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BackgroundGeneral obesity is a well-established risk factor for gallstone disease (GSD), but whether central obesity contributes additional independent risk remains controversial. We aimed to comprehensively clarify the effect of body fat distribution on GSD.MethodsWe first investigated the observational association of central adiposity, characterized by waist-to-hip ratio (WHR), with GSD risk using data from UK Biobank (N=472,050). We then explored the genetic relationship using summary statistics from the largest genome-wide association study of GSD (ncase=43,639, ncontrol=506,798) as well as WHR, with and without adjusting for body mass index (BMI) (WHR: n=697,734; WHRadjBMI: n=694,649).ResultsObservational analysis demonstrated an increased risk of GSD with one unit increase in WHR (HR=1.18, 95%CI=1.14-1.21). A positive WHR-GSD genetic correlation (rg =0.41, P=1.42×10-52) was observed, driven by yet independent of BMI (WHRadjBMI: rg =0.19, P=6.89×10-16). Cross-trait meta-analysis identified four novel pleiotropic loci underlying WHR and GSD with biological mechanisms outside of BMI. Mendelian randomization confirmed a robust WHR-GSD causal relationship (OR=1.50, 95%CI=1.35-1.65) which attenuated yet remained significant after adjusting for BMI (OR=1.17, 95%CI=1.09-1.26). Furthermore, observational analysis confirmed a positive association between general obesity and GSD, corroborated by a shared genetic basis (rg =0.40, P=2.16×10-43), multiple novel pleiotropic loci (N=11) and a causal relationship (OR=1.67, 95%CI=1.56-1.78).ConclusionBoth observational and genetic analyses consistently provide evidence on an association of central obesity with an increased risk of GSD, independent of general obesity. Our work highlights the need of considering both general and central obesity in the clinical management of GSD.

Objective: This study established an index system for assessing forest fire spread hazards and conducted a forest fire spread hazard assessment in the mountainous district of Beijing (including Fangshan, Mentougou, Changping, Yanqing, Huairou, Miyun, and Pinggu). The relationship between forested landscape spatial pattern and forest fire spread hazard was explored; this method provided the basis for the establishment of a landscape forest fire security guarantee system. Methods: The forest fire spread hazard assessment index system was constructed from four aspects: forest fuel, meteorological factors, topographic factors, and fire behavior. The weighted comprehensive evaluation method and area-weighted average method were used to calculate the forest fire spread hazard indices at the subcompartment scale and township scale. Moran’s I index was selected as the spatial autocorrelation index to analyze the autocorrelation degree and spatial distribution of the forest fire spread hazard index. Eleven representative landscape pattern indices were selected to analyze the main landscape spatial pattern affecting forest fire spread hazard by correlation analysis and principal component analysis. Results: (1) The areas with high, medium–high, medium-low, and low forest fire spread hazard grades accounted for 39.87%, 33.10%, 11.37%, and 15.66% of the study area, respectively, at the subcompartment scale and for 52.36%, 22.58%, 18.39%, and 6.67% of the study area, respectively, at the township scale. (2) The forest fire spread hazard index results obtained at the subcompartment and township scales in the Mountainous District of Beijing showed a spatial agglomeration distribution law. (3) The forest fire spread hazard was influenced mainly by landscape diversity (SHDI and PRD), landscape aggregation (AI, CONTAG, and PD), and landscape area (TA). Conclusions: The overall forest fire spread hazard in the mountainous district of Beijing showed a gradual increase from plains to mountainous areas. The land types of the high-spread hazard subcompartment mainly included general shrubbery and coniferous forestlands, and the dominant species in the high-spread hazard arbor forest subcompartment were mainly Platycladus orientalis, Pinus tabuliformis, and Quercus mongolica.

