Clinical and experimental rheumatology最新文献

{"title":"Optimism in inclusion body myositis: a double-blind randomised controlled phase III trial investigating the effect of sirolimus on disease progression in patients with IBM as measured by the IBM Functional Rating Scale.","authors":"Umesh A Badrising, Robert Henderson, Stephen Reddel, Alastair Corbett, Christina Liang, Katrina Reardon, Roula Ghaoui, Max Bulsara, Stefen Brady, Anna Brusch, Doris Chan, Jerome D Coudert, Timothy Fairchild, Gayatri Jain, Matthew C Kiernan, Dag Leonard, Thomas Lloyd, Jens Schmidt, Mike P McDermott, Lauren Sanders, Christine Lowe, Anneke J van der Kooi, Chris Weihl, Payam Mohassel, Marion Simpson, Antonia Carroll, Ian Cooper, Kelly Beer, Krystyne Hiscock, Susan Walters, Annik Panicker, Althea Doverty, Andrew Heim, Marjolein van Heur-Neuman, Olivier Benveniste, Mazen M Dimachkie, Merrilee Needham","doi":"10.55563/clinexprheumatol/zvffa0","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/zvffa0","url":null,"abstract":"<p><strong>Objectives: </strong>Inclusion body myositis (IBM) is a complex inflammatory muscle disease in adults over 40, with histological features of autoinflammation, cell stress and autophagic abnormalities, and marked clinically by relentless progression with no effective disease-modifying therapy. Sirolimus (rapamycin) may help maintain function by inhibiting T effector cells, preserving T regulatory cells, inducing autophagy, and improving mitochondrial function. This international trial follows a phase II pilot study.</p><p><strong>Methods: </strong>This phase IIb/III double-blind, randomised, controlled trial (RCT) of sirolimus involves 140 IBM patients randomly assigned with equal allocation to sirolimus (2 mg) or matching placebo. This RCT aims to assess the efficacy of sirolimus compared to placebo in slowing or stabilising IBM progression, as measured by the mean change in patient function using the IBM Functional Rating Scale (IBM-FRS) from Baseline to Week 84. Secondary outcomes will evaluate efficacy and safety to inform future clinical trial design.</p><p><strong>Results: </strong>Ethical approval has been granted in Australia (St Vincent's Hospital Melbourne HREC-D 311/20) and the USA (University of Kansas Medical Center Human Research Protection Program FWA no. 00003411), with European approval pending. The protocol is version 3.0 (02-Dec-2022).</p><p><strong>Trial registration: </strong>ANZCTR: ACTRN12620001226998p, ClinicalTrials.gov: NCT04789070, UTN: U1111-1258-1354, and EU CT 2024-514575-17-00.</p><p><strong>Conclusions: </strong>This phase IIb/III trial builds on prior findings to assess sirolimus's potential in slowing or halting IBM progression, preserving patient function and independence, and advancing IBM therapeutic strategies and trial design.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":"43 2","pages":"316-325"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic inflammatory myopathies: one year in review 2024.","authors":"Federico Fattorini, Edoardo Conticini, Eduardo Dourado, Francesca Bottazzi, Lorenza Bruno, Michele Diomedi, Jens Schmidt, Linda Carli, Lorenzo Cavagna, Simone Barsotti","doi":"10.55563/clinexprheumatol/yizkja","DOIUrl":"10.55563/clinexprheumatol/yizkja","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases characterised by skeletal muscle inflammation and frequently by other organs involvement, in particular lung and skin, but also joints, heart and gastrointestinal tract.Although they are rare diseases, the literature on IIMs has been growing rapidly and many studies have been published in order to clarify the pathogenesis and to better define diagnosis, clinical manifestations (muscular and extra-muscular) and treatment. The purpose of this review is to summarise the most relevant contributions published over the last year on this topic.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":"43 2","pages":"167-177"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated myositis before and after the COVID-19 pandemic onset: a comment.