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12 result(s) for "Lew, Bark-Lynn"
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Ethnic-Specific and UV-Independent Mutational Signatures of Basal Cell Carcinoma in Koreans
Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology.
Incidence of New-Onset Inflammatory Bowel Disease, Oral and Gastrointestinal Candidiasis, Herpes Zoster, Pulmonary Tuberculosis, and Major Cardiovascular Events in Patients with Moderate-to-Severe Psoriasis Exposed to Biologics
The multicenter, retrospective cohort study was aimed at examining adverse events in biologic-treated patients with moderate-to-severe psoriasis by using a real-world database. Thus, we analyzed exposure-adjusted incidence rates for new-onset inflammatory bowel disease (IBD), oral and gastrointestinal candidiasis, pulmonary tuberculosis, herpes zoster, and major cardiovascular events (MACEs) in biologic-treated patients with moderate-to-severe psoriasis. Overall, 2085 patients were found to have been exposed to tumor necrosis factor (TNF)-α, interleukin (IL)-12/23, IL-17, and IL-23 inhibitors (n = 463, 540, 635, and 447, respectively). No patient developed new-onset IBD. The incidence rates of oral and gastrointestinal candidiasis were comparable between patients treated with IL-23 and IL-17 inhibitors (5.6 and 5.3 per 1000 PY, respectively). None treated with IL-17 or IL-23 inhibitors reported pulmonary tuberculosis. The incidence rate of herpes zoster was the highest in patients treated with TNF-α inhibitors (17.0 per 1000 PY), followed by IL-17, IL-23, and IL-12/23 inhibitors (13.3, 7.8, and 2.7 per 1000 PY, respectively). MACEs were not reported in patients treated with IL-17 inhibitors but were reported in those treated with TNF-α, IL-23, and IL-12/23 inhibitors (incidence: 5.6, 3.8, and 1.8 per 1000 PY, respectively). The study indicated favorable safety profiles of biologics in Korean patients with moderate-to-severe psoriasis.
Serial Hydrolysis for the Simultaneous Analysis of Catecholamines and Steroids in the Urine of Patients with Alopecia Areata
Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography–tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4–122.9% and 88.8–123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4–21.5% and 2.0–21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.
Human dermal fibroblast‐derived extracellular matrix reduces postinflammatory hyperpigmentation after fractional carbon dioxide laser facial resurfacing in Asians
Background Extracellular matrix (ECM) components promote the development of skin wounds by providing biological scaffolds and regenerative microenvironments. Aims To evaluate the beneficial effects of human dermal fibroblast‐derived ECM after fractional carbon dioxide laser resurfacing in Asians. Patients/Methods In this double‐blind, randomized, vehicle‐controlled, split‐face study, 15 participants with features of facial skin aging were treated with a single session of fractional carbon dioxide laser, followed by the application of either ECM (ECM group) or placebo (control group). In vivo skin parameters were measured at baseline and after 4 and 12 weeks of treatment using the Antera 3D®, Cutometer® MPA580, Dermascan®, and Tewameter®. Results A total of 14 participants (mean age 45.1 ± 9.7 years) completed the study. The change in melanin level was significantly lower in the ECM group than in the control group at week 12 (p < 0.05). Transient increase in erythema level was observed at week 4 in the control group, and the change in the erythema level was greater in the control group than in the ECM group (p = 0.014). Though the ECM group showed improvements in the dermal density, texture, transepidermal water loss, marionette lines (volume, maximum depth, and average depth), and nasolabial folds (volume, maximum depth, and length), no significant differences were found between the two groups. Treatment‐related adverse events were not reported. Conclusions We suggest that human dermal fibroblast‐derived ECM may be used as adjunctive therapy after fractional carbon dioxide resurfacing to prevent postinflammatory hyperpigmentation in Asians.
Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia
Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher's exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.
Long‐Term Efficacy and Safety of Low‐Level Laser Therapy for Androgenetic Alopecia: A 12‐Month Prospective Trial
Background Low‐level laser therapy (LLLT) has emerged as a nonpharmacologic intervention for androgenetic alopecia (AGA), but evidence on its long‐term efficacy remains limited. Objective To evaluate the 12‐month effectiveness and safety of a home‐use helmet‐type LLLT device in individuals with AGA. Materials and Methods This prospective, open‐label study enrolled 68 patients (51 men, 17 women) with mild to severe AGA. Participants used a helmet‐type LLLT device emitting red light (646–675 nm) three times per week for 20 min over 48 weeks. Hair density and shaft thickness were assessed using phototrichogram at predefined intervals. Additional evaluations included blinded global photographic assessments and patient‐reported outcomes. Results Hair density increased significantly from a baseline mean of 99.2 ± 27.7 to 124.2 ± 33.1 hairs/cm2 at 48 weeks (mean change +25.0 ± 28.1, p < 0.0001). Mean hair shaft thickness rose from 65.1 ± 11.8 to 74.9 ± 12.6 μm (p < 0.0001), reflecting an approximate 15% improvement. Gains were consistent across sexes and AGA severity levels. By Week 48, 59% of participants were rated as improved based on global photographs, and over 85% expressed satisfaction with treatment. No adverse events related to the device were reported, and adherence was high throughout the study. Conclusion Twelve months of home‐use LLLT resulted in sustained improvements in hair density and thickness with excellent tolerability. These findings support its role as a safe, effective, and user‐friendly long‐term therapeutic option for patients with AGA.
