Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

Background: Artificial intelligence (AI) applications in dermatology have expanded beyond diagnosis and have shifted towards assessing disease severity. Objectives: To qualitatively and quantitatively evaluate the performance of image-based AI models in severity assessment for various skin diseases. Methods: In this systematic review and meta-analysis, we collected studies using four electronic databases, including PubMed, Embase, Institute of Electrical and Electronics Engineers Xplore and Web of Science, published from 1 January 2017 to 6 April 2023, and updated the search in November 2023. Studies assessing the performance of deep learning AI models on the severity of skin diseases were included. We excluded studies that utilized a nonvalidated severity index, lacked clinical images, and assessed wounds, ulcers or burns. Two independent reviewers extracted prespecified study characteristics for the summary table. For the meta-analysis, contingency tables were extracted, when possible, and reconstructed for each severity measure. Accuracy was calculated using a bivariate model in Metandi package, and meta-regression was performed by disease type and scoring system. This study was registered with PROSPERO (CRD42023487228). Results: Our initial search identified 7737 records. After duplicate removal and abstract screening, we reviewed the full text of 192 articles and included 45 studies for systematic review and 19 for meta-analysis. The pooled sensitivity and specificity of AI models were 80.5% [95% confidence interval (CI) 76.2–84.2] and 96.2% (95% CI 94.9–97.2), respectively. Moreover, pooled sensitivity differed by disease (atopic dermatitis 91.8% vs. acne 80.7%, P = 0.005; acne 80.4% vs. psoriasis 71.1%, P = 0.044) and scoring system [Eczema Area and Severity Index 97.3% vs. Investigator’s Global Assessment (IGA) for atopic dermatitis 78.9%, P < 0.001; Hayashi Grading 89.7% vs. IGA for acne 69.8%, P < 0.001]. Conclusions: Our findings show that current AI models exhibit a high level of capacity in disease severity assessment. Nevertheless, efforts are urgently needed to improve transparency in data reporting and conduct high-quality prospective studies using objective reference standards in clinical settings to generate reliable evidence.

Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the LINE-1 retrotransposons. The ectopic expression of LINE-1 has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that LINE-1 reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of LINE-1 and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind LINE-1 mRNA were measured using RT-qPCR, and the expression of miR-16 was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces LINE-1 reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in miR-16 expression.

Soft tissue sarcomas (STS) are rare and heterogeneous, with cutaneous STS (CSTS) lacking recent epidemiological data. This study analyses CSTS incidence from 2000 to 2019 using SEER data, identifying 18 181 cases. CSTS was more common in men and non-Hispanic Whites, with Kaposi sarcoma (KS) and dermatofibrosarcoma protuberans (DFSP) being predominant. The overall CSTS incidence was 11.2 per 1 000 000 person-years, with KS having the highest rate. The study reveals a 1.4% annual decline in CSTS rates and highlights ethnic disparities, especially in KS incidence among Non-Hispanic Black patients.