Clinical & Developmental Immunology最新文献

{"title":"The Interplay between the bone and the immune system.","authors":"Giorgio Mori, Patrizia D'Amelio, Roberta Faccio, Giacomina Brunetti","doi":"10.1155/2013/720504","DOIUrl":"10.1155/2013/720504","url":null,"abstract":"<p><p>In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"720504"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31648768","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":"Correlation of increased blood levels of GITR and GITRL with disease severity in patients with primary Sjögren's syndrome.","authors":"Xiaoxia Gan,&nbsp;Xiaoke Feng,&nbsp;Lei Gu,&nbsp;Wenfeng Tan,&nbsp;Xiaoxuan Sun,&nbsp;Chengyin Lv,&nbsp;Miaojia Zhang","doi":"10.1155/2013/340751","DOIUrl":"https://doi.org/10.1155/2013/340751","url":null,"abstract":"<p><p>Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a type I transmembrane protein belonging to the TNFR superfamily. After activated by its ligand GITRL, GITR could influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases included rheumatoid arthritis and autoimmune thyroid disease. We previously reported that serum GITRL levels are increased in systemic lupus erythematosus (SLE) patients compared with healthy controls (HC). Here, we tested serum soluble GITR (sGITR) and GITRL levels in 41 primary Sjögren's syndrome (pSS) patients and 29 HC by ELISA and correlated sGITR and GITRL levels with clinical and laboratory variables. GITR and GITRL expression in labial salivary glands was detected by immunohistochemistry. pSS patients had significantly increased serum levels of sGITR and GITRL compared with controls (GITR: 5.66 ± 3.56 ng/mL versus 0.50 ± 0.31 ng/mL; P < 0.0001; GITRL: 6.17 ± 7.10 ng/mL versus 0.36 ± 0.28 ng/mL; P < 0.0001). Serum sGITR and GITRL levels were positively correlated with IgG (GITRL: r = 0.6084, P < 0.0001; sGITR: r = 0.6820, P < 0.0001) and ESR (GITRL: r = 0.8315, P < 0.0001; sGITR: r = 0.7448, P < 0.0001). Moreover, GITR and GITRL are readily detected in the lymphocytic foci and periductal areas of the LSGs. In contrast, the LSGs of HC subjects did not express GITR or GITRL. Our findings indicate the possible involvement of GITR-GITRL pathway in the pathogenesis of pSS. Further studies may facilitate the development of targeting this molecule pathway for the treatment of pSS. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"340751"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/340751","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31648831","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 immunologic basis for severe neonatal herpes disease and potential strategies for therapeutic intervention.","authors":"Soren Gantt,&nbsp;William J Muller","doi":"10.1155/2013/369172","DOIUrl":"https://doi.org/10.1155/2013/369172","url":null,"abstract":"<p><p>Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world's population. Infection is life-long and can cause periodic mucocutaneous symptoms, but it only rarely causes life-threatening disease among immunocompetent children and adults. However, when HSV infection occurs during the neonatal period, viral replication is poorly controlled and a large proportion of infants die or develop disability even with optimal antiviral therapy. Increasingly, specific differences are being elucidated between the immune system of newborns and those of older children and adults, which predispose to severe infections and reflect the transition from fetal to postnatal life. Studies in healthy individuals of different ages, individuals with primary or acquired immunodeficiencies, and animal models have contributed to our understanding of the mechanisms that control HSV infection and how these may be impaired during the neonatal period. This paper outlines our current understanding of innate and adaptive immunity to HSV infection, immunologic differences in early infancy that may account for the manifestations of neonatal HSV infection, and the potential of interventions to augment neonatal immune protection against HSV disease.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"369172"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/369172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31468354","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 and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.","authors":"Gianluigi Zaza,&nbsp;Paola Tomei,&nbsp;Paolo Ria,&nbsp;Simona Granata,&nbsp;Luigino Boschiero,&nbsp;Antonio Lupo","doi":"10.1155/2013/403280","DOIUrl":"https://doi.org/10.1155/2013/403280","url":null,"abstract":"<p><p>The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"403280"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/403280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40259862","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":"P53 and expression of immunological markers may identify early stage thyroid tumors.","authors":"Marjory Alana Marcello,&nbsp;Elaine Cristina Morari,&nbsp;Lucas Leite Cunha,&nbsp;Aline Carolina De Nadai Silva,&nbsp;Dirce Maria Carraro,&nbsp;André Lopes Carvalho,&nbsp;Fernando Augusto Soares,&nbsp;José Vassallo,&nbsp;Laura Sterian Ward","doi":"10.1155/2013/846584","DOIUrl":"https://doi.org/10.1155/2013/846584","url":null,"abstract":"<p><strong>Background: </strong>Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC).</p><p><strong>Methods: </strong>ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also, TP53 was sequenced in 78 out of 164 patients with papillary thyroid carcinoma.</p><p><strong>Results: </strong>P53 expression was observed more frequently in malignant than in benign lesions (P < 0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller (P = 0.0015), unique tumors (P = 0.0286), with thyroiditis (P = 0.0486) and without metastasis at diagnosis (P = 0.0201). TAM was more frequent in P53 negative tumors (P = 0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC (P < 0.001).</p><p><strong>Conclusions: </strong>We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"846584"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/846584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40276453","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":"Complement in human disease.","authors":"Michael A Flierl,&nbsp;Daniel Rittirsch,&nbsp;Markus S Huber-Lang,&nbsp;Philip F Stahel","doi":"10.1155/2013/920474","DOIUrl":"https://doi.org/10.1155/2013/920474","url":null,"abstract":"As part of innate immunity, the complement system embodies the “first line of defense” to various initial insults, including trauma, infection, hemorrhage, ischemia, and autoimmunity. While of beneficial intention, excessive complement activation can inadvertently damage healthy host tissues and thereby exacerbate the initial pathological events by causing an “innocent bystander effect.” \u0000 \u0000“Complementology” represents a rapidly evolving field. Recent scientific efforts have identified novel complement activation pathways and select complement-inhibiting compounds, which have been shown to ameliorate myriad autoimmune or inflammatory conditions. These findings have renewed the enthusiasm for novel pharmacological strategies targeting numerous inflammatory conditions, which currently elude successful transfer “from bench to bedside,” such as acute lung injury, sepsis, burn, ischemia-reperfusion injury, traumatic brain injury, and kidney disease. \u0000 \u0000The abundant involvement of the complement system in human health and disease is reflected by the wide range of topics covered in this special issue of Clinical and Developmental Immunology. \u0000 \u0000B. Nilsson and N. Ekdahl provide a summarizing article on current indications, techniques, sampling, and interpretations for clinical complement analyses. In addition, an easy-to-follow algorithm is provided for routine laboratory operations. \u0000 \u0000G. Cazander et al. illustrate the success of targeted complement inhibition of complement in wound healing and demonstrate how revesal of complement hyperactivity using several complement inhibitors has resulted in novel and innovative wound care strategies, which may soon be subject of clinical trials. \u0000 \u0000K. J. Welsh et al. challenge recent evidence that complement plays a critical role in the host defense against Mycobacterium tuberculosis. Following aerosol challenge with Mycobacterium tuberculosis, the authors demonstrate that “C7-knockout” mice had markedly reduced liver colony forming units and lung occlusion in conjunction with significantly increased total lymphocytes, decreased macrophages, and increased numbers of CD4+ cells. In line, expression of lung IFN-γ and TNF-α was increased in these animals, underscoring a crucial role of C7 in the disease manifestation of Mycobacterium tuberculosis. \u0000 \u0000S. R. Stowell et al.'s manuscript reviews the role of complement in transfusion-related mortality. This is of particular interest, as excessive complement activation during transfusion represents one of the most common features associated with fatality. The treating physician is furthermore provided with several strategies aiming to immunomodulate the complement system during incompatible red blood cell transfusions. \u0000 \u0000In two reviews, F. Bu et al. and S. F. Heeringa and colleagues review complement involvement in renal disease. Bu reviews the pathogenetic role of genetic variations in complement genes and complement dysregulation at the cell surface results in different","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"920474"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/920474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31323023","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 review on JC virus infection in kidney transplant recipients.","authors":"Serena Delbue,&nbsp;Mariano Ferraresso,&nbsp;Luciana Ghio,&nbsp;Camilla Carloni,&nbsp;Silvia Carluccio,&nbsp;Mirco Belingheri,&nbsp;Alberto Edefonti,&nbsp;Pasquale Ferrante","doi":"10.1155/2013/926391","DOIUrl":"https://doi.org/10.1155/2013/926391","url":null,"abstract":"<p><p>The polyomavirus (PyV), JC virus (JCV), is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). Although the reactivation of another human PyV, BK virus (BKV), is relatively common and its association with the polyomavirus associated nephropathy (PyVAN) following renal transplantation is proven, JCV replication and its impact on graft function and survival are less well studied. Here we describe the biology of JCV and its pathological features and we review the literature regarding the JCV infection analyzed in the setting of transplantations.