{"title":"Members of 3-O-Sulfotransferases (3-OST) Family: A Valuable Tool from Zebrafish to Humans for Understanding Herpes Simplex Virus Entry.","authors":"John Baldwin, Deepak Shukla, Vaibhav Tiwari","doi":"10.2174/1874357901307010005","DOIUrl":"https://doi.org/10.2174/1874357901307010005","url":null,"abstract":"<p><p>The journey of many viruses to infect cells begins when the virus first binds to cell surface heparan sulfate (HS). The initial step of cell attachment or binding during herpes simplex virus type-1 (HSV-1) entry is mediated by envelope glycoprotein B (gB) and C (gC). The binding is followed by fusion between virus envelope and cell membrane during which HSV-1 glycoprotein D (gD) interacts with a modified form of HS know as 3-O-sulfated heparan sulfate (3-OS HS). The rare modification of 3-O-sulfation on HS chain is governed by enzymes known as 3-O-sulfotransferase (3-OST). Currently, there are seven isoforms of human 3-OSTs that have been identified, and with the exception of 3-OST-1, all other 3-OST isoforms allow HSV-1 entry and spread. Recently, the product of the zebrafish (ZF)-encoded 3-OST-3 was also recognized as a gD receptor, which mediates HSV-1 entry and cell-cell fusion similar to human 3-OST-3. Interestingly, the ZF system expresses multiple isoforms of 3-OST which could be very useful for studying the involvement of HS and 3-OS HS in virus tropism and virus-induced inflammation. In addition, therapeutic targeting of 3-OST generated HS is likely to bring about novel interventions against HSV-1. In this review we have taken a closer look at the potential of both human and ZF encoded 3-OSTs as valuable tools in HSV entry and inflammation studies.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"7 ","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/42/TOVJ-7-5.PMC3553493.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31195170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Innocent O Maranga, Lynne Hampson, Anthony W Oliver, Xiaotong He, Peter Gichangi, Farzana Rana, Anselmy Opiyo, Ian N Hampson
{"title":"HIV Infection Alters the Spectrum of HPV Subtypes Found in Cervical Smears and Carcinomas from Kenyan Women.","authors":"Innocent O Maranga, Lynne Hampson, Anthony W Oliver, Xiaotong He, Peter Gichangi, Farzana Rana, Anselmy Opiyo, Ian N Hampson","doi":"10.2174/1874357901307010019","DOIUrl":"https://doi.org/10.2174/1874357901307010019","url":null,"abstract":"<p><p>Infection with high risk HPV is implicated in pre-cancerous squamous intraepithelial lesions and their progression to cervical cancer. In the developed countries, infection with HPV 16 and 18 accounts for ~70% of cervical cancers, but it has been established that HPV type prevalence differs according to worldwide geographical location. In sub Saharan Africa infection with HPV is known to be augmented by HIV, which is endemic in this region. It is not yet clear, however, whether this ultimately influences progression to cervical cancer. Papillocheck(TM) and multiplex PCR were used to determine the range of HPV genotypes found in cervical smears and carcinomas from HIV positive and negative Kenyan women. Smear samples from HIV-positive women had a higher prevalence of: multiple HPV infections; high-risk HPVs 52, 58, 68, potential high risk 53/70, low-risk 44/55 and abnormal cytology compared to HIV-negative women. A low overall prevalence (~8%) of types 16/18 was found in all smear samples tested (n = 224) although this increased in invasive cervical carcinoma tissues to ~80% for HIV-negative and ~46% for HIV-positive women. Furthermore, HPV45 was more common in cervical carcinoma tissues from HIV-positive women. In summary HIV infection appears to alter the spectrum of HPV types found in both cervical smears and invasive cervical carcinomas. It is hypothesised there could be a complex interplay between these viruses which could either positively or negatively influence the rate of progression to cervical cancer.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"7 ","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/3f/TOVJ-7-19.PMC3594704.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31309581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of hepatitis B virus mutations on its replication and liver disease severity.","authors":"Abdulrahim Hakami, Abdelwahid Ali, Ahmed Hakami","doi":"10.2174/1874357901307010012","DOIUrl":"10.2174/1874357901307010012","url":null,"abstract":"<p><p>Hepatitis B virus (HBV), nowadays, is one of the major human pathogens worldwide. Approximately, 400 million people worldwide have chronic HBV infection. Only 5% of persons infected during adulthood develop chronic infection. The reverse is true for those infected at birth or in early childhood, i.e. more than 90% of these persons progress to chronic infection. Currently, eight different genotypes o f HBV have been identified, differing in nucleotide sequence by greater than 8%. In addition, numerous subgenotypes have a l s o been recognized based on the nucleotide sequence variability of 4- 8%. It has invariably been found that these genotypes and mutations play a pivotal role in the liver disease aggravation and