Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by sensitivity to sunlight and predisposition to cutaneous malignancies. There are various types, including the Variant type, which does not manifest with acute sunburn reactions. This results to the development of multiple malignancies that are often discovered at late stages, making management more challenging. This is a case of a 54-year-old Filipino female presenting with multiple basal cell carcinomas (BCCs) on several areas of the face and advanced cutaneous squamous cell carcinoma (cSCC) on the right zygomatic area, treated with imiquimod 5% cream and external beam radiation therapy, respectively. There was an excellent response of the BCCs to imiquimod 5% cream and good tumoral response of the SCC to radiation therapy, with tolerable side effects, highlighting the use of these palliative treatment modalities for XP patients with multiple, unresectable, or difficult-to-treat cutaneous malignancies.

WSWs have the potential to reliably and continuously screen for AFib and detect it in a timely manner.The inconclusive results produced by WSWs are a significant problem. Once the inconclusive results are rectified, WSWs may be used for widespread screening of AFib in those people who are at high risk of developing AFib.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Objective: Problematic use of social media (PUSM) may affect sleep quality and self-stigma in people with schizophrenia and consequently reduce their quality of life (QoL). This longitudinal study investigated if sleep quality and self-stigma mediated relationships between PUSM and QoL. Methods: One-hundred-and-ninety-three outpatients with schizophrenia were recruited from a psychiatric center in Taiwan from April 2019 to August 2021 and participated in a longitudinal study at intervals of three months between measurements. QoL was assessed using the World Health Organization Quality of Life Questionnaire Brief Version; sleep quality using the Pittsburgh Sleep Quality Index; self-stigma using the Self-Stigma Scale-Short; and PUSM using the Bergen Social Media Addiction Scale. Via SPSS 20.0, general estimating equation models assessed temporal associations between variables. Via R software, mediating effects of self-stigma and sleep quality were examined through Monte Carlo simulations with 20,000 repetitions. Results: Mean scores of physical, psychological, social and environmental QoL ranged from 11.86 to 13.02. Mean scores of sleep quality and self-stigma were 9.1±4.5 and 2.2±0.8, respectively. Sleep quality and self-stigma were directly related to QoL (p<0.001) and mediated indirect relationships between PUSM and all components of QoL with a range of 95% confidence intervals spanning from -0.0591 to -0.0107 for physical QoL; -0.0564 to -0.0095 for psychological QoL; -0.0292 to -0.0035 for social QoL; and -0.0357 to -0.0052 for environmental QoL. Conclusion Sleep quality and self-stigma mediated relationships between PUSM and QoL in people with schizophrenia. Developing interventions targeting PUSM, sleep, and self-stigma may help improve QoL in people with schizophrenia.

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases.Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients.We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies.A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. Conclusions The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects* ; Exanthema/chemically induced* ; Far East ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Thiohydantoins/adverse effects*

BACKGROUND: Particulate matter (PM) < 2.5 μm (PM METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM RESULTS: DLEC1 methylation and PM CONCLUSIONS We found significant positive associations between PM
Adult ; Aged ; Air Pollutants/adverse effects* ; DNA Methylation/drug effects* ; Environmental Exposure/adverse effects* ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Particulate Matter/adverse effects* ; Taiwan ; Tumor Suppressor Proteins/metabolism*

Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.
Astrocytoma ; genetics ; metabolism ; pathology ; Cell Adhesion Molecules ; genetics ; metabolism ; Cell Line, Tumor ; Central Nervous System Neoplasms ; genetics ; metabolism ; pathology ; CpG Islands ; genetics ; DNA Methylation ; Down-Regulation ; Gene Deletion ; Glioblastoma ; genetics ; metabolism ; pathology ; Humans ; Oligodendroglioma ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; Survival Rate

It is not yet understood how the enhanced expression of pancreatic adenocarcinoma up-regulated factor (PAUF; a novel oncogene identified in our recent studies), contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up-regulates the expression and transcriptional activity of beta-catenin while the suppression of PAUF by shRNA down-regulates beta-catenin. The induction of beta-catenin by PAUF is mediated by the activities of Akt and GSK-3beta, but inhibition of downstream ERK does not reduce beta-catenin expression. To test whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated signaling pathway for the stabilization of beta-catenin, we examined the phosphorylation status of beta-catenin in the presence of PAUF compared with that of beta-catenin during treatment with Wnt3a or dibutyryl cAMP, a cell permeable cyclic AMP analogue. PAUF expression induces phosphorylation at Ser-33/37/Thr-41 and Ser-675 of beta-catenin but no phosphorylation at Ser-45, indicating that a unique phosphorylation pattern of beta-catenin is caused by PAUF. Finally, the expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of beta-catenin, leading to a rapid proliferation of pancreatic cells; conversely decreased PAUF expression (by shRNA) results in the reduced proliferation of pancreatic cells. Treatment with hexachlorophene (an inhibitor of beta-catenin) reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken together, we propose that PAUF can up-regulate and stabilize beta-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells.
*Adenocarcinoma/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/metabolism ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3/metabolism ; HEK293 Cells ; Humans ; Lectins/genetics/*metabolism ; *Pancreatic Neoplasms/metabolism/pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Signal Transduction ; *Up-Regulation ; beta Catenin/genetics/*metabolism