bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Inactivation of Acetyl-Co A acetyltransferase 1 promotes the proliferation and metastasis of nasopharyngeal carcinoma via decreasing ketogenesis
Authors: Lu Yunliang , Zhou Xiaohui , Zhao Weilin , Liao Zhipeng , Li Bo , Yang Yanping , Zhong Xuemin , Mo Yingxi , Li Ping , Huang Guangwu , Xiao Xue , Zhang Zhe , Zhou Xiaoying
Published: September 2020

Background

Acy1 Coenzyme A Acyltransferases1 (ACAT1) is a key enzyme in the metabolism of ketone bodies, but its expression and biological function in the pathogenesis of NPC remains underexplored.
Methods

The mRNA and protein expression levels of ACAT1 in NPC and normal control tissues were analyzed by qPCR and immunohistochemistry staining, respectively. GEO database was applied for meta-analysis of ACAT1 mRNA expression and DNA promoter methylation. The role of ACAT1 in NPC proliferation was examined by CCK8 and colony formation assays in vitro and tumorigenicity in vivo. The wound healing and transwell assays were used for analyzing the migratory and invasive ability. cDNA microarray analysis was performed to identify the genes involved in epithelial-mesenchymal transition and dysregulated by ACAT1. These changes were further confirmed by western blot.
Results

We found that ACAT1 is inactivated in NPC cell lines and primary tissues. DNA microarray data showed higher methylation in the CpG island region of ACAT1 in NPC than normal tissues. The demethylating reagent 5-aza-dC significantly restored the transcription of ACAT1 in NPC cell lines, suggesting that ACAT1 was inactivated by DNA promoter hypermethylation. Ectopic overexpression of ACAT1 remarkably suppressed the proliferation and colony formation of NPC cells in vitro. As well, the tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. In addition, the migratory and invasive capacities of NPC cells was inhibited by ACAT1 overexpression. Importantly, the higher level of ACAT1 was accompanied by an increased expression of CDH1, EPCAM, and a decreased expression of vimentin and SPARC. This strongly indicates that ACAT1 is able to affect the epithelial-mesenchymal transition in NPC, thereby controlling cellular motility. In addition, we found that ACAT1 expression increases the intracellular level of β-HB. Moreover, exogenous β-HB remarkably inhibits the growth of NPC cells in a dose-dependent manner.
Conclusions

We have discovered that the ketone body metabolism enzyme ACAT1 is epigenetically downregulated in NPC and acts as a potential tumor suppressor in NPC. Our findings highlight the possibility of using the modulation of ketone body metabolism as effective adjuvant therapy for NPC.
Exosomes miR-184 and miR-3913-5p are involved in Osimertinib resistance in non-small cell lung cancer patients with exon 21 L858R mutation
Authors: Li Xinying , Chen Cen , Wang Zimu , Liu Jiaxin , Sun Wei , Shen Kaikai , Lv Yanlin , Zhu Suhua , Zhan Ping , Zhang Fang , Liu Hongbin , Lv Tangfeng , Song Yong
Published: September 2020

Background

The third-generation of EGFR-TKI Osimertinib has become an important treatment option for patients with EGFR-mutant advanced NSCLC. In recent years, more and more studies have begun to pay attention to the ability of miRNAs in exosomes secreted by tumor cells to transmit resistance information. The mechanisms of exosomal miRNAs involved in Osimertinib resistance need to be studied.
Methods

We constructed an Osimertinib-resistant cell line H1975-OR, and collected the exosomes from the cells of the drug-resistant strain and the sensitive strain, and extracted respective RNA for sequencing. We also compared miRNAs in serum exosomes of three patients before and after resistance to Osimertinib. Enlarged samples were then validated in 64 NSCLC patients.
Results

Cluster analysis of target genes revealed that miRNAs in exosomes participate in Osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality, PI3K pathway activation). MiR-184 and miR-3913-5p increased significantly in serum exosomes of patients with later Osimertinib resistance. These two miRNAs mainly cause EGFR resistance in two types of NSCLC patients, EGFR exon 21 L858R mutation and T790M positive.
Conclusions

Exosomes miR-184 and miR-3913-5p mainly cause Osimertinib resistance in lung cancer patients containing EGFR exon 21 L858R+ and T790M+. They are regarded as important biomarkers of third-generation EGFR-TKI resistance. This not only enriches the application of liquid biopsy in lung cancer drug resistance, but also provides a direction for future targeted drug research.
Genome-Wide Association Study to Identify SNPs and Haplotypes Associated with Reproductive Performance and Egg Quality Traits in Geese
Authors: Gao Guangliang , Gao Dengfeng , Zhao Xianzhi , Xu Songsong , Zhang Keshan , Wu Rui , Yin Chunhui , Li Jing , Xie Youhui , Hu Silu , Wang Qigui
Published: September 2020

