bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and optimization of HPLC-MS method for simultaneous determination of four terpene trilactones in Ginkgo biloba leaf extracts based on Quality by Design principles
Authors: Zhang Sijie , Wu Linlin , Wang Xiaoping , Gong Xingchu , Qu Haibin 
Published: May 2020

Abstract
Background

Ginkgo biloba leaf extract (EGBL) is one of the most commonly used and most studied herbal medicines around the world. Taking into account that previously reported HPLC-ELSD methods for terpene trilactones determination in EGBL are time-consuming with complicated sample preparation, it is reasonable and meaningful to developing a simple, sensitive and robust HPLC-MS method based on a novel analytical quality by design (AQbD) approach.
Methods

Firstly, analytical target profile (ATP) and systematic risk analysis were carried out to identify potential critical method attributes (CMAs) and critical method parameters (CMPs). Secondly, CMPs were identified using a standard partial regression coefficient method. Thirdly, Box-Behnken design (BBD) was employed to establish the quantitative relationship between CMAs and CMPs. Fourthly, the Monte Carlo simulation method was used to build hypercube design space. Then, the verification experiments were performed. Fifthly, the optimized method was validated and utilized. Finally, the paired t test was used to compare the developed method with HPLC-ELSD.
Results

After the screening experiments, flow rate of mobile phase, the proportion of formic acid in the mobile phase, gas flow rate and gas temperature were identified as CMPs. Models to quantitatively describe the relationship between CMAs and CMPs were built. The operational hypercube design spaces of the HPLC-MS method for terpene trilactones analysis in EGBL were successfully calculated and found to be robust, which led to the analytical control strategy. The verification experiments were successfully performed within the design space and model was found to be accurate. The method had been successfully used for quality analysis of development batches of EGBL and obtained almost identical results to data determinated using HPLC.
Conclusions

In this work, an analytical control strategy for HPLC-MS method for terpene trilactones analysis in EGBL was developed using AQbD concepts, which is promising for application to other Chinese medicines. The developed HPLC-MS method is an alternative method for quantification of terpene trilactones in commercial EGBL and will be applicable throughout the life cycle of the product.
Ambient PM2.5 induces brain injury through PI3K/AKT/FoxO1 pathway
Authors: Song Liying , Pan Kun , Du Xihano , Jiang Shuo , Zeng Xuejiao , Zhang Jia , Lei Lei , Zhang Mengdi , Zhang Yuwen , Zhou Ji , Xie Yuquan , Zhao Jinzhuo 
Published: May 2020

Abstract
Background Fine particulate matter (PM 2.5 )-induced neurological and mental diseases, such as cognitive impairment and stroke, tend to cause disability. In this study, we plan to find the appropriate biological indicators reflecting the early effects of PM 2.5 exposure and explore the toxicity of inhaling PM 2.5 along with its pathological mechanism on nervous system. Methods Male C57BL/6 mice were divided into 6 groups and exposed to concentrated PM 2.5 or filtered air for 2, 4 and 6 months, respectively. Their performances of ethology were tested by Morris water maze, elevated plus maze and buried food pellet test. Weight of whole brain and olfactory bulbs were recorded when the mice were sacrificed and the brain structure was observed by HE staining. ROS, SOD, IL-6, TNF-α, IL-1β, BDNF, β-hydroxybutyric, IgG, albumin, fibrinogen and plasminogen were tested. The mRNA expressions of the cortex were detected by RNA sequencing and real-time PCR, and the corresponding proteins were detected by Western blot. Results The spatial learning memory ability were impaired and the mice performed anxiously after PM 2.5 exposure. Relative brain weight decreased along with age and PM 2.5 inhaled exposure exceeded the process. But neuronal morphology, inflammatory cytokines, ROS, β-hydroxybutyric, BDNF, IgG and fibrinogen did not change. Intriguingly, SOD and albumin decreased, while plasminogen increased after PM 2.5 exposure. PI3K-AKT-FoxO1 pathway was activated after 6-month PM 2.5 exposure. Conclusion Albumin, A/G value and plasminogen are main serum indicators of early-stage (2 month) PM 2.5 exposure, and long-term (6 month) PM 2.5 exposure induced brain injury potentially through the activation of PI3K/AKT/FoxO1 pathway.
A knowledge based hierarchical reliability allocation (HIRAL) approach for shipboard systems
Authors: Cicek Kadir 
Published: May 2020

