This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors(ICIs)by conducting systematic literature search in electronic databases up to May 31,2021.The main...This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors(ICIs)by conducting systematic literature search in electronic databases up to May 31,2021.The main outcomes including overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and durable clinical benefit(DCB)were correlated with tumor genomic features.A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies.The Kirsten rat sarcoma viral oncogene homolog G12C(KRAS^(G12C))mutation combined with tumor protein P53(TP53)mutation revealed the promising efficacy of ICI therapy in these patients.Furthermore,patients with epidermal growth factor receptor(EGFR)classical activating mutations(including EGFRL858Rand EGFRΔ19)exhibited worse outcomes to ICIs in OS(adjusted hazard ratio(HR),1.40;95%confidence interval(CI),1.01-1.95;P=0.0411)and PFS(adjusted HR,1.98;95%CI,1.49-2.63;P<0.0001),while classical activating mutations with EGFR^(T790)Mshowed no difference compared to classical activating mutations without EGFR^(T790)Min OS(adjusted HR,0.96;95%CI,0.48-1.94;P=0.9157)or PFS(adjusted HR,0.72;95%CI,0.39-1.35;P=0.3050).Of note,for patients harboring the Usher syndrome type-2A(USH2A)missense mutation,correspondingly better outcomes were observed in OS(adjusted HR,0.52;95%CI,0.32-0.82;P=0.0077),PFS(adjusted HR,0.51;95%CI,0.38-0.69;P<0.0001),DCB(adjusted odds ratio(OR),4.74;95%CI,2.75-8.17;P<0.0001),and ORR(adjusted OR,3.45;95%CI,1.88-6.33;P<0.0001).Our findings indicated that,USH2A missense mutations and the KRAS^(G12C)mutation combined with TP53 mutation were associated with better efficacy and survival outcomes,but EGFR classical mutations irrespective of combination with EGFR^(T790)Mshowed the opposite role in the ICI therapy among lung cancer patients.Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.展开更多
Objective To compare the diagnostic efficiency of the thyroid imaging reporting and data system(TIRADS),the Bethesda system for reporting thyroid cytopathology(BSRTC)and BRAFV600Edetection,and their combined use in th...Objective To compare the diagnostic efficiency of the thyroid imaging reporting and data system(TIRADS),the Bethesda system for reporting thyroid cytopathology(BSRTC)and BRAFV600Edetection,and their combined use in the differentiation between benign and malignant thyroid nodules.Methods One hundred展开更多
Impact statement We have developed the GReedy Accumulated strategy for Protein Engineering(GRAPE)to improve enzyme stability across various applications,combining advanced computational methods with a unique clusterin...Impact statement We have developed the GReedy Accumulated strategy for Protein Engineering(GRAPE)to improve enzyme stability across various applications,combining advanced computational methods with a unique clustering and greedy accumulation approach to efficiently explore epistatic effects with minimal experimental effort.To make this strategy accessible to nonexperts,we introduced GRAPE‐WEB,an automated,user‐friendly web server that allows the design,inspection,and combination of stabilizing mutations without requiring extensive bioinformatics knowledge.展开更多
To address the issue of accurately extracting fault characteristic information of railway freight car bearings under noisy conditions,this paper proposes a fault diagnosis method based on Adaptive Chirp Mode Decomposi...To address the issue of accurately extracting fault characteristic information of railway freight car bearings under noisy conditions,this paper proposes a fault diagnosis method based on Adaptive Chirp Mode Decomposition(ACMD)and an optimized Maximum Correlation Kurtosis Deconvolution(MCKD)using a Sparrow Search Algorithm Combining Sine-Cosine and Cauchy Mutation(SCSSA).Firstly,ACMD is used to decompose and reconstruct the original fault signal to obtain several Intrinsic Mode Functions(IMFs).Then,the IMFs are filtered according to the Gini coefficient indicator,with the IMF having the largest Gini coefficient selected as the optimal component.Secondly,the SCSSA is employed to iteratively optimize the filter length L,fault signal period T,and displacement parameter M in the MCKD algorithm,determining the optimal parameter combination for MCKD.This avoids the limitations of manual settings and enhances the accuracy of fault diagnosis.The optimized MCKD is then applied to the optimal component,and deconvolution is performed using maximum correlation kurtosis as the criterion to extract fault characteristic information through its envelope spectrum.To verify the effectiveness and generalizability of the proposed method,simulations,experimental signals from the Case Western Reserve University Bearing Center,and actual measured signals from railway freight car bearing 353130B are used to analyze inner ring faults.The experimental results demonstrate that the method can accurately extract fault characteristic information of railway freight car bearings under noise interference and identify the fault type.展开更多
