Clinical features of patients with MOG-IgG associated disorders and analysis of the relationship between fibrinogen-to-albumin ratio and the severity at disease onset

ObjectiveThe study aimed to investigate the differences in clinical features between pediatric and adult patients with first-episode MOG-IgG associated disorders (MOGAD) and evaluate the relationship between the fibrinogen-to-albumin ratio (FAR) and the severity of neurological deficits at disease onset.MethodsWe retrospectively collected and analyzed biochemical test results, imaging characteristics, clinical manifestations, expanded disability status scale (EDSS) score, and FAR. The Spearman correlation analysis and logistic regression models were used to examine the association between FAR and severity. Receiver operating characteristic (ROC) curve analysis was to analyze the predictive ability of FAR for the severity of neurological deficits.ResultsFever (50.0%), headache (36.1%), and blurred vision (27.8%) were the most common clinical manifestations in the pediatric group (<18 years old). However, in the adult group (≥18 years old), the most common symptoms were blurred vision (45.7%), paralysis (37.0%), and paresthesia (32.6%). Fever was more common in the pediatric group, while paresthesia was more common in the adult patients, with all differences statistically significant (P < 0.05). The most frequent clinical phenotype in the pediatric group was acute disseminated encephalomyelitis (ADEM; 41.7%), whereas optic neuritis (ON; 32.6%) and transverse myelitis (TM; 26.1%) were more common in the adult group. The differences in clinical phenotype between the two groups were statistically significant (P < 0.05). In both pediatric and adult patients, cortical/subcortical and brainstem lesions were the most common lesions on cranial magnetic resonance imaging (MRI), whereas, for spinal MRI, cervical and thoracic spinal cord lesions were the most commonly observed. According to binary logistic regression analysis, FAR was an independent risk factor for the severity of neurological deficits (odds ratio = 1.717; 95% confidence interval = 1.191–2.477; P = 0.004). FAR (r = 0.359, P = 0.001) was positively correlated with the initial EDSS score. The area under the ROC curve was 0.749.ConclusionThe current study found age-dependent phenotypes in MOGAD patients as ADEM was more commonly observed in patients < 18 years old, while ON and TM were more frequently found in patients ≥18 years old. A high FAR level was an independent indicator for more severe neurological deficits at disease onset in patients with a first episode of MOGAD

Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index

The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI)

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Study of Excavation Stability and Treatment Measures of the Side Slope of Anti-Dip Bedding Highway

In order to improve the slope safety of the side slope of anti-dip bedding highway, this paper analyzes the stability of the excavation by using the finite difference numerical simulation technique. The development process of the disaster under the three excavation conditions and the whole process of the slip surface of the anti dip bedding rock slope are revealed; The method of determining the potential slip surface is introduced, that is to say, the slope is unstable and slip by reducing the material parameters of the slope, and then the position of the slip surface is judged by the difference of the displacement value. The research results have important significance for understanding the development mechanism of slope disaster and adopting corresponding engineering measures for different stages of slope

Study of Excavation Stability and Treatment Measures of the Side Slope of Anti-Dip Bedding Highway

In order to improve the slope safety of the side slope of anti-dip bedding highway, this paper analyzes the stability of the excavation by using the finite difference numerical simulation technique. The development process of the disaster under the three excavation conditions and the whole process of the slip surface of the anti dip bedding rock slope are revealed; The method of determining the potential slip surface is introduced, that is to say, the slope is unstable and slip by reducing the material parameters of the slope, and then the position of the slip surface is judged by the difference of the displacement value. The research results have important significance for understanding the development mechanism of slope disaster and adopting corresponding engineering measures for different stages of slope

Defining Insight: A Study Examining Implicit Theories of Insight Experience

Accounts of insight experiences have already been used to define insight or distinguish insight from noninsight; but the nature of the experience remains unclear. This research takes a quantitative approach to assessing the implicit conceptual structure of everyday insight experience in 2 studies. The aim of Study 1 was to collect descriptions of everyday insight experiences: participants were required to give as many brief descriptions as possible of experience of insight in diverse naturalistic settings. The participants provided a total of 99 categories of terms including 22 principal terms. In Study 2 the underlying structure of this set of terms was extracted through multidimensional scaling (MDS), and the 22 principal terms were further clustered. The results showed that the terms scattered in various dimensional positions and the 22 principal terms were grouped in 4 clusters. Together these 2 studies suggest that the experience of everyday insight is a multidimensional construct encompassing positive affect at the moment of insight; phenomenological experiences relating to the dynamic insight process, particularly the process of sudden restructuring; solution-related cognitive responses; and postinsight reflections. The main implications of the research are discussed

A Composite Matching Layer with Anti-Reflection Characteristics for Broadband Acoustic Scattering Reduction

A composite matching layer composed of periodically arranged scatters with anti-reflection (AR) characteristics is proposed for broadband scattering reduction. The anti-reflection structure is composed of periodically arranged metal foam scatters, and it is the first attempt to be applied in the field of suppressing acoustic reflection. A complete theoretical model is developed to reveal the mechanism of scattering reduction and acoustic absorption based on effective medium theory and the transfer matrix method. The correctness and effectiveness of the theoretical model are verified by the finite element method (FEM), showing acoustic reflectance of less than 13.5% at broadband frequencies. The variation trends of reflectance are deeply investigated. The superior acoustic scattering reduction performance suggests that the matching layer possesses potential for acoustic imaging equipment and acoustic stealth