BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
Over the past few years,China’s higher education institutions have experienced remarkable growth in online teaching.However,it remains uncertain whether and how the sense of presence perceived by students affects the...Over the past few years,China’s higher education institutions have experienced remarkable growth in online teaching.However,it remains uncertain whether and how the sense of presence perceived by students affects their online learning outcomes when teachers use online teaching media for communication.This sense specifically pertains to the extent to which students perceive themselves as“real persons”and establish connections with others.Therefore,this study constructs a conceptual model elucidating the impact of presence on students’online learning outcomes and empirically examines the mechanism through which three types of presence influence students’online learning.The test results of the structural equation modeling(SEM)indicate that:(a)teaching presence,social presence,and cognitive presence all exhibit significantly positive outcomes on students’online learning outcomes;(b)these three types of presence can also indirectly and positively influence students’online learning outcomes through the mediating effect of flow experience and learning satisfaction;and(c)flow experience and learning satisfaction play a sequential mediating role in the process by which presence impacts students’online learning outcomes.We hope that the relevant research findings may contribute to unveiling the“black box”of the impact of presence on students’online learning outcomes and offer valuable insights for college educators to overcome online teaching constraints and enhance online teaching quality.展开更多
BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure...BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.展开更多
Until now the genus Amana(Liliaceae),known as ’East Asian tulips’,has contained just seven species.In this study,a phylogenomic and integrative taxonomic approach was used to reveal two new species,Amana nanyueensis...Until now the genus Amana(Liliaceae),known as ’East Asian tulips’,has contained just seven species.In this study,a phylogenomic and integrative taxonomic approach was used to reveal two new species,Amana nanyueensis from Central China and A.tianmuensis from East China.A.nanyueensis resembles Amana edulis in possessing a densely villous-woolly bulb tunic and two opposite bracts,but differs in its leaves and anthers.Amana tianmuensis resembles Amana erythronioides in possessing three verticillate bracts and yellow anthers,but differs in aspects of its leaves and bulbs.These four species are clearly separated from each other in principal components analysis based on morphology.Phylogenomic analyses based on plastid CDS further support the species delimitation of A.nanyueensis and A.tianmuensis and suggests they are closely related to A.edulis.Cytological analysis shows that A.nanyueensis and A tianmuensis are both diploid(2n=2x=24),different from A edulis,which is either diploid(northern populations) or tetraploid(southern populations,2n=4x=48).The pollen morphology of A.nanyueensis is similar to other Amana species(single-groove germination aperture),but A.tianmuensis is quite different because of the presence of a sulcus membrane,which creates the illusion of double grooves.Ecological niche modelling also revealed a niche differentiation between A.edulis,A.nanyueensis and A.tianmuensis.展开更多
We extend two adaptive step-size methods for solving two-dimensional or multi-dimensional generalized nonlinear Schr ¨odinger equation(GNLSE): one is the conservation quantity error adaptive step-control method(R...We extend two adaptive step-size methods for solving two-dimensional or multi-dimensional generalized nonlinear Schr ¨odinger equation(GNLSE): one is the conservation quantity error adaptive step-control method(RK4IP-CQE), and the other is the local error adaptive step-control method(RK4IP-LEM). The methods are developed in the vector form of fourthorder Runge–Kutta iterative scheme in the interaction picture by converting a vector equation in frequency domain. By simulating the supercontinuum generated from the high birefringence photonic crystal fiber, the calculation accuracies and the efficiencies of the two adaptive step-size methods are discussed. The simulation results show that the two methods have the same global average error, while RK4IP-LEM spends more time than RK4IP-CQE. The decrease of huge calculation time is due to the differences in the convergences of the relative photon number error and the approximated local error between these two adaptive step-size algorithms.展开更多
The key advantage of unmanned swarm operation is its autonomous cooperation. How to improve the proportion of cooperators is one of the key issues of autonomous collaboration in unmanned swarm operations. This work pr...The key advantage of unmanned swarm operation is its autonomous cooperation. How to improve the proportion of cooperators is one of the key issues of autonomous collaboration in unmanned swarm operations. This work proposes a strategy dominance mechanism of autonomous collaboration in unmanned swarm within the framework of public goods game. It starts with the requirement analysis of autonomous collaboration in unmanned swarm;and an aspiration-driven multiplayer evolutionary game model is established based on the requirement. Then the average abundance function and strategy dominance condition of the model are constructed by theoretical derivation. Furthermore, the evolutionary mechanism of parameter adjustment in swarm cooperation is revealed via simulation,and the influences of the multiplication factor r, aspiration levelα, threshold m and other parameters on the strategy dominance conditions were simulated for both linear and threshold public goods games(PGGs) to determine the strategy dominance characteristics;Finally, deliberate proposals are suggested to provide a meaningful exploration in the actual control of unmanned swarm cooperation.展开更多
