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Background: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations. The objective of this study was to compare, for the first time, the efficacy of DDEA 2.32% gel BID and DDEA 1.16% gel QID. Methods: This was a phase 3, randomized, double-blind, multicenter, active-controlled, parallel-group study conducted in China from October 2019 to November 2020, designed to determine the noninferiority of DDEA 2.32% gel BID relative to DDEA 1.16% gel QID for treatment of grade I–II ankle sprain. At study entry, patients must have had pain on movement (POM) ≥50 mm on a 100-mm visual analogue scale (VAS), and not received any pain medication. The primary efficacy endpoint was the noninferiority of DDEA 2.32% gel BID vs DDEA 1.16% gel QID for POM as assessed by the patient using the 100-mm VAS, conducted on day 5. Secondary endpoints included measures of ankle tenderness, joint function, swelling, and patient-reported pain intensity and pain relief. Results: A total of 302 patients were randomized and 95.4% completed the study. The mean (SD) change in POM from baseline to day 5 using the 100-mm VAS was − 42.8 mm (19.7 mm) with DDEA 2.32% gel BID and − 43.1 mm (18.1 mm) with DDEA 1.16% gel QID for the per-protocol population. The least squares mean difference (DDEA gel 2.32% – DDEA gel 1.16%) at this timepoint was 1.11 mm (95% CI − 3.00, 5.22; P = 0.595), and the upper limit (5.22 mm) of the 95% CI was less than the noninferiority margin of 13 mm, demonstrating that DDEA 2.32% gel BID was noninferior to DDEA 1.16% gel QID. Similar trends were seen for the secondary efficacy endpoints. There was no significant difference in the incidence of treatment-emergent adverse events or adverse events adjudicated as being treatment related. All treatment-related adverse events were dermatological; one patient discontinued from the DDEA 2.32% gel BID arm due to application-site inflammation. Conclusions: DDEA 2.32% gel BID offers a convenient alternative to DDEA 1.16% gel QID, with similar pain reduction and relief, anti-inflammatory effects, and tolerability. Trial registration: NCT04052620. [ABSTRACT FROM AUTHOR]

• Applicability of the Witczak 1-40D model was evaluated. • Artificial intelligence model was employed to correct the inaccuracy of the Witczak 1-40D model. • Adaptive inertia weight and the Levy flight method were combined in BAS algorithm. The applicability of the widely used Witczak model was evaluated for the first time regarding the asphalt mixtures produced in the East part of China. 16 asphalt mixtures by 2 binders and 8 aggregate gradations were designed and the dynamic modulus testing was performed under various loading temperatures and frequencies. The results obtained are similar to previous studies from different countries (areas): the dynamic modulus of the asphalt mixture in the low-temperature region is overestimated. So then, a hybrid artificial intelligence algorithm to replace the traditional Witcazak model is implemented in this paper to correct the overestimation, using the same input parameters in the Witczak model. A modified beetle antennae search (BAS) algorithm was proposed in this study to improve the searching efficiency in the random forest (RF) model. The calculation process showed fast convergence and higher efficiency. The comparative results between the predicted and actual dynamic modulus showed higher prediction accuracy at all the temperature and frequency ranges, overcoming the weaknesses of the traditional Witczak model. The variable importance results showed that G* and phase angle of the binders have the greatest impact on the dynamic modulus. Volumetric properties also show certain influence ability, but the change of the variable controlling aggregate gradation has a weak influence on the dynamic modulus. [ABSTRACT FROM AUTHOR]

Background: The Omicron SARS-CoV-2 variant has spread quickly worldwide due to its effects on virus transmission and vaccine effectiveness. Interferon(IFN) has been shown to have a protective effect against SARS-CoV because of its broad antiviral activity. This study aimed to analyze the treatment effects of IFN α-2b spray in virus clearance of the Omicron SARS-CoV-2 variant., Methods: We examined the effectiveness and safety of IFN α-2b spray in Shanghai, China, with participants infected with the Omicron SARS-CoV-2 variant in an open, prospective cohort study from April 16th to May 5th, 2022., Results: A total of 871 confirmed patients were enrolled in this study. Four hundred and thirteen patients were allocated to the IFN α-2b spray group, and 458 patients were allocated to the control group. The viral shedding time was significantly different between experimental group and control group (11.90 vs.12.58, P < 0.05). In the experimental group, the median administration time since the first positive test for SARS-CoV-2 was three days, ranging from 0 to 15 days. There was no obvious adverse effect associated with the spray of IFN α-2b. The univariate Cox regression analysis revealed that the administration time since the first positive test ≤3 days was a protective factor associated with viral shedding time (HR 0.81 95% CI 0.74-0.87, P < 0.05). Subgroup analysis showed that the viral shedding time was 10.41 (4.00-16.00) days in the ≤3 days group, which was significantly less than that in the control group (12.58, 95% CI: 7.00-19.15, P < 0.0001) and in the >3 days group (13.56, 95%CI: 7.00-22.25, P < 0.0001)., Conclusions: IFN α-2b spray shortened the viral shedding time of the Omicron SARS-CoV-2 variant when administrated within three days since the first positive test for SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Pan, Sun, Zhou, Huang, Chen, Zhang, Zhu, Li, Zhang and Gao.)