Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and ...Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.展开更多
Glacial meltwater constitutes a vital component of the water supply in arid and semi-arid areas.However,the influence of glacial melting on runoff and evapotranspiration under global warming remains insufficiently und...Glacial meltwater constitutes a vital component of the water supply in arid and semi-arid areas.However,the influence of glacial melting on runoff and evapotranspiration under global warming remains insufficiently understood.Previous studies coupling the Soil and Water Assessment Tool(SWAT)model with glacier modules often failed to consider the spatial heterogeneity of temperature during glacial melting,potentially leading to biased estimates of meltwater volume.In this study,we developed a glacier-coupled SWAT(SWAT-glacier)model considering the digital elevation model(DEM)based temperature-driven glacial melt processes to elucidate the impact of glacial melting on hydrological processes across four river basins(Dongda,Xiying,Jinta,and Zamu)of the upper Shiyang River Basin(SYRB)in northwestern China from 1986 to 2021.Compared with the standard SWAT model,the proposed SWAT-glacier model significantly improved the simulation accuracy for both runoff and evapotranspiration.Specifically,in comparison with the standard SWAT model,the Nash-Sutcliffe efficiency of the SWAT-glacier model showed a relative improvement of approximately 0.42%–9.16%and 1.50%–10.15%for runoff and evapotranspiration,respectively,in the four river basins during the validation period.Annual glacial runoff occurred predominantly from May to October,whereas glacial melt-induced evapotranspiration peaked between June and August.From 1986 to 2021,the average contributions of glacial melt to runoff were 6.97%for Dongda,3.06%for Xiying,2.70%for Jinta,and 0.67%for Zamu,whereas its contributions to evapotranspiration were 9.06%,5.14%,3.21%,and 1.59%,respectively.This study presents a SWAT-glacier modeling framework that enhances the simulation of hydrological processes in cold regions.The proposed methodology can be extended to other glacierized basins to provide valuable insights into water resource management under climate change.展开更多
The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter ...The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter less than 2.5μm)composition in Dunkerque,Northern France.Semi-diurnal PM_(2.5)samples were collected using a high volume sampler in winter 2010 and spring 2011 and were analyzed for trace metals,water-soluble ions,and total carbon using inductively coupled plasma–atomic emission spectrometry(ICP-AES),ICP-mass spectrometry(ICP-MS),ionic chromatography and micro elemental carbon analyzer.The elemental composition shows that NO_(3)^(-),SO_(4)^(2-),NH_4~+and total carbon are the main PM_(2.5)constituents.Trace metals data were interpreted using concentration roses and both influences of integrated steelworks and electric steel plant were evidenced.The distinction between the two sources is made possible by the use Zn/Fe and Zn/Mn diagnostic ratios.Moreover Rb/Cr,Pb/Cr and Cu/Cd combination ratio are proposed to distinguish the ISW-sintering stack from the ISW-fugitive emissions.The a priori knowledge on the influencing source was introduced in the CW-NMF to guide the calculation.Eleven source profiles with various contributions were identified:8 are characteristics of coastal urban background site profiles and 3 are related to the steelmaking activities.Between them,secondary nitrates,secondary sulfates and combustion profiles give the highest contributions and account for 93%of the PM_(2.5)concentration.The steelwork facilities contribute in about 2%of the total PM_(2.5)concentration and appear to be the main source of Cr,Cu,Fe,Mn,Zn.展开更多
为了寻求合理简化的流域地形指数水文模型TOPMODEL(Topographic Index model)用于大尺度的陆面模式,推导了土壤表层饱和导水率k0、衰减因子f和地下水补给速率R空间都可变的扩展的TOPMODEL,并将f空间非均匀分布的TOPMODEL与陆面模式SSiB...为了寻求合理简化的流域地形指数水文模型TOPMODEL(Topographic Index model)用于大尺度的陆面模式,推导了土壤表层饱和导水率k0、衰减因子f和地下水补给速率R空间都可变的扩展的TOPMODEL,并将f空间非均匀分布的TOPMODEL与陆面模式SSiB4耦合(SSiB4/GTOP)。通过耦合模型在f空间非均匀条件下进行实际流域的水文模拟,分析f空间非均匀对流域土壤湿度、蒸散发、地表径流、基流和总径流的影响。主要结论有:(1)k0和R的空间变化并不改变经典TOPMODEL原有关系式,只要定义新的地形指数,k0和R空间非均匀TOPMODEL与空间均匀的TOPMODEL并无区别;(2) f空间变化条件下由于局地的地下水埋深还与局地的f值有关,地形指数相同的区域具有水文相似性这一结论不再成立;(3)与f空间均匀的模拟结果相比较,f随海拔高度h i增加而线性减小使模拟的流域土壤湿度、地表径流和流域蒸散减小但使基流和总径流增加;(4) f空间非均匀对流域水文模拟结果有影响,但其影响明显小于流域地形因子的影响。展开更多
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Background:Establishing an appropriate prognostic model for PCa is essential for its effective treatment.Glycolysis is a vital energy-harvesting mechanism for tumors.Developing a prognostic model for PCa based on glyc...Background:Establishing an appropriate prognostic model for PCa is essential for its effective treatment.Glycolysis is a vital energy-harvesting mechanism for tumors.Developing a prognostic model for PCa based on glycolysis-related genes is novel and has great potential.Methods:First,gene expression and clinical data of PCa patients were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),and glycolysis-related genes were obtained from the Molecular Signatures Database(MSigDB).Gene enrichment analysis was performed to verify that glycolysis functions were enriched in the genes we obtained,which were