Objective:This study aimed to evaluate the cost–effectiveness of durvalumab combined with tremelimumab versus sorafenib as the first-line treatment for advanced unresectable hepatocellular carcinoma(uHCC)from the per...Objective:This study aimed to evaluate the cost–effectiveness of durvalumab combined with tremelimumab versus sorafenib as the first-line treatment for advanced unresectable hepatocellular carcinoma(uHCC)from the perspective of China’s healthcare system.Methods:Utilizing data from the HIMALAYA clinical trial,a partitioned survival model was developed to simulate clinical pathways,costs,and outcomes.Incremental cost‒effectiveness ratios(ICERs)were calculated through cost‒utility analysis,with robustness assessed via one-way and probabilistic sensitivity analyses.Results:Total costs for the durvalumab‒tremelimumab regimen reached 152,729.04 USD(1.96 quality-adjusted life years,QALYs),whereas they reached 147,406.75 USD(1.48 QALYs)for sorafenib.The ICER of 11,027.79 USD per QALY remained substantially below China’s willingness-to-pay(WTP)threshold of 36,622.13 USD per QALY.Sensitivity analyses confirmed tremelimumab pricing and discount rates as primary determinants of cost‒effectiveness.Conclusion:Within China’s healthcare framework,durvalumab‒tremelimumab is cost effective as a first-line therapy for uHCC,contingent on formulary inclusion and price adjustments.展开更多
Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygos...Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.展开更多
Genetically modified(GM)crops that impart herbicide resistance,improved tolerance to biotic and abiotic stresses,and enhanced yield or nutritional quality have been developed and grown worldwide(ISAAA Brief 55-2019:In...Genetically modified(GM)crops that impart herbicide resistance,improved tolerance to biotic and abiotic stresses,and enhanced yield or nutritional quality have been developed and grown worldwide(ISAAA Brief 55-2019:International Servicefor theAcquisition ofAgri-biotech Applications(ISAAA),2019).In response topublic concern on genetically modified organisms(GMOs),DNA-based and protein-based methods have been developed to detect GMOs infood/feed samples(Fraitureetal.,2015).These methods,however,require expensive equipment and technical expertise and are unsuitable for field diagnosis(DNA-based methods)or cannot detect non-coding sequences such as promoters or terminators(protein-based methods).展开更多
Papaya(Carica papaya)is a promising model system for genetic and genomic studies of fruit traits and sex determination in tropical trees and fruits.However,the genomic basis of the artificial selection for key fruit t...Papaya(Carica papaya)is a promising model system for genetic and genomic studies of fruit traits and sex determination in tropical trees and fruits.However,the genomic basis of the artificial selection for key fruit traits and commercially crucial hermaphroditism remains poorly understood.In this study,we assembled the genomes for two phenotypically divergent hermaphroditic cultivars,including their haplotype-phased sex-determining regions(SDRs).Population genomic analyses of wild,common-type(for vegetable use),and fruit-type(for fresh consumption)papayas revealed a clear domestication history and geographic spread model.By combining genome-wide association study(GWAS),selection scan,and functional validation,we revealed a stepwise selection targeting CpPUP11 and Cp/CMT during domestication and improvement to reshape fruit size,and artificial selection on CpMAPK1,CpCOX,CpCIN,and CpUBE3 during the improvement process to increase fruit sweetness and vitamin C content.Furthermore,we demonstrated the independent origins of two hermaphroditic lineages through polyphyletic selection from wild male populations,resulting in two distinct hermaphrodite-specific Yh regions(HSY1 and HSY3).This transition was driven by selection targeting male-biased genes,which exhibited stable dominance in their methylation and transcription.Notably,we identified a hermaphrodite-specific,selectively fixed 13-bp insertion in the male-biased gene CpPGLP1A(HSY3-TR-13bp),which is strongly associated with the male-to-hermaphrodite transition.Collectively,our study provides novel insights into the genomic architecture of papaya domestication,revealing a trajectory of stepwise selection reshaping fruit traits and male-biased selection driving the emergence of a novel hermaphroditic sexual system.展开更多
基金supported by the National Natural Science Foundation of China(12231017,72171216,12171449)the National Key R&D Program of China(2022YFA1003803)+1 种基金the Fundamental Research Funds for the Central Universities(WK3470000027)the Innovative Development Funds of Anhui Province Federation of Social Sciences(2022CX081).
