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Translesion Synthesis DNA Polymerase Gene Expression Is Impacted by Age and IGF-1 in Epidermal Human Skin 翻译合成DNA聚合酶基因表达受年龄和IGF-1的影响
Pub Date : 2025-09-02 DOI: 10.1016/j.xjidi.2025.100409
Stanley D. Rider Jr. , Madison S. Owens , Craig A. Rohan , Jeffrey B. Travers , Michael G. Kemp
Regions of sun-exposed skin are prone to carcinogenesis in geriatric individuals and exhibit a reduced ability to remove mutagenic UV photoproducts from DNA. To determine whether geriatric skin may be more reliant on translesion synthesis (TLS) DNA polymerases to replicate unrepaired UV photoproducts, we examined the expression of TLS polymerases in the epidermis of young and geriatric individuals. Although significant differences were not observed between these 2 age groups, the expression of the TLS polymerase genes POLH, POLI, POLK, REV1, and REV7 were found to be inversely correlated with the skin aging biomarker gene COL1A1 but not with S100A7 among geriatric individuals. We further examined the effect of UVB exposure on TLS polymerase expression and found that mRNA levels of POLI, POLK, and REV1 were elevated in UVB-irradiated geriatric skin relative to those in young adult skin. Consistent with prior studies linking reduced insulin-like growth factor-1 production and signaling with altered UVB responses, studies with cultured keratinocytes and geriatric skin indicated that deficient insulin-like growth factor-1 signaling is associated with a stronger UVB-dependent induction of REV1. In summary, this work suggests that alterations to TLS polymerase gene expression in UVB-irradiated geriatric skin should be considered in future studies of skin cancer in human subjects.
在老年人中,暴露在阳光下的皮肤区域容易发生癌变,并且从DNA中去除诱变紫外线光产物的能力降低。为了确定老年皮肤是否更依赖于翻译合成(TLS) DNA聚合酶来复制未修复的紫外线光产物,我们检测了年轻人和老年人表皮中TLS聚合酶的表达。虽然在这两个年龄组之间没有观察到显著差异,但在老年个体中发现TLS聚合酶基因POLH、POLI、POLK、REV1和REV7的表达与皮肤衰老生物标志物基因COL1A1呈负相关,而与S100A7不相关。我们进一步研究了UVB暴露对TLS聚合酶表达的影响,发现与年轻成人皮肤相比,UVB照射的老年人皮肤中POLI、POLK和REV1的mRNA水平升高。先前的研究将胰岛素样生长因子-1的产生和信号传导减少与UVB反应改变联系起来,与此一致的是,对培养的角质形成细胞和老年皮肤的研究表明,缺乏胰岛素样生长因子-1信号传导与更强的UVB依赖性诱导REV1相关。总之,这项工作表明,在未来的人类皮肤癌研究中,应该考虑uvb照射下老年皮肤中TLS聚合酶基因表达的改变。
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引用次数: 0
Racial Differences in Work Relative Value Units for Outpatient Pediatric Dermatology Visits 儿童皮肤科门诊就诊工作相对价值单位的种族差异
Pub Date : 2025-09-02 DOI: 10.1016/j.xjidi.2025.100411
Udeyvir S. Cheema , Beiyu Liu , Ethan Borre , Cynthia L. Green , Lauren A.V. Orenstein , Suephy C. Chen
Measures of clinical productivity may tilt financial incentives toward providing care to specific patient populations, reinforcing inequitable care. Race, sex, and age have been shown to influence differences in work relative value units (wRVUs) generated during adult dermatology encounters. We sought to identify the association of patient race and sex with wRVUs generated by outpatient pediatric dermatology encounters. A total of 22,434 encounters among 10,063 unique patients were included; most encounters were with female (12,639 [56.3%]) and White (13,036 [58.1%]) individuals. The mean (SD) wRVUs per encounter was 1.57 (0.76). Visits with Asian patients, Black patients, and patients of other races generated 0.21 (95% confidence interval [CI] = 0.16–0.25), 0.19 (95% CI = 0.16–0.22), and 0.14 (95% CI = 0.10–0.17) fewer wRVUs per encounter, respectively, than pediatric outpatient dermatology visits with White patients (P < .001 for all). There was no significant association between sex and wRVUs per encounter. Laser treatment for vascular lesions was a mediator for the observed differences in wRVUs by race (60.5% [95% CI = 45.8–75.1%] for Asian race, 62.4% [95% CI = 52.9–71.9%] for Black race, and 53.3% [95% CI = 31.7–74.9%] for other races). Variations in wRVUs by patient race may create inadvertent incentives at the health systems level to prioritize certain groups.
