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Penile squamous cell carcinoma (PSCC) is a rare genitourinary malignancy, and factors of its tumor microenvironment (TME) could serve as prognostic indicators for tumor recurrence and metastasis. Here, we generated a comprehensive single-cell map of PSCC (66421 cells) and identified 9 distinct cell populations with samples from nine tumor samples and six adjacent normal samples. Among the malignant cells, SEMA3Chigh Mals was found to be associated with epithelial-mesenchymal transition. T cells in tumor tissues are in a highly exhausted state, while SPP1high TAMs were observed to promote tumor progression. Cancer-associated fibroblasts were found to interact with malignant cells to facilitate EMT through several pathways. Notably, there is a specific type of pericyte called POSTN+ pericytes, which can promote angiogenesis and extracellular matrix remodeling in PSCC. Finally, SEMA3C was identified as an effective biomarker reflecting cancer stage and microvessel density. Overall, we investigated the heterogeneity of TME from a single-cell perspective and demonstrated that SEMA3C serve as an effective biomarker for predicting lymph node metastasis and prognosis in PSCC. These findings may offer valuable insights for future therapeutic strategies.

Introduction: Molluscum contagiosum (MC) is an easily transmitted poxvirus infection most commonly affecting children, where it normally causes multiple benign papules associated with itching, pain, and inflammation. Typical treatment guidance includes a watch and wait approach over 2 to 4 years with no current consensus on the best form of active therapy. This retrospective chart review aimed to determine whether microwave therapy could be a suitable and safe treatment modality for children and adults with MC. Methods: 35 patients were treated at a single podiatry clinic in Geelong, Australia, with microwave energy in up to 3 sessions, 4 weeks apart, being monitored for resolution and adverse events. Results: All patients’ lesions resolved after an average of 2.1 treatments. There was no difference in the number of treatments required for children versus adults to achieve complete resolution. Treatment-associated pain was transient, localized, and tolerable. No other adverse events were observed. Conclusion: These outcomes suggest that microwave therapy has the potential to be a new modality for the treatment of MC as it can be highly efficacious, safe, and equally applicable to children and adults.

Published data suggest that knee brace use may reduce the risk of primary noncontact knee ligament injury. However, the use of knee braces remains contentious due to concerns about performance hindrance. As knee brace use is a potentially modifiable risk factor, this study aimed to identify whether after 17.5 hours of functional knee brace (FKB) use, discounting and continued use of FKB hamper performance during anaerobic and aerobic tasks. Prospective repeated-measures crossover study. Academic laboratory testing. Twenty-seven healthy male provincial basketball and national field hockey athletes. Over 6 days of 12 testing sessions, during 3 test conditions (nonbraced, braced, and removed brace or continued brace use), anaerobic and aerobic performance was evaluated after removing a custom-fitting FKB after 17.5 hours and with continued FKB for 21.0 hours. Anaerobic and aerobic, predicted maximum oxygen uptake (V̇O 2max ), performance. In the anaerobic endurance test, after 17.5 hours of FKB use, FKB removal led to a slower performance of nonsignificant 0.27 ± 0.26 s and higher fatigue levels ( P = 0.741, 95% CI, 16.00-17.23, Cohen effect size (ES) = small); continued FKB use for 21 hours resulted in nonsignificantly 0.25 ± 0.24 s faster performance and lower fatigue levels ( P = 0.626, 95% CI, 15.96-16.94, ES = trivial). In the aerobic capacity test, FKB removal resulted in a nonsignificantly lower V̇O 2max (3.0 ± 0.5 mL·kg -1 ·minute -1 , P = 0.518, 95% CI, 43.58-45.62, ES = large); continued FKB use led to a significantly higher V̇O 2max (1.5 ± 0.5 mL·kg -1 ·minute -1 , P = 0.005, 95% CI, 46.72-48.54, ES = large). Removal of FKB led to lower performance levels in both tests, while prolonged FKB use resulted in greater anaerobic endurance, lower fatigue level, and significantly higher aerobic capacity performance. These findings should help the decision-making process of practitioners about FKB use and performance.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by intense itching, redness, and eczema. It significantly impacts the quality of life of affected individuals, often requiring long-term management strategies. Abrocitinib, an oral Janus kinase 1 (JAK1) inhibitor, is approved for the treatment of moderate-to-severe AD. Phase 2 and phase 3 abrocitinib randomized clinical trials in the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) clinical development program have demonstrated the efficacy and safety of abrocitinib in both adults and adolescents with moderate-to-severe AD. This review article explores the benefit-risk profile of a flexible abrocitinib dosing approach, tailoring dose based on individualized treatment of patients and highlighting the available supportive data from the JADE randomized clinical trials for healthcare professionals as part of joint provider-patient decisionmaking. Dosing flexibility and maintenance with the lowest effective dose is necessary to treat patients according to their individual disease course while minimizing safety risks. Safety data indicate that incidence of treatment-emergent adverse events is reflective of the current dosage, with no carry-over risk from a previous higher dosage. Overall, abrocitinib represents a valuable AD therapy that can be administered according to individual patient needs.Graphical abstract available for this article.

For the first time, the study God in the Netherlands 1966-2024 has taken migration background into account in its analyses. This reflects the changes in Christian communities in the Netherlands as a result of migration since 1966. Around one million Christians with a migration background now live in the Netherlands. This article focuses on how the developments outlined in God in the Netherlands are affecting Christian communities with a non-Western migration background in the Netherlands. I highlight a number of themes that are relevant to these communities. For each theme, I summarize the information that can be obtained from God in the Netherlands, supplementing it with data from other studies and practical experiences. While many of the developments addressed in God in the Netherlands are relevant to non-Western migrant Christians, their starting point is different. First generation migrants are rarely socialized in a secular or secularizing society—they enter it at the moment of migration. This article highlights some of the implications of this.

