Computationally designed peptide macrocycle inhibitors of New Delhi metallo-ß-lactamase 1.

The rise of antibiotic resistance calls for new therapeutics targeting resistance factors such as the New Delhi metallo-ß-lactamase 1 (NDM-1), a bacterial enzyme that degrades ß-lactam antibiotics. We present structure-guided computational methods for designing peptide macrocycles built from mixtures of l- and d-amino acids that are able to bind to and inhibit targets of therapeutic interest. Our methods explicitly consider the propensity of a peptide to favor a binding-competent conformation, which we found to predict rank order of experimentally observed IC50 values across seven designed NDM-1- inhibiting peptides. We were able to determine X-ray crystal structures of three of the designed inhibitors in complex with NDM-1, and in all three the conformation of the peptide is very close to the computationally designed model. In two of the three structures, the binding mode with NDM-1 is also very similar to the design model, while in the third, we observed an alternative binding mode likely arising from internal symmetry in the shape of the design combined with flexibility of the target. Although challenges remain in robustly predicting target backbone changes, binding mode, and the effects of mutations on binding affinity, our methods for designing ordered, binding-competent macrocycles should have broad applicability to a wide range of therapeutic targets.

Improved Short-Term Prognosis of Pediatric Partial-Thickness Burns: Emergency Conservative Debridement Under Topical Anesthesia.

OBJECTIVES: Early wound management for pediatric patients with partial-thickness burns in the emergency department remains debatable. This study aims to evaluate the value of emergency conservative debridement under topical anesthesia in improving short-term prognosis of pediatric partial-thickness burns. METHODS: This retrospective cohort study enrolled children with partial-thickness thermal burns presenting to the emergency department within 6 hours postburn. All the enrolled patients were divided into 2 groups: the debridement group and the dressing group. The associations between emergency conservative debridement and time to reepithelialization was analyzed by using Kaplan-Meier curves with log rank test and multivariate Cox regression analysis. Moreover, the associations between emergency conservative debridement and in-hospital cost and length of stay were also evaluated. RESULTS: All baseline characteristics between groups were comparable (all P > 0.05). Emergency conservative debridement under topical anesthesia significantly decreased the median value of time to reepithelialization (13 vs 14 days, P = 0.02). Cox regression analysis showed that emergency conservative debridement significantly improved wound reepithelialization after adjusting for burn size (odds ratio, 4.07; 95% confidence interval, 1.64-10.11; P < 0.01). The mean length of stay of patients receiving conservative wound debridement was lower than that of patients in the wound dressing group (14.3 ± 7.3 vs 18.8 ± 10.4 days, P < 0.01), but not in terms of mean in-hospital cost per 1% total body surface area (2.8 ± 1.9 vs 3.0 ± 2.1 × 103 RMB per 1% total body surface area, P = 0.58). CONCLUSIONS: Emergency conservative debridement of pediatric partial-thickness burns under topical anesthesia significantly improves the wound healing outcomes without increasing health care burden.

The epidemiology of alcohol burns at a major burn centre in North China.

This study was designed to explore the epidemiological characteristics and potential preventive strategies of alcohol burns. In this five-year, retrospective study, 163 patients with alcohol burns (admitted from 1 January 2015 to 31 May 2020 were included. There was a male-to-female ratio of 1.1:1, a mean age of 34.1±16.8 years, and a mean burn size of 13.3±13.7% total body surface area (TBSA). The number of patients with alcohol burns was similar year by year during the five-year period. Just over half of patients (n=84, 51.5%) sustained a third-degree burn injury, which was significantly associated with a longer hospital stay and the need for surgery. The most prevalent aetiology was cupping (n=49, 29.5%), followed by cooking hotpot (n=37, 22.7%). Of the patients, seven (4.29%) sustained injuries during experiments at school and one patient sustained injury when using alcohol spray for disinfection against COVID-19. The incidence of facial burn injury (n=105, 64.4%) was significantly higher than previously reported data (33.2%). The result of the study showed that cupping and hotpot were the main causes of alcohol burns in Beijing, which should be taken into consideration for prevention. It is necessary to strengthen safety management of classes at school where experiments are undertaken and to educate the general public on the proper means of disinfecting against COVID-19.

Small but Nontrivial: A Comparison of Six Strategies to Handle Cross-Loadings in Bifactor Predictive Models.

The bifactor model is a promising alternative to traditional modeling techniques for studying the predictive validity of hierarchical constructs. However, no study to date has systematically examined the influence of cross-loadings on the estimation of regression coefficients in bifactor predictive models. Therefore, we present a systematic examination of the statistical performance of six modeling strategies to handle cross-loadings in bifactor predictive models: structural equation modeling (SEM), exploratory structural equation modeling (ESEM) with target rotation, Bayesian structural equation modeling (BSEM), and each of the three with augmentation. Results revealed four clear patterns: 1) forcing even small cross-loadings to zero was detrimental to empirical identification, estimation bias, power and Type I error rates; 2) the performance of ESEM with target rotation was unexpectedly weak; 3) augmented BSEM had satisfactory performance in an absolute sense and outperformed the other five strategies across most conditions; 4) augmentation improved the performance of ESEM and SEM, although the degree of improvement was not as substantial as that of BSEM. In addition, we also presented an empirical example to show the feasibility of the proposed approach. Overall, these findings can help users of bifactor predictive models design better studies, choose more appropriate analytical strategies, and obtain more reliable results. Implications, limitations, and future directions are discussed.

Characteristics and aetiology of low-temperature burns in Beijing of China.

This study was designed to analyse the characteristics and aetiology of low-temperature burns and explore the prevention and treatment strategies. In total, 206 patients hospitalised with low-temperature burns in a major burn center in Beijing from 2017 to 2021 were included. There were 35-49 cases per year, with an average of 41 ± 4.5 cases. The prevalence of low-temperature burns was higher in female than in male and are mainly resulted from two kinds of incidents: unintended burns from heat treatment (50.97%, 105/206) and improper use of heating devices to keep warm (43.69%, 90/206). Most cases occurred in autumn (33.01%, 68/206) and the least in spring (17.96%, 37/206); cases in summer (24.27%, 50/206) and winter (24.76%, 51/206) accounted for nearly a quadrant respectively. Low-temperature burns in summer were mainly unintended burns from heat treatment (80%, 40/50), whereas in autumn were mainly resulted from improper use of heating devices to keep warm (55.88%, 38/68), the difference was statistically significant (χ2  = 42.801, P < .001). Of all the cases, the burn size ranged from 0.2% to 5% TBSA, mostly less than 1% (85.92%, 177/206); third-degree burns accounted for 98.54% (203/206). Patients admitted after 3 weeks post-injury accounted for 42.23% (87/206). All patients were cured, and most of them were by surgeries (70.87%, 146/206). The results of the study show that low-temperature burn injury features a predictable morbidity among different seasons, a higher prevalence in adult women and a frequent occurrence at home. The wounds of low-temperature burns are often small in size but deep in depth, and can be easily misdiagnosed as superficial burns. However, most low-temperature burn wounds require surgical treatment. The study also suggests that based on the characteristics and aetiology of low-temperature burns, targeted prevention and treatment measures should be mapped out.

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers.

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

Data Filtering Method for Intelligent Vehicle Shared Autonomy Based on a Dynamic Time Warping Algorithm.

