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

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

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

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

The trans-ancestral genomic architecture of glycemic traits

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

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

Prognosis and Influencing Factors of Patients with Malignant Melanoma

Background Malignant melanoma (MM) is caused by the malignant transformation of epidermal melanocytes with extremely high malignant degree, and its prevention and treatment is a key issue in the field of dermatology. Objective To investigate the prognosis of patients with MM, and influencing factors of the prognosis of patients with MM. Methods A total of 205 patients with malignant melanoma from the First Affiliated Hospital of Shanxi Medical University from January 2006 to December 2021 were selected as the subjects. The clinical data were obtained by collecting information from electronic medical records of patients, the overall survival (OS) was confirmed by telephone follow-up, and the last follow-up visit until 2022-12-31. The survival curve was plotted by the Kaplan-Meier method, and Log-rank test was used to compare the survival curves of different influencing factors. Multivariate Cox proportional hazard regression model was used to analyze the influencing factors of survival outcome in MM patients. Results The 1-year overall survival, 3-year overall survival, and 5-year overall survival rates of MM patients were 94.6% (194/205) , 81.9% (168/205) and 72.6% (149/205) , respectively, the mean OS was 71.77 months and the median OS was 66.83 months. The results of survival curve analysis showed statistically significant differences when comparing the OS of MM patients with different genders, ages, tumor thicknesses, tumor ulcers, lymph node metastases, and neutrophil-to-lymphocyte ratios (NLR) (P&lt;0.05) . Multivariate Cox regression analysis showed that male (HR=1.644, 95%CI=1.148-2.498) , tumor thickness &gt;1.94 mm (HR=2.466, 95%CI=1.419-4.284) , tumor ulcer (HR=1.821, 95%CI=1.225-2.708) , lymph node metastasis (HR=1.999, 95%CI=1.305-2.892) , and NLR≥3 (HR=1.873, 95%CI=1.108-3.166) were the influencing factors of survival outcome in MM patients (P&lt;0.05) . Conclusion Male, tumor thickness &gt;1.94 mm, tumor ulcer, lymph node metastasis and NLR≥3 are poor prognostic factors for MM patients. Medical workers can focus on MM patients with the above poor prognostic factors and enhance care to improve their survival rate, thus better guiding the clinic treatment

Efficacy and safety of 3D reconstruction and basket multi‐electrode renal denervation (RDN) for refractory hypertensive patients with chronic kidney disease

Abstract Renal Artery Sympathetic Denervation (RDN) can lower blood pressure. Different ablation catheters (single electrode, multi‐electrode) have different scopes of ablation (renal artery main stem and branches). Few studies have compared the advantages and disadvantages of different ablation catheters and different procedures in terms of antihypertensive efficacy. To compare the efficacy and safety of 3D reconstruction radiofrequency ablation (3DRA) and basket multi‐electrode radiofrequency ablation (BMRA) in Renal Artery Sympathetic Denervation. Fifty‐three patients with Refractory hypertension (RHT) were divided into BMRA, (n = 28) and 3DRA(n = 25). BMRA group used a stereobasket multi‐electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120 s per site. 3DRA group used a NavStar pressure‐monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40 s per site, and an ablation energy of 12 W. Baseline and RDN parameters and complications were compared in both groups. Home and 24 h ambulatory blood pressure, type of anti‐hypertensive medication taken, and serum creatinine were followed up at 1, 3, 6, 12, and 24 months after the RDN. There were no differences in baseline characteristics between the two groups. (23.14 ± 2.00)months of follow‐up in the BMRA group resulted in a total of (25.86 ± 8.61) loci ablation. (19.28 ± 7.40)months of follow‐up in the 3DRA group resulted in a total of (21.04 ± 6.47)loci ablation. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline(H‐SBP/mmHg: BMRA 149.9 ± 10.59 vs. baseline 168.36 ± 12.76; 3DRA 152.6 ± 14.91 vs. 164.89 ± 12.96, both p < .05). The proportion of people with 24 h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. At each follow‐up time point, there were no differences in home and 24‐h flow SBP, DBP, or Scr between the two groups. There were two cases of severe renal artery complications from implanted vascular stents and one case of femoral artery pseudoaneurysm in the 3DRA group. At follow‐up, 1 (1.9%) patient in the 3DRA group died of unexplained death and 1 (1.9%) patient developed heart failure, and 1 (1.9%) patient in the BMRA group died of unexplained death. Basket multi‐electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in reducing systolic blood pressure

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

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