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

{"title":"The Influence of Blue Light Exposure on Reconstructed 3-Dimensional Skin Model: Molecular Changes and Gene Expression Profile","authors":"Juliana Carvalhães Lago ,&nbsp;Melissa Dibbernn Ganzerla ,&nbsp;Ana Luisa Abrahão Dias ,&nbsp;Joice Panzarin Savietto","doi":"10.1016/j.xjidi.2023.100252","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100252","url":null,"abstract":"<div><p>Recent studies have provided information about digital eye strain and the potential damage that blue light from digital devices can cause to the eyes. In this study, we analyzed the influence of blue light exposure on reconstructed 3-dimensional skin model using RNA sequencing to identify the expression of transcripts and abnormal events. Three-dimensional skin was exposed to visible light spectrum and isolated blue wavelength for 1, 2, and 4 hours to represent acute exposure and 1 hour over 4 sequential days to represent repeated exposure, respectively, in this in vitro model. We compared gene expression levels with those of unexposed control. Samples submitted to repeated exposure showed reduced <em>AK2</em> and <em>DDX47</em>, whereas they showed increased <em>PABPC3</em> gene expression, revealing a significantly negative impact. RT-PCR validation assay with exposed 3-dimensional skin compared with unexposed control regarding 1 and 4 days of incubation showed increased IL-6 signaling mechanism activation and signal transducer and activator of transcription 3 gene <em>STAT3</em> gene expression, whereas it showed decreased peroxisome proliferator–activated receptor signaling mechanism activation, suggesting an influence on inflammatory pathways. We also demonstrate upregulated gene expression of <em>KIT</em>, <em>MAPK2</em>, and <em>PI3KC</em> in samples from exposed condition, corroborating previous findings related to pigmentation signaling stimuli. These results reveal, to our knowledge, previously unreported data that enable studies on molecular response correlation of in vitro digital blue light exposure and human skin studies.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000784/pdfft?md5=08dc530c0237759cfbbc90392adda77b&pid=1-s2.0-S2667026723000784-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674542","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":"ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201","authors":"Paul Changelian ,&nbsp;Canxin Xu ,&nbsp;Steve Mnich ,&nbsp;Heidi Hope ,&nbsp;Kourtney Kostecki ,&nbsp;Jeff Hirsch ,&nbsp;Chin-Yi Loh ,&nbsp;David Anderson ,&nbsp;James Blinn ,&nbsp;Susan Hockerman ,&nbsp;Evan Dick ,&nbsp;Walter Smith ,&nbsp;Joseph Monahan ,&nbsp;Tooraj Raoof ,&nbsp;Seth Forman ,&nbsp;David Burt ,&nbsp;Brad Barnes ,&nbsp;David Gordon ,&nbsp;Neal Walker ,&nbsp;John Sudzina ,&nbsp;Jon Jacobsen","doi":"10.1016/j.xjidi.2023.100251","DOIUrl":"10.1016/j.xjidi.2023.100251","url":null,"abstract":"<div><h3>Introduction</h3><p>Atopic dermatitis, a chronic, pruritic skin disease, affects 10–30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects.</p></div><div><h3>Primary objective</h3><p>The primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis.</p></div><div><h3>Design</h3><p>ATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks.</p></div><div><h3>Primary endpoint</h3><p>The primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline.</p></div><div><h3>Results</h3><p>Reduction was significantly greater in the ATI-1777–treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [<em>P</em> &lt; .001]). Average plasma concentrations of ATI-1777 were &lt;5% of the half-maximal inhibitory concentration of ATI-1777 for inhibiting Jak1/3. No deaths or serious adverse events were reported.</p></div><div><h3>Conclusion</h3><p>Topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of atopic dermatitis.</p></div><div><h3>Trial Registration</h3><p>The study was registered at <span>ClinicalTrials.gov</span><svg><path></path></svg> with the number NCT04598269.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000772/pdfft?md5=78250cf1d25122b4519a0a1e75ccb92f&pid=1-s2.0-S2667026723000772-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139299399","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":"Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing","authors":"Yonghao Cao ,&nbsp;Bohdan P. Harvey ,&nbsp;Liang Jin ,&nbsp;Susan Westmoreland ,&nbsp;Jing Wang ,&nbsp;Munish Puri ,&nbsp;Yingli Yang ,&nbsp;Holly M. Robb ,&nbsp;Sultan Tanriverdi ,&nbsp;Chenqi Hu ,&nbsp;Xue Wang ,&nbsp;Xiaofeng Xin ,&nbsp;Yingchun Liu ,&nbsp;Michael P. Macoritto ,&nbsp;Kathleen M. Smith ,&nbsp;Yu Tian ,&nbsp;Kevin White ,&nbsp;Timothy R.D.J. Radstake ,&nbsp;Zehra Kaymakcalan","doi":"10.1016/j.xjidi.2023.100250","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100250","url":null,"abstract":"<div><p>Adalimumab but neither etanercept nor certolizumab-pegol has been reported to induce a wound-healing profile in vitro by regulating macrophage differentiation and matrix metalloproteinase expression, which may underlie the differences in efficacy between various TNF-α inhibitors in impaired wound healing in patients with hidradenitis suppurativa, a chronic inflammatory skin disease. To examine and compare the efficacy of various TNF inhibitors in cutaneous wound healing in vivo, a human TNF knock-in Lepr^db/db mouse model was established to model the impaired cutaneous wound healing as seen in hidradenitis suppurativa. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound-healing signatures that may underlie the differential efficacy of these inhibitors in accelerating cutaneous wound healing. Taken together, these data revealed that TNF inhibitors exhibited differential levels of efficacy in accelerating cutaneous wound healing in the impaired wound-healing model in vivo.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000760/pdfft?md5=f4ab8caac6cdc9955299fd7f7706a2ea&pid=1-s2.0-S2667026723000760-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038398","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":"Identification of Collagen-Suppressive Agents in Keloidal Fibroblasts Using a High-Content, Phenotype-Based Drug Screen","authors":"Anpuchchelvi Rajadurai ,&nbsp;Hensin Tsao","doi":"10.1016/j.xjidi.2023.100248","DOIUrl":"10.1016/j.xjidi.2023.100248","url":null,"abstract":"<div><p>Keloids are characterized by excessive extracellular collagen and exaggerated scarring. Large-volume lesions can be functionally debilitating, therapeutically intractable, and psychologically devastating. A key barrier to translational momentum for novel antikeloid agents is the lack of a faithful high-content screen. We devised, to our knowledge, a previously unreported phenotype-based assay that measures secreted collagen by keloidal fibroblasts in tissue hypoxic conditions (1% oxygen). Four keloidal fibroblasts and 1 normal dermal fibroblast line were exposed to 199 kinase inhibitors. Of 199 kinase inhibitors, 41 (21%) and 71 (36%) increased and decreased the <span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm (mean collagen inhibition normalized to viability) by more than 10%, respectively. The most collagen suppressive agents were CGP60474 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.36), KIN001-244 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.55), and RAF265 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.58). The top candidate, CGP60474, consistently abolished collagens I and VII production, exhibited minimal global toxicity, and induced a fivefold increase in phosphorylated extracellular signal–regulated kinase. This proof-of-concept high-content screen can identify drugs that appear to target critical keloidal pathophysiology—collagen secretion.