used in nonnegative matrix factorization(NMF)to identify clusters.The correlation between clusters and clinical features was discussed,and the differentially expressed genes(DEGs)between the two clusters were investigated.Based on the DEGs,we investigated the biological differences between clusters,including immune cell infiltration,mutation,tumor immune dysfunction and exclusion,immune function,and checkpoint genes.To establish the prognostic model,the genes were filtered based on univariable Cox regression,LASSO,and multivariable Cox regression.Kaplan–Meier analysis and receiver operating characteristic analysis validated the prognostic value of the model.A nomogram of the risk score calculated by the prognostic model and clinical characteristics was constructed to quantitatively estimate the survival probability for PCa patients in the clinical setting.Result:The genes obtained from MSigDB were enriched in glycolysis functions.Two clusters were identified by NMF analysis based on 272 glycolysis-related genes,and a prognostic model based on DEGs between the two clusters was finally established.The prognostic model consisted of LAMPS,SPRN,ATOH1,TANC1,ETV1,TDRD1,KLK14,MESP2,POSTN,CRIP2,NAT1,AKR7A3,PODXL,CARTPT,and PCDHGB2.All sample,training,and test cohorts from The Cancer Genome Atlas(TCGA)and the external validation cohort from GEO showed significant differences between the high-risk and low-risk groups.The area under the ROC curve showed great performance of this prognostic model.Conclusion:A prognostic model based on glycolysis-related genes was established,with great performance and potential significance to the clinical application.展开更多
Rank determination issue is one of the most significant issues in non-negative matrix factorization (NMF) research. However, rank determination problem has not received so much emphasis as sparseness regularization pr...Rank determination issue is one of the most significant issues in non-negative matrix factorization (NMF) research. However, rank determination problem has not received so much emphasis as sparseness regularization problem. Usually, the rank of base matrix needs to be assumed. In this paper, we propose an unsupervised multi-level non-negative matrix factorization model to extract the hidden data structure and seek the rank of base matrix. From machine learning point of view, the learning result depends on its prior knowledge. In our unsupervised multi-level model, we construct a three-level data structure for non-negative matrix factorization algorithm. Such a construction could apply more prior knowledge to the algorithm and obtain a better approximation of real data structure. The final bases selection is achieved through L2-norm optimization. We implement our experiment via binary datasets. The results demonstrate that our approach is able to retrieve the hidden structure of data, thus determine the correct rank of base matrix.展开更多
基金supported by ScientificResearch Fund of National Health Commission of the People’s Republic of China-Major Science and Technology Program for Medicine and Health in Zhejiang Province(WKJ-ZJ-2406).
文摘Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.
基金supported by the National Key Research and Development Program of China(2022YFD1900501)the Gansu Provincial Water Conservancy Scientific Experimental Research and Technology Extension Project(25GSLK044,26GSLK093).
文摘Glacial meltwater constitutes a vital component of the water supply in arid and semi-arid areas.However,the influence of glacial melting on runoff and evapotranspiration under global warming remains insufficiently understood.Previous studies coupling the Soil and Water Assessment Tool(SWAT)model with glacier modules often failed to consider the spatial heterogeneity of temperature during glacial melting,potentially leading to biased estimates of meltwater volume.In this study,we developed a glacier-coupled SWAT(SWAT-glacier)model considering the digital elevation model(DEM)based temperature-driven glacial melt processes to elucidate the impact of glacial melting on hydrological processes across four river basins(Dongda,Xiying,Jinta,and Zamu)of the upper Shiyang River Basin(SYRB)in northwestern China from 1986 to 2021.Compared with the standard SWAT model,the proposed SWAT-glacier model significantly improved the simulation accuracy for both runoff and evapotranspiration.Specifically,in comparison with the standard SWAT model,the Nash-Sutcliffe efficiency of the SWAT-glacier model showed a relative improvement of approximately 0.42%–9.16%and 1.50%–10.15%for runoff and evapotranspiration,respectively,in the four river basins during the validation period.Annual glacial runoff occurred predominantly from May to October,whereas glacial melt-induced evapotranspiration peaked between June and August.From 1986 to 2021,the average contributions of glacial melt to runoff were 6.97%for Dongda,3.06%for Xiying,2.70%for Jinta,and 0.67%for Zamu,whereas its contributions to evapotranspiration were 9.06%,5.14%,3.21%,and 1.59%,respectively.This study presents a SWAT-glacier modeling framework that enhances the simulation of hydrological processes in cold regions.The proposed methodology can be extended to other glacierized basins to provide valuable insights into water resource management under climate change.
