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The weapon-target allocation (WTA) problem is a fundamental subject of defense-related applications research, and previous studies assume that the parameters in the model are determinate. For the real battlefield, asymmetric information usually leads to the failure of the above assumption, and there are uncertain factors whose frequency is hard to pinpoint. Based on uncertainty theory, we study a WTA problem in indeterminate battlefield in this paper. First, we analyze the uncertain factors in indeterminate battlefield and their influence on WTA problem. Then, considering the target threat value, the protected asset value and the extra cost of interception as uncertain variables, the uncertain multi-objective dynamic WTA (UMDWTA) model is established, where three indices including the value of destruction of targets, the value of surviving assets and the cost of operation are regarded as objective functions, and on this basis, an equivalent transformation is presented to convert the UMDWTA model into a determinate multi-objective programming (MOP) problem by expected value and standard deviation principle. To solve the proposed model efficiently, an improved multi-objective evolutionary algorithm based on decomposition (MOEA/D) is designed, which employs three new evolutionary operators and the weight vectors adaptation mechanism to improve the convergence and uniformity of the Pareto front obtained. Finally, a case of the UMDWTA problem is carried out to be solved by the designed algorithm, and the results verify the feasibility of the proposed model. [ABSTRACT FROM AUTHOR]

Introduction: N-methyl-D-aspartate receptor (NMDAR) is one of the main receptor of the excitatory neurotransmitter glutamate in the brain, which is the key determinant of the excitatory/inhibitory balance of neural network. GluN2A/GRIN2A is one of the subunits of NMDAR and plays an important role in epilepsy. Approximately 78% of patients with GluN2A/Grin2a mutations have epilepsy, and the underlying mechanism of this association is not well characterized. Methods: We constructed a mouse model of hyperthermic seizure, and conducted in vitro and in vivo electrophysiological and behavioral studies to clarify the pathogenic characteristics and mechanism of GluN2A/GRIN2A-V685G mutation. In addition, the drug efavirenz (EFV), which is used to treat HIV infection, was administrated to mutant animals to assess whether it can restore the loss of function. Results: Mutant mice showed no significant change in the mRNA or protein expressions of NMDAR compared with wild type (WT) mice. Mice with GluN2A/GRIN2A-V685G mutation exhibited shorter latency to seizure, increased frequency of seizure-like events, decreased peak current and current area of NMDAR excitatory postsynaptic current, and decreased event frequency of micro-inhibitory postsynaptic current, compared to WT mice. They also exhibited decreased threshold, increased amplitude, increased input resistance, and increased root number of action potential. EFV administration reversed these changes. The loss-of-function (LoF) mutation of NMDAR changed the excitatory/inhibitory balance of neural network, rendering animal more prone to seizures. Discussion: EFV was indicated to hold its potential in the treatment of inherited epilepsy. [ABSTRACT FROM AUTHOR]

Background: China’s southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing. Methods: Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy. Results: In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations. Conclusions: These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature. Methods: First, differentially expressed lncRNAs (DE-lncRNAs) from the TCGALUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in highand low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective. Conclusion: A total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed. [ABSTRACT FROM AUTHOR]

Purpose The influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in China was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated. Materials and Methods Overall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or total cholesterol (TC) with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia, and normal FBG/non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model. Results During 1,134,843.68 person-years follow-up, a total of 388 PLC cases occurred. We found the elevated FBG and hypocholesterolemia increase the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (hazard artio [HR], 1.19; 95% confidence interval [CI], 0.88 to 1.62) and hypocholesterolemia/normal FBG group (HR, 1.53; 95% CI, 1.19 to 1.97), and in the hypocholesterolemia/elevated FBG group (HR, 3.16; 95% CI, 2.13 to 4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease. Conclusion Elevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated. [ABSTRACT FROM AUTHOR]

Based on the very low frequency (VLF) signals observed on the ground in mid-latitude areas of China from February 2016 to February 2019, atmospheric noise in the 3-30 kHz band is investigated in detail. The statistical analysis indicates that the seasonal variations of the atmospheric noise of different bands are similar in the general trend but different in magnitude, the largest of which can reach 10 dB. According to the accuracy analysis of the atmospheric noise model by the Consultative Committee of International Radio (CCIR), despite the valid long-term variation of the atmospheric noise provided by the CCIR at the observation station, it overestimates the atmospheric noise level and thus, is unable to show the detailed characteristics of the short-term variation of the atmospheric noise. Combined with the global lightning observation, the correlation between atmospheric noise and global lightning activities is analyzed to find that the lightning within a range of 3,500 km can dominate the atmospheric noise at the observation site, along with distant lightning playing a minor role. Not only do the results deepen our understanding of the distribution of atmospheric noise in mid-latitudes in China, but they also reveal the correlation between atmospheric noise and global lightning, thereby benefiting the study of VLF signal propagation and its communication application. [ABSTRACT FROM AUTHOR]

Background: Vortioxetine is an investigational multimodal antidepressant. We conducted this meta-analysis to assess the efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder (MDD). Methods: Randomized controlled trials (RCTs) published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed to assess the treatment effects and safety profiles of patients with MDD who were treated with 10 mg vortioxetine. The outcome measures included response rate, remission rate, changes from baseline in Montgomery-Asberg Depres-sion Rating Scale (MADRS), Hamilton Rating Scale for Depression (24-items) (HAM-D24 Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Improvement (CGI-I) scores. Results were expressed with risk ratio or weighted mean difference with 95% confidence intervals. Pooled results were calculated using a fixed-effects model or a random- effects model according to the heterogeneity among included trials. Results: Six RCTs with a total of 1,801 patients met the inclusion criteria and were included in this meta-analysis. The 10 mg vortioxetine dose significantly increased the response rate and remission rate in the treatment of MDD compared with placebo. Moreover, there was a statistically significant reduction from baseline in the MADRS, HAM-D24, CGI-S, and CGI-I scores with 10 mg vortioxetine vs placebo. The incidence of treatment-emergent adverse events such as nausea, vomiting, constipation, and hyperhidrosis was higher in the 10 mg vortioxetine group than in the placebo group. Conclusion: Vortioxetine 10 mg can significantly increase the response rate and remission rate, and reduce the MADRS, HAM-D24, CGI-S, and CGI-I scores in patients with MDD with an acceptable risk of treatment-emergent adverse events. Further well-conducted, large-scale trials are needed to validate these findings. [ABSTRACT FROM AUTHOR]