SpatialSPM: statistical parametric mapping for the comparison of gene expression pattern images in multiple spatial transcriptomic datasets.

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.

Dermoscopic Evaluation of Inflammatory Nail Disorders and Their Mimics.

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.

Surgical management of lipomas: Proposal of the Z-incision design and surgical algorithm based on tumor size.

Surgical excision is the treatment of choice for lipomas. However, linear incision methods or minimal extraction techniques often do not provide a sufficient surgical view. Therefore, removing large lipomas is often difficult. To present the Z-incision and half Z-incision designs for lipoma extraction, this retrospective study analyzed lipomas surgically excised at our institution between September 2015 and December 2018. The area of surgical field exposed by the Z-incision versus that exposed by the linear incision was calculated using a schematic model. Cure rate, complications, and surgical field area were investigated. A total of 84 lipomas were included. A Z- or half Z-incision was used to treat 30 lipomas, while a linear incision was used to treat 54 lipomas. The mean diameter of the mass in the Z- or half Z-incision group was 47.7 mm (range, 15-160 mm), larger than that in the linear incision group (25.5 mm; range, 7-59 mm) (p < .001). The Z-incision involved making rectangular windows by lifting 2 triangular flaps. According to our mathematical model, the Z-incision provided a larger surgical field area than that provided by the linear incision based on stretched angles (1.81 times larger at 30° and 3.14 times larger at 15°). The Z- and half Z-incisions were successfully performed in all but 1 lipoma (29 lipomas, 96.7%). There was 1 lipoma that resulted in postoperative complications (seroma, 3.3%). The Z-incision design can be a useful alternative technique for the extirpation of lipomas, especially large lipomas. Here, we proposed a surgical algorithm for lipoma surgery based on tumor size.

Misclassification of study designs in the dermatology literature.

BACKGROUND: The appropriate classification of study designs is important for review and assessment of the relevant scientific literature as a basis for decision making; however, little is known about whether study designs have been appropriately reported in the dermatology literature. OBJECTIVE: We aimed to validate the study designs in the dermatology literature and investigate discrepancies between author-reported and actual study designs. METHODS: We reviewed all issues of 3 major dermatology journals from January to December 2016. A total of 295 original articles investigating associations between exposures and health outcomes were included for analysis. We used a validated algorithm to classify the study designs. RESULTS: Among the 295 articles, 174 (59.0%) clearly mentioned the study design in the text. All interventional studies were correctly classified on the basis of study design (n = 42); however, 35 of 132 observational studies (26.5%) showed discrepancies between the author-reported and actual study design. When the author-reported design was a prospective cohort, retrospective cohort, or case-control study (n = 61), approximately half of the studies were misclassified by the authors (n = 30). LIMITATIONS: We analyzed only 3 journals in the dermatology field. CONCLUSIONS: Our findings revealed substantial discrepancies between author-reported and actual study designs in the dermatologic literature, particularly among observational studies.

A Novel Window Technique Using CO2 Laser, and a Review of Methods for Nail Matrix Biopsy of Longitudinal Melanonychia.

BACKGROUND: Nail matrix histopathological examination is essential to diagnose longitudinal melanonychia (LM). Several methods for nail matrix biopsy have been introduced but are often difficult to perform because of their invasiveness and technical difficulty. Therefore, a less invasive and novel biopsy technique is needed. OBJECTIVE: To introduce a window technique for nail matrix biopsy. MATERIALS AND METHODS: We retrospectively reviewed the medical records and histopathological specimens of patients with LM who underwent the window technique for nail matrix biopsy at our institution between September 2015 and December 2016. RESULTS: Eleven cases from 10 patients with LM were subjected to our tailored window technique assisted by carbon dioxide (CO2) laser and dermoscopy. We performed nail plate dermoscopy to select the biopsy site and used CO2 laser to create the window in the proximal nail plate. Nail matrix pigmentation was carefully investigated using intraoperative dermoscopy. The technique established appropriate diagnosis in 11 LM cases, without significant complications, as follows: melanoma in situ (4 cases) and nail matrix activation (7 cases). CONCLUSION: The window technique assisted by CO2 laser and dermoscopy can be a minimally invasive and effective method for nail matrix LM biopsy under local anesthesia.

