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

{"title":"Cover","authors":"","doi":"10.1016/S2667-0267(25)00104-3","DOIUrl":"10.1016/S2667-0267(25)00104-3","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100448"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022446","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}

{"title":"Remote Skin and Blood Sampling for Translational Connective Tissue Disorder Research: A Proof-of-Concept Pilot Study","authors":"Dany Alkurdi ,&nbsp;Saeed Shakiba ,&nbsp;Isabel Okinedo ,&nbsp;Faradia Kernizan ,&nbsp;Ümmügülsüm Yildiz-Altay ,&nbsp;Jane Vongvirath ,&nbsp;Diana Reusch ,&nbsp;Jillian Richmond","doi":"10.1016/j.xjidi.2025.100421","DOIUrl":"10.1016/j.xjidi.2025.100421","url":null,"abstract":"<div><div>Remote, noninvasive biospecimen collection methods can address geographic and mobility-related barriers to participation in translational research for connective tissue disorders. We evaluated the feasibility of combining noninvasive skin tape stripping and Tasso capillary blood collection to molecularly profile lupus and morphea in remote settings using mailed kits. RNA extraction was optimized from 20 serial tape strips per site, with overnight shipping and scraping samples in buffer without sonication, yielding the highest concentration and quality. We enrolled 8 patients with lupus, 3 patients with morphea, and 8 healthy controls. Microarray analysis identified upregulation of <em>CXCL9</em>, <em>CCR6</em>, and <em>PDGFRA</em> in lupus and morphea skin. Proteomic analysis revealed elevated IFN-γ, TNFRSF4, and ANGPT2 in lupus serum, with lower IL-13 than in controls. Morphea samples showed increased expression of markers, including <em>PDGFRA</em>, <em>P2RX1</em>, and <em>KALRN</em>. Distinct gene expression signatures of <em>CTGF</em>, <em>TNFRSF4</em>, and <em>MAFB</em> in lupus skin and <em>ALOX15</em>, <em>KALRN</em>, and <em>P2RX1</em> in morphea skin enabled differentiation between morphea and lupus. CXCL9 and IFN-γ biomarkers were confirmed in other publicly available datasets at both the protein and RNA levels. These findings provide proof of concept that remote RNA and protein profiling is feasible and reproducibly identifies canonical and, to our knowledge, previously unreported disease markers; however, the small number of patients and the lack of more complete characterization of the participants studied require that further studies are needed to establish the role of these findings in the pathogenesis of lupus and morphea. This approach enables broader inclusion of underserved patients and offers a scalable model for remote biomarker studies in dermatologic and autoimmune research.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100421"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364377","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}

{"title":"High Prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients with Hidradenitis Suppurativa: A Guide to Easily Assess the Clinical Risk of Comorbid Liver Disease","authors":"Verena G. Frings ,&nbsp;Maxine Gläsel ,&nbsp;Monika Rau ,&nbsp;Andreas Geier ,&nbsp;Janik Fleißner ,&nbsp;Dagmar Presser ,&nbsp;Matthias Goebeler ,&nbsp;Andreas Kerstan","doi":"10.1016/j.xjidi.2025.100419","DOIUrl":"10.1016/j.xjidi.2025.100419","url":null,"abstract":"<div><div>Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with considerable comorbidity. The link between HS and metabolic dysfunction–associated steatotic liver disease (MASLD) is of particular interest owing to shared inflammatory pathways. This study applies the new MASLD nomenclature in a HS cohort. Our study aims to investigate the prevalence of MASLD in HS using transient elastography and to develop a clinical algorithm for assessing the MASLD risk. A cross-sectional study was conducted involving 94 patients with HS. Noninvasive methods were employed to diagnose MASLD. The clinical diagnosis was based on altered transient elastography–controlled attenuation parameter as surrogate for liver steatosis and the presence of cardiometabolic risk factors after excluding secondary causes of steatosis. Statistical analyses included logistic regression models to identify predictors of MASLD risk. The study found a prevalence of MASLD as high as 75% measured by high-accuracy transient elastography among patients with HS. Multivariable logistic regression analysis showed a strong within-cohort association between HS and MASLD. The newly developed clinical algorithm integrating transient elastography and the Fatty Liver Index effectively stratified MASLD risk. Our findings underscore the importance of routine MASLD screening in HS. The proposed clinical algorithm offers a straightforward approach for assessing MASLD risk in HS.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100419"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364464","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}