文摘Objective:This study aimed to evaluate the cost–effectiveness of durvalumab combined with tremelimumab versus sorafenib as the first-line treatment for advanced unresectable hepatocellular carcinoma(uHCC)from the perspective of China’s healthcare system.Methods:Utilizing data from the HIMALAYA clinical trial,a partitioned survival model was developed to simulate clinical pathways,costs,and outcomes.Incremental cost‒effectiveness ratios(ICERs)were calculated through cost‒utility analysis,with robustness assessed via one-way and probabilistic sensitivity analyses.Results:Total costs for the durvalumab‒tremelimumab regimen reached 152,729.04 USD(1.96 quality-adjusted life years,QALYs),whereas they reached 147,406.75 USD(1.48 QALYs)for sorafenib.The ICER of 11,027.79 USD per QALY remained substantially below China’s willingness-to-pay(WTP)threshold of 36,622.13 USD per QALY.Sensitivity analyses confirmed tremelimumab pricing and discount rates as primary determinants of cost‒effectiveness.Conclusion:Within China’s healthcare framework,durvalumab‒tremelimumab is cost effective as a first-line therapy for uHCC,contingent on formulary inclusion and price adjustments.
基金supported by the National Key Research and Development Program of China(grant no.2019YFD1000500)the 2020 Research Program of Sanya Yazhou Bay Science and Technology City(grant no.SKJC-2020-02-002)+2 种基金the Central Public-Interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences(grant nos.1630012019009,1630052016005,1630052016006,1630052017021,and 1630052019023)the Central Public-Interest Scientific Institution Basal Research Fund for Innovative Research Team Program of CATAS(grant nos.17CXTD-28 and 1630052017017)the ear-marked fund for Modern Agro-industry Technology Research System(grant no.nycytx-11).
文摘Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.
基金funded by Hainan Province's Major Scientific and Technological Project“Biosafety Preventionand Control in Southern Breeding Area"(ZDKJ202002)the researchwas also supported by the innovation platform for Academicians of Hainan Province.
文摘Genetically modified(GM)crops that impart herbicide resistance,improved tolerance to biotic and abiotic stresses,and enhanced yield or nutritional quality have been developed and grown worldwide(ISAAA Brief 55-2019:International Servicefor theAcquisition ofAgri-biotech Applications(ISAAA),2019).In response topublic concern on genetically modified organisms(GMOs),DNA-based and protein-based methods have been developed to detect GMOs infood/feed samples(Fraitureetal.,2015).These methods,however,require expensive equipment and technical expertise and are unsuitable for field diagnosis(DNA-based methods)or cannot detect non-coding sequences such as promoters or terminators(protein-based methods).
基金supported by the Key Research and Development Project of Hainan Province(ZDYF2025XDNY120 to H.Z.)the Project of State Key Laboratory of Tropical Crop Breeding(No.NKLTCBCXTD16 to C.J.)+3 种基金the National Natural Science Foundation of China(32472698 to C.J.)the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences(1630052020007 to C.J.)the Social Public-interest Scientific Institution Reform Special Fund(1630052024002 to C.J.)the Hainan Province Science and Technology Special Fund(ZDYF2022XDNY257 and ZDYF2024XDNY179 to R.J.).
文摘Papaya(Carica papaya)is a promising model system for genetic and genomic studies of fruit traits and sex determination in tropical trees and fruits.However,the genomic basis of the artificial selection for key fruit traits and commercially crucial hermaphroditism remains poorly understood.In this study,we assembled the genomes for two phenotypically divergent hermaphroditic cultivars,including their haplotype-phased sex-determining regions(SDRs).Population genomic analyses of wild,common-type(for vegetable use),and fruit-type(for fresh consumption)papayas revealed a clear domestication history and geographic spread model.By combining genome-wide association study(GWAS),selection scan,and functional validation,we revealed a stepwise selection targeting CpPUP11 and Cp/CMT during domestication and improvement to reshape fruit size,and artificial selection on CpMAPK1,CpCOX,CpCIN,and CpUBE3 during the improvement process to increase fruit sweetness and vitamin C content.Furthermore,we demonstrated the independent origins of two hermaphroditic lineages through polyphyletic selection from wild male populations,resulting in two distinct hermaphrodite-specific Yh regions(HSY1 and HSY3).This transition was driven by selection targeting male-biased genes,which exhibited stable dominance in their methylation and transcription.Notably,we identified a hermaphrodite-specific,selectively fixed 13-bp insertion in the male-biased gene CpPGLP1A(HSY3-TR-13bp),which is strongly associated with the male-to-hermaphrodite transition.Collectively,our study provides novel insights into the genomic architecture of papaya domestication,revealing a trajectory of stepwise selection reshaping fruit traits and male-biased selection driving the emergence of a novel hermaphroditic sexual system.
