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Cross Validation Based Model Averaging for Varying-Coefficient Models with Response Missing at Random
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作者 Huixin Li Xiuli Wang 《Journal of Applied Mathematics and Physics》 2024年第3期764-777,共14页
In this paper, a model averaging method is proposed for varying-coefficient models with response missing at random by establishing a weight selection criterion based on cross-validation. Under certain regularity condi... In this paper, a model averaging method is proposed for varying-coefficient models with response missing at random by establishing a weight selection criterion based on cross-validation. Under certain regularity conditions, it is proved that the proposed method is asymptotically optimal in the sense of achieving the minimum squared error. 展开更多
关键词 Response Missing at Random model Averaging Asymptotic Optimality B-Spline Approximation
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The Latest Progress in Varying-coefficient Models 被引量:2
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作者 LU Yi-qiang LI Yu-ping 《Chinese Quarterly Journal of Mathematics》 CSCD 2009年第4期475-484,共10页
Varying-coefficient models are a useful extension of classical linear model. They are widely applied to economics, biomedicine, epidemiology, and so on. There are extensive studies on them in the latest three decade y... Varying-coefficient models are a useful extension of classical linear model. They are widely applied to economics, biomedicine, epidemiology, and so on. There are extensive studies on them in the latest three decade years. In this paper, many of models related to varying-coefficient models are gathered up. All kinds of the estimation procedures and theory of hypothesis test on the varying-coefficients model are summarized. Prom my opinion, some aspects waiting to study are proposed. 展开更多
关键词 varying-coefficient model B-spline estimation local estimation generalized likelihood ratio test sieve empirical likelihood
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Generalized Likelihood Ratio Tests for Varying-Coefficient Models with Censored Data
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作者 Rong Jiang Wei-Min Qian 《Open Journal of Statistics》 2011年第1期19-23,共5页
In this paper, we extend the generalized likelihood ratio test to the varying-coefficient models with censored data. We investigate the asymptotic behavior of the proposed test and demonstrate that its limiting null d... In this paper, we extend the generalized likelihood ratio test to the varying-coefficient models with censored data. We investigate the asymptotic behavior of the proposed test and demonstrate that its limiting null distribution follows a distribution, with the scale constant and the number of degree of freedom being independent of nuisance parameters or functions, which is called the wilks phenomenon. Both simulated and real data examples are given to illustrate the performance of the testing approach. 展开更多
关键词 VARYING COEFFICIENT model GENERALIZED LIKELIHOOD RATIO Test Local Linear Method Wilks Phenomenon CENSORING
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Identification of Non-Varying Coefficients in Varying-Coefficient Models 被引量:1
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作者 Chang-linMei Chun-xiaZhang 《Acta Mathematicae Applicatae Sinica》 SCIE CSCD 2005年第1期135-144,共10页
A partially varying-coefficient model is one of the useful modelling tools.In this model, some coefficients of a linear model are kept to be constant whilst the others areallowed to vary with another factor. However, ... A partially varying-coefficient model is one of the useful modelling tools.In this model, some coefficients of a linear model are kept to be constant whilst the others areallowed to vary with another factor. However, rarely can the analysts know a priori whichcoefficients can be assumed to be constant and which ones are varying with the given factor.Therefore, the identification problem of the constant coefficients should be solved before thepartially varying-coefficient model is used to analyze a real-world data set. In this article, asimple test method is proposed to achieve this task, in which the test statistic is constructed asthe sample variance of the estimates of each coefficient function in a well-knownvarying-coefficient model. Moreover two procedures, called F-approximation and three-moment χ~2approximation, are employed to derive the p-value of the test. Furthermore, some simulations areconducted to examine the performance of the test and the results are satisfactory. 展开更多
关键词 varying-coefficient model partially varying-coefficient model local linearfitting three-moment χ~2 approximation F-approximation
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Variable selection for single-index varying-coefficient model 被引量:2
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作者 Sanying FENG Liugen XUE 《Frontiers of Mathematics in China》 SCIE CSCD 2013年第3期541-565,共25页
We consider the problem of variable selection for single-index varying-coefficient model, and present a regularized variable selection procedure by combining basis function approximations with SCAD penalty. The propos... We consider the problem of variable selection for single-index varying-coefficient model, and present a regularized variable selection procedure by combining basis function approximations with SCAD penalty. The proposed procedure simultaneously selects significant covariates with functional coefficients and local significant variables with parametric coefficients. With appropriate selection of the tuning parameters, the consistency of the variable selection procedure and the oracle property of the estimators are established. The proposed method can naturally be applied to deal with pure single-index model and varying-coefficient model. Finite sample performances of the proposed method are illustrated by a simulation study and the real data analysis. 展开更多
