Chuhsing Kate Hsiao

Schizotypy in community samples : The three-factor structure and correlation with sustained attention

The authors examined cross-cultural applicability of the Schizotypal Personality Questionnaire (SPQ), the Perceptual Aberration Scale (PAS), and the Continuous Performance Test in community samples of Taiwanese adults and adolescents. The authors tested hypotheses that a 3-factor structure of the SPQ (Cognitive-Perceptual, Interpersonal, and Disorganization: A. Raine et al., 1994) exists for both samples and that the Interpersonal factor is associated with poorer attention. The authors replicated the 3-factor model for both samples, and they externally validated the model in adults: The Interpersonal factor and possibly the Disorganization factor were associated with poorer attention, whereas the Cognitive-Perceptual factor was not. The PAS differed from the Cognitive-Perceptual factor in its consistent association with poorer attention in both samples. These have important implications for the scales in the early detection of the schizotypy in various cultures.

Changes in Serum Levels of HBV DNA and Alanine Aminotransferase Determine Risk for Hepatocellular Carcinoma

BACKGROUND & AIMS It is not clear whether risk for hepatocellular carcinoma can be accurately determined from long-term changes in serum levels of hepatitis B virus (HBV) DNA or alanine aminotransferase (ALT). METHODS We measured serum levels of HBV DNA and ALT at enrollment and during follow-up analysis of 3160 participants in the REVEAL-HBV study. Development of hepatocellular carcinoma was determined from follow-up examinations and computerized linkage with National Cancer Registry and National Death Certification profiles. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS During 38,330 person-years of follow-up, 81 participants developed hepatocellular carcinoma (incidence rate, 211.3/100,000 person-years). The risk for hepatocellular carcinoma was only slightly higher for participants whose follow-up levels of HBV DNA spontaneously decreased to <10,000 copies/mL compared with those with baseline levels of HBV DNA<10,000 copies/mL (control group; HR, 2.25; 95% CI, 0.68-7.37). Compared with the control group, the HRs (95% CI) for long-term levels of HBV DNA that persisted at 10,000 to 100,000 copies/mL, decreased to/persisted at 100,000 to 1,000,000 copies/mL, or decreased to/persisted at 1,000,000 to 10,000,000 copies/mL were 3.12 (1.09-8.89), 8.85 (3.85-20.35), and 16.78 (7.33-38.39), respectively. A gradient in ALT level was significantly associated with hepatocellular carcinoma risk: from all low-normal, to ever high-normal, to transient abnormal, to persistent abnormal (Ptrend<.001). CONCLUSIONS Long-term changes in serum levels of HBV DNA and ALT are independent predictors of risk for hepatocellular carcinoma. Regular monitoring of levels of HBV DNA and ALT is important in clinical management of chronic carriers of HBV.

miRSystem: An Integrated System for Characterizing Enriched Functions and Pathways of MicroRNA Targets

Background Many prediction tools for microRNA (miRNA) targets have been developed, but inconsistent predictions were observed across multiple algorithms, which can make further analysis difficult. Moreover, the nomenclature of human miRNAs changes rapidly. To address these issues, we developed a web-based system, miRSystem, for converting queried miRNAs to the latest annotation and predicting the function of miRNA by integrating miRNA target gene prediction and function/pathway analyses. Results First, queried miRNA IDs were converted to the latest annotated version to prevent potential conflicts resulting from multiple aliases. Next, by combining seven algorithms and two validated databases, potential gene targets of miRNAs and their functions were predicted based on the consistency across independent algorithms and observed/expected ratios. Lastly, five pathway databases were included to characterize the enriched pathways of target genes through bootstrap approaches. Based on the enriched pathways of target genes, the functions of queried miRNAs could be predicted. Conclusions MiRSystem is a user-friendly tool for predicting the target genes and their associated pathways for many miRNAs simultaneously. The web server and the documentation are freely available at http://mirsystem.cgm.ntu.edu.tw/.

Identification of a Novel Biomarker, SEMA5A, for Non–Small Cell Lung Carcinoma in Nonsmoking Women

Background: Although cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family. Methods: Sixty pairs of tumor and adjacent normal lung tissue specimens were analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially expressed genes in tumor tissues were identified by a paired t test and validated by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was conducted by using Ingenuity Pathway Analysis as well as gene set enrichment analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to evaluate the association of SEMA5A expression and clinical outcome. Results: We identified 687 differentially expressed genes in non–small cell lung carcinoma (NSCLC). Many of these genes, most notably the semaphorin family, were participants in the axon guidance signaling pathway. The downregulation of SEMA5A in tumor tissue, both at the transcriptional and translational levels, was associated with poor survival among nonsmoking women with NSCLC. Conclusions: In summary, several semaphorin gene family members were identified as potential therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for NSCLC, which may also be gender specific in Taiwanese patients. Impact: A novel biomarker for NSCLC is identified. Cancer Epidemiol Biomarkers Prev; 19(10); 2590–7. ©2010 AACR.

