Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma.

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Trajectory of problematic internet use across the college years: The role of peer internet overuse behavior and peer attitude toward internet overuse.

INTRODUCTION: College students are at high risk of problematic internet use (PIU). A great amount of research has focused on the PIU among college students. However, little is known about the change pattern of PIU across the college years. Moreover, how peer internet overuse behavior and peer attitude toward internet overuse work together to shape college students' PIU trajectory, and whether such peer contagion effects are equal for all students remain unclear. The present study used latent growth curve model to examine these issues. METHODS: A total of 2572 Chinese college students (Mage = 18.37, SD = 0.85; 65% girls) participated in the study. They completed questionnaires regarding demographics, peer internet overuse behavior, peer attitude toward internet overuse, and friendship satisfaction at Wave 1, and PIU at Waves 1-4. RESULTS: After controlling for covariates, the findings revealed that (a) PIU slightly increased before the second year of college and then declined rapidly; (b) both peer internet overuse behavior and peer attitude toward internet overuse were related to the PIU at baseline; however, only peer internet overuse behavior was associated with the change of PIU; and (c) the effect of peer internet overuse behavior on PIU change was moderated by friendship satisfaction and gender. CONCLUSIONS: These findings emphasized the dynamic and context-sensitive nature of PIU and clarified how peer contagion unfolded with peer internet overuse behavior and peer attitude toward internet overuse. Theoretical implications and application of these findings are discussed.

A four-wave, cross-lagged model of problematic internet use and mental health among Chinese college students: Disaggregation of within-person and between-person effects.

Based on 4 annual waves of data from a large sample of Chinese college students (N = 2,329, Mage = 18.40 years old, SD = .85; 63.10% females), this study examines the within-person and between-person effects in the association between problematic Internet use (PIU) and mental health issues. Results of analyses using the developmental equilibrium model (i.e., an autoregressive, cross-lagged panel model) demonstrate a reciprocal positive association between PIU and mental health issues consistently across waves. In contrast, results of analyses utilizing the random intercept, cross-lagged panel model (i.e., a model that can disaggregate within-person and between-person effects) indicate a unidirectional positive within-person effect from PIU to mental health issues (rather than the reverse) consistently over time, while controlling for the between-person effects that exist when comparing different individuals. Such findings highlight the importance of disaggregating within-person and between-person effects in understanding the nature of the temporal dynamics of the association between PIU and mental health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Internet addiction, problematic internet use, nonproblematic internet use among Chinese adolescents: Individual, parental, peer, and sociodemographic correlates.

Internet addiction has been typically conceptualized as either a continuous construct or a dichotomous construct. Limited research has differentiated adolescents with problematic Internet use (PIU) from the Internet addiction group (IA) and/or nonproblematic Internet use group (NPIU) and examined the potential correlates. To fill this gap, based on data obtained from 956 Chinese adolescents (11-19 years, 47% male), this study examined if adolescents with PIU is a distinctive group from the IA and NPIU. This study also examined factors from different ecological levels that may differentiate among the three groups, including individual, parental, peer, and sociodemographic factors. Results indicated that IA, PIU, and NPIU differed significantly on scores of Young's Diagnostic Questionnaire (YDQ). Critical factors emerging from different ecological levels could differentiate between PIU and NPIU and between IA and NPIU. Such findings suggest that PIU may represent a distinct, intermediate group of Internet users. The potential theoretical and practical implications of identifying PIU were also discussed. (PsycINFO Database Record

Chinese college freshmen's mental health problems and their subsequent help-seeking behaviors: A cohort design (2005-2011).

Based on cohort data obtained from 13,085 college freshmen's (2005 to 2011) SCL-90 (the Symptom Check-List-90) reports and their subsequent 4-year psychological counseling help-seeking records, this study examined the association between college students' mental health problems and help-seeking behaviors across four college years. Female students' mental health problems and help-seeking behaviors increased from the 2005 to the 2011 cohorts and no changes emerged for male students across cohorts. Overall, male students reported higher levels of mental health problems than did female students in the first college year, whereas female students reported more help-seeking behaviors than did male students in the following four college years. College students' mental health problems was associated positively with help-seeking behaviors. College students were more likely to seek help from the college psychological counselling center when they experienced relatively few or quite a lot of mental health issues (i.e., an inversed U shape). Implications for future studies and practices are discussed.