Paediatric nail matrix nevi show age-dependent clinical and dermoscopic patterns. In this retrospective cohort, acquired lesions more often presented as narrow, regular, single-colour bands than congenital or congenital-type lesions. These findings suggest that age at onset may help refine the evaluation of paediatric longitudinal melanonychia.

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.

Spatial transcriptomic (ST) techniques help us understand the gene expression levels in specific parts of tissues and organs, providing insights into their biological functions. Even though ST dataset provides information on the gene expression and its location for each sample, it is challenging to compare spatial gene expression patterns across tissue samples with different shapes and coordinates. Here, we propose a method, SpatialSPM, that reconstructs ST data into multi-dimensional image matrices to ensure comparability across different samples through spatial registration process. We demonstrated the applicability of this method by kidney and mouse olfactory bulb datasets as well as mouse brain ST datasets to investigate and directly compare gene expression in a specific anatomical region of interest, pixel by pixel, across various biological statuses. Beyond traditional analyses, SpatialSPM is capable of generating statistical parametric maps, including T-scores and Pearson correlation coefficients. This feature enables the identification of specific regions exhibiting differentially expressed genes across tissue samples, enhancing the depth and specificity of ST studies. Our approach provides an efficient way to analyze ST datasets and may offer detailed insights into various biological conditions.

Department of Dermatology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; College of Pharmacy, Chungnam National University, Daejeon, Korea; Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea; Division of Clinical Epidemiology, Medical Research Collaborating Center, Biomedical Research Institution, Seoul National University Hospital, Seoul, Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea; Department of Dermatology, Dongguk University Ilsan Hospital, Goyang, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

INTRODUCTION:Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. OBJECTIVES:To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. METHODS:The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. RESULTS:During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs. CONCLUSIONS:Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.

Spatial transcriptomics (ST) technologies provide comprehensive biological insights regarding cell-cell interactions and peri-cellular microenvironments. ST technologies are divided into two categories: imaging-based (I-B) and barcode-based (B-B). I-B ST technologies provide high resolution and sensitivity but have limited gene coverage. B-B ST technologies can analyze the whole transcriptome but have lower spatial resolution. To address these limitations, we propose a deep learning-based model that integrates I-B and B-B ST technologies to increase gene coverage while preserving high resolution. A model, trained by a neural network with an adversarial loss based on I-B and B-B datasets from human breast cancer tissue, was able to extend gene coverage to whole transcripts-level and accurately predict gene expression patterns in the I-B dataset with a high resolution. This novel methodology, named GeneDART, could enable researchers to utilize B-B and I-B ST datasets in a complementary way.

Background: Female pattern hair loss (FPHL), the most common cause of alopecia in adult women, is classified into two subtypes: early onset and late onset (or postmenopausal). Little is known about the clinical features and genetic characteristics of early onset female pattern hair loss (eFPHL). Objectives: To investigate the clinical features and genetic characteristics of eFPHL. Methods: Patients with eFPHL and controls without eFPHL were prospectively recruited. The demographic and clinical features were collected. Single nucleotide polymorphisms (SNPs) located around the selected 30 candidate genes potentially associated with eFPHL were evaluated. Results: eFPHL patients (n = 63) manifested a decreased hair shaft density and cross-sectional area of the hair shaft compared to the control group (n = 341). eFPHL is associated with androgen-related features, including scalp greasiness, folliculitis, hirsutism, and polycystic ovary syndrome. Scalp pain and itching have been reported more frequently in patients with eFPHL. Forty-nine SNPs located around PPARGC1A, ABCC4, CYP11B2, FSHB, and CYP19A1 were found to be significant for eFPHL, including two PPARGC1A-associated SNPs: rs186530605 and rs192713767 (p = 3.94 x 10(-11)). Conclusions: This study provided clinical features and genetic variants for eFPHL, which could provide insight into the underlying pathologic etiology. Considering the limited number of patients, a large-scale study is required in the future. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.

