Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T t...Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in China's Mainland. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.展开更多
Interval prediction of wind power,which features the upper and lower limits of wind power at a given confidence level,plays a significant role in accurate prediction and stability of the power grid integrated with win...Interval prediction of wind power,which features the upper and lower limits of wind power at a given confidence level,plays a significant role in accurate prediction and stability of the power grid integrated with wind power.However,the conventional methods of interval prediction are commonly based on a hypothetic probability distribution function,which neglects the correlations among various variables,leading to the decrease of prediction accuracy.Therefore,we improve the multi-objective interval prediction based on the conditional copula function,through which we can fully utilize the correlations among variables to improve prediction accuracy without an assumed probability distribution function.We use the multi-objective optimization method of nondominated sorting genetic algorithm-II(NSGA-II)to obtain the optimal solution set.The particular best solution is weighted by the prediction interval average width(PIAW)and prediction interval coverage probability(PICP)to pick the optimized solution in practical examples.Finally,we apply the proposed method to three wind power plants in different cities in China as examples forvalidation and obtain higher prediction accuracy compared with other methods,i.e.,relevance vector machine(RVM),artificial neural network(ANN),and particle swarm optimization kernel extreme learning machine(PSO-KELM).These results demonstrate the superiority and practicability of this method in interval prediction of wind power.展开更多
Background:The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.Methods:MEDLINE,EMBASE...Background:The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.Methods:MEDLINE,EMBASE and CENTRAL databases were searched for randomized controlled trials(RCTs)that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock.Two reviewers independently performed study selection,data extraction and quality assessment.Both short-term mortality and change in the sequential organ failure assessment(SOFA)score from baseline(delta SOFA)were set as the primary outcomes.Secondary endpoints included intensive care unit(ICU)mortality,new onset of acute kidney injury,total adverse events,ICU and hospital length of stay,duration of vasopressor usage and ventilator-free days.Meanwhile,trial sequential analysis was conducted for primary outcomes.Results:Eight RCTs with 1428 patients were included in the current study.The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo{risk ratio(RR),1.02[95%confidence interval(CI),0.87 to 1.20],p=0.81,I2=0%;risk difference(RD),0[95%CI,−0.04 to 0.05]}.Nevertheless,the combination therapy was associated with significant reduction in SOFA score[mean difference(MD),−0.63,(95%CI,−0.96 to−0.29,p<0.001,I^(2)=0%]and vasopressors duration(MD,−22.11[95%CI,−30.46 to−13.77],p<0.001,I2=6%).Additionally,there were no statistical differences in the pooled estimate for other outcomes.Conclusions:In the current meta-analysis,the combination therapy of vitamin C and thiamine,with or without hydrocortisone had no impact on short-term mortality when compared with placebo,but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.展开更多
In this paper,we investigate the statistical signal-processing algorithm to measure the instant local clock jump from the timing data of multiple pulsars.Our algorithm is based on the framework of Bayesian statistics....In this paper,we investigate the statistical signal-processing algorithm to measure the instant local clock jump from the timing data of multiple pulsars.Our algorithm is based on the framework of Bayesian statistics.In order to make the Bayesian algorithm applicable with limited computational resources,we dedicated our efforts to the analytic marginalization of irrelevant parameters.We found that the widely used parameter for pulsar timing systematics,the"Efac"parameter,can be analytically marginalized.This reduces the Gaussian likelihood to a function very similar to the Student’s t-distribution.Our iterative method to solve the maximum likelihood estimator is also explained in the paper.Using pulsar timing data from the Yunnan Kunming 40-m radio telescope,we demonstrate the application of the method,where 80-ns level precision for the clock jump can be achieved.Such a precision is comparable to that of current commercial time transferring service using satellites.We expect that the current method could help developing the autonomous pulsar time scale.展开更多
基金supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09101002,2018ZX09101002-001-001,and 2018ZX09101002-001-002,China)sponsored by National Natural Science Foundation of China (81830054,91859205,81988101,81722034,and 81802878)+1 种基金Shanghai Pujiang Program (2019PJD059,China),Shanghai Sailing Program (18YF1400200,China)Key Discipline Project of Shanghai Municipal Education Commission (201901070007E00065,China)。
文摘Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in China's Mainland. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
基金supported by the National Natural Science Foundation of China(No.51507141)Key research and development plan of Shaanxi Province(No.2018ZDCXL-GY-10-04)+1 种基金the National Key Research and Development Program of China(No.2016YFC0401409)the Shaanxi provincial education office fund(No.17JK0547).
