目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区...目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区生存模型,模拟时限为5年,循环周期为28 d。比较NG方案和吉西他滨(gemcitabine,G)方案一线治疗局部晚期或转移性K-Ras野生型胰腺癌的经济性。以质量调整生命年(quality-adjusted life year,QALY)作为产出指标并计算增量成本-效果比(incremental cost-effectiveness ratio,ICER),采用单因素敏感性分析及概率敏感性分析评价模型参数变化对结果稳健性的影响。结果:基础分析结果显示,相较于G方案,NG方案人均成本增加304806.15元,人均效用增加0.16 QALYs,ICER为1865405.26元/QALY,高于本研究设定的268074.00元/QALY的意愿支付(willingness-to-pay,WTP)阈值。单因素敏感性分析结果表明,尼妥珠单抗的成本、肿瘤稳定状态效用和肿瘤进展状态效用对ICER的影响较大。概率敏感性分析结果显示,在WTP阈值为268074.00元/QALY时,NG方案具有经济性的概率为0。结论:与G方案相比,NG方案作为一线药物治疗局部晚期或转移性K-Ras野生型胰腺癌不具有经济性。展开更多
The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motio...The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motion from cardiac computed tomography angiographic(CTA)images.This paper presents a comprehensive performance evaluation of the DVC method,specifically focusing on tracking the motion of the left atrium using cardiac CTA data.The study employed a comparative experimental approach while simultaneously optimizing the existing DVC algorithm.Multiple sets of controlled experiments were designed to conduct quantitative analyses on the parameters“radius”and“step”.The results revealed that the optimized DVC algorithm enhanced tracking accuracy within a reasonable computational time.These findings contributed to the understanding of the efficacy and limitations of the DVC algorithm in analyzing heart deformation.展开更多
The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the...The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the stability of underground mining engineering,this paper simulates the generation of different degrees of initial defects inside the CTB by adding different contents of air-entraining agent(AEA),investigates the acoustic emission RA/AF eigenvalues of CTB with different contents of AEA under uniaxial compression,and adopts various denoising algorithms(e.g.,moving average smoothing,median filtering,and outlier detection)to improve the accuracy of the data.The variance and autocorrelation coefficients of RA/AF parameters were analyzed in conjunction with the critical slowing down(CSD)theory.The results show that the acoustic emission RA/AF values can be used to characterize the progressive damage evolution of CTB.The denoising algorithm processed the AE signals to reduce the effects of extraneous noise and anomalous spikes.Changes in the variance curves provide clear precursor information,while abrupt changes in the autocorrelation coefficient can be used as an auxiliary localization warning signal.The phenomenon of dramatic increase in the variance and autocorrelation coefficient curves during the compression-tightening stage,which is influenced by the initial defects,can lead to false warnings.As the initial defects of the CTB increase,its instability precursor time and instability time are prolonged,the peak stress decreases,and the time difference between the CTB and the instability damage is smaller.The results provide a new method for real-time monitoring and early warning of CTB instability damage.展开更多
Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the p...Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the precancerous scribble(scrib)mutant clones,in Drosophila imaginal discs.The activation of Ras,Yki,or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth.Whether these signals converge to adopt a common mechanism to overcome the elimination pressure posed by cell competition remains unclear.Using single-cell transcriptomics,we find that a critical converging point downstream of Ras,Yki,and Notch signals is the upregulation of Upd2,an IL-6 family cytokine.Overexpression of Upd2 is sufficient to rescue the scrib mutant clones from elimination.Depletion of Upd2 blocks the growth of the scrib mutant clones with active Ras,Yki,and Notch signals.Moreover,Upd2 overexpression promotes robust intestinal stem cell(ISC)proliferation,while Upd2 is intrinsically required in ISCs for the growth of the adult intestine.Together,these results identify Upd2 as a crucial cell fitness factor that sustains tissue growth but can potentiate tumorigenesis when deregulated.展开更多
The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on elimin...The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).展开更多
文摘目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区生存模型,模拟时限为5年,循环周期为28 d。比较NG方案和吉西他滨(gemcitabine,G)方案一线治疗局部晚期或转移性K-Ras野生型胰腺癌的经济性。以质量调整生命年(quality-adjusted life year,QALY)作为产出指标并计算增量成本-效果比(incremental cost-effectiveness ratio,ICER),采用单因素敏感性分析及概率敏感性分析评价模型参数变化对结果稳健性的影响。结果:基础分析结果显示,相较于G方案,NG方案人均成本增加304806.15元,人均效用增加0.16 QALYs,ICER为1865405.26元/QALY,高于本研究设定的268074.00元/QALY的意愿支付(willingness-to-pay,WTP)阈值。单因素敏感性分析结果表明,尼妥珠单抗的成本、肿瘤稳定状态效用和肿瘤进展状态效用对ICER的影响较大。概率敏感性分析结果显示,在WTP阈值为268074.00元/QALY时,NG方案具有经济性的概率为0。结论:与G方案相比,NG方案作为一线药物治疗局部晚期或转移性K-Ras野生型胰腺癌不具有经济性。
基金supported by the Australian Research Council(ARC)(Grant No.DP200103492)the National Natural Science Foundation of China(Grant Nos.12172089,12372307,and 61821002)+2 种基金Medical Research Future Fund(Grant Nos.2016165 and 2023977)the CBT Early Career Researcher Grant funded and the Roland Bishop Biomedical Engineering Research Award by Queensland University of Technologythe Springboard Funding and the Global Collaboration Funding by London South Bank University.Computational resources and services used in this work were provided by the High-Performance Computing and Research Support Group,Queensland University of Technology,Brisbane,Australia.