Background: Geese are one of the most economically important waterfowl worldwide. However, suboptimal reproductive performance hinders the development of the goose rearing industry. With the increasing public concern surrounding animal health and the regulation of the goose rearing industry, reproductive performance and egg quality have become a major focus for researchers. To promote the accuracy of selective breeding and identify important candidate genes associated with reproductive performance and egg quality traits, we examined the birth body weight (BBW), egg number at 48 weeks (EN48), egg number at 60 weeks (EN60) and egg yolk color (EYC) among 209 Sichuan White geese using a genome-wide association study (GWAS).Results: In this study, we obtained 2.896 Tb of raw whole-genome sequencing data with a mean depth coverage of 12.44. A total of 9,279,339 single nucleotide polymorphisms (SNPs) were identified in the goose genome. The GWAS analysis showed that 26 SNPs were significantly associated with the examined birth body weight (BBW), egg number in 48- and 60-week-old geese (EN48 and EN60) traits and egg yolk color (EYC), respectively. Notably, two genomic regions, a 28.85 kb genomic region (4512855bp ~ 4541709bp) on chromosome 35, and 294.57kb genomic region (21069009 b ~ 21363580 bp) located on chromosome 5, were significantly associated with egg number in 48- and 60-week-old geese (EN40 and EN60) egg yolk color (EYC), respectively. In addition, we performed the MALDI-TOP MS method to detected SNPs and haplotypes markers for EN48, EN60 and EYC traits were identified in the candidate gene TMEM161A, CALCR, TFPI2, and GLP1R, respectivelyConclusions: The SNPs, haplotypes markers and genes identified in this study can be used for marker-assisted selection of reproductive performance and egg quality traits in geese, promoting the accuracy of selective breeding. In addition, the identified candidate genes significantly associated with the traits provide a foundation for a better understanding of the mechanisms underlying reproduction and egg quality in geese.
Remodelling Macroeconomic Trilemma and Central Bank Behaviour in Nigeria: A Markov-Switching Approach
Authors: AYINDE Taofeek Olusola , S. BANKOLE Abiodun
Published: September 2020

This study investigates macroeconomic trilemma and Central Bank behavior in Nigeria. The period of investigation spans the quarterly period of 1981–2017. Upon the data stability condition of Zivot-Andrew unit-root test with structural breaks, the Markov Switching Dynamic Regression was employed as the technique of analysis. With a validated trilemma hypothesis, the study found that the trilemma constraints hold for the Nigerian economy but at the expense of the autonomy of the monetary authority. Being the policy variable of the Central Bank of Nigeria, the exchange rate was found to follow two regimes of fixed and managed-float regimes. The results also showed that political risk was found insensitive to the regimes of exchange rate while the foreign sector was considered as a moderating factor for the behavior of the monetary authority; irrespective of the exchange rate regime.JEL Classifications: F41, E32, E52, C22, E58.
The Effect of Acupuncture on MiRNA Expression Profiles in the Ovaries of Rats with PCOS and Insulin Resistance
Authors: Zhang Chunren , Yu Chuyi , Huang Shiya , Lin Zengxian , Zheng Ruqun , Su Yufei , Lin Han , Li Juan , Li Kunyin , Ma Hongxia
Published: September 2020

Background: Polycystic ovary syndrome (PCOS) is one of the most commonendocrine and metabolic diseases of women of reproductive age. The majorcharacteristics of PCOS are anovulation, hyperandrogenism, infertility, and insulinresistance. Previous studies showed that acupuncture could promote menstruation,decrease testosterone levels, increase insulin sensitivity, and improve frequency ofovulation in women with PCOS. However, the mechanism of how acupunctureregulates the reproductive and metabolic abnormalities of PCOS remains unclear. Thepresent study investigated the differential expression of miRNAs in the ovaries of ratswith PCOS and insulin resistance (IR) after electroacupuncture (EA) treatment.Methods: A rat model of PCOS with IR was established by letrozole and a high-fatdiet. Rats in the PCOS+EA group received acupuncture treatment five times a week forfour weeks. The differentially expressed miRNAs of three rat ovaries of each group(n=3/group) were identified by deep sequencing. The differentially expressed miRNAsare shown by a hierarchical clustering heatmap and volcano plot. Gene ontology (GO)analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysiswere conducted to explore the potential target genes of the differentially expressedmiRNAs and identify their putative biological function. Eight of the differentiallyexpressed miRNAs were selected for validation by real-time quantitative PCR (qRTPCR).Results: The rats in the PCOS+EA group had significantly decreased body weight andincreased insulin sensitivity compared with the rats in the PCOS group. EA tend toreduce testosterone levels in the rats with PCOS and insulin resistance. The rats in thePCOS+EA group displayed fewer large cystic follicles, fewer atretic antral follicles,and more corpora lutea than the rats in the PCOS group. A total of 23 differentiallyexpressed miRNAs were identified in the PCOS with IR group after EA treatment,including 15 miRNAs that were upregulated and 8 miRNAs that were downregulated.GO and KEGG pathway analyses indicated that the predicted target genes were relatedto cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed thatmiRNA-181 was significantly downregulated in the rat ovaries of the PCOS+EA groupcompared with the PCOS group.Conclusion: Our results indicate that differentially expressed miRNAs may mediate the effect of acupuncture on insulin sensitivity in PCOS with IR. It will be beneficial to study the mechanism of acupuncture in improving insulin resistance in women with PCOS.
Allergen Specific Treg Upregulated by Lung-stage Schistosome Infection Alleviates Allergic Airway Inflammation via Inhibiting IgE Secretion
Authors: Li Zhi dan , Zhang Wei , Luo Fang , Li Jian , Yang Wen bin , Zhu Bing kuan , Wu Qun feng , Wang Xiao ling , Sun Cheng song , Xie Yu xiang , Xu Bin , Wang Zhao jun , Qian Feng , Wan Yan min , Chen Jia xu , Hu Wei
Published: September 2020