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.55563/clinexprheumatol/mxdet4","DOIUrl":"10.55563/clinexprheumatol/mxdet4","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"387"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple-combination therapy did not improve prognosis in anti-MDA5 positive dermatomyositis: a multicentre longitudinal cohort study.","authors":"Hanxiao You, Chengyin Lv, Lingxiao Xu, Lei Wang, Ting Liu, Fenghong Yuan, Wei Yan, Hua Wei, Jiajia Wang, Deqian Meng, Wenfeng Tan","doi":"10.55563/clinexprheumatol/jmpuxa","DOIUrl":"10.55563/clinexprheumatol/jmpuxa","url":null,"abstract":"<p><strong>Objectives: </strong>Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is frequently linked with interstitial lung disease (ILD), especially the rapidly progressive ILD (RP-ILD). We conduct this research to evaluate the efficacy and safety of triple-combination (triple-combo) therapy consisting of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide in treating MDA5+ DM patients with ILD.</p><p><strong>Methods: </strong>A multicentre longitudinal cohort study involving 115 MDA5+ DM patients from the Nanjing Medical University Myositis Associated ILD (NMMI) cohort was conducted between January 2019 and November 2022. Patients were categorised into triple-combo and non-triple therapy groups, and their outcomes were assessed.</p><p><strong>Results: </strong>Contrary to expectations, triple-combo therapy did not improve the prognosis for MDA5+ DM patients but was linked to increased mortality rates, especially among those at high risk for RP-ILD.</p><p><strong>Conclusions: </strong>Our study suggests that triple-combo therapy might not be effective in improving prognosis in MDA5+ DM patients. Further research is needed to establish safer and more effective treatment modalities for this patient population.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"251-259"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human epididymitis protein 4 as a biomarker of interstitial lung disease in patients with idiopathic inflammatory myopathies.","authors":"Elisabetta Zanatta, Beatrice Moccaldi, Andrea Martini, Luana Ienna, Roberto Depascale, Marco Binda, Mariele Gatto, Margherita Zen, Marta Tonello, Anna Ghirardello, Chiara Giraudo, Elisabetta Balestro, Mario Plebani, Daniela Basso, Andrea Doria, Luca Iaccarino","doi":"10.55563/clinexprheumatol/s73lah","DOIUrl":"10.55563/clinexprheumatol/s73lah","url":null,"abstract":"<p><strong>Objectives: </strong>Human epididymis protein 4 (HE4) inhibits the degradation of type I collagen, thus promoting fibrosis. We aimed to investigate serum HE4 levels in patients with idiopathic inflammatory myopathies (IIMs), as potential biomarker of interstitial lung disease (ILD).</p><p><strong>Methods: </strong>IIMs patients followed in our centre between June 2020 and January 2023 were enrolled. ILD was detected by high-resolution computed tomography (CT) and pulmonary function tests. Serum HE4 levels were measured in patients and controls. Progressive fibrosing (PF-) ILD was evaluated in patients with available 2-year follow-up (INBUILD criteria).</p><p><strong>Resilts: </strong>We enrolled 90 consecutive IIMs patients (68% females, mean age 59.5 [52.75- 66.0] years) and 42 healthy, age- and sexmatched controls. ILD was diagnosed in 44 (49%) patients. Serum HE4 levels were higher in IIMs patients than controls: 78.55 [54.6-114.4] vs. 51.05 [41.8-62.8] pmol/L (p=0.001). IIMs-ILD patients had higher levels of HE4 vs. those without ILD (193.7 [78.92-137.42] vs. 58.15 [48.32-79] pmol/L, p<0.0001). Serum HE4 levels correlated inversely with diffusing capacity for carbon monoxide (rho=-0.556, p<0.0001) and total lung capacity (rho=-0.459, p=0.001). Serum HE4 levels were the only variable independently associated with IIMs-ILD in two models of multivariate analysis: OR 1.063 (CI 95% 1.02-1.108), p=0.004, and OR 1.059 (CI 95% 1.020-1.099), p=0.003. PF-ILD was detected in 39.4% of IIMs-ILD patients with available follow-up (33/44), without any significant association with baseline serum HE4 levels.</p><p><strong>Conclusions: </strong>HE4 might be a useful biomarker in the identification and assessment of ILD in IIMs patients.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"269-275"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful management of pulmonary hypertension with baricitinib in a dermatomyositis patient.","authors":"Chiara Rizzo, Federica Camarda, Lidia La Barbera, Giuliana Guggino","doi":"10.55563/clinexprheumatol/c6an8c","DOIUrl":"10.55563/clinexprheumatol/c6an8c","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"390"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilising bioinformatics and systems biology methods to uncover the impact of dermatomyositis on interstitial lung disease.","authors":"Rui Ding, Di Liang, Shimei Huang, Xiaojing Huang, Bo Wei, Sirui Wan, Hongjian Zhang, Zheng Wan","doi":"10.55563/clinexprheumatol/fok820","DOIUrl":"10.55563/clinexprheumatol/fok820","url":null,"abstract":"<p><strong>Objectives: </strong>Dermatomyositis (DM) is frequently associated with interstitial lung disease (ILD); however, the molecular mechanisms underlying this association remain unclear. This study aimed to employ bioinformatics approaches to identify potential molecular mechanisms linking DM and ILD.