Purpose: This paper studies the characteristics of the seedling regeneration, stand structures, undergrowth biomasses, litter amounts and soil water contents of planted forests of Pinus tabuliformis in the Liaoheyuan Nature Reserve after a fire disturbance in 2014 and analyzes the significant factors affecting seedling regeneration to offer a scientific basis for the ecological restoration of vegetation in burned areas. Methods: Plots of forest stands that experienced different fire severities (high severity, moderate severity, low severity) and control sample plots were used to study the significance of differences in seedling regeneration, stand structure, undergrowth biomass, litter amount and soil water content characteristics among stands under the effects of different fire severities by using single element variance analysis. The major factors affecting seedling regeneration characteristics were also analyzed here by using correlation and principal component analyses. Results: (1) There was no significant difference in the density and growth characteristics (base diameter, plant height and crown diameter) of regenerated seedlings of Pinus tabuliformis under the different fire severities (P ​> ​0.05), and the spatial distribution of regenerated seedlings fit the aggregated distribution pattern. (2) There was no significant difference in diameter at breast height (DBH), plant height or crown diameter of Pinus tabuliformis under different fire severities (P ​> ​0.05), but there were highly significant differences in scorch height, biomass of undergrowth woody plants, biomass of undergrowth herbs, undecomposed litter amount, semidecomposed litter amount and soil water content under different the fire severities (P ​

BackgroundPrevious studies have suggested associations between addictive behavior and gallstone disease (GSD) risk, yet conflicting results exist. It also remains unclear whether this association is causal or due to confounding or reverse associations. The present study aims to systematically analyze the epidemiological evidence for these associations, as well as estimate the potential causal relationships using Mendelian randomization (MR).MethodsWe analyzed four common addictive behaviors, including cigarette smoking, alcohol intake, coffee, and tea consumption (N = 126,906–4,584,729 participants) in this meta-analysis based on longitudinal studies. The two-sample MR was conducted using summary data from genome-wide associations with European ancestry (up to 1.2 million individuals).ResultsAn observational association of GSD risk was identified for smoking [RR: 1.17 (95% CI: 1.06–1.29)], drinking alcohol [0.84 (0.78–0.91)], consuming coffee [0.86 (0.79–0.93)], and tea [1.08 (1.04–1.12)]. Also, there was a linear relationship between smoking (pack-years), alcohol drinking (days per week), coffee consumption (cups per day), and GSD risk. Our MRs supported a causality of GSD incidence with lifetime smoking [1.008 (1.003–1.013), P = 0.001], current smoking [1.007 (1.002–1.011), P = 0.004], problematic alcohol use (PAU) [1.014 (1.001–1.026), P = 0.029], decaffeinated coffee intake (1.127 [1.043–1.217], P = 0.002), as well as caffeine-metabolism [0.997 (0.995–0.999), P = 0.013], and tea consumption [0.990 (0.982–0.997), P = 0.008], respectively.ConclusionOur study suggests cigarette smoking, alcohol abuse, and decaffeinated coffee are causal risk factors for GSD, whereas tea consumption can decrease the risk of gallstones due to the effect of caffeine metabolism or polyphenol intake.

Abstract Objective To explore the prevalence and its associated metabolic factors of thyroid nodules (TNs) among subjects who participated in the physical examinations in Chongqing, China. Methods The participants from the Health Management Center of JinShan Hospital of Chongqing Medical University, between September 2015 and May 2020, were included in this study. All of the participants underwent thyroid ultrasonography, anthropometric measurements, and serum examinations. Differences in the TNs prevalence were compared with the chi-square test or Wilcoxon rang-sum test. Multivariable logistic regression analyses were used to estimate the metabolic factors associated with TNs and multiple thyroid nodules (MTNs). Results Of the included 121,702 participants, 41,547 had TNs, and 20,899 had MTNs, with the prevalence of 34.1 and 17.0 %, respectively. Women had a significantly higher prevalence of TNs than men (40.6 % vs. 29.8 %; χ 2 = 1517.33, P

BackgroundObservational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.MethodsA systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.ResultsA total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, P

BackgroundGenetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes.MethodsWe searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence.ResultsWe included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn’s disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions.ConclusionsOur study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases.

