M Torres, L Fraile, Jm Echevarria, B Hernandez Novoa, M Ortiz
{"title":"Human Papillomavirus (HPV) Genotyping: Automation and Application in Routine Laboratory Testing.","authors":"M Torres, L Fraile, Jm Echevarria, B Hernandez Novoa, M Ortiz","doi":"10.2174/1874357901206010144","DOIUrl":"https://doi.org/10.2174/1874357901206010144","url":null,"abstract":"<p><p>A large number of assays designed for genotyping human papillomaviruses (HPV) have been developed in the last years. They perform within a wide range of analytical sensitivity and specificity values for the different viral types, and are used either for diagnosis, epidemiological studies, evaluation of vaccines and implementing and monitoring of vaccination programs. Methods for specific genotyping of HPV-16 and HPV-18 are also useful for the prevention of cervical cancer in screening programs. Some commercial tests are, in addition, fully or partially automated. Automation of HPV genotyping presents advantages such as the simplicity of the testing procedure for the operator, the ability to process a large number of samples in a short time, and the reduction of human errors from manual operations, allowing a better quality assurance and a reduction of cost. The present review collects information about the current HPV genotyping tests, with special attention to practical aspects influencing their use in clinical laboratories.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"144-50"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874357901206010144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31127016","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}
Amanda Clarke, Stephen Kerr, Adam Honeybrook, David A Cooper, Anchalee Avihingsanon, Chris Duncombe, Praphan Phanuphak, Kiat Ruxrungtham, Jintanat Ananworanich, John Kaldor
{"title":"Adherence and Risk Behaviour in Patients with HIV Infection Receiving Antiretroviral Therapy in Bangkok.","authors":"Amanda Clarke, Stephen Kerr, Adam Honeybrook, David A Cooper, Anchalee Avihingsanon, Chris Duncombe, Praphan Phanuphak, Kiat Ruxrungtham, Jintanat Ananworanich, John Kaldor","doi":"10.2174/1874357901206010023","DOIUrl":"https://doi.org/10.2174/1874357901206010023","url":null,"abstract":"<p><p>It could be postulated that due to lifestyle factors, patients with poor antiretroviral therapy (ART) adherence may also have risky sexual behaviour potentially leading to HIV transmission. There are limited data regarding unprotected sex risk and ART adherence in resource limited settings and our study set out to investigate these in an HIV clinic in Bangkok. Patients completed an anonymous questionnaire regarding their relationship details, ART adherence, sexual behaviour, alcohol and drug use and HIV transmission beliefs. Laboratory findings and medical history were also collected. Unprotected sex risk (USR) was defined as inconsistent condom use with a partner of negative or unknown HIV status. Five hundred and twelve patients completed the questionnaire. Fifty seven per cent of patients reported having taken ARV >95% of the time in the last month and 58% had been sexually active in the previous 30 days. Only 27 patients (5%) were classified as having USR in our cohort. Multivariate analysis showed USR was associated with female gender (OR 2.9, 95% CI 1.2-7.0, p0.02) but not with adherence, age, type or number of partners, recreational drug or alcohol use nor beliefs about HIV transmission whilst taking ART. Levels of USR in this resource limited setting were reassuringly low and not associated with poor ART adherence; as all USR patients had undetectable viral loads onward HIV transmission risk is likely to be low but not negligible. Nonetheless condom negotiation techniques, particularly in women, may be useful in this group.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"23-8"},"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/93/16/TOVJ-6-23.PMC3296110.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30506457","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":"Automation in the virology laboratory: contribution to improve the viral diagnosis.","authors":"Fernando Cobo","doi":"10.2174/1874357901206010103","DOIUrl":"https://doi.org/10.2174/1874357901206010103","url":null,"abstract":"Automation in the microbiology laboratory has revolutionized the way in which the microbiologists can diagnose human pathogens, including viruses. Automated techniques are now commonly used to diagnose viral diseases and manage patients with these kinds of infections. The use of this technology at the viral laboratory has been facilitated by the introduction of a growing number of commercially available tests for viral diagnosis. Technological advances in molecular diagnosis such as real time-PCR techniques, nucleic acid sequencing, DNA microarrays and proteomics have quickly developed the