Abstract
Reliability has become a greater concern in ship-board systems due to increasing technology, system complexity and multiple design demands. Enhancement the reliability of ship-board systems promotes to ensure safe and continuous operation onboard a ship. To enhance the reliability of ship-board system, it is essential to figure out each individual component reliability. Within this scope, reliability allocation analysis turns into an onerous task to enhance the reliability of ship-board systems through identification of possible component-based design, construction and operation optimizations. This study proposes a hybrid reliability allocation methodology based on hierarchical structure with the integration of analytic hierarchy process (AHP), data envelopment analysis (DEA) and feasibility of objectives (FOO) methods. The proposed methodology provides reliability allocation analysis for systems with any number of components. Also, the study figures out the usefulness of the adaptation of AHP-DEA into reliability allocation analysis. To demonstrate the applicability of proposed methodology, a case study on steering gear system is presented.
Hybrid Grid Generation for Viscous Flow Simulations in Complex Geometries
Authors: Ye Hongfei , Liu Yang , Chen Bo , Liu Zhiwei , Zheng Jianjing , Pang Yufei , Chen Jianjun 
Published: May 2020

Abstract
In this paper, we present a hybrid grid generation approach for viscous flow simulations by marching a surface triangulation on viscous walls along certain directions. Focuses are on the computing strategies used to determine the marching directions and distances since these strategies determine the quality of the resulting elements and the reliability of the meshing procedure to a large extent. With respect to marching direction, three strategies featured with different levels of efficiencies and robustness performance are combined to compute the initial normals at front nodes to balance the trade-off between efficiency and robustness. A novel weighted strategy is used in the normal smoothing scheme, which evidently reduce the possibility of early stop of front generation at complex corners. With respect to marching distances, the distance settings at concave and/or convex corners are locally adjusted to smooth the front shape at first; a further adjustment is then conducted for front nodes in the neighbourhood of gaps between opposite viscous boundaries. These efforts, plus other special treatments such as multi-normal generation and fast detection of local/global intersection, as a whole enable the setup of a hybrid mesher that could generate qualitied viscous grids for geometries with industry-level complexities.
Polymorphisms in the airway epithelium related genes CDHR3 and EMSY are associated with asthma susceptibility
Authors: Zhang Miao miao , Chen Guo , Wang Yu , Wu Shou quan , Sandford Andrew J , He Jian-Qing 
Published: June 2020

Abstract
Background: As a main line of defense of the respiratory tract, the airway epithelium plays an important role in the pathogenesis of asthma. CDHR3 and EMSY were reported to be expressed in the human airway epithelium. Although previous genome-wide association studies found that the two genes were associated with asthma susceptibility, similar observations have not been made in the Chinese Han population. Methods: A total of 300 asthma patients and 418 healthy controls who were unrelated Chinese Han individuals were enrolled. Tag-single nucleotide polymorphisms (Tag-SNPs) were genotyped and the associations between SNPs and asthma risk were analyzed by binary logistic regression analysis. Results: After adjusting for confounding factors, the A allele of rs3847076 in CDHR3 was associated with increased susceptibility to asthma (OR = 1.407, 95% CI: 1.030-1.923). For the EMSY gene, the T alleles of both rs2508746 and rs12278256 were related with decreased susceptibility to asthma (additive model: OR = 0.718, 95% CI: 0.536-0.961; OR = 0.558, 95% CI: 0.332-0.937, respectively). In addition, the GG genotype of rs1892953 showed an association with increased asthma risk under the recessive model (OR = 1.667, 95% CI: 1.104-2.518) and the GATCTGAGT haplotype in EMSY was associated with reduced asthma risk (P = 0.037). Conclusions: This study identified novel associations of rs3847076 in CDHR3, as well as rs1892953, rs2508746 and rs12278256 in EMSY with adult asthma susceptibility in the Chinese Han population. Our observations suggest that CDHR3 and EMSY may play important roles in the pathogenesis of asthma in Chinese individuals. Further study with larger sample size is needed.
Covid 19 pandemic: Paranasal diagnostic imaging in patients with olfactory loss
Authors: Yıldız Erkan , Balcı Aydın , Selendili Okan , Kuzu Selçuk 
Published: May 2020