Dermal fibroblasts lose stem cell potency after birth, which prevents regenerative healing. However, the underlying intracellular mechanisms are largely unknown. We uncover the postnatal maturation of papillary fibroblasts (PFs) driven by the extensive Twist2-mediated remodeling of chromatin accessibility. A loss of the regenerative ability of postnatal PFs occurs with decreased H3K27ac levels. Single-cell transcriptomics, assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) reveal the postnatal maturation trajectory associated with the loss of the regenerative trajectory in PFs, which is characterized by a marked decrease in chromatin accessibility and H3K27ac modifications. Histone deacetylase inhibition delays spontaneous chromatin remodeling, thus maintaining the regenerative ability of postnatal PFs. Genomic analysis identifies Twist2 as a major regulator within chromatin regions with decreased accessibility during the postnatal period. When Twist2 is genetically deleted in dermal fibroblasts, the intracellular cascade of postnatal maturation is significantly delayed. Our findings reveal the comprehensive intracellular mechanisms underlying intrinsic postnatal changes in dermal fibroblasts.

Background Topical timolol is widely used for treatment of superficial infantile hemangioma (IH). However, little is known about factors that affect the response to topical timolol treatment. Objective This study aimed to investigate the efficacy, safety, and predictive value for good response to topical timolol for IH. Methods A retrospective review of medical records and clinical photos of 328 patients with IH treated with topical timolol 0.5% solution was conducted. Serial clinical photographs were compared with those at the initial visit using a 100-mm visual analogue scale (VAS). Treatment response was defined as an improvement of at least 75% from baseline in IH lesions within 12 months of treatment. Results Overall, IH patients treated with topical timolol showed significant improvement from baseline, showing that the final VAS score within 12 months of treatment was 69.7±20.4. The multivariable logistic regression analysis showed age at initiation of treatment (p=0.007), length of gestation and fetal growth (p=0.03), depth (p=0.01), and flexural area (p=0.007) were significantly associated with treatment response. Only four patients (1.1%) reported local irritation. Conclusion This study demonstrated that topical timolol treatment was an effective and well-tolerated treatment for IHs. Physicians are encouraged to consider several patient- or lesional factors that might affect treatment response to achieve better clinical outcomes.

Particulate matter (PM) is among the leading environmental causes of diseases worldwide, and increases mortality and morbidity from cardiovascular and respiratory diseases [1]. Interestingly, increasing evidence suggests that PM is related to hair growth. PM of small diameters can penetrate hair follicles (HFs) in vivo and induce cutaneous inflammatory responses [2]. Recently, an epidemiological study demonstrated that PM concentration partially corresponds to the flare pattern of alopecia areata, the most common inflammatory hair loss disorder [3].

BACKGROUND:Psoriasis is a common immunologic chronic skin disease that affects at least 100 million individuals worldwide. Adiponectin is associated with psoriasis and suppresses psoriasiform inflammation. Recently, a small-sized transdermally deliverable 5-mer peptide (GLYYF; P5) was discovered as a potential adiponectin receptor 1 agonist. OBJECTIVES:To confirm reduction in adiponectin protein level in the human skin and investigate whether functional adiponectin replenishment by topical P5 application improves psoriasiform skin inflammation. METHODS:Adiponectin protein expression in the skin of individuals with psoriasis and normal skin was examined by immunofluorescence staining. Imiquimod-induced psoriasis-like skin inflammation was induced in wild-type (WT) and adiponectin-deficient (Adipoq-/-) mice. Vehicle and P5 were topically applied to the back skin and ears of mice. Histological study, reverse-transcription quantitative polymerase chain reaction, multiplex-bead array assay, and flow cytometric analysis were performed. RESULTS:Adiponectin protein expression was downregulated both in the epidermis and dermis of psoriatic lesions as compared to that in the normal skin. Topically applied P5 attenuated the severity of imiquimod-induced psoriatic dermatitis in both WT and Adipoq-/- mice by decreasing the expression of psoriasis-related cytokines (Il17a, Il1b, Il6, and Tnfa). P5 application significantly reduced the proportion of interleukin-17A-producing γδT cells. CONCLUSION:Transdermally deliverable adiponectin receptor 1 agonist, P5, can be a potential peptide drug to manage psoriasis by mediating the anti-psoriatic effect of adiponectin.