{"title":"Topical Salbutamol Cutaneous Gel Is Safe in a Double-Blind, Placebo-Controlled, Randomized Trial of Scarring from Sutured Wound Margins on the Arms of Healthy Human Volunteers","authors":"Graham A. Johnston ,&nbsp;Gareth Squire ,&nbsp;Shaun Barber ,&nbsp;David Fairlamb ,&nbsp;Christine E. Pullar","doi":"10.1016/j.xjidi.2025.100426","DOIUrl":"10.1016/j.xjidi.2025.100426","url":null,"abstract":"<div><h3>Background</h3><div>Salbutamol is a well-established β2-adrenergic receptor agonist used clinically for the reversal of bronchospasm. A functional β2-adrenergic receptor agonist network exists in the skin, which can alter skin cell migration and proliferation, inhibit angiogenesis, and alter wound re-epithelialization, suggesting a potential role for a β2-adrenergic receptor agonist applied topically for the prevention and treatment of scarring. Reduced scarring has been observed in an in vivo pig model, whereby a 50% reduction in skin scar area and hyperpigmentation was observed after topical application of salbutamol. Objectives: We conducted a double-blind, placebo-controlled, randomized, dose-escalation clinical trial. This was designed to investigate both the safety and efficacy of topical salbutamol for the improvement of scar appearance when applied as a cutaneous gel to sutured wound margins on the arms of healthy volunteers. Methods: In a phase I, single-center, double-blind, placebo (vehicle) controlled, randomized, dose-escalation trial on 45 healthy human volunteers, 1 ml salbutamol topical gel was administered once daily to one 2-cm full-thickness incision site on each arm of the trial participants for 60 days. Each participant was allocated to only 1 dosing group (group 1: 2.5 mM, group 2: 5 mM, and group 3: 10 mM). Pharmacokinetic and clinical assessments of safety and efficacy were performed over a 12-month period. Scarring was assessed by validated clinical scoring systems by both investigator and participant over 12 months. Results: In healthy human volunteers, tolerability assessments indicated zero incidences of edema, exudate, bleeding, or infection at any salbutamol-treated site irrespective of dose. All participants at every time point had peak plasma levels of salbutamol below the prespecified limit of 30 ng/ml. In efficacy assessments of the scars, no statistically significant improvements were noted in the mean difference between salbutamol-treated scars at any dose compared with placebo at months 7, 9, or 12 for either the investigator or participants’ assessments. Conclusions: There are no clinically significant safety signals after the cutaneous administration of salbutamol gel (0.2–10 mM) in humans either local to the site of injury and drug administration or arising from systemic exposure to salbutamol, but the extent of salbutamol absorption decreases as the wound heals, confirming that re-epithelialization of the wound limits the potential for systemic absorption. This trial was prospectively registered with the Medicines and Healthcare products Regulatory Agency with the European Union Drug Regulating Authorities Clinical Trials (EudraCT number: 2017-003118-15).</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100426"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839771","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}

{"title":"ZNF750 Loss of Function Drives Spontaneous Psoriasiform Skin Inflammation","authors":"Hilla Levi ,&nbsp;Topaz Alfer ,&nbsp;Roi Gazit ,&nbsp;Idan Cohen","doi":"10.1016/j.xjidi.2025.100416","DOIUrl":"10.1016/j.xjidi.2025.100416","url":null,"abstract":"<div><div>Epidermal keratinocytes are not only crucial for maintaining skin barrier physical functions but also play various roles in the initiation, progression, and maintenance phases of skin inflammation. ZNF750 is an epithelial-specific transcription factor expressed in differentiating keratinocytes, whose activity is required for keratinocyte terminal differentiation. In humans, <em>ZNF750</em> sequence variant causes psoriasis-like skin disease. In this study, using a genetic mouse model to study the role played by ZNF750 in epidermal homeostasis, we reveal that ZNF750 activity is essential for preventing skin inflammation. We show that a loss of ZNF750 activity results in the rapid development of psoriasiform skin lesions. Molecular dissection further demonstrated an impaired balance between epidermal cell proliferation and differentiation, induction of proinflammatory factors by <em>Znf750</em>-deficient keratinocytes, and a massive immune cell infiltration. Altogether, our study highlights the importance of keratinocytes in inflammatory skin disease pathogenesis, demonstrating ZNF750 loss-of-function sufficiency in driving severe psoriasiform skin inflammation, which resembles the diseased human condition in patients with pathogenic <em>ZNF750</em> sequence variants.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100416"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242407","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}

{"title":"Assessment of Primary Malignancy Risk after Initiation of Biologic Therapy in Patients with Psoriasis","authors":"Chunghwan Ro ,&nbsp;Ana Ormaza Vera ,&nbsp;Waleed Adawi ,&nbsp;Alexander Yap ,&nbsp;Clinton W. Enos","doi":"10.1016/j.xjidi.2025.100397","DOIUrl":"10.1016/j.xjidi.2025.100397","url":null,"abstract":"<div><div>Limited evidence exists regarding the long-term oncologic safety of biologic therapies, particularly IL-17 inhibitors and IL-23 inhibitors, in the management of psoriasis. This propensity score–matched retrospective cohort study assessed the risk of developing a primary malignancy within 10 years after exposure to a Food and Drug Administration–approved biologic among patients with psoriasis compared with that among biologic-naïve controls. After propensity score matching, 32,230 biologic-exposed patients were further grouped into cohorts of TNF inhibitors (n = 16,011), IL-23 inhibitors (n = 5604), IL-12/23 inhibitors (n =3856), and IL-17 inhibitors (n = 5467). During a 10-year period, TNF inhibitor–treated patients had a reduced risk of developing any primary malignancy compared with biologic-naïve patients with psoriasis (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.73–0.87). Similarly, a lower incidence of any malignancy was observed among patients on IL-23 inhibitors (HR = 0.83; 95% CI = 0.68–1.02), IL-12/23 inhibitors (HR = 0.85; 95% CI = 0.71–1.03), or IL-17 inhibitors (HR = 0.87; 95% CI = 0.73–1.04); however, the differences did not reach statistical significance. TNF inhibitor users were less likely to develop nonmelanoma skin cancer (HR = 0.82; 95% CI = 0.71–0.96) than controls, and the risk of nonmelanoma skin cancer did not significantly differ among users of IL-23 inhibitors (HR = 1.09; 95% CI = 0.77–1.55), IL-12/23 inhibitors (HR = 1.22; 95% CI = 0.90–1.64), or IL-17 inhibitors (HR = 1.03; 95% CI = 0.77–1.38). Exposure to any biologic class did not associate with the risk of developing melanoma or lymphoid/hematopoietic malignancies. Overall, these results provide evidence for the long-term oncologic safety of biologic therapies in the management of psoriasis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100397"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739006","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}

