bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.