JID innovations : skin science from molecules to population health最新文献

{"title":"Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study","authors":"Caroline J. Stone ,&nbsp;Geeta Ahuja ,&nbsp;Lais Lopes Almeida Gomes ,&nbsp;Joy Poroye ,&nbsp;Daniella Forman Faden ,&nbsp;Lillian Xie ,&nbsp;Rui Feng ,&nbsp;Barbara White ,&nbsp;Victoria P. Werth","doi":"10.1016/j.xjidi.2024.100311","DOIUrl":"10.1016/j.xjidi.2024.100311","url":null,"abstract":"<div><h3>Background</h3><div>Dermatomyositis (DM) is a rare autoimmune condition involving skin manifestations often resistant to standard treatments such as immunosuppressants and antimalarials. Biopsies show elevated inflammatory cells such as CD4+ T cells, dendritic cells, and cytokines. Lenabasum, a selective cannabinoid receptor 2 agonist, has demonstrated significant benefits in treating autoimmune skin diseases. Objectives: This study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug’s long-term effectiveness and assessing disease manifestation recurrence. Methods: The phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE as well as on control subjects with DM who did not participate in the lenabasum trial. Results: By week 68, patients exhibited reductions in Cutaneous Dermatomyositis Disease Area and Severity Index activity score (−21.8), Patient Skin Activity Visual Analog Scale (−3.0), and Skindex-29 (−28.0) from OLE baseline. After OLE, 58.3% maintained stable disease, significantly higher than controls (<em>P</em> = .035), with 41.7% not experiencing flares compared with 91.6% of controls. In addition, 50% of patients reported sustained pruritus improvement. Conclusions: Data from OLE and subsequent follow-up periods demonstrate lenabasum’s efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM. Trial Registration: This study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span>, with <span><span>NCT02466243</span><svg><path></path></svg></span>. Study registration was first submitted on June 2, 2015.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100311"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358428","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":"Type 2 Cytokine–Dependent Skin Barrier Regulation in Personalized 2-Dimensional and 3-Dimensional Skin Models of Atopic Dermatitis: A Pilot Study","authors":"Hila Emmert ,&nbsp;Franziska Rademacher ,&nbsp;Matthias Hübenthal ,&nbsp;Regine Gläser ,&nbsp;Hanne Norsgaard ,&nbsp;Stephan Weidinger ,&nbsp;Jürgen Harder","doi":"10.1016/j.xjidi.2024.100309","DOIUrl":"10.1016/j.xjidi.2024.100309","url":null,"abstract":"<div><div>Keratinocytes (KCs) from healthy donors stimulated with type 2 cytokines are often used to experimentally study atopic dermatitis (AD) inflammatory responses. Owing to potential intrinsic alterations, it seems favorable to use KCs from patients with AD. KCs isolated from hair follicles offer a noninvasive approach to investigate AD-derived KCs. To evaluate whether such AD-derived KCs are suitable to mimic AD inflammatory responses, we compared hair follicle–derived KCs from healthy donors with those from patients with AD in a type 2 cytokine environment. Stimulation of AD-derived KCs with IL-4 and IL-13 induced higher expression changes of AD-associated markers than that of healthy KCs. The combination of IL-4 and IL-13 generally induced highest expression changes, but IL-13 alone also induced significant changes of AD-specific markers. Similar to the 2-dimensional cultures, IL-4/IL-13 stimulation of 3-dimensional skin models generated with AD-derived KCs modulated the expression of several AD-relevant factors. Whole-transcriptome analysis revealed that IL-4 and IL-13 acted similarly on these 3-dimensional skin models. Histologically, IL-13 alone and in combination with IL-4 increased epidermal spongiosis, a histological hallmark of AD skin. Taken together, our pilot study suggests that hair follicle–derived KCs from patients with AD represent a useful model system to study AD-related inflammation in a personalized in vitro model.