Development of sustained attention assessed using the Continuous Performance Test among children 6-15 years of age

The Continuous Performance Test (CPT) is a widely used measure of sustained attention, which may rely on the efficiency of cognitive inhibition. We examined the relationships of age and sex with CPT performance among 341 randomly selected school children 6–15 years of age. Multiple regression analyses revealed that the hit rate, false alarm rate, and sensitivity of both the undegraded and the degraded CPT were associated with age by a quadratic relationship. The age–development curves for the hit rate and sensitivity were convex, whereas that for the false alarm rate was concave. Sex was associated with the hit rate and sensitivity on the degraded CPT only. Our findings are consistent with the hypothesis that sustained attention develops during the primary school ages. The data reported are essential for identifying children with conditions associated with sustained attention deficit, such as attention-deficit hyperactivity disorder, as well as those at an increased risk for developing schizophrenia.

Regression-Based Association Analysis with Clustered Haplotypes through Use of Genotypes

Haplotype-based association analysis has been recognized as a tool with high resolution and potentially great power for identifying modest etiological effects of genes. However, in practice, its efficacy has not been as successfully reproduced as expected in theory. One primary cause is that such analysis tends to require a large number of parameters to capture the abundant haplotype varieties, and many of those are expended on rare haplotypes for which studies would have insufficient power to detect association even if it existed. To concentrate statistical power on more-relevant inferences, in this study, we developed a regression-based approach using clustered haplotypes to assess haplotype-phenotype association. Specifically, we generalized the probabilistic clustering methods of Tzeng to the generalized linear model (GLM) framework established by Schaid et al. The proposed method uses unphased genotypes and incorporates both phase uncertainty and clustering uncertainty. Its GLM framework allows adjustment of covariates and can model qualitative and quantitative traits. It can also evaluate the overall haplotype association or the individual haplotype effects. We applied the proposed approach to study the association between hypertriglyceridemia and the apolipoprotein A5 gene. Through simulation studies, we assessed the performance of the proposed approach and demonstrate its validity and power in testing for haplotype-trait association.

Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma

Background and aims The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk. Methods This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers. Results The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30–75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither. Conclusions Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.

Nonlinear Regression Analysis

Nonlinear regression analysis is a very popular technique in mathematical and social sciences as well as in engineering. In this article, we offer an introduction of theories and methods of nonlinear regression. Least-squares with Gauss–Newton method is the most widely used approach to parameters estimation. Under the normality assumption of errors, the least-squares estimates equal the maximum likelihood estimates. The predicted values of the responses can be biased because of the intrinsic nonlinearity of the model. Even if the degree of intrinsic nonlinearity is slight, the least-squares estimates of the parameters may still be hard to converge due to the parameter-effects nonlinearity. The intrinsic nonlinearity is invariant to reparametrization, while the parameter-effects nonlinearity can be corrected by a suitable reparametrization. We also discuss techniques from geometric viewpoints for estimation and inferences as well as for assessing their statistical properties.

Performance on the Wisconsin Card Sorting Test among adolescents in Taiwan: Norms, factorial structure, and relation to schizotypy

The aims of this study were to assess developmental trends in performance on the Wisconsin Card Sorting Test (WCST) among 817 randomly selected adolescents aged 13-15 years, and to explore WCST performance factor structure and relationship to schizotypy. The results showed that of the nine WCST indexes, only the Categories Achieved and Failure to Maintain Set scores were associated with age, and only the Learning to Learn scores reached adult levels. Factor analysis of WCST performance scores yielded a three-factor structure. Psychometrically defined schizotypic subjects did not perform significantly worse than control subjects on any WCST indexes. These findings suggest that performance on various WCST indexes might indicate developmental changes at different ages, and deficits in WCST performance might not be sensitive indicators of vulnerability to schizophrenia in adolescence.

First Untoward Events and Reasons for Tooth Extraction after Nonsurgical Endodontic Treatment in Taiwan

In this study, 857 teeth having undergone nonsurgical root canal treatment (NSRCT) in Taiwan in 2000 were evaluated during a 5-year follow-up period for first untoward events and reasons for tooth extractions. First untoward events occurred in 83 (9.7%) teeth during this follow-up period, and nonsurgical retreatment was performed for 20 (24.1%), 4 (4.8%) received apical surgery, and 59 (71.1%) were extracted. By the end of this 5-year follow-up period a total of 64 (7.5%) teeth had been extracted. There were 65 reasons for tooth extraction given by the 56 performing dentists who responded to the extraction reason questionnaires; 6 (10.7%) were attributed to endodontically related diseases, 15 (26.8%) to periodontal diseases, 26 (46.4%) to large decay or unrestorable tooth, and 18 (32.1%) to tooth fracture. The conclusion was that 7.5% of the NSRCT teeth were extracted by the end of the 5-year follow-up period, and only 10.7% of these teeth were extracted as a result of endodontically related diseases.