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000747/pdfft?md5=69233229cb67e080c243959f33927281&pid=1-s2.0-S2667026723000747-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298649","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":"En Route to Targeted Ribosome Editing to Replenish Skin Anchor Protein LAMB3 in Junctional Epidermolysis Bullosa","authors":"Bjoern Wimmer ,&nbsp;Andreas Friedrich ,&nbsp;Katharina Poeltner ,&nbsp;Genevieve Edobor ,&nbsp;Claudia Mosshammer ,&nbsp;Gazmend Temaj ,&nbsp;Adriana Rathner ,&nbsp;Thomas Karl ,&nbsp;Jan Krauss ,&nbsp;Joerg von Hagen ,&nbsp;Christopher Gerner ,&nbsp;Michael Breitenbach ,&nbsp;Helmut Hintner ,&nbsp;Johann W. Bauer ,&nbsp;Hannelore Breitenbach-Koller","doi":"10.1016/j.xjidi.2023.100240","DOIUrl":"10.1016/j.xjidi.2023.100240","url":null,"abstract":"<div><p>Severe junctional epidermolysis bullosa is a rare genetic, postpartum lethal skin disease, predominantly caused by nonsense/premature termination codon (PTC) sequence variants in <em>LAMB3</em> gene. <em>LAMB3</em> encodes LAMB3, the β subunit of epidermal–dermal skin anchor laminin 332. Most translational reads of a PTC mRNA deliver truncated, nonfunctional proteins, whereas an endogenous PTC readthrough mechanism produces full-length protein at minimal and insufficient levels. Conventional translational readthrough-inducing drugs amplify endogenous PTC readthrough; however, translational readthrough-inducing drugs are either proteotoxic or nonselective. Ribosome editing is a more selective and less toxic strategy. This technique identified ribosomal protein L35/uL29 (ie, RpL35) and RpL35-ligands repurposable drugs artesunate and atazanavir as molecular tools to increase production levels of full-length LAMB3. To evaluate ligand activity in living cells, we monitored artesunate and atazanavir treatment by dual luciferase reporter assays. Production levels of full-length LAMB3 increased up to 200% upon artesunate treatment, up to 150% upon atazanavir treatment, and up to 170% upon combinatorial treatment of RpL35 ligands at reduced drug dosage, with an unrelated PTC reporter being nonresponsive. Proof of bioactivity of RpL35 ligands in selective increase of full-length LAMB3 provides the basis for an alternative, targeted therapeutic route to replenish LAMB3 in severe junctional epidermolysis bullosa.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000668/pdfft?md5=fdfc75a682b9369e4d5f25ea8475ea44&pid=1-s2.0-S2667026723000668-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135615075","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":"Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis","authors":"Sundus S. Lateef ,&nbsp;Grace A. Ward ,&nbsp;Haiou Li ,&nbsp;Carla Pantoja ,&nbsp;Elizabeth Florida ,&nbsp;Christin G. Hong ,&nbsp;Justin Rodante ,&nbsp;Andrew Keel ,&nbsp;Marcus Y. Chen ,&nbsp;Alexander V. Sorokin ,&nbsp;Martin P. Playford ,&nbsp;Nehal N. Mehta","doi":"10.1016/j.xjidi.2023.100243","DOIUrl":"10.1016/j.xjidi.2023.100243","url":null,"abstract":"<div><p>Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; <em>P</em> = .006). Importantly, ox-mtDNA was positively associated with IL-17a (β = 0.25; <em>P</em> = .03) and low-density granulocytes (β = 0.37; <em>P</em> = .005) but negatively associated with high-density lipoprotein-cholesterol (β = −0.29; <em>P</em> = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (β = 0.19; <em>P</em> = .003). Biologic-naïve patients with PSO receiving anti–IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; <em>P</em> = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; <em>P</em> = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000693/pdfft?md5=a3ffc8a314f631e47e11add3d33b50dd&pid=1-s2.0-S2667026723000693-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135410791","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":"Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics","authors":"Yuuki Nishimura ,&nbsp;Eijitsu Ryo ,&nbsp;Satoshi Inoue ,&nbsp;Masahito Kawazu ,&nbsp;Toshihide Ueno ,&nbsp;Kenjiro Namikawa ,&nbsp;Akira Takahashi ,&nbsp;Dai Ogata ,&nbsp;Akihiko Yoshida ,&nbsp;Naoya Yamazaki ,&nbsp;Hiroyuki Mano ,&nbsp;Yasushi Yatabe ,&nbsp;Taisuke Mori","doi":"10.1016/j.xjidi.2023.100229","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100229","url":null,"abstract":"<div><p>Cutaneous adnexal tumors are neoplasms that arise from skin appendages. Their morphologic diversity and phenotypic variability with rare progression to malignancy make them difficult to diagnose and