Background. Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist regarding the timing of helminth infection and the underlying mechanisms. Moreover, the therapeutic effects of schistosome infection on asthma were rarely investigated. Methods. The mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). Lung pathology, inflammatory cytokines, IgE and frequency of Treg were measured to evaluate the therapeutic effect. The modulation of allergen specific Treg were elucidated by adoptive transfer and Treg deletion in vivo. Finally, RNAseq was employed to explore the key molecules and pathways that might contribute to Treg upregulation. Results. We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. Conclusions. Our results proved that lung-stage schistosome infection could relieve OVA induced AAI in mouse model by the upregulated OVA specific Treg, which may facilitate the discovery of a new therapy for asthma.
Early Risk Factors for Extrapulmonary Organ Injury in Adult COVID-19 Patients
Authors: Huang Fang , Ma Wenxia , Jin Jun , Zheng Hui , Ye Yan , Chen Hui , Su Nan , Li Xinyue , Li Xiaoping , Lu Xiangqiong , He Yang , Wang Yuyu , Li Yongsheng , Wang Jun
Published: September 2020

Objective COVID-19 is becoming a global pandemic and often develops extrapulmonary organ injury. However, the risk factors for extrapulmonary organ injury are still unclear. We aim to explore the risk factors for extrapulmonary organ injury for COVID-19 and the association between extrapulmonary organ injury and the prognosis of COVID-19 patients. Methods This is a single-center, retrospective, observational study and total 349 confirmed COVID-19 patients admitted to Tongji Hospital from January 25 to February 25, 2020 were enrolled. We collected demographic, clinical, laboratory and treatment data from electronic medical records. Potential risk factors for extrapulmonary organ injury of COVID-19 patients were analyzed by a multivariable binary logistic model, and multivariable COX proportional hazard regression model was used for survival analysis in the patients with extrapulmonary organ injury. Results Average age of the included patients was 61.73±14.64 years. In the final logistic model, variables including aged 60 or older (OR 1.826, 95% CI 1.060-3.142), ARDS (OR 2.748, 95% CI 1.051-7.185), lymphocytes count lower than 1.1 ×109/L (OR 0.478, 95% CI 0.240-0.949), level of IL-6 greater than 7 pg/ml (OR 1.664, 95% CI 1.005-2.751) and D-Dimer greater than 0.5 μg/ml (OR 2.190, 95% CI 1.176-4.084) were significantly associated with the extrapulmonary organ injury. Kaplan-Meier curve and log-rank test showed that the probabilities of survival for patients with extrapulmonary organ injury were significantly lower than those without extrapulmonary organ injury.between Multivariate COX proportional hazards model showed that only myocardial injury (P=0.000, HR: 5.068, 95% CI: 2.728-9.417) and circulatory system injury (P=0.000, HR: 4.076, 95% CI: 2.216-7.498) were the independent factors associated with COVID-19 patients’ poor prognosis. Conclusion Older age, lymphocytopenia, high level of D-Dimer and IL-6 and the severity of lung injury were the high-risk factors of extrapulmonary organ injury in COVID-19 patients. Myocardial and circulatory system injury were the most important risk factors related to poor outcomes of COVID-19 patients. It may help clinicians to identify extrapulmonary organ injury early and provide relevant management strategy.
LncRNA SNHG22 Sponges miR-128-3p to Promote Progression of Colorectal Cancer through Upregulating E2F3
Authors: Jianning Yao , Chunfeng Wang , Xuyang Dong , Yanzhen Zhang , Yanle Li , Haining Zhou , Dongyao Zhao
Published: September 2020

Background: Long non-coding RNA (lncRNA) termed small nucleolar RNA host gene 22 (SNHG22) has been reported as a crucial regulator in several types of human cancers. In this study, we aimed to evaluate the function and mechanism of SNHG22 in colorectal cancer (CRC) progression. Methods: Quantitative RT-PCR (qRT-PCR) was used to detect the expression of SNHG22 in adenoma, tumor tissues (TTs), and adjacent nontumorous tissues (ANTs). The biological behaviors of SNHG22 in CRC cell lines were explored both in vitro (CCK-8 assay, flow cytometry, wound scratch, and transwell assays) and in vivo (nude mouse xenograft model). The interaction between SNHG22 and miR-128-3p, and the target genes of miR-128-3p were explored by online tools, qRT-PCR, western blot, and dual-luciferase reporter assay. Results: SNHG22 expression was gradually upregulated in ANTs, adenoma, and TTs. High expression levels of SNHG22 were significantly related to advanced clinicopathological factors and worse survival in patients with CRC. SNHG22 knockdown markedly prohibited CRC cell proliferation, migration, and invasion; and drove cell apoptosis in vitro; and hindered tumor growth in vivo. Mechanistic investigation showed that SNHG22 could bind to microRNA-128-3p (miR-128-3p) and attenuate its inhibitory effects on the expression levels and activity of E2F3. Rescue experiments exhibited that miR-128-3p inhibition or E2F3 upregulation can offset the functions of SNHG22 knockdown in CRC cells. Conclusion: Our findings support the existence of an interactive regulatory network of SNHG22, miR-128-3p, and E2F3 in CRC cell lines, indicating that the SNHG22/miR-128-3p/E2F3 axis is a novel diagnostic and therapeutic target in CRC.
Prognostic value of the systemic immune-inflammation index in patients with biliary tract cancer: a systematic review and meta-analysis
Authors: Zhou Faquan , Chen Shi , Xiong Yiquan , Yuan Xiaohui , Sun Hongyu , Tang Lijun
Published: September 2020

