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Diagnosis of acral lentiginous melanoma in situ (ALMIS) is challenging. However, data regarding ALMIS are limited in the literature. The aim of this study was to investigate the clinical and dermoscopic features of ALMIS on palmoplantar surfaces. Patients with ALMIS and available dermoscopic images were retrospectively reviewed at our institution between January 2013 and February 2020. Clinical and dermoscopic features were analysed and compared between small (< 15 mm) and large (≥ 15 mm) ALMIS. Twenty-one patients with ALMIS were included in this study. Mean patient age was 58.5 (range 39–76) years; most lesions were located on the sole (90.5%). The mean maximal diameter was 19.9 ± 13.7 mm (mean ± standard deviation). Statistical analysis of dermoscopic features revealed that parallel ridge patterns (54.5% vs. 100%, P = 0.035), irregular diffuse pigmentation (27.3% vs. 100%, P = 0.001) and grey colour (18.2% vs. 90%, P = 0.002) were significantly less frequent in small lesions than in large lesions. We have also illustrated two unique cases of small ALMIS; their evolution and follow-up dermoscopic examination are provided. In conclusion, this study described detailed dermoscopic findings of ALMIS. Based on the present study and a review of the literature, we proposed a dermoscopic algorithm for the diagnosis of ALMIS.

Onychomycosis is a common fungal nail infection. Accurate diagnosis is critical as onychomycosis is transmissible between humans and impacts patients' quality of life. Combining clinical examination with mycological testing ensures accurate diagnosis. Conventional diagnostic techniques, including potassium hydroxide testing, fungal culture and histopathology of nail clippings, detect fungal species within nails. New diagnostic tools have been developed recently which either improve detection of onychomycosis clinically, including dermoscopy, reflectance confocal microscopy and artificial intelligence, or mycologically, such as molecular assays. Dermoscopy is cost-effective and non-invasive, allowing clinicians to discern microscopic features of onychomycosis and fungal melanonychia. Reflectance confocal microscopy enables clinicians to observe bright filamentous septate hyphae at near histologic resolution by the bedside. Artificial intelligence may prompt patients to seek further assessment for nails that are suspicious for onychomycosis. This review evaluates the current landscape of diagnostic techniques for onychomycosis.

Chronic inflammatory skin diseases (CISDs) negatively impact a large number of patients. Injection of triamcinolone acetonide (TA), an anti‐inflammatory steroid drug, directly into the dermis of diseased skin using needle‐syringe systems is a long‐established procedure for treating recalcitrant lichenified lesions of CISDs, referred to as TA intralesional injection (TAILI). However, TAILI causes severe pain, causing patients to be stressed and reluctant to undergo treatment. Furthermore, the practitioner dependency on the amount and depth of the injected TA makes it difficult to predict the prognosis. Here, candle flame (“candlelit”)‐shaped TA‐loaded dissolving microneedles (Candlelit‐DMN) are designed and fabricated out of biocompatible and biodegradable molecules. Candlelit‐DMN distributes TA evenly across human skin tissue. Conjoined with the applicator, Candlelit‐DMN is efficiently inserted into human skin in a standardized manner, enabling TA to be delivered within the target layer. In an in vivo skin inflammation mouse model, Candlelit‐DMN inserted with the applicator effectively alleviates inflammation by suppressing inflammatory cell infiltration and cytokine gene expression, to the same extent as TAILI. This Candlelit‐DMN with the applicator arouses the interest of dermatologists, who prefer it to the current TAILI procedure. Candle flame‐shaped triamcinolone acetonide‐loaded dissolving microneedle is designed and fabricated, out of biocompatible molecules. With an applicator, the microneedles are efficiently inserted into human skin in a standardized manner without pain, enabling the drug to be delivered within the target layer. In an in vivo skin inflammation mouse model, the microneedles inserted with the applicator effectively alleviate inflammation.

