Finely tuning spectral characteristics of the epsilon-negative(ε'<0,EN) response is full of challenges when its regulatory mechanism in metacomposites is not yet clear.Herein,we have meticulously designed Cu/C...Finely tuning spectral characteristics of the epsilon-negative(ε'<0,EN) response is full of challenges when its regulatory mechanism in metacomposites is not yet clear.Herein,we have meticulously designed Cu/CaCu_(3)Ti_(4)O_(12)(Cu/CCTO) percolative metacomposites,successfully achieved both epsilon-negative and ε'-near-zero(ENZ)responses in the radio-frequency band.Before percolation,a large number of electric dipoles in the metacomposites achieved resonance characteristics near the ENZ point under the excitation of radio frequency electromagnetic fields,and as the Cu content increased,the ENZ frequency varied from 942,858,862 to 632 MHz.展开更多
Since its inception,the epsilon distribution has piqued the interest of statisticians.It has been successfully used to solve a variety of statistical problems.In this article,we propose to use the quadratic rank trans...Since its inception,the epsilon distribution has piqued the interest of statisticians.It has been successfully used to solve a variety of statistical problems.In this article,we propose to use the quadratic rank transmutation map mechanism to extend this distribution.This mechanism is not new;it was already used to improve the modeling capabilities of a number of existing distributions.For the original epsilon distribution,we expect the same benefits.As a result,we implement the transmuted epsilon distribution as a flexible three-parameter distribution with a bounded domain.We demonstrate its key features,focusing on the properties of its distributional mechanism and conducting quantile and moment analyses.Applications of the model are presented using two data sets.We also perform a regression analysis based on this distribution.展开更多
BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To ...BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To identify POLE non-EDMs and EDMs in CRC,and to determine their associations with accompanying mutations and microsatellite instability(MSI).METHODS In this retrospective study,next-generation sequencing was performed using a targeted colon cancer panel(Qiagen,DHS-003Z)on 356 CRC patients.Of these,191 patients were found to carry POLE mutations.For these patients,MSI status was assessed using both real-time PCR(EasyPGX^(■)Ready MSI kit)and immunohistochemistry,and accompanying somatic mutations were investigated.RESULTS POLE mutations were identified in 53.65%of the CRC patients.Among the POLE-mutant patients,87.96%were classified as pMMR(MSI-L),and 12.04%as dMMR(MSI-H).The most frequently observed POLE non-EDM variant was exon 34 c.4337_4338delTG p.V1446fs*3.The POLE EDMs were present in exon 14,with two specific variants p.Y458F(0.52%)and p.Y468N(0.52%).The most common pathogenic variants accompanying the POLE mutations were in MLH3,MSH3,KRAS,PIK3CA,and BRAF genes.POLE mutations were associated with a high mutational burden and MSI in CRC,particularly in the dMMR phenotype.This association suggests that POLE mutations may serve as important biomarkers for understanding the genetic profile of the disease and may be used in the clinical management of CRC.CONCLUSION POLE mutations,especially non-EDMs,are frequent in MSI-L CRC and often co-occur with MLH3,MSH3,KRAS,PIK3CA,and BRAF,highlighting their potential role in tumor biology and as biomarkers for personalized treatment.Functional validation and multicenter studies are needed.展开更多
BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(H...BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(HbA1c)reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM.Although both factors have been individually linked to neurobehavioral deficits,it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.AIM To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.METHODS Of 636 T2DM patients were recruited from five medical centers in Wuhan,Hubei Province,China.APOE genotyping was evaluated by polymerase chain reaction using Gerard’s method.Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test,respectively.Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.RESULTS APOE4 was associated with increased risks of cognitive impairment[odds ratios(OR)=1.815,P=0.021]and olfactory dysfunction(OR=2.588,P<0.001).Higher HbA1c levels were also related to worse cognitive(OR=1.189,P<0.001)and olfactory performance(OR=1.149,P=0.011).HbA1c exerted a moderating effect,yet not a mediating effect,between APOE4 and its impacts on cognition and olfaction.Specifically,a higher level of HbA1c exacerbated the damaging effect of APOE4,as shown by significant interaction effects on both cognitive impairment(OR=2.687,P<0.001)and olfactory dysfunction(OR=1.440,P=0.027).CONCLUSION Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4.These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.展开更多
基金supported by the National Natural Science Foundation of China(No.52461002)
文摘Finely tuning spectral characteristics of the epsilon-negative(ε'<0,EN) response is full of challenges when its regulatory mechanism in metacomposites is not yet clear.Herein,we have meticulously designed Cu/CaCu_(3)Ti_(4)O_(12)(Cu/CCTO) percolative metacomposites,successfully achieved both epsilon-negative and ε'-near-zero(ENZ)responses in the radio-frequency band.Before percolation,a large number of electric dipoles in the metacomposites achieved resonance characteristics near the ENZ point under the excitation of radio frequency electromagnetic fields,and as the Cu content increased,the ENZ frequency varied from 942,858,862 to 632 MHz.