Background: The systemic immune-inflammation index (SII) has been found to predict outcomes in many tumors. The purpose of this study was to determine the prognostic value of SII in biliary tract cancer.Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, CBM, Wanfang and VIP databases from its inception until May 18, 2020. Pooled hazard ratio and 95% confidence interval were calculated to assess the prognostic role of SII in patients with BTC. The main outcomes included the overall survival, cancer-specific survival, disease-free survival and recurrence-free survival. Stata 12.0 was used for statistical analysis.Results: A total of 8 studies involving 2249 patients were eventually included. The results showed that elevated SII was significantly associated with poorer OS (HR=1.56, 95% CI: 1.23–1.99, P<0.001, I2 = 68.1%), poorer DFS/RFS (HR=1.42, 95%CI:1.09–1.84, P =0.009) and poorer CSS (HR =1.55, 95% CI: 1.09–2.21, P<0.014). Subgroup analysis further verified the above results. Conclusions: Higher SII is a predictor of poor prognosis in BTC patients. SII can serve as a useful prognostic indicator and help to evaluate the prognosis and formulate treatment strategies.Registered in PROSPERO: CRD42020184556
Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis
Authors: Arai Kazumori , Ishimatsu Hisato , Iwasaki Tomohiro , Tsuchiya Chinatsu , Sonoda Akihiro , Ohata Ko
Published: September 2020

Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial–mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Recently, the involvement of S100A10 in EMT has been reported. Furthermore, a recent study suggested that S100A10 and ANX A2 are related to the budding of a special type of CRC cells.Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, which originates from TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders.Conclusions Membranous S100A10 is related to the TB of CRC during oncogenesis. This is possibly due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.
Up-regulation of FN1, Activation of Maturation Promoting Factor and Associated Signaling Pathway Facilitates Epithelial-Mesenchymal Transition, Inhibits Apoptosis and Elevates Proliferation Rate of Breast Cancer Cells: In Silico Analysis of Microarray Datasets
Authors: Hameed Yasir , Ejaz Samina
Published: September 2020

Background: Knowing that the molecular mechanisms underlying breast cancer (BC) are not yet fully understood it was considered worth to launch investigation for the detection of key molecular pathways and associated genes and proteins. Methods: In total two microarray based datasets (GSE10810 and GSE29431), consisting of 89 breast cancer samples and 31 controls, were retrieved from the Gene Expression Omnibus (GEO) database and processed to identify the differentially expressed genes (DEGs). The pathway and functional enrichment analyses of DEGs were performed using DAVID online tool. Protein-Protein interaction (PPI) network was constructed using an online tool STRING and visualized through Cytoscape software to identify the significant module and hub genes via MCODE and Cytohubba applications. The identified hub genes were then further analyzed to document their response in Kaplan-Meier (KM) survival curve analysis, investigate differential expression profile and its correlation with promoter’s methylation status, and finally for the construction of the gene-drug interaction network. Results: In total 449 DEGs were detected including 151 up-regulated and 298 down-regulated genes. The identified DEGs were enriched in various cancer related biological functions and pathways. Based on PPI network analysis of the DEGs, six hub genes, CDK1, FN1, AURKA, CCNB2, BIRC5, and TOP2A, were correlated with worse overall survival (OS) of the breast cancer patients. Conclusion: The extensive in silico analysis has been helpful to evaluate evidence highlighting the prominent role played by the identified hub genes in stimulating breast tumor growth through the activation of Maturation Promoting Factor (MPF), PI3K/AKT signaling, and associated pathways that could be targeted for devising effective treatment strategies.
High-Efficiency Production of the Bisabolene from Waste Cooking Oil By Metabolically Engineered Yarrowia Lipolytica
Authors: Zhao Yakun , Zhu Kun , Li Jian , Zhao Yu , Li Shenglong , Zhang Cuiying , Xiao Dongguang , Yu Aiqun
Published: September 2020

