bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Fluid Dynamics Study of a Nonpremixed Turbulent Flame Using openfoam: Effect of Chemical Mechanisms and Turbulence Models
Authors: Noume Hermann Chopkap , Bomba Valentin , Obounou Marcel , Fouda Henri Ekobena , Sapnken Flavian Emmanuel 
Published: January 2021

Abstract
This article presents a study of the influence of chemical mechanisms and turbulence models on Reynolds-averaged Navier–Stokes (RANS) simulations of the CH4/H2/N2-air turbulent diffusion flame, i.e., the so-called DLR-A flame. The first part of this study is focused on the assessment of the influence of four chemical models on predicted profiles of the DLR-A flame. The chemical mechanisms considered are as follows: (i) a C2 compact skeletal mechanism, which is derived from the GRI3.0 mechanism using an improved multistage reduction method, (ii) a C1 skeletal mechanism containing 41 elementary reactions amongst 16 species, (iii) the global mechanism by Jones and Lindstedt, (iv) and a global scheme consisting of the overall reactions of methane and dihydrogen. RANS numerical results (e.g., velocities, temperature, species, or the heat production rate profiles) obtained running the reactingFOAM solver with the four chemical mechanisms as well as the standard k − ɛ model, the partially stirred reactor (PaSR) combustion model, and the P − 1 radiation model indicate that the C2 skeletal mechanism yields the best agreement with measurements. In the second part of this study, four turbulence models, namely, the standard k − ɛ model, the renormalization group (RNG) k − ɛ model, realizable k − ɛ model, and the k − ω shear stress transport (SST) model, are considered to evaluate their effects on the DLR-A flame simulation results obtained with the C2 skeletal mechanism. Results reveal that the predictions obtained with the standard k − ɛ and the RNG k − ɛ models are in very good agreement with the experimental data. Hence, for simple jet flame with moderately high Reynolds number such as the DLR-A flame, the standard k-epsilon can model the turbulence with a very good accuracy.
Design and Analysis of a Water-Cooling System in a New Yokeless and Segmented Armature Axial In-Wheel Motor for Electric Vehicles
Authors: Luo Liang , Chang Jiujian , Wu Jinglai , Zhu Bo , Zheng Minyi , Zhang Nong 
Published: January 2021

Abstract
An in-wheel motor, as a key part of an in-wheel driving system, needs to satisfy strict restrictions on thermal balance for increasingly high-power density in limited space and weight. Therefore, a new in-wheel motor with an innovative water-cooling system for one newly developed electric vehicle was developed. Based on the mechanical structure of the motor, all potential water-cooling layouts were first designed with consideration of mechanical strength and manufacturability. A thermal conjugate simulation model of the developed in-wheel motor was then built, and its thermally fluid–solid interactions were investigated in this study. All potential water-path layouts of the motor were compared regarding the cooling effect and fluid resistance, which impact the performance of the motor. Fluid flow velocity and fluid state, determined by the water-path layout, significantly impact the cooling effect of the motor. The well-designed water-cooling system significantly reduces the motor’s temperature at a low cost on required coolant-driven pressure which benefits the efficiency of the developed motor. A prototype of the developed motor with the optimal water-path layout was built and tested on the test rig. The developed motor provides outstanding thermal performance.
Quantitative reconstruction of pore-pressure history in sedimentary basins using fluid escape pipes
Authors: Cartwright Joe , Kirkham Chris , Foschi Martino , Hodgson Neil , Rodriguez Karyna , James David 
Published: January 2021

Abstract
We present a novel method to reconstruct the pressure conditions responsible for the formation of fluid escape pipes in sedimentary basins. We analyzed the episodic venting of high-pressure fluids from the crests of a large anticlinal structure that formed off the coast of Lebanon in the past 1.7 m.y. In total, 21 fluid escape pipes formed at intervals of 50–100 k.y. and transected over 3 km of claystone and evaporite sealing units to reach the seabed. From fracture criteria obtained from nearby drilling, we calculated that overpressures in excess of 30 MPa were required for their formation, with pressure recharge of up to 2 MPa occurring after each pipe-forming event, resulting in a sawtooth pressure-time evolution. This pressure-time evolution is most easily explained by tectonic overpressuring due to active folding of the main source aquifer while in a confined geometry.
Roles of the BAP1 Tumor Suppressor in Cell Metabolism
Authors: Han Anna , Purwin Timothy J. , Aplin Andrew E. 
Published: January 2021

AbstractBRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell-cycle regulation, cell death, and differentiation. Recent studies have demonstrated that BAP1 is also involved in several aspects of cellular metabolism, including metabolic homeostasis, glucose utilization, control of ferroptosis, and stress response. A better knowledge of the metabolic roles of cancer-associated genes is important to understanding tumor initiation and progression, as well as highlighting potential therapeutic avenues. With this review, we summarize the current knowledge regarding BAP1-mediated regulation of metabolic activities that may support new strategies to treat BAP1-mutated cancers.
Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10
Authors: Wainberg Zev A. , Fuchs Charles S. , Tabernero Josep , Shitara Kohei , Muro Kei , Van Cutsem Eric , Bang Yung-Jue , Chung Hyun Cheol , Yamaguchi Kensei , Varga Eniko , Chen Jen-Shi , Hochhauser Daniel , Thuss-Patience Peter , Al-Batran Salah-Eddin , Garrido Marcelo , Kher Uma , Shih Chie-Schin , Shah Sukrut , Bhagia Pooja , Chao Joseph 
Published: January 2021

Abstract

Purpose:
Pembrolizumab demonstrated efficacy in PD-L1–positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials.

Patients and Methods:
Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, n = 46; post hoc), KEYNOTE-061 (pembrolizumab, n = 53; chemotherapy, n = 55; post hoc), and KEYNOTE-062 (pembrolizumab, n = 92; chemotherapy, n = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

Results:
In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8–11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41–1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56–1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3–7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49–0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79–1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+).

Conclusions:
This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.
E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice
Authors: Xu Yanni , Liu Chang , Han Xiaowan , Jia Xiaojian , Li Yongzhen , Liu Chao , Li Ni , Liu Lunming , Liu Peng , Jiang Xinhai , Wang Weizhi , Wang Xiao , Li Yining , Chen Mingzhu , Luo Jinque , Zuo Xuan , Han Jiangxue , Wang Li , Du Yu , Xu Yang , Jiang Jian-Dong , Hong Bin , Si Shuyi 
Published: January 2021

Objective:
Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation.

Approach and Results:

E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of
3
H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with
3
H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE
−/−
mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway.

Conclusions:
E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.
Aortic Regurgitation Is Associated With Ascending Aortic Remodeling in the Nondilated Aorta
Authors: Balint Brittany , Federspiel Jan M. , Schwab Tanja , Ehrlich Tristan , Ramsthaler Frank , Schäfers Hans-Joachim 
Published: January 2021

Objective:
The probability of aortic complications in patients with bicuspid aortic valve is higher in association with aortic regurgitation (AR) compared with aortic stenosis (AS) or normally functioning valves. The objective of this study was to determine whether this is related to the specific characteristics of aneurysmatic dilatation that includes AR or whether AR itself has a negative impact on the aortic wall, independent of aneurysmatic dilatation.

Approach and Results:

Nondilated aortic specimens were harvested intraoperatively from individuals with tricuspid aortic valves and either AS (n=10) or AR (n=16). For controls, nondilated aortas were harvested during autopsies from individuals with tricuspid aortic valves and no evidence of aortic valve disease (n=10). Histological and immunohistochemical analyses revealed that compared with control aortas, overall medial degeneration was more severe in AR-aortas (
P
=0.005) but not AS-aortas (
P
=0.23). This pathological remodeling included mucoid extracellular matrix accumulation (
P
=0.005), elastin loss (
P
=0.003), elastin fragmentation (
P
=0.008), and decreased expression of fibrillin (
P
=0.003) and collagen (
P
=0.008). Furthermore, eNOS (endothelial nitric oxide synthase) expression was decreased in the intima (
P
=0.0008) and in vasa vasorum (
P
=0.004) of AR-aortas but not AS-aortas (all
P
>0.05). Likewise, subendothelial apoptosis was increased in AR-aortas (
P
=0.03) but not AS-aortas (
P
=0.50).

Conclusions:
AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR.

Graphic Abstract:
A graphic abstract is available for this article.
Time Delay, Infarct Size, and Microvascular Obstruction After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction
Authors: Redfors Björn , Mohebi Reza , Giustino Gennaro , Chen Shmuel , Selker Harry P. , Thiele Holger , Patel Manesh R. , Udelson James E. , Ohman E. Magnus , Eitel Ingo , Granger Christopher B. , Maehara Akiko , Ali Ziad A. , Ben-Yehuda Ori , Stone Gregg W. 
Published: January 2021

Background:
Symptom-to-balloon time (SBT) and door-to-balloon time (DBT) are both considered important metrics in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment–elevation myocardial infarction (STEMI). We sought to assess the relationship of SBT and DBT with infarct size and microvascular obstruction (MVO) after pPCI.

Methods:
Individual patient data for 3115 ST-segment–elevation myocardial infarction patients undergoing pPCI in 10 randomized trials were pooled. Infarct size (% left ventricular mass) was assessed within 1 month after randomization by technetium-99 m sestamibi single-photon emission computerized tomography (3 studies) or cardiac magnetic resonance imaging (7 studies). MVO was assessed by cardiac magnetic resonance. Patients were stratified by short (≤2 hours), intermediate (2–4 hours), or long (>4 hours) SBTs, and by short (≤45 minutes), intermediate (45–90 minutes), or long (>90 minutes) DBTs.

Results:
Median [interquartile range] SBT and DBT were 185 [130–269] and 46 [28–83] minutes, respectively. Median [interquartile range] time to infarct size assessment after pPCI was 5 [3–12] days. There was a stepwise increase in infarct size according to SBT category (adjusted difference, 2.0% [95% CI, 0.4–3.5] for intermediate versus short SBT and 4.4% [95% CI, 2.7–6.1] for long versus short SBT) but not according to DBT category (adjusted difference, 0.4% [95% CI, −1.2 to 1.9] for intermediate versus short DBT and −0.1% [95% CI, −1.0 to 3.0] for long versus short SBT). MVO was greater in patients with long versus short SBT (adjusted difference, 0.9% [95% CI, 0.3–1.4]) but was not different between patients with intermediate versus short SBT (adjusted difference, 0.1 [95% CI, −0.4 to 0.6]). There was no difference in MVO according to DBT. Results were similar in multivariable analysis with SBT and DBT included as continuous variables.

Conclusions:
Among 3115 patients with ST-segment–elevation myocardial infarction undergoing infarct size assessment after pPCI, SBT was more strongly correlated with infarct size and MVO than DBT.
Long‐Term Survival of Patients With Left Ventricular Noncompaction
Authors: Vaidya Vaibhav R. , Lyle Melissa , Miranda William R. , Farwati Medhat , Isath Ameesh , Patlolla Sri Harsha , Hodge David O. , Asirvatham Samuel J. , Kapa Suraj , Deshmukh Abhishek J. , Foley Thomas A. , Michelena Hector I. , Connolly Heidi M. , Melduni Rowlens M. 
Published: January 2021

Background
The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC.

Methods and Results

339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end‐diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow‐up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02–1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17–4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21–3.68) were associated with all‐cause mortality. Compared with the expected survival for age‐ and sex‐matched US population, patients with LVNC had reduced overall survival (
P
<0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population.

Conclusions
Overall survival is reduced in patients with LVNC compared with the expected survival of age‐ and sex‐matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.
Coxsackievirus B3 Infection Early in Pregnancy Induces Congenital Heart Defects Through Suppression of Fetal Cardiomyocyte Proliferation
Authors: Sharma Vipul , Goessling Lisa S. , Brar Anoop K. , Joshi Chetanchandra S. , Mysorekar Indira U. , Eghtesady Pirooz 
Published: January 2021

Background
Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation.

Methods and Results
We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose‐response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double‐outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3‐exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor‐β1, and extracellular matrix proteins were the most highly enriched in CVB3‐infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls.