Abstract Background The identification of the homogeneous and heterogeneous risk factors for different types of metastases in colorectal cancer (CRC) may shed light on the aetiology and help individualize prophylactic treatment. The present study characterized the incidence differences and identified the homogeneous and heterogeneous risk factors associated with distant metastases in CRC. Methods CRC patients registered in the SEER database between 2010 and 2016 were included in this study. Logistic regression was used to analyse homogeneous and heterogeneous risk factors for the occurrence of different types of metastases. Nomograms were constructed to predict the risk for developing metastases, and the performance was quantitatively assessed using the receiver operating characteristics (ROC) curve and calibration curve. Results A total of 204,595 eligible CRC patients were included in our study, and 17.07% of them had distant metastases. The overall incidences of liver metastases, lung metastases, bone metastases, and brain metastases were 15.34%, 5.22%, 1.26%, and 0.29%, respectively. The incidence of distant metastases differed by age, gender, and the original CRC sites. Poorly differentiated grade, more lymphatic metastasis, higher carcinoembryonic antigen (CEA), and different metastatic organs were all positively associated with four patterns of metastases. In contrast, age, sex, race, insurance status, position, and T stage were heterogeneously associated with metastases. The calibration and ROC curves exhibited good performance for predicting distant metastases. Conclusions The incidence of distant metastases in CRC exhibited distinct differences, and the patients had homogeneous and heterogeneous associated risk factors. Although limited risk factors were included in the present study, the established nomogram showed good prediction performance.

A closed loop two-phase thermosiphon is supposed as an effective heat transfer unit for improving the heat transfer in the latent heat storage devices, which has a simple structure and natural circulation. An experimental study and theoretical analysis were conducted to evaluate the heat transfer performance. The effects of height difference, filling ratio, and condenser temperature were investigated relative to changes in pressure and evaporator temperature. The results indicate that heat transfer performance is improved with an increase in height difference and a decrease in condenser temperature. Meanwhile, a closed loop thermosiphon with medium filling ratios of 44.5% and 49.9% shows the best heat transfer performance. Furthermore, the subcooling phenomenon occurs at large filling ratios of 68.1% and 67.1% and the superheating phenomenon occurs at small filling ratios of 27.3% and 31.1%.

This paper presents the results of the simulations of the thermal storage and thermal release processes in a spouted bed using a self-developed computational fluid dynamics–discrete element method (CFD–DEM) model to analyze the thermal energy storage (TES) characteristics of the spouted bed with varying nozzle numbers. The thermal storage capacity, thermal release capacity and thermal storage efficiency were analyzed. Additionally, the effects of gas inlet jet number and gas flowrate on the thermal storage characteristics are discussed. The results showed that a higher number of nozzles resulted in a faster change of particle temperature, higher gas phase temperature field update rate and a higher thermal storage capacity. However, when the number of nozzles is increased from 1 to 2 and then 3, the rate of increase in total thermal storage and total thermal release decreases, and the increase in thermal release is always higher than the increase in thermal storage. When the number of nozzles is increased from one through three, the thermal efficiency increased from 52.9% to 75.6%, establishing that a higher number of nozzles improves the thermal efficiency.

Purpose – This paper examines whether there are differences in the nature of the price discovery process across established versus emerging stock markets using a twenty-country sample. Design/methodology/approach – The authors analyse security returns for traces of predictability or non-randomness using variance ratio tests, Granger-Causality models and runs tests. Findings – The findings pinpoint at predictabilities which seem inconsistent with market efficiency, and they suggest that the inherent cause of predictability differs across groups. Research limitations/implications – The authors present empirical evidence which may be used to attain a deeper understanding of the links between predictability and market efficiency, in view of the conflicting evidence in prior literature. Practical implications – Whilst the pricing process in emerging markets may be hindered by delayed adjustments, in case of established markets it seems that there is a higher tendency for price reversals which could be due to prior over-reactions. Originality/value – This study presents evidence of substantial differences in predictability across developed and emerging markets which was gleaned through the rigorous application of different empirical tests.