Background: The natural plant product bisabolene serves as a precursor for the production of a wide range of industrially relevant chemicals. However, the low abundance of bisabolene in plants renders their isolation from plant sources economically inviable. Therefore, creation of microbial cell factories for bisabolene production supported by synthetic biology and metabolic engineering strategies presents a more competitive and environmentally sustainable method for industrial production of bisabolene.Results: In this proof-of-principle study, for the first time, we engineered the oleaginous yeast Yarrowia lipolytica to produce α-bisabolene, β-bisabolene and γ-bisabolene through heterologous expression of the α-bisabolene synthase from Abies grandis, the β-bisabolene synthase gene from Zingiber officinale and the γ-bisabolene synthase gene from Helianthus annuus, respectively. Subsequently, metabolic engineering approaches, including overexpression of the endogenous mevalonate pathway genes and introduction of heterologous multidrug efflux transporters, were employed to improve bisabolene production. Furthermore, the fermentation conditions were optimized to maximize de novo bisabolene production by the engineered Y. lipolytica strains from glucose. Our engineering strategies have led to engineered Y. lipolytica strains that produce 282.6 mg/L α-bisabolene, 48.3 mg/L β-bisabolene and 5.3 mg/L γ-bisabolene. Finally, we explored the potential of the engineered Y. lipolytica strains for bisabolene production from waste cooking oil. The results showed that α-bisabolene, β-bisabolene and γ-bisabolene could be produced at the respective titers of 973.0 mg/L, 68.2 mg/L, 20.2 mg/L in shake flasks. These titers correspond to 2433-fold, 340-fold and 404-fold enhancement in bisabolene production, respectively, over the parent strain.Conclusions: To our knowledge, this is the first report of bisabolene production in Y. lipolytica. These findings provide valuable insights into the engineering of Y. lipolytica for higher-level production of bisabolene and its utilization in converting waste cooking oil into various industrially valuable products.
Synthesis and Application of Assessment Framework for Human Resources for Health Policy Implementation: Gaps in India’s National Health Policy
Authors: Dubey Sweta , Vasa Jeel , zadey siddhesh
Published: September 2020

Background: Human Resources for Health (HRH) are crucial to improve health services coverage and population health outcomes. The World Health Organization (WHO) promotes four dimensions - availability, accessibility, acceptability, and quality (AAAQ) for HRH strengthening. Integrating AAAQ dimensions in policymaking is essential to reduce the critical shortage of HRH in India. Methods: We created a multilevel framework consisting of implementable strategies and actions that can improve AAAQ dimensions. We assessed and monitored the incorporation of dimensions in HRH-related recommendations of all versions of the National Health Policy of India (NHPI) policies using this framework. Recommendations were coded using this framework and classified according to targeted dimensions and cadres. We formulated dimension-wise normalized indices to calculate HRH deficits for pre-NHPI years and assess situational deficiencies. Finally, we evaluated whether or not the HRH recommendations of NHPIs addressed the deficient cadres and dimensions for the corresponding year. Results: We observed that HRH availability and quality were focused more in NHPI compared to accessibility and acceptability. Doctors were prioritized over auxiliary nurses-midwives and health assistants. AAAQ indices showed deficits in all dimensions in almost all cadres over the years. The cadres focused by NHPI recommendations did not completely correspond to the deficient cadres. Conclusion: The framework and indices based method can help identify the gaps between targeted and needed dimensions and cadres for effective HRH strengthening in countries. At the global level, the application of framework and indices will allow a comparison of the strengths and weaknesses of HRH-related policies and indicate implementation strategies and actions.
Development of a reverse transcription recombinase polymerase amplification assay with lateral flow dipstick for rapid detection of classical swine fever virus
Authors: Fan Jindai , Zhang Yuanyuan , Chen Wenxian , Zhang Jingyuan , Liu Chenchen , Zhang Mengru , Ding Hongxing , Yi Lin , Chen Jinding , Zhao Mingqiu
Published: September 2020

Background: Classical swine fever (CSF), caused by the infection of Classical swine fever virus (CSFV), is a highly contagious disease of pigs and has caused significant economic losses in the pig industry. The rapid and effective detection of CSFV would contribute to the eradication program against CSF. Thus, this study aimed to develop a rapid and simple method for CSFV detection.Results: Here, a new method based on reverse transcription recombinase polymerase amplification (RT-RPA) coupled with lateral flow dipstick (LFD) was established for detecting CSFV. The RPA assay could be completed within 20 min at 37oC and the results of the RPA assay could be visualized by LFD assay with the naked-eye inspection. This RT-RPA-LFD assay could be used to detect CSFV specifically, with no cross-reaction with other pathogens. Its detection limit was 10 pg of CSFV cDNA. Importantly, the RT-RPA-LFD assay has a good performance on the CSFV detection for clinical samples.Conclusions: The established RT-RPA-LFD assay greatly reduced the need for professional staff and sophisticated instruments and made disease detection convenient and feasible. This method would be useful for the prevention and control of CSF, especially in resource-limited settings.
Cluster Analysis of Visual Differences on Pairs of SARS-CoV-2 Genomes
Authors: Zhu Minghan , Zheng Jeffrey
Published: September 2020

This paper represents sample results for the C2 and C3 modules of the MAS. Genomic index maps were generated for SARS-CoV-2 genomes from different samples worldwide, and eleven other viral genomes were selected for comparisons. Each 2D genomic index map acts as a pair of X-Y coordinate scatter points located in a specific geometric region restricted. Supported by the principle of entropy invariance and visual distributions, it is convenient to identify the variations of SARS-CoV-2 genomes in the global scope. In view of this powerful transformation structure, future exploration of the detailed systematic expansion of theory and medical applications for COVID-19 patients is required.
Evaluation of Therapeutic Effect and Mechanism of Traditional Chinese Medicine on Non-Proliferative Diabetic Retinopathy
Authors: an Xuedong , Jin De , Duan Liyun , Zhao Yiru , Zhao Shenghui , Zhou Rongrong , Duan Yingying , Lian Fengmei , Tong Xiaolin
Published: September 2020

