bluuebunny/crossref_metadata_2025_split huggingface dataset:
OPC UA: Kommunikation und Security
Authors: Jänicke Lutz , Förder Torsten 
Published: March 2020

OPC UA ist ein wichtiges Element in der Umsetzung von Industrie 4.0. Aufgrund der Vernetzung und Verflechtung von Systemen und Organisationen ist Industrie 4.0 ohne Security nicht denkbar. Insofern müssen die Security-Konzepte von OPC UA die heute schon vorhandenen und zukünftig zu erwartenden Anforderungen erfüllen. Eine Analyse des Status Quo für die lokale Anwendung von OPC UA wie auch für die unternehmensübergreifende Kommunikation zeigt, dass Anpassungs- und Erweiterungsbedarfbesteht, um Einsatzmöglichkeiten zu erweitern und die Anwendbarkeit zu verbessern.
Influence of urokinase gene-knockout in C57BL/6-PlautmI. IBugThisPlau6FDhu/GFDhu mice on growth factors in malignant melanoma
Authors: Frantsiyants E. M. , Kaplieva I. V. , Neskubina I. V. , Bandovkina V. A. , Trepitaki L. K. , Surikova E. I. , Cheryarina N. D. , Nemashkalova L. A. , Lesovaya N. S. 
Published: March 2020

Purpose of the study. Studying characteristics of the growth factor dynamics in the intact skin, tumors and perifocal tissues of melanoma in urokinase (uPA) gene-knockout mice.Materials and methods. The study included male and female С57 ВL/6 mice (n=47) and C57BL/6‑Plautm1.1BugThisPlauGFDhu/GFDhu mice with uPA gene-knockout (n=31). В16/F10 melanoma was transplanted subcutaneously at a dose of 0.5 mL (1:10 in normal saline). Intact mice of the same strain served as controls. Levels of VEGFA, VEGFC, sVEGFR1, sVEGFR3, IGF1, IGF2, TGFβ1 and FGF21 were determined by ELISA in the skin, tumor and perifocal tissues isolated on the 21st day of the tumor growth.Results. uPA gene-knockout inhibited the growth (mostly in females) and metastasis (predominantly in males) of melanoma in mice. Inhibition of the migration of malignant cells in males could be due to low levels of TGF-β1 compared to С57 ВL/6 mice: in the skin – by 5.0 times, in tumors – by 1.8 times and in perifocal tissues – by 6.1 times. In uPA gene-knockout females, lower levels of TGF-β1 were observed in tumors – by 1.4 times inhibited metastasis, but not completely, and solitary metastatic foci were registered in the lungs. Нigh levels of IGF1 in tissues of all uPA gene-knockout mice (males: in tumors by 1.4 times, in perifocal tissues by 2.6 times, in the skin by 3.6 times; females: in tumors by 2.6 times, in perifocal tissues by 25.0 times, in the skin by 13.9 times, compared to С57 ВL/6 mice) could maintain the metastatic phenotype of cancer cells (in females) or hiher proliferative activity of melanoma cells (in males). Lower levels of FGF‑21 in tumors (males – by 5.3 times, females – by 18.4 times), perifocal tissues (males – by 9.6 times, females – by 8,5 times) and skin (males – by 6.7 times, females – by 3.3 times) in uPA gene-knockout animals could be due to the IGF‑1 growth, as their reciprocal interaction is known. Interestingly, a significant, although lesser than in mice with a normal genotype, accumulation of VEGFA in melanoma tissues was observed: in males – in tumors by 44.9 times, in perifocal tissues by 6.8 times, in the skin by 2.4 times; in females – in tumors by 5.6 times, in perifocal tissues by 2.6 times, in the skin by 3.3 times, compared to the corresponding intact controls, due to the probable involvement of the uPA receptor (uPAR) in the implementation of VEGF-induced processes.Conclusion. Changing the activity of a system of some growth factors, uPA gene-knockout modifies melanoma metabolism by inhibiting its growth and eliminating or reducing its metastatic activity.
Üçüncü Basamak Bir Üniversite Hastanesinde Asistan ve Uzman Doktorların İş Doyumu ve Motivasyonunu Etkileyen Faktörler
Authors: Gökaslan Serkan , Kanad Nazmi 
Published: March 2020