virology field and created new opportunities for improve the diagnosis. \u0000 \u0000With regard to viral pathogens, the goals in performing virology automated techniques are to provide timely results useful for high-quality patient care at a reasonable cost. One of the main advantages of automated methods is that these techniques can be performed quickly if there are adequate laboratory resources. The development of rapid and sensitive diagnostic methods provides the opportunity to detect viruses at an early stage, so rapid results are associated with improvements in patients’ diagnosis. Moreover, automation by mean of these above mentioned methods has dramatically reduced the dependency on culture-based methods. \u0000 \u0000The main purpose of the hot-topic about automation in the virology laboratory is to give an overview of the main automated techniques for the diagnosis of the most important viral diseases. \u0000 \u0000Dr. Avivar has provided a comprehensive review of the main strategies for the successful implementation of viral laboratory automation. He has analyzed the current situation of laboratories with regard the automation as well as their associated costs, reflecting new criteria and ideas for the organization of new biotechnology laboratories from his own point of view. \u0000 \u0000Dr. Cabezas-Fernandez and Dr. Cabeza-Barrera have analyzed the current state of the art for the diagnosis of both hepatitis B (HBV) and hepatitis C (HCV) viruses, two of the most clinically relevant viruses, above all in our health area in which a high rate of immigrant population coming from Africa and Eastern European countries is present. \u0000 \u0000Dr. Alvarez et al. have reviewed the main systems for the diagnosis and monitoring of HIV infection, giving us an overview of the main aspects relating to the automated methods available for laboratory diagnosis as well as for monitoring of the HIV infection and determination of resistance to antiretroviral and viral tropism. \u0000 \u0000Furthermore, Dr. Ortiz et al. have provided a review about the current human papillomavirus (HPV) genotyping tests in order to diagnose this kind of viruses; these are considered important pathogens distributed worldwide mainly causing cervical cancer in women. \u0000 \u0000Meanwhile, Dr. Perez-Ruiz et al. have reviewed the main advances in clinical virology for detecting respiratory viruses with automated methods. \u0000 \u0000Finally, this hot topic has bee","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"103"},"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/3b/3b/TOVJ-6-103.PMC3522102.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31129669","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":"Early events in herpes simplex virus lifecycle with implications for an infection of lifetime.","authors":"Sarah Salameh, Urmi Sheth, Deepak Shukla","doi":"10.2174/1874357901206010001","DOIUrl":"https://doi.org/10.2174/1874357901206010001","url":null,"abstract":"<p><p>Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral \"surfing\" along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor α, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, which helps in the evasion of physical barriers as well as several components of the innate and adaptive immune responses. The spread may be facilitated by membrane fusion, movement across tight junctions, transfer across neuronal synapses, or the recruitment of actin-containing structures. This review summarizes some of the recent advances in our understanding of HSV entry and cell-to-cell spread.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"1-6"},"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/df/58/TOVJ-6-1.PMC3267084.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30424674","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}
Cesar Mauricio Rueda Rios, Paula Andrea Velilla, Maria Teresa Rugeles
{"title":"Chronically HIV-1 Infected Patients Exhibit Low Frequencies of CD25+ Regulatory T Cells.","authors":"Cesar Mauricio Rueda Rios, Paula Andrea Velilla, Maria Teresa Rugeles","doi":"10.2174/1874357901206010049","DOIUrl":"https://doi.org/10.2174/1874357901206010049","url":null,"abstract":"<p><p>The characterization of regulatory T cells (Treg) during HIV infection has become of particular interest considering their potential role in the pathogenesis of the acquired immunodeficiency syndrome. Different reports on Tregs in HIV-infected patients vary greatly, depending on the state of disease progression, anatomical compartment, and the phenotypic markers used to define this cell subpopulation. To determine the frequency of Tregs we included paired samples from peripheral blood and rectal biopsies from controls and chronic HIV patients with or without detectable viral load. Tregs were determined by flow cytometry using three different protocols: CD4(+)Foxp3(+); CD4(+)Foxp3(+)CD127(Low/-), and CD4(+)CD25(+)CD127(Low/-). In addition, and with the purpose to compare the different protocols we also characterized Tregs in peripheral blood of HIV negative individuals with influenza like symptoms. Here, we report that Treg characterization in HIV-infected patients as CD4(+)Foxp3(+) and CD4(+)Foxp3(+)CD127(Low/-) cells was similar, indicating that both protocols represent a suitable method to determine the frequency of Tregs in peripheral blood mononuclear cells (PBMC) and gut associated lymphoid tissue (GALT). In contrast, in HIV but not in flu-like patients, detection of Tregs as CD4(+)CD25(+)CD127(Low/- )cells resulted in a significantly lower percentage of these cells. In both, HIV patients and controls the frequency of Treg was significantly higher in GALT compared to PBMC. The frequency of Tregs in PBMC and GALT using CD4(+)Foxp3(+) and CD4(+)Foxp3(+)CD127(Low/-) was higher in HIV patients than in controls. Similarly, the frequency of Treg using any protocol was higher in flu-like patients compared to controls. The results suggest that relying on the expression of CD25 could be unsuitable to characterize Tregs in PBMC and GALT samples from a chronic infection such as HIV.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"49-58"},"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/55/b6/TOVJ-6-49.PMC3350015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30615655","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}
Hoyin Mok, Xing Cheng, Qi Xu, James R Zengel, Bandita Parhy, Jackie Zhao, C Kathy Wang, Hong Jin
{"title":"Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350.","authors":"Hoyin Mok, Xing Cheng, Qi Xu, James R Zengel, Bandita Parhy, Jackie Zhao, C Kathy Wang, Hong Jin","doi":"10.2174/1874357901206010012","DOIUrl":"https://doi.org/10.2174/1874357901206010012","url":null,"abstract":"<p><p>Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3(rd) position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"12-22"},"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/5e/bf/TOVJ-6-12.PMC3286841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30501019","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":"Genotype distribution of human papillomaviruses in Japanese women with abnormal cervical cytology.","authors":"Kazunari Kondo, Asami Uenoyama, Ryo Kitagawa, Hajime Tsunoda, Rika Kusumoto-Matsuo, Seiichiro Mori, Yoshiyuki Ishii, Takamasa Takeuchi, Tadahito Kanda, Iwao Kukimoto","doi":"10.2174/1874357901206010277","DOIUrl":"https://doi.org/10.2174/1874357901206010277","url":null,"abstract":"<p><p>We report the prevalence and genotype distribution of human papillomaviruses (HPVs) among Japanese women with abnormal cervical cytology using the PGMY-CHUV assay, one of PGMY-PCR-based lineblot assays that was validated and shown to be suitable for the detection of multiple HPV types in a specimen with minimum bias. Total DNA was extracted from cervical exfoliated cells collected from 326 outpatients with abnormal Pap smears. Overall, 307 specimens (94%) were HPV-positive, 30% of which contained multiple genotypes. The prevalence of HPV DNA was 83% (49/59 samples) in atypical squamous cells of undetermined significance (ASC-US); 91% (20/22 samples) in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); 97% (130/134 samples) in low-grade squamous intraepithelial lesion (LSIL); and 99% (85/86 samples) in high-grade squamous intraepithelial lesion (HSIL). Three most frequent HPV types detected in HSIL were HPV16 (36%), HPV52 (24%), and HPV58 (14%). Our results suggest that multiple HPV infections are more prevalent in Japanese women than previously reported, and confirm that HPV52 and 58 are more dominant in their cervical precancerous lesions when compared to those reported in Western countries.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"277-83"},"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/2f/22/TOVJ-6-277.PMC3547357.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31179845","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}
Karolina Tarasiuk, Grzegorz Woźniakowski, Elżbieta Samorek-Salamonowicz