The maintenance of genetic integrity is critical for stem cells to ensure homeostasis and regeneration. Little is known about how adult stem cells respond to irreversible DNA damage, resulting in loss of regeneration in humans. Here, we establish a permanent regeneration loss model using cycling human hair follicles treated with alkylating agents: busulfan followed by cyclophosphamide. We uncover the underlying mechanisms by which hair follicle stem cells (HFSCs) lose their pool. In contrast to immediate destructive changes in rapidly proliferating hair matrix cells, quiescent HFSCs show unexpected massive proliferation after busulfan and then undergo large-scale apoptosis following cyclophosphamide. HFSC proliferation is activated through PI3K/Akt pathway, and depletion is driven by p53/p38-induced cell death. RNA-seq analysis shows that HFSCs experience mitotic catastrophe with G2/M checkpoint activation. Our findings indicate that priming mobilization causes stem cells to lose their resistance to DNA damage, resulting in permanent loss of regeneration after alkylating chemotherapy. Hair follicles (HFs) are sensitive to chemotherapy but recover from quiescent HF stem cells, although sometimes chemotherapy results in permanent loss. Here, Kim et al. establish a model of permanent chemotherapy-induced alopecia to uncover the underlying mechanisms depleting human HF stem cells.

Background Neoadjuvant chemo-immunotherapy has shown promise in improving survival outcomes for non-small cell lung cancer (NSCLC) patients, with pathologic response serving as a critical predictor of long-term outcomes. However, manual assessment of pathologic response is labor-intensive and subject to inter-observer variability. This study aimed to develop an automated AI-based solution to address these limitations. Methods We developed an AI-powered patch-based image analysis model to quantify residual viable tumor (RVT) in hematoxylin and eosin (H&E)-stained whole slide images. The model was evaluated on resected specimens from 47 NSCLC patients treated with neoadjuvant chemo-immunotherapy. The AI-derived estimates of RVT were compared with visual assessments by a board-certified pathologist. Statistical analysis included Pearson’s correlation for continuous tumor estimation and Cohen’s Kappa for concordance in major pathologic response (MPR) and pathologic complete response (pCR) classification. Results The AI model demonstrated a strong correlation with the pathologist’s continuous estimation of RVT ( r  = 0.77, p  < 0.001, confidence interval [CI]: 0.73–0.81). In the assessment of clinical endpoints, the model achieved an 89.36% concordance rate for MPR (Kappa = 0.79, p  < 0.001, CI: 0.61–0.96) and 89.36% concordance rate for pCR (Kappa = 0.56, p  < 0.001, CI: 0.24–0.89) when compared with the board-certified pathologist. Conclusions Our AI-powered model demonstrates potential as a decision-support tool for pathologic response assessments in NSCLC patients treated with neoadjuvant chemo-immunotherapy.

The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl–Pro–His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.