基金financially supported by the Nord-Pas-de-Calais Region Councilthe Ministry of Higher Education and Research+1 种基金the European Regional Development FundsAdib Kfoury acknowledges the“Pole Metropolitain Cote d'Opale”(PMCO)for its PhD financial support
文摘The constrained weighted-non-negative matrix factorization(CW-NMF)hybrid receptor model was applied to study the influence of steelmaking activities on PM_(2.5)(particulate matter with equivalent aerodynamic diameter less than 2.5μm)composition in Dunkerque,Northern France.Semi-diurnal PM_(2.5)samples were collected using a high volume sampler in winter 2010 and spring 2011 and were analyzed for trace metals,water-soluble ions,and total carbon using inductively coupled plasma–atomic emission spectrometry(ICP-AES),ICP-mass spectrometry(ICP-MS),ionic chromatography and micro elemental carbon analyzer.The elemental composition shows that NO_(3)^(-),SO_(4)^(2-),NH_4~+and total carbon are the main PM_(2.5)constituents.Trace metals data were interpreted using concentration roses and both influences of integrated steelworks and electric steel plant were evidenced.The distinction between the two sources is made possible by the use Zn/Fe and Zn/Mn diagnostic ratios.Moreover Rb/Cr,Pb/Cr and Cu/Cd combination ratio are proposed to distinguish the ISW-sintering stack from the ISW-fugitive emissions.The a priori knowledge on the influencing source was introduced in the CW-NMF to guide the calculation.Eleven source profiles with various contributions were identified:8 are characteristics of coastal urban background site profiles and 3 are related to the steelmaking activities.Between them,secondary nitrates,secondary sulfates and combustion profiles give the highest contributions and account for 93%of the PM_(2.5)concentration.The steelwork facilities contribute in about 2%of the total PM_(2.5)concentration and appear to be the main source of Cr,Cu,Fe,Mn,Zn.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金supported by the Public Health Research Project in Futian District,Shenzhen(Grant Nos.FTWS2020026,FTWS2021073).
文摘Background:Establishing an appropriate prognostic model for PCa is essential for its effective treatment.Glycolysis is a vital energy-harvesting mechanism for tumors.Developing a prognostic model for PCa based on glycolysis-related genes is novel and has great potential.Methods:First,gene expression and clinical data of PCa patients were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),and glycolysis-related genes were obtained from the Molecular Signatures Database(MSigDB).Gene enrichment analysis was performed to verify that glycolysis functions were enriched in the genes we obtained,which were used in nonnegative matrix factorization(NMF)to identify clusters.The correlation between clusters and clinical features was discussed,and the differentially expressed genes(DEGs)between the two clusters were investigated.Based on the DEGs,we investigated the biological differences between clusters,including immune cell infiltration,mutation,tumor immune dysfunction and exclusion,immune function,and checkpoint genes.To establish the prognostic model,the genes were filtered based on univariable Cox regression,LASSO,and multivariable Cox regression.Kaplan–Meier analysis and receiver operating characteristic analysis validated the prognostic value of the model.A nomogram of the risk score calculated by the prognostic model and clinical characteristics was constructed to quantitatively estimate the survival probability for PCa patients in the clinical setting.Result:The genes obtained from MSigDB were enriched in glycolysis functions.Two clusters were identified by NMF analysis based on 272 glycolysis-related genes,and a prognostic model based on DEGs between the two clusters was finally established.The prognostic model consisted of LAMPS,SPRN,ATOH1,TANC1,ETV1,TDRD1,KLK14,MESP2,POSTN,CRIP2,NAT1,AKR7A3,PODXL,CARTPT,and PCDHGB2.All sample,training,and test cohorts from The Cancer Genome Atlas(TCGA)and the external validation cohort from GEO showed significant differences between the high-risk and low-risk groups.The area under the ROC curve showed great performance of this prognostic model.Conclusion:A prognostic model based on glycolysis-related genes was established,with great performance and potential significance to the clinical application.
文摘Rank determination issue is one of the most significant issues in non-negative matrix factorization (NMF) research. However, rank determination problem has not received so much emphasis as sparseness regularization problem. Usually, the rank of base matrix needs to be assumed. In this paper, we propose an unsupervised multi-level non-negative matrix factorization model to extract the hidden data structure and seek the rank of base matrix. From machine learning point of view, the learning result depends on its prior knowledge. In our unsupervised multi-level model, we construct a three-level data structure for non-negative matrix factorization algorithm. Such a construction could apply more prior knowledge to the algorithm and obtain a better approximation of real data structure. The final bases selection is achieved through L2-norm optimization. We implement our experiment via binary datasets. The results demonstrate that our approach is able to retrieve the hidden structure of data, thus determine the correct rank of base matrix.