Objective: To review the therapeutic effect and mechanism of traditional Chinese medicine (TCM) on non-proliferative diabetic retinopathy (NPDR).Methods: Randomized controlled studies (RCTs) on NPDR treatment with TCM was conducted by searching China National Knowledge Internet, Wanfang Database, Chinese Biomedical Literature Database, PubMed, EMBASE, Cochrane database. The search date was up to December 24, 2019. At the same time, the mechanism of NPDR with TCM include studies was conducted by searching China National Knowledge Internet, Wanfang Database, PubMed.Results: 3208 related literatures were retrieved and 36 RCTs were included, including 3691 patients. The overall curative effect was significant [n = 4028, RR 1.20 (1.16, 1.25), P < 0.00001, I2 = 35%] with Qiming granule, Compound Xueshuantong capsule, no matter treated with TCM alone or combined with chemical drugs, it could show significant advantages. At the same time, TCM can effectively improve the fundus, and vision, reduce macular thickness, and microangioma of NPDR patients. TCM can reduce the generation of vascular endothelial growth factor and improve the blood retinal barrier through polyol pathway, oxidative stress pathway, etc.Conclusion: Our study shows that TCM has a significant effect on NPDR, and can significantly improve vision, reduce microangioma and macular thickness, and is safe. TCM mainly protects retinal neurons and blood retinal barrier through polyol pathway, which suggests that TCM can prevent macular edema and neovascularization in NPDR patients. However, in consideration of the quality of literature, the results of this study should be carefully considered.
Cross-Sectional Associations Between 24-hour Activity Behaviours and Mental Health Indicators in Children and Adolescents: A Compositional Data Analysis
Authors: Fairclough Stuart J , Tyler Richard , Dainty Jack R. , Dumuid Dorothea , Richardson Cassandra , Shepstone Lee , Atkin Andrew J.
Published: September 2020

Background. The prevalence of mental ill health increases with age through childhood and adolescence and likely impairs mental and physical health in adulthood. Little is known about the combined influence of sleep, sedentary time (ST), and physical activity on youth mental health. This study examined associations between youth 24-hour activity behaviour compositions and mental health indicators, and investigated predicted differences in mental health when time was reallocated between activity behaviours.Methods. Demographic information and anthropometric data were collected from 359 participants (aged 9-13 years; 50.7% girls). 24-hour activity behaviours (sleep, ST, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA)) were assessed using a wrist accelerometer, worn for 7 days. Validated questionnaires measured self-esteem, depressive symptomology, overall emotional and behavioural mental health, internalising problems, externalising problems, and prosocial behaviour. A computerised cognitive test battery assessed executive functions of switching, spatial working memory, and inhibition. Linear mixed models examined associations between activity behaviour compositions and mental health indicators for all participants and separately by primary and secondary school. Post-hoc analyses modelled the influence of reallocating fixed durations of time between activity behaviours on mental health.Results. For all participants ST was associated with worse internalising problems, relative to the other activity behaviours. Among primary school participants, relative to the other activity behaviours, ST was associated with poorer prosocial behaviour, and LPA was associated with worse switching and inhibition test scores. For all participants, reallocating time to ST from sleep and MVPA was associated with higher internalising problems. Among primary school participants, reallocating time to ST from any other behaviour was associated with poorer prosocial behaviour, and reallocating time to LPA from any other behaviour was associated with lower cognitive function.Conclusions. Relative to other activity behaviours, ST and LPA were significantly and unfavourably associated with some mental health indicators. These associations were strongest among primary school participants with no significant relationships observed for the secondary school participants. Replacing MVPA with ST or LPA reflected the greatest unfavourable predicted changes in mental health indicators. Our results provide further evidence for the influence of daily activity behaviours on youth mental health.
Effects of COVID19 Pandemic on Pediatric Kidney Transplant in the United States
Authors: Charnaya Olga , Chiang Teresa Po-Yu , Wang Richard , Motter Jennifer , Boyarsky Brian , King Elizabeth , Werbel William , Durand Christine M. , Avery Robin , Segev Dorry , Massie Allan , Garonzik-Wang Jacqueline
Published: September 2020

In March 2020, COVID-19 infections began to rise exponentially in the United States, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the United States compared to the same time the previous year. We saw an initial decrease in DDKT and LDKT by 47% and 82% compared to expected events and then a continual increase, with numbers reaching expected pre-pandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85) and LDKT (IRR 0.17 0.38 0.84) in states with high vs low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar cPRA, waitlist time and cause of ESRD as before the pandemic. The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the United States, but has not had a sustained effect.
Study on the Necessity of Establishing Customized Limits for the Daily QA Program Performed With Daily QA3
Authors: Jin Xiaoli , Xing Xiaofen
Published: September 2020

