456 research outputs found

    A model of online protection to reduce children's online risk exposure: empirical evidence from Asia

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    Children are surrounded by a variety of digital media and are exposed to potential risks that come with such easy accessibility. Learning how to be safe online is an important consideration for both children and their caregivers. The present study proposes an integrated model of online safety based on constructs from protection motivation theory and the health belief model, namely perceived severity of (and susceptibility to) risk, online self-efficacy, online privacy concern, and digital literacy. The study comprised a survey conducted among 420 schoolchildren aged 9–16 years. Using partial least squares-structural equation modelling, the results illustrated the presence of a negative effect of ‘perceived severity of online risk’ toward online risks, whereas the effect of ‘digital literacy’ was found to be positive. Children whose perception of online risks was more severe were less exposed to online risks if they had higher ‘online privacy concerns’ than the children with higher ‘digital literacy’ who are more exposed to online risk. Results of the study show that engaging in safe online behaviour requires children to have a high perception regarding severity of online risks as well as knowledge of online privacy concerns. Online risks and opportunities occur in parallel. Consequently, the factors that increase or decrease risk may also increase or decrease the benefits

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy

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    <p>Abstract</p> <p>Background</p> <p>Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few.</p> <p>Methods</p> <p>We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed.</p> <p>Results</p> <p>A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease.</p> <p>Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments.</p> <p>Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the103 patients. OS was significantly influenced by grade (<it>p </it>= .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (<it>p </it>= .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (<it>p </it>= .011).</p> <p>Conclusions</p> <p>OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted.</p

    Matrix Development in Self-Assembly of Articular Cartilage

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    Articular cartilage is a highly functional tissue which covers the ends of long bones and serves to ensure proper joint movement. A tissue engineering approach that recapitulates the developmental characteristics of articular cartilage can be used to examine the maturation and degeneration of cartilage and produce fully functional neotissue replacements for diseased tissue.This study examined the development of articular cartilage neotissue within a self-assembling process in two phases. In the first phase, articular cartilage constructs were examined at 1, 4, 7, 10, 14, 28, 42, and 56 days immunohistochemically, histologically, and through biochemical analysis for total collagen and glycosaminoglycan (GAG) content. Based on statistical changes in GAG and collagen levels, four time points from the first phase (7, 14, 28, and 56 days) were chosen to carry into the second phase, where the constructs were studied in terms of their mechanical characteristics, relative amounts of collagen types II and VI, and specific GAG types (chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and hyaluronan). Collagen type VI was present in initial abundance and then localized to a pericellular distribution at 4 wks. N-cadherin activity also spiked at early stages of neotissue development, suggesting that self-assembly is mediated through a minimization of free energy. The percentage of collagen type II to total collagen significantly increased over time, while the proportion of collagen type VI to total collagen decreased between 1 and 2 wks. The chondroitin 6- to 4- sulfate ratio decreased steadily during construct maturation. In addition, the compressive properties reached a plateau and tensile characteristics peaked at 4 wks.The indices of cartilage formation examined in this study suggest that tissue maturation in self-assembled articular cartilage mirrors known developmental processes for native tissue. In terms of tissue engineering, it is suggested that exogenous stimulation may be necessary after 4 wks to further augment the functionality of developing constructs

    The Increase in Balloon Size to Over 15 mm Does Not Affect the Development of Pancreatitis After Endoscopic Papillary Large Balloon Dilatation for Bile Duct Stone Removal

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    BACKGROUND: Endoscopic papillary large balloon dilatation (EPLBD) after endoscopic sphincterotomy (EST) has recently become widely used for common bile duct (CBD) stone removal, but many clinicians remain concerned about post-procedural pancreatitis with increasing the balloon size to over 15 mm. AIMS: We aimed to evaluate the safety and efficacy of EPLBD with a relatively large balloon (15-20 mm) after EST and to evaluate the factors related to post-EPLBD pancreatitis. METHODS: A retrospective review was undertaken of the endoscopic database of 101 patients with CBD stones who underwent EPLBD using a larger balloon size of over 15 mm (15-20 mm). Clinical parameters, endoscopic data, and outcomes were analyzed. RESULTS: The mean age of the subjects was 69 years. All patients had a dilated CBD of over 11 mm (mean = 22.6 mm). The mean size of balloon used in EPLBD was 17.1 ± 1.9 mm (range 15-20 mm). Mechanical lithotripsy was required in seven patients (6.9%). The rate of complete stone removal in the first session was 92.1%. Post-procedural pancreatitis developed in five cases (5.4%), but none were graded as severe. The smaller dilatation of the CBD, longer cannulation time, and longer time for stone removal were associated with post-procedural pancreatitis, but larger size of balloon did not affect the development of post-EPLBD pancreatitis. CONCLUSIONS: EPLBD with a large balloon of over 15 mm with EST is an effective and safe procedure with a very low probability of severe post-procedural pancreatitis. Post-EPLBD pancreatitis was not associated with larger balloon size, but was associated with longer procedure time and smaller dilatation of the CBD.ope

    Automatic prediction of catalytic residues by modeling residue structural neighborhood

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    Background: Prediction of catalytic residues is a major step in characterizing the function of enzymes. In its simpler formulation, the problem can be cast into a binary classification task at the residue level, by predicting whether the residue is directly involved in the catalytic process. The task is quite hard also when structural information is available, due to the rather wide range of roles a functional residue can play and to the large imbalance between the number of catalytic and non-catalytic residues.Results: We developed an effective representation of structural information by modeling spherical regions around candidate residues, and extracting statistics on the properties of their content such as physico-chemical properties, atomic density, flexibility, presence of water molecules. We trained an SVM classifier combining our features with sequence-based information and previously developed 3D features, and compared its performance with the most recent state-of-the-art approaches on different benchmark datasets. We further analyzed the discriminant power of the information provided by the presence of heterogens in the residue neighborhood.Conclusions: Our structure-based method achieves consistent improvements on all tested datasets over both sequence-based and structure-based state-of-the-art approaches. Structural neighborhood information is shown to be responsible for such results, and predicting the presence of nearby heterogens seems to be a promising direction for further improvements.Journal ArticleResearch Support, N.I.H. Extramuralinfo:eu-repo/semantics/publishe

    Global Developmental Gene Expression and Pathway Analysis of Normal Brain Development and Mouse Models of Human Neuronal Migration Defects

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    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases

    Clinicopathological characteristics and treatment strategies in early gastric cancer: a retrospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Both endoscopic and surgical approaches are employed in the treatment of early gastric cancer (EGC). The aim of this study was to establish appropriate treatment strategies for early gastric cancer.</p> <p>Methods</p> <p>We retrospectively examined clinicopathological data of EGC patients who had undergone surgery.</p> <p>Results</p> <p>A total of 327 patients (204 males and 123 females, mean age 63.2 years) were eligible for inclusion in the study. The median follow-up period was 31 months. Of 161 mucosal (pT1a) tumors, 87 were mainly undifferentiated and 110 had an undifferentiated component. Four patients with pT1a tumors had lymph node metastases; all these tumors were signet-ring cell carcinomas and were macroscopic type 0-IIc with ulceration, and only one of them had lymphatic invasion. Among patients with submucosal tumors, four of 43 patients with pT1b1 tumors and 37 of 123 patients with pT1b2 tumors had nodal metastases. Lymph node metastases were significantly higher in mixed undifferentiated type group than differentiated type group for both groups, pT1a-pT1b1 (p = 0.0251) and pT1b2 (p = 0.0430) subgroups. Only four of 45 patients with nodal metastases were diagnosed preoperatively by computed tomography (sensitivity 8.9%, specificity 96.2%). Nine patients with pT1b tumors had recurrence after surgery, and died. The sites of initial recurrence were liver, bone, peritoneum, distant nodes, and the surgical anastomosis.</p> <p>Conclusions</p> <p>The incidence of nodal metastases was approximately 5% in undifferentiated type mucosal (pT1a) tumors, and higher in submucosal (pT1b) tumors. The sensitivity of preoperative diagnosis of nodal metastases in EGC using computed tomography was relatively low in this study. Therefore at present surgery with adequate lymphadenectomy should be performed as curative treatment for undifferentiated type EGC.</p

    Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: Which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study

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    <p>Abstract</p> <p>Background</p> <p>There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC). The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT) alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection.</p> <p>Methods</p> <p>We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital.</p> <p>Results</p> <p>Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS) rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04), respectively, and 3-year overall survival (OS) rates were 30.8% and 62.6% (p < 0.01), respectively. CCRT followed by adjuvant chemotherapy showed longer survival than did CCRT alone, especially in R1 resection (microscopically positive margins) or negative lymph node.</p> <p>Conclusion</p> <p>Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.</p
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