Dermoscopic patterns of fungal melanonychia: A comparative study with other causes of melanonychia.

BACKGROUND: Diagnosing fungal melanonychia (FM) is often difficult because it mimics melanonychia caused by other factors. Dermoscopy is helpful in the setting of nail pigmentation. However, the diagnostic characteristics of FM on dermoscopy are not fully elucidated. OBJECTIVE: We sought to determine the dermoscopic characteristics of FM. METHODS: We evaluated the dermoscopic patterns of FM diagnosed at 2 university hospitals from January 2010 to February 2016. We included nail matrix melanocytic activation, nail matrix nevi, and nail unit malignant melanomas as control groups for comparison. RESULTS: In all, 18 FM, 24 melanocytic activation of the nail matrix, 27 nail matrix nevi, and 11 malignant melanoma cases were analyzed. Statistical analysis revealed that yellow color, multicolor pattern, nonlongitudinal homogenous pattern, reverse triangular pattern, subungual keratosis, white or yellow streaks, and scales on the nail were more frequent in FM. However, gray color, longitudinal pattern, and pseudo-Hutchinson sign were less frequent in FM than in controls. LIMITATIONS: This was a retrospective study from 2 university hospitals, with a small sample size. CONCLUSION: The results revealed distinctive dermoscopic patterns for FM. Therefore, dermoscopy can be a useful ancillary tool for diagnosing FM.

Dermoscopic features of nail matrix nevus (NMN) in adults and children: A comparative analysis.

BACKGROUND: Nail matrix nevus (NMN) is one cause of longitudinal melanonychia. The typical dermoscopic patterns of NMNs are well established. However, little is known about how the dermoscopic characteristics of NMNs differ between adults and children. OBJECTIVE: We sought to compare the dermoscopic characteristics of NMNs between adults and children. METHODS: We retrospectively reviewed the medical records of patients in whom NMN was diagnosed between 2005 and 2014. RESULTS: The dermoscopic findings of 58 NMNs from 56 children and 35 NMNs from 34 adults were analyzed. Pigmentation tended to be broader in children, without statistical significance (P = .062). Moreover, NMNs in children were darker and multicolored (P < .001). Pseudo-Hutchinson sign (P = .004), triangular sign (P = .001), and dots/globules (P = .004) were detected more commonly in children. An irregular pattern and Hutchinson sign were also found more frequently in children, without statistical significance (P = .071 and P = .249, respectively). LIMITATIONS: This was a retrospective study in a tertiary-level hospital. CONCLUSION: The dermoscopic findings showed that NMNs have more melanoma-associated features in children than in adults.

Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles.

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 3ß/ß-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.

Identifying patients with deteriorating generalized pustular psoriasis: Development of a prediction model.

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.

Diagnostic accuracy of dermoscopy for onychomycosis: A systematic review.

Background: Dermoscopy 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. Methods: We 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. Results: We 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%). Conclusion: This study highlights the commonly identified dermoscopic features of onychomycosis. Recognizing such characteristic dermoscopic features of onychomycosis can assist clinicians diagnose onychomycosis by the bedside.

Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts.

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.

Adiponectin-derived pentapeptide ameliorates psoriasiform skin inflammation by suppressing IL-17 production in γδT cells.

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.

Early onset female pattern hair loss: A case-control study for analyzing clinical features and genetic variants.

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 × 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.

Good Clinical Responders to Topical Timolol in Patients with Infantile Hemangiomas: A 7-Year Retrospective Study of 328 Korean Patients.

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.

Diagnosis of Onychomycosis: From Conventional Techniques and Dermoscopy to Artificial Intelligence.

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.

High-Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis.

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.