Background: Due to no corresponding action limits for some new daily QA items , limits of the monthly or annual QA procedures have to be used for daily QA program at present. The general purpose of this paper is to discuss whether it is feasible to do so.Methods: 3 groups daily quality control process during 2017-2019 performed with Daily QA3 were analyzed using SPC. In Calculation of capability indices for output, daily QA tolerance ±3% in the TG142 was used as specification limit, while for flatness and symmetry, annual QA tolerance ±1% was used. An appropriate number of data points were analyzed , capability indices (Cp, Cpk, Cpm and Cpmk) were calculated, and customized tolerance and action limits were established for each process. Meanwhile, the locations of the UCL、CL、LCL in I-MR charts of daily QA performed by 5 therapists in turns were compared with that of daily QA performed by only one physicist during the same period . Results: Process capability indices of output were all ≥1, some were even up to 3-4. While, for symmetry, most of them failed to meet the requirements. For the same daily QA item, the calculated customized limit of different quality control processes were quite different. For the daily QA performed with only one physicist, the range of UCL and LCL was smaller or the central line was closer to the target value 0 in I-MR charts.Conclusions: It is necessary to establish customized limits for daily QA program performed with Daily QA3, because customized limits and improved operation constancy both can improve the daily quality control level.
ISLAMIC THEOLOGY IN THE SEVENTEENTH CENTURY ACEH
Authors: Siraj Fuad Mahbub
Published: September 2020

This paper examines ‘Abd al-Ra’ūf al-Sinkili’s concept of tawhid. Using a historical approach and content analysis, this paper argues that tawhid is an important aspect in Islam and becomes an interesting discourse in the Islamic intellectual tradition, especially Sufism. ‘Abd al-Ra’ūf al-Sinkili stated that the first commitment for a human being is to accept the Oneness of Allah, and purity it from all things inappropriate to Him with the statement of lā ilaha illā Allāh. This affirms that Allah is believed to be the only Being. There is no existence without the existence of Allah (lā ilāha illā Allāh). This statement of creed implies two meanings: to negate any existence (al-nafyu), and to confirm only one existence (al-ithbāt), which is the existence of al-Haqq (the true Being). Al-Sinkili also states that Allah is One, without our attempt to make Him One. Allah is true without a need to truth legitimation from humans.
Air Quality Assessment by Statistical Learning-Based Regularization
Authors: TÜTMEZ Bülent
Published: September 2020

PM10 can be stated as a particulate matter smaller than 10 micrometer and it can be suspended in the air. The incremental concentration of PM10 affects both human and environment drastically. In this study, an air quality assessment by exhibiting the potential relationships among the secondary indicators and PM10 has been focused. For the analyses, statistical learning-based regularization procedures such as Ridge, the Lasso and Elastic-net algorithms have been practiced. In particular, use of Elastic-net algorithm in predicting PM10 concentration includes a novelty. As a result of the computational studies, it has been recorded that all the models showed high accuracy capacities. However, the elastic-net model outperforms the other models both accuracy and robustness (stability). Considering the error measurements (MSE and MAPE), the best numerical results have been provided by the Elastic-net model. Use of machine learning-based regularization algorithms in environmental problems can provide accurate model structures as well as generality and transparency.
Evaluation of the trophic status in a Mediterranean reservoir under climate change: An integrated modelling approach
Authors: Almeida Carina , Branco Paulo , Segurado Pedro , Ramos Tiago B. , Ferreira Teresa , Neves Ramiro , de Oliveira Rodrigo Proença
Published: September 2020

This study describes an integrated modelling approach to better understand the trophic status of the Montargil reservoir (southern Portugal) under climate change scenarios. The SWAT and CE-QUAL-W2 models were applied to the basin and reservoir, respectively, for simulating water and nutrient dynamics while considering one climatic scenario and two decadal timelines (2025–2034 and 2055–2064). Model simulations showed that the dissolved oxygen concentration in the reservoir's hypolimnion is expected to decrease by 60% in both decadal timelines, while the chlorophyll-a concentration in the reservoir's epiliminion is expected to increase by 25%. The total phosphorus concentration (TP) is predicted to increase in the water column surface by 63% and in the hypolimion by 90% during the 2030 timeline. These results are even more severe during the 2060 timeline. Under this climate change scenario, the reservoir showed a eutrophic state during 70–80% of both timelines. Even considering measures that involve decreases in 30 to 35% of water use, the eutrophic state is not expected to improve.
Extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli presence in urban aquatic environments in Kanpur, India
Authors: Johnson Ann , Ginn Olivia , Bivins Aaron , Rocha-Melogno Lucas , Tripathi Sachchida Nand , Brown Joe
Published: September 2020

In India, high rates of antibiotic consumption and poor sanitation infrastructure combine to pose a significant risk to the public through the environmental transmission of antimicrobial resistance (AMR). The WHO has declared extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli a key indicator for the surveillance of AMR worldwide. In the current study, we measured the prevalence of AMR bacteria in an urban aquatic environment in India by detecting metabolically active ESBL-positive E. coli. Water samples were collected in duplicate from 16 representative environmental water sources including open canals, drains, and rivers around Kanpur, Uttar Pradesh. We detected culturable E. coli in environmental water at 11 (69%) of the sites. Out of the 11 sites that were positive for culturable E. coli, ESBL-producing E. coli was observed at 7 (64%). The prevalence of ESBL-producing E. coli detected in the urban aquatic environment suggests a threat of AMR bacteria to this region.
Hemşirelik Öğrencilerinin Hemşirelik Mesleği Algılarının İncelenmesi
Authors: Ünsal Ayla , Güven Şefika Dilek
Published: September 2020

