Current research on robot calibration can be roughly classified into two categories,and both of them have certain inherent limitations.Model-based methods are difficult to model and compensate the pose errors arising ...Current research on robot calibration can be roughly classified into two categories,and both of them have certain inherent limitations.Model-based methods are difficult to model and compensate the pose errors arising from configuration-dependent geometric and non-geometric source errors,whereas the accuracy of data-driven methods depends on a large amount of measurement data.Using a 5-DOF(degrees of freedom)hybrid machining robot as an exemplar,this study presents a model data-driven approach for the calibration of robotic manipulators.An f-DOF realistic robot containing various source errors is visualized as a 6-DOF fictitious robot having error-free parameters,but erroneous actuated/virtual joint motions.The calibration process essentially involves four steps:(1)formulating the linear map relating the pose error twist to the joint motion errors,(2)parameterizing the joint motion errors using second-order polynomials in terms of nominal actuated joint variables,(3)identifying the polynomial coefficients using the weighted least squares plus principal component analysis,and(4)compensating the compensable pose errors by updating the nominal actuated joint variables.The merit of this approach is that it enables compensation of the pose errors caused by configuration-dependent geometric and non-geometric source errors using finite measurement configurations.Experimental studies on a prototype machine illustrate the effectiveness of the proposed approach.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart fro...BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient(MMR-P)or microsatellite stable(MSS)counterparts.CRCs have several prognostic factors,including stage,tumor differentiation,location,lymphovascular and perineural invasion,tumor budding,tumor infiltrating lymphocytes,lymph node yield(LNY),and lymph node ratio(LNR).AIM To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.METHODS This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment.Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides.MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.RESULTS Of the 223 patients in our study,87(39.01%)were MMR-D/MSI-H CRCs while 136(60.99%)were MMR-P/MSS CRCs.The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors,including location,stage,tumor budding,lymphovascular and perineural invasion,lymphocytic response,LNY,LNR,and size of uninvolved lymph nodes.LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group(P=0.003 and P<0.001,respectively).Also,the interquartile range of the largest uninvolved lymph node was 1 cm(0.8 cm-1.2 cm)in MMR-D/MSI-H CRCs compared to 0.7 cm(0.6 cm-0.97 cm)in MMRP/MSS CRCs.The overall survival for the MMR-P/MSS CRC group was 71%at five years,and the MMR-D/MSIH CRC group was 92%at five years(P<0.001).CONCLUSION MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics,including an enhanced immune response.This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.展开更多
Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECK...Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.展开更多
BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the...BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.展开更多
The rapid urbanization and structural imbalances in Chinese megacities have exacerbated the housing supplydemand mismatch,creating an urgent need for fine-scale diagnostic tools.This study addresses this critical gap ...The rapid urbanization and structural imbalances in Chinese megacities have exacerbated the housing supplydemand mismatch,creating an urgent need for fine-scale diagnostic tools.This study addresses this critical gap by developing the Housing Contradiction Evaluation Weighted Index(HCEWI)model,making three key contributions to high-resolution housing monitoring.First,we establish a tripartite theoretical framework integrating dynamic population pressure(PPI),housing supply potential(HSI),and functional diversity(HHI).The PPI innovatively combines mobile signaling data with principal component analysis to capture real-time commuting patterns,while the HSI introduces a novel dual-criteria system based on Local Climate Zones(LCZ),weighted by building density and residential function ratio.Second,we develop a spatiotemporal coupling architecture featuring an entropy-weighted dynamic integration mechanism with self-correcting modules,demonstrating robust performance