bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of succinate dehydrogenase candidate fungicides via lead optimization for effective resistance management of Fusarium oxysporum f. sp. capsici
Authors: Iftikhar Sehrish , Bengyella Louis , Shahid Ahmad Ali , Nawaz Kiran , Anwar Waheed , Ali Sajid 
Published: June 2021

Abstract
Fusarium wilt of chili caused by the fungus Fusarium oxysporum f. sp. capsici (FCO) severely reduces the production of chili worldwide. There is growing evidence of resistance to commercial fungicides targeting succinate dehydrogenase (Sdh) of FCO soliciting the development of new Sdh inhibitors (SdhIs). In the current work, optimize docking and virtual screening were used to mine twelve SdhIs from the ZINC database, followed by in vitro antifungal evaluation on spore and radial mycelium development. Four new promising SdhIs exhibiting a mean mycelium inhibition rate greater than 85.6% (F = 155.8, P = 0.001, P < 0.05) were observed on ten strains of virulent resistant FCO. Importantly, three of the discovered molecules exhibited potent spore germination inhibition (≥ 80%, P = 00.1, P < 0.05) compared to the commonly used fungicide penthiopyrad. A significant positive correlation (r* ≥ 0.67, P < 0.05) between the activities of the newly discovered SdhIs compared to penthiopyrad against all tested FCO strains indicated a broad-spectrum fungicidal activity. The current findings indicate that the four SdhI’s discovered could judiciously replace certain commercial SdhIs displaying resistance against F. oxysporum f. sp. capsici.
Metabolic Profiling, ADME Pharmacokinetics, Molecular Docking Studies and Antibacterial Potential of Phyllanthus muellerianus Leaves
Authors: Obuotor Tolulope , AMOS KOLAWOLE , apalowo oladayo , AKANMO Adio 
Published: June 2021

Abstract
Global increase in the level of antimicrobial resistance among bacterial pathogens has prompted the search for alternative treatment from medicinal plants. Phyllanthus muellerianus (PM) leaves has been used traditionally against microorganisms of medical importance, hence the need to evaluate the pharmacological pathways and mode of actions using in vitro and in silico approaches. Clinical isolates of eight (8) microorganisms associated with urinary tract infections (UTIs) were obtained and identified using morphological and biochemical methods. Phyllanthus muellerianus (PM) leaves were extracted and purified by solvent partitioning. Ethyl acetate fraction of PM had the highest yield and zone diameter range from 13.5±1.00mm to 28±1.53mm. The rate of protein leakage per time interval of Staphylococcus aureus increased from 9.29 μg/ml at 0 minute to 17.43 μg/ml at 120 minutes while leakage in Candida albicans also increased from 8.57 μg/ml at 0 minute to 70.43 μg/ml at 120 minutes. GCMS fingerprints, pharmacodynamics and pharmacokinetic studies revealed the active agent as quindoline, an azaindole and isotere of indoles having a binding energy of -9.1 kcal/mol. Analyses of the structural and atomic orientations of quindoline, and superimposition on ciprofloxacin, a common antibiotic revealed an interesting comparison, effecting a stronger binding affinity of Quindoline-HMG-CoA complex.
Basal Ganglia Infarction a Rare Neurological Manifestation of COVID-19 in an Elderly Patient: A Case Report
Authors: Kamal Manar Ahmed 
Published: June 2021

Abstract
Background: Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide since the first cases were observed in Wuhan, China. Patients with COVID-19 develop multiple neurological symptoms, including headache, disturbed consciousness, and paresthesia, in addition to systemic and respiratory symptoms. Case presentation: We presented a 57-years-old woman admitted to the emergency department (ED) - in December 2020 - with complaints of slurred speech, confusion, and left upper limb weakness after one week of positive nasopharyngeal swab sample for SARS-CoV-2. Conclusion: This case report concludes that unilateral acute basal ganglia infarction may be a unique neurological manifestation after COVID-19 infection in an elderly patient.
The Antitumor Activity of Pseudoginsengenin DQ Against Hypopharyngeal Cancer Cells via Targeting HIF-1α-GLUT1 Pathway
Authors: Wang Sanchun , Cai Yu , Feng Qingjie , Gao Jing , Teng Bo 
Published: June 2021