临床生产力的措施可能会使财政激励倾向于为特定的患者群体提供护理,从而加剧不公平的护理。种族、性别和年龄已被证明会影响成人皮肤科就诊期间产生的工作相对价值单位(wRVUs)的差异。我们试图确定患者种族和性别与门诊儿科皮肤科就诊产生的wrvu的关系。在10063例特殊患者中,共纳入22434例病例;以雌性(12,639[56.3%])和白种(13,036[58.1%])居多。每次接触的平均(SD) wRVUs为1.57(0.76)。与白人患者相比,亚洲患者、黑人患者和其他种族患者每次就诊的wrvu分别减少0.21(95%可信区间[CI] = 0.16-0.25)、0.19 (95% CI = 0.16-0.22)和0.14 (95% CI = 0.10-0.17) (P < 0.001)。性别和每次接触的wrvu之间没有明显的联系。激光治疗血管病变是观察到的不同种族wRVUs差异的中介因素(亚洲种族为60.5% [95% CI = 45.8-75.1%],黑人为62.4% [95% CI = 52.9-71.9%],其他种族为53.3% [95% CI = 31.7-74.9%])。不同种族患者wrvu的差异可能会在卫生系统层面无意中产生优先考虑某些群体的激励。
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引用次数: 0
Assessing Treatment Efficacy for Dermatologic Immune-Related Adverse Events: A Systematic Review 评估皮肤免疫相关不良事件的治疗效果:一项系统综述
Pub Date : 2025-09-02 DOI: 10.1016/j.xjidi.2025.100410
Christian L. Bailey-Burke , Kristin A. Tissera , Lauren Baughman , Samantha A. Polly , Meenal Kheterpal
The management of dermatologic immune–related adverse events (D-irAEs) remains inconsistent owing to variability in treatment responses and a lack of standardized guidelines. Establishing evidence-based recommendations is critical to improving patient outcomes and minimizing interruptions in immune checkpoint inhibitor therapy. This review aims to systematically evaluate the level of evidence for reported D-irAE treatments and provide insights to guide clinical decision making. Of the D-irAEs identified, those that were commonly reported include maculopapular, lichenoid, psoriasiform, immunobullous (including bullous pemphigoid), granulomatous, vitiligo, and potentially life-threatening erosive mucocutaneous conditions (such as erythema multiforme, Steven–Johnson syndrome, and toxic epidermal necrosis). Treatments ranged from corticosteroids (topical, oral, intravenous) to biologics (eg, omalizumab, rituximab) and oral immunomodulators (eg, methotrexate, apremilast), with topical and oral corticosteroids, along with apremilast, receiving the strongest evidence rating (3B). Although the strongest evidence supports corticosteroids, most treatments for D-irAEs lack robust validation owing to limitations in study type (ie, randomized control trials and prospective cohort studies). This underscores the importance of multidisciplinary approaches to optimize D-irAE management and support continuity in cancer care. Future research should prioritize randomized control trials and prospective cohort studies to aid in standardizing D-irAE treatment protocols to solidify treatment consensus.
由于治疗反应的差异和缺乏标准化的指南,皮肤免疫相关不良事件(D-irAEs)的管理仍然不一致。建立基于证据的建议对于改善患者预后和尽量减少免疫检查点抑制剂治疗的中断至关重要。本综述旨在系统地评估已报道的D-irAE治疗的证据水平,并为指导临床决策提供见解。在已确定的d - irae中,通常报道的包括黄斑丘疹、类地衣、牛皮癣、免疫大疱性(包括大疱性类天疱疮)、肉芽肿、白癜风和可能危及生命的糜烂性粘膜皮肤病(如多形性红斑、史蒂文-约翰逊综合征和中毒性表皮坏死)。治疗范围从皮质类固醇(局部、口服、静脉注射)到生物制剂(例如,奥玛珠单抗、利妥昔单抗)和口服免疫调节剂(例如,甲氨喋呤、阿普米司特),局部和口服皮质类固醇以及阿普米司特获得最强证据评级(3B)。尽管最有力的证据支持皮质类固醇,但由于研究类型的限制(即随机对照试验和前瞻性队列研究),大多数d - irae治疗缺乏强有力的验证。这强调了多学科方法优化D-irAE管理和支持癌症治疗连续性的重要性。未来的研究应优先考虑随机对照试验和前瞻性队列研究,以帮助标准化D-irAE治疗方案,以巩固治疗共识。
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引用次数: 0
Cover 封面
Pub Date : 2025-09-01 DOI: 10.1016/S2667-0267(25)00068-2
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引用次数: 0
Stimulation of Skin Pigmentation with UVR Is a Risk Factor for Cholelithiasis 紫外线照射刺激皮肤色素沉着是胆石症的危险因素
Pub Date : 2025-08-25 DOI: 10.1016/j.xjidi.2025.100408
Stanislav Pavel , Patrick A. Riley
Long-term clinical experience suggested that skin fairness is one of the risk factors for developing cholelithiasis. However, it was unclear how to connect skin color with the development of gallstones. The discovery of reactive melanin precursors resulted in the hypothesis that some of these compounds could be excreted via bile and form the basis of gallstones. There are indications that the excretion of these compounds from melanocytes is higher in individuals with less pigmented skin who were irradiated by UV radiation. A clinical study revealed that people with fair skin who like sunbathing run a very high risk of developing cholelithiasis. We also present several studies that report a significant increase in cholelithiasis among psoriasis patients. Most gallstones remain asymptomatic. However, some patients may develop symptoms shortly after the gallstones are formed. We cite several investigations that found the highest frequency of cholecystectomies and cases of acute pancreatitis in the summer and the lowest in the winter. We propose that skin fairness should be considered a real risk factor for cholelithiasis, but only in combination with UV stimulation of cutaneous pigmentation. In this review, we discuss the laboratory and clinical work that can be connected to this hypothesis.