Introduction: Abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is approved in patients aged ≥12 years at the recommended doses of 100 mg and 200 mg for the treatment of moderate-to-severe atopic dermatitis (AD). JADE REAL (NCT04564755) was a global, open-label expanded access protocol initiated in 2020 (completed September 2024) to provide access to abrocitinib for patients with moderate-to-severe AD. This analysis evaluated dosing patterns and incidence of treatment-emergent adverse events (TEAEs) leading to a change in dose of abrocitinib inpatients with moderate-to-severe AD in an expanded access protocol simulating real-world use of abrocitinib. Procedure/Study: Eligible patients aged ≥12 years with moderate-to-severe AD initiated once-daily abrocitinib 100 mg or 200 mg (plus topical medication as needed). The dose could be changed throughout the treatment period. Initial dosing and the proportion of patients with continuous dosing, ≥1 dose change and >1 dose change were assessed. Safety was assessed via TEAE monitoring. Results: Of 312 patients, 120 (38.5%) and 192 (61.5%) patients initiated abrocitinib 100 mg and 200 mg, respectively (mean [SD] treatment duration: 379.1 days [203.3]). More patients of ages ≥12–18 and ≥65 years, Black/African American race, and with moderate AD initiated abrocitinib 100 mg, while more patients of ages ≥18–<65 years, Asian race, and with severe AD initiated abrocitinib 200 mg. Of patients who initiated abrocitinib 100 mg and 200 mg, 78 (65.0%) and 119 (62.0%) received continuous dosing, and 42 (35.0%) and 73 (38.0%) patients had ≥1 dose change, including 12 (28.6%) and 33 (45.2%) patients with >1 dose change, respectively. TEAEs led to dose reduction in 27 patients (8.7%), notably nausea (n=4 [1.3%]), thrombocytopenia (n=4 [1.3%]), acne (n=3 [1.0%]), fatigue (n=3 [1.0%]), and folliculitis (n=3 [1.0%]). TEAEs led to a dose escalation in 12 patients (3.8%); AD was the only TEAE that occurred in ≥1% of patients (n=10 [3.2%]) which led to a dose escalation. Conclusion: Most patients received consistent abrocitinib dosing throughout the study. TEAEs were not the primary reason leading to dosage reduction. These results may support clinical decision making around initial dose selection and dosage changes. JADE REAL demonstrated the potential benefits of flexible dosing and may simulate the real-world use of oral Janus kinase inhibitors. Funding/Disclosures: This study was funded by Pfizer.

The results of a previous phase IIa trial suggested efficacy of the anti-C5a compound vilobelimab in a small number of patients with severe hidradenitis suppurativa (HS) refractory to adalimumab treatment. To study the efficacy of vilobelimab in a larger-scale randomized phase IIb trial (SHINE) of patients with moderate-to-severe HS. In total, 177 patients with moderate-to-severe HS were treated either with placebo or one of four doses of vilobelimab, a monoclonal antibody that targets the complement split product C5a. Hidradenitis Suppurativa Clinical Response (HiSCR) at 16 weeks was the primary endpoint. Those who achieved HiSCR switched to open-label low-dose vilobelimab; those who did not were switched to medium-dose vilobelimab. The trial was registered with the EU Clinical Trials Register (EudraCT number 2017-004501-40) and ClinicalTrials.gov (NCT03487276). The study did not meet the primary endpoint, perhaps due, in part, to an unexpectedly high HiSCR placebo response rate of 47.1%. HS flares decreased and post hoc analysis showed that high-dose vilobelimab significantly decreased the median draining tunnel counts and IHS4 score by 63%. Following the switch to medium-dose vilobelimab at week 16, 45.5% of those who did not respond to treatment achieved HiSCR at week 40. Compared with placebo, vilobelimab treatment did not result in significant HiSCR improvements in patients with moderate-to-severe HS. Post hoc analysis revealed significant effects for the highest tested dose on draining tunnel reduction and IHS4 score, which captures reductions in draining tunnels. These findings warrant further investigation.

ABSTRACTDysregulated copper homeostasis is implicated in inflammatory skin diseases such as psoriasis and atopic dermatitis (AD), but the role of cuproptosis remains poorly defined. This study aimed to elucidate the role and mechanism of cuproptosis in inflammatory skin diseases. Transcriptome analysis of patient lesions revealed significant alterations in cuproptosis‐related genes correlating with disease‐specific pathological features. These cuproptosis‐related gene expression signatures demonstrated strong clinical relevance to therapeutic efficacy in both psoriasis and AD cohorts. Functional validation using disease models showed that pharmacologically inhibiting cuproptosis with the copper chelator tetrathiomolybdate (TTM), or genetically knocking down the copper importer SLC31A1, effectively alleviated chronic skin inflammation and hallmark pathological changes induced by imiquimod (IMQ) or calcipotriol (MC903). Mechanistically, we uncovered that SLC31A1‐mediated cuproptosis promotes intracellular α‐ketoglutarate (α‐KG) accumulation, driving activation of the lysine demethylase KDM5B. Activated KDM5B specifically demethylates H3K4me3 marks at the promoter of the ferroptosis regulator ferritin heavy chain 1 (FTH1), suppressing its transcription and consequently sensitizing keratinocytes to ferroptotic cell death, thereby amplifying inflammatory tissue damage. Our findings establish a fundamental pathogenic SLC31A1/KDM5B/FTH1 molecular axis linking dysregulated copper metabolism and cuproptosis to ferroptosis execution in psoriasis and AD, providing significant mechanistic insights and pinpointing promising therapeutic targets for these refractory skin disorders.