Abstract
Objective: COVID-19; It is an infectious disease that starts with cold symptoms and causes Acute Respiratory Failure, causing deaths all over the world. Besides the common symptoms of the disease such as fever, dyspnea and cough, recently, a “sudden loss of smell” has been added as a diagnostic symptom.Materials and Methods: Clinical and demographic features, Tomography results, and odor test scores of 40 patients diagnosed as sudden olfactory loss using Connecticut (CCCRC) Olfactory Test ”will be evaluated together, and odor disorder and clinical and radiological findings will be compared.Results: There was no significant difference in smell loss in terms of gender. No relationship was found between smoking and degree of smell disorder. (p> 0.05) When we evaluated the paranasal CTs taken from our patients with odor loss, 2 patients' CT showed pathological findings (p <0.05). As the patients' illness worsened, an increase in the degree of odor loss was observed (p <0.05). Between the CCCRC score and presence of PNS CT findings, a significant statistical relationship was found (p = 0.0012)Conclusion : Olfactory loss was not related to age, gender, smoking. PNS CT findings were significantly correlated with the degree of olfactory loss. In patients with olfactory loss, evaluation with a PNS CT may be diagnostic in terms of COVID-19. However, in order for this examination to be diagnostic, a larger patient series is needed.
An Autonomic Approach to Enhance Web Application Availability
Authors: Fakhouri Hussam N. 
Published: May 2020

Abstract
Autonomic computing is one of the fascinating features that enable the system to automatically manage itself, diagnose itself, detect the error that cause the failure, then recover and reconfigure the system. The concept of software, systems and web self healing is widely used in many software such as windows operating system which restores and recover tools. Since of the aim of the self healing software feature is to fast recover the application and keep running it and available for 24/7 as optimal as possible then it will a suitable to apply this capability to the web applications to fast recover from any unexpected change that may happen. This paper proposes a self-healing system that monitor, diagnose, check and heal web applications automatically and immediately with unnoticeable recovery time. To test the practical applicability of the proposed methodology, an application has been developed to demonstrate the methodology and apply it for real time web applications. The results of experiments performed on different scenarios demonstrated the ability of the proposed approach to heal web applications and to increase its availability.
Higher prevalence of ESBL producing uropathogenic Escherichia coli among Diabetic patients from a Tertiary Care Hospital of Kathmandu
Authors: Nayaju Tulsi , Upreti Milan Kumar , Ghimire Alina , Shrestha Basudha , Maharjan Basanta , Joshi Rajesh Dhoj , Lekhak Binod , Shrestha Upendra Thapa 
Published: June 2020

Abstract
Background: The increased rate of urinary tract infection (UTI) in immunocompromised patients especially diabetic patients is a major public health problem in adults. Moreover, the infection with multidrug resistant strains producing extended spectrum beta-lactamase (ESBL) is a key obstacle in disease management among such vulnerable population. An immediate proper treatment depends on rapid diagnosis of UTI and screening of antimicrobial resistant pattern with highly sensitive methods which also reduces the possible urinary complications among the diabetic patients. Hence, this study was aimed to determine the occurrence of antibiotic resistant genes for β-lactamases; blTEM and blaCTX-M in uropathogenic Escherichia coli isolates from UTI suspected diabetic and non-diabetic patients. attendingMethods: A hospital-based cross-sectional study was conducted in Kathmandu Model Hospital in association with Central Department of Microbiology, TU from June to December 2018. A total of 1267 non-duplicate mid-stream urine specimens from diabetic and non-diabetic patients were obtained and processed immediately for isolation of uropathogens. The isolates were subjected for antibiotic susceptibility testing and ESBL confirmation. Finally, blaTEM and blaCTX-M ESBL genes were screened by using specific primers.Results: The overall prevalence of the urinary tract infection UTI was found to be 17.20%(218/1267) , out of which diabetic patients were significantly more infected with UTI accounting for 32.29%(31/96) as compared to non-diabetic persons, 15.97%(187/1171). A total of 221 bacterial were from 218 culture positive specimens in which E . coli was a most predominate one; 67.9%(150/221.). Forty-four percent (66/150) of the total E. coli was MDR and 37.33%(56/150) were ESBL producers. Among 56 isolates, 92.3%(12/13) from diabetic patents and 83.0% (44/53) were from non-diabetic patients. Furthermore, 84.85% of the screened ESBL producers were confirmed to possess either single or both of the blaTEM and blaCTX-M genes . The blaTEM and blaCTX-M genes were detected in 53.57% and 87.5% of the phenotypically ESBL confirmed E. coli .Conclusions: The UTI infection is an increasing problem in diabetic patients and infection with multidrug resistant strains specially ESBL producing uropathogens are causing a huge problem in disease management leading to high rate of mortality and morbidity of diabetic patients.
Immunohistochemical Expression of Interleukin-17 and Hormonal Receptors in Benign and Malignant Breast Lesions
Authors: Ali Eman , Masri Mai , Siddig Emmanuel Edwar , Ahmed Ayman , Muneer Mohamed , Mohamed Nouh Saad , Edris Ali Mahmoud 
Published: June 2020