classify, and there is currently no established treatment strategy. To overcome these difficulties, this study investigated the transcription factor SOX9 expression, morphology, and genetics of skin adnexal tumors for understanding their biology, especially their histogenesis. We showed that cutaneous adnexal tumors and their nontumor counterparts of skin and appendages exhibit expression patterns similar to that of SOX9. Its expression intensity and pattern, as well as histopathologic evaluation of tumors, were analyzed using digital images of 69 normal skin adnexal 9-type organs and 185 skin adnexal 29-type tumors as references. It was possible to distinguish basal cell carcinoma from squamous cell carcinoma, sebaceous carcinoma, and pilomatrixoma with significant differences, along with porocarcinoma from squamous cell carcinoma. Furthermore, unsupervised machine learning “computational pathology” was used to derive a multiregion whole-exome sequencing fusion method termed “genocomputed pathology.” The genocomputed pathology of three representable adnexal carcinomas (porocarcinoma, hidradenocarcinoma, and spiradenocarcinoma) was evaluated for total nine cases. We showed that there was more heterogeneity than expected within the tumors as well as the coexistence of components lacking driver fusion genes. The presence or absence of potential driver genes, such as <em>PIK3CA</em>, <em>YAP1</em>, and <em>PTEN</em>, in each region was identified, highlighting a therapeutic strategy for cutaneous adnexal carcinoma encompassing heterogeneous tumors.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000553/pdfft?md5=5bafdd911a89cbf7bbf564649a7f0837&pid=1-s2.0-S2667026723000553-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92042333","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":"Association of Cardiovascular Disease in Patients with Mycosis Fungoides and Sézary Syndrome Compared to a Matched Control Cohort","authors":"Courtney M. Johnson ,&nbsp;Sai M. Talluru ,&nbsp;Bianka Bubic ,&nbsp;Michelle Colbert ,&nbsp;Priyanka Kumar ,&nbsp;Hua-ling Tsai ,&nbsp;Ravi Varadhan ,&nbsp;Sima Rozati","doi":"10.1016/j.xjidi.2023.100219","DOIUrl":"10.1016/j.xjidi.2023.100219","url":null,"abstract":"<div><p>Mycosis fungoides/Sézary syndrome (MF/SS) produces a low-grade chronic inflammatory state that may be associated with an increased risk of cardiovascular (CV) events, as seen in other chronic, systemic dermatologic diseases. To assess this association, a retrospective, cross-sectional study was designed in which 421 patients with a biopsy-proven diagnosis of MF/SS were compared with a control cohort of 4,210 age-, gender-, and race-matched patients randomly selected from the National Health and Nutritional Evaluation Survey database. The MF/SS cohort had a 14% prevalence of CV events, which was not statistically different from the control population’s prevalence of 13%. In the MF/SS cohort, a multivariable logistic regression model showed that older patients (OR = 1.05 for each year of age, 95% confidence interval = 1.02–1.07) and those diagnosed with hypertension (OR = 3.40, 95% confidence interval = 1.71–6.75) had a higher risk of a CV event (<em>P</em> &lt; 0.001). Risk factors such as gender, race, smoking, diabetes, and obesity were not significantly associated with CV events. Findings suggest that in the MF/SS population, advancing age and hypertension are risk factors for CV events, requiring clinical recognition and management. In addition, further research is needed to understand the complex interplay of how chronic inflammation in MF/SS impacts the immune development of CV disease.