İş doyumu, sağlık çalışanlarının iş verimini
arttıran önemli faktörlerin başında gelmektedir. İş doyumu ve motivasyonu ile yapılan
hizmetin kalitesi ve etkinliği arasında pozitif bir ilişki vardır. Doktorların
iş doyum düzeyleri; kişilik karakteri, çalışma ortamında yaşanan sıkıntılar gibi pek çok parametreden etkilenmektedir. Araştırma doktorların iş doyumu ve
iş doyumunu etkileyen faktörleri tanımlamak ve araştırmak amacıyla planlandı. Araştırmaya Afyonkarahisar Sağlık
Bilimleri Üniversitesi Hastanesi’nde çalışan 80 asistan doktor ve 26 uzman
doktor alındı. Doktorların demografik özellikleri kayıt edildi ve iş tatmin
düzeyleri Minnesota İş Tatmin Ölçeği kullanılarak hesaplandı. Veriler arasındaki
ilişkiye kategorik veriler için Pearson chi-square, sayısal veriler için
Pearson korelasyon analizi ile bakıldı.
Asistanların ve uzmanların iş tatmini puan ortalaması sırasıyla 3,19 ve 3,53
olduğu saptandı.

Çalışma sonucunda, hekimlerin iş tatminleri üzerinde çalışma
şartlarının iyileştirilmesinin ve ekonomik olarak motivasyonlarının
artırılmasının önemli yer tuttuğu gözlenmiştir.
Better pulmonary function is associated with greater handgrip strength in a healthy Chinese Han population
Authors: Chen Liangmei , Liu Xiaomin , Wang Qian , Jia Linpei , Song Kangkang , Nie Sasa , Zhang Yinping , Cao Dan , Zhao Delong , Li Zuoxiang , Dong Zheyi , Zheng Ying , Duan Shuwei , Sun Xuefeng , Feng Zhe , Cai Guangyan , Zhang Weiguang , Chen Xiangmei 
Published: March 2020

Abstract
Background: Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analyzed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters. Methods: HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student’s t-tests or Mann–Whitney U-tests were used for continuous variables. Pearson correlation analysis was used between normally distributed variables, and Spearman correlation analysis was used for non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set at p <0.01. Results: Cross-sectional data were available for 1519 subjects (59.0% females, 57.9±13.1 years old). Males had higher average HGS than females (40.2 vs 25.0 kg, p <0.01 ), as well as better pulmonary function. Both HGS and pulmonary function parameters were significantly inversely correlated with age (r ≤ -0.30, p < 0.01). Maximum value of vital capacity (VC max), forced expiratory volume in 3 second (FEV3) and forced vital capacity (FVC) were strongly correlated with HGS among the pulmonary function indices (r=0.72, 0.70 and 0.69, respectively, p <0.001). In multivariate linear regression analysis, HGS and height were positively correlated, while age and pulse pressure were negatively correlated with HGS. In male, FVC, VC max and FEV3 increased by 0.02L, 0.023L and 0.03L in per 1 kg increase in HGS, respectively. The coefficients of HGS in female was smaller than those in male. Conclusions: Both pulmonary function and HGS were inversely correlated with age, and better pulmonary function was associated with greater handgrip strength.
Dysfunction of Shh signaling impaired trophoblast motility and autophagy is involved in poor placentation of recurrent miscarriage
Authors: Pan Yibin , Yan Lili , Chen Qiaoqiao , Wei Cheng , Dai Yongdong , Tong Xiaomei , Zhu Haiyan , Lu Meifei , Zhang Yanling , Jin Xiaoying , Zhang Tai , Lin Xiaona , Zhang Songying 
Published: March 2020

Abstract
Background: In early pregnancy, the placenta anchors the conceptus and supports embryonic development and survival. This study aimed to investigate the underlying functions of Shh signaling on recurrent miscarriage, an serious disorder of pregnancy. Methods: Immunofluorescence and immunohistochemistry were used to detect protein expression and its location in placental tissues. Quantitative real-time RT-PCR and Western blot analysis were performed to examine mRNA and protein levels, respectively. Lentiviruses expressing short hairpin RNA were used to knock down the target genes. Cell invasion and migration were performed by with or without Matrigel-coated transwell, respectively. Primary trophoblast migration was performed by villous explant assay. RNA-sequence was used to investigate the genes transcription profile. CCK-8 assay was used to evaluate cell viability. Flow cytometry was used to evaluate cell apoptosis. Results: Our results showed that Shh and Gli2 were mainly located in cytotrophoblasts (CTBs), Ptch was mainly located in syncytiotrophoblasts (STBs), while Smo and Gli3 were expressed in both CTBs and STBs. Compared to the gestational age-matched normal human placenta, the expression of Shh was significantly decreased in recurrent miscarriage. Furthermore, inhibition of Shh signaling impaired motility of JAR cells via regulating the expression of Gli2 and Gli3 to decrease AKT Ser473 phosphorylation, elevate E-cadherin and VEGFA. Intriguingly, inhibition of Shh signaling also enhanced autophagy and autolysosome. Additionally, knockdown BECN1 reversed the effect of Gant61 on motility inhibition. Conclusion: Our results indicated that dysfunction of Shh signaling impaired trophoblast motility, angiogenesis and activated autophagy in villous trophoblast, which would contribute to the pathophysiology of recurrent miscarriage.
The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis
Authors: Gu Lihu , Li Shengnan , Du Nannan , Yao Qigu , Fu Xiaojun , Lou Yuanmei , Wang Mengru , Mao Feiyan , Mao Danyi , Khadaroo Parikshit Asutosh , Tang Yingying 
Published: March 2020

Abstract
Background: Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab-ipilimumab combination therapy in cancer treatment. Methods: We examined data from PubMed, Web of science, EBSCO and Cochrane library. Eleven articles fulfilled our criteria, which we divided into 3 groups; nivolumab and ipilimumab versus ipilimumab, nivolumab and ipilimumab versus ipilimumab and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR) and TRAEs in any grade and grade 3 or higher. Results: Compared with ipilimumab alone, the combined immunotherapy had better CR (RR: 4.89, p <0.001), PR (RR: 2.75, p <0.001), and ORR (RR: 3.31, p <0.001). The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p <0.001) and PR (RR: 1.50, p <0.001) than nivolumab alone. Finally, N1I3 showed better PR (RR: 1.35, p =0.006) and ORR (RR: 1.21, p =0.03) than N3I1. The incidence of any TRAEs was similar between the both groups (RR: 1.05, p =0.06). However, the incidence of serious adverse events (grade 3 or higher) were lower in group N3I1 than group N1I3 (RR: 1.51, p <0.001). Conclusion: This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of ipilimumab or nivolumab monotherapy. In the combination group, N1I3 combination was more effective than N3I1. Although the side effects were slightly increased in group N1I3, the overall safety was acceptable.
Validity and Reliability of the Amharic Version of the HLS-EU-Q47 Survey Questionnaire among Urban School Adolescents and University students in Dire Dawa, Ethiopia
Authors: Hassen Hailemariam Mamo , Behera Manas Ranjan , Jena Pratap Kumar , Satpathy Sudhir K Kumar 
Published: March 2020