A broadband(BB)mode is observed by collective Thomson scattering diagnostics in repeatable shots of EAST and analyzed for the first time.This BB mode usually grows during L–H transitions,featuring a BB quasi-coherent...A broadband(BB)mode is observed by collective Thomson scattering diagnostics in repeatable shots of EAST and analyzed for the first time.This BB mode usually grows during L–H transitions,featuring a BB quasi-coherent mode with increasing frequency.During H-mode operations,it is characterized by steady-state BB in the high-frequency range(f~200–2000 k Hz),at the electron scale(k_(θ)ρ_(s)=1–2),mainly driven by the density gradient,and is sensitive to the value ofηein the region of interest(ρ=0.4–0.8),wherehe=(R/L_(Te))/(R/L_(ne))is the ratio of the normalized electron temperature gradient and density gradient,and the regionρ=0.4–0.8 usually has a relatively low collisionality(v_(eff)<5).The frequency of BB is found to be dependent on the electron temperature and density gradient,which is a typical feature of electron-driven turbulence.A negative correlation between the energy confinement and the intensity of the BB turbulence during H-mode has been found,which indicates a strong electron thermal transport induced by the BB turbulence.The BB significantly decreases the electron temperature and causes flatter electron temperature profiles in the region of interest(ρ=0.4–0.8),thus makingηedecrease and the BB destabilize further.These characteristics of BB are related to the theoretical density gradient-driven trapped electron mode.It should be noted that this mode is not observed by other diagnostics in EAST,and shows very different features to the coherent modes in the edge.展开更多
Since the successful implantation of the first cardiac pacemaker(PM)in 1958,PM has been widely used in clinical practice.With the advancement of interventional technology,PMs have become smaller and more effective.Des...Since the successful implantation of the first cardiac pacemaker(PM)in 1958,PM has been widely used in clinical practice.With the advancement of interventional technology,PMs have become smaller and more effective.Despite continuous improvements,traditional PMs remain associated with a proportional risk of immediate-and short-term complications(9%–12%),[1]which are mainly related to electrodes or pockets.Short-term complications include pneumothorax,cardiac tamponade.展开更多
基金Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
基金the project“Research on the Evaluation Mechanism of College Ideological and Political Education:A Perspective on Teacher-Student Development,”funded by Zhejiang Provincial College Ideological and Political Education Research Project.
文摘Over the past few years,China’s higher education institutions have experienced remarkable growth in online teaching.However,it remains uncertain whether and how the sense of presence perceived by students affects their online learning outcomes when teachers use online teaching media for communication.This sense specifically pertains to the extent to which students perceive themselves as“real persons”and establish connections with others.Therefore,this study constructs a conceptual model elucidating the impact of presence on students’online learning outcomes and empirically examines the mechanism through which three types of presence influence students’online learning.The test results of the structural equation modeling(SEM)indicate that:(a)teaching presence,social presence,and cognitive presence all exhibit significantly positive outcomes on students’online learning outcomes;(b)these three types of presence can also indirectly and positively influence students’online learning outcomes through the mediating effect of flow experience and learning satisfaction;and(c)flow experience and learning satisfaction play a sequential mediating role in the process by which presence impacts students’online learning outcomes.We hope that the relevant research findings may contribute to unveiling the“black box”of the impact of presence on students’online learning outcomes and offer valuable insights for college educators to overcome online teaching constraints and enhance online teaching quality.
基金National Natural Science Foundation of China,No.81973398,No.81730103,No.81573507 and No.82020108031The National Key Research and Development Program,No.2017YFC0909300 and No.2016YFC0905001+5 种基金Guangdong Provincial Key Laboratory of Construction Foundation,No.2017B030314030 and No.2020B1212060034Science and Technology Program of Guangzhou,No.201607020031National Engineering and Technology Research Center for New Drug Druggability Evaluation(Seed Program of Guangdong Province),No.2017B090903004The 111 Project,No.B16047China Postdoctoral Science Foundation,No.2019M66324,No.2020M683140 and No.2020M683139Natural Science Foundation of Guangdong Province,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment failure.TiPN is rarely predictable and recognized,especially in CD.It is necessary to develop a risk model to predict TiPN occurrence.AIM To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables.METHODS A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model.The National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess TiPN.With 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 score.RESULTS The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>0.87.Among these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8).Overall,compared with other state-of-the-art classifiers such as ET,GBDT and RF,XGBoost algorithm not only showed a more stable performance,but also yielded higher ROC-AUC and PRC-AUC scores,demonstrating its high accuracy in prediction of TiPN occurrence.CONCLUSION The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables.With the ability to identify high-risk patients using single nucleotide polymorphisms,it offers a feasible option for improving thalidomide efficacy in CD patients.