Abstract
Background
The ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside Protopanaxadiol (PPD), the octanone Pseudoginsengenin DQ (PDQ) may have stronger pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumor activity and molecular mechanism against hypopharyngeal cancer cells remains unclear.
Methods
Cell Counting Kit-8, cell cycle assay and cell apoptosis assay were conducted to detect FADU cells proliferation, cell phase and apoptosis. The interactions between PDQ and HIF-1α were investigated by a molecular docking study. The expression of HIF-1α, GLUT1, apoptosis related proteins was tested by western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. Glucose uptake assay was used to assess the glucose uptake capacity of FADU cells.
Results
PDQ was found to suppress the proliferation, reduce glucose uptake, induce the cell cycle arrest and apoptosis of FaDu cells. Molecular docking study demonstrated that PDQ could interact with the active site of HIF-1α. PDQ decreased the expression and mRNA levels of HIF-1α and its downstream factor GLUT1. Moreover, dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane but also inhibited its clustering.
Conclusion
Our work elucidated that the antitumor effect of PDQ is related to its downregulation of HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.
USF1 Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway
Authors: Wang Yu , Zhao Yunxia , Zhang Xiangwei , Jiang Yuanzhu , Ma Wei , Zhang Lin , dong wei 
Published: June 2021

Abstract
Background: We aimed at investigation of the effect and the underlying neurotrophin signaling pathway of the upstream transcription factor 1 (USF1) in lung adenocarcinoma (LUAD).Methods: The Cancer Genome Atlas (TCGA) database was used to analyze USF1 expression data and to extract patients’ clinical records. Immunohistochemical assay and Western blotting (WB) were used to determine the expression levels of USF1 in LUAD. The neurotrophin signaling pathway was analyzed by bioinformatic analysis while the expression of all related proteins was determined by WB. In addition cellular viability, proliferation, migration and invasion potential were investigated by the CCK-8, colony formation, wound healing and transwell. Meanwhile, the effect of USF1 in LUAD progression was investigated in a mouse model. The link between USF1 and UGT1A3 (UDP Glucuronosyltransferase Family 1 Member A3) was studied by the dual-luciferase reporter assay. Results: We have detected a high expression level of USF1 in LUAD, which was associated with advanced tumor stage, nodal metastasis, and poor patient’s survival rate. The knockdown of USF1 inhibited cellular viability, proliferation, migration and invasion. Meanwhile, USF1 knockdown inhibited tumor growth in a mouse model. Besides, USF1 targeted UGT1A3, which was proven by the fact that the USF1 knockdown decreased the expression level of UGT1A3, whereas the upregulated expression of UGT1A3 increased cellular viability and proliferation. We have proved that the neurotrophin signaling pathway in LUAD was activated by USF1 and UGT1A3. The expression of the related proteins was also inhibited by the USF1 knockdown, while the overexpression of IRAK increased cancer cells’ migration and invasion potential.Conclusion: USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.
Construction of Intelligent Integrated Model Framework for the Workshop Manufacturing System Via Digital Twin
Authors: Zhang Zhongyu , Zhu Zhenjie , Zhang Jinsheng , Wang Jingkun 
Published: June 2021