BackgroundProstate cancer is the second most common cancer in males worldwide, and multitudes of factors have been reported to be associated with prostate cancer risk.ObjectivesWe aim to conduct the phenome-wide exposed-omics analysis of the risk factors for prostate cancer and verify the causal associations between them.MethodsWe comprehensively searched published systematic reviews and meta-analyses of cohort studies and conducted another systematic review and meta-analysis of the Mendelian randomization studies investigating the associations between extrinsic exposures and prostate cancer, thus to find all of the potential risk factors for prostate cancer. Then, we launched a phenome-wide two-sample Mendelian randomization analysis to validate the potentially causal relationships using the PRACTICAL consortium and UK Biobank.ResultsWe found a total of 55 extrinsic exposures for prostate cancer risk. The causal effect of 30 potential extrinsic exposures on prostate cancer were assessed, and the results showed docosahexaenoic acid (DHA) [odds ratio (OR)=0.806, 95% confidence interval (CI): 0.661-0.984, p=0.034], insulin-like growth factor binding protein 3 (IGFBP-3) (OR=1.0002, 95%CI: 1.00004-1.0004, p=0.016), systemic lupus erythematosus (SLE) (OR=0.9993, 95%CI: 0.9986-0.99997, p=0.039), and body mass index (BMI) (OR=0.995, 95%CI: 0.990-0.9999, p=0.046) were associated with prostate cancer risk. However, no association was found between the other 26 factors and prostate cancer risk.ConclusionsOur study discovered the phenome-wide exposed-omics risk factors profile of prostate cancer, and verified that the IGFBP-3, DHA, BMI, and SLE were causally related to prostate cancer risk. The results may provide new insight into the study of the pathogenesis of prostate cancer.

Four coordination polymers have been synthesized by using Zn(II)/Cd(II) salt and bis(imidazole) ligand in the presence of the different flexible phenylenediacetate isomers under hydrothermal conditions. The flexible trans-conformation pda and biyb ligands in complexes 1, 3, 4 afford the 2D (4,4)-connected layer, which are further stacked in an offset fashion with an ABAB sequence to propagate into a 3D supramolecular architecture through strong C–H···π and C–H⋯O interactions. Differently, the flexible cis-conformation pda and biyb ligands in 2 can be seen as “V” type building block, linking Zn(II) atoms to form a 3D helix network. The structural diversity of these complexes is mainly attributed to the different coordination modes and isomer conformations of the flexible phenylenediacetic acids and bis(imidazole) ligand. The fluorescence property application and mechanisms of four complexes for detecting antibiotic cefixime (CEF) have been researched. Compared with 1, 3, 4 complex 2 has higher quenching percentage, this may be because 2 is a 3D structure with a large hole (18.99 × 20.02 Å window). The detection limits of complexes 1–4 have been measured to be 0.23 μΜ, 0.34 μΜ, 0.37 μΜ, 0.38 μΜ, respectively. The theoretic calculation and UV–vis absorption experiments confirmed that the fluorescence quenching of complexes 1–4 toward cefixime (CEF) should be attributed to the electron transfer and the fluorescence inner filter effect between the fluorescent matter and the analyte.