长期临床经验提示,皮肤白皙度是发生胆石症的危险因素之一。然而,如何将肤色与胆结石的发展联系起来还不清楚。活性黑色素前体的发现导致了一种假设,即这些化合物中的一些可以通过胆汁排出并形成胆结石的基础。有迹象表明,在受到紫外线照射的皮肤色素较少的个体中,这些化合物从黑素细胞中排出的量更高。一项临床研究表明,喜欢日光浴的白皙皮肤的人患胆石症的风险非常高。我们还报告了几项研究,报告了银屑病患者胆石症的显著增加。大多数胆结石没有症状。然而,有些病人可能在胆结石形成后不久就出现症状。我们引用了几项调查,发现夏季胆囊切除术和急性胰腺炎的发生率最高,而冬季最低。我们建议,皮肤白皙应该被认为是胆石症的一个真正的危险因素,但只有在紫外线刺激皮肤色素沉着的情况下。在这篇综述中,我们讨论了与这一假设相关的实验室和临床工作。
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引用次数: 0
Characterizing Keratinocyte-Derived Extracellular Vesicles in UVB-Irradiated Murine Skin uvb照射小鼠皮肤中角质形成细胞来源的细胞外囊泡的表征
Pub Date : 2025-08-21 DOI: 10.1016/j.xjidi.2025.100406
Ahmed Eldaboush , Cristina Ricco , Luca Musante , Rohan Dhiman , Ming-Lin Liu , Victoria P. Werth
UVB radiation is a potent trigger for photosensitive autoimmune diseases, yet the mechanism through which UVB-induced superficial epidermal damage drives deeper systemic inflammation remains poorly understood. Extracellular vesicles (EVs) have emerged as key mediators of UVB-induced immune activation and have also been specifically implicated in the pathogenesis of multiple photosensitive autoimmune diseases, therefore suggesting the possibility that UVB-induced EVs could be involved in driving this systemic inflammation. In this study, C57BL/6 mice were exposed to repeated dorsal UVB irradiation, and dermal tissue was processed to isolate EVs through sequential ultracentrifugation and density-gradient purification. Transmission electron microscopy, ExoView, immunogold labeling, and western blotting confirmed the presence of EVs within the dermis, including those expressing cytokeratin 10, a keratinocyte differentiation marker. UVB-irradiated dermal EVs showed significantly higher cytokeratin 10 expression than sham controls, supporting their keratinocyte origin and demonstrating that EVs can traverse the epidermal–dermal junction. These findings provide direct evidence that UVB triggers the release of keratinocyte-derived EVs into the dermis, where they may serve as vehicles for inflammatory signaling and immune modulation. The identification of cytokeratin 10–positive EVs as mediators of epidermal–dermal crosstalk highlights a potential mechanism linking UVB exposure to systemic autoimmunity and suggests, to our knowledge, a previously unreported therapeutic targets to mitigate photodamage.
