Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblast...Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.展开更多
This study aimed to investigate the mechanism of mineral spontaneous combustion in an open pit. On the study of coal and mineral mixture in open pit mines, as well as through the specifc surface area and Search Engine...This study aimed to investigate the mechanism of mineral spontaneous combustion in an open pit. On the study of coal and mineral mixture in open pit mines, as well as through the specifc surface area and Search Engine Marketing (SEM) experiments, the specifc surface area and aperture characteristics of distribution of open pit coal sample and pit mineral mixture samples were analyzed. Thermal analysis experiments were used to divide the oxidation process was divided into three stages, and the thermal behavior characteristics of experimental samples were characterized. On the basis of the stage division, we explored the transfer law of the key active functional groups of the experimental samples. The apparent activation energy calculation of the key active groups, performed by combining the Achar diferential method with the Coats–Redfern integral method, microstructural and oxidation kinetic properties were revealed. The resulted showed that the mixed sample had high ash, the fxed carbon content was reduced, the specifc surface area was far lower than the raw coal, the large aperture distribution was slightly higher than the medium hole, the micropore was exceptionally low, the gas adsorption capacity was weaker than the raw coal, the pit coal sample had the exceedingly more active functional groups, easy to react with oxygen, more likely to occur naturally, and its harm was relatively large. The mixed sample contained the highest C–O–C functional group absorbance. The functional groups were mainly infuenced by the self-OH content, alkyl side chain, and fatty hydrocarbon in the sample. The main functional groups of the four-like mixture had the highest apparent activation energy, and the two reactions were higher in the low-temperature oxidation phase.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82173593,32300473)Guangzhou Science and Technology Project(No.2025A04J4537,2025A04J4696)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220053)Postdoctoral Science Foundation of Jiangsu Province(No.2021K524C).
文摘Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.
基金Financial support for this study was kindly provided by the National Natural Science Foundation Project of China(5217-4202)Young Elite Scientists Sponsorship Program of China Association for Science,and Technology(2021QNRC001).
文摘This study aimed to investigate the mechanism of mineral spontaneous combustion in an open pit. On the study of coal and mineral mixture in open pit mines, as well as through the specifc surface area and Search Engine Marketing (SEM) experiments, the specifc surface area and aperture characteristics of distribution of open pit coal sample and pit mineral mixture samples were analyzed. Thermal analysis experiments were used to divide the oxidation process was divided into three stages, and the thermal behavior characteristics of experimental samples were characterized. On the basis of the stage division, we explored the transfer law of the key active functional groups of the experimental samples. The apparent activation energy calculation of the key active groups, performed by combining the Achar diferential method with the Coats–Redfern integral method, microstructural and oxidation kinetic properties were revealed. The resulted showed that the mixed sample had high ash, the fxed carbon content was reduced, the specifc surface area was far lower than the raw coal, the large aperture distribution was slightly higher than the medium hole, the micropore was exceptionally low, the gas adsorption capacity was weaker than the raw coal, the pit coal sample had the exceedingly more active functional groups, easy to react with oxygen, more likely to occur naturally, and its harm was relatively large. The mixed sample contained the highest C–O–C functional group absorbance. The functional groups were mainly infuenced by the self-OH content, alkyl side chain, and fatty hydrocarbon in the sample. The main functional groups of the four-like mixture had the highest apparent activation energy, and the two reactions were higher in the low-temperature oxidation phase.