文摘Since its inception,the epsilon distribution has piqued the interest of statisticians.It has been successfully used to solve a variety of statistical problems.In this article,we propose to use the quadratic rank transmutation map mechanism to extend this distribution.This mechanism is not new;it was already used to improve the modeling capabilities of a number of existing distributions.For the original epsilon distribution,we expect the same benefits.As a result,we implement the transmuted epsilon distribution as a flexible three-parameter distribution with a bounded domain.We demonstrate its key features,focusing on the properties of its distributional mechanism and conducting quantile and moment analyses.Applications of the model are presented using two data sets.We also perform a regression analysis based on this distribution.
文摘BACKGROUND Although the relationship between somatic DNA polymerase epsilon(POLE)exonuclease domain mutations(EDMs)and colorectal cancer(CRC)is well established,the role of POLE non-EDMs in CRC remains unclear.AIM To identify POLE non-EDMs and EDMs in CRC,and to determine their associations with accompanying mutations and microsatellite instability(MSI).METHODS In this retrospective study,next-generation sequencing was performed using a targeted colon cancer panel(Qiagen,DHS-003Z)on 356 CRC patients.Of these,191 patients were found to carry POLE mutations.For these patients,MSI status was assessed using both real-time PCR(EasyPGX^(■)Ready MSI kit)and immunohistochemistry,and accompanying somatic mutations were investigated.RESULTS POLE mutations were identified in 53.65%of the CRC patients.Among the POLE-mutant patients,87.96%were classified as pMMR(MSI-L),and 12.04%as dMMR(MSI-H).The most frequently observed POLE non-EDM variant was exon 34 c.4337_4338delTG p.V1446fs*3.The POLE EDMs were present in exon 14,with two specific variants p.Y458F(0.52%)and p.Y468N(0.52%).The most common pathogenic variants accompanying the POLE mutations were in MLH3,MSH3,KRAS,PIK3CA,and BRAF genes.POLE mutations were associated with a high mutational burden and MSI in CRC,particularly in the dMMR phenotype.This association suggests that POLE mutations may serve as important biomarkers for understanding the genetic profile of the disease and may be used in the clinical management of CRC.CONCLUSION POLE mutations,especially non-EDMs,are frequent in MSI-L CRC and often co-occur with MLH3,MSH3,KRAS,PIK3CA,and BRAF,highlighting their potential role in tumor biology and as biomarkers for personalized treatment.Functional validation and multicenter studies are needed.
基金Supported by the China Postdoctoral Science Foundation General Program,No.2024M762504the Intramural Research Program of Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology,No.2023 LYYYGZRP0004.
文摘BACKGROUND Apolipoprotein E epsilon 4(APOE4)is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus(T2DM)and Alzheimer’s disease,while glycated hemoglobin(HbA1c)reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM.Although both factors have been individually linked to neurobehavioral deficits,it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.AIM To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.METHODS Of 636 T2DM patients were recruited from five medical centers in Wuhan,Hubei Province,China.APOE genotyping was evaluated by polymerase chain reaction using Gerard’s method.Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test,respectively.Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.RESULTS APOE4 was associated with increased risks of cognitive impairment[odds ratios(OR)=1.815,P=0.021]and olfactory dysfunction(OR=2.588,P<0.001).Higher HbA1c levels were also related to worse cognitive(OR=1.189,P<0.001)and olfactory performance(OR=1.149,P=0.011).HbA1c exerted a moderating effect,yet not a mediating effect,between APOE4 and its impacts on cognition and olfaction.Specifically,a higher level of HbA1c exacerbated the damaging effect of APOE4,as shown by significant interaction effects on both cognitive impairment(OR=2.687,P<0.001)and olfactory dysfunction(OR=1.440,P=0.027).CONCLUSION Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4.These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.
