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

{"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}

{"title":"Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses","authors":"Maxime Sintès ,&nbsp;Petra Kovjenic ,&nbsp;Liasmine Haine (Hablal) ,&nbsp;Kevin Serror ,&nbsp;Mohamed Beladjine ,&nbsp;Véronique Parietti (Montcuquet) ,&nbsp;Marine Delagrange ,&nbsp;Bertrand Ducos ,&nbsp;Jean-David Bouaziz ,&nbsp;David Boccara ,&nbsp;Maurice Mimoun ,&nbsp;Armand Bensussan ,&nbsp;Martine Bagot ,&nbsp;Nicolas Huang ,&nbsp;Laurence Michel","doi":"10.1016/j.xjidi.2024.100273","DOIUrl":"10.1016/j.xjidi.2024.100273","url":null,"abstract":"<div><p>Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A– or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B–coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000201/pdfft?md5=5840a5e889e492fcc62f06d177b01f94&pid=1-s2.0-S2667026724000201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403255","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":"Image Quality Assessment Using Convolutional Neural Network in Clinical Skin Images","authors":"Hyeon Ki Jeong ,&nbsp;Christine Park ,&nbsp;Simon W. Jiang ,&nbsp;Matilda Nicholas ,&nbsp;Suephy Chen ,&nbsp;Ricardo Henao ,&nbsp;Meenal Kheterpal","doi":"10.1016/j.xjidi.2024.100285","DOIUrl":"https://doi.org/10.1016/j.xjidi.2024.100285","url":null,"abstract":"<div><p>The image quality received for clinical evaluation is often suboptimal. The goal is to develop an image quality analysis tool to assess patient- and primary care physician–derived images using deep learning model. Dataset included patient- and primary care physician–derived images from August 21, 2018 to June 30, 2022 with 4 unique quality labels. VGG16 model was fine tuned with input data, and optimal threshold was determined by Youden’s index. Ordinal labels were transformed to binary labels using a majority vote because model distinguishes between 2 categories (good vs bad). At a threshold of 0.587, area under the curve for the test set was 0.885 (95% confidence interval = 0.838–0.933); sensitivity, specificity, positive predictive value, and negative predictive value were 0.829, 0.784, 0.906, and 0.645, respectively. Independent validation of 300 additional images (from patients and primary care physicians) demonstrated area under the curve of 0.864 (95% confidence interval = 0.818–0.909) and area under the curve of 0.902 (95% confidence interval = 0.85–0.95), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 300 images were 0.827, 0.800, 0.959, and 0.450, respectively. We demonstrate a practical approach improving the image quality for clinical workflow. Although users may have to capture additional images, this is offset by the improved workload and efficiency for clinical teams.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000328/pdfft?md5=3096c45a51c4538d05749966b424a85b&pid=1-s2.0-S2667026724000328-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141486565","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":"Characterization of Reconstructed Human Epidermis in a Chemically-Defined, Animal Origin-Free Cell Culture","authors":"Julia Bajsert ,&nbsp;Valérie De Glas ,&nbsp;Emilie Faway ,&nbsp;Catherine Lambert de Rouvroit ,&nbsp;Miguel Pérez-Aso ,&nbsp;Paul W. Cook ,&nbsp;Yves Poumay","doi":"10.1016/j.xjidi.2024.100298","DOIUrl":"10.1016/j.xjidi.2024.100298","url":null,"abstract":"<div><p>The Reconstructed Human Epidermis (RHE) model derived from epidermal keratinocytes offers an ethical and scientific alternative to animal experimentation, particularly in cutaneous toxicology and dermatological research, where the elimination of animal cruelty is of paramount importance. Thus, we compared commercially available chemically defined animal origin-free (cdAOF) supplements, designed for regenerative medicine, to the widely utilized supplement (human keratinocyte growth supplement), which contains growth factors and bovine pituitary extract. Herein we present the extended characterization of RHE derived from newborn, adult, and immortalized N/telomerase reverse transcriptase keratinocytes under cdAOF conditions. Culture of RHE in the cdAOF media produced histological features that were similar to that produced using human keratinocyte growth supplement, with the exception that the basal keratinocytes were less cylindrical. Additionally, immunolocalization of involucrin in the basal layer and increased mRNA expression of several inflammatory-proliferative markers were observed under cdAOF conditions. In RHEs cultured in cdAOF media, expression and immunolocalization of other expected markers of keratinization were similar, while monitoring of barrier function (transepithelial electrical resistance) revealed results that were statistically equal to, or lower than those observed in RHE cultured in human keratinocyte growth supplement. Our study indicates that reconstruction of RHE was accomplished under cdAOF culture conditions and that further refinement could promote an expanded use beyond regenerative medicine, for in vitro toxicology applications.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000456/pdfft?md5=727f6880ad1ae8364d70328a593b5c15&pid=1-s2.0-S2667026724000456-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951884","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}