virus replication. The precore mutations (G1896A) and the double mutation (T1762/A1764) in the basal core promoter are important mutations that alter expression of the hepatitis B e antigen (HBeAg). The HBeAg is important for establishing viral persistence. The precore G1896A mutation abrogates the expression of HBeAg. Numerous other mutations alter the disease severity and progression. It is predictive that the infected patient has high risk of hepatocellular carcinoma if the genotype C is incriminated or if HBV possesses basal core promoter double mutation. Association of the remaining genotypes have been noted but with less degree than genotype C. Phenotypic assays of the different HBV protein markers with different molecular techniques illustrate the replication efficiency of the virus in cell lines. This review will discuss various mutations into their association with liver disease severity and progression as well as virus replication.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"7 ","pages":"12-8"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/03/TOVJ-7-12.PMC3565227.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31321856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jose A Garcia-Rivera, Kai Lin, Sam Hopkins, Matthew A Gregory, Barrie Wilkinson, Philippe A Gallay
{"title":"Development of a flow cytometry live cell assay for the screening of inhibitors of hepatitis C virus (HCV) replication.","authors":"Jose A Garcia-Rivera, Kai Lin, Sam Hopkins, Matthew A Gregory, Barrie Wilkinson, Philippe A Gallay","doi":"10.2174/1874357901206010097","DOIUrl":"https://doi.org/10.2174/1874357901206010097","url":null,"abstract":"<p><p>In this study, we established a flow cytometry live cell-based assay that permits the screening of hepatitis C virus (HCV) inhibitors. Specifically, we created a stable cell line, which harbors a subgenomic replicon encoding an NS5A-YFP fusion protein. This system allows direct measurement of YFP fluorescence in live hepatoma cells in which the HCV replicon replicates. We demonstrated that this stable fluorescent system permits the rapid and sensitive quantification of HCV replication inhibition by direct-acting antiviral agents (DAA) including protease and NS5A inhibitors and host-targeting antiviral agents (HTA) including cyclophilin inhibitors. This flow cytometry-based live cell assay is well suited for multiple applications such as the evaluation of HCV replication as well as antiviral drug screening.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"97-102"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/76/TOVJ-6-97.PMC3514710.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31115287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The immune response to papillomavirus during infection persistence and regression.","authors":"Merilyn H Hibma","doi":"10.2174/1874357901206010241","DOIUrl":"https://doi.org/10.2174/1874357901206010241","url":null,"abstract":"<p><p>Human papillomavirus (HPV) infections cause a significant global health burden, predominantly due to HPV-associated cancers. HPV infects only the epidermal cells of cutaneous and mucosal skin, without penetration into the dermal tissues. Infections may persist for months or years, contributed by an array of viral immune evasion mechanisms. However in the majority of cases immunity-based regression of HPV lesions does eventually occur. The role of the innate immune response to HPV in persistence and regression of HPV infection is not well understood. Although an initial inflammatory infiltrate may contribute to disease regression, sustained inflammation at the HPV-induced lesions, characterized by macrophage and neutrophil infiltration, has been observed in persistence. Pathogen-associated molecular patterns (PAMPs) are important in innate recognition. The double stranded DNA and an L1 and L2 capsid components of the HPV virion are potential PAMPs that can trigger signaling through cellular pattern recognition receptors, including toll-like receptors (TLR). TLR expression is increased in regressing HPV disease but is reduced in persistent lesions, suggesting a role for TLR in HPV regression. With regard to the adaptive immune response, a key indicator of regression in humans is infiltration of the lesion with both CD4 and CD8 T cells. In individuals with persistent lesions, CD8 T cell and immune suppressive regulatory T cells (Tregs) infiltrate the infection site. There is no association between persistence or regression and the presence of serum antibodies to the viral capsid antigens of HPV. There is still much to be learned about the immunological events that trigger regression of HPV disease. Understanding the viral and host factors that influence persistence and regression is important for the development of better immunotherapeutic treatments for HPV-associated disease.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"241-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/07/TOVJ-6-241.PMC3547310.