Autoimmune Diseases最新文献

{"title":"Genes associated with SLE are targets of recent positive selection.","authors":"Paula S Ramos, Stephanie R Shaftman, Ralph C Ward, Carl D Langefeld","doi":"10.1155/2014/203435","DOIUrl":"10.1155/2014/203435","url":null,"abstract":"<p><p>The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, including PTPN22, TNFSF4, TET3-DGUOK, TNIP1, UHRF1BP1, BLK, and ITGAM genes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"203435"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32170477","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":"A comparison of anti-nuclear antibody quantification using automated enzyme immunoassays and immunofluorescence assays.","authors":"Renata Baronaite,&nbsp;Merete Engelhart,&nbsp;Troels Mørk Hansen,&nbsp;Gorm Thamsborg,&nbsp;Hanne Slott Jensen,&nbsp;Steen Stender,&nbsp;Pal Bela Szecsi","doi":"10.1155/2014/534759","DOIUrl":"https://doi.org/10.1155/2014/534759","url":null,"abstract":"<p><p>Anti-nuclear antibodies (ANA) have traditionally been evaluated using indirect fluorescence assays (IFA) with HEp-2 cells. Quantitative immunoassays (EIA) have replaced the use of HEp-2 cells in some laboratories. Here, we evaluated ANA in 400 consecutive and unselected routinely referred patients using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique patients were compared. The majority of the results were the same between the two methods (n = 325, 84%); however, 8% (n = 30) yielded equivocal results (equivocal-negative and equivocal-positive) and 8% (n = 31) yielded divergent results (positive-negative). The results showed fairly good agreement, with Cohen's kappa value of 0.30 (95% confidence interval (CI) = 0.14-0.46), which decreased to 0.23 (95% CI = 0.06-0.40) when the results for dsDNA were omitted. The EIA method was less reliable for assessing nuclear and speckled reactivity patterns, whereas the IFA method presented difficulties detecting dsDNA and Ro activity. The automated EIA method was performed in a similar way to the conventional IFA method using HEp-2 cells; thus, automated EIA may be used as a screening test. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"534759"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/534759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174769","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":"Systemic lupus erythematosus 2014.","authors":"Juan-Manuel Anaya,&nbsp;Yehuda Shoenfeld,&nbsp;Ricard Cervera","doi":"10.1155/2014/274323","DOIUrl":"https://doi.org/10.1155/2014/274323","url":null,"abstract":"Systemic lupus erythematosus (SLE, lupus) is the prototype of systemic autoimmune disease (AD). Immune system activation in SLE is characterized by exaggerated B-cell and T-cell responses and loss of immune tolerance against self-antigens. Production and defective elimination of antibodies, circulation and tissue deposition of immune complexes, and complement and cytokine activation contribute to clinical manifestations that range from fatigue and joint pain to severe, life-threatening organ damage [1]. In this special issue, nine papers were selected covering important topics of the disease from B lymphocytes (e.g., autoantibodies and B-cell depletion therapy), immunosenescence, and genetics to disease complications such as cardiovascular disease (CVD), preeclampsia, fatigue, and depression. B lymphocytes are the effectors of humoral immunity, providing defense from pathogens through different functions including antibody production. In the context of ADs, B lymphocytes play an essential role by not only producing autoantibodies but also functioning as antigen presenting cells and as a source of cytokines as pointed out by G. J. Tobon and colleagues, who reviewed the functions of B lymphocytes in autoimmunity and ADs with a special focus on their abnormalities in SLE. We recognize today that disease manifestations are determined by the diversity of autoantibodies appearing in SLE [2, 3]. This explains the different clinical presentations within individuals with SLE. In this issue, E. Cozzani and colleagues reviewed the most important autoantibodies in SLE and their correlation between immunopathological features and clinical aspects. Recommendations for determining anti-nuclear antibodies, anti-double stranded DNA antibodies, specific antibodies, and validation of methods have been published elsewhere [4]. Given that autoantibody production is the hallmark of SLE, it is not surprising that B-cell depletion therapy is a promising therapeutic option in the management of SLE. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has been used off-license in the management of severe refractory SLE since 2002. In this special issue, F. Bonilla-Abadia and colleagues report the results of a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with RTX as remission induction therapy and maintenance. They observed a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease suggesting that RTX could be effective and safe in patients with SLE refractory to conventional therapy. An important matter about SLE for 2014 will be the progress and even release of results of the ongoing trials with the new biological therapies including epratuzumab, a humanized anti-CD22 monoclonal antibody, and subcutaneous belimumab, a human monoclonal antibody that inhibits B-lymphocyte stimulator, as well as the investigator-in","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"274323"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/274323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32303184","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":"An update in guillain-barré syndrome.","authors":"J B Winer","doi":"10.1155/2014/793024","DOIUrl":"https://doi.org/10.1155/2014/793024","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) was first described in 1916 (Guillain G, 1916) and is approaching its 100th anniversary. Our knowledge of the syndrome has hugely expanded since that time. Once originally considered to be only