{"title":"Characterization of Malignant Adnexal Tumors of the Head and Neck by Targeted Analysis of Cancer Genes and Human Papillomavirus 42","authors":"Eleanor Dowell ,&nbsp;Ruchika Mahapatra ,&nbsp;Justin Bishop ,&nbsp;Andrew Matsumoto ,&nbsp;Alexandra Callan ,&nbsp;Travis W. Vandergriff ,&nbsp;Aya Alame ,&nbsp;Greg Hosler ,&nbsp;Jeffrey Gagan ,&nbsp;Rajiv I. Nijhawan ,&nbsp;Richard C. Wang","doi":"10.1016/j.xjidi.2025.100398","DOIUrl":"10.1016/j.xjidi.2025.100398","url":null,"abstract":"<div><div>Malignant adnexal tumors of the head and neck, including syringoid eccrine carcinoma and microcystic adnexal carcinoma, are rare tumors that are thought to arise in adnexal epithelium. The etiopathogenesis of these tumors is poorly understood, and the precise classification of these tumors can be challenging. Human papillomavirus 42 (HPV42) promotes the development of digital papillary adenocarcinoma, a rare adnexal tumor of the extremities and genital skin. Malignant adnexal tumors of the head and neck were assessed through targeted RNA sequencing of the cancer exome and specific RT-PCR for HPV42. Of the 9 cases identified, 7 yielded RNA of sufficient quality for RNA sequencing. Unexpectedly, these analyses revealed a <em>MYB:</em><em>:</em><em>NFIB</em> fusion in 1 case, suggesting a molecular diagnosis of adenoid cystic carcinoma. Mutations in <em>TP53</em> were identified in 2 cases, and a missense mutation in <em>Jak1</em> (p.Ser914Asn) was identified in 1 case. For the 6 cases with sufficient RNA, transcripts for the early region of HPV42 could not be identified by RT-PCR. In situ hybridization and RT-PCR confirmed the presence of HPV42 in digital papillary adenocarcinoma. Our study confirms the presence of mutations in <em>TP53</em> and <em>Jak1</em> and suggests that HPV42 does not contribute to malignant adnexal tumors of the head and neck.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100398"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026687","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}

{"title":"Translesion Synthesis DNA Polymerase Gene Expression Is Impacted by Age and IGF-1 in Epidermal Human Skin","authors":"Stanley D. Rider Jr. ,&nbsp;Madison S. Owens ,&nbsp;Craig A. Rohan ,&nbsp;Jeffrey B. Travers ,&nbsp;Michael G. Kemp","doi":"10.1016/j.xjidi.2025.100409","DOIUrl":"10.1016/j.xjidi.2025.100409","url":null,"abstract":"<div><div>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 <em>POLH</em>, <em>POLI</em>, <em>POLK</em>, <em>REV1</em>, and <em>REV7</em> were found to be inversely correlated with the skin aging biomarker gene <em>COL1A1</em> but not with <em>S100A7</em> among geriatric individuals. We further examined the effect of UVB exposure on TLS polymerase expression and found that mRNA levels of <em>POLI</em>, <em>POLK</em>, and <em>REV1</em> 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 <em>REV1</em>. 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.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100409"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157758","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}

{"title":"Automated Detection of Benign and Malignant Skin Lesions from Reflectance Confocal Microscopy Images Using Deep Learning","authors":"Jesutofunmi A. Omiye ,&nbsp;Babar K. Rao ,&nbsp;Shazli Razi ,&nbsp;Nadiya Chuchvara ,&nbsp;Fred M. Baik ,&nbsp;Roxana Daneshjou ,&nbsp;Lisa C. Zaba","doi":"10.1016/j.xjidi.2025.100404","DOIUrl":"10.1016/j.xjidi.2025.100404","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100404"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219078","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}

{"title":"Cover","authors":"","doi":"10.1016/S2667-0267(25)00083-9","DOIUrl":"10.1016/S2667-0267(25)00083-9","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 6","pages":"Article 100427"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570749","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}