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100219"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000449/pdfft?md5=1823e23e49d646385c6e02392f357c7c&pid=1-s2.0-S2667026723000449-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42373997","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":"Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo","authors":"Sarem Rashid ,&nbsp;Ivan Molotkov ,&nbsp;Nikolai Klebanov ,&nbsp;Michael Shaughnessy ,&nbsp;Mark J. Daly ,&nbsp;Mykyta Artomov ,&nbsp;Hensin Tsao","doi":"10.1016/j.xjidi.2023.100217","DOIUrl":"10.1016/j.xjidi.2023.100217","url":null,"abstract":"<div><p>Several observational studies have demonstrated a consistent pattern of decreased melanoma risk among patients with vitiligo. More recently, this finding has been supported by a suggested genetic relationship between the two entities, with certain variants significantly associated with an increased risk of melanoma, basal cell carcinoma, and squamous cell carcinoma but a decreased risk of vitiligo. We compared 48 associated variants from a recently published GWAS and identified three variants—located in the <em>TYR</em>, <em>MC1R-DEF8</em>, and <em>RALY-EIF2S</em><em>2-ASIP</em><em>-AHCY-ITCH</em> loci— that correlated with an increased risk for melanoma, basal cell carcinoma, and squamous cell carcinoma and a decreased risk for vitiligo. We then used results of skin cancers and vitiligo GWAS to compare the shared genetic properties between these two traits through an unbiased Mendelian randomization analysis. Our results suggest that the inverse genetic relationship between common skin cancers and vitiligo is broader than previously reported owing to the influence of shared genome-wide significant associations.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000425/pdfft?md5=8381d676045e8e78ae5bdadbf53fc0a2&pid=1-s2.0-S2667026723000425-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55189324","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":"Incident Comorbidity, Resource Use, and All-Cause Mortality Associated with Prurigo Nodularis: A United Kingdom Retrospective Database Analysis","authors":"Christopher Ll Morgan ,&nbsp;Melissa Thomas ,&nbsp;Benjamin R. Heywood ,&nbsp;Sonja Ständer ,&nbsp;Shawn G. Kwatra ,&nbsp;Zarif K. Jabbar-Lopez ,&nbsp;Christophe Piketty ,&nbsp;Sylvie Gabriel ,&nbsp;Jorge Puelles","doi":"10.1016/j.xjidi.2023.100233","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100233","url":null,"abstract":"<div><p>We described comorbidity, resource utilization, and mortality for patients with prurigo nodularis (PN) using data from the Clinical Practice Research Datalink. Patients with incident PN (2008–2018) were selected and matched to controls. Of 2,416 patients with PN, 2,409 (99.7%) were matched to controls. Prevalence of atopic dermatitis (relative risk [RR] = 2.571; 95% confidence interval [CI] = 2.356–2.806), depression (RR = 1.705; 95% CI = 1.566–1.856), anxiety (RR = 1.540; 95% CI = 1.407–1.686), coronary heart disease (RR = 1.575; 95% CI = 1.388–1.787), chronic kidney disease (RR = 1.529; 95% CI = 1.329–1.759), and type 2 diabetes mellitus (RR = 1.836; 95% CI = 1.597–2.111) was significantly higher for patients with PN. Subsequent risk of atopic dermatitis (hazard ratio = 6.58; 95% CI = 5.17– 8.37), depression (hazard ratio = 1.61; 95% CI = 1.30–1.99), and coronary heart disease (hazard ratio = 1.37; 95% CI = 1.09–1.74) were significantly increased. Resource utilization was increased in all settings: incidence rate ratio = 1.48 (95% CI = 1.47–1.49) for primary care, incident rate ratio = 1.80 (95% CI = 1.75–1.85) for inpatients, incident rate ratio = 2.15 (95% CI = 2.13–2.18) for outpatients, and incidence rate ratio = 1.32 (95% CI = 1.27–1.36) for accident and emergency. Respective cost ratios were 1.78 (95% CI = 1.67–1.90), 1.52 (95% CI = 1.20–1.94), 2.34 (95% CI = 2.13–2.58), and 1.55 (95% CI = 1.33–1.80). Total primary and secondary healthcare costs were £2,531 versus £1,333, a cost ratio of 1.62 (95% CI = 1.36–1.94). The adjusted hazard ratio for mortality was 1.37 (95% CI = 1.14–1.66). Patients with PN had significantly increased rates of comorbidity, healthcare resources utilization, and mortality compared with matched controls.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100233"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000590/pdfft?md5=e6112ce8dfb42814b16c9e19cdb004fb&pid=1-s2.0-S2667026723000590-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92042334","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}