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Abstract Background Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. Methods We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. Results In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P

Abstract Background This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school. Methods The study included 38 adolescents (12–18 years old) who were not attending school and 35 healthy controls (12–18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence. Results Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR)

Abstract Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC. Results It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend

Abstract Background Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis‐related genes on survival in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HBV‐HCC) patients remains unknown. Methods We used two‐stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis‐related genes and overall survival (OS) of 866 HBV‐HCC patients. Results We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV‐HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67–0.89, p

BackgroundAlthough the sphingolipid metabolism pathway is known to play a significant role in tumor progression, there have been few studies on how genetic variants in the sphingolipid metabolism pathway genes affect the survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).MethodsWe utilized available genotyping data to conduct multivariate Cox proportional hazards regression model analysis, examining the associations of 12,188 single nucleotide polymorphisms (SNPs) in 86 sphingolipid metabolism pathway genes on the survival of 866 HBV-HCC patients, and the model was also used in additive interaction analysis. We used bioinformatics functional prediction and expression quantitative trait locus (eQTL) analysis to explore the potential functions of SNPs and to evaluate the association of SNPs with the corresponding mRNA expression, respectively. We also used the online database TIMER2.0 (http://timer.comp-genomics.org/) to analyze the relationship between the corresponding mRNA expression levels and immune cell infiltration.ResultsOur study found that GBA2 rs1570247 G>A was significantly associated with elevated survival of HBV-HCC patients [(hazards ratio (HR)=0.74, 95% confidence interval (CI)=0.64-0.86, PA in sphingolipid metabolism pathway may be a key factor for survival of HBV-HCC patients by regulating the expression of corresponding genes and affecting the infiltration level of immune cells.

BackgroundNon-suicidal self-injury (NSSI) is common in adolescent MDD, which is also a risk factor for suicide. However, there is few research on biomarkers and predictors about treatment response of NSSI. The purpose of this study was to find the difference of P300 between adolescent MDD with NSSI and healthy controls, and to explore whether the baseline electrophysiological level can predict the change of NSSI after treatment.MethodsWe collected 62 first-episode drug-naïve MDD adolescents with NSSI (MDD with NSSI group) and 44 healthy controls (HC group). The demographic data, HAMD score, self-injury frequency and electrophysiological level of NSSI group and HC group were collected. The HAMD score, frequency of NSSI in was also collected after 8 weeks of antidepressant treatment.ResultsCompared to HC, the latency of the N2, P3a, and P3b components were significantly prolonged, whereas the amplitude of P3a and P3b were decreased in the MDD with NSSI group (P < 0.001). The frequency of self-injury decreased significantly after treatment (P < 0.001). Regression analysis showed that the amplitudes of P3b had a significant positive predictive effect on the rate of change of NSSI frequency after 8 weeks.ConclusionP3b at baseline can be used as potential predictor for the reduction of NSSI in adolescent MDD.

BackgroundThe NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs.MethodsWe used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival.ResultsA total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (PA) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively.ConclusionOur study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression.

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P

Abstract MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07–2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04–3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09–2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03–3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.

Background: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. Methods: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosisrelated genes and overall survival (OS) of 866 HBV-HCC patients. Results: We identified that two potentially functional SNPs (CREB3 rs10814274 C>T and GALNT14 rs17010547 T>C) were significantly independently associated with the OS of HBV-HCC patients (CT+TT verse CC, hazards ratio (HR)=0.77, 95% confidence interval (CI)=0.67–0.89, p<0.001 for rs10814274 and TC+CC verse TT, HR=0.66, 95% CI=0.53–0.82, p<0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1–2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR=0.56, 95% CI=0.45– 0.70, p<0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. Conclusion: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The NF-kB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NFkB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs. Methods: We used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-kB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival. Results: A total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (P<0.05, BFDP<0.8). Further eQTL analysis demonstrated that significant correlations between the rs2074292 (G>A) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95% CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively. Conclusion: Our study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression. [ABSTRACT FROM AUTHOR]

Activation of a single incomplete P element induces recombination at a rate of ∼0.5–1% in the male germline of Drosophila. Male recombination rises by an order of magnitude to ∼20% if homologous P elements are involved. The high rate of recombination suggests the possibility that sister-chromatid exchange (SCE) might be elevated to a similar extent, since homologous Pelements must always be present in sister chromatids. This possibility was tested by recombining a single P element onto a ring-X chromosome and using sex-ratio distortion to measure the loss of the ring-X due to SCE in the male germline. The results confirmed a rate of loss comparable to that expected with homologous elements, although the rate of loss was variable. Both SCE and recombination results are consistent with the ‘hybrid element insertion’ model, in which the left and right ends from different elements associate, providing that insertion occurs preferentially in the vicinity of a P-element end. For autosomes, hybrid element formation may thus occur at a much higher rate than the 0.5–1% implied by single element recombination, with only a small minority of hybrid element excision events being resolved by recombination. [ABSTRACT FROM AUTHOR]

In order to determine the location and type of rice chalkiness accurately, image processing techniques were adopted to process acquired rice kernel images. Connected rice kernels were separated from each other using a convex point matching method. Chalkiness was extracted according to the differences in grayscale levels between chalky and normal regions in the rice kernel and chalky rice kernels were classified by a support vector machine (SVM). The results showed that 2-5 connected rice kernels could be separated accurately using this method and chalky areas could be extracted. The classification accuracy for indica rice and japonica rice reached 98.5% and 97.6%, respectively, by using SVM. Hence, the measurement results are accurate and reliable, and the presented work provides a theoretical and practical basis for the further application of computer vision technology to chalkiness detection. [ABSTRACT FROM AUTHOR]