Abstract
Objectives:IL17 is a critical pro-inflammatory cytokine that is involved in inflammation, multidrug resistance and growth persistence pathways in cancer. This study is aiming at studying the expression of IL17 and hormonal receptors expressionin benign and malignant breast lesions using immunohistochemical staining methods.Results:A total of 137 cases of breast lesions were studied,97 (70.8%) were malignant and 40 (29.2%) were benign cases. Age range for malignant and benign cases were between 26 to 80 years [mean age 50±2 years], and 20 to 70 years[mean age 41±4 years], respectively, Odds ratio= 2.3 [1.78-1.99, 95% CI].The majority of the histopathological diagnosis of the benign and malignant lesions were 21 (15.3%) fibro-adenomas and 87 (63.5%) invasive ductal carcinoma, respectively. Expression of IL17 and age were insignificantly negatively correlated for both groups; benign cases [r= -0.054, P value 0.742] and malignant cases [r= -0.080, P value 0.444]. IL17 expression was showing insignificant association with age group, P value 0.065. IL17 expression showed a statistical significance based on the different histopathological diagnosis, P value 0.035. Expression levels of estrogen, progesterone, and human epidermal receptors were showing insignificant difference among IL17 expression categories, P values 0.678, 0.623, and 0.361, respectively.
Identification of Key Genes and MicroRNAs in Gastric Cancer via miRNA-mRNA Regulatory Network
Authors: Huang Chao , Zhu Xiaojian , Zhao Jiefeng , Bu Fanqin , Huang Jun , Zhu Zhengming 
Published: June 2020

Abstract
Background

Gastric cancer (GC) is a malignant tumor with high mortality. MicroRNAs (miRNAs) participate in various biological processes and disease pathogenesis by targeting messenger RNA (mRNA). The purpose of this study was to identify potential prognostic molecular markers of GC and to characterize the molecular mechanisms of GC.
Methods

A gene expression profiling dataset (GSE54129) and miRNA expression profiling dataset (GSE113486) were downloaded from the Gene Expression Omnibus (GEO) database. A miRNA-mRNA interaction network was established. Functional and pathway enrichment analyses were performed for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using FunRich, the clusterProfiler package, and DIANA-mirPath. Survival analysis of key molecular markers was performed using the online tool Kaplan-Meier Plotter and the database OncomiR. Finally, experiments were carried out to verify the expression levels and biological functions of a key gene.
Results

A total of 390 DEMs and 341 DEGs were identified. Ultimately, 45 genes and 31 miRNAs were selected to establish a miRNA-mRNA regulatory network. Four hub genes (ZFPM2, FUT9, NEUROD1 and LIPH) and six miRNAs (hsa-let-7d-5p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-133b, hsa-miR-130a-3p and hsa-miR-124-3p) were identified in the network. DEGs and DEMs were associated with ECM-receptor interactions and metabolic pathways. Two genes (ZFPM2 and LIPH) and two miRNAs (hsa-miR-23a-3p and hsa-miR-130a-3p) were observed to be related to the prognosis of GC. ZFPM2 was highly expressed in GC tissues and various GC cell lines and could promote the proliferation, invasion and migration of GC cells.
Conclusion