关键词 Single-index varying-coefficient model variable selection SCAD oracle property
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Quantile Regression of Ultra-high Dimensional Partially Linear Varying-coefficient Model with Missing Observations 被引量:1
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作者 Bao Hua Wang Han Ying Liang 《Acta Mathematica Sinica,English Series》 SCIE CSCD 2023年第9期1701-1726,共26页
In this paper,we focus on the partially linear varying-coefficient quantile regression with missing observations under ultra-high dimension,where the missing observations include either responses or covariates or the ... In this paper,we focus on the partially linear varying-coefficient quantile regression with missing observations under ultra-high dimension,where the missing observations include either responses or covariates or the responses and part of the covariates are missing at random,and the ultra-high dimension implies that the dimension of parameter is much larger than sample size.Based on the B-spline method for the varying coefficient functions,we study the consistency of the oracle estimator which is obtained only using active covariates whose coefficients are nonzero.At the same time,we discuss the asymptotic normality of the oracle estimator for the linear parameter.Note that the active covariates are unknown in practice,non-convex penalized estimator is investigated for simultaneous variable selection and estimation,whose oracle property is also established.Finite sample behavior of the proposed methods is investigated via simulations and real data analysis. 展开更多
关键词 Missing observation oracle property partially linear varying-coefficient model quantile regression ultra-high dimension
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Influence Diagnostics in Partially Varying-Coefficient Models
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作者 Chun-xia Zhang Chang-lin Mei Jiang-she Zhang 《Acta Mathematicae Applicatae Sinica》 SCIE CSCD 2007年第4期619-628,共10页
When a real-world data set is fitted to a specific type of models, it is often encountered that one or a set of observations have undue influence on the model fitting, which may lead to misleading conclusions. Therefo... When a real-world data set is fitted to a specific type of models, it is often encountered that one or a set of observations have undue influence on the model fitting, which may lead to misleading conclusions. Therefore, it is necessary for data analysts to identify these influential observations and assess their impact on various aspects of model fitting. In this paper, one type of modified Cook's distances is defined to gauge the influence of one or a set observations on the estimate of the constant coefficient part in partially varying- coefficient models, and the Cook's distances are expressed as functions of the corresponding residuals and leverages. Meanwhile, a bootstrap procedure is suggested to derive the reference values for the proposed Cook's distances. Some simulations are conducted, and a real-world data set is further analyzed to examine the performance of the proposed method. The experimental results are satisfactory. 展开更多
关键词 Partially varying-coefficient model influential observation Cook's distance cross-validation
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Variable Selection for Varying-Coefficient Models with Missing Response at Random
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作者 Pei Kin ZHAO Liu Gen XUE 《Journal of Mathematical Research and Exposition》 CSCD 2011年第2期251-260,共10页
In this paper,we present a variable selection procedure by combining basis function approximations with penalized estimating equations for varying-coefficient models with missing response at random.With appropriate se... In this paper,we present a variable selection procedure by combining basis function approximations with penalized estimating equations for varying-coefficient models with missing response at random.With appropriate selection of the tuning parameters,we establish the consistency of the variable selection procedure and the optimal convergence rate of the regularized estimators.A simulation study is undertaken to assess the finite sample performance of the proposed variable selection procedure. 展开更多
关键词 varying-coefficient model variable selection missing data
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Statistical Diagnostic for Varying-Coefficient Single-Index Models Based on Empirical Likelihood Method 被引量:1
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作者 王淑玲 邓小洪 廖大庆 《Journal of Donghua University(English Edition)》 EI CAS 2014年第4期493-496,共4页
Varying-coefficient single-index model( VCSIM) avoids the so-called "curse of dimensionality " and is flexible enough to include several important statistical models. This paper considers statistical diagnos... Varying-coefficient single-index model( VCSIM) avoids the so-called "curse of dimensionality " and is flexible enough to include several important statistical models. This paper considers statistical diagnosis for VCSIM. First,the parametric estimation equation is established based on empirical likelihood. Then,some diagnosis statistics are defined. At last, an example is given to illustrate all the results. 展开更多
关键词 varying-coefficient single-index model(VCSIM) empirical likelihood OUTLIERS influence analysis
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STRONG CONVERGENCE RATES OF SEVERAL ESTIMATORS IN SEMIPARAMETRIC VARYING-COEFFICIENT PARTIALLY LINEAR MODELS 被引量:1
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作者 周勇 尤进红 王晓婧 《Acta Mathematica Scientia》 SCIE CSCD 2009年第5期1113-1127,共15页
This article is concerned with the estimating problem of semiparametric varyingcoefficient partially linear regression models. By combining the local polynomial and least squares procedures Fan and Huang (2005) prop... This article is concerned with the estimating problem of semiparametric varyingcoefficient partially linear regression models. By combining the local polynomial and least squares procedures Fan and Huang (2005) proposed a profile least squares estimator for the parametric component and established its asymptotic normality. We further show that the profile least squares estimator can achieve the law of iterated logarithm. Moreover, we study the estimators of the functions characterizing the non-linear part as well as the error variance. The strong convergence rate and the law of iterated logarithm are derived for them, respectively. 展开更多
关键词 partially linear regression model varying-coefficient profile leastsquares error variance strong convergence rate law of iterated logarithm
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Estimating the Size of an Open Population with Massive Datasets Based on a Generalized Varying-Coefficient Model
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作者 LI Haoqi LI Yuan 《Journal of Systems Science & Complexity》 SCIE EI CSCD 2022年第3期1116-1136,共21页
A generalized varying-coefficient model is proposed to estimate a population size at a specific time from multiple lists of an open population.The research datasets have millions of records with a very long time span(... A generalized varying-coefficient model is proposed to estimate a population size at a specific time from multiple lists of an open population.The research datasets have millions of records with a very long time span(38 years),bringing challenges to calculations.The authors develop a regularization iterative algorithm to overcome this difficulty.The asymptotic distribution of the proposed estimators is derived.Simulation studies show that the procedure works well.The method is applied to estimate the number of drug abusers in Hong Kong,China over the period 1977–2014. 展开更多
关键词 Drug abusers generalized varying-coefficient multiple-list open population
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Comparative analysis of empirical and deep learning models for ionospheric sporadic E layer prediction
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作者 BingKun Yu PengHao Tian +6 位作者 XiangHui Xue Christopher JScott HaiLun Ye JianFei Wu Wen Yi TingDi Chen XianKang Dou 《Earth and Planetary Physics》 EI CAS 2025年第1期10-19,共10页
Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,... Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular. 展开更多
关键词 ionospheric sporadic E layer radio occultation ionosondes numerical model deep learning model artificial intelligence
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Dynamics of a Stochastic Epidemic Model with Age-group
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作者 LAN Xiaomin CHEN Guangmin +5 位作者 ZHOU Ruiyang ZHENG Kuicheng CAI Shaojian WEI Fengying JIN Zhen MAO Xuerong 《应用数学》 北大核心 2025年第1期294-307,共14页
A stochastic epidemic model with two age groups is established in this study,in which the susceptible(S),the exposed(E),the infected(I),the hospitalized(H)and the recovered(R)are involved within the total population,t... A stochastic epidemic model with two age groups is established in this study,in which the susceptible(S),the exposed(E),the infected(I),the hospitalized(H)and the recovered(R)are involved within the total population,the aging rates between two age groups are set to be constant.The existence-and-uniqueness of global positive solution is firstly showed.Then,by constructing several appropriate Lyapunov functions and using the high-dimensional Itô’s formula,the sufficient conditions for the stochastic extinction and stochastic persistence of the exposed individuals and the infected individuals are obtained.The stochastic extinction indicator and the stochastic persistence indicator are less-valued expressions compared with the basic reproduction number.Meanwhile,the main results of this study are modified into multi-age groups.Furthermore,by using the surveillance data for Fujian Provincial Center for Disease Control and Prevention,Fuzhou COVID-19 epidemic is chosen to carry out the numerical simulations,which show that the age group of the population plays the vital role when studying infectious diseases. 展开更多
关键词 Epidemic model Age groups PERSISTENCE EXTINCTION
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Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis
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作者 Li Xu Huiming Xu Changyong Tang 《Neural Regeneration Research》 SCIE CAS 2025年第2期354-365,共12页
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem... Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials. 展开更多
关键词 AQUAPORIN-4 experimental model neuromyelitis optica spectrum disorder PATHOGENESIS
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Solar flare forecasting based on a Fusion Model
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作者 YiYang Li ShiYong Huang +4 位作者 SiBo Xu ZhiGang Yuan Kui Jiang QiYang Xiong RenTong Lin 《Earth and Planetary Physics》 EI CAS 2025年第1期171-181,共11页
Solar flare prediction is an important subject in the field of space weather.Deep learning technology has greatly promoted the development of this subject.In this study,we propose a novel solar flare forecasting model... Solar flare prediction is an important subject in the field of space weather.Deep learning technology has greatly promoted the development of this subject.In this study,we propose a novel solar flare forecasting model integrating Deep Residual Network(ResNet)and Support Vector Machine(SVM)for both≥C-class(C,M,and X classes)and≥M-class(M and X classes)flares.We collected samples of magnetograms from May 1,2010 to September 13,2018 from Space-weather Helioseismic and Magnetic Imager(HMI)Active Region Patches and then used a cross-validation method to obtain seven independent data sets.We then utilized five metrics to evaluate our fusion model,based on intermediate-output extracted by ResNet and SVM using the Gaussian kernel function.Our results show that the primary metric true skill statistics(TSS)achieves a value of 0.708±0.027 for≥C-class prediction,and of 0.758±0.042 for≥M-class prediction;these values indicate that our approach performs significantly better than those of previous studies.The metrics of our fusion model’s performance on the seven datasets indicate that the model is quite stable and robust,suggesting that fusion models that integrate an excellent baseline network with SVM can achieve improved performance in solar flare prediction.Besides,we also discuss the performance impact of architectural innovation in our fusion model. 展开更多