Abstract
Background: Comprehensive tool is not available to assess health literacy status across different languages, contexts and population structures except European health literacy survey scale (HLS-EU-Q47) which is widely used adapted and tested in different countries and languages. However, it was not tested for Ethiopian populations. This study aim was to validate and test the reliability of the Amharic version of the HLS-EU-Q47 survey questionnaire (HLS-Amh) among school adolescents and university students in Dire Dawa, Ethiopia. Method: A cross-sectional study with multistage random sampling was done on urban school adolescents and university students from public schools and Dire Dawa University in Dire Dawa city, Ethiopia, Africa. After translating HLS‐EU‐Q47 into Amharic by translation and back- translation, data was collected using a self-reported questionnaire from samples of 744 participants with 9% non-response rate in October and November, 2018. Confirmatory factor analysis and correlation analysis was done using SPSS and AMOS. Goodness of fit indices, item-scale convergent validity, Pearson correlation coefficient, floor and ceiling effects, Cronbach's alpha and split-half spearman-brown coefficient was computed taking the cut-off values from guidelines and literatures. Ethical issue was contemplated and informed consent was obtained from institutions and participants. Result: Amharic version of HLS- EU-Q47, (HLS-Amh) was reliable but weak for its validity to measure health literacy among urban school adolescents and university students in Dire Dawa, Ethiopia. Goodness-of-fit indices (GFI, AGFI, CFI and IFI) were within range of 0.90-0.80. Although, RMSEA indices were less 0.10, others have made it insufficient to be said as a good model-data fit and was not tolerable for its validity, and the model lacked strength to meet the model-fit indices satisfaction with higher apparent floor/ceiling effects. However, it showed high levels of internal consistency of reliability with relatively higher Cronbach’s alpha coefficient (α=0.910). Conclusions: HLS-Amh was reliable but weak for its validity on these population groups. It can be used for a general survey on awareness and knowledge other than screening substantial and clinical related inquiries. It needs further adaptation and validation for comprehensiveness for demographic, multi-lingual and cultural contexts in Ethiopia.
A quasi-experimental and Guided Social Media Intervention to Improve Mental Health Literacy Level of Urban School Adolescents in Ethiopia: A Detailed Study Protocol
Authors: Hassen Hailemariam Mamo , Behera Manas Ranjan , Jena Pratap Kumar , Satpathy Sudhir Kumar 
Published: March 2020

Abstract
Background: Studies showed Ethiopian adolescents have lower knowledge and awareness about resilient and risk factors and preventive methods of mental health problems that increases mental health promotion and prevention gap. Addressing this gap in school settings using technology assisted mental health promotion platforms could help improve mental health literacy level. Therefore, evaluating effectiveness outcomes of guided social media intervention to improve mental health literacy of school adolescents is convenient issue. Methods: Quantitative and quasi-experimental study will be used among urban school adolescent in Dire Dawa, Ethiopia. Following pretest measure among adolescents who have smart phones or social media access and age > 15 years old, participants will be assigned by regression discontinuity design as good as random and then mental health literacy module will be delivered through face book/telegram group to be created for about four weeks and posttest will be done after lapse of a week. Control group will receive posts on effective academic studying skills. Adapted and tested questionnaire in convenient local languages along with English version will be used. Inferential statistics will be applied with significance level of p<0.05. Informed voluntary consent will be obtained from participants, their parents/guardians and school directors. Ethical approval is already obtained.Discussion: Mental health promotion in school settings most importantly using technology assisted mental health promotion platforms supposed to be cost-effective, accessible, acceptable, adoptable, appropriate, feasible, reliable, scalable and sustainable approach helping tailor mental health literacy focused mental health first aid practices still deficient and new for Ethiopia. The study will test the hypothesis whether social media is effective channel of intervention in improving mental health literacy level of urban school adolescents.
Genome-wide mapping of alternative splicing in the elite wheat cultivar Xiaoyan 6
Authors: Mao Hude , Zhang Jin , Guo Lijian , Chi Qing , Mei Fangming , Liu Xiangli , Zhao Huixian 
Published: March 2020

Abstract
Background: Triticum aestivum, or common wheat, is a globally important cereal crop. Alternative splicing (AS) is an important post-transcriptional regulation mechanism in higher eukaryotes, but the knowledge of AS in wheat is limited at present. Results: In this study, we performed AS mapping from the elite, high-yielding wheat cultivar Xiaoyan 6. We identified 18,960 and 25,133 novel protein-coding genes and transcript models that were not annotated in the draft genome of wheat cultivar Chinese Spring. We also found that 18,868 genes were alternatively spliced, and classified four major AS types, including alternative acceptor sites (AA), intron retention (IR), alternative donor sites (AD), and exon skipping (ES). Further analysis determined that differences in the AS frequency and AS types displayed a positive correlation with exon number and intron length and were negatively correlated with the GC content, but were not correlated with gene transcriptional level. Furthermore, we identified 2,737 seed-specific AS genes in wheat cultivar Xiaoyan 6, and demonstrated that the number of AS genes in the grain decreased with seed development, suggesting that the earlier developmental stages are more important and complex than are the later stages. In addition, the grain-specific AS genes that were ubiquitously significantly up-regulated during seed development were associated with metabolism-related pathways, indicating that AS of metabolism-related genes is crucial for grain filling in wheat. Conclusions: Through transcriptome analysis, over ten thousand AS genes were identified and characterized in wheat cultivar Xiaoyan 6. Our study provides a comprehensive view of AS in the wheat cultivar Xiaoyan 6 and provides new insights into the complexity of AS in wheat. The data generated in this study provides a foundation for further studies of seed development in wheat.
Evaluation of ATP-PostC protective effect on myocardial function: A speckle tracking echocardiography study in ischemia-reperfusion injury
Authors: Ren Min , Li Keting , Liu Xuemei , Yang Hongyu , Jiang Zhonghui , Wu Xinyu , Liu Yujie 
Published: March 2020

