Journal of dermatological science最新文献

英文中文

Mechanical stiffness promotes skin fibrosis through FAPα-AKT signaling pathway 机械硬度通过 FAPα-AKT 信号通路促进皮肤纤维化

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/j.jdermsci.2023.12.004

Jiahao He , Bin Fang , Shengzhou Shan , Qingfeng Li

Background

Myofibroblasts contribute to the excessive production, remodeling and cross-linking of the extracellular matrix that characterizes the progression of skin fibrosis. An important insight into the pathogenesis of tissue fibrosis has been the discovery that increased matrix stiffness during fibrosis progression is involved in myofibroblast activation. However, mechanistic basis for this phenomenon remains elusive.

Objective

To explore the role of fibroblast activation protein-α (FAPα) in mechanical stiffness-induced skin fibrosis progression.

Methods

RNA-seq was performed to compare differential genes of mouse dermal fibroblasts (MDFs) grown on low or high stiffness plates. This process identified FAPα, which is a membrane protein usually overexpressed in activated fibroblasts, as a suitable candidate. In vitro assay, we investigate the role of FAPα in mechanical stiffness-induced MDFs activation and downstream pathway. By establishing mouse skin fibrosis model and intradermally administrating FAPα adeno-associated virus (AAV) or a selective Fap inhibitor FAPi, we explore the role of FAPα in skin fibrosis in vivo.

Results

We show that FAPα, a membrane protein highly expressed in myofibroblasts of skin fibrotic tissues, is regulated by increased matrix stiffness. Genetic deletion or pharmacological inhibition of FAPα significantly inhibits mechanical stiffness-induced activation of myofibroblasts in vitro. Mechanistically, FAPα promotes myofibroblast activation by stimulating the PI3K-Akt pathway. Furthermore, we showed that administration of the inhibitor FAPi or FAPα targeted knockdown ameliorated the progression of skin fibrosis.

Conclusion

Taken together, we identify FAPα as an important driver of mechanical stiffness-induced skin fibrosis and a potential therapeutic target for the treatment of skin fibrosis.

背景肌成纤维细胞促成了细胞外基质的过度产生、重塑和交联，这是皮肤纤维化进展的特征。对组织纤维化发病机制的一个重要发现是，纤维化进展过程中基质硬度的增加与肌成纤维细胞的活化有关。目的探索成纤维细胞活化蛋白-α（FAPα）在机械硬度诱导的皮肤纤维化进展中的作用。方法对生长在低硬度或高硬度平板上的小鼠真皮成纤维细胞（MDFs）的不同基因进行了RNA-seq比较。这一过程确定了 FAPα（一种通常在活化成纤维细胞中过度表达的膜蛋白）为合适的候选基因。在体外试验中，我们研究了 FAPα 在机械刚度诱导的 MDFs 激活中的作用及其下游途径。通过建立小鼠皮肤纤维化模型和皮内注射 FAPα 腺相关病毒（AAV）或选择性 Fap 抑制剂 FAPi，我们探讨了 FAPα 在体内皮肤纤维化中的作用。基因缺失或药物抑制 FAPα 能显著抑制机械硬度诱导的体外肌成纤维细胞活化。从机制上讲，FAPα通过刺激PI3K-Akt通路促进肌成纤维细胞的活化。结论综上所述，我们发现 FAPα 是机械僵化诱导的皮肤纤维化的重要驱动因素，也是治疗皮肤纤维化的潜在治疗靶点。

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引用次数: 0

Resident memory T cell contributes to the phenotype of inflammatory vitiligo 驻留记忆 T 细胞对炎性白癜风的表型有影响

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/j.jdermsci.2024.01.002

Ken Okamura , Takanobu Kabasawa , Toru Saito , Yosuke Arai , Mitsuru Futakuchi , Tamio Suzuki

引用次数: 0

Exosomes containing miR-1469 regulate natural killer cells by targeting CD122 in non-segmental vitiligo 含有 miR-1469 的外泌体通过靶向 CD122 调控非节段性白癜风患者的自然杀伤细胞

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/j.jdermsci.2023.12.006

Yujia Wei , Ting Zhou , Ronghua Pan , Xiaoqi Nie , Zhong Liu , Zeqi Shi , Ying Zeng , Ri Zhang , Yunhua Deng , Dong Li

Background

Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet.

