55 research outputs found

    Accuracy of triage strategies for human papillomavirus DNA-positive women in low-resource settings: A cross-sectional study in China

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    CareHPV is a human papillomavirus (HPV) DNA test for low-resource settings (LRS). This study assesses optimum triage strategies for careHPV-positive women in LRS

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

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    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

    An interlaboratory comparison of aerosol inorganic ion measurements by ion chromatography : Implications for aerosol pH estimate

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    Water-soluble inorganic ions such as ammonium, nitrate and sulfate are major components of fine aerosols in the atmosphere and are widely used in the estimation of aerosol acidity. However, different experimental practices and instrumentation may lead to uncertainties in ion concentrations. Here, an intercomparison experiment was conducted in 10 different laboratories (labs) to investigate the consistency of inorganic ion concentrations and resultant aerosol acidity estimates using the same set of aerosol filter samples. The results mostly exhibited good agreement for major ions Cl-, SO2-4, NO-3, NHC4 and KC. However, F-, Mg2C and Ca2C were observed with more variations across the different labs. The Aerosol Chemical Speciation Monitor (ACSM) data of nonrefractory SO2-4, NO-3 and NHC4 generally correlated very well with the filter-analysis-based data in our study, but the absolute concentrations differ by up to 42 %. Cl-from the two methods are correlated, but the concentration differ by more than a factor of 3. The analyses of certified reference materials (CRMs) generally showed a good detection accuracy (DA) of all ions in all the labs, the majority of which ranged between 90 % and 110 %. The DA was also used to correct the ion concentrations to showcase the importance of using CRMs for calibration check and quality control. Better agreements were found for Cl-, SO2-4, NO-3, NHC4 and KC across the labs after their concentrations were corrected with DA; the coefficient of variation (CV) of Cl-, SO2-4, NO-3, NHC4 and KC decreased by 1.7 %, 3.4 %, 3.4 %, 1.2 % and 2.6 %, respectively, after DA correction. We found that the ratio of anion to cation equivalent concentrations (AE/CE) and ion balance (anions-cations) are not good indicators for aerosol acidity estimates, as the results in different labs did not agree well with each other. In situ aerosol pH calculated from the ISORROPIA II thermodynamic equilibrium model with measured ion and ammonia concentrations showed a similar trend and good agreement across the 10 labs. Our results indicate that although there are important uncertainties in aerosol ion concentration measurements, the estimated aerosol pH from the ISORROPIA II model is more consistent

    Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

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    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

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    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

    The trans-ancestral genomic architecture of glycemic traits

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    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

    Present Geothermal Field and Roadway Heat Damage Characteristics in Zhujidong Coal Mine Area of Huainan City, Anhui Province, China

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    With the normalization of deep mining, the problem of mine thermal damage has been widely concerned. In this paper, 64 logging temperature data of surface boreholes of Zhujidong coalfield in Huainan City, Anhui Province, China, were summarized and sorted. The temperature data of 12 measuring points at the current main working level of −906 m and −965 m were measured. The ground temperature conditions of the vertical direction, horizontal direction, and main coal seam floor in the coalfield were analyzed. The characteristics of the present geothermal field and roadway heat damage, and its influencing factors were discussed. The results showed that the geothermal gradients of this area are between 1.7 ℃/hm and 3.6 ℃/hm, and the average geothermal gradient is 2.607 ℃/hm. It shows the transmission of warming in the vertical direction and horizontal direction shows the ground temperature lowering from south to north, east to west. The geothermal field in this area is mainly affected by the geological structure, and the thermal physical properties of rocks, magmatic rocks and groundwater activities also have a certain effect. At present, most of the main work level has reached the first heat hazard area, and some are in the second heat hazard area, according to Chinese regulations. The working face temperature is keeping above 28 7 ℃ and the relative humidity is being maintained above 70% for a long time. The problem of heat damage is extremely serious. It is suggested to construct the thermal environment control measures combining active and passive ways

    Synthesis, characterisation and carbon dioxide capture capacities of hierarchically porous Starbons®

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    The synthesis of hierarchically porous Starbon® based materials from initially highly mesoporous Starbons® is reported. Mesoporous starbons® are prepared from three different biopolymers: starch, alginic acid and pectin and each is then activated using three different activating agents: potassium hydroxide, carbon dioxide and oxygen to give a set of hierarchically porous Starbons® which retain the mesopores of the precursor whilst becoming predominantly microporous. The hierarchically porous materials are characterised using nitrogen porosimetry, CHN analysis, ICP-OES, XPS, SEM and TEM imaging. It is shown that the hierarchically porous Starbons® have higher carbon dioxide adsorption capacities than either the mesoporous Starbon® precursors or conventional microporous activated carbon. The materials show selectivities of up to 64 for adsorption of carbon dioxide versus nitrogen and only lose only 3-7% of their carbon dioxide adsorption capacities when the carbon dioxide is saturated with water. The carbon dioxide capture capacity of all 50 Starbon® materials showed a strong and positive linear correlation with the product of the materials ultramicropore surface area and ratio of ultramicropore (0.4-0.7 nm) volume to total pore volume

    The Effect and Mechanism of TLR9/KLF4 in FFA-Induced Adipocyte Inflammation

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    Objective. Current research has reported that obesity is a chronic inflammatory state, which is closely related with excessive accumulation of free fatty acid, while the specific mechanism that high level of FFA causes inflammation is not very clear. Thus, our research intended to observe the high FFA effects on TLR9/KLF4 expression and the downstream inflammatory factors, to explore the mechanism of inflammatory response suppressed by TLR9/KLF4. Methods. qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of TLR9, KLF4, and key inflammation-related factors. ELISA was used to detect the release level of inflammatory cytokines. The triglyceride (TG) and glucose (GLU) testing cassettes were used to detect the TG and GLU levels in culture medium. Results. In the omental tissue of obese individuals (OB), we found that TLR9, KLF4, mRNA, and the protein expression levels were lower than those of the normal weight control (NC) group. Similarly, in the omental tissue of high-fat diet (HFD) rats, we found that the mRNA expression levels of TLR9 and KLF4 were lower than those of the normal diet control group. In mature adipocytes, we found that KLF4 played an important anti-inflammatory role; moreover, PA can promote the development of inflammation by inhibiting KLF4 expression; TLR9 has a positive regulation function on KLF4 expression, but unrelated to PA. Conclusions. TLR9/KLF4 is involved in regulating FFA-induced adipocyte inflammation

    Few-layered MoS2 with S-vacancies anchored on N-doped carbon flower for high performance sodium storage

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    Molybdenum disulfide (MoS2) has been regarded as a promising anode material for sodium ion batteries (SIBs) due to its high theoretical capacity and graphene-like layered structure. However, the intrinsically low conductivity and large volume expansion during charge discharge cycling have become two key challenges hindering the practical application of MoS2 electrodes. Here, few-layered MoS2 nanosheets with S-vacancies are anchored on a 3D flower-like N-doped carbon frameworks (NCF@V-MoS2) by facile hydrothermal method and chemical etching strategy. The introduction of S-vacancies onto MoS2 nanosheet surface not only adjusts the electronic structure and intrinsically improves the conductivity, but also enlarges the interlayer distance and accelerates Na+ diffusion. The density functional theory calculations reveal that the existence of S-vacancies strongly accelerates Na' absorption ability. Benefiting the synergistic effect of the conductive NCF and V-MoS2, the as-synthesized NCF@V-MoS2 yields a high specific capacity with excellent rate performance and cycling stability. This novel design strategy holds great promise for the development and application of high-performance SIBs in the future. (C) 2021 Elsevier B.V. All rights reserved
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