关键词 solar flare pace weather deep learning Fusion model
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Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models
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作者 Duc-Dam Nguyen Nguyen Viet Tiep +5 位作者 Quynh-Anh Thi Bui Hiep Van Le Indra Prakash Romulus Costache Manish Pandey Binh Thai Pham 《Computer Modeling in Engineering & Sciences》 SCIE EI 2025年第1期467-500,共34页
This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble lear... This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and AB-RBFN.Additionally,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and validation.The models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to roads.These factors were instrumental in predicting the output variable,which was the probability of landslide occurrence.Statistical analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other models.The AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of 0.926.These results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making. 展开更多
关键词 Landslide susceptibility map spatial analysis ensemble modelling information values(IV)
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Global Piecewise Analysis of HIV Model with Bi-Infectious Categories under Ordinary Derivative and Non-Singular Operator with Neural Network Approach
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作者 Ghaliah Alhamzi Badr Saad TAlkahtani +1 位作者 Ravi Shanker Dubey Mati ur Rahman 《Computer Modeling in Engineering & Sciences》 SCIE EI 2025年第1期609-633,共25页
This study directs the discussion of HIV disease with a novel kind of complex dynamical generalized and piecewise operator in the sense of classical and Atangana Baleanu(AB)derivatives having arbitrary order.The HIV i... This study directs the discussion of HIV disease with a novel kind of complex dynamical generalized and piecewise operator in the sense of classical and Atangana Baleanu(AB)derivatives having arbitrary order.The HIV infection model has a susceptible class,a recovered class,along with a case of infection divided into three sub-different levels or categories and the recovered class.The total time interval is converted into two,which are further investigated for ordinary and fractional order operators of the AB derivative,respectively.The proposed model is tested separately for unique solutions and existence on bi intervals.The numerical solution of the proposed model is treated by the piece-wise numerical iterative scheme of Newtons Polynomial.The proposed method is established for piece-wise derivatives under natural order and non-singular Mittag-Leffler Law.The cross-over or bending characteristics in the dynamical system of HIV are easily examined by the aspect of this research having a memory effect for controlling the said disease.This study uses the neural network(NN)technique to obtain a better set of weights with low residual errors,and the epochs number is considered 1000.The obtained figures represent the approximate solution and absolute error which are tested with NN to train the data accurately. 展开更多
关键词 HIV infection model qualitative scheme approximate solution piecewise global operator neural network
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Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study
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作者 Jun-Yi Zhan Jie Chen +7 位作者 Jin-Zhong Yu Fei-Peng Xu Fei-Fei Xing De-Xin Wang Ming-Yan Yang Feng Xing Jian Wang Yong-Ping Mu 《World Journal of Gastroenterology》 SCIE CAS 2025年第2期85-101,共17页
BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized p... BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.AIM To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.METHODS This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 year.The least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic model.Internal validation was performed with bootstrap resampling.We assessed the discrimination,calibration and accuracy of the model,and performed patient risk stratification.RESULTS Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)model.In predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation cohort.Furthermore,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both cohorts.CONCLUSION We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients. 展开更多
关键词 Esophagogastric variceal bleeding Variceal rebleeding Liver cirrhosis Prognostic model Risk stratification Secondary prophylaxis
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High-throughput screening of CO_(2) cycloaddition MOF catalyst with an explainable machine learning model
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作者 Xuefeng Bai Yi Li +3 位作者 Yabo Xie Qiancheng Chen Xin Zhang Jian-Rong Li 《Green Energy & Environment》 SCIE EI CAS 2025年第1期132-138,共7页
The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF str... The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction. 展开更多
关键词 Metal-organic frameworks High-throughput screening Machine learning Explainable model CO_(2)cycloaddition
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Exploiting fly models to investigate rare human neurological disorders
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作者 Tomomi Tanaka Hyung-Lok Chung 《Neural Regeneration Research》 SCIE CAS 2025年第1期21-28,共8页
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio... Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases. 展开更多
关键词 ACOX1 Drosophila melanogaster GLIA lipid metabolism model organisms NEUROINFLAMMATION neurologic disorders NEURON rare disease VLCFA
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