Objective

To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV.

Methods

High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques.

Results

MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells.

Conclusion

Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV.

背景血浆外泌体microRNA（miRNA）已被用作各种疾病的潜在生物标记物，并已被研究是否可能参与了白癜风的发病机制。方法通过高通量测序确定非节段性白癜风（NSV）患者血浆外泌体miRNA的表达谱。结果MiR-1469被确定为候选生物标志物，它在NSV患者循环外泌体中的表达显著增加。循环外泌体可被NK细胞内化，并通过传递miR-1469提高NK细胞的增殖活力和IFN-γ分泌能力。进一步研究发现，miR-1469 的预测靶标 CD122 的上调可部分逆转 miR-1469 对自然杀伤细胞的影响。外泌体 miR-1469 可能是疾病活动性的生物标志物，可作为治疗药物靶点，对抗 NSV 患者的先天性免疫。本研究为了解外泌体miRNA在NSV中的作用提供了新的视角，并提出了NK细胞miR-1469-CD122-IFN-γ通路是NSV发病机制的基础。

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引用次数: 0

Transcriptome network analysis of inflammation and fibrosis in keloids 瘢痕疙瘩炎症和纤维化的转录组网络分析

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/j.jdermsci.2023.12.007

Jiayi Mao , Lu Chen , Shutong Qian , Yuhuan Wang , Binfan Zhao , Qiuyu Zhao , Bolun Lu , Xiyuan Mao , Peisong Zhai , Yuguang Zhang , Liucheng Zhang , Xiaoming Sun

Background

Keloid (KL) is a common benign skin tumor. KL is typically characterized by significant fibrosis and an intensive inflammatory response. Therefore, a comprehensive understanding of the interactions between cellular inflammation and fibrotic cells is essential to elucidate the mechanisms driving the progression of KL and to develop therapeutics.

Objective

Investigate the transcriptome landscape of inflammation and fibrosis in keloid scars.

Methods

In this paper, we performed transcriptome sequencing and microRNA (miRNA) sequencing on unselected live cells from six human keloid tissues and normal skin tissues to elucidate a comprehensive transcriptome landscape. In addition, we used single-cell RNA sequencing (scRNA-seq) analysis to analyze intercellular communication networks and enrich fibroblast populations in two additional keloid and normal skin samples to study fibroblast diversity.

Results

By RNA sequencing and a miRNA-mRNA-PPI network analysis, we identified miR-615–5p and miR-122b-3p as possible miRNAs associated with keloids, as they differed most significantly in keloids. Similarly, COL3A1, COL1A2, THBS2, TNC, IGTA, THBS4, TGFB3 as genes with significant differences in keloid may be associated with keloid development. Using single-cell RNA sequencing data from 24,086 cells collected from normal or keloid, we report reconstructed intercellular signaling network analysis and aggregation to modules associated with specific cell subpopulations at the cellular level for keloid alterations.

Conclusions

Our multitranscriptomic dataset delineates inflammatory and fibro heterogeneity of human keloids, underlining the importance of intercellular crosstalk between inflammatory cells and fibro cells and revealing potential therapeutic targets.

