, smoking, 5 vital signs, 21 labs, 18 medications (current and past), 40 ECG and 44 echocardiographic measurements, 43 comorbidities, 7 time / cyclical features, 6 past utilization metrics and 4 social metrics (e.g. distance to healthcare facilities).

Results:
XGBoost achieved the best performance with areas under the ROC curve (AUC) of 0.82, 0.81 and 0.78 for 3, 6, 12-month models, and average precision scores (AP) of 0.31, 0.36 and 0.37, respectively, while the commonly used Charlson Comorbidity Index had poor performance with AUCs of 0.63 - 0.64 and APs of 0.1 - 0.17. Past utilization was the best predictor of future utilization. Targeting patients with the top 5 and 10% highest risk for utilization achieved sensitivities of 26 and 40% and positive predictive values of 50 and 38% (12-month model, Figure).

Conclusions:
Machine learning can be used to predict which patients will have high future healthcare utilization. This may help target populations for intervention programs aimed at reducing utilization.
Abstract 13259: Differences in Glucose Readings Between Right Arm and Left Arm Using a Continuous Glucose Monitor
Authors: Liu Xiaohan , Kawakatsu Sonoko , Tran Brandon , Tran Brittany , Manzanero Lucy , Shih Eric , Shek Allen , Lim Jeremy , Shah Sachin A
Published: November 2020

Introduction:
Poorly controlled diabetes increases the risk of cardiovascular disease and associated complications. Continuous glucose monitoring (CGM) devices are tools that allow clinicians and patients to gather real-time glucose levels to enhance glycemic control. CGM devices are increasingly used to optimize diabetes management, but there is no guidance on whether glucose readings differ when a CGM device is placed on the right versus the left arm. We assessed the hypothesis that a difference in time-matched glucose levels will be observed between the right and left arm.

Methods:
This prospective trial enrolled 46 adult volunteers to simultaneously wear CGM sensors on the right and left arms. Glucose readings were collected every 15 minutes over a 12-14 days study period. To assess if any observed inter-arm differences were a result of perfusion, participants were randomized to perform a daily 20-minute unilateral arm exercise using an assigned arm on Days 1-6, and to use the alternate arm from Day 7 to Days 12-14. Differences in glucose readings between the right and left arm were compared using the paired sample t-test.

Results:
A total of 41,288 time-matched glucose level pairs were collected and the mean glucose reading in the right arm was higher than that of the left arm by 3.7±10.6 mg/dL (p<0.001). Glucose readings were in hypoglycemic range (<70 mg/dL) for 22.1% of the time in the right arm and 29.8% of the time in the left arm (p<0.001), in euglycemic range (70-180 mg/dL) for 75.2% of the time in the right arm and 67.5% in the left arm (p<0.001), and in hyperglycemic range (>180 mg/dL) for 2.8% of the time in both arms (p=0.83). The difference in glucose levels between the arms was similar before and during exercise [4.0±10.2 mg/dL vs. 4.3±10.1 mg/dL, p=0.77].

Conclusions:
In conclusion, glucose levels and time in hypoglycemia and euglycemia significantly differ based on arm selection during CGM device placement. This finding is unrelated to differences in perfusion induced by unilateral arm exercise. If these findings are further validated in patients with diabetes, arm selection during CGM device placement could impact therapy decisions, clinical trial design, and interpretation.
Abstract 13280: Obesity is Associated With 1-year Atrial Fibrillation Recurrence After Catheter Ablation in Caucasians but Not in African Americans
Authors: Kong Nathan , Shatz Dalise , Besser Stephanie , Aziz Zaid , OZCAN Cevher , Broman Michael , Beaser Andrew , Upadhyay Gaurav A , Nayak Hemal , Tung Roderick
Published: November 2020

Introduction:
Observational studies have noted an association between body mass index (BMI) and recurrence of atrial fibrillation (AF) after catheter ablation. However, there is limited data on this association in a multi-racial cohort. We seek to describe AF recurrence after pulmonary vein isolation (PVI) of obese and non-obese patients stratified by race.

Hypothesis:
The association between BMI and recurrence of AF after PVI differs between Caucasians and African Americans.

Methods:
Caucasian and African American patients undergoing PVI at the University of Chicago from March 2016 to November 2018 were included. Patients were followed for up to 12 months. Not obese was characterized by BMI < 30kg/m
2
and obese as BMI ≥ 30kg/m
2
.

Results:
Among 217 consecutive patients, 69 (31.8%) were female with an average age of 64.2 years (range 24 - 89). Forty-four (20.3%) of patients were African American. There were 105 (48.4%) obese patients. No differences were observed in rates of valvular disease between non-obese and obese patients. Obesity was significant in determining time to AF recurrence after PVI (adjusted hazard ratio [aHR] 3.17, 95% CI 1.71 to 5.87, p < 0.001). When adjusted for age, gender, smoking status, hypertension, diabetes, heart failure, estimated glomerular filtration rate, and type of atrial fibrillation, Caucasians had a significant association between obesity and time to recurrence (aHR 3.34, 95% CI 1.91 to 5.85), whereas African Americans had no association between obesity and time to recurrence (aHR 0.87, 95% CI 0.31 - 2.42). This association remained when stratified by AF type.

Conclusions:
In this multi-racial registry of patients undergoing catheter based PVI, a BMI ≥ 30 kg/m
2
was associated with a higher likelihood of atrial fibrillation recurrence within 12 months for the Caucasian group but not amongst African Americans. These results suggest that in African Americans, obesity is less associated with recurrence of atrial fibrillation after PVI.
Abstract 13286: Finding the Missing Heritability of Serum Lipids: Leveraging the Relatedness in a Large-scale Biobank
Authors: Chen Hung-hsin , Bohlender Ryan J , Petty Lauren E , Wells Quinn , Huff Chad , Below Jennifer
Published: November 2020

Introduction:
High prevalence of dyslipidemia in the United States results in elevated risk of cardiovascular disease. Although the high heritability of serum lipids has motivated many genome-wide association studies (GWAS), much of the heritability is still unexplained. Genomic regions shared with identity by descent (IBD) are inherited from the same common ancestor without recombination, and can be observed in both close and distant relatives. IBD segments provide an opportunity to discover genes that harbor low frequency, large effect variants that are undetectable in GWAS due to low power at rare and heterogeneous alleles.

Methods:
The Vanderbilt biobank (BioVU) comprises over 280,000 DNA samples from participants with linked electronic medical record (EMR). In this study, we extracted 18,337 European dyslipidemia cases, who have either diagnosed dyslipidemia or record of taking lipid-lowering drugs in linked EMR, and 18,337 sex, age, and ancestry-matched controls. The pairwise IBD shared segments were identified by GERMLINE using genotype data. To assess enrichment of IBD, we compared local shared IBD rates in case-case pairs and case-control pairs.

Results:
The greatest enrichment of IBD sharing was found on chromosome 5 (chr5: 169-171 MB, p-value=3.3х10
-5
), and another three suggested regions were from chromosome 10, 18 and 22 (chr10: 86-87 MB, p-value=5.5х10
-4
, chr18: 10-11 MB, p-value=5.3х10
-4
, and chr22: 49.3-49.7 MB, p-value=2.1х10
-4
). To further explore the molecular function, we used PrediXcan to impute the genetically regulated expression of the genes which locate within 1 MB of identified regions. A total of 31 unique genes in these regions exhibit significantly different predicted expression between risk IBD segment carriers and non-carriers, and are also significantly correlated with at least one serum lipids level. For instance, a novel long non-coding RNA, LINC01310, from chr22 associated with total glyceride (p-value=5.3х10
-
3
) and expressed a lower level in risk people carrying the risk-associated IBD segment (p-value=1.2х10
-
6
).

Conclusions:
Our results identity four genomic segments enriched in dyslipidemia cases, and, using GReX, we demonstrate the potential function of novel genes on the regulation of serum lipids.