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[...]small molecule inhibitors (SMIs) have gained considerable attention among researchers, owing to the simplified synthesis processes, low-cost production, and the possibility of oral or topical administration. [14] Upper respiratory tract infections, nasopharyngitis, and headache were the most common AEs, and there was an increased risk of herpes zoster, serious infections, including tuberculosis, pneumonia, and influenza, as well as laboratory abnormalities in the tofacitinib treatment group. [...]routine laboratory monitoring is necessary when tofacitinib is prescribed in clinical settings. [...]tofacitinib has not received approval for the treatment of plaque psoriasis. [19] Upper respiratory tract infections and herpes zoster infection were reported to be the treatment-related AEs. Because the earlier pan-JAK inhibitor is relatively non-specific and has a high prevalence of AEs, selective TYK2 inhibitors have been developed.

Background Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. Objective We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. Methods Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator’s Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. Results In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator’s Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients’ quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. Conclusions Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. Clinical Trial Registration ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

UVA1 phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of palmoplantar pustulosis (PPP). The purpose of this study was to compare the efficacy of UVA1 and narrowband UVB (NB-UVB) therapy in the treatment of PPP. Patients with PPP were randomly assigned to either UVA1 or NB-UVB therapy according to a left-right randomization table. Both treatments were performed three times weekly for up to 30 sessions. Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally 64 patients completed the study. Both UVA1 and NB-UVB therapy showed a statistically significant reduction of PPPASI score compared with the baseline value at the end of the treatment period ( P  < 0.05). There was a significantly greater mean reduction of PPPASI score in the UVA1 treated group when compared to the NB-UVB treated patients at 30 sessions (6.0 ± 2.4 vs. 4.4 ± 1.4, P  < 0.05). No phototoxic reaction or bullous changes were observed in either group. Both NB-UVB and UVA1 phototherapy of PPP resulted in significant improvement. UVA1 phototherapy was more effective than NB-UVB irradiation in the treatment of PPP.

In this study, we report the effect of Zn doping on the thermoelectric properties of Co1−xZnxSbS0.85Se0.15 solid solutions (x = 0, 0.02, 0.05, 0.08). The results show the dimensionless figure of merit (zT) increases from 0.17 to 0.34 at 875 K for Co0.95Zn0.05SbS0.85Se0.15 sample, due to the noticeable decrease in the lattice thermal conductivity by introducing point defect, which is further confirmed by an analysis based on the Debye–Callaway–Klemens model. Meanwhile, the thermoelectric power factor is maintained at high temperatures. This work highlights the important role of point defect in improving the thermoelectric performance of CoSbS-based compounds.

Abstract Nail disease in psoriasis has been found to be associated with psoriatic arthritis (PsA); however, which subtype of nail disease holds greater relevance to PsA remains unclear. This study was performed to explore the associations between three subtypes of fingernail disease (pitting, onycholysis, and hyperkeratosis) and PsA among patients with psoriasis. Patients with psoriasis attending five dermatology clinics in Shanghai between January 2020 and May 2021 were examined for skin, joint, and fingernail changes. Multivariate logistic regression analyses were utilized to test the strength of associations between subtypes of fingernail disease and PsA. The receiver operator characteristic (ROC) curve with area under curve (AUC) was used to evaluate their accuracies in diagnosing PsA. Sensitivity and specificity were also calculated. Of 1985 patients with psoriasis included, 228 (11.5%) patients were diagnosed with PsA, and the remaining patients were cutaneous-only psoriasis (PsC). One-hundred and fifty-seven (68.9%) patients with PsA and 748 (42.6%) patients with PsC had fingernail disease. Adjusted models showed that onycholysis and hyperkeratosis were the only type of fingernail disease independently associated with PsA. This association was further confirmed by the forward conditional stepwise regression model (OR, 95% CI for onycholysis: 2.34, 1.79 to 4.27, p < 0.01; for hyperkeratosis: 1.62, 1.12 to 2.66, p = 0.037). ROC analysis showed that, compared to pitting and hyperkeratosis, onycholysis had higher AUC (0.630) and sensitivity (52.6%). The psoriatic fingernail onycholysis and hyperkeratosis hold greater relevance to PsA than pitting. Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis.Key Points• Psoriatic fingernail onycholysis and hyperkeratosis, rather than pitting, are significantly associated with PsA• Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis

Palmoplantar pustulosis (PPP) is recalcitrant to traditional topical and systemic therapies. Ultraviolet A1 (UVA1) phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of PPP. The purpose of this study was to evaluate the efficacy and safety of UVA1 therapy for the treatment of PPP. Patients with PPP were treated with UVA1 irradiation three times a week for up to 30 sessions and had a 3-month follow-up visit. UVA1 therapy was conducted with a fixed dose (80 J/cm 2 ). Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally, 62 patients completed the study. The mean PPPASI score decreased from a baseline value of 9.4 ± 2.8 to a value of 4.9 ± 2.4 at 15 sessions, 1.7 ± 1.9 at 30 sessions, and 2.0 ± 2.1 at follow-up visit. A reduction of 75 % in the PPPASI score was observed in 4 (6.5 %) patients at 15 sessions and 45 (72.6 %) patients at 30 sessions. The adverse effects were limited including burning sensation, pruritus, and hyperpigmentation. UVA1 is an effective therapy for PPP with mild side effects.

Background: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions. Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan-Meier curves and Log rank tests. Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence. Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients. Keywords: biologics, drug survival, real-world, psoriasis, ixekizumab, secukinumab, guselkumab, adalimumab

By using the stochastic martingale theory, convergence properties of stochastic gradient (SG) identification algorithms are studied under weak conditions. The analysis indicates that the parameter estimates by the SG algorithms consistently converge to the true parameters, as long as the information vector is persistently exciting (i.e., the data product moment matrix has a bounded condition number) and that the process noises are zero mean and uncorrelated. These results remove the strict assumptions, made in existing references, that the noise variances and high-order moments exist, and the processes are stationary and ergodic and the strong persistent excitation condition holds. This contribution greatly relaxes the convergence conditions of stochastic gradient algorithms. The simulation results with bounded and unbounded noise variances confirm the convergence conclusions proposed.