The expression levels of ZFPM2, LIPH, hsa-miR-23a-3p and hsa-miR-130a-3p were closely related to the prognosis of GC. ZFPM2 may serve as a potential molecular marker and therapeutic target for GC. ECM receptor interactions and metabolic abnormalities play a critical role in the GC progression.
Mathematical model of transmission dynamics with mitigation and health measures for SARS-CoV-2 infection in European countries
Authors: Sankhwar Shweta , Kumar Narender , Dohare Ravins 
Published: May 2020

Abstract
The pandemic of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) continue to pose a serious threat to global health resulting in disease COVID-19. No specific drug or vaccine is available against this infection. Therefore, the prevention is only way to reduce the spread of infection. The pandemic needs an enhanced mathematical model, therefore, we propose a SEIAJR compartmental mathematical model to estimate the basic reproduction number (R0 ) and the transmission dynamics of four European countries (Germany, United Kingdom, Switzerland and Spain). The proposed mathematical model incorporates mitigation and healthcare measures as recommended by ECDC (European Centre for Disease Prevention and Control). The simulation of proposed model is done in two phases. First-phase simulation estimates basic reproduction number and mitigation rate according to active infected cases in all four European countries. R0 estimate 2.82 - 3.3 for considered European countries. Second-phase simulation predicts the dynamics of infection on the estimated R0 with varying mitigation rate and constant healthcare rate. This study predicts that no more mitigation is required to invade the infection. The current mitigation and healthcare measures are enough to stop the propogation of infection, however, infection would last by end of July 2020. The developed mathematical model would also be applicable to portray the infection trasmission dynamics for other geographical regions with varying parameters.
Severe immune thrombocytopenic purpura in critical COVID-19: a case report
Authors: Lévesque Valérie , Milaire Émilie , Corsilli Daniel , Rioux-Massé Benjamin , Carrier François Martin 
Published: May 2020

Abstract
Purpose: COVID-19 is a new disease with many undescribed clinical manifestations. Material and methods: We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient.Results: A patient presented a severe episode of immune thrombocytopenia (< 10 x 109/L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high dose dexamethasone to observe an increase in platelet count. Conclusion: COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.
Revisiting the role of vitamin D levels in the prevention of COVID-19 infection and mortality in European countries post infections peak
Authors: Singh Samer , Kaur Rajinder , Singh Rakesh Kumar 
Published: June 2020

Abstract
Various studies are underway to identify protective variables for the COVID-19 pandemic. We hypothesized that if indeed the Vitamin D levels would be protective in the European population, as recently proposed, the correlation would become more robust when the countries had passed the infection peak as on May 12, 2020, compared to April 8, 2020, when the majority had not. Comparative analysis of data from the mentioned stages indicated a significant increase in negative correlation of vitamin D levels with COVID-19 cases per million population in later stage (r(20): -0.5504; R2=0.3029; p-value: 0.0119 vs r(20): -0.4435; R2=0.1967; p-value: 0.0501) whereas the correlation with deaths per million population became insignificant (r(20): -0.3935; R2=0.1549; p-value: 0.0860 vs r(20): -0.4378; R2=0.1917; p-value: 0.0535). Considering divergence of vitamin D levels from the mean in subgroups, e.g. children, women, aged, dedicated exploratory studies with carefully chosen matched target groups is advisable.
Evolution of effective serial interval of SARS-CoV-2 by non-pharmaceutical interventions
Authors: Ali Sheikh Taslim , Wang Lin , Lau Eric H. Y. , Xu Xiao-Ke , Du Zhanwei , Wu Ye , Leung Gabriel M. , Cowling Benjamin J. 
Published: June 2020

Abstract
Studies of novel coronavirus disease (COVID-19) have reported varying estimates of epidemiological parameters such as serial intervals and reproduction numbers. By compiling a unique line-list database of transmission pairs in mainland China, we demonstrated that serial intervals of COVID-19 have shortened substantially from a mean of 7.8 days to 2.6 days within a month. This change is driven by enhanced non-pharmaceutical interventions, in particular case isolation. We also demonstrated that using real-time estimation of serial intervals allowing for variation over time would provide more accurate estimates of reproduction numbers, than by using conventional definition of fixed serial interval distributions. These findings are essential to improve the assessment of transmission dynamics, forecasting future incidence, and estimating the impact of control measures.