背景瘢痕疙瘩（KL）是一种常见的良性皮肤肿瘤。瘢痕疙瘩的典型特征是明显的纤维化和密集的炎症反应。因此，全面了解细胞炎症和纤维化细胞之间的相互作用对于阐明KL进展的驱动机制和开发治疗方法至关重要。方法本文中，我们对来自6个人类瘢痕疙瘩组织和正常皮肤组织的未选择活细胞进行了转录组测序和microRNA（miRNA）测序，以阐明全面的转录组图谱。结果通过RNA测序和miRNA-mRNA-PPI网络分析，我们发现miR-615-5p和miR-122b-3p可能与瘢痕疙瘩有关，因为它们在瘢痕疙瘩中差异最大。同样，在瘢痕疙瘩中差异显著的 COL3A1、COL1A2、THBS2、TNC、IGTA、THBS4、TGFB3 基因也可能与瘢痕疙瘩的发生有关。结论我们的多转录组数据集描述了人类瘢痕疙瘩的炎症和纤维异质性，强调了炎症细胞和纤维细胞之间细胞间串联的重要性，并揭示了潜在的治疗靶点。

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引用次数: 0

The novel adiponectin receptor agonist APN5N alleviates sensitive skin by upregulating adiponectin expression 新型脂肪直通素受体激动剂 APN5N 通过上调脂肪直通素的表达缓解敏感性皮肤

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/j.jdermsci.2023.12.002

Eun Ju Kim , Qing-Ling Quan , Soo Ick Cho , Yeon Kyung Kim , Dong Hun Lee , Jin Ho Chung

引用次数: 0

Editor's Choice 编辑推荐

IF 4.6

Journal of dermatological science

Pub Date : 2024-02-01 DOI: 10.1016/S0923-1811(24)00024-0

引用次数: 0

Cross-sectional nationwide epidemiologic survey on quality of life and treatment efficacy in Japanese patients with congenital ichthyoses 日本先天性鱼鳞病患者生活质量及治疗效果的横断面全国流行病学调查。

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.002

Yuika Suzuki , Kana Tanahashi , Chiaki Terashima-Murase , Takuya Takeichi , Yumiko Kobayashi , Fumie Kinoshita , Masashi Akiyama

Background

Congenital ichthyoses sometimes present with severe skin symptoms that significantly affect the patient’s quality of life (QOL). Symptomatic treatments are the mainstay therapies, and their efficacy is limited and inadequate.

Objective

To assess the disease severity and QOL in patients with congenital ichthyoses, and to investigate the effectiveness of current treatments.

Methods

We conducted a questionnaire-based Japan-wide epidemiological survey of patients with congenital ichthyosis who received medical care from 1 January 2016–31 December 2020. Effectiveness of past and current treatments was assessed. The outcomes were the physician’s assessment, disease severity assessed using the clinical ichthyosis score (CIS), and the disease burden estimated using the Dermatology Life Quality Index (DLQI), the Children’s Dermatology Life Quality Index (CDLQI), and the Infants’ Dermatitis Quality of Life Index.

Results

One hundred patients with 14 ichthyosis subtypes from 47 institutes were included in the final analysis. The CDLQI score showed a positive correlation with CIS (rs = 0.59, p = 0.004), while the DLQI score showed no significant correlation (rs = 0.13, p = 0.33). All existing medications were effective for many patients. Etretinate improved QOL and reduced CIS, but side effects including bone growth retardation were reported. Decreased treatment willingness was observed in patients with very low and very high CIS.

Conclusion

QOL scores were found to correlate with CIS in children, but not in adults. Considering the adverse events, it is speculated that etretinate is not indicated for children with mild cases. Petrolatum was the most commonly used medication, even in patients who were reluctant to receive treatment.

背景:先天性鱼鳞病有时会出现严重的皮肤症状，严重影响患者的生活质量。对症治疗是主要的治疗方法，但其疗效有限且不足。目的:评价先天性鱼鳞病患者的病情严重程度和生活质量，探讨目前治疗的效果。方法:对2016年1月1日至2020年12月31日期间接受治疗的先天性鱼鳞病患者进行全日本流行病学问卷调查。评估过去和目前治疗的有效性。结果是医生的评估，使用临床鱼鳞病评分(CIS)评估疾病严重程度，以及使用皮肤病生活质量指数(DLQI)，儿童皮肤病生活质量指数(CDLQI)和婴儿皮炎生活质量指数估计疾病负担。结果:最终纳入47个研究所的14种鱼鳞病亚型100例患者。CDLQI评分与CIS呈正相关(rs = 0.59, p = 0.004)， DLQI评分与CIS无显著相关(rs = 0.13, p = 0.33)。所有现有的药物对许多病人都有效。异维甲酸改善了患者的生活质量，降低了CIS，但副作用包括骨生长迟缓。在非常低和非常高的CIS患者中观察到治疗意愿降低。结论:儿童的生活质量评分与CIS有相关性，成人无相关性。考虑到不良事件，推测依替坦不适用于轻度患儿。凡士林是最常用的药物，即使对不愿接受治疗的患者也是如此。

