Brain MRI Radiomics Analysis of School-Aged Children with Tetralogy of Fallot.

INTRODUCTION: Radiomics could be potential imaging biomarkers by capturing and analyzing the features. Children and adolescents with CHD have worse neurodevelopmental and functional outcomes compared with their peers. Early diagnosis and intervention are the necessity to improve neurological outcomes in CHD patients. METHODS: School-aged TOF patients and their healthy peers were recruited for MRI and neurodevelopmental assessment. LASSO regression was used for dimension reduction. ROC curve graph showed the performance of the model. RESULTS: Six related features were finally selected for modeling. The final model AUC was 0.750. The radiomics features can be potential significant predictors for neurodevelopmental diagnoses. CONCLUSION: The radiomics on the conventional MRI can help predict the neurodevelopment of school-aged children and provide parents with rehabilitation advice as early as possible.

The Effect of Abnormal Regional Homogeneity and Spontaneous Low-Frequency Brain Activity on Lower Cognitive Ability: A Cross-Sectional Study on Postoperative Children With Tetralogy of Fallot.

Despite intracardiac malformation correction, children with Tetralogy of Fallot (TOF) may still suffer from brain injury. This cross-sectional study was primarily designed to determine the relationship between blood oxygenation level-dependent (BOLD) signal changes after surgery and cognition in school-aged children with TOF. To evaluate the differences between TOF children (n = 9) and healthy children (n = 9), resting-state functional magnetic resonance imaging (rs-fMRI) and the Wechsler Intelligence Scale for Children-Chinese revised edition (WISC-CR) were conducted in this study. The results showed that TOF children had a lower full-scale intelligence quotient (FSIQ, 95.444 ± 5.354, p = 0.022) and verbal intelligence quotient (VIQ, 92.444 ± 4.708, p = 0.003) than healthy children (FSIQ = 118.500 ± 4.330;VIQ = 124.250 ± 4.404), and that significant differences in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) existed between the two groups. Besides, VIQ had significantly positive correlations with the decreased ALFF value of the middle inferior occipital gyrus (MIOG, beta = 0.908, p = 0.012) after fully adjusting for all covariates. In addition, elevated ReHo values of the left and right precuneus were positively related to ALFF in the MIOG. This study revealed that brain injury substantially influences neural activity and cognition in postoperative TOF children, providing direct evidence of an association between BOLD signal changes and the VIQ and prompting further attention to language development in TOF children.

Effects of Exercise Training in Postoperative Patients With Congenital Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background The purpose of this meta-analysis is to assess the effects of exercise training on quality of life, specific biomarkers, exercise capacity, and vascular function in congenital heart disease (CHD) subjects after surgery. Methods and Results We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from the date of the inception of the database through April 2019. Altogether, 1161 records were identified in the literature search. Studies evaluating outcomes before and after exercise training among postoperative patients with congenital heart disease were included. The assessed outcomes were exercise capacity, vascular function, serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and quality of life. We analyzed heterogeneity by using the I2 statistic and evaluated the evidence quality according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Nine randomized controlled trials were included. The evidence indicated that exercise interventions increased the one of the quality of life questionnaire score (mean difference=3.19 [95% CI, 0.23, 6.16]; P=0.03; I2=39%) from the score before the interventions. However, no alterations in exercise capacity, vascular function, NT-proBNP or quality of life were observed after exercise training. The results of the subgroup analysis showed that NT-proBNP levels were lower in the group with exercise training than in the group without exercise training over the same duration of follow-up. The evidence quality was generally assessed to be low. Conclusions In conclusion, there is insufficient evidence to suggest that physical exercise improves long-term follow-up outcomes of congenital heart disease, although it has some minor effects on quality of life.

Associations between lead concentrations and cardiovascular risk factors in U.S. adolescents.