Big data already covers intelligent vehicles and is driving the autonomous driving industry's transformation. However, the large amounts of driving data generated will result in complex issues and a huge workload for the test and verification processes of an autonomous driving system. Only effective and precise data extraction and recording aimed at the challenges of low efficiency, poor quality, and a long-time limit for traditional data acquisition can substantially reduce the algorithm development cycle. Based on the premise of driver-dominated vehicle movement, the virtual decision-making of autonomous driving systems under the accompanying state was considered as a reference. Based on a dynamic time warping algorithm and forming a data filtering approach under a dynamic time window, an automatic trigger recording control model for human-vehicle difference feature data was suggested. In this method, the data dimension was minimized, and the efficiency of the data mining was improved. The experimental findings showed that the suggested model decreased recorded invalid data by 75.35% on average and saved about 2.65 TB of data storage space per hour. Compared with industrial-grade methods, it saves an average of 307 GB of storage space per hour.

Platelet distribution width associated with short-term prognosis and cost in paediatrics with partial-thickness thermal burns: A retrospective comparative study.

Platelets exert important roles in burn wound healing and involving in inflammatory regulation and tissue repair. Platelet distribution width (PDW) is an indicator representing platelet morphology and activation. In this study, we try to evaluate the value of PDW in predicting short-term prognosis and cost of paediatrics with partial-thickness thermal burns. This retrospective study enrolled 73 children with partial-thickness thermal burns. The Ability of PDW to predict wound healing was evaluated by receiver operating characteristic (ROC) curve. All 73 patients were assigned into high and low PDW group according to optimal cut-off value from ROC curve. Associations between PDW and 2-weeks healing rate, time to wound healing, in-hospital cost and length of stay were evaluated. Furthermore, Univariate and multivariate logistic regression analysis were used to furtherly evaluate the significance of PDW in wound healing. We found that all baseline characteristics between groups were comparable (all P > .05). High PDW group had a significant higher 2-weeks wound healing rate than those with a low PDW (66.7% versus 32.6%, P < .01). Moreover, the mean time to wound healing of high PDW was obviously shorter than that of low PDW group (15.4 ± 10.1 vs 20.7 ± 10.9, P = .04). Univariate (OR: 0.24, 95%CI: 0.09-0.65, P < .01) and multivariate (OR: 0.15, 95CI%:0.05-0.52, P < .01) analysis confirmed PDW as an independent marker for wound healing. Patients in high PDW group had a significant lower medical burden than low PDW group, including in-hospital cost (13.7 ± 10.6 vs 21.9 ± 16.7, ×103RMB, P = .02) and length of stay (12.2 ± 8.8 vs 19.0 ± 10.8 days, P < .01). In conclusion, PDW can sever as a potential indictor to predict the short-term prognosis of paediatrics with partial thickness thermal burns.

A Brain-Inspired Decision-Making Linear Neural Network and Its Application in Automatic Drive.

Brain-like intelligent decision-making is a prevailing trend in today's world. However, inspired by bionics and computer science, the linear neural network has become one of the main means to realize human-like decision-making and control. This paper proposes a method for classifying drivers' driving behaviors based on the fuzzy algorithm and establish a brain-inspired decision-making linear neural network. Firstly, different driver experimental data samples were obtained through the driving simulator. Then, an objective fuzzy classification algorithm was designed to distinguish different driving behaviors in terms of experimental data. In addition, a brain-inspired linear neural network was established to realize human-like decision-making and control. Finally, the accuracy of the proposed method was verified by training and testing. This study extracts the driving characteristics of drivers through driving simulator tests, which provides a driving behavior reference for the human-like decision-making of an intelligent vehicle.

Degradation of phenol by coal-based carbon membrane integrating sulfate radicals-based advanced oxidation processes.

Phenol, as a representative organic pollutant in aquatic environments, has posed a serious threat to humans and ecosystem. In this work, a novel integration system combined coal-based carbon membrane with sulfate radicals-based advanced oxidation processes (SR-AOPs) was designed for degradation of phenol. The integrated system achieved 100% removal efficiency under the optimal condition (peroxydisulfate dosage is 0.2 g/L, at alkaline condition with 2 mL/min flow velocity). The quenching experiments revealed that the efficient removal of phenol by the integrated system were attributed to the co-existence of radical and nonradical mechanisms. This study proposes a green and efficient technique for the removal of phenol.