Williams syndrome(WS)is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23,characterized by intellectual disability,distinctive craniofacial and dental features,and cardiovascular problems.Pre...Williams syndrome(WS)is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23,characterized by intellectual disability,distinctive craniofacial and dental features,and cardiovascular problems.Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes.Here,we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2,as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2.To investigate the potential involvement of RFC2 in WS pathogenicity,we generate a rfc2 knockout(KO)zebrafish using CRISPR-Cas9 technology.Additionally,we generate a KO zebrafish of its paralog gene,rfc5,to better understand the functions of these RFC genes in development and disease.Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS,including small head and brain,jaw and dental defects,and vascular problems.RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish.In addition,heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion.These results suggest that RFC2 may contribute to the pathogenicity of WS,as evidenced by the zebrafish model.展开更多
To improve the accuracy of indirect tensile strength for a transversely isotropic rock in the Brazilian test, this study considered the three-dimensional (3D) deformation and the nonlinear stress–strain relationship....To improve the accuracy of indirect tensile strength for a transversely isotropic rock in the Brazilian test, this study considered the three-dimensional (3D) deformation and the nonlinear stress–strain relationship. A parametric study of a numerical Brazilian test was performed for a general range of elastic constants, revealing that the 3D modeling evaluated the indirect tensile strength up to 40% higher than the plane stress modeling. For the actual Asan gneiss, the 3D model evaluated the indirect tensile strength up to 10% higher and slightly enhanced the accuracy of deformation estimation compared with the plane stress model. The nonlinearity in stress–strain curve of Asan gneiss under uniaxial compression was then considered, such that the evaluated indirect tensile strength was affected by up to 10% and its anisotropy agreed well with the physical intuition. The estimation of deformation was significantly enhanced. The further validation on the nonlinear model is expected as future research.展开更多
Background Although smoking is classified as a risk factor for severe COVID-19 outcomes,there is a scarcity of studies on prevalence of smoking during the COVID-19 pandemic.Thus,this study aims to analyze the trends o...Background Although smoking is classified as a risk factor for severe COVID-19 outcomes,there is a scarcity of studies on prevalence of smoking during the COVID-19 pandemic.Thus,this study aims to analyze the trends of prevalence of smoking in adolescents over the COVID-19 pandemic period.Methods The present study used data from middle to high school adolescents between 2005 and 2021 who participated in the Korea Youth Risk Behavior Web-based Survey(KYRBS).We evaluated the smoking prevalence(ever or daily)by year groups and estimated the slope in smoking prevalence before and during the pandemic.Results A total of 1,137,823 adolescents participated in the study[mean age,15.04 years[95%confidence interval(CI)15.03-15.06];and male,52.4%(95%CI 51.7-53.1)].The prevalence of ever smokers was 27.7%(95%CI 27.3-28.1)between 2005 and 2008 but decreased to 9.8%(95%CI 9.3-10.3)in 2021.A consistent trend was found in daily smokers,as the estimates decreased from 5.4%(95%CI 5.2-5.6)between 2005 and 2008 to 2.3%(95%CI 2.1-2.5)in 2021.However,the downward slope in the overall prevalence of ever smokers and daily smokers became less pronounced in the COVID-19 pandemic period than in the pre-pandemic period.In the subgroup with substance use,the decreasing slope in daily smokers was significantly more pronounced during the pandemic than during the pre-pandemic period.Conclusions The proportion of ever smokers and daily smokers showed a less pronounced decreasing trend during the pandemic.The findings of our study provide an overall understanding of the pandemic's impact on smoking prevalence in adolescents.展开更多
基金supported by the National Research Foundation of Korea grant funded by the Korean government(MIST)(2020R1A5A8017671,2022R1A2C100677813,and RS-2024-00349650)。
文摘Williams syndrome(WS)is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23,characterized by intellectual disability,distinctive craniofacial and dental features,and cardiovascular problems.Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes.Here,we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2,as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2.To investigate the potential involvement of RFC2 in WS pathogenicity,we generate a rfc2 knockout(KO)zebrafish using CRISPR-Cas9 technology.Additionally,we generate a KO zebrafish of its paralog gene,rfc5,to better understand the functions of these RFC genes in development and disease.Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS,including small head and brain,jaw and dental defects,and vascular problems.RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish.In addition,heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion.These results suggest that RFC2 may contribute to the pathogenicity of WS,as evidenced by the zebrafish model.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(Grant No.2023R1 A2C1004298)a grant from the Human Resources Development program(Grant No.20204010600250)of the Korea Institute of Energy Technology Evaluation and Planning(KETEP),funded by the Ministry of Trade,Industry,and Energy of the Korean Government.
文摘To improve the accuracy of indirect tensile strength for a transversely isotropic rock in the Brazilian test, this study considered the three-dimensional (3D) deformation and the nonlinear stress–strain relationship. A parametric study of a numerical Brazilian test was performed for a general range of elastic constants, revealing that the 3D modeling evaluated the indirect tensile strength up to 40% higher than the plane stress modeling. For the actual Asan gneiss, the 3D model evaluated the indirect tensile strength up to 10% higher and slightly enhanced the accuracy of deformation estimation compared with the plane stress model. The nonlinearity in stress–strain curve of Asan gneiss under uniaxial compression was then considered, such that the evaluated indirect tensile strength was affected by up to 10% and its anisotropy agreed well with the physical intuition. The estimation of deformation was significantly enhanced. The further validation on the nonlinear model is expected as future research.
基金supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HV22C0233)the National Research Foundation of Korea(NRF)grant funded by the Korea government(NRF2021R1I1A2059735)。
文摘Background Although smoking is classified as a risk factor for severe COVID-19 outcomes,there is a scarcity of studies on prevalence of smoking during the COVID-19 pandemic.Thus,this study aims to analyze the trends of prevalence of smoking in adolescents over the COVID-19 pandemic period.Methods The present study used data from middle to high school adolescents between 2005 and 2021 who participated in the Korea Youth Risk Behavior Web-based Survey(KYRBS).We evaluated the smoking prevalence(ever or daily)by year groups and estimated the slope in smoking prevalence before and during the pandemic.Results A total of 1,137,823 adolescents participated in the study[mean age,15.04 years[95%confidence interval(CI)15.03-15.06];and male,52.4%(95%CI 51.7-53.1)].The prevalence of ever smokers was 27.7%(95%CI 27.3-28.1)between 2005 and 2008 but decreased to 9.8%(95%CI 9.3-10.3)in 2021.A consistent trend was found in daily smokers,as the estimates decreased from 5.4%(95%CI 5.2-5.6)between 2005 and 2008 to 2.3%(95%CI 2.1-2.5)in 2021.However,the downward slope in the overall prevalence of ever smokers and daily smokers became less pronounced in the COVID-19 pandemic period than in the pre-pandemic period.In the subgroup with substance use,the decreasing slope in daily smokers was significantly more pronounced during the pandemic than during the pre-pandemic period.Conclusions The proportion of ever smokers and daily smokers showed a less pronounced decreasing trend during the pandemic.The findings of our study provide an overall understanding of the pandemic's impact on smoking prevalence in adolescents.