Little is known regarding the effects of environmental lead exposure on cardiovascular risk factors in the adolescent population. We studied 11,662 subjects included in the National Health and Nutrition Examination Survey (NHANES) 1999-2012. Blood lead levels were analysed for their association with cardiovascular risk factors (CVRF). Regression coefficients (Beta) and 95% confidence intervals (CIs) of blood lead in association with CVRF (e.g., total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure) were estimated using multivariate and generalized linear regression after adjusting for age, gender, ethnicity, serum cotinine, body mass index (BMI), physical activity, and household income. We identified a strong positive association between blood lead (coefficient = 0.022, 95% CI 0.003, 0.041; P = 0.022) and LDL-cholesterol in adolescents (age 12-19 years). However, no associations with other CVRFs were found in the overall population. In the generalized linear models, participants with the highest lead levels demonstrated a 1.87% (95% CI 0.73%, 3.02%) greater increase in serum LDL-cholesterol (p for trend = 0.031) when compared to participants with the lowest lead levels. These results provide epidemiological evidence that low levels of blood lead are positively associated with LDL-cholesterol in the adolescent population.

Fluorescent cross-linked supramolecular polymers constructed from a novel self-complementary AABB-type heteromultitopic monomer.

A novel AABB-type heteromultitopic monomer (), having a self-complementary perpendicular structure, could solely self-assemble to fluorescent cross-linked supramolecular polymers. Interestingly, the supramolecular gel film shows a sensitive fluorescence change on exposure to acid and base vapor, endowing this system with a potential application in gas detection.

Evaluation of regulatory genetic variants in POU5F1 and risk of congenital heart disease in Han Chinese.

OCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%-5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10(-6)]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.

Association analysis identifies new risk loci for congenital heart disease in Chinese populations.

Our previous genome-wide association study (GWAS) identified two susceptibility loci for congenital heart disease (CHD) in Han Chinese. Here we identify additional loci by testing promising associations in an extended 3-stage validation consisting of 6,053 CHD cases and 7,410 controls. We find GW significant (P<5.0 × 10(-8)) evidence of 4 additional CHD susceptibility loci at 4q31.22 (rs1400558, upstream of EDNRA, Pall=1.63 × 10(-9)), 9p24.2 (rs7863990, close to SMARCA2, Pall=3.71 × 10(-14)), 12q24.13 (rs2433752, upstream of TBX3 and TBX5, Pall=1.04 × 10(-10)) and 20q12 (rs490514, in PTPRT, Pall=1.20 × 10(-13)). Moreover, the data from previous European GWAS supports that rs490514 is associated with the risk of CHD (P=3.40 × 10(-3)). These results enhance our understanding of CHD susceptibility.

Association of aminoacyl-tRNA synthetases gene polymorphisms with the risk of congenital heart disease in the Chinese Han population.

Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function in a versatile manner beyond translation. Eight core ARSs (EPRS, MRS, QRS, RRS, IRS, LRS, KRS, DRS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC).We hypothesize that the single-nucleotide polymorphisms (SNPs) of the eight core ARS coding genes might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study of 984 CHD cases and 2953 non-CHD controls in the Chinese Han population to evaluate the associations of 16 potentially functional SNPs within the eight ARS coding genes with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248 [G/A; odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.81-0.99; P = 3.81×10(-2)], rs2230301 [A/C; OR = 0.73, 95%CI = 0.60-0.90, P = 3.81×10(-2)], rs1061160 [G/A; OR = 1.18, 95%CI = 1.06-1.31; P = 3.53×10(-3)] and rs5030754 [G/A; OR = 1.39, 95%CI = 1.11-1.75; P = 4.47×10(-3)] of EPRS gene. After multiple comparisons, rs1061248 conferred no predisposition to CHD. Additionally, a combined analysis showed a significant dosage-response effect of CHD risk among individuals carrying the different number of risk alleles (Ptrend = 5.00×10(-4)). Compared with individuals with "0-2" risk allele, those carrying "3", "4" or "5 or more" risk alleles had a 0.97-, 1.25- or 1.38-fold increased risk of CHD, respectively. These findings indicate that genetic variants of the EPRS gene may influence the individual susceptibility to CHD in the Chinese Han population.

