Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

Bioactive pulvinones from a marine algicolous fungus Aspergillus terreus NTU243.

Marine fungi are regarded as an under-explored source of structurally interesting and bioactive natural products with the potential to provide attractive lead compounds for drug discovery. In this study, several fungal strains were isolated from marine algae collected from the northeastern coast of Taiwan. In the preliminary antimicrobial screening against bacteria and fungi, the ethyl acetate extract of the fermented products of Aspergillus terreus NTU243 derived from a green alga Ulva lactuca was found to exhibit significant antimicrobial activities. Therefore, bioassay-guided separations of the active principle from liquid and solid fermented products of A. terreus NTU243 were undertaken, which resulted in the isolation and purification of 16 compounds. Their structures were elucidated by spectroscopic analysis to be four previously undescribed aspulvinones S-V as well as twelve known compounds. All the isolates were assessed for anti-inflammatory activity by measuring the amount of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 cells, and aspulvinone V, butyrolactone I, and (+)-terrein inhibited 45.0%, 34.5%, and 49.2% of NO production, respectively, at 10 µM concentration. Additionally, zymography showed that the conditioned medium of THP-1 cells post-LPS challenged significantly enhanced matrix metalloproteinase (MMP)-9-mediated gelatinolysis, and pretreatment with aspulvinones U and V significantly attenuated MMP-9-mediated gelatinolysis by 56.0% and 67.8%, separately.

Fair and Effective Policing for Neighborhood Safety: Understanding and Overcoming Selection Biases.

An accurate crime prediction and risk estimation can help improve the efficiency and effectiveness of policing activities. However, reports have revealed that biases like racial prejudice could exist in policing enforcement, and trained predictors may inherit them. In this work, we study the possible reasons and countermeasures to this problem, using records from the New York frisk and search program (NYCSF) as the dataset. Concretely, we provide analysis on the possible origin of this phenomenon from the perspective of risk discrepancy, and study it with the scope of selection bias. Motivated by theories in causal inference, we propose a re-weighting approach based on propensity score to balance the data distribution, with respect to the identified treatment: search action. Naively applying existing re-weighting approaches in causal inference is not suitable as the weight is passively estimated from observational data. Inspired by adversarial learning techniques, we formulate the predictor training and re-weighting as a min-max game, so that the re-weighting scale can be automatically learned. Specifically, the proposed approach aims to train a model that: 1) able to balance the data distribution in the searched and un-searched groups; 2) remain discriminative between treatment interventions. Extensive evaluations on real-world dataset are conducted, and results validate the effectiveness of the proposed framework.

Towards Semantically-Rich Spatial Network Representation Learning via Automated Feature Topic Pairing.

Automated characterization of spatial data is a kind of critical geographical intelligence. As an emerging technique for characterization, spatial Representation Learning (SRL) uses deep neural networks (DNNs) to learn non-linear embedded features of spatial data for characterization. However, SRL extracts features by internal layers of DNNs, and thus suffers from lacking semantic labels. Texts of spatial entities, on the other hand, provide semantic understanding of latent feature labels, but is insensible to deep SRL models. How can we teach a SRL model to discover appropriate topic labels in texts and pair learned features with the labels? This paper formulates a new problem: feature-topic pairing, and proposes a novel Particle Swarm Optimization (PSO) based deep learning framework. Specifically, we formulate the feature-topic pairing problem into an automated alignment task between 1) a latent embedding feature space and 2) a textual semantic topic space. We decompose the alignment of the two spaces into: 1) point-wise alignment, denoting the correlation between a topic distribution and an embedding vector; 2) pair-wise alignment, denoting the consistency between a feature-feature similarity matrix and a topic-topic similarity matrix. We design a PSO based solver to simultaneously select an optimal set of topics and learn corresponding features based on the selected topics. We develop a closed loop algorithm to iterate between 1) minimizing losses of representation reconstruction and feature-topic alignment and 2) searching the best topics. Finally, we present extensive experiments to demonstrate the enhanced performance of our method.

Measuring Urban Vibrancy of Residential Communities Using Big Crowdsourced Geotagged Data.