Generalized pustular psoriasis (GPP) is a life-threatening condition; however, little is known about the factors that can predict GPP patients manifesting a deteriorating course. To investigate the demographics and clinical features of adult inpatient GPP and propose a prediction model for detecting fatal GPP (fGPP) and GPP requiring intensive care unit admission (iGPP) patients, a nationwide population-based retrospective cohort study was conducted. The adult inpatients with GPP from January 2007 to December 2020 were assessed. The 800 cases were aged 51.0 years (median [interquartile range, 37.0-64.0]). Overall, 21 iGPP (64.0 years [54.0-77.0]) and 17 fGPP (75.0 years [68.0-77.0]) cases were identified as deteriorating GPP. Renal disease (odds ratio [OR], 7.31), myocardial infarction history (OR, 4.29), liver disease (OR, 2.82), and diabetes mellitus (OR, 2.34) were identified as predictors for iGPP. For fGPP, myocardial infarction history (OR, 5.10) and psoriasis history (OR, 3.13) were established as predictors. A prediction model with scores ranging 0-11 points showed a reliable diagnostic value in detecting deteriorating GPP (area under the curve = 0.75 for iGPP and 0.83 for fGPP). In conclusion, this study provides the clinical features of deteriorating GPP. A prediction model may help physicians to identify patients with deteriorating GPP.

BackgroundDermoscopy is a non-invasive adjuvant diagnostic tool that allows clinicians to visualize microscopic features of cutaneous disorders. Recent studies have demonstrated that dermoscopy can be used to diagnose onychomycosis. We performed this systematic review to identify the characteristic dermoscopic features of onychomycosis and understand their diagnostic utility.MethodsWe searched the Medline, Embase, Scopus, and Cochrane databases from conception until May 2021. Studies on the dermoscopic features of onychomycosis were screened. The exclusion criteria were as follows: fewer than 5 cases of onychomycosis, review articles, and studies including onychomycosis cases that were not mycologically verified. Studies on fungal melanonychia were analyzed separately. We adhered to the MOOSE guidelines. Independent data extraction was performed. Data were pooled using a random effects model to account for study heterogeneity. The primary outcome was the diagnostic accuracy of the dermoscopic features of onychomycosis. This was determined by pooling the sensitivity and specificity values of the dermoscopic features identified during the systematic review using the DerSimonian-Laird method. Meta-DiSc version 1.4 and Review Manager 5.4.1 were used to calculate these values.ResultsWe analyzed 19 articles on 1693 cases of onychomycosis and 5 articles on 148 cases of fungal melanonychia. Commonly reported dermoscopic features of onychomycosis were spikes or spiked pattern (509, 30.1%), jagged or spiked edges or jagged edge with spikes (188, 11.1%), jagged proximal edge (175, 10.3%), subungual hyperkeratosis (131, 7.7%), ruins appearance, aspect or pattern (573, 33.8%), and longitudinal striae (929, 54.9%). Commonly reported features of fungal melanonychia included multicolor (101, 68.2%), non-longitudinal homogenous pigmentation (75, 50.7%) and longitudinal white or yellow streaks (52, 31.5%).ConclusionThis study highlights the commonly identified dermoscopic features of onychomycosis. Recognizing such characteristic dermoscopic features of onychomycosis can assist clinicians diagnose onychomycosis by the bedside.

Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0–43%), NRAS (0–31%), KIT (0–50%), NF1 (0–50%), and GNAQ (0–25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

The environment surrounding a newborn undergoes remarkable changes throughout the birth. Specifically, the initial warm, humid, and relatively sterile conditions become cool, dry, and full of exposome (pathogens and mechanical stress). Neonatal skin protects newborns from the surrounding environment. However, it scores as functionally incompetent according to non-invasive, on-surface measurements [ 1 Fluhr J.W. Bellemère G. Ferrari C. De Belilovsky C. Boyer G. Lachmann N. et al. age-dependent transformation of skin biomechanical properties and micromorphology during infancy and childhood. J. Invest. Dermatol. 2019; 139: 464-466 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar , 2 Fluhr J.W. Darlenski R. Taieb A. Hachem J.P. Baudouin C. Msika P. et al. Functional skin adaptation in infancy - almost complete but not fully competent. Exp. Dermatol. 2010; 19: 483-492 Crossref PubMed Scopus (102) Google Scholar ]. With the limited availability of human newborn skin tissue, transcriptomic studies on postnatal maturation remain rare. To fill this knowledge gap, our study assessed a mouse skin single-cell RNA sequencing (scRNA-seq) dataset to investigate transcriptomic changes occurring during the neonatal maturation period. We focused on interfollicular keratinocytes (IFKs), the primary cells in the epidermis. The results point to primary candidate genes related to postnatal maturation, including biomechanical change [ [1] Fluhr J.W. Bellemère G. Ferrari C. De Belilovsky C. Boyer G. Lachmann N. et al. age-dependent transformation of skin biomechanical properties and micromorphology during infancy and childhood. J. Invest. Dermatol. 2019; 139: 464-466 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ].

Nail dermoscopy (onychoscopy) is a valuable diagnostic tool for evaluating diseases in the nail apparatus. It is non-invasive, allowing clinicians to prioritize particular nails for biopsy. Thus, it can improve diagnostic accuracy and expedite treatment. Evaluating inflammatory nail disorders using onychoscopy is a relatively new approach to clinical assessment and has the potential to augment clinical care. This review highlights key dermoscopic features of major inflammatory nail disorders, including trachyonychia, nail psoriasis, nail lichen planus, onychotillomania, nail lichen striatus and allergic contact dermatitis due to artificial nails. It also illustrates their management and differential diagnoses, including onychomycosis, onycholysis, nail dystrophy due to systemic amyloidosis and malignant nail tumours. Limitations of this review included the low amount of literature on this topic and non-standardized terminology used among research-ers. As onychoscopy is a relatively new technique, further studies and standardization of terminology are warranted to consolidate the role of dermoscopy in evaluating inflammatory nail disorders.

Dissolving microneedles (DMN) supplemented with therapeutic molecules have been developed to enhance transdermal delivery efficiency of topically applied drugs in a minimally invasive manner. However, the dose of the drugs in DMN system is limited owing to the low solubility of drug. In fact, although triamcinolone acetonide (TA) is one of the most widely prescribed drugs for relieving atopic dermatitis (AD), its poor dissolving nature makes it difficult to design and fabricate DMN containing therapeutic dosage of TA. In this study, TA suspension is introduced to encapsulate therapeutic dosage of TA. Sonication and composition optimization of polymers is key to fabricate high dose TA-DMN to induce particle size reduction and dispersion stability of suspension, respectively. After confirming the physical performance of TA-DMN using the selected formulation in vitro, the anti-inflammatory effects of TA-DMN are evaluated in vivo using a mouse model affected with skin inflammation to mimic AD in humans. Herein, high-dose TA-DMN is presented as a candidate agent for relieving AD and, furthermore, for wide application in the treatment of skin inflammatory diseases in which high-dose steroid drugs are required.

Journal of the European Academy of Dermatology and VenereologyVolume 35, Issue 7 p. e464-e466 Letter To The Editor Dermoscopic patterns of green nail syndrome J. Ohn, J. Ohn Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, KoreaSearch for more papers by this authorK. Hur, K. Hur orcid.org/0000-0003-0928-951X Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, KoreaSearch for more papers by this authorH. Park, H. Park Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Department of Dermatology, Seoul Metropolitan Government - Seoul National University Borame Medical Center, Seoul, KoreaSearch for more papers by this authorS. Cho, S. Cho orcid.org/0000-0003-2468-485X Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Department of Dermatology, Seoul Metropolitan Government - Seoul National University Borame Medical Center, Seoul, KoreaSearch for more papers by this authorJ.-H. Mun, Corresponding Author J.-H. Mun jehomun@gmail.com orcid.org/0000-0002-0734-2850 Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Correspondence: Je-Ho Mun. E-mail: jehomun@gmail.comSearch for more papers by this author J. Ohn, J. Ohn Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, KoreaSearch for more papers by this authorK. Hur, K. Hur orcid.org/0000-0003-0928-951X Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, KoreaSearch for more papers by this authorH. Park, H. Park Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Department of Dermatology, Seoul Metropolitan Government - Seoul National University Borame Medical Center, Seoul, KoreaSearch for more papers by this authorS. Cho, S. Cho orcid.org/0000-0003-2468-485X Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Department of Dermatology, Seoul Metropolitan Government - Seoul National University Borame Medical Center, Seoul, KoreaSearch for more papers by this authorJ.-H. Mun, Corresponding Author J.-H. Mun jehomun@gmail.com orcid.org/0000-0002-0734-2850 Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea Institute of Human-Environment Interface Biology, Seoul National University, Seoul, Korea Correspondence: Je-Ho Mun. E-mail: jehomun@gmail.comSearch for more papers by this author First published: 16 March 2021 https://doi.org/10.1111/jdv.17224Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume35, Issue7July 2021Pages e464-e466 RelatedInformation