文摘The accurate assessment of cardiac motion is crucial for diagnosing and monitoring cardiovascular diseases.In this context,digital volume correlation(DVC)has emerged as a promising technique for tracking cardiac motion from cardiac computed tomography angiographic(CTA)images.This paper presents a comprehensive performance evaluation of the DVC method,specifically focusing on tracking the motion of the left atrium using cardiac CTA data.The study employed a comparative experimental approach while simultaneously optimizing the existing DVC algorithm.Multiple sets of controlled experiments were designed to conduct quantitative analyses on the parameters“radius”and“step”.The results revealed that the optimized DVC algorithm enhanced tracking accuracy within a reasonable computational time.These findings contributed to the understanding of the efficacy and limitations of the DVC algorithm in analyzing heart deformation.
基金Projects(52374138,51764013)supported by the National Natural Science Foundation of ChinaProject(20204BCJ22005)supported by the Training Plan for Academic and Technical Leaders of Major Disciplines of Jiangxi Province,China+1 种基金Project(2019M652277)supported by the China Postdoctoral Science FoundationProject(20192ACBL21014)supported by the Natural Science Youth Foundation Key Projects of Jiangxi Province,China。
文摘The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the stability of underground mining engineering,this paper simulates the generation of different degrees of initial defects inside the CTB by adding different contents of air-entraining agent(AEA),investigates the acoustic emission RA/AF eigenvalues of CTB with different contents of AEA under uniaxial compression,and adopts various denoising algorithms(e.g.,moving average smoothing,median filtering,and outlier detection)to improve the accuracy of the data.The variance and autocorrelation coefficients of RA/AF parameters were analyzed in conjunction with the critical slowing down(CSD)theory.The results show that the acoustic emission RA/AF values can be used to characterize the progressive damage evolution of CTB.The denoising algorithm processed the AE signals to reduce the effects of extraneous noise and anomalous spikes.Changes in the variance curves provide clear precursor information,while abrupt changes in the autocorrelation coefficient can be used as an auxiliary localization warning signal.The phenomenon of dramatic increase in the variance and autocorrelation coefficient curves during the compression-tightening stage,which is influenced by the initial defects,can lead to false warnings.As the initial defects of the CTB increase,its instability precursor time and instability time are prolonged,the peak stress decreases,and the time difference between the CTB and the instability damage is smaller.The results provide a new method for real-time monitoring and early warning of CTB instability damage.
基金supported by grants to Yan Yan from the Research Grants Council of the Hong Kong Special Administrative Region(GRF16103620,GRF16104324,T13-602/21N)from Shenzhen Science and Technology Innovation Commission(JCYJ20200109140201722)+1 种基金to Toyotaka Ishibashi from the National Natural Science Foundation of China(32170548)to Zongzhao Zhai from the National Natural Science Foundation of China(32170509 and 31871469).
文摘Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community.A classical model is the removal of polarity-deficient clones,such as the precancerous scribble(scrib)mutant clones,in Drosophila imaginal discs.The activation of Ras,Yki,or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth.Whether these signals converge to adopt a common mechanism to overcome the elimination pressure posed by cell competition remains unclear.Using single-cell transcriptomics,we find that a critical converging point downstream of Ras,Yki,and Notch signals is the upregulation of Upd2,an IL-6 family cytokine.Overexpression of Upd2 is sufficient to rescue the scrib mutant clones from elimination.Depletion of Upd2 blocks the growth of the scrib mutant clones with active Ras,Yki,and Notch signals.Moreover,Upd2 overexpression promotes robust intestinal stem cell(ISC)proliferation,while Upd2 is intrinsically required in ISCs for the growth of the adult intestine.Together,these results identify Upd2 as a crucial cell fitness factor that sustains tissue growth but can potentiate tumorigenesis when deregulated.
文摘The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).