Conclusions
We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes.
Arrhythmic Risk Profile and Outcomes of Patients Undergoing Cardiac Sympathetic Denervation for Recurrent Monomorphic Ventricular Tachycardia After Ablation
Authors: Dusi Veronica , Gornbein Jeffrey , Do Duc H. , Sorg Julie M. , Khakpour Houman , Krokhaleva Yuliya , Ajijola Olujimi A. , Macias Carlos , Bradfield Jason S. , Buch Eric , Fujimura Osamu A. , Boyle Noel G. , Yanagawa Jane , Lee Jay M. , Shivkumar Kalyanam , Vaseghi Marmar 
Published: January 2021

Background
Cardiac sympathetic denervation (CSD) has been used as a bailout strategy for refractory ventricular tachycardia (VT). Risk of VT recurrence in patients with scar‐related monomorphic VT referred for CSD and the extent to which CSD can modify this risk is unknown. We aimed to quantify arrhythmia recurrence risk and impact of CSD in this population.

Methods and Results

Adjusted competing risk time to event models were developed to adjust for risk of VT recurrence and sustained VT/implantable cardioverter–defibrillator shocks after VT ablation based on patient comorbidities at the time of VT ablation. Adjusted VT and implantable cardioverter–defibrillator shock recurrence rates were estimated for the subgroup who subsequently required CSD after ablation. The expected adjusted recurrence rates were then compared with the observed rates after CSD. Data from 381 patients with scar‐mediated monomorphic VT who underwent VT ablation were analyzed, excluding patients with polymorphic VT. Sixty eight patients underwent CSD for recurrent VT. CSD reduced the expected adjusted VT recurrence rate by 36% (expected rate of 5.61 versus observed rate of 3.58 per 100 person‐months,
P
=0.01) and the sustained VT/implantable cardioverter–defibrillator shock rates by 34% (expected rate of 4.34 versus observed 2.85 per 100 person‐months,
P
=0.03). The median number of sustained VT/implantable cardioverter–defibrillator shocks in the year before versus the year after CSD was reduced by 90% (10 versus 1,
P
<0.0001).

Conclusions
Patients referred for CSD for refractory scar‐mediated monomorphic VT are at a higher risk of VT recurrence after ablation as compared with those not requiring CSD, mostly because of their cardiac comorbidities. CSD significantly reduced both the expected risk of recurrences and VT burden.
The Investigation of Left Atrial Structure and Stroke Etiology: The I‐LASER Study
Authors: Johansen Michelle C. , Doria de Vasconcellos Henrique , Nazarian Saman , Lima Joao A. C. , Gottesman Rebecca F. 
Published: January 2021

Background

Left atrial (LA) function is important in stroke, but often poorly characterized. We evaluated the association of 2‐dimensional speckle tracking echocardiography LA variables with stroke subtype (cardioembolic stroke [CS]
or
cryptogenic stroke versus other). The hypothesis is worse LA active function is associated with CS, but not cryptogenic strokes.

Methods and Results
In this prospective cohort (2017–2019), left ventricular/LA structure and function were quantified by 2‐dimensional and speckle tracking echocardiography in 151 patients with stroke. Strain/strain rate curves for the 3 components of the LA cycle, ie, (1) Reservoir (global longitudinal strain [Srmax]), (2) Conductive (early LA Sr [Sre]), and (3) Active (late LA strain [Sra]) were evaluated, masked to stroke subtype. Associations of cardiac features with stroke subtype were tested using multivariable logistic regressions. Odds of CS were increased in patients with a larger LA systolic diameter (odds ratio [OR], 2.96, 95% CI, 1.14–7.69) but reduced in patients with a higher Srmax (better reservoir) (OR, 0.80, 95% CI, 0.67–0.97). Lower Sra (worse function) was associated with an increased odds of CS (OR, 1.72, 95% CI, 1.07–2.76) but not independent of atrial fibrillation. Higher active LA emptying fraction (better active phase) was associated with reduced odds of CS (OR, 0.74, 95% CI, 0.57–0.95) or cryptogenic stroke (OR, 0.82, 95% CI, 0.68–0.98) versus other subtypes; other associations between cryptogenic stroke and speckle tracking echocardiography were not found.

Conclusions
Markers of LA structure and function were associated with CS. Similar associations were not found for cryptogenic stroke, which might suggest different underlying mechanisms, given study limitations. Further understanding could aid stroke diagnosis and secondary stroke prevention research.