</p><p><strong>Methods: </strong>GSE46239 and GSE47162 were analysed to identify common differentially expressed genes (DEGs). These DEGs underwent Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed to identify hub genes and transcriptional regulators. Potential therapeutic drugs were predicted using the Drug-Gene Interaction Database (DGIDB).</p><p><strong>Results: </strong>A total of 122 common DEGs were identified between the DM and ILD datasets. These DEGs were significantly enriched in signal transduction, transcriptional regulation, inflammation, and cell proliferation. Key pathways included the NOD-like receptor signalling pathway, cytokine-cytokine receptor interaction, and TNF signalling pathway. PPI network analysis revealed the top 10 hub genes: CD163, GZMB, IRF4, CCR7, MMP9, AIF1, CXCL10, CCL5, IRF8, and NLRP3. Additionally, interactions between hub genes and transcription factors/miRNAs were constructed. Eleven drugs targeting four hub genes (CXCL10, MMP9, GZMB, and NLRP3) were predicted using the DGIDB.</p><p><strong>Conclusions: </strong>In summary, the study identified 10 key genes involved in the molecular pathogenesis of DM and ILD. Moreover, 11 potential drugs were identified that may offer viable therapeutic options for treating DM and ILD in the future.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"282-289"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Myositis Clinical Trials Consortium: an international collaborative initiative to promote clinical trials in adult and juvenile myositis.","authors":"Anuradha Bishnoi, Iris Yan Ki Tang, Akira Yoshida, Faye M Pais, Sabeena Y Usman, Solciris A Dominguez, Chengappa G Kavadichanda, Daphne Rivero-Gallegos, Eduardo Dourado, Edoardo Conticini, Francisca Bozán, Gayathri Tulluru, James B Lilleker, Kaushik Sreerama Reddy, Océane Landon-Cardinal, Rachid Smaili, Shiri Keret, Thomas Khoo, Ting-Yuan Lan, Valérie Leclair, Chester V Oddis, Jiří Vencovský, Masataka Kuwana, Prateek C Gandiga, Rohit Aggarwal","doi":"10.55563/clinexprheumatol/k7665a","DOIUrl":"10.55563/clinexprheumatol/k7665a","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies (IIM), or myositis, are a heterogeneous group of systemic autoimmune disorders that are associated with significant morbidity and mortality. Conducting high-quality clinical trials in IIM is challenging due to the rare and variable presentations of disease. To address this challenge, the Myositis Clinical Trials Consortium (MCTC) was formed. MCTC is a collaborative international alliance dedicated to facilitating, promoting, coordinating and conducting clinical trials and related research in IIM. This partnership works to advance the discovery of effective evidence-based treatments for IIM by integrating a diverse group of clinical investigators, research professionals, medical centres, patient groups, and industry partners. The Steering Committee, Core Group, and Paediatric Subcommittee of MCTC are comprised of myositis experts and junior investigators from around the world, representing a diversity of genders, geographies, and subspecialties. MCTC works alongside other current myositis organisations to complement existing work by concentrating on the operationalisation of clinical trials. Our pilot Myositis Investigators' Information Survey gathered responses from 173 myositis investigators globally and found considerable variability in proficiency with outcome measures, geographic disparities in patient recruitment, and a significant disconnect between investigators' routine myositis patient load and clinical trial enrolment. MCTC will meet the need to support and diversify myositis clinical trials by facilitating trial planning, feasibility assessments, site selection, and the training and mentoring of junior investigators/centres to establish their readiness for clinical trial participation. Through experienced leadership, strategic collaborations, and interdisciplinary discussions, MCTC will establish standards for IIM clinical trial design, protocols, and outcome measures in myositis.