Background Hypopharyngeal squamous cell carcinoma (SCC) is an aggressive malignancy with a poor prognosis, particularly in advanced stages. Concurrent chemoradiotherapy (CCRT) is frequently employed to preserve the larynx, but resistance to CCRT remains a significant clinical challenge. Understanding the tumor microenvironment (TME) in CCRT‐resistant cases is crucial for identifying predictive biomarkers and developing targeted therapies to improve outcomes. Methods This study analyzed tissue samples from patients with advanced hypopharyngeal SCC who were either resistant to CCRT or had not received CCRT. Spatial transcriptomics (ST) was used to explore the spatial molecular signatures within the TME of these samples, focusing on the interactions between immune cells and malignant cells. Results We identified six distinct cellular clusters in the hypopharyngeal SCC tissues, with a signature cluster more prominently present in CCRT‐resistant samples. The SPP1 gene was significantly overexpressed in these samples, specifically in macrophages, and was associated with increased ligand–receptor interactions involving malignant cells via CD44 and ITGB1. These interactions were primarily observed in peri‐tumoral and intratumoral regions, indicating a role for SPP1+ macrophages in modulating the TME and contributing to CCRT resistance. Further analysis revealed that SPP1‐mediated cell–cell interactions predominantly occurred between macrophages and malignant epithelial cells, highlighting their potential role in driving therapeutic resistance. Conclusions Our findings suggest that SPP1‐expressing macrophages play a pivotal role in the development of CCRT resistance in hypopharyngeal SCC through specific interactions with malignant cells. The spatial distribution of these macrophages and their interaction with cancer cells suggest a mechanism by which the TME contributes to therapeutic failure. These insights could inform the development of novel targeted therapies aimed at overcoming CCRT resistance, ultimately improving patient outcomes.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein–Barr virus (EBV)-associated lymphoproliferative disease. The disease course of HVLPD varies from an indolent course to progression to aggressive lymphoma. We investigated the characteristics of HVLPD in Korean patients. HVLPD patients at Seoul National University Hospital between 1988 and 2019 were retrospectively analyzed. This study included 26 HVLPD patients who all presented with recurrent papulovesicular and necrotic eruption on the face, neck, and extremities. EBV was detected from the skin tissues of all patients. HVLPD was diagnosed during childhood (age < 18 years) in seven patients (26.9%) and in adulthood (age ≥ 18 years) in 19 cases (73.1%). The median age at diagnosis was 24.0 years (range 7–70 years). HVLPD has various clinical courses, from an indolent course to progression to systemic lymphoma. Fourteen patients (53.8%) developed lymphoma: systemic EBV-positive T-cell lymphoma (n = 9, 34.6%); extranodal natural killer/T-cell lymphoma, nasal type (n = 3, 11.5%); aggressive natural killer/T-cell leukemia (n = 1, 3.8%); and EBV-positive Hodgkin lymphoma (n = 1, 3.8%). Mortality due to HVLPD occurred in five patients (26.3%) in the adult group, while it was one patient (14.3%) in the child group. As lymphoma progression and mortality occur not only in childhood but also in adulthood, adult-onset cases may need more careful monitoring.

Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5‐mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo . Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia. SYNOPSIS This study presents an adiponectin‐derived, transdermally deliverable pentapeptide (GLYYF) that promotes hair growth by activating AdipoR1. We discovered a small transdermally deliverable 5‐mer peptide (GLYYF: P5) that activates AdipoR1. P5 promotes hair growth by activating AdipoR1 and could be potentially used as a topically applicable molecule for treatment of alopecia patients. Furthermore, we identified a position and essential amino acid residues on AdipoR1 involved in binding of adiponectin protein. Graphical Abstract This study presents an adiponectin‐derived, transdermally deliverable pentapeptide (GLYYF) that promotes hair growth by activating AdipoR1.

Alopecia arises due to inadequate hair follicle (HF) stem cell activation or proliferation, resulting in prolongation of the telogen phase of the hair cycle. Increasing therapeutic and cosmetic demand for alleviating alopecia has driven research toward the discovery or synthesis of novel compounds that can promote hair growth by inducing HF stem cell activation or proliferation and initiating the anagen phase. Although several methods for evaluating the hair growth-promoting effects of candidate compounds are being used, most of these methods are difficult to use for large scale simultaneous screening of various compounds. Herein, we introduce a simple and reliable in vitro assay for the simultaneous screening of the hair growth-promoting effects of candidate compounds on a large scale. In this study, we first established a 3D co-culture system of human dermal papilla (hDP) cells and human outer root sheath (hORS) cells in an ultra-low attachment 96-well plate, where the two cell types constituted a polar elongated structure, named “two-cell assemblage (TCA).” We observed that the long axis length of the TCA gradually increased for 5 days, maintaining biological functional integrity as reflected by the increased expression levels of hair growth-associated genes after treatment with hair growth-promoting molecules. Interestingly, the elongation of the TCA was more prominent following treatment with the hair growth-promoting molecules (which occurred in a dose-dependent manner), compared to the control group ( p < 0.05). Accordingly, we set the long axis length of the TCA as an endpoint of this assay, using a micro confocal high-content imaging system to measure the length, which can provide reproducible and reliable results in an adequate timescale. The advantages of this assay are: (i) it is physiologically and practically advantageous as it uses 3D cultured two-type human cells which are easily available; (ii) it is simple as it uses length as the only endpoint; and (iii) it is a high throughput system, which screens various compounds simultaneously. In conclusion, the “TCA” assay could serve as an easy and reliable method to validate the hair growth-promoting effect of a large volume of library molecules.