UVB辐射是光敏性自身免疫性疾病的有力触发因素,但UVB诱导的表皮浅表损伤驱动更深层次全身性炎症的机制尚不清楚。细胞外囊泡(EVs)已成为uvb诱导的免疫激活的关键介质,并且还特别涉及多种光敏性自身免疫性疾病的发病机制,因此表明uvb诱导的EVs可能参与驱动这种全身性炎症。在本研究中,C57BL/6小鼠反复暴露于背部UVB照射下,对真皮组织进行连续超离心和密度梯度纯化,分离出ev。透射电镜、ExoView、免疫金标记和western blotting证实真皮内存在ev,包括表达角质细胞分化标志物细胞角蛋白10的ev。uvb照射下的真皮EVs的细胞角蛋白10表达明显高于假对照,支持其角质细胞来源,并表明EVs可以穿过表皮-真皮交界处。这些发现提供了直接证据,表明UVB触发角质细胞衍生的ev释放到真皮层,在那里它们可能作为炎症信号和免疫调节的载体。细胞角蛋白10阳性ev作为表皮-真皮串音介质的鉴定突出了UVB暴露与系统性自身免疫之间的潜在机制,并提示,据我们所知,以前未报道的治疗靶点可以减轻光损伤。
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引用次数: 0
Paraprotein-Negative IL-1–Mediated Inflammatory Dermatosis: An Update on Schnitzler-Like Syndrome in the Absence of a Gammopathy 副蛋白阴性il -1介导的炎症性皮肤病:无Gammopathy的schnitzler样综合征的最新进展
Pub Date : 2025-08-20 DOI: 10.1016/j.xjidi.2025.100405
Rizwan Ahmad , Jean Dunne , Katie Ridge , Nicole Fagan , Niall Conlon
Schnitzler syndrome (SchS) is a rare autoinflammatory condition characterized by chronic urticaria and systemic inflammation. Obligate diagnostic criteria include the presence of a monoclonal IgM or IgG band, with nearly all cases demonstrating a prompt response to IL-1 blockade. Recently, "Schnitzler-like" cases without a paraprotein have been reported. Although the exact nature of their relation to the original eponymous syndrome remains unclear, these cases share similar clinical features and response to IL-1 inhibition. Diagnostic delay is common in autoinflammatory syndromes, and the need to recognize potentially emerging cases is important. We present the case of a male aged 47 years with refractory urticaria, joint pain, and systemic inflammation resembling SchS but without detectable paraprotein, consistent with recently proposed paraprotein-negative IL-1–mediated inflammatory dermatosis (PANID). After failing conventional therapies, the patient achieved rapid and sustained remission with IL-1 blockade. This case underscores the importance of recognizing autoinflammatory syndromes, including PANID, in patients with refractory urticaria with associated inflammatory features. It also highlights the importance of a therapeutic trial of IL-1 inhibition.
施尼茨勒综合征(SchS)是一种罕见的自身炎症性疾病,以慢性荨麻疹和全身炎症为特征。必要的诊断标准包括单克隆IgM或IgG条带的存在,几乎所有病例都表现出对IL-1阻断的迅速反应。最近,没有旁蛋白的“Schnitzler-like”病例也有报道。虽然它们与原始同名综合征的确切关系尚不清楚,但这些病例具有相似的临床特征和对IL-1抑制的反应。诊断延迟在自身炎症综合征中很常见,识别潜在新发病例的必要性很重要。我们报告了一例47岁男性难治性荨麻疹、关节疼痛和系统性炎症,类似于SchS,但没有检测到副蛋白,与最近提出的副蛋白阴性il -1介导的炎症性皮肤病(PANID)一致。在常规治疗失败后,患者通过IL-1阻断实现了快速和持续的缓解。本病例强调了在伴有相关炎症特征的难治性荨麻疹患者中识别自身炎症综合征(包括PANID)的重要性。它还强调了IL-1抑制治疗试验的重要性。
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引用次数: 0
Corrigendum to ‘Factors Associated with Adoption of Immune Checkpoint Inhibitor Treatment for Advanced Melanoma: A SEER-Medicare Cohort Study’ JID Innovations, Volume 4, Issue 4, July 2024, 100289 《采用免疫检查点抑制剂治疗晚期黑色素瘤的相关因素:一项SEER-Medicare队列研究》的勘误表《JID创新》,第4卷,第4期,2024年7月,100289
Pub Date : 2025-08-18 DOI: 10.1016/j.xjidi.2025.100407
Cassandra Mohr , Kaiping Liao , Candice L. Hinkston , Mackenzie R. Wehner , Meng Li
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引用次数: 0
Automated Detection of Benign and Malignant Skin Lesions from Reflectance Confocal Microscopy Images Using Deep Learning 利用深度学习从反射共聚焦显微镜图像中自动检测良性和恶性皮肤病变
Pub Date : 2025-08-08 DOI: 10.1016/j.xjidi.2025.100404
Jesutofunmi A. Omiye , Babar K. Rao , Shazli Razi , Nadiya Chuchvara , Fred M. Baik , Roxana Daneshjou , Lisa C. Zaba