基金the National Natural Science Foundation of China(Nos.21976155,81802881,and 81773016)the Zhejiang Provincial Natural Science Foundation of China(No.LY18C060001)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(No.2019-I2M-5-044),China。
文摘This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors(ICIs)by conducting systematic literature search in electronic databases up to May 31,2021.The main outcomes including overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and durable clinical benefit(DCB)were correlated with tumor genomic features.A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies.The Kirsten rat sarcoma viral oncogene homolog G12C(KRAS^(G12C))mutation combined with tumor protein P53(TP53)mutation revealed the promising efficacy of ICI therapy in these patients.Furthermore,patients with epidermal growth factor receptor(EGFR)classical activating mutations(including EGFRL858Rand EGFRΔ19)exhibited worse outcomes to ICIs in OS(adjusted hazard ratio(HR),1.40;95%confidence interval(CI),1.01-1.95;P=0.0411)and PFS(adjusted HR,1.98;95%CI,1.49-2.63;P<0.0001),while classical activating mutations with EGFR^(T790)Mshowed no difference compared to classical activating mutations without EGFR^(T790)Min OS(adjusted HR,0.96;95%CI,0.48-1.94;P=0.9157)or PFS(adjusted HR,0.72;95%CI,0.39-1.35;P=0.3050).Of note,for patients harboring the Usher syndrome type-2A(USH2A)missense mutation,correspondingly better outcomes were observed in OS(adjusted HR,0.52;95%CI,0.32-0.82;P=0.0077),PFS(adjusted HR,0.51;95%CI,0.38-0.69;P<0.0001),DCB(adjusted odds ratio(OR),4.74;95%CI,2.75-8.17;P<0.0001),and ORR(adjusted OR,3.45;95%CI,1.88-6.33;P<0.0001).Our findings indicated that,USH2A missense mutations and the KRAS^(G12C)mutation combined with TP53 mutation were associated with better efficacy and survival outcomes,but EGFR classical mutations irrespective of combination with EGFR^(T790)Mshowed the opposite role in the ICI therapy among lung cancer patients.Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
文摘Objective To compare the diagnostic efficiency of the thyroid imaging reporting and data system(TIRADS),the Bethesda system for reporting thyroid cytopathology(BSRTC)and BRAFV600Edetection,and their combined use in the differentiation between benign and malignant thyroid nodules.Methods One hundred
基金supported by the National Key R&D Program of China(grant no.2021YFC2103600)the National Natural Science Foundation of China(31822002,32170033,and 32422001)+2 种基金the Key Research Program of Frontier Sciences(ZDBS‐LY‐SM014)the Biological Resources Program(KFJBRP‐009 and KFJ‐BRP‐017‐58)from the Chinese Academy of Sciences,the Informatization Plan of Chinese Academy of Sciences(CAS‐WX2021SF‐0111)the Youth Innovation Promotion Association CAS(2022086).
文摘Impact statement We have developed the GReedy Accumulated strategy for Protein Engineering(GRAPE)to improve enzyme stability across various applications,combining advanced computational methods with a unique clustering and greedy accumulation approach to efficiently explore epistatic effects with minimal experimental effort.To make this strategy accessible to nonexperts,we introduced GRAPE‐WEB,an automated,user‐friendly web server that allows the design,inspection,and combination of stabilizing mutations without requiring extensive bioinformatics knowledge.
文摘To address the issue of accurately extracting fault characteristic information of railway freight car bearings under noisy conditions,this paper proposes a fault diagnosis method based on Adaptive Chirp Mode Decomposition(ACMD)and an optimized Maximum Correlation Kurtosis Deconvolution(MCKD)using a Sparrow Search Algorithm Combining Sine-Cosine and Cauchy Mutation(SCSSA).Firstly,ACMD is used to decompose and reconstruct the original fault signal to obtain several Intrinsic Mode Functions(IMFs).Then,the IMFs are filtered according to the Gini coefficient indicator,with the IMF having the largest Gini coefficient selected as the optimal component.Secondly,the SCSSA is employed to iteratively optimize the filter length L,fault signal period T,and displacement parameter M in the MCKD algorithm,determining the optimal parameter combination for MCKD.This avoids the limitations of manual settings and enhances the accuracy of fault diagnosis.The optimized MCKD is then applied to the optimal component,and deconvolution is performed using maximum correlation kurtosis as the criterion to extract fault characteristic information through its envelope spectrum.To verify the effectiveness and generalizability of the proposed method,simulations,experimental signals from the Case Western Reserve University Bearing Center,and actual measured signals from railway freight car bearing 353130B are used to analyze inner ring faults.The experimental results demonstrate that the method can accurately extract fault characteristic information of railway freight car bearings under noise interference and identify the fault type.
