Experimental Dermatology最新文献

{"title":"Delta opioid receptor expression correlates to skin ageing and melanin expression in Asian women","authors":"Paul L. Bigliardi,&nbsp;Sydney Lo,&nbsp;Elena Bigliardi,&nbsp;Yuri Dancik,&nbsp;Emmanuelle Leblanc-Noblesse,&nbsp;Mei Bigliardi-Qi","doi":"10.1111/exd.15096","DOIUrl":"https://doi.org/10.1111/exd.15096","url":null,"abstract":"<p>While the evidence for the implication of opioid receptors (OPr) in ageing is growing, there is, to our knowledge, no study focusing directly on changes in vivo cutaneous OPr expression with increasing age. We thus investigated OPr expression in 30 healthy female Asian volunteers in Southern China whose ages range from the early 20s to the early 60s. Excisional biopsies were taken from the sun-exposed extensor area of the lower arm and the photo-protected area of the upper inner arm. The thickness of the epidermal layers, melanin content, as well as expression of mu-opioid receptors (MOPr) and delta-opioid receptors (DOPr) were compared between different age ranges and photo-exposure status. Significant increased epidermal hypertrophy on the extensor surface was observed. There was significant reduction of DOPr in the epidermis with increasing age, independent of photo-ageing. The increase of melanin was significantly correlated with epidermal DOPr expression, not with MOPr expression. DOPr expression could thus serve as a marker for real biological ageing unaffected by chronic photo-exposure. Additionally, DOPr expression was inversely correlated with the deposition of melanin. Based on these results, we hypothesise that regulation of DOPr expression could be used to improve aged skin, including hyperpigmentation.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in mouse epidermal DNA methylation during development of squamous cell carcinoma in response to UVR","authors":"Olivia Luxford Meyer,&nbsp;Jeppe Dyrberg Andersen,&nbsp;Claus Børsting,&nbsp;Niels Morling,&nbsp;Mikkel Meyer Andersen,&nbsp;Hans Christian Wulf,&nbsp;Peter Alshede Philipsen,&nbsp;Catharina Margrethe Lerche","doi":"10.1111/exd.15123","DOIUrl":"https://doi.org/10.1111/exd.15123","url":null,"abstract":"<p>Squamous cell carcinoma (SCC) is a common skin cancer, often caused by exposure to ultraviolet radiation (UVR). Recent studies have shown that changes in DNA methylation play a crucial role in the development of cancers. However, methylation patterns of SCC are not well characterised. Identifying biomarkers for the risk of developing SCC could be helpful for early detection and diagnosis and can potentially improve treatment and prevention strategies. This study aimed to investigate methylation changes in the epidermis of mice exposed to UVR for 24 weeks. We examined the DNA methylation levels of 260 199 CpGs using the Illumina Infinium Mouse Methylation BeadChip and studied the epidermis of UVR-exposed and unexposed mice every 4 weeks for 24 weeks (<i>n</i> = 39). We identified CpGs with large differences in methylation levels (<i>β</i>-values) between UVR-exposed and unexposed mice. We also observed differences in the epigenetic age of these mice. We identified CpGs in <i>Rev</i>, <i>Ipmk</i>, <i>Rad51b</i>, <i>Fgfr2</i>, <i>Fgfr3</i> and <i>Ctnnb1</i> that may serve as potential biomarkers for SCC risk and could be helpful for the early detection and prevention of SCC. Further investigations are necessary to determine the biological functions and clinical significance of these CpGs.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering dermatological distinctions: Cornulin as a discriminant biomarker between basal cell carcinoma and squamous cell carcinoma detected through e-biopsy and machine learning","authors":"Edward Vitkin,&nbsp;Julia Wise,&nbsp;Ariel Berl,&nbsp;Ofir Shir-az,&nbsp;Vladimir Kravtsov,&nbsp;Zohar Yakhini,&nbsp;Avshalom Shalom,&nbsp;Alexander Golberg","doi":"10.1111/exd.15124","DOIUrl":"https://doi.org/10.1111/exd.15124","url":null,"abstract":"<p>Clinical misdiagnosis between cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) poses treatment challenges and carries risks of recurrence, metastases and increased morbidity and mortality. We aimed to identify discriminant proteins markers for cSCC and BCC using a minimally invasive proteome sampling method called e-biopsy, employing electroporation for non-thermal cell permeabilization and machine learning. E-biopsy facilitated ex vivo proteome extraction from 21 cSCC and 21 BCC pathologically validated human cancers. LC/MS/MS profiling of 126 proteomes was followed by machine learning analysis to identify proteins distinguishing cSCC from BCC. For identified panel validation, we used proteomes sampled by e-biopsy from unrelated 20 cSCC and 46 BCC human cancers, and differential expression analysis of published transcriptomics. Cornulin, the most commonly chosen discriminative biomarker by machine learning models, was also validated using fluorescent immunohistochemistry. One hundred and ninety-two proteomes sampled from one hundred eight patients were analysed. Machine learning-based approaches resulted in a set of 11 potential biomarker proteins that can be used to construct a patient classification model with 95.2% average cross-validation accuracy, BCC precision of 93.6 ± 14.5%, cSCC precision of 98.4 ± 7.2%, specificity of 97.7 ± 11.8% and sensitivity 92.7 ± 15.3%. Protein–protein interaction analysis revealed a novel interaction network connecting 10 of the 11 resulted proteins. Histological and transcriptomic validation confirmed cornulin as a discriminant marker significantly lower in cSCC than in BCC. E-biopsy combined with machine learning provides a novel approach to molecular sampling from skin for biomarker detection and differential expression analysis between cSCC and BCC.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A collagen biostimulator improves photoaging pigmentation","authors":"Jin Cheol Kim,&nbsp;Dong Chan Kim,&nbsp;Hyoung Soo Park,&nbsp;Suk Bae Seo,&nbsp;Hee Young Kang","doi":"10.1111/exd.15090","DOIUrl":"https://doi.org/10.1111/exd.15090","url":null,"abstract":"<p>Photoaging pigmentation conditions such as senile lentigo and melasma show epidermal melanogenic activity and dermal abnormalities, including collagen degradation. A dermal rejuvenation strategy with skin-lightening therapy directly acting on melanocytes is suggested for photoaging pigmentation. This study investigates whether collagen biostimulation can result in skin lightening of photoaging skin. A split-face clinical trial was conducted, involving 40 subjects with facial melasma and senile lentigo. Subjects received a poly-DL-lactic acid (PDLLA) treatment on one side of their face, whereas the contralateral side received a treatment of normal saline as a control. Assessments were scheduled every month after completing treatments for up to 3 months. Pigmentation was evaluated using the L* value as measured with a chromameter and by investigator global assessment scores (IGA). Subjects reported different outcomes in terms of overall skin quality, including pigmentation, wrinkles and elasticity. Skin biopsies were obtained before the treatment and 4 weeks after completing the treatment. Fontana-Masson, Masson-Trichrome and Verhoeff-van Gieson staining, and fibroblast-specific protein 1 (FSP1) immunostaining were conducted. The PDLLA treatment demonstrated significant improvements in the L* values and IGA scores from 8 weeks after the subject completed their treatments. These improvements were sustained over a 12-week assessment period. The subjects reported substantial reductions in both pigmentation and wrinkle severity and elasticity throughout the assessment period. Fontana-Masson staining showed a marked decrease in pigmentation upon a PDLLA injection compared to the baseline values. Increased immunogenicity of FSP1 and increases in collagen and elastic fibre staining were observed. This study demonstrated remarkable improvements in photoaging pigmentation along with collagen production with a collagen biostimulator. Thus, collagen biostimulators represent a promising therapeutic approach for addressing photoaging signs associated with melasma and senile lentigo. (ClinicalTrials.gov Identifier: NCT05913102).</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The novel prognostic marker SPOCK2 regulates tumour progression in melanoma","authors":"Ji Young Kang,&nbsp;Hyeijin Cho,&nbsp;Minchan Gil,&nbsp;Haeryung Lee,&nbsp;Soochul Park,&nbsp;Kyung Eun Kim","doi":"10.1111/exd.15092","DOIUrl":"10.1111/exd.15092","url":null,"abstract":"<p>Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that <i>SPOCK2</i> plays important roles in the progression of various human cancers; however, the role of <i>SPOCK2</i> in melanoma remains unknown. Therefore, this study investigated the roles of <i>SPOCK2</i> and the related mechanisms in melanoma progression. To evaluate the clinical significance of <i>SPOCK2</i> expression in patients with melanoma, we analysed the association between <i>SPOCK2</i> expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of <i>Spock2</i> in melanoma progression in vitro and in vivo, we knocked down <i>Spock2</i> in the B16F10 melanoma cell line. High <i>SPOCK2</i> levels were positively associated with good prognosis and long survival rate of patients with melanoma. <i>Spock2</i> knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, <i>Spock2</i> downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in <i>Spock2</i> knockdown cells. Therefore, <i>Spock2</i> could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, <i>Spock2</i> knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that <i>SPOCK2</i> plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the metabolic landscape of cutaneous melanoma: Insights from single-cell sequencing analysis and machine learning for prognostic assessment of lactate metabolism","authors":"Jiaheng Xie,&nbsp;Pengpeng Zhang,&nbsp;Chenfeng Ma,&nbsp;Qikai Tang,&nbsp;Xinxin Zhou,&nbsp;Xiaolong Xu,&nbsp;Min Zhang,&nbsp;Songyun Zhao,&nbsp;Liping Zhou,&nbsp;Min Qi","doi":"10.1111/exd.15119","DOIUrl":"10.1111/exd.15119","url":null,"abstract":"<p>This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the ‘AUCell’ package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein–protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between diabetes mellitus and atopic dermatitis","authors":"Dongyun Lei,&nbsp;Jiechen Zhang,&nbsp;Tingting Zhu,&nbsp;Litao Zhang,&nbsp;Mao-Qiang Man","doi":"10.1111/exd.15116","DOIUrl":"10.1111/exd.15116","url":null,"abstract":"<p>Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of macrophage migration inhibitory factor family and CD74 in the pathogenesis of melanoma","authors":"Keiji Tanese,&nbsp;Dai Ogata","doi":"10.1111/exd.15122","DOIUrl":"10.1111/exd.15122","url":null,"abstract":"<p>Melanoma is an aggressive tumour with poor prognosis that arises from the malignant transformation of melanocytes. Over the past few decades, intense research into the pathogenesis of melanoma has led to the development of BRAF and immune checkpoint inhibitors, including antibodies against programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which have shown clinically significant efficacy. However, some tumours do not respond to these therapies initially or become treatment resistant. Most melanoma tissues appear to possess biological characteristics that allow them to evade these treatments, and identifying these characteristics is one of the major challenges facing cancer researchers. One such characteristic that has recently gained attention is the role of macrophage migration inhibitory factor (MIF) and its receptor CD74. This review outlines the cellular and molecular functions of CD74, MIF and their family of proteins. We then review their roles in tumours based on previous reports, highlight their pathological significance in melanoma and discuss their potential as therapeutic targets.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging","authors":"Xiaozhen Peng,&nbsp;Yun Zhong,&nbsp;Rui Mao,&nbsp;Fanping He,&nbsp;Yufan Cheng,&nbsp;Mengting Chen,&nbsp;Lei Zhou,&nbsp;Hongfu Xie,&nbsp;Ji Li,&nbsp;Yiya Zhang","doi":"10.1111/exd.15120","DOIUrl":"10.1111/exd.15120","url":null,"abstract":"<p>Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H₂O₂-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible role of β-hydroxybutyrate in inducing inflammation in alopecia areata","authors":"Jung-Min Shin,&nbsp;Seungjin Son,&nbsp;Kyung Eun Jung,&nbsp;Chang Deok Kim,&nbsp;Young Lee","doi":"10.1111/exd.15117","DOIUrl":"10.1111/exd.15117","url":null,"abstract":"<p>Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non-scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti-inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta-hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}