demyelinating in pathology we now recognise both axonal and demyelinating subtypes. Numerous triggering or antecedent events including infections are recognised and GBS is considered an immunological response to these. GBS is now considered to be a clinical syndrome of an acute inflammatory neuropathy encompassing a number of subtypes with evidence of different immunological mechanisms. Some of these are clearly understood while others remain to be fully elucidated. Complement fixing antibodies against peripheral nerve gangliosides alone and in combination are increasingly recognised as an important mechanism of nerve damage. New antibodies against other nerve antigens such as neurofascin have been recently described. Research databases have been set up to look at factors associated with prognosis and the influence of intravenous immunoglobulin (IvIg) pharmacokinetics in therapy. Exciting new studies are in progress to examine a possible role for complement inhibition in the treatment of the syndrome. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"793024"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/793024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32101941","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":"Mercury, autoimmunity, and environmental factors on cheyenne river sioux tribal lands.","authors":"Jennifer Ong,&nbsp;Esther Erdei,&nbsp;Robert L Rubin,&nbsp;Curtis Miller,&nbsp;Carlyle Ducheneaux,&nbsp;Marcia O'Leary,&nbsp;Bernadette Pacheco,&nbsp;Michael Mahler,&nbsp;Patricia Nez Henderson,&nbsp;K Michael Pollard,&nbsp;Johnnye L Lewis","doi":"10.1155/2014/325461","DOIUrl":"https://doi.org/10.1155/2014/325461","url":null,"abstract":"<p><p>Mercury (Hg), shown to induce autoimmune disease in rodents, is a ubiquitous toxicant throughout Cheyenne River Sioux Tribe (CRST) lands. CRST members may be exposed to Hg through fish consumption (FC), an important component of native culture that may supplement household subsistence. Our goals were to ascertain whether total blood Hg levels (THg) reflect Hg exposure through FC and smoking, and determine whether THg is associated with the presence of anti-nuclear antibody (ANA) and specific autoantibodies (sAuAb). We recruited 75 participants who regularly consume fish from CRST waters. Hg exposure through FC and smoking were assessed via questionnaires. Whole blood samples were collected from participants, and THg was measured using ICP-MS. ANA and sAuAb in serum were modeled using demographic and exposure information as predictors. Female gender, age, and FC were significant predictors of THg and sAuAb; self-reported smoking was not. 31% of participants tested positive for ANA ≥ 2+. Although ANA was not significantly associated with Hg, the interactions of gender with Hg and proximity to arsenic deposits were statistically significant (P < 0.05). FC resulted in a detectable body burden of Hg, but THg alone did not correlate with the presence of ANA or sAuAb in this population. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"325461"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/325461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32372644","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":"Coeliac disease.","authors":"Raffaella Nenna,&nbsp;Stefano Guandalini,&nbsp;Alina Popp,&nbsp;Kalle Kurppa","doi":"10.1155/2014/623784","DOIUrl":"https://doi.org/10.1155/2014/623784","url":null,"abstract":"Celiac disease is an autoimmune disorder, caused by a permanent intolerance to gluten contained in wheat and to similar prolamines present in barley and rye. It is a common disease as its prevalence, in Caucasian populations, is about 1%. There are several patterns of clinical presentation: typical (with gastrointestinal symptoms), atypical (extraintestinal manifestations), and silent forms, all characterized by typical histological lesions in the small bowel mucosa. Nowadays the gluten-free diet for life is the only therapy available for CD. Considerable progress has been made due to advances in molecular biology, which have allowed better understanding of the genetic mechanisms involved in CD and the identification of new pathogenetic pathways that have the potential to be targeted by new drugs. In this special issue, we have invited authors to contribute original papers that will stimulate the continuing efforts to understand the pathogenesis and heterogeneous clinical presentation of celiac disease. Immunogenic peptides, created by deamidation of food-derived gliadin peptides by small intestinal tissue transglu-taminase, are presented by antigen-presenting cells, mostly dendritic cells bearing HLA-DQ2 and DQ8 molecules, to proinflammatory CD4+ T cells, activating them. E. Liu et al. investigated peripheral T cell responses from young children with newly diagnosed CD prior to treatment with a gluten-free diet, finding that T cell reactivity is heterogeneous but favors reactivity with í µí»¼-gliadin epitopes more than í µí»¾-gliadin. Metabolomics is a rapidly emerging new concept in science that appears to have relevant application also in the field of celiac disease. In their meticulous review, A. Cal-abrò et al. highlight the metabolomics perspective on celiac disease. Furthermore, the growing recognition of the important role of gut microbiota in the development of celiac disease and other food-related disorders is addressed and thoroughly reviewed. Healing of the small bowel mucosa is directly dependent on the adherence to the gluten-free diet, and its assessment by noninvasive tools has been a long-time objective of research in celiac disease, with the aim of establishing suitable minimally invasive methods both for diagnosing and for adequate follow-up of celiac disease and of the adequacy of the gluten-free diet. In their study, E. Trigoni et al. concluded that anti-endomysium antibodies had better ability, at least in adult individuals, than anti-tissue transglutaminase to predict celiac disease and to assess the gluten-free diet in the critical period