Abstract
With the drastic development of the globally advanced manufacturing industry, transition of the original production pattern from traditional industries to advanced intelligence is completed with the least delay possible, which are still facing new challenges. Because the timeliness, stability and reliability of them is significantly restricted due to lack of the real-time communication. Therefore, an intelligent workshop manufacturing system model framework based on digital twin is proposed in this paper, driving the deep inform integration among the physical entity, data collection, and information decision-making. The conceptual and obscure of the traditional digital twin is refined, optimized, and upgraded on the basis of the four-dimension collaborative model thinking. A refined nine-layer intelligent digital twin model framework is established. Firstly, the physical evaluation is refined into entity layer, auxiliary layer and interface layer, scientifically managing the physical resources as well as the operation and maintenance of the instrument, and coordinating the overall system. Secondly, dividing the data evaluation into the data layer and the processing layer can greatly improve the flexible response-ability and ensure the synchronization of the real-time data. Finally, the system evaluation is subdivided into information layer, algorithm layer, scheduling layer, and functional layer, developing flexible manufacturing plan more reasonably, shortening production cycle, and reducing logistics cost. Simultaneously, combining SLP and artificial bee colony are applied to investigate the production system optimization of the textile workshop. The results indicate that the production efficiency of the optimized production system is increased by 34.46%.
Association of Sequential Organ Failure Assessment (SOFA) components with mortality
Authors: Pölkki Anssi , Pekkarinen Pirkka T , Takala Jukka , Selander Tuomas , Reinikainen Matti 
Published: June 2021

Abstract
BackgroundSequential Organ Failure Assessment (SOFA) is a practical and widely used method to describe and quantify the presence and severity of organ system dysfunctions and failures. Some proposals suggest that SOFA could be employed as an endpoint in interventional trials. To justify this, all SOFA components should have comparable weights as organ dysfunction measures. In this study we aimed to investigate whether the associations of different SOFA components with in-hospital mortality are comparable.MethodsWe performed a study based on nationwide register data on adult patients admitted to 26 Finnish intensive care units (ICUs) during 2012−2015. We determined the SOFA score as the maximum score in the first 24 hours after ICU admission. We defined organ failure as an organ-specific SOFA score of three or higher. We evaluated the association of different SOFA component scores with mortality using multivariable logistic regression analysis. ResultsOur study population comprised 63,756 ICU patients. Overall hospital mortality was 10.7%. In-hospital mortality was 22.5% for patients with respiratory failure, 34.8% for those with coagulation failure, 40.1% for those with hepatic failure, 14.9% for those with cardiovascular failure, 26.9% for those with neurologic failure and 34.6% for the patients with renal failure. The age-adjusted odds ratio for in-hospital death was 2.41 [95% confidence interval (CI) 2.27-2.56] for respiratory failure, 4.04 (95% CI 3.57-4.57) for coagulation failure, 4.24 (95% CI 3.47-5.17), for hepatic failure, 1.57 (95% CI 1.47-1.67) for cardiovascular failure, 5.00 (95% CI 4.71-5.30) for neurologic failure, and 4.93 (95% CI 4.58-5.32) for renal failure. Organ failure combinations including cardiovascular failure were associated with lower mortality than other organ failure combinations.ConclusionsAll SOFA components are associated with mortality, but their weights are not comparable. High cardiovascular SOFA scores do not imply an equally high risk as high scores of other components.
Sustaining the Oil and Gas Multinationals’ Operations Through Corporate Social Responsibility Practices
Authors: Gyane Ama Twumwaa , Nunoo Edward Kweku , Suleman Shafic , Essandoh-Yeddu Joseph 
Published: June 2021

Abstract
The objective of this study is to provide empirical evidence from the perspective of prudent corporate social responsibility practices by oil and gas multinationals in emerging economies on how investments in and disclosure of the practices can enhance financial sustainability. Accounting-based measures on investments, financial performance, disclosures of activities and panel data set on company size (total assets) over a 10-year period (t) were analysed. Findings show that multinationals with interests in emerging economies take key aspects of their corporate social responsibility practices seriously. There was a significant positive relationship (p=0.0035<0.05) between investments in corporate social responsibility practices and sustainability of financial performance. No significant relationship (p=0.4409 > 0.05) was established between disclosure and financial performance. The paper concludes, by supporting the preposition with scientific data, that functional corporate social responsibility practices yield sustained dividend by presenting a stronger financial outlook for multinational oil and gas companies who engage in it. This is prudent for poverty alleviation initiatives and key to achieving the sustainable development goals and targets in emerging economies where they operate.
Two-Dimensional Simulation of Frost Formation on the NACA0012 Airfoil under Strong Convection by Using the P-VOF Method
Authors: Xia Bin , Xu Xianghua , Liang Xingang 
Published: June 2021