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31179840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Human Papillomavirus (HPV) Vaccines: A Novel Approach.","authors":"Kei Kawana, Katsuyuki Adachi, Satoko Kojima, Shiro Kozuma, Tomoyuki Fujii","doi":"10.2174/1874357901206010264","DOIUrl":"https://doi.org/10.2174/1874357901206010264","url":null,"abstract":"<p><p>Cervical cancer is the second largest cause of cancer-related death in women worldwide, and it occurs following persistent infection, sometimes for decades, with a specific subset of human papillomavirus (HPV) types; the approximately 13 oncogenic subtypes. Prophylactic vaccines against HPV infections hold promise for cost-effective reductions in the incidence of cervical cancer, but this may not be enough. Two prophylactic HPV vaccines are presently available and both contain L1 virus-like particles (VLPs) derived from the HPV subtypes most frequently associated with cervical cancer, HPV-16 and -18. Since the L1-VLP vaccines can only effectively prevent infection by the specific HPV subtype against which the vaccine was developed, cervical cancers caused by high-risk HPV subtypes other than HPV-16 and -18 may still occur in recipients of the current HPV vaccines. Furthermore, HPV vaccination coverage for adolescents is insufficient in most countries and therefore even HPV-16 and -18 infections are unlikely to be fully eradicated using the existing strategies. The development of HPV therapeutic vaccines remains essential. Many therapeutic vaccines aimed at clearing HPV-related cervical lesions have been developed and tested in patients with HPV16-positive cervical intraepithelial lesions (CIN) or cervical cancers. To date, definitive clinical efficacy and appropriate immunological responses have never been demonstrated for cervical neoplasia although promising results have been reported in patients with vulvar intraepithelial neoplasia. Here we discuss shortcomings of previous HPV therapeutic vaccine candidates and propose a novel vaccination strategy that leverages newly gained knowledge about mucosal immunity and the induction of mucosal immune responses.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"264-9"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/f9/TOVJ-6-264.PMC3547358.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31179843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bogumil Kaczkowski, Marya Morevati, Maria Rossing, Finn Cilius, Bodil Norrild
{"title":"A Decade of Global mRNA and miRNA Profiling of HPV-Positive Cell Lines and Clinical Specimens.","authors":"Bogumil Kaczkowski, Marya Morevati, Maria Rossing, Finn Cilius, Bodil Norrild","doi":"10.2174/1874357901206010216","DOIUrl":"https://doi.org/10.2174/1874357901206010216","url":null,"abstract":"<p><p>For more than a decade, global gene expression profiling has been extensively used to elucidate the biology of human papillomaviruses (HPV) and their role in cervical- and head-and-neck cancers. Since 2008, the expression profiling of miRNAs has been reported in multiple HPV studies. Two major strategies have been employed in the gene and miRNA profiling studies: In the first approach, HPV positive tumors were compared to normal tissues or to HPV negative tumors. The second strategy relied on analysis of cell cultures transfected with single HPV oncogenes or with HPV genomes compared to untransfected cells considered as models for the development of premalignant and malignant transformations.In this review, we summarize what we have learned from a decade of global expression profiling studies. We performed comprehensive analysis of the overlap of the lists of differentially expressed genes and microRNAs, in both tissue samples and cell culture based studies. The review focuses mainly on HPV16, however reports from other HPV species are used as references. We discuss the low degree of consensus among different studies and the limitation of differential expression analysis as well as the fragmented miRNA-mRNA target correlation evidence. Furthermore, we propose an approach for future research to include more comprehensive miRNA-mRNA target correlation analysis and to apply systems biology/gene networks methodology.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"216-31"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/39/TOVJ-6-216.PMC3547333.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31181444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ONCOGENIC HUMAN PAPILLOMAVIRUSES: High-Risk Human Papillomaviruses: Towards a Better Understanding of the Mechanisms of Viral Transformation, Latency and Immune-Escape.","authors":"A Cid Arregui, P Gariglio, T Kanda, J Doorbar","doi":"10.2174/1874357901206010160","DOIUrl":"https://doi.org/10.2174/1874357901206010160","url":null,"abstract":"High-risk human papillomaviruses (HR-HPVs) cause mucosal epithelial malignancies, most notably cervical intraepithelial neoplasia (CIN) and cancer of the uterine cervix. Prophylactic vaccines based on the L1 capsid proteins of the most prevalent HR-HPV types have been commercialized, and recent studies have shown that crossneutralization epitopes are present in the L2 minor capsid protein of HR-HPVs, thus giving hope for the prevention of many HPV-associated cancers. However, the high prevalence of HPV infections worldwide and the morbidity