Abstract
Background: Ischemia-reperfusion injury (IRI) seriously affects the prognosis of patients. We sought to use speckle tracking echocardiography (STE) to accurately evaluate the effect of drugs. Methods: In this study, STE was used to quantitatively evaluate the changes of myocardial function before and after reperfusion in myocardial ischemia rabbits with ischemia postconditioning (I-PostC) or ATP postconditioning. The variations of the left ventricular (LV) longitudinal, circumferential and radial myocardium were detected by STE technique. Meanwhile, a series of biochemical experiments were performed including myocardial enzymes assay, myocardial infarction size assay and TUNEL assay. Results: After ligation of coronary artery for 45 min, the strain and strain rate curves of left ventricular myocardium was disordered. The most STE parameters were significantly diminished and the time of reaching peak was delayed. After reperfusion for 120 min, the parameters (longitudinal, circumferential, radial strain and strain rate, as well as ventricular torsion function) were obvious recovery in I-PostC and ATP postconditioning groups. The sensitivity and specificity of global circumferential peak strain (GCSp), global longitudinal peak strain (GLSp), peak twist (Ptw) and peak twisting velocity (PTV) to diagnose myocardial infarction rabbits were 86.1% and 75%, 79.2% and 72.5%, 79.2% and 75%, 66.7% and 70.8%, respectively. The levels of aspartate aminotransferase (AST) and creatine phosphokinase isozyme (CKMB) were up-regulated in I/R group. AST and lactate dehydrogenase (LDH) values significantly reduced in the other three groups. The Bax expression was decreased, simultaneously, the Bcl-2 expression was increased after I-PostC and ATP postconditioning treatment. Conclusions: The application of STE in the assessment of IRI has high accuracy and reproducibility. Therefore, ATP has an important clinical value as a pharmacologic postconditioning drug.
Identification of novel candidate biomarkers and efficacious small molecule drugs for pancreatic adenocarcinoma based on comprehensive bioinformatics technology
Authors: Yang Jie , Wang Peng , Li Yuan-Yuan 
Published: March 2020

Abstract
Background: Pancreatic adenocarcinoma (PAAD) is considered as one of most serious solid tumors with high mortality as well as incidence. We performed this present study to screen out novel biomarkers and potential efficacious small drugs in PAAD using integrated bioinformatics analyses. Methods: Expression profiles derived from TCGA and GTEx datasets were integrated by following bioinformatics methods: DEGs analysis, WGCNA, KEGG and GO enrichment analyses. Kaplan-Meier method was conducted to assess the prognostic performance of genes, and the predictive value of identified genes was determined by the ROC analysis. CMap analysis was utilized to identify the related small molecule drugs in PAAD. Results: A total of 4777 DEGs containing 2536 up-regulated and 2241 down-regulated genes were identified. WGCNA identified six modules that were related with clinical characteristics, and functional enrichment analyses showed that all genes of blue module were enriched in EMT, PI3K/Akt signaling pathway and other important biological processes and pathways. Moreover, three genes ( ITGB1 , ITGB5 , and OSMR ) of blue module were determined as key genes with higher expression levels and significant prognostic value. ROC analysis revealed that these three genes had excellent diagnostic efficiency for PAAD. These three key genes were highly regulated in PAAD tissues compared with normal controls. A panel of small molecule drugs including thapsigargin, viomycin, adiphenine, and CP-690334-01 were screened out to treat PAAD. Conclusion: In conclusion, our findings identified three key genes implicated in PAAD and screened out several potential small drugs to treat it, which may shed novel insights into the development of PAAD and its treatment.