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"202-210"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleural effusion as a predictor of rapidly progressive interstitial lung disease and mortality in idiopathic inflammatory myopathies.","authors":"Xiao Liang, Huaming Ren, Fei Xiao, Songyuan Zheng, Ran Wang, Chuping Huang, Jinger Guo, Juan Li, Junqing Zhu","doi":"10.55563/clinexprheumatol/ve77nv","DOIUrl":"10.55563/clinexprheumatol/ve77nv","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the clinical significance of pleural effusion in adult patients with idiopathic inflammatory myopathies (IIM).</p><p><strong>Methods: </strong>We assessed a cohort of 158 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without pleural effusion.</p><p><strong>Results: </strong>Of those 158 IIM patients, 28 (17.7%) developed pleural effusion. 125 (79.1%) IIM patients had interstitial lung disease (ILD), 26 (20.8%) of which developed pleural effusion. Notably, pleural effusion was associated with a higher incidence of lower lung zone consolidation, rapidly progressive ILD (RP-ILD) and elevated high-resolution computed tomography (HRCT) score, and could robustly predict RP-ILD independently [HR 7.863 (2.160-28.617), p=0.002] in IIM-ILD patients. IIM patients with pleural effusion presented with increased systemic inflammatory response, including more fever, elevated white blood cell count, neutrophil/lymphocyte ratio, C-reactive protein, and erythrocyte sedimentation rate, alongside reduced lymphocyte percentage. Pleural effusion was also associated with more ILD, lower lung zone consolidation, pericardial effusion and RP-ILD, higher HRCT score, and lower HB and albumin levels in IIM. Except for neutrophil/lymphocyte ratio, ILD and pericardial effusion, other correlative variables were potential predictors of higher mortality in IIM. Furthermore, pleural effusion remained an independent predictor of higher mortality in IIM [HR 5.05 (1.633-15.62), p=0.005].</p><p><strong>Conclusions: </strong>Pleural effusion showed a significant positive association with severe phenotypes of ILD and was the powerful predictor of RP-ILD in IIM-ILD. Furthermore, pleural effusion could reveal adverse disease phenotypes with higher systemic inflammatory level and predict higher mortality independently in IIM.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"221-229"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD44 is associated with muscle inflammation in polymyositis and skin damage in idiopathic inflammatory myopathy.","authors":"Yueyuan Zhou, Yangfan Zhao, Geng Yin, Limei Kang, Xiaoyan Zhu, Qibing Xie","doi":"10.55563/clinexprheumatol/hlk85n","DOIUrl":"10.55563/clinexprheumatol/hlk85n","url":null,"abstract":"<p><strong>Objectives: </strong>Idiopathic inflammatory myopathy (IIM) is a group of systemic autoimmune diseases characterised by muscle involvement. This study aims to reveal the characteristics of IIM subtypes and explore the molecular mechanisms underlying IIM.</p><p><strong>Methods: </strong>The STRING database was utilised to construct a protein-protein interaction network of differentially expressed genes obtained from the GSE128470, GSE3112, and GSE39454 datasets. The immune cell infiltration level was assessed by CIBERSORT in polymyositis (PM). Experimental autoimmune myositis (EAM) model mice were constructed for experimental verification. Serum levels of soluble CD44 (sCD44) were measured using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The upregulated hub gene CD44 was highly expressed in inflammatory cells infiltrating the skeletal muscle of patients with PM and in EAM mice. CD44 was correlated with both M1 macrophages (r=0.57, p<0.0001) and M2 macrophages (r=0.57, p<0.0001) in PM. Additionally, CD44+F4/80+ macrophages in skeletal muscle were increased (p<0.0001) and CD44 showed a stronger association with markers of M1 macrophage in EAM mice. Moreover, serum sCD44 levels were elevated in patients with IIM (p=0.0024), PM (p=0.0332) and dermatomyositis (p=0.0001) notably in the anti-melanoma differentiation-associated gene 5 antibody positive subtype (p=0.0007). sCD44 levels also positively correlated with visual analogue score (r=0.4424, p=0.0013), myositis intention to treat activity index (r=0.3938, p=0.0047), skin damage score (r=0.3796, p=0.0101) and skin activity score (r=0.4625, p=0.0014) in patients with IIM.</p><p><strong>Conclusions: </strong>This study suggests that macrophages expressing CD44 may be involved in the pathogenesis of PM, and sCD44 could serve as a potential marker for skin damage and activity in IIM.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"241-250"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}