{"title":"Occurrence of chicken parvovirus infection in poland.","authors":"Karolina Tarasiuk, Grzegorz Woźniakowski, Elżbieta Samorek-Salamonowicz","doi":"10.2174/1874357901206010007","DOIUrl":"https://doi.org/10.2174/1874357901206010007","url":null,"abstract":"<p><p>The aim of the foregoing study was the determination of the occurrence of parvovirus in chicken flocks from different regions of Poland during 2002-2011. The material used for this study originated from chickens showing clinical symptoms of stunting and emaciation. For the quick detection of genetic material of the viruses in field samples, real-time PCR was applied. The conducted study implied on the occurrence of parvoviral infections in Poland in approximately 18% of investigated chicken flocks. However, their exact role remains still unknown.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":" ","pages":"7-11"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874357901206010007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40141353","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 biology of papillomavirus latency.","authors":"Gareth Adam Maglennon, John Doorbar","doi":"10.2174/1874357901206010190","DOIUrl":"10.2174/1874357901206010190","url":null,"abstract":"<p><p>The presence of viral DNA in the absence of disease has suggested that papillomaviruses, like many other viruses, can exist as latent infections in the skin or other epithelial sites. In animal models, where detailed investigation has been carried out, papillomavirus DNA can be found at sites of previous infection following immune regression, with the site of latent infection being the epithelial basal layer. Such studies suggest that immune surveillance can restrict viral gene expression in the basal and parabasal layers without efficiently suppressing viral genome replication, most probably through the action of memory T-cells in the skin or dermis. Although gradual papillomavirus genome loss appears to occur over time at latent sites, immunosuppression can arrest this, and can lead to an elevation in viral genome copy number in experimental systems. In addition to immune-mediated latency, it appears that a similar situation can be achieved following infection at low virus titres and/or infection at epithelial sites where the virus life cycle is not properly supported. Such silent of asymptomatic infections do not necessarily involve the host immune system and may be controlled by different mechanisms. It appears that virus reactivation can be triggered by mechanical irritation, wounding or by UV irradiation which changes the local environment. Although the duration of papillomavirus latency in humans is not yet known, it is likely that some of the basic principles will resemble those elucidated in these model systems, and that persistence in the absence of disease may be the default outcome for at least some period of time following regression.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"190-7"},"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/c7/30/TOVJ-6-190.PMC3547330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31181441","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}
Sascha Bossow, Sabine Schlecht, Rainer Schubbert, Matthias Pfeiffer, Wolfgang J Neubert, Marian Wiegand
{"title":"Evaluation of nucleocapsid and phosphoprotein p functionality as critical factors during the early phase of paramyxoviral infection.","authors":"Sascha Bossow, Sabine Schlecht, Rainer Schubbert, Matthias Pfeiffer, Wolfgang J Neubert, Marian Wiegand","doi":"10.2174/1874357901206010073","DOIUrl":"https://doi.org/10.2174/1874357901206010073","url":null,"abstract":"<p><p>In the beginning of a paramyxovirus infection after cell entry viral survival depends on efficient primary (1°) transcription and on the stability of only one input nucleocapsid. Here we examined the influence of the viral polymerase co-factor phosphoprotein P on the very early phase of an infection, i.e. before progeny nucleocapsids are synthesized. We used a novel set-up with Sendai virus (SeV) mutants incapable of genome replication: SeV-ΔP with the entire P ORF deleted, SeV-PΔ2-77 with the deletion of aa 2-77. These mutants allow maintaining the state of the very beginning of an infection when statistically one viral genome is present in the cell. This single genome serves as template for transcription. During SeV-ΔP infections only early 1° transcription takes place at low levels. However, when the truncated P protein is expressed in SeV-PΔ2-77 infections, 1° transcription levels rise significantly up to an 8-fold increased amount of viral mRNA. This shows that the P protein is able to support transcription and thereby mediates the transition from early to late 1° transcription. Importantly, nucleocapsids of both mutants could be shown to remain stable and functional for at least 5 days - even without de novo P protein synthesis. These results describe a novel function of the P protein: enhancing viral gene expression even before genome replication has started. Thus, the since long postulated supportive function of the P protein is not related to stabilization of the nucleocapsid but rather enhances the processivity of the viral polymerase during late 1° and secondary (2°) transcription and genome replication.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"73-81"},"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/d0/5b/TOVJ-6-73.PMC3391653.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30757157","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}