基金supported by the National Natural Science Foundation of China (Grant No.31970225)the Zhejiang Provincial Natural Science Foundation (Grant No.LY19C030007)theNSFC-NSF Dimensions of Biodiversity Program (Grant No.31461123001)。
文摘Until now the genus Amana(Liliaceae),known as ’East Asian tulips’,has contained just seven species.In this study,a phylogenomic and integrative taxonomic approach was used to reveal two new species,Amana nanyueensis from Central China and A.tianmuensis from East China.A.nanyueensis resembles Amana edulis in possessing a densely villous-woolly bulb tunic and two opposite bracts,but differs in its leaves and anthers.Amana tianmuensis resembles Amana erythronioides in possessing three verticillate bracts and yellow anthers,but differs in aspects of its leaves and bulbs.These four species are clearly separated from each other in principal components analysis based on morphology.Phylogenomic analyses based on plastid CDS further support the species delimitation of A.nanyueensis and A.tianmuensis and suggests they are closely related to A.edulis.Cytological analysis shows that A.nanyueensis and A tianmuensis are both diploid(2n=2x=24),different from A edulis,which is either diploid(northern populations) or tetraploid(southern populations,2n=4x=48).The pollen morphology of A.nanyueensis is similar to other Amana species(single-groove germination aperture),but A.tianmuensis is quite different because of the presence of a sulcus membrane,which creates the illusion of double grooves.Ecological niche modelling also revealed a niche differentiation between A.edulis,A.nanyueensis and A.tianmuensis.
基金supported by the National Key Research and Development Program of China (Grant Nos. 2021YFC2201803 and 2020YFC2200104)。
文摘We extend two adaptive step-size methods for solving two-dimensional or multi-dimensional generalized nonlinear Schr ¨odinger equation(GNLSE): one is the conservation quantity error adaptive step-control method(RK4IP-CQE), and the other is the local error adaptive step-control method(RK4IP-LEM). The methods are developed in the vector form of fourthorder Runge–Kutta iterative scheme in the interaction picture by converting a vector equation in frequency domain. By simulating the supercontinuum generated from the high birefringence photonic crystal fiber, the calculation accuracies and the efficiencies of the two adaptive step-size methods are discussed. The simulation results show that the two methods have the same global average error, while RK4IP-LEM spends more time than RK4IP-CQE. The decrease of huge calculation time is due to the differences in the convergences of the relative photon number error and the approximated local error between these two adaptive step-size algorithms.
基金supported by the National Natural Science Foundation of China(71901217)the National Key R&D Program of China(2018YFC0806900).
文摘The key advantage of unmanned swarm operation is its autonomous cooperation. How to improve the proportion of cooperators is one of the key issues of autonomous collaboration in unmanned swarm operations. This work proposes a strategy dominance mechanism of autonomous collaboration in unmanned swarm within the framework of public goods game. It starts with the requirement analysis of autonomous collaboration in unmanned swarm;and an aspiration-driven multiplayer evolutionary game model is established based on the requirement. Then the average abundance function and strategy dominance condition of the model are constructed by theoretical derivation. Furthermore, the evolutionary mechanism of parameter adjustment in swarm cooperation is revealed via simulation,and the influences of the multiplication factor r, aspiration levelα, threshold m and other parameters on the strategy dominance conditions were simulated for both linear and threshold public goods games(PGGs) to determine the strategy dominance characteristics;Finally, deliberate proposals are suggested to provide a meaningful exploration in the actual control of unmanned swarm cooperation.
基金supported by National Natural Science Foundation of China(No.11875286)the National Key R&D Program of China(No.2019YFE03010002)CAS President’s International Fellowship Initiative(No.2022VMB0007)。
文摘A broadband(BB)mode is observed by collective Thomson scattering diagnostics in repeatable shots of EAST and analyzed for the first time.This BB mode usually grows during L–H transitions,featuring a BB quasi-coherent mode with increasing frequency.During H-mode operations,it is characterized by steady-state BB in the high-frequency range(f~200–2000 k Hz),at the electron scale(k_(θ)ρ_(s)=1–2),mainly driven by the density gradient,and is sensitive to the value ofηein the region of interest(ρ=0.4–0.8),wherehe=(R/L_(Te))/(R/L_(ne))is the ratio of the normalized electron temperature gradient and density gradient,and the regionρ=0.4–0.8 usually has a relatively low collisionality(v_(eff)<5).The frequency of BB is found to be dependent on the electron temperature and density gradient,which is a typical feature of electron-driven turbulence.A negative correlation between the energy confinement and the intensity of the BB turbulence during H-mode has been found,which indicates a strong electron thermal transport induced by the BB turbulence.The BB significantly decreases the electron temperature and causes flatter electron temperature profiles in the region of interest(ρ=0.4–0.8),thus makingηedecrease and the BB destabilize further.These characteristics of BB are related to the theoretical density gradient-driven trapped electron mode.It should be noted that this mode is not observed by other diagnostics in EAST,and shows very different features to the coherent modes in the edge.
文摘Since the successful implantation of the first cardiac pacemaker(PM)in 1958,PM has been widely used in clinical practice.With the advancement of interventional technology,PMs have become smaller and more effective.Despite continuous improvements,traditional PMs remain associated with a proportional risk of immediate-and short-term complications(9%–12%),[1]which are mainly related to electrodes or pockets.Short-term complications include pneumothorax,cardiac tamponade.