Cross-sectional study of psychiatric comorbidities in patients with atopic dermatitis and nonatopic eczema, urticaria, and psoriasis
Recent data suggest depression has been linked to chronic skin diseases, including atopic dermatitis (AD), urticaria, and psoriasis. This study compared mental illnesses in patients with AD with those of patients with nonatopic eczema, urticaria, and psoriasis in Korea. A cross-sectional study design was used, analyzing data from the 2015 Korean National Health Insurance Research Database, a survey of 42,641 AD and 139,486 non-AD (nonatopic eczema, urticaria, and psoriasis) patients (103,938 males, 78,189 females) classified by age: infant, aged 0-3 years; early childhood, aged 4-8 years; late childhood, aged 9-12 years; adolescent, aged 13-18 years; adult, aged 19-64 years; elderly, aged above 65 years. Multiple logistic regression analysis was performed, and the odds ratio (OR) of various mental illnesses - attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), conduct disorder, depression, anxiety, suicidal ideation, schizophrenia, and sleep disorder - were calculated for patients with and without AD. The incidence of depression was not significantly different between AD and non-AD patients. Severe AD showed a high OR of depression (moderate AD OR=1.75; severe AD OR=3.15, <0.0001). Patients with AD had significantly higher incidence of ADHD (OR=1.48; 95% CI=1.27-1.72), ASD (OR=1.54; 95% CI=1.19-1.99), and conduct disorder (OR=2.88; 95% CI=1.52-5.45). Patients with AD were not found to have higher incidence of depression than non-AD patients. However, severe AD patients were determined to have a significantly higher incidence of depression. Therefore, the severity of dermatitis is thought to contribute to depression. Mental illnesses found to be significantly higher in AD patients were ADHD, ASD, and conduct disorder.
Alterations in Pattern Baldness According to Sex: Hair Metabolomics Approach
Pattern baldness has been associated with the male hormone, dihydrotestosterone. In this study, we tried to determine how the overall metabolic pathways of pattern baldness differ in patients and in normal controls. Our study aimed to identify alterations in hair metabolomic profiles in order to identify possible markers of pattern baldness according to sex. Untargeted metabolomics profiling in pattern baldness patients and control subjects was conducted using ultra-performance liquid chromatography-mass spectrometry. To identify significantly altered metabolic pathways, partial least squares discriminant analysis was performed. Our analysis indicated differences in steroid biosynthesis pathway in both males and females. However, there was a remarkable difference in the androgen metabolic pathway in males, and the estrogen metabolic and arachidonic acid pathways in females. For the first time, we were able to confirm the metabolic pathway in pattern baldness patients using hair samples. Our finding improves understanding of pattern baldness and highlights the need to link pattern baldness and sex-related differences.
Sex-related differences in urinary immune-related metabolic profiling of alopecia areata patients
IntroductionAlopecia areata is a well-known autoimmune disease affecting humans. Polyamines are closely associated with proliferation and inflammation, and steroid hormones are involved in immune responses. Additionally, bile acids play roles in immune homeostasis by activating various signaling pathways; however, the roles of these substances and their metabolites in alopecia areata remain unclear.ObjectivesIn this study, we aimed to identify differences in metabolite levels in urine samples from patients with alopecia areata and healthy controls.MethodsTo assess polyamine, androgen, and bile acid concentrations, we performed high-performance liquid chromatography–tandem mass spectrometry.ResultsOur results showed that spermine and dehydroepiandrosterone levels differed significantly between male patients and controls, whereas ursodeoxycholic acid levels were significantly higher in female patients with alopecia areata than in controls.ConclusionOur findings suggested different urinary polyamine, androgen, and bile acid concentrations between alopecia areata patients and normal controls. Additionally, levels of endogenous substances varied according to sex, and this should be considered when developing appropriate treatments and diagnostic techniques. Our findings improve our understanding of polyamine, androgen, and bile acid profiles in patients with alopecia areata and highlight the need to consider sex-related differences.