of the first semester after diagnosis and the beginning of the diet. Among the atypical clinical forms of …","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"623784"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/623784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32472054","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":"Rituximab for remission induction and maintenance in refractory systemic lupus erythematosus.","authors":"Fabio Bonilla-Abadía,&nbsp;Nicolás Coronel Restrepo,&nbsp;Gabriel J Tobón,&nbsp;Andrés F Echeverri,&nbsp;Evelyn Muñoz-Buitrón,&nbsp;Andres Mauricio Castro,&nbsp;Mercedes Andrade Bejarano,&nbsp;Carlos A Cañas","doi":"10.1155/2014/731806","DOIUrl":"https://doi.org/10.1155/2014/731806","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with high morbidity if untreated. Sometimes, despite aggressive treatments, the disease remains active with cumulative organic damage. We conducted a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with rituximab (RTX) as remission induction therapy and maintenance. There was a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease. RTX appeared to be effective and safe for the induction and maintenance of remission in patient with SLE refractory to conventional treatment. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"731806"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/731806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32115381","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 role of decay accelerating factor in environmentally induced and idiopathic systemic autoimmune disease.","authors":"Christopher B Toomey,&nbsp;David M Cauvi,&nbsp;Kenneth M Pollard","doi":"10.1155/2014/452853","DOIUrl":"https://doi.org/10.1155/2014/452853","url":null,"abstract":"<p><p>Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"452853"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/452853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174768","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":"Idiopathic uveitis and familial mediterranean Fever: is there any relationship?","authors":"Farhad Salehzadeh,&nbsp;Ozra Yasrebi,&nbsp;Mahsa Hosseini Khotbesara,&nbsp;Maryam Hosseini Khotbesara","doi":"10.1155/2014/238931","DOIUrl":"https://doi.org/10.1155/2014/238931","url":null,"abstract":"<p><p>Introduction. Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by attacks of fever and polyserositis. FMF is often associated with other autoimmune diseases such as rheumatoid arthritis, polyarteritis nodosa (PAN), and Behcet. Uveitis is an inflammatory process caused by underlying infectious and inflammatory disorders. This study investigates the probable relationship between idiopathic uveitis and FMF. Methods. Patients with idiopathic uveitis were analyzed for the 12 most common MEFV mutations (P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, E148Q) by a reverse hybridization assay (FMF StripAssay,Vienna lab,Vienna, Austria). Results. 12 patients with idiopathic uveitis were enrolled in this study. 10 of them were female. The youngest patient was a 7-year-old child and the oldest was 57. The most common complaints of patients were blurred vision and then eye redness. One patient was heterozygous for R761H. Genetic analysis of the 12 most common MEFV mutations in the patients with idiopathic uveitis didnot have any positive results. Conclusion. According to the analysis of the 12 most common MEFV gene mutations, FMF is not an underlying cause of idiopathic uveitis. On the other hand, uveitis merely could not be the first presentation of FMF. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"238931"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/238931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32172138","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":"CD8+DR+ T-Cells and C3 Complement Serum Concentration as Potential Biomarkers in Thrombotic Antiphospholipid Syndrome.","authors":"Elizabeth Sarmiento,&nbsp;Jonathan Dale,&nbsp;Mauricio Arraya,&nbsp;Antonio Gallego,&nbsp;Nallibe Lanio,&nbsp;Joaquin Navarro,&nbsp;Javier Carbone","doi":"10.1155/2014/868652","DOIUrl":"https://doi.org/10.1155/2014/868652","url":null,"abstract":"<p><p>Purpose. To assess complement factors and T lymphocyte activation subset abnormalities in patients with thrombotic antiphospholipid syndrome (APS) as potential biomarkers for development of clinical complications. Methods. We assessed C3, C4, factor B concentrations (nephelometry), complement haemolytic functional activity (CH100, radial immune diffusion), and the activation status of CD4+ and CD8+ T-cells (three-colour flow cytometry) in patients with thrombotic APS. Antiphospholipid (aPL) positive patients without APS-related clinical criteria, systemic lupus erythematosus (SLE) patients, and healthy individuals were evaluated as controls. A clinical followup was performed to assess the potential relationship between the immunological parameters and development of APS-related complications. Results. Lower concentrations of C3 and higher levels of CD8+DR+ cells were risk factors for development of APS-related complications during followup, including rethrombosis and neuropsychiatric symptoms. Patients with diagnosed thrombotic APS had significantly lower levels of C3, C4, and CH100 as well as higher percentages of activated CD4+DR+ and of CD8+DR+ T-cells than healthy controls but similar to that observed in autoimmune disease controls. Conclusion. Lower C3 and C4 complement levels and higher percentages of CD8+DR+ T-cells were observed in thrombotic APS patients. The potential role of these abnormalities as biomarkers of clinical outcome warrants further evaluation in a multicenter study. </p>","PeriodicalId":46314,"journal":{"name":"Autoimmune Diseases","volume":"2014 ","pages":"868652"},"PeriodicalIF":4.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/868652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32472055","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}