against data noise.Third,our 25-month longitudinal analysis in Shenzhen reveals significant findings,including persistent bipolar clustering patterns,contrasting volatility between peripheral and core areas,and seasonal policy responsiveness.Methodologically,we advance urban diagnostics through 500-meter grid monthly monitoring and process-oriented temporal operators that reveal“tentacle-like”spatial restructuring along transit corridors.Our findings provide a replicable framework for precision housing governance and demonstrate the transformative potential of mobile signaling data in implementing China’s“city-specific policy”approach.We further propose targeted intervention strategies,including balance regulation for high-contradiction zones,Transit-Oriented Development(TOD)activation for low-contradiction clusters,and dynamic land conversion mechanisms for transitional areas.展开更多
为提高零中频接收机中正交(in-phase quadrature,IQ)失配信号校正的收敛速度与鲁棒性,本文将Kalman滤波算法与盲源分离结构结合,提出了一种基于双通道Kalman滤波的校正算法。该算法通过状态空间建模与协方差自适应更新,能够在动态环境...为提高零中频接收机中正交(in-phase quadrature,IQ)失配信号校正的收敛速度与鲁棒性,本文将Kalman滤波算法与盲源分离结构结合,提出了一种基于双通道Kalman滤波的校正算法。该算法通过状态空间建模与协方差自适应更新,能够在动态环境下实现更高效、稳定的参数估计,从而实现对IQ失配信号的有效补偿。将本文算法与最小均方算法(least mean square,LMS)、归一化最小均方算法(normalized least mean square,NLMS)和仿射投影算法(affine projection algorithm,APA)进行对比仿真,结果显示,校正后信号的镜像抑制比(image rejection ratio,IRR)均达到约45 dB,但双通道Kalman滤波算法对应的IRR曲面图更加平滑,同时,16QAM和16PSK调制方式下该算法的误符号率最低,表明本文算法能够有效实现IQ失配校正,具有较好的稳定性。本文算法迭代约50次时,均方误差收敛趋近于0,而LMS、NLMS和APA算法则分别需要迭代约500次、400次和200次才能够收敛,表明该算法具有较好的收敛性。通过参数的敏感性仿真分析,在较大的参数范围内本文算法达到的IRR差别甚微,具有良好的鲁棒性。展开更多
基金Supported by National Natural Science Foundation of China(Grant Nos.52325501,U24B2047).
文摘Current research on robot calibration can be roughly classified into two categories,and both of them have certain inherent limitations.Model-based methods are difficult to model and compensate the pose errors arising from configuration-dependent geometric and non-geometric source errors,whereas the accuracy of data-driven methods depends on a large amount of measurement data.Using a 5-DOF(degrees of freedom)hybrid machining robot as an exemplar,this study presents a model data-driven approach for the calibration of robotic manipulators.An f-DOF realistic robot containing various source errors is visualized as a 6-DOF fictitious robot having error-free parameters,but erroneous actuated/virtual joint motions.The calibration process essentially involves four steps:(1)formulating the linear map relating the pose error twist to the joint motion errors,(2)parameterizing the joint motion errors using second-order polynomials in terms of nominal actuated joint variables,(3)identifying the polynomial coefficients using the weighted least squares plus principal component analysis,and(4)compensating the compensable pose errors by updating the nominal actuated joint variables.The merit of this approach is that it enables compensation of the pose errors caused by configuration-dependent geometric and non-geometric source errors using finite measurement configurations.Experimental studies on a prototype machine illustrate the effectiveness of the proposed approach.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
文摘BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient(MMR-P)or microsatellite stable(MSS)counterparts.CRCs have several prognostic factors,including stage,tumor differentiation,location,lymphovascular and perineural invasion,tumor budding,tumor infiltrating lymphocytes,lymph node yield(LNY),and lymph node ratio(LNR).AIM To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.METHODS This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment.Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides.MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.RESULTS Of the 223 patients in our study,87(39.01%)were MMR-D/MSI-H CRCs while 136(60.99%)were MMR-P/MSS CRCs.The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors,including location,stage,tumor budding,lymphovascular and perineural invasion,lymphocytic response,LNY,LNR,and size of uninvolved lymph nodes.LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group(P=0.003 and P<0.001,respectively).Also,the interquartile range of the largest uninvolved lymph node was 1 cm(0.8 cm-1.2 cm)in MMR-D/MSI-H CRCs compared to 0.7 cm(0.6 cm-0.97 cm)in MMRP/MSS CRCs.The overall survival for the MMR-P/MSS CRC group was 71%at five years,and the MMR-D/MSIH CRC group was 92%at five years(P<0.001).CONCLUSION MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics,including an enhanced immune response.This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.