The pervasiveness of mobile and sensing technologies today has facilitated the creation of Big Crowdsourced Geotagged Data (BCGD) from individual users in real time and at different locations in the city. Such ubiquitous user-generated data allow us to infer various patterns of human behavior, which helps us understand the interactions between humans and cities. In this article, we aim to analyze BCGD, including mobile consumption check-ins, urban geography data, and human mobility data, to learn a model that can unveil the impact of urban geography and human mobility on the vibrancy of residential communities. Vibrant communities are defined as places that show diverse and frequent consumer activities. To effectively identify such vibrant communities, we propose a supervised data mining system to learn and mimic the unique spatial configuration patterns and social interaction patterns of vibrant communities using urban geography and human mobility data. Specifically, to prepare the benchmark vibrancy scores of communities for training, we first propose a fused scoring method by fusing the frequency and the diversity of consumer activities using mobile check-in data. Besides, we define and extract the features of spatial configuration and social interaction for each community by mining urban geography and human mobility data. In addition, we strategically combine a pairwise ranking objective with a sparsity regularization to learn a predictor of community vibrancy. And we develop an effective solution for the optimization problem. Finally, our experiment is instantiated on BCGD including real estate, point of interests, taxi and bus GPS trajectories, and mobile check-ins in Beijing. The experimental results demonstrate the competitive performances of both the extracted features and the proposed model. Our results suggest that a structurally diverse community usually shows higher social interaction and better business performance, and incompatible land uses may decrease the vibrancy of a community. Our studies demonstrate the potential of how to best make use of BCGD to create local economic matrices and sustain urban vibrancy in a fast, cheap, and meaningful way.

Upregulation of miR-150-5p alleviates LPS-induced inflammatory response and apoptosis of RAW264.7 macrophages by targeting Notch1.

Circulating miR-150-5p has been identified as a prognostic marker in patients with critical illness and sepsis. Herein, we aimed to further explore the role and underlying mechanism of miR-150-5p in sepsis. Quantitative real-time-PCR assay was performed to detect the expression of miR-150-5p upon stimulation with lipopolysaccharide (LPS) in RAW264.7 cells. The levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß were measured by ELISA assay. Cell apoptosis was determined using flow cytometry. Western blot was used to assess notch receptor 1 (Notch1) expression in LPS-induced RAW264.7 cells. Dual-luciferase reporter assay was employed to validate the target of miR-150-5p. Our data showed that miR-150-5p was downregulated and Notch1 was upregulated in LPS-stimulated RAW264.7 cells. miR-150-5p overexpression or Notch1 silencing alleviated LPS-induced inflammatory response and apoptosis in RAW264.7 cells. Moreover, Notch1 was a direct target of miR-150-5p. Notch1 abated miR-150-5p-mediated anti-inflammation and anti-apoptosis in LPS-induced RAW264.7 cells. miR-150-5p alleviated LPS-induced inflammatory response and apoptosis at least partly by targeting Notch1 in RAW264.7 cells, highlighting miR-150-5p as a target in the development of anti-inflammation and anti-apoptosis drugs for sepsis treatment.

Association of ERAP1 gene polymorphisms with the susceptibility to psoriasis vulgaris: A case-control study.

Psoriasis vulgaris (PsV), also known as plaque psoriasis, is a life-threatening autoimmune skin disease. Inflammatory factors may contribute to the development of PsV. Present study aimed to explore the association of endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms (rs26653 and rs27524) with PsV susceptibility in a Chinese Han population. Subgroup analysis was also performed based on the onset of PsV.Present case-control study included 143 patients with PsV and 149 healthy controls. Direct sequencing method was used for genotyping ERAP1 polymorphisms. Chi-squared test was used to estimate the association between ERAP1 polymorphisms and PsV susceptibility. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess association strength.The polymorphism rs26653 was positively correlated with PsV susceptibility (CC vs GG, P = .047, OR = 1.964, 95% CI = 1.006-3.834; C vs G, P = .042, OR = 1.403, 95% CI = 1.011-1.946). Meanwhile, its CC genotype and C allele were positively associated with the early onset of PsV (P = .036, OR = 2.080, 95% CI = 1.044-4.145; P = .034, OR = 1.443, 95% CI = 1.028-2.024) and increased PsV risk in the subgroup with family history (P = .029, OR = 2.149, 95% CI = 1.075-4.296; P = .027, OR = 1.466, 95% CI = 1.044-2.059).ERAP1 gene rs26653 polymorphism may increase the risk of PsV in Chinese Han population.

Genetic association between CD86 polymorphisms and the risk of sepsis in a Chinese Han population.

