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Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene–environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.
Autoimmune thyroiditis (AIT) has a complex aetiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signalling pathway-related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas, iodine-adequate areas and water-based iodine-excess areas from Shandong Province of China as survey sites. Totally, 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes’ DNA methylation levels and mRNA expression levels, respectively. We found that death associated protein kinase 1 (DAPK1) DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t = 2·7715, P = 0·0059; t = 2·4638, P = 0·0143 in female). There were differences in DAPK1 (t = 2·5384, P = 0·0121), TNF superfamily member 8 (t = 2·1667, P = 0·0334) and TNF-α-induced protein 8 (TNFAIP8) (t = 2·5672, P = 0·0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1 (t = 4·329, P < 0·001) and TNFAIP8 (t = 3·775, P < 0·001) in the cases was increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signalling pathway-related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent.
In this paper, we developed a new navigation system, called ATCM, which detects obstacles in a sliding window with an adaptive threshold clustering algorithm, classifies the detected obstacles with a decision tree, heuristically predicts potential collision and finds optimal path with a simplified Morphin algorithm. This system has the merits of optimal free-collision path, small memory size and less computing complexity, compared with the state of the arts in robot navigation. The modular design of 6-steps navigation provides a holistic methodology to implement and verify the performance of a robot’s navigation system. The experiments on simulation and a physical robot for the eight scenarios demonstrate that the robot can effectively and efficiently avoid potential collisions with any static or dynamic obstacles in its surrounding environment. Compared with the particle swarm optimisation, the dynamic window approach and the traditional Morphin algorithm for the autonomous navigation of a mobile robot in a static environment, ATCM achieved the shortest path with higher efficiency.
The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child–Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.
Emerging evidence has been revealed that high fat diet (HFD) correlate with insulin resistance (IR) which could be induced by endoplasmic reticulum stress (ERS). Recently, obesity or HFD induced nonalcoholic fatty liver disease (NAFLD) could promote alteration of iron metabolism. Disorder of iron metabolism have been linked to unnormal metabolism of glucose and lipid. Herein, we investigated the effect of impaired iron homeostasis on hepatic IR, focusing on ferritinophagy. Male C57/6J mice were administered with HFD (60% energy from fat) or LFD (10% energy from fat) for 10 weeks (n = 10), and Palmitic acid (PA)-insulin treated HepG2 cells were also established. Hepatic IR as evidenced by increased hepatic steatosis and decreased of p-AKT (48%, p < 0.0005), p-GSK-3β (34%, p < 0.05) in the liver of HFD mice. In addition, decreased iron level and expression NCOA4, as well as increased up-regulation of IRE1α and EIF2α were observed in HFD liver. By using desferrioxamine (DFO) and ferric ammonium citrate (FAC), we examined iron level on IRE1α and EIF2α. And glucose uptake assay shown that FAC supplementation, and ERS inhibitors of 4-PBA and STF could improve the glucose uptake of HepG2 cells in the presence of PA. Furthermore, we evaluated the glucose uptake of HepG2 cells incubated with adenovirus which mediated overexpression of NCOA4, FAC, 4-PBA (ERS inhibitor) or STF (IRE1 inhibitor). Taken together, deficiency of iron induced by impaired ferritinophagy induced hepatic IR, partly by aggravating hepatic ERS, especially IRE1 signal pathway in vivo and vitro. These findings provide evidence and new insight for therapeutic strategy of iron deficiency in NAFLD.
To provide scientific, theoretical support for the improvement of medical disaster training, we systematically analyzed the National Disaster Life Support (NDLS) Course and established a training curriculum with feedback based on the current status of disaster medicine in China.
The gray prediction model is applied to long-term forecast research on course effect. In line with the hypothesis, the NDLS course with feedback capability is more scientific and standardized.
The current training NDLS course system is suitable for Chinese medical disasters. After accepting the course training, audiences’ capabilities were enhanced. In the constructed GM (1,1) model prediction, the developing coefficients of the pretest and the posttest are 0.04 and 0.057, respectively. In light of the coefficient, the model is appropriate for the long-term prediction. The predicted results can be used as the basis for constructing training closed-loop optimization feedback. It can indicate that the course system has a good effect as well.
According to the constructed GM model, the NDLS course system is scientific, practical, and operational. The research results can provide reference for relevant departments and be used for the construction of similar training course systems.
Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of ‘adequate iodine’ (100–199 µg/l) be revised to ‘sufficient iodine’ (100–299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.