Bu araştırmanın amacı, hemşirelik öğrencilerinin hemşirelik mesleği algılarının incelenmesidir. Tanımlayıcı nitelikteki bu araştırmada örneklem yöntemi kullanılmamıştır. İki üniversitenin sağlık yüksekokulundaki birinci ve dördüncü sınıf 334 hemşirelik öğrencisi arasından 322 gönüllü öğrenci veri toplama formlarını doldurmuştur. Veri toplama formları olarak soru formu ve Hemşirelik Mesleğini Algılama Ölçeği (HMAÖ) kullanılmıştır. HMAÖ’nin, mesleki nitelikler ve mesleki statü olmak üzere iki alt boyutu bulunmaktadır. Araştırma etik ilkeler ve gönüllülük doğrultusunda yürütülmüştür. İstatistik analiz olarak yüzde, ortalama, cronbach’s alpha, bağımsız gruplarda t testi, one-way ANOVA ve LSD post hoct test yapılmıştır. Bu çalışmada, ölçeğin Cronbach alfa katsayısı 0,94, alt boyutlarından “mesleki niteliklerin” 0,95, “mesleki statünün” 0,79 olarak bulunmuştur. Öğrencilerin yaş ortalaması 20,29±1,98 ve %69,9’u kızdır. Öğrencilerin %66,1’i üniversite sınavında hemşireliği birinci sırada tercih ettiğini, %6,2’si hemşireliği sevmediğini, %36,6’sı mezun olunca hastanede yönetici hemşire olarak çalışmak istediğini ve %53,7’si kendini mesleğe hazır hissettiğini belirtmiştir. Öğrencilerin %42,9’unun okula gelmeden önce meslek hakkında olumlu düşündüğü saptanmıştır. Öğrencilerin HMAÖ toplam ölçek puan ortalamaları 84,04±19,10’dur. Bu ortalama öğrencilerin mesleki algı düzeylerinin oldukça iyi olduğunu göstermektedir. Mesleki nitelikler alt boyutu ile cinsiyet (p
Quantitative Sensory Testing Protocols to Evaluate Central and Peripheral Sensitization in Knee OA: A Protocol for a Scoping Review
Authors: Rudy-Froese Benjamin , Rankin Jonathan , Hoyt Curtis , Ramsahoi Keenu , Gareau Liam , Howatt William , Carlesso Lisa C.
Published: September 2020

Background:

Quantitative sensory testing (QST) methods have become widely used for
the assessment of nervous system sensitization to nociceptive signalling in studies of people with
knee osteoarthritis (OA). However, few standardised QST protocols have been developed. Variability
in their execution may lead to differences in their interpretation.

Objective:

The proposed scoping review will seek to identify various QST methodologies being
used in the assessment of sensitization and how sensitization is being defined in people with knee
OA.

Methods and Analysis:

This scoping review will be guided by existing scoping review methodologies.
Relevant studies will be extracted from the following electronic databases: Medical Literature
Analysis and Retrieval System Online, ExcerptaMedica Database, Allied and Complementary
Medicine Database and the Cumulative Index to Nursing Allied Health Literature. Independent
screening of the abstracts and full articles and data extraction will be performed in pairs. Information
extracted will focus on qualitative and quantitative data relevant to the content of the protocols
from included studies. Data will be summarised in order to draw conclusions on the common elements
used in QST protocols and definitions of sensitization for knee OA.

Conclusion:

This scoping review will provide insight into the most common methods of QST used
in the assessment of nociceptive signaling in people with knee OA. This will potentially identify areas
where a systematic review or other primary research may be required in order to develop fixed
evidence-based protocols for QST in patients with knee OA.
Antimicrobials Misuse/Overuse: Adverse Effect, Mechanism, Challenges and Strategies to Combat Resistance
Authors: Mittal Amit K. , Bhardwaj Rohit , Mishra Priya , Rajput Satyendra K.
Published: September 2020

Overuse and misuse of antibiotics are the first risk factors for the development of antibiotics resistance. Inadequate professional competence of health care physicians might worsen the complications associated with antibiotics resistance. Antibiotic resistance is a global issue; however, the epicenter of this misfortune is Asian regions due to the easy accessibility of the strongest antibiotics without prescriptions or diagnoses. High effectiveness and easy accessibility of antibiotics lead to overuse/misuse and encouraging bacteria to develop the resistance. The over-usage and mis-usage of antibiotics are antibiotic abuse, which increase the potentially serious impact on human health. Bestowing to WHO guidelines, the resistance has led to spread worldwide and classifying resistance is a serious health problem. Furthermore, resistance claims uncertainty to predict the future. This review summarizes the major antibiotics involved in drug resistance, mechanism, prescribed dosage with a disease condition, proposed policies and guidelines to combat antibiotic resistance associated problems.