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"926391"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/926391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31251903","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":"How to translate basic knowledge into clinical application of biologic therapy in spondyloarthritis.","authors":"Chung-Tei Chou","doi":"10.1155/2013/369202","DOIUrl":"https://doi.org/10.1155/2013/369202","url":null,"abstract":"<p><p>Spondyloarthritis (SpA) is a family of many diseases, and these diseases share some clinical, genetic, and radiologic features. The disease process in the spine at the beginning is spinal inflammation, in which TNF α is the principal cytokine involved. Therefore, the dramatic clinical and pathologic response of anti-TNF α therapy in SpA is based upon the presence of increased TNF α in synovial tissues and sacroiliac joints, which perpetuates chronic inflammation. The increased Toll-like receptors (TCR) 2 and 4 in the serum, peripheral blood mononuclear cells, or synovial tissues of ankylosing spondyloarthritis (AS) or SpA patients suggest that SpA is highly associated with innate immunity. Any drug including anti-TNF α blocker which can downregulate the TCR, infiltrated neutrophils, or CD163+ macrophages in the synovial tissue is the rationale for the management of SpA. Like rheumatoid arthritis, the increased TH22 and TH17 cells either in blood, synovial fluid, or synovial tissues were also demonstrated in SpA. Thus, TH17 and TH22 may be reasonable cellular targets for therapeutic intervention. Drugs (anti-IL6R or anti-IL6) which can reduce the binding of IL6 and IL6R to the cell surface may be beneficial in SpA. Many proteins are implicated in the new bone formation (syndesmophyte) or ankylosis in AS or SpA. The enhanced BMP and Wnt pathway will activate osteoblasts which promote the new bone formation. However, no drug including anti-TNF α can stop or prevent the syndesmophyte in AS. In summary, looking for new targeting therapies for either anti-inflammation (beyond anti-TNF) or anti-bone formation (including anti-TGF β or PDGF) is warranted in the future. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"369202"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/369202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31212197","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":"Immunogenetic study in Chinese population with ankylosing spondylitis: are there specific genes recently disclosed?","authors":"Jiayu Zhai,&nbsp;Ju Rong,&nbsp;Qiuxia Li,&nbsp;Jieruo Gu","doi":"10.1155/2013/419357","DOIUrl":"https://doi.org/10.1155/2013/419357","url":null,"abstract":"<p><strong>Purpose: </strong>Ankylosing spondylitis (AS) is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population.</p><p><strong>Recent findings: </strong>In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC), ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions.</p><p><strong>Summary: </strong>This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"419357"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/419357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31232412","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":"Conversion to sirolimus therapy in kidney transplant recipients with new onset diabetes mellitus after transplantation.","authors":"Massimiliano Veroux,&nbsp;Tiziano Tallarita,&nbsp;Daniela Corona,&nbsp;Nunziata Sinagra,&nbsp;Alessia Giaquinta,&nbsp;Domenico Zerbo,&nbsp;Carmela Guerrieri,&nbsp;Antonino D'Assoro,&nbsp;Sebastiano Cimino,&nbsp;Pierfrancesco Veroux","doi":"10.1155/2013/496974","DOIUrl":"https://doi.org/10.1155/2013/496974","url":null,"abstract":"<p><p>New-onset diabetes mellitus after transplantation (NODAT) may complicate 2-50% of kidney transplantation, and it is associated with reduced graft and patient survivals. In this retrospective study, we applied a conversion protocol to sirolimus in a cohort of kidney transplant recipients with NODAT. Among 344 kidney transplant recipients, 29 patients developed a NODAT (6.6%) and continued with a reduced dose of calcineurin inhibitors (CNI) (8 patients, Group A) or were converted to sirolimus (SIR) (21 patients, Group B). NODAT resolved in 37.5% and in 80% patients in Group A and Group B, respectively. In Group A, patient and graft survivals were 100% and 75%, respectively, not significantly different from Group B (83.4% and 68%, resp., P = 0.847). Graft function improved after conversion to sirolimus therapy: serum creatinine was 1.8 ± 0.7 mg/dL at the time of conversion and 1.6 ± 0.4 mg/dL five years after conversion to sirolimus therapy (P < 0.05), while in the group of patients remaining with a reduced dose of CNI, serum creatinine was 1.7 ± 0.6 mg/dL at the time of conversion and 1.65 ± 0.6 mg/dL at five-year followup (P = 0.732). This study demonstrated that the conversion from CNI to SIR in patients could improve significantly the metabolic parameters of patients with NODAT, without increasing the risk of acute graft rejection.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"496974"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/496974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31502452","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}