Abstract
A newly developed frosting simulation method, pseudo-VOF (p-VOF) method, has applied to simulate the dynamic frost formation on the NACA0012 airfoil under strong convection. The p-VOF method is a pseudo volume of fraction simulation method of the multiphase flow with phase change. By solving a simplified mass conservation equation explicitly instead of the original volume fraction equations in CFD software, the efficiency and robustness of calculation are greatly improved. This progress makes it possible to predict a long-time frost formation. The p-VOF method was successfully applied to the simulation of dynamic frosting on the two-dimensional NACA0012 airfoil under strong convection conditions with constant frost physical properties. The simulation result shows that the average thickness of the frost layer increases, and the frost bulges and flow separation appear earlier, when the airfoil surface temperature decreases or the air humidity increases. The frost bulges and flow separation appear earlier, when the air velocity is faster, the growth rate of the frost layer at the early stage is greater, but the final frost layer is thinner.
Comprehensive Analysis of Tumor Immune Microenvironment and Prognosis of m6A-Related lncRNAs in Gastric Cancer
Authors: Wang Yi , Zhu Gui-Qi , Tian Di , Zhou Chang-Wu , Li Na , Feng Ying , Zeng Meng-Su 
Published: June 2021

Abstract
Background N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play pivotal role in gastric cancer (GC) progression. The emergence of immunotherapy in GC has created a paradigm shift in the approach of treatment, whereas there is significant heterogeneity with regard to degree of treatment responses, which results from the variability of tumor immune microenvironment (TIME). How the interplay between them enrolled in the shaping of TIME remains unclear. Methods The RNA sequencing and clinical data of GC patients were collected from TCGA database. Pearson correlation test and univariate Cox analysis were used to screen out m6A-related lncRNAs. Consensus clustering was implemented to classify GC patients into 2 subtypes. Survival analysis, the infiltration of immune cells, Gene set enrichment analysis (GSEA) and the mutation profiles were analyzed and compared between two clusters. Then least absolute shrinkage and selection operator (LASSO) COX regression was implemented to select pivotal genes and risk score model was constructed accordingly. The prognosis value of the risk model was explored. In addition, the discrepancies of response to immune checkpoints inhibitor (ICIs) therapy were compared between different risk groups. Finally, we performed qRT-PCR to detect the expression pattern in 35 tumor tissues and paired adjacent normal tissue, and validated the prognostic value of risk model in the our cohort (N=35). Results The expression profiles of 23 lncRNAs were included to cluster patients into different subtypes. Cluster1 with worse prognosis harbored higher immune score, stromal score, ESTIMATE score and mutation rate of genes. Different immune cell infiltration pattern were also displayed between different clusters. GSEA showed that cluster1 was preferentially enriched with tumor hallmarks and tumor correlated biological pathways. Next, 9 lncRNAs were selected by LASSO regression model to construct risk model. Patients in the high risk group had poor prognosis. The prognosis value of this model was also validated in our cohort. As for predicting responses to the ICIs therapy, we found that patients from high risk group had lower TMB score and lower proportion of MSI-H subtype. Moreover, patients had distinct immunophenoscores in different risk groups. Conclusion Our study revealed that the potential interplay between m6A modification and lncRNAs might have critical role in predicting GC prognosis, sculpting TIME landscape and predicting the responses to immune checkpoints inhibitors therapy.
How Equitable Are the Distributions of the Physical Activity and Accessibility Benefits of Bicycle Infrastructure?
Authors: Standen Christopher , Crane Melanie , Greaves Stephen , Collins Andrew , Rissel Chris 
Published: June 2021

