Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation.

BackgroundThe core domains of social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder (PD) with and without agoraphobia (GA), and specific phobia (SP) are cognitive and physical symptoms that are related to the experience of fear and anxiety. It remains unclear whether these highly comorbid conditions that constitute the anxiety disorder subgroups of the Diagnostic and Statistical Manual for Mental Disorders – Fifth Edition (DSM-5) represent distinct disorders or alternative presentations of a single underlying pathology.MethodsA systematic search of voxel-based morphometry (VBM) studies of SAD, GAD, PD, GA, and SP was performed with an effect-size signed differential mapping (ES-SDM) meta-analysis to estimate the clusters of significant gray matter differences between patients and controls.ResultsTwenty-four studies were eligible for inclusion in the meta-analysis. Reductions in the right anterior cingulate gyrus and the left inferior frontal gyrus gray matter volumes (GMVs) were noted in patients with anxiety disorders when potential confounders, such as comorbid major depressive disorder (MDD), age, and antidepressant use were controlled for. We also demonstrated increased GMVs in the right dorsolateral prefrontal cortex (DLPFC) in comorbid depression-anxiety (CDA), drug-naïve and adult patients. Furthermore, we identified a reduced left middle temporal gyrus and right precentral gyrus in anxiety patients without comorbid MDD.ConclusionOur findings indicate that a reduced volume of the right ventral anterior cingulate gyrus and left inferior frontal gyrus is common in anxiety disorders and is independent of comorbid depression, medication use, and age. This generic effect supports the notion that the four types of anxiety disorders have a clear degree of overlap that may reflect shared etiological mechanisms. The results are consistent with neuroanatomical DLPFC models of physiological responses, such as worry and fear, and the importance of the ventral anterior cingulate (ACC)/medial prefrontal cortex (mPFC) in mediating anxiety symptoms.

The positioning accuracy of the existing vehicular Global Positioning System (GPS) is far from sufficient to support autonomous driving and ITS applications. To remedy that, leading methods such as ranging and cooperation have improved the positioning accuracy to varying degrees, but they are still full of challenges in practical applications. Especially for cooperative positioning, in addition to the performance of methods, cooperators may provide false data due to attacks or selfishness, which can seriously affect the positioning accuracy. By fully exploiting the characteristics of blockchain and edge computing, this paper proposes a vehicular blockchain-based secure and efficient GPS positioning error evolution sharing framework, which improves vehicle positioning accuracy from ensuring security and credibility of cooperators and data. First, by analyzing the GPS error, a bridge can be established between the sensor-rich vehicles and the common vehicles to achieve cooperation by sharing the positioning error evolution at a specific time and location. Particularly, the positioning error evolution is obtained by a deep neural network (DNN)-based prediction algorithm running on the edge server. We further propose to use blockchain technology for storage and sharing the evolution of positioning errors, mainly to guarantee the security of cooperative vehicles and mobile edge computing nodes (MECNs). In addition, the corresponding smart contracts are designed to automate and efficiently perform storage and sharing tasks as well as solve inconsistencies in time scales. Extensive simulations based on actual data indicate the accuracy and security of our proposal in terms of positioning error correction and data sharing.

Edge caching is being explored as a promising technology to alleviate the network burden of cellular networks by separating the computing functionalities away from cellular base stations. However, the service capability of existing caching scheme is limited by fixed edge infrastructure when facing the uncertainties of users' requests and locations. The vehicular caching, which uses the moving vehicles as cache carriers, is regard as an efficient method to solve the problem above. This paper studies the effectiveness of vehicular caching scheme in content centric networks by developing optimization model towards the minimization of network energy consumption. Particularly, we model the interactions between caching vehicles and mobile users as a 2-D Markov process, in order to characterize the network availability of mobile users. Based on the developed model, we propose an online vehicular caching design by optimizing network energy efficiency. Specifically, the problem of caching decision making is firstly formulated as a fractional optimization model, towards the optimal energy efficiency. Using nonlinear fractional programming technology and Lyapunov optimization theory, we derive the theoretical solution for the optimization model. An online caching algorithm to enable the optimal vehicular caching is developed based on the solution. Finally, extensive simulations are conducted to examine the performance of our proposal. By comparison, our online caching scheme outperforms the existing scheme in terms of energy efficiency, hit ratio, cache utilization, and system gain.

Studies of schizophrenia at drug-naive state and on antipsychotic medication have reported a number of regions of gray-matter (GM) abnormalities but the reports have been inconsistent. The aim of this study was to conduct multimodal meta-analysis to compare the cross-sectional voxel-based morphometry studies of brain GM in antipsychotic-naive first-episode schizophrenia (AN-FES) and those with antipsychotic treatment within 1 year (AT-FES) to determine the similarities and differences in these groups. We conducted two separate meta-analyses containing 24 studies with a sample size of 801 patients and 957 healthy controls. A multimodal meta-analysis method was used to compare the findings between AN-FES and AT-FES. Meta-regression analyses were done to determine the influence of different variables including age, duration of illness, and positive and negative symptom scores. Finally, jack-knife analyses were done to test the robustness of the results. AN-FES and AT-FES showed common patterns of GM abnormalities in frontal (gyrus rectus), superior temporal, left hippocampal and insular cortex. GM in the left supramarginal gyrus and left middle temporal gyrus were found to be increased in AN-FES but decreased in AT-FES, whereas left median cingulate/paracingulate gyri and right hippocampus GM was decreased in AN-FES but increased in AT-FES. Findings suggest that both AN-FES and AT-FES share frontal, temporal and insular regions as common anatomical regions to be affected indicating these to be the primary regions of GM abnormalities in both groups.

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