Reflectance confocal microscopy offers a noninvasive approach for diagnosing skin lesions at the point of care, but it remains underutilized owing to the specialized skill required for interpretation. Artificial intelligence provides an opportunity to automate this process. We developed deep learning models to automate the analysis of reflectance confocal microscopy block images. Reflectance confocal microscopy images acquired from 3rd and 4th generation VivaScope 1500 devices were preprocessed and split for training and testing. Two models were developed: a modified convolutional neural network ResNet-18, for skin layer detection, and a ResNet-34 integrated with a gated recurrent unit for lesion classification. The models were pretrained on 3rd generation images and fine tuned on 4th generation data, utilizing 5-fold cross-validation. Our cohort included 845 patients, 1147 lesions, and 4391 VivaBlock images. The layer detection model identified the dermis, epidermis, and dermoepidermal junction, achieving an area under the curve of 0.70, 0.71, and 0.57, respectively. The lesion classification model distinguished malignant from benign lesions with an area under the curve of 0.80 and specificity of 0.91. Our convolutional neural network gated recurrent unit approach effectively distinguished benign from malignant lesions, showing impressive diagnostic accuracy mimicking expert dermatological assessments. This highlights artificial intelligence's potential in improving reflectance confocal microscopy image interpretation, reducing unnecessary biopsies, and paves the way for future research.
反射共聚焦显微镜为诊断皮肤病变提供了一种非侵入性的方法,但由于解释所需的专业技能,它仍然未得到充分利用。人工智能为自动化这一过程提供了机会。我们开发了深度学习模型来自动分析反射共聚焦显微镜块图像。从第三代和第四代VivaScope 1500设备获得的反射共聚焦显微镜图像进行预处理和分割,用于训练和测试。开发了两种模型:用于皮肤层检测的改进卷积神经网络ResNet-18,以及与门控复发单元集成的用于病变分类的ResNet-34。模型在第三代图像上进行预训练,并在第四代数据上进行微调,利用5倍交叉验证。我们的队列包括845名患者、1147个病变和4391张VivaBlock图像。层检测模型对真皮层、表皮、皮表皮连接处进行了识别,曲线下面积分别为0.70、0.71、0.57。病变分类模型区分良恶性病变的曲线下面积为0.80,特异性为0.91。我们的卷积神经网络门控复发单元方法有效地区分了良性和恶性病变,显示出令人印象深刻的诊断准确性,模拟了皮肤科专家的评估。这凸显了人工智能在改善反射共聚焦显微镜图像解释、减少不必要的活检方面的潜力,并为未来的研究铺平了道路。
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引用次数: 0
Circulating CLA+ Memory T Cells in Skin Diseases: A Translational Perspective 循环CLA+记忆T细胞在皮肤病中的作用
Pub Date : 2025-08-05 DOI: 10.1016/j.xjidi.2025.100403
Tali Czarnowicki , Lea Tordjman , Irene García-Jiménez , Luis F. Santamaria-Babí
Circulating cutaneous lymphocyte-associated antigen–positive T cells constitute a subset of memory T cells with a unique phenotype, effector function, and therapeutic relevance because they reflect the regional functions of the cutaneous immune system. These cells are involved in the pathological mechanisms of diverse cutaneous diseases. This review brings updated translational insights into these cells and identifies key questions for future research in the field.
循环皮肤淋巴细胞相关抗原阳性T细胞构成记忆T细胞的一个亚群,具有独特的表型、效应功能和治疗相关性,因为它们反映了皮肤免疫系统的区域功能。这些细胞参与多种皮肤疾病的病理机制。这篇综述为这些细胞带来了最新的翻译见解,并确定了该领域未来研究的关键问题。
{"title":"Circulating CLA+ Memory T Cells in Skin Diseases: A Translational Perspective","authors":"Tali Czarnowicki ,&nbsp;Lea Tordjman ,&nbsp;Irene García-Jiménez ,&nbsp;Luis F. Santamaria-Babí","doi":"10.1016/j.xjidi.2025.100403","DOIUrl":"10.1016/j.xjidi.2025.100403","url":null,"abstract":"<div><div>Circulating cutaneous lymphocyte-associated antigen–positive T cells constitute a subset of memory T cells with a unique phenotype, effector function, and therapeutic relevance because they reflect the regional functions of the cutaneous immune system. These cells are involved in the pathological mechanisms of diverse cutaneous diseases. This review brings updated translational insights into these cells and identifies key questions for future research in the field.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100403"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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JID innovations : skin science from molecules to population health
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