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引用次数: 0

EDA-A2 increases lipid production in EDA2R-expressing human sebocytes EDA-A2增加表达eda2r的人脂质细胞的脂质生成。

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.11.005

Mi Hee Kwack, Ons Ben Hamida, Weon Ju Lee, Moon Kyu Kim

引用次数: 0

Comparison of skin barrier abnormalities and epidermal ceramide profiles among three ω-O-acylceramide synthesis-deficient mouse strains 比较三种ω-O-甘油酰胺合成缺陷小鼠品系的皮肤屏障异常和表皮神经酰胺特征

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.12.003

Yuta Yamamoto, Takayuki Sassa, Akio Kihara

Background

The epidermis contains many structurally diverse ceramides, which form the skin permeability barrier (skin barrier). Mutations in genes involved in the synthesis of ω-O-acylceramides (acylceramides) and protein-bound ceramides cause ichthyosis.

Objective

We aimed to elucidate the relationship between the degree of skin barrier impairment and changes in epidermal ceramide profiles caused by mutations in acylceramide synthesis genes.

Methods

Knockout (KO) mice of three genes—fatty acid (FA) ω-hydroxylase Cyp4f39 (human CYP4F22 ortholog), FA elongase Elovl1, and acyl-CoA synthetase Fatp4—were subjected to transepidermal water loss measurement, toluidine blue staining, and epidermal ceramide profiling via liquid chromatography coupled with tandem mass spectrometry.

Results

Transepidermal water loss was highest in Cyp4f39 KO mice, followed by Elovl1 KO and Fatp4 KO mice, and Cyp4f39 KO mice also showed the strongest degree of toluidine blue staining. In Cyp4f39 KO, Elovl1 KO, and Fatp4 KO mice, acylceramide levels were 0.6%, 1.6%, and 12%, respectively, of those in wild-type mice. Protein-bound ceramide levels were 0.2%, 30%, and 33%, respectively, of those in wild-type mice. We also observed a near-complete absence of ω-hydroxy ceramides in Cyp4f39 KO mice, reduced total ceramide levels and shortened FA moieties in Elovl1 KO mice, and increased hydroxylated ceramide levels and slightly shortened FA moieties in Fatp4 KO mice.

Conclusions

The degree of reduction in protein-bound ceramide levels is probably related to the severity of skin barrier defects in these three strains. However, reduced acylceramide levels and other changes in ceramide composition unique to each KO strain are also involved.

背景表皮中含有许多结构各异的神经酰胺，它们构成了皮肤的通透性屏障（皮肤屏障）。参与合成ω-O-酰基甘油酰胺（酰基甘油酰胺）和蛋白结合神经酰胺的基因发生突变会导致鱼鳞病。目的我们旨在阐明皮肤屏障受损程度与酰基甘油酰胺合成基因突变导致的表皮神经酰胺谱变化之间的关系。方法对脂肪酸（FA）ω-羟化酶 Cyp4f39（人类 CYP4F22 同源物）、FA 延长酶 Elovl1 和酰基-CoA 合成酶 Fatp4 这三个基因的基因敲除（KO）小鼠进行经表皮失水测量、甲苯胺蓝染色和液相色谱-串联质谱表皮神经酰胺谱分析。结果 Cyp4f39 KO小鼠的经表皮失水率最高，其次是Elovl1 KO和Fatp4 KO小鼠，Cyp4f39 KO小鼠的甲苯胺蓝染色程度也最强。在 Cyp4f39 KO、Elovl1 KO 和 Fatp4 KO 小鼠中，酰基神经酰胺水平分别是野生型小鼠的 0.6%、1.6% 和 12%。蛋白结合的神经酰胺水平分别为野生型小鼠的 0.2%、30% 和 33%。我们还观察到，在 Cyp4f39 KO 小鼠中，ω-羟基神经酰胺几乎完全缺失；在 Elovl1 KO 小鼠中，总神经酰胺水平降低，FA 分子缩短；在 Fatp4 KO 小鼠中，羟基化神经酰胺水平升高，FA 分子略有缩短。然而，酰基神经酰胺水平的降低和每个 KO 株系特有的神经酰胺组成的其他变化也与此有关。

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引用次数: 0

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway 低剂量咪喹莫特通过 ROS 介导的途径诱导黑色素瘤细胞的黑色素生成

IF 4.6

Journal of dermatological science

Pub Date : 2024-01-01 DOI: 10.1016/j.jdermsci.2023.12.005

Zheng-Yi Li , Shu-Hao Chang , Kuang-Ting Liu , Alaina Edelie Wu , Chien-Sheng Hsu , Shi-Wei Huang , Mu-Chi Chung , Shih-Chung Wang , Jun-Kai Kao , Yi-Ju Chen , Jeng-Jer Shieh

Background

Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity.

Objective

To explore whether IMQ could induce melanogenesis in melanoma cells.

Methods

The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not.

Results

We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity.

Conclusions

Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

背景黑色素生成是黑色素成熟的过程，它不仅能保护皮肤免受紫外线辐射，还在黑色素瘤的抗原性方面发挥着重要作用。方法本研究利用小鼠黑色素瘤细胞系B16F10、小鼠永生黑色素细胞Melan-A以及人黑色素瘤细胞系MNT-1、C32和A375。色素水平通过离心后的细胞团进行观察。细胞内和细胞外黑色素水平分别通过 NaOH 提取的细胞裂解液和细胞培养培养基的吸光度进行检测。用免疫印迹法检测黑色素生成相关蛋白的表达。细胞内环磷酸腺苷的含量由 cAMP Glo 检测试剂盒进行评估。结果我们证明，低剂量的IMQ可诱导B16F10细胞的黑色素生成。IMQ诱导小眼球相关转录因子（MITF）核转位，上调黑色素生成相关蛋白的表达，增加酪氨酸酶（TYR）活性，导致B16F10细胞色素沉着。接着，我们发现 IMQ 诱导的黑色素生成是由细胞内过量的 cAMP 积累激活的，而这种积累是通过 IMQ 介导的 PDE4B 抑制来调节的。结论低剂量 IMQ 可通过黑色素瘤细胞中的 ROS/PDE4B/PKA 通路激活黑色素生成。

{"title":"Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway","authors":"Zheng-Yi Li , Shu-Hao Chang , Kuang-Ting Liu , Alaina Edelie Wu , Chien-Sheng Hsu , Shi-Wei Huang , Mu-Chi Chung , Shih-Chung Wang , Jun-Kai Kao , Yi-Ju Chen , Jeng-Jer Shieh","doi":"10.1016/j.jdermsci.2023.12.005","DOIUrl":"10.1016/j.jdermsci.2023.12.005","url":null,"abstract":"<div><h3>Background</h3><p>Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity.</p></div><div><h3>Objective</h3><p>To explore whether IMQ could induce melanogenesis in melanoma cells.</p></div><div><h3>Methods</h3><p>The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not.</p></div><div><h3>Results</h3><p>We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity.</p></div><div><h3>Conclusions</h3><p>Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181123002682/pdfft?md5=e1076029cba3585ea1eb90f735db9d14&pid=1-s2.0-S0923181123002682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139020882","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}

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