and mortality associated with them warrant further research to improve our understanding of HPV pathogenesis, and to develop new generations of prophylactic vaccines and effective immunotherapy strategies. Furthermore, there is a need for a better understanding of the virus life cycle and how this is influenced by the epithelial site, the mechanisms of viral persistence, regression and reactivation, and for detailed molecular studies that clarify the cellular pathways altered by the viral oncoproteins. This special issue was aimed to underline some of those aspects of current HPV research. The E2 gene product of oncogenic HPVs is a transcriptional repressor that controls expression of the viral oncogenes. Integration of the viral DNA in the host genome resulting in disruption of the sequence encoding E2 was postulated more than two decades ago to be critical in the progression from premalignant lesions to cancer. However,","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"160-2"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/6c/TOVJ-6-160.PMC3552290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31185064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction of an automated system for the diagnosis and quantification of hepatitis B and hepatitis C viruses.","authors":"Mt Cabezas-Fernandez, Mi Cabeza-Barrera","doi":"10.2174/1874357901206010122","DOIUrl":"10.2174/1874357901206010122","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections pose major public health problems because of their prevalence worldwide. Consequently, screening for these infections is an important part of routine laboratory activity. Serological and molecular markers are key elements in diagnosis, prognosis and treatment monitoring for HBV and HCV infections. Today, automated chemiluminescence immunoassay (CLIA) analyzers are widely used for virological diagnosis, particularly in high-volume clinical laboratories. Molecular biology techniques are routinely used to detect and quantify viral genomes as well as to analyze their sequence; in order to determine their genotype and detect resistance to antiviral drugs. Real-time PCR, which provides high sensitivity and a broad dynamic range, has gradually replaced other signal and target amplification technologies for the quantification and detection of nucleic acid. The next-generation DNA sequencing techniques are still restricted to research laboratories.The serological and molecular marker methods available for HBV and HCV are discussed in this article, along with their utility and limitations for use in Chronic Hepatitis B (CHB) diagnosis and monitoring.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":" ","pages":"122-34"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/fa/TOVJ-6-122.PMC3531716.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40206152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takeshi Shimamura, David Jeng, Alexandra Lucas, Karim Essani
{"title":"Suppression of neointimal hyperplasia following angioplasty-induced vascular injury in pigs infected with swinepox virus.","authors":"Takeshi Shimamura, David Jeng, Alexandra Lucas, Karim Essani","doi":"10.2174/1874357901206010091","DOIUrl":"https://doi.org/10.2174/1874357901206010091","url":null,"abstract":"<p><p>Many patients suffering from angina pectoris are treated with percutaneous coronary intervention (PCI) and quickly develop angiographic renarrowing, or restenosis, at the site of PCI treatment. Restenosis is thought to arise from the combinatorial activation of thrombotic and inflammatory responses. The inflammatory response responsible for restenosis is also thought to involve the activation of a cascade of serine proteases and its subsequent regulation. Poxviruses are known to possess a variety of immunomodulatory strategies, some of which target serine proteases, cytokines, and chemokines. To this end we evaluated whether systemic species-specific swinepox virus (SPV) infection could induce sufficient host-immune modulation to promote an anti-inflammatory and anti-proliferative effect, thereby preventing restenosis. Two groups of domestic feeder pigs were used - the first group was experimentally infected with SPV (n= 11) and the second group served as an uninfected control (n= 5). A week after infection, the pigs were anesthetized and percutaneous transluminal coronary angioplasty (PTCA) was performed in the left anterior descending coronary artery using X-ray fluoroscopy to visualize the balloon and record angiograms. Three weeks post infection, the pigs were euthanized and balloon angioplasty injured arteries were harvested and examined. We observed a statistically significant reduction of restenosis in SPV-infected pigs (p = 0.05) compared to control pigs and conclude that systemic swinepox virus infection causes sufficient host immune suppression to significantly reduce restenosis in pigs after balloon angioplasty injury.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"91-6"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/ff/TOVJ-6-91.PMC3486964.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31034322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}