A new yttrium-zirconium-pillared montmorillonite (Y-Zr-MMT), was synthesized, characterized and used as a Ce catalyst support. The Y-Zr-MMT is a good support for dispersing cerium active sites and it is responsible for the high activity in the total oxidation of acetone, toluene and ethyl acetate. The Y-Zr-MMT shows greater advantages than the conventional alumina/cordierite honeycomb supports such as large specific surface area, lower cost and easier preparation. Catalytic tests demonstrated that Ce/Y-Zr-MMT (Ce loading 8.0%) was the most active, with the total oxidation of acetone, toluene and ethyl acetate being achieved at 220, 300 and 220°C, respectively. The catalyst displayed better activity for the oxidation of acetone and ethyl acetate than a conventional, supported Pd-catalyst under similar conditions. The special structure of the yttrium-doped zirconium-pillared montmorillonite can strengthen the interaction between the CeO2 and Zr-MMT support and improve the dispersion of the Ce particles, which enhances the catalytic activity for the oxidation of VOCs. The new catalyst, 8.0%Ce/Y-Zr-MMT, could be promising for industrial applications due to its high catalytic activity and low cost. The support and the catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and BET specific surface area measurements.
A novel robust scheme for Transfer Alignment (TA) is proposed for improving the accuracy of the navigation of a Hypersonic Cruise Vehicle (HCV). The main goal is to instil robustness in the safety and accuracy of the attitude determination, despite mode uncertainties. This article focuses on Robust Sparse-Grid Quadrature Filtering (R-SGQF) using two given robust factors for norm-bounded model uncertainties in non-linear systems. Missile dynamic and measurement model uncertainties are established to validate TA technologies. The nominal stability of the R-SGQF is defined by estimating error dynamics. The technique gives sufficient conditions for the R-SGQF in terms of two parameterised Riccati equations. Robust stability is analysed using Lyapunov theory and the accuracy level of the Sparse-Grid Quadrature (SGQ) algorithm. Embedding the SGQ technique into the robust filter structure, R-SGQF is not only of robust stability against uncertainty but also of higher accuracy. The simulation results of the TA algorithm demonstrate that attitude determinations validate the effectiveness of the R-SGQF algorithm.
The Centers for Disease Control and Prevention (CDC) has developed an approach to ventilator-associated events (VAE) surveillance. Using these methods, this study was performed to investigate VAE incidences and to test whether VAEs are associated with poorer outcomes in China.
A 4-month, prospective multicenter surveillance study between April and July 2013.
Our study included 15 adult intensive care units (ICUs) of 15 hospitals in China.
Patients admitted to ICUs during the study period
Patients on mechanical ventilation (MV) were monitored for VAEs: ventilator-associated conditions (VACs), infection-related ventilator-associated complications (IVACs), and possible or probable ventilator-associated pneumonia (VAP). Patients with and without VACs were compared with regard to duration of MV, ICU length of stay (LOS), overall hospital LOS, and mortality rate.
During the study period, 2,356 of the 5,256 patients admitted to ICUs received MV for 8,438 ventilator days. Of these patients, 636 were on MV >2 days. VACs were identified in 94 cases (4.0%; 11.1 cases per 1,000 ventilator days), including 31 patients with IVACs and 16 with possible VAP but none with probable VAP. Compared with patients without VACs, patients with VACs had longer ICU LOS (by 6.2 days), longer duration on MV (by 7.7 days), and higher hospital mortality rate (50.0% vs 27.3%). The mortality rate attributable to VACs was 11.7%. Compared with those with VACs alone, patients with IVACs had longer duration on MV and increased ICU LOS but no higher mortality rates.
In China, surveillance of VACs and IVACs is able to identify MV patients with poorer outcomes. However, surveillance of possible and probable VAP can be problematic.
Infect. Control Hosp. Epidemiol. 2015;36(12):1388–1395
Gaussian process regression (GPR) is used in a Spare-grid Quadrature Kalman filter (SGQKF) for Strap-down Inertial Navigation System (SINS)/odometer integrated navigation to bridge uncertain observation outages and maintain an estimate of the evolving SINS biases. The SGQKF uses nonlinearized dynamic models with complex stochastic nonlinearities so the performance degrades significantly during observation outages owing to the uncertainties and noise. The GPR calculates the residual output after factoring in the contributions of the parametric model that is used as a nonlinear SINS error predictor integrated into the SGQKF. The sensor measurements and SINS output deviations from the odometer are collected in a data set during observation availability. The GPR is then applied to predict SINS deviations from the odometer and then the predicted SINS deviations are fed to the SGQKF as an actual update to estimate all SINS biases during observation outages. We demonstrate our method's effectiveness in bridging uncertain observation outages in simulations and in real road tests. The results agree with the theoretical analysis, which demonstrate that SGQKF using GPR can maintain an estimate of the evolving SINS biases during signal outages.
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