BACKGROUND: Sepsis is a clinical syndrome that is frequently observed after injury or infection, representing a leading cause of mortality worldwide. CD86 (B7-2) is a co-stimulatory molecule on antigen-presenting cells, and plays critical roles in immune responses. METHODS: A total of 135 sepsis patients and 151 healthy controls were recruited in the current case-control study. Hardy-Weinberg equilibrium (HWE) conformity was examined to assess the representativeness of the study population. CD86 gene polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relative expression of CD86 mRNA was estimated via quantitative real-time PCR (qRT-PCR). Chi-square test was performed to estimate the associations between CD86 gene polymorphisms and sepsis risk, and the results were presented through odds ratio (OR) and 95% confidence intervals (CI). RESULTS: The genotype distributions of CD86 polymorphisms in the case and control groups conformed to HWE. The GA genotype of the polymorphism rs1129055 was significantly correlated with an increased risk of sepsis (OR = 2.540, 95%CI = 1.288-5.008). The TT genotype of rs1915087 was a risk factor for sepsis (OR = 2.769, 95%CI = 1.292-5.935). High linkage disequilibrium was observed between the two polymorphisms (D' = 1.0, r2 = 0.955). However, no significant association was observed between CD86 polymorphisms and its gene expressions (P > 0.05 for all). CONCLUSION: CD86 gene polymorphisms rs1129055 and rs1915087 may increase the risk of sepsis.

The Effect of Continuous Sedation Therapy on Immunomodulation, Plasma Levels of Antioxidants, and Indicators of Tissue Repair in Post-Burn Sepsis Patients.

Our objective was to investigate the effect of continuous therapeutic sedation on the immune response, plasma levels of antioxidants, and tissue repair indicators in burn-induced sepsis patients. A total of 104 burn-induced sepsis patients hospitalized during March, 2008 to March, 2013 were selected for the study and randomly divided into the experimental and control groups, each with 53 cases. All of these patients received conventional treatment and the patients in the experimental group were given an additional therapy of continuous sedation. The number of T lymphocytes, plasma levels of tissue repair indicators, and antioxidants were measured before and after the treatment. Continuous midazolam treatment induced a significant increase in plasma levels of gelsolin, heat shock protein 70, nitric oxide, superoxide dismutase, and tumor necrosis factor-alpha (p < 0.05). Likewise, the relative counts of CD3(+), CD4(+), CD8(+) T lymphocytes, T cells exhibiting HLA-DR and CD4(+)/CD8(+) ratio were significantly increased in the patients treated with midazolam. No adverse reaction including respiratory depression, midazolam resistance, or withdrawal syndrome was observed. Continuous sedation therapy was found to enhance immune response, increase the plasma levels of antioxidants, and tissue protective/repair mediators in burn-induced sepsis patients. This therapy caused no adverse reaction or over-inhibition of the oxidative stress suggesting its effectiveness in improving the prognosis without the risk of safety.

Improvement in the repair of defects in maxillofacial soft tissue in irradiated minipigs by a mixture of adipose-derived stem cells and platelet-rich fibrin.

To find out if adipose-derived stem cells (ASC) and platelet-rich fibrin (PRF), alone or combined, had any effect on the repair of maxillofacial soft tissue defects in irradiated minipigs, ASC were isolated, characterised, and expanded. Twenty female minipigs, the right parotid glands of which had been irradiated, were randomly divided into 4 groups of 5 each: those in the first group were injected with both ASC and PRF (combined group), the second group was injected with ASC alone (ASC group), the third group with PRF alone (PRF group), and the fourth group with phosphate buffer saline (PBS) (control group). Six months after the last injection, the size and depth of each defect were assessed, and subcutaneous tissues were harvested, stained with haematoxylin and eosin, and examined immunohistologically and for apoptosis. Expanded cells were successfully isolated and identified. Six months after injection the defects in the 3 treated groups were significantly smaller (p<0.001) and shallower (p<0.001) than those in the control group. Those in the combined group were the smallest and shallowest. Haematoxylin and eosin showed that the 3 treated groups contained more subcutaneous adipose tissue than the control group, and also had significantly greater vascular density (p<0.001) and fewer apoptotic cells (p<0.001). Both ASC and PRF facilitate the repair of defects in maxillofacial soft tissue in irradiated minipigs, and their combined use is more effective than their use as single agents.

Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model.

AIMS: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. METHODS: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. RESULTS: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. CONCLUSION: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions.