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This study investigated hepatitis B virus (HBV) single-nucleotide variants (SNVs) and deletion mutations linked with hepatocellular carcinoma (HCC). Ninety-three HCC patients and 108 non-HCC patients were enrolled for HBV genome-wide next-generation sequencing (NGS) analysis. A systematic literature review and a meta-analysis were performed to validate NGS-defined HCC-associated SNVs and deletions. The experimental results identified 60 NGS-defined HCC-associated SNVs, including 41 novel SNVs, and their pathogenic frequencies. Each SNV was specific for either genotype B (n = 24) or genotype C (n = 34), except for nt53C, which was present in both genotypes. The pathogenic frequencies of these HCC-associated SNVs showed a distinct U-shaped distribution pattern. According to the meta-analysis and literature review, 167 HBV variants from 109 publications were categorized into four levels (A-D) of supporting evidence that they are associated with HCC. The proportion of NGS-defined HCC-associated SNVs among these HBV variants declined significantly from 75% of 12 HCC-associated variants by meta-analysis (Level A) to 0% of 10 HCC-unassociated variants by meta-analysis (Level D) (P < 0.0001). PreS deletions were significantly associated with HCC, in terms of deletion index, for both genotypes B (P = 0.030) and C (P = 0.049). For genotype C, preS deletions involving a specific fragment (nt2977-3013) were significantly associated with HCC (HCC versus non-HCC, 6/34 versus 0/32, P = 0.025). Meta-analysis of preS deletions showed significant association with HCC (summary odds ratio 3.0; 95% confidence interval 2.3-3.9). Transfection of Huh7 cells showed that all of the five novel NGS-defined HCC-associated SNVs in the small surface region influenced hepatocarcinogenesis pathways, including endoplasmic reticulum-stress and DNA repair systems, as shown by microarray, real-time polymerase chain reaction and western blot analysis. Their carcinogenic mechanisms are worthy of further research. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

In educational measurement, the construction of parallel test forms is often a combinatorial optimization problem that involves the time-consuming selection of items to construct tests having approximately the same test information functions (TIFs) and constraints. This article proposes a novel method, genetic algorithm (GA), to construct parallel test forms effectively. The sum of squared errors of the generated TIFs produced by GA were compared with those of the Swanson and Stocking method, and the Wang and Ackerman method. Experimental results show that tests constructed using GA yielded lower error, and an average improvement ratio above 90%.

Both the viral titer and the genotype significantly determine clinical outcomes and responses to antiviral treatment in chronic hepatitis B virus (HBV) infection. A method was developed for large-scale A-to-G genotypingwith simultaneous viral quantification. The assay was run on a LightCycler instrument using hybridization probes. The genotype was determined from the melting points of the probes in a two-step manner. Set 1 amplicons differentiated genotypes B, E, and F from A, C, D, and G and simultaneously quantified viremia by real-time PCR. Melting curve analysis using the set 2-1 amplicon or the set 2-2 amplicon reaction mixture was then used to differentiate these genotype groups into single genotypes. HBV DNA quantification was consistent with that of the Amplicor assay and linear in a range from 10 2 to 10 13 copies/ml. By comparison with the restriction fragment length polymorphism method, 92.3% of 441 samples were accurately genotyped by the current assay. The method should be useful for genotyping and quantification of HBV DNA in areas where all genotypes exist.Hepatitis B virus (HBV) infection is an important public health problem chronically infecting more than 350 million people worldwide. The infection can cause acute and chronic liver disease, including cirrhosis and hepatocellular carcinoma. HBV has a circular genome of approximately 3,200 base pairs and is divided into genotypes A to H, with an intergenotypic diversity of at least 8% in the full genome sequence (1,10,12,13,17). The genotypes have distinct geographic distributions, and accumulating evidence indicates that genotyping is of clinical importance, because the genotypes correlate with the severity of liver disease. HBV genotype C is associated with more severe liver disease than genotype B (3, 5, 6), and patients infected with genotype B have a lower rate of positive hepatitis B virus e antigen (HBeAg) and 1 decade earlier spontaneous HBeAg seroconversion than genotype C-infected patients (14). Moreover, patients infected with genotypes C and D seem to have a lower response rate to alpha interferon than those infected with genotypes A and B (5), and the risk of emergence of lamivudine resistance-associated mutations has been reported to be higher in genotype A-infected patients than in genotype D-infected patients (2, 20).Several methods for genotyping HBV have been reported, including melting curve analysis (MCA) (16, 19), restriction fragment length polymorphism (RFLP) (7, 8), post-PCR hybridization or line probe assay (4), PCR with genotype-specific primers (9), and enzyme-linked immunosorbent assay-based methods (18). One genotyping method was shown to also quantitate HBV viremia (19), but that method was limited to distinguishing between genotypes B and C, which are prevalent in Asia. In this study, an efficient PCR-based method was developed to combine quantification of HBV DNA and genotyping with differentiation of HBV genotypes A to G. The results showed consistency with currently available viral-load quantification and efficie...

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The relative positions of the sun, moon, and earth, their movements, and their relationships are abstract and difficult to understand astronomical concepts in elementary school science. This study proposes a three-dimensional (3-D) virtual reality (VR) model named the Sun and Moon System. This e-learning resource was designed by combining Microsoft Direct3D Library, C++ programming language, and Autodesk 3 Ds Max for constructing models. This learning environment provides a way for teachers to integrate information and technology into their science teaching. Furthermore, this study explored how teaching with the Sun and Moon System affected 128 Taiwanese fourthgrade students' science achievement. Four classes were randomly divided into comparison and treatment groups. The results show that: (a) students in the treatment group achieved significantly better grades than those in the comparison group under traditional class instruction and (b) the questionnaire results revealed that more than two thirds of the treatment group liked to use the 3-D VR model and would like to introduce it to their classmates. Based on these positive results, we are encouraged to develop more 3-D VR learning environments.

Objectives: Eight genotypes (A–H) of hepatitis B virus (HBV) are known with variations in nucleotide sequences greater than 8%. Several recent publications found that the clinical course and outcome of antiviral therapy depended on the genotype of the infecting HBV strain. Large epidemiological studies will require the availability of a system which is rapid, reliable and can be performed on a large number of samples. Methods: To establish a simple and accurate genotyping method, the study collected 369 HBV complete genomic sequences from the GenBank database. Type-specific primers were also designed that separated HBV genotypes A to G by multiplex polymerase chain reaction. Results: By comparison with the traditional restriction fragment length polymorphism method, over 93% of 441 samples were accurately genotyped by current assay, with a higher detection rate and sensitivity to detect mixed HBV infections. Conclusions: This methodology can be applied only to areas prevalent with HBV genotypes A to G. However, it provides an efficient alternative for clinical diagnosis and large-scale studies.

Although digital media literacy is recognized as the essential competencies required for living in a new media age, it just starts to gain focus in Taiwan's elementary education. One of the reasons is examination-oriented education, with the result that diverts scarce resources away from this informal learning. The other reason is that educators tend to think digital media education as a series of purely technical operation, which might lead student digital media learning to mindless work. Therefore, this study designed a media exhibition based on Kolb's experiential learning model for teaching students concepts of stop-motion films and techniques of film production. A design experiment involved 247 third-grade elementary students that were grouped to visit the experiential exhibition. The findings suggest that the students have improved their knowledge of stop-motion films. Analysis of these produced films also shows that they have improved their media ability to represent their ideas and communicate with others. Through the analysis of the influence of demographics on the knowledge test, the findings revealed that the experiential exhibition is more effective for female elementary students and students' relevant previous experiences may not affect their acquired knowledge. Given those results and observations, we believe that the proposed experiential exhibition is a promising way to carry out digital media literacy education in elementary schools.Although digital media literacy is recognized as the essential competencies required for living in a new media age, it just starts to gain focus in Taiwan's elementary education. One of the reasons is examination-oriented education, with the result that diverts scarce resources away from this informal learning. The other reason is that educators tend to think digital media education as a series of purely technical operation, which might lead student digital media learning to mindless work. Therefore, this study designed a media exhibition based on Kolb's experiential learning model for teaching students concepts of stop-motion films and techniques of film production. A design experiment involved 247 third-grade elementary students that were grouped to visit the experiential exhibition. The findings suggest that the students have improved their knowledge of stop-motion films. Analysis of these produced films also shows that they have improved their media ability to represent their ideas and communicate with others. Through the analysis of the influence of demographics on the knowledge test, the findings revealed that the experiential exhibition is more effective for female elementary students and students' relevant previous experiences may not affect their acquired knowledge. Given those results and observations, we believe that the proposed experiential exhibition is a promising way to carry out digital media literacy education in elementary schools. A pesar de que la alfabetización digital en medios se reconoce como una de las competencias esenciales necesarias para vivir en una nueva era de los medios de comunicación, solo acaba de empezar a ganar atención en la educación primaria de Taiwán. Una de las razones es la educación orientada a los exámenes, y como consecuencia, el que se desvíe muy pocos recursos para este aprendizaje informal. La otra razón es que los educadores tienden a pensar en la educación en medios digitales como una serie de operaciones puramente técnicas, lo que podría llevar a los estudiantes de medios digitales a aprender a trabajar sin sentido. Por lo tanto, este estudio diseñó una exhibición de contenidos basada en el modelo de aprendizaje experiencial de Kolb con el fin de enseñar a los estudiantes conceptos de videos stop-motion y técnicas de producción cinematográfica. El experimento diseñado involucró a 247 estudiantes de tercer grado de primaria que fueron agrupados para visitar la exposición experiencial. Los hallazgos sugieren una mejora en los estudiantes de su conocimiento de videos stop-motion. El análisis de los vídeos producidos también muestra que han mejorado su capacidad mediática para representar sus ideas y comunicarse con los demás. A través del análisis de la influencia de la demografía en la prueba de conocimiento, los hallazgos revelan que la exposición experiencial es más efectiva para los estudiantes de primaria femeninos, y que las experiencias anteriores relevantes de los estudiantes no deberían afectar a los conocimientos adquiridos. Teniendo en cuenta estos resultados y observaciones, creemos que la exposición experimental propuesta es una forma prometedora de llevar a cabo la educación en alfabetización digital en las escuelas primarias.