Abstract
BackgroundCycling for transport provides many health and social benefits – including physical activity and independent access to jobs, education, social opportunities, health care and other services (accessibility). However, inequalities exist for some population groups in the opportunity to reach everyday destinations, and public transport stops, by bicycle – owing in part to their greater aversion to riding in amongst motor vehicle traffic. Health equity can therefore be improved by providing separated cycleway networks that give people the opportunity to access places by bicycle using traffic-free routes. The aim of this study was to assess the health equity benefits of two bicycle infrastructure development scenarios – a single cycleway, and a complete network of cycleways – by examining the distribution of physical activity and accessibility benefits across gender, age and income groups.MethodsTravel survey data collected from residents in Sydney (Australia) were used to train a predictive transport mode choice model, which was then used to forecast the impact of the two scenarios on transport mode choice, physical activity and accessibility. Accessibility was measured using a utility-based accessibility measure derived from the mode choice model. The distribution of forecast physical activity and accessibility benefits was then calculated across gender, age and income groups.ResultsThe modelled physical activity and accessibility measures improve in both intervention scenarios. However, in the single cycleway scenario, the benefits are greatest for the male, high-income and older age groups. In the complete network scenario, the benefits are more equally distributed. Forecast increases in cycling time are largely offset by decreases in walking time – though the latter is typically low-intensity physical activity, which confers a lesser health benefit than moderate-intensity cycling.ConclusionsSeparated cycleway infrastructure can be used to improve health equity by providing greater opportunities for transport cycling in population groups more averse to riding amongst motor vehicle traffic. Disparities in the opportunity to access services and economic/social activities by bicycle – and incorporate more physical activity into everyday travel – could be addressed with connected, traffic-free cycleway networks that cater to people of all genders, ages and incomes.
Associations Between Elemental Constituents of Fine Particulate Matter and Subclinical Atherosclerosis in Adolescents and Young Adults
Authors: Chen Szu-Ying , Wu Charlene , Wu Chang-Fu , Chan Chang-Chuan , Hwang Jing-Shiang , Su Ta-Chen 
Published: June 2021

Abstract
BackgroundExisting studies have demonstrated the relationships between particulate matter (PM) exposure and subclinical atherosclerosis; however, whether PM and its elemental constituents predispose to atherosclerosis remains unclear in adolescents and young adults. This cross-sectional study included 789 subjects between the ages of 12 to 30 years who lived in Taipei metropolis since childhood. Health examination and carotid intima-media thickness (CIMT) measurements were performed between 2006 and 2008. Land use regression (LUR) model was used to estimate participants’ one-year exposure to fine particulate matter (PM2.5) and eight elemental constituents, i.e., silicon (Si), sulfur (S), titanium (Ti), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), and zinc (Zn). The associations between percent differences in CIMT at common carotid artery (CCA) segments and air pollutants were analyzed.ResultsAn interquartile range increment of PM2.5 (4.5 μg/m3), Fe (34.7 ng/m3), and Zn (20.7 ng/m3) are associated with 0.77% (95% confidence interval; 95%CI: 0.05 to 1.50), 0.83% (0.01 to 1.65), and 1.22% (0.35 to 2.10) higher for combined CIMT, respectively; while Mn (2.0 ng/m3) exposure is associated with 0.31% (0.01 to 0.60) higher for right CIMT. Stratified analyses show PM2.5 and elemental constituents, especially Zn, are associated with CIMT among subjects who are 18 years or older, females, lower household income, non-smokers, normal weight, non-hypertensive, non-hyperglycemic, or non-hypercholesterolemic. ConclusionsLong-term exposures to PM2.5 and elemental constituents mainly originating from traffic and industry operations are associated with subclinical atherosclerosis in young population. Individual characteristics, health behaviors, and biometric measures, may modify air pollution-related subclinical atherosclerosis.