Abstract Background Inconsistencies have existed in research findings on the association between cardiovascular disease (CVD) and single nucleotide polymorphisms (SNPs) of ADIPOQ, triggering this up-to-date meta-analysis. Methods We searched for relevant studies in PubMed, EMBASE, Cochrane Library, CNKI, CBM, VIP, and WanFang databases up to 1st July 2017. We included 19,106 cases and 31,629 controls from 65 published articles in this meta-analysis. STATA 12.0 software was used for all statistical analyses. Results Our results showed that rs266729 polymorphism was associated with the increased risk of CVD in dominant model or in heterozygote model; rs2241766 polymorphism was associated with the increased risk of CVD in the genetic models (allelic, dominant, recessive, heterozygote, and homozygote). In subgroup analysis, significant associations were found in different subgroups with the three SNPs. Meta-regression and subgroup analysis showed that heterogeneity might be explained by other confounding factors. Sensitivity analysis revealed that the results of our meta-analysis were stable and robust. In addition, the results of trial sequential analysis showed that evidences of our results are sufficient to reach concrete conclusions. Conclusions In conclusion, our meta-analysis found significant increased CVD risk is associated with rs266729 and rs2241766, but not associated with rs1501299.

Epigenetic regulation plays a key role in cortical development. Here the authors show that Rcor2, a co-repressor of the histone demethylase LSD1/KDM1A complex, regulates neural progenitor cell proliferation and cortical neurogenesis by repressing sonic hedgehog signaling.

C23H21NO6, triclinic, P1̄ (no. 2), a = 7.624(4) Å, b = 9.197(5) Å, c = 15.058(5) Å, α = 94.13(3)°, β = 102.27(3)°, γ = 106.72(3)°, V = 977.9(8) Å3, Z = 2, Rgt(F) = 0.0662, wRref(F2) = 0.1733, T = 296(2) K.

C23H21NO5, monoclinic, P21/c (no. 14), a = 15.829(11) Å, b = 8.294(6) Å, c = 14.718(10) Å, β = 93.339(12)°, V = 1929(2) Å3, Z = 4, Rgt(F) = 0.073, wRref(F2) = 0.206, T = 296(2) K.

This article describes the design, fabrication, and flight test evaluation of a morphing geometry quadcopter capable of changing its intersection angle in-flight. The experiments were conducted at the Aircraft Computational and Resource Aware Fault Tolerance (AirCRAFT) Lab, Parks College of Engineering, Aviation and Technology at Saint Louis University, St. Louis, MO. The flight test matrix included flights in a “Figure-8” trajectory in two different morphing configurations (21° and 27°), as well as the nominal geometry configuration, two different flight velocities (1.5 m/s and 2.5 m/s), two different number of waypoints, and in three planes—horizontal, inclined, and double inclined. All the experiments were conducted using standard, off-the-shelf flight controller (Pixhawk) and autopilot firmware. Simulations of the morphed geometry indicate a reduction in pitch damping (42% for 21° morphing and 57.3% for 27° morphing) and roll damping (63.5% for 21° morphing and 65% for 27° morphing). Flight tests also demonstrated that the dynamic stability in roll and pitch dynamics were reduced, but the quadcopter was still stable under morphed geometry conditions. Morphed geometry also has an effect on the flight performance—with a higher number of waypoints (30) and higher velocity (2.5 m/s), the roll dynamics performed better as compared to the lower waypoints and lower velocity condition. The yaw dynamics remained consistent through all the flight conditions, and were not significantly affected by asymmetrical morphing of the quadcopter geometry. We also determined that higher waypoint and flight velocity conditions led to a small performance improvement in tracking the desired trajectory as well.

This article describes the data acquired from multiple flights of a custom-built quadcopter. The Quadcopter was programmed to fly a pre-defined “Figure-8” flight path, at a constant altitude. The data set includes flights with a varying number of waypoints (10 and 15 waypoints in each lobe of the “Figure-8”) and at two different velocities (1.5 and 2.5 m/s). The data also contains information on the output of the flight controller in terms of the Pulse Width Modulation (PWM) signals to each of the four Electronic Speed Controllers (ESC) driving the motors, the recorded outputs of the Inertial Measurement Unit (linear accelerations ax, ay, az and angular velocities p, q, r), GPS data (Latitude, Longitude, altitude, Horizontal Dilution of Precision (HDOP) and Vertical Dilution of Precision (VDOP). The data are included as Supplemental Material.