{"title":"Crescentic glomerulonephritis due to linear IgA anti-glomerular basement membrane disease: report of a rare case.","authors":"A G Monich, R F Romani, J L S Carneiro","doi":"10.1590/1414-431X2024e13466","DOIUrl":"10.1590/1414-431X2024e13466","url":null,"abstract":"<p><p>Anti-glomerular basement membrane (GBM) disease is a rare and severe vasculitis that affects the glomerular and pulmonary capillaries and has an incidence of less than 2 cases per million individuals per year. Anti-GBM disease is mediated by autoantibodies against the α3 chain of type IV collagen. In the majority of cases, the autoantibodies are of the immunoglobulin G (IgG) class, with rare cases being mediated by immunoglobulin M (IgM) or immunoglobulin A (IgA); there are less than 15 IgA-mediated cases reported in the literature worldwide. The classic form of this disease manifests with rapidly progressive glomerulonephritis (RPGN), with or without pulmonary hemorrhage, and the diagnosis consists of identifying high titers of autoantibodies in the serum and/or deposited in the tissues. IgA antibodies are not identified in routine immunoassay tests, and renal biopsy with immunofluorescence is essential for diagnosis. We present a case of RPGN due to anti-GBM disease with linear IgA deposition, whose diagnosis was made exclusively by renal biopsy and with an unfavorable prognosis.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"25-hydroxycholesterol aggravates oxygen-glucose deprivation/reoxygenation-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cardiomyocytes.","authors":"Tao Jiang, Yong Li","doi":"10.1590/1414-431X2024e13299","DOIUrl":"10.1590/1414-431X2024e13299","url":null,"abstract":"<p><p>25-hydroxycholesterol (25-HC) plays a role in the regulation of cell survival and immunity. However, the effect of 25-HC on myocardial ischemia/reperfusion (MI/R) injury remains unknown. Our present study aimed to investigate whether 25-HC aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. The overlapping differentially expressed genes (DEGs) in MI/R were identified from the GSE775, GSE45818, GSE58486, and GSE46395 datasets in Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the database of Annotation, Visualization and Integration Discovery (DAVID). The protein-protein interaction (PPI) network of the overlapping DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These bioinformatics analyses indicated that cholesterol 25-hydroxylase (CH25H) was one of the crucial genes in MI/R injury. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate MI/R injury. Western blot and RT-qPCR analysis demonstrated that CH25H was significantly upregulated in OGD/R-stimulated H9C2 cardiomyocytes. Moreover, knockdown of CH25H inhibited the OGD/R-induced pyroptosis and nod-like receptor protein 3 (NLRP3) inflammasome activation, as demonstrated by cell counting kit-8 (CCK8), lactate dehydrogenase (LDH), RT-qPCR, and western blotting assays. Conversely, 25-HC, which is synthesized by CH25H, promoted activation of NLRP3 inflammasome in OGD/R-stimulated H9C2 cardiomyocytes. In addition, the NLRP3 inhibitor BAY11-7082 attenuated 25-HC-induced H9C2 cell injury and pyroptosis under OGD/R condition. In conclusion, 25-HC could aggravate OGD/R-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cells.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An extensive analysis of the prognostic and immune role of FOXO1 in various types of cancer.","authors":"Jie Li, Chao Wang, Xiao Xu, Jun Chen, Haijun Guo","doi":"10.1590/1414-431X2024e13378","DOIUrl":"10.1590/1414-431X2024e13378","url":null,"abstract":"<p><p>Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. C. Almeida, Vanessa K S Lage, R. Taiar, J.M. Santos, F. A. D. Paula, A. Rapin, D. Sá-Caputo, M. Bernardo-Filho, A. Lacerda, V.A. Mendonça
{"title":"Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial","authors":"H. C. Almeida, Vanessa K S Lage, R. Taiar, J.M. Santos, F. A. D. Paula, A. Rapin, D. Sá-Caputo, M. Bernardo-Filho, A. Lacerda, V.A. Mendonça","doi":"10.1590/1414-431X2024e13282","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13282","url":null,"abstract":"Abstract Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684662","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}
F.J.W.S. Siqueira, F.A.P. Rodrigues, S. A. Ribeiro, H.N. Veras, F.C.S. Ferreira, R.C.L. Siqueira, A. A. Santos, A. Havt, A.A.M. Lima
{"title":"Induced acute hyperglycemia modifies the barrier function of the intestinal epithelium by tissue inflammation and tight junction disruption resulting in hydroelectrolytic secretion in an animal model","authors":"F.J.W.S. Siqueira, F.A.P. Rodrigues, S. A. Ribeiro, H.N. Veras, F.C.S. Ferreira, R.C.L. Siqueira, A. A. Santos, A. Havt, A.A.M. Lima","doi":"10.1590/1414-431X2024e13309","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13309","url":null,"abstract":"Abstract Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na+, K+, Cl-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683112","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}