基金supported by The National Key Research and Development Program of China(Grant no.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant no.K-20230085)+5 种基金Post-doctoral Innovative Talent Support Program(Grant no.BX2023375)Lingyan Project of Zhejiang Provincial Department of Science and Technology(Grant no.2025C02059)the National Natural Science Foundation of China(Grant nos.82304946,82473489,and 82403546)Natural Science Foundation of Zhejiang Province(Grant nos.LR21H280001,LGF22H160056,ZCLQN25H1602,and LMS25H160006)Medicine and Health Science Fund of Zhejiang Province Health Commission(Grant nos.2025KY047 and 2022KY658)Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission(Grant no.2022ZA023).
文摘Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.
文摘BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.
基金National Natural Science Foundation of China(No.42101346)Undergraduate Training Programs for Innovation and Entrepreneurship of Wuhan University(GeoAI Special Project)(No.202510486196).
文摘The rapid urbanization and structural imbalances in Chinese megacities have exacerbated the housing supplydemand mismatch,creating an urgent need for fine-scale diagnostic tools.This study addresses this critical gap by developing the Housing Contradiction Evaluation Weighted Index(HCEWI)model,making three key contributions to high-resolution housing monitoring.First,we establish a tripartite theoretical framework integrating dynamic population pressure(PPI),housing supply potential(HSI),and functional diversity(HHI).The PPI innovatively combines mobile signaling data with principal component analysis to capture real-time commuting patterns,while the HSI introduces a novel dual-criteria system based on Local Climate Zones(LCZ),weighted by building density and residential function ratio.Second,we develop a spatiotemporal coupling architecture featuring an entropy-weighted dynamic integration mechanism with self-correcting modules,demonstrating robust performance against data noise.Third,our 25-month longitudinal analysis in Shenzhen reveals significant findings,including persistent bipolar clustering patterns,contrasting volatility between peripheral and core areas,and seasonal policy responsiveness.Methodologically,we advance urban diagnostics through 500-meter grid monthly monitoring and process-oriented temporal operators that reveal“tentacle-like”spatial restructuring along transit corridors.Our findings provide a replicable framework for precision housing governance and demonstrate the transformative potential of mobile signaling data in implementing China’s“city-specific policy”approach.We further propose targeted intervention strategies,including balance regulation for high-contradiction zones,Transit-Oriented Development(TOD)activation for low-contradiction clusters,and dynamic land conversion mechanisms for transitional areas.
文摘为提高零中频接收机中正交(in-phase quadrature,IQ)失配信号校正的收敛速度与鲁棒性,本文将Kalman滤波算法与盲源分离结构结合,提出了一种基于双通道Kalman滤波的校正算法。该算法通过状态空间建模与协方差自适应更新,能够在动态环境下实现更高效、稳定的参数估计,从而实现对IQ失配信号的有效补偿。将本文算法与最小均方算法(least mean square,LMS)、归一化最小均方算法(normalized least mean square,NLMS)和仿射投影算法(affine projection algorithm,APA)进行对比仿真,结果显示,校正后信号的镜像抑制比(image rejection ratio,IRR)均达到约45 dB,但双通道Kalman滤波算法对应的IRR曲面图更加平滑,同时,16QAM和16PSK调制方式下该算法的误符号率最低,表明本文算法能够有效实现IQ失配校正,具有较好的稳定性。本文算法迭代约50次时,均方误差收敛趋近于0,而LMS、NLMS和APA算法则分别需要迭代约500次、400次和200次才能够收敛,表明该算法具有较好的收敛性。通过参数的敏感性仿真分析,在较大的参数范围内本文算法达到的IRR差别甚微,具有良好的鲁棒性。