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100309"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323252","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":"Keratinocyte Integrin α3β1 Promotes Efficient Healing of Wound Epidermis","authors":"Sanjana Dhulipalla ,&nbsp;Giesse Albeche Duarte ,&nbsp;Lei Wu ,&nbsp;Mathieu R. DiPersio ,&nbsp;John M. Lamar ,&nbsp;C. Michael DiPersio ,&nbsp;Whitney M. Longmate","doi":"10.1016/j.xjidi.2024.100310","DOIUrl":"10.1016/j.xjidi.2024.100310","url":null,"abstract":"<div><div>To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14^Cre-ERT::α3^flx/flx mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed <em>Itga3</em> alleles (α3^flx/flx) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen. This allows for the elucidation of α3β1-dependent wound healing in adult skin, free from compensatory mechanisms that may occur after embryonic deletion of epidermal α3β1 in the widely used constitutive α3β1-knockout mouse. We found that re-epithelializing wound gaps are larger in inducible α3 epidermal knockout mice than in control mice, indicating delayed healing, and that epidermal integrin α3β1 promotes healing of wounds, at least in part by enhancing keratinocyte proliferation. This work provides essential rationale for future studies to investigate integrin α3β1 as a therapeutic target to facilitate wound healing.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100310"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318704","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":"Treatment of Bullous Pemphigoid with Avdoralimab: Multicenter, Randomized, Open-Labeled Phase 2 Study","authors":"Thierry Passeron ,&nbsp;Eric Fontas ,&nbsp;Thierry Boye ,&nbsp;Marie-Aleth Richard ,&nbsp;Emmanuel Delaporte ,&nbsp;Olivier Dereure","doi":"10.1016/j.xjidi.2024.100307","DOIUrl":"10.1016/j.xjidi.2024.100307","url":null,"abstract":"<div><p>Rationale: Experimental data support the role for C5a–C5aR1 axis activation in bullous pemphigoid. We assessed the efficacy and safety of avdoralimab, a specific anti-C5aR1 mAb, for treating bullous pemphigoid. Methods: We conducted a phase 2 open-labeled randomized multicenter study. Patients with proven bullous pemphigoid were randomized (1:1) to receive superpotent topical steroids alone (group A) or with avdoralimab (group B). All patients received 0.05% clobetasol propionate cream until 15 days after the healing of lesions. Patients in group B additionally received 3 injections of avdoralimab every week for 12 weeks. The main criterion of evaluation was the proportion of patients with initial control of disease activity still in complete clinical remission at 3 months with no relapse during the study period. Results: Fifteen patients were randomized: 7 to group A and 8 to group B. Two patients in group A and in group B achieved control of disease activity at week 4. Only 1 patient was still in complete clinical remission at week 12 in group B, and none was in group A. No adverse event related to the treatment was reported. Conclusions: This proof-of-concept pilot study did not show preliminary signal of additional avdoralimab efficiency compared with superpotent topical steroids alone.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100307"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000547/pdfft?md5=cf74e6a8b3d32a0c392c744888692cbd&pid=1-s2.0-S2667026724000547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173031","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":"Analysis of Circadian Clock Gene Expression in Human Skin Explants","authors":"William Cvammen ,&nbsp;Michael G. Kemp","doi":"10.1016/j.xjidi.2024.100308","DOIUrl":"10.1016/j.xjidi.2024.100308","url":null,"abstract":"<div><p>Many aspects of skin biochemistry and physiology are known to vary over the course of the 24-hour day. Traditional approaches to study circadian rhythms in the skin have employed rodents or human subjects, which limit the experimental variables that can be studied. Although explants derived from discarded surgical skin are a commonly used model in the skin biology field, circadian rhythms have yet to be examined ex vivo. In this study, using human panniculectomy skin, we used RT-qPCR to monitor the epidermal expression of 4 core circadian clock genes over the course of 1 day ex vivo. Although significant interindividual variability in overall gene expression profiles was observed, robust circadian oscillations were observed in many of the genes and individual explants. Comparison of our gene expression data with microarray data from 2 previous human-subject studies involving primarily young adult White males revealed both similarities and differences, including greater distribution in the time of day of peak expression in the skin explants. This increased variability appears to be due in part to the increased age and altered sex distribution of the donated skin. Nonetheless, our results indicate that skin explants offer an additional experimental system for studying circadian skin biology.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100308"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000559/pdfft?md5=0fc82d246813430bc50adaf134a4928d&pid=1-s2.0-S2667026724000559-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229783","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 Tensioned Human Skin Explant Model Used for Preliminary Assessment of Chemexfoliant-Stimulated Bioeffects","authors":"Michael J. Conneely ,&nbsp;Jin Namkoong ,&nbsp;Francis Allison ,&nbsp;S. Kyoko Hirata Tsutsumi ,&nbsp;Dominic Grussu ,&nbsp;Ryan Willis ,&nbsp;Kyle Henderson ,&nbsp;Paul A. Campbell ,&nbsp;Melissa Moy ,&nbsp;Ewelina Lesniak ,&nbsp;Joanna Wu ,&nbsp;Robyn P. Hickerson","doi":"10.1016/j.xjidi.2024.100305","DOIUrl":"10.1016/j.xjidi.2024.100305","url":null,"abstract":"<div><div>A tensioned ex vivo full-thickness human skin explant platform was used to assess the bioeffects arising from application of several commercial chemexfoliation agents. Although such treatments are well-established, and improved understanding of the underlying mechanistic processes continues to emerge, research into the optimum treatments for specific skin types/conditions is still needed for enhanced efficacy while minimizing recovery time. The 3 commercial chemexfoliation agents employed all contained trichloroacetic acid at well-defined concentrations (6, 10, and 20%) and were applied to the explants’ stratum corneum. Subsequently, measurements of dermal remodeling factors (COL1A1, ELN, HAS2, HAS3, and procollagen type I) and inflammatory marker (IL-1b) were undertaken using qPCR and immunofluorescent analyses. Statistical analysis of these data facilitated the establishment of benchmarking biological responses to these trichloroacetic acid–containing agents against untreated controls. The performance of an innovative trichloroacetic acid–free chemexfoliation agent was then measured and, upon comparison with the previous benchmarking data, indicated that dermal remodeling factors could be upregulated in fashion comparable with that of the trichloroacetic acid–containing agents but with significant suppression of inflammatory response. Our measurements thus underscore the promise of the tensioned explant over prolonged study periods and also that potentially valuable insights to guide preclinical strategies may be forthcoming from the protocol developed.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100305"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358495","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":"Differential Expression Analysis of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Proteomic Profiles Sampled with Electroporation-Based Biopsy","authors":"Edward Vitkin ,&nbsp;Julia Wise ,&nbsp;Ariel Berl ,&nbsp;Ofir Shir-az ,&nbsp;Batel Gabay ,&nbsp;Amrita Singh ,&nbsp;Vladimir Kravtsov ,&nbsp;Zohar Yakhini ,&nbsp;Avshalom Shalom ,&nbsp;Alexander Golberg","doi":"10.1016/j.xjidi.2024.100304","DOIUrl":"10.1016/j.xjidi.2024.100304","url":null,"abstract":"<div><div>Clinical misdiagnosis between cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) affects treatment plans. We report a tissue sampling approach with molecular biopsy using electroporation. This method, coined electroporation-based biopsy (e-biopsy), enables nondestructive nonthermal permeabilization of cells in the skin for vacuum-assisted extraction of biomolecules. We used e-biopsy for ex vivo proteome extraction from 3 locations per patient in 21 cSCC, 20 BCC, and 7 actinic keratosis human skin samples. Using liquid chromatography with tandem mass spectrometry, we identified 5966 proteins observed with nonzero intensity in at least 1 sample. The intrapatient Pearson correlation of 0.888 ± 0.065 for patients with BCC, 0.858 ± 0.077 for patients with cSCC, and 0.876 ± 0.116 for those with solar actinic keratosis indicates high consistency of the e-biopsy sampling. The mass spectra presented significantly different proteome profiles for cSCC, BCC, and solar actinic keratosis, with several hundreds of proteins differentially expressed. Notably, our study showed that proteomes sampled with e-biopsy from cSCC and BCC lesions are different and that proteins of <em>CRNN</em>, <em>SULT1E1</em>, and <em>ITPK1</em> genes are significantly overexpressed in BCC in comparison with those in cSCC. Our results provide evidence that the e-biopsy approach could potentially be used as a tool to support cutaneous lesions classification with molecular pathology.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446133","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":"Update on the Pathogenesis of Keloid Formation","authors":"David I. Latoni ,&nbsp;Danica C. McDaniel ,&nbsp;Hensin Tsao ,&nbsp;Sandy S. Tsao","doi":"10.1016/j.xjidi.2024.100299","DOIUrl":"10.1016/j.xjidi.2024.100299","url":null,"abstract":"<div><p>Keloids are abnormal skin growths occurring in a significant portion of the global population. Despite their pervasiveness, the underlying pathophysiology of this scarring process is yet to be fully understood. In this review article, we delve into the current literature on the pathophysiological mechanisms of keloids. We take a top-down approach, first looking at host factors such as genetics and endocrine factors and then taking a more granular approach describing specific control factors such as germline keloid predisposition variants, epigenetics and transcriptomics, inflammatory and immune dysregulation, and the role of profibrotic and angiogenic cell signaling pathways. We then discuss current knowledge gaps, propose further research avenues, and explore potential future treatment options considering our increased understanding of keloid pathogenesis.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000468/pdfft?md5=d8dbe4af64f3a3426966133bf7f489bb&pid=1-s2.0-S2667026724000468-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848383","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":"Observations from Statistical Review Editors: A Commentary","authors":"Matt Spick ,&nbsp;Jan Higgins ,&nbsp;Cynthia L. Green ,&nbsp;Roland Matsouaka ,&nbsp;Daniel B. Shin ,&nbsp;Russell P. Hall III ,&nbsp;Nophar Geifman","doi":"10.1016/j.xjidi.2024.100302","DOIUrl":"10.1016/j.xjidi.2024.100302","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100302"},"PeriodicalIF":0.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000493/pdfft?md5=97c3630d4e746cb820f0b1b9e037f9df&pid=1-s2.0-S2667026724000493-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839868","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":"Noninvasive Technologies for the Diagnosis of Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis","authors":"Carina Nogueira Garcia ,&nbsp;Christoph Wies ,&nbsp;Katja Hauser ,&nbsp;Titus J. Brinker","doi":"10.1016/j.xjidi.2024.100303","DOIUrl":"10.1016/j.xjidi.2024.100303","url":null,"abstract":"<div><p>Early cutaneous squamous cell carcinoma (cSCC) diagnosis is essential to initiate adequate targeted treatment. Noninvasive diagnostic technologies could overcome the need of multiple biopsies and reduce tumor recurrence. To assess performance of noninvasive technologies for cSCC diagnostics, 947 relevant records were identified through a systematic literature search. Among the 15 selected studies within this systematic review, 7 were included in the meta-analysis, comprising of 1144 patients, 224 cSCC lesions, and 1729 clinical diagnoses. Overall, the sensitivity values are 92% (95% confidence interval [CI] = 86.6–96.4%) for high-frequency ultrasound, 75% (95% CI = 65.7–86.2%) for optical coherence tomography, and 63% (95% CI = 51.3–69.1%) for reflectance confocal microscopy. The overall specificity values are 88% (95% CI = 82.7–92.5%), 95% (95% CI = 92.7–97.3%), and 96% (95% CI = 94.8–97.4%), respectively. Physician’s expertise is key for high diagnostic performance of investigated devices. This can be justified by the provision of additional tissue information, which requires physician interpretation, despite insufficient standardized diagnostic criteria. Furthermore, few deep learning studies were identified. Thus, integration of deep learning into the investigated devices is a potential investigating field in cSCC diagnosis.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400050X/pdfft?md5=e2d200dbc371629064d1b3b62bc3f822&pid=1-s2.0-S266702672400050X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843941","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}