Replication of the 4p16 susceptibility locus in congenital heart disease in Han Chinese populations.

Congenital heart disease (CHD) is the most common form of congenital human birth anomalies and a leading cause of perinatal and infant mortality. Some studies including our published genome-wide association study (GWAS) of CHD have indicated that genetic variants may contribute to the risk of CHD. Recently, Cordell et al. published a GWAS of multiple CHD phenotypes in European Caucasians and identified 3 susceptibility loci (rs870142, rs16835979 and rs6824295) for ostium secundum atrial septal defect (ASD) at chromosome 4p16. However, whether these loci at 4p16 confer the predisposition to CHD in Chinese population is unclear. In the current study, we first analyzed the associations between these 3 single nucleotide polymorphisms (SNPs) at 4p16 and CHD risk by using our existing genome-wide scan data and found all of the 3 SNPs showed significant associations with ASD in the same direction as that observed in Cordell's study, but not with other subtypes- ventricular septal defect (VSD) and ASD combined VSD. As these 3 SNPs were in high linkage disequilibrium (LD) in Chinese population, we selected one SNP with the lowest P value in our GWAS scan (rs16835979) to perform a replication study with additional 1,709 CHD cases with multiple phenotypes and 1,962 controls. The significant association was also observed only within the ASD subgroup, which was heterogeneous from other disease groups. In combined GWAS and replication samples, the minor allele of rs16835979 remained significant association with the risk of ASD (OR = 1.22, 95% CI = 1.08-1.38, P = 0.001). Our findings suggest that susceptibility loci of ASD identified from Cordell's European GWAS are generalizable to Chinese population, and such investigation may provide new insights into the roles of genetic variants in the etiology of different CHD phenotypes.

Common variations in BMP4 confer genetic susceptibility to sporadic congenital heart disease in a Han Chinese population.

Congenital heart disease (CHD) is the most common birth defect in humans. The genetic causes of sporadic CHD remain largely unknown. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor-ß (TGF-ß) family, is required for normal heart development. Loss of BMP4 gene expression in mice is associated with septal defects, defective endocardial cushion remodeling, and abnormal semilunar valve formation. This study evaluated the contribution of single nucleotide polymorphisms (SNPs) in BMP4 to CHD susceptibility in a case-control study of 575 patients with CHD and 844 non-CHD control subjects in a Chinese population. The BMP4 SNP rs762642 was associated with CHD in an additive model (odds ratio [OR]add 1.22; 95 % confidence interval [CI] 1.04-1.43; P add = 0.02). Stratified analysis by CHD subtypes showed a significant association only between rs762642 and atrial septal defect (ORadd 1.33; 95 % CI 1.04-1.72; P add = 0.03) in the additive model. This study was the first to indicate that a common variant of BMP4 may contribute to susceptibility to sporadic CHD in a Chinese population.

Genetic variants at 10p11 confer risk of Tetralogy of Fallot in Chinese of Nanjing.

A recent genome-wide association study (GWAS) has identified a new subset of susceptibility loci of Tetralogy of Fallot (TOF), one form of cyanotic congenital heart disease (CHD), on chromosomes 10p11, 10p14, 12q24, 13q31, 15q13 and 16q12 in Europeans. In the current study, we conducted a case-control study in a Chinese population including 1,010 CHD cases [atrial septal defect (ASD), ventricular septal defect (VSD) and TOF] and 1,962 controls to evaluate the associations of these loci with risk of CHD. We found that rs2228638 in NRP1 on 10p11 was significantly increased the risk of TOF (OR = 1.52, 95% CI = 1.13-2.04, P = 0.006), but not in other subgroups including ASD and VSD. In addition, no significant associations were observed between the other loci and the risk of ASD, VSD or TOF. Our results suggested that the genetic variants on 10p11 may serve as candidate markers for TOF susceptibility in Chinese population.