Anquan Hu, Heyan Qin, Shina Wu, Xiaolin Zhao, Yumeng Li, Feng Chen, Tao Liu
{"title":"Development and validation of a clinical prediction model for prognostic factors in patients with primary pontine hemorrhage","authors":"Anquan Hu, Heyan Qin, Shina Wu, Xiaolin Zhao, Yumeng Li, Feng Chen, Tao Liu","doi":"10.1590/1414-431X2024e13359","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13359","url":null,"abstract":"Abstract We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683318","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}
M. R. Lima, B. J. Moreira, R. Bertuzzi, A. Lima-Silva
{"title":"Could nanotechnology improve exercise performance? Evidence from animal studies","authors":"M. R. Lima, B. J. Moreira, R. Bertuzzi, A. Lima-Silva","doi":"10.1590/1414-431X2024e13360","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13360","url":null,"abstract":"Abstract This review provides the current state of knowledge regarding the use of nutritional nanocompounds on exercise performance. The reviewed studies used the following nanocompounds: resveratrol-loaded lipid nanoparticles, folic acid into layered hydroxide nanoparticle, redox-active nanoparticles with nitroxide radicals, and iron into liposomes. Most of these nutritional nanocompounds seem to improve performance in endurance exercise compared to the active compound in the non-nanoencapsulated form and/or placebo. Nutritional nanocompounds also induced the following physiological and metabolic alterations: 1) improved antioxidant activity and reduced oxidative stress; 2) reduction in inflammation status; 3) maintenance of muscle integrity; 4) improvement in mitochondrial function and quality; 5) enhanced glucose levels during exercise; 6) higher muscle and hepatic glycogen levels; and 7) increased serum and liver iron content. However, all the reviewed studies were conducted in animals (mice and rats). In conclusion, nutritional nanocompounds are a promising approach to improving exercise performance. As the studies using nutritional nanocompounds were all conducted in animals, further studies in humans are necessary to better understand the application of nutritional nanocompounds in sport and exercise science.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685915","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}
E.M.S. Martins, Luís Cláudio Nascimento da Silva, M.S. Carmo
{"title":"Probiotics, prebiotics, and synbiotics in childhood diarrhea","authors":"E.M.S. Martins, Luís Cláudio Nascimento da Silva, M.S. Carmo","doi":"10.1590/1414-431X2024e13205","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13205","url":null,"abstract":"Abstract Acute diarrhea is the second leading cause of morbidity and mortality attributed to infections in children under five years of age worldwide, with 1.7 million annual estimated cases and more than 500,000 deaths. Although hydroelectrolytic replacement is the gold standard in treating diarrhea, it does not interfere with the restoration of the intestinal microbiota. Several studies have searched for an adequate alternative in restructuring intestinal homeostasis, finding that treatments based on probiotics, prebiotics, and synbiotics are effective, which made such treatments increasingly present in clinical practice by reducing illness duration with minimal side effects. However, there are still controversies regarding some unwanted reactions in patients. The diversity of strains and the peculiarities of the pathogens that cause diarrhea require further studies to develop effective protocols for prevention and treatment. Here, we provide a descriptive review of childhood diarrhea, emphasizing treatment with probiotics, prebiotics, and synbiotics.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683127","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}
Zhanhui Wang, B. Hu, Xiaoming Chen, Zheng Zhang, Lu Liu, Nan Li, Chun Liang
{"title":"Integrative analyses of genetic characteristics associated with skeletal endothelial cells","authors":"Zhanhui Wang, B. Hu, Xiaoming Chen, Zheng Zhang, Lu Liu, Nan Li, Chun Liang","doi":"10.1590/1414-431X2024e13339","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13339","url":null,"abstract":"Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140682493","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}
Xiaoyu Zheng, Xiaoqin Xie, Wei Wang, Liang Wang, Bing Tan
{"title":"Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis.","authors":"Xiaoyu Zheng, Xiaoqin Xie, Wei Wang, Liang Wang, Bing Tan","doi":"10.1590/1414-431X2024e13351","DOIUrl":"10.1590/1414-431X2024e13351","url":null,"abstract":"<p><p>The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}