文摘Interval prediction of wind power,which features the upper and lower limits of wind power at a given confidence level,plays a significant role in accurate prediction and stability of the power grid integrated with wind power.However,the conventional methods of interval prediction are commonly based on a hypothetic probability distribution function,which neglects the correlations among various variables,leading to the decrease of prediction accuracy.Therefore,we improve the multi-objective interval prediction based on the conditional copula function,through which we can fully utilize the correlations among variables to improve prediction accuracy without an assumed probability distribution function.We use the multi-objective optimization method of nondominated sorting genetic algorithm-II(NSGA-II)to obtain the optimal solution set.The particular best solution is weighted by the prediction interval average width(PIAW)and prediction interval coverage probability(PICP)to pick the optimized solution in practical examples.Finally,we apply the proposed method to three wind power plants in different cities in China as examples forvalidation and obtain higher prediction accuracy compared with other methods,i.e.,relevance vector machine(RVM),artificial neural network(ANN),and particle swarm optimization kernel extreme learning machine(PSO-KELM).These results demonstrate the superiority and practicability of this method in interval prediction of wind power.
基金supported by grants from the National Natural Science Foundation of China(Nos.81730057,81801935,82002071)the Key Project of Military Medical Innovation Program of Chinese PLA(No.18CXZ026)+3 种基金the National Key Research and Development Program of China(No.2017YFC1103302)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)Achievements Supportive Fund(2018-CGPZ-B03)Chinese Postdoctoral Science Foundation Grant(2019 M664003).
文摘Background:The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.Methods:MEDLINE,EMBASE and CENTRAL databases were searched for randomized controlled trials(RCTs)that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock.Two reviewers independently performed study selection,data extraction and quality assessment.Both short-term mortality and change in the sequential organ failure assessment(SOFA)score from baseline(delta SOFA)were set as the primary outcomes.Secondary endpoints included intensive care unit(ICU)mortality,new onset of acute kidney injury,total adverse events,ICU and hospital length of stay,duration of vasopressor usage and ventilator-free days.Meanwhile,trial sequential analysis was conducted for primary outcomes.Results:Eight RCTs with 1428 patients were included in the current study.The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo{risk ratio(RR),1.02[95%confidence interval(CI),0.87 to 1.20],p=0.81,I2=0%;risk difference(RD),0[95%CI,−0.04 to 0.05]}.Nevertheless,the combination therapy was associated with significant reduction in SOFA score[mean difference(MD),−0.63,(95%CI,−0.96 to−0.29,p<0.001,I^(2)=0%]and vasopressors duration(MD,−22.11[95%CI,−30.46 to−13.77],p<0.001,I2=6%).Additionally,there were no statistical differences in the pooled estimate for other outcomes.Conclusions:In the current meta-analysis,the combination therapy of vitamin C and thiamine,with or without hydrocortisone had no impact on short-term mortality when compared with placebo,but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB23010200)the National Natural Science Foundation of China(Grant Nos.U15311243,and 11690024)+1 种基金the National Basic Research Program of China(Grant No.2015CB857101)the funding from Tian Shan Chuang Xin Tuan Dui and the Max-Planck Partner Group
文摘In this paper,we investigate the statistical signal-processing algorithm to measure the instant local clock jump from the timing data of multiple pulsars.Our algorithm is based on the framework of Bayesian statistics.In order to make the Bayesian algorithm applicable with limited computational resources,we dedicated our efforts to the analytic marginalization of irrelevant parameters.We found that the widely used parameter for pulsar timing systematics,the"Efac"parameter,can be analytically marginalized.This reduces the Gaussian likelihood to a function very similar to the Student’s t-distribution.Our iterative method to solve the maximum likelihood estimator is also explained in the paper.Using pulsar timing data from the Yunnan Kunming 40-m radio telescope,we demonstrate the application of the method,where 80-ns level precision for the clock jump can be achieved.Such a precision is comparable to that of current commercial time transferring service using satellites.We expect that the current method could help developing the autonomous pulsar time scale.
