Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus

BACKGROUND: Meningiomas are the most common intracranial neoplasias, representing a clinically and histopathologically heterogeneous group of tumors. The neurofibromatosis type 2 (NF2) tumor suppressor is the only gene known to be frequently involved in early development of meningiomas. The objective of this study was to identify genetic and/or epigenetic factors contributing to the development of these tumors. A large set of sporadic meningiomas were analyzed for presence of 22q macro-mutations using array-CGH in order to identify tumors carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also comprehensively studied for point mutations within coding and conserved non-coding sequences. Furthermore, CpG methylation within the NF2 promoter region was thoroughly analyzed. RESULTS: Monosomy 22 was the predominant finding, detected in 47% of meningiomas. Thirteen percent of the tumors contained interstitial/terminal deletions and gains, present singly or in combinations. We defined at least two minimal overlapping regions outside the NF2 locus that are small enough (~550 kb and ~250 kb) to allow analysis of a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations could be identified in 35% (17 out of 49) of tumors. Furthermore, the majority of tumors (9 out of 12) with interstitial/terminal deletions did not have any detectable NF2 mutations. Methylation within the NF2 promoter region was only identified at a single CpG site in one tumor sample. CONCLUSION: We confirmed previous findings of pronounced differences in mutation frequency between different histopathological subtypes. There is a higher frequency of biallelic NF2 inactivation in fibroblastic (52%) compared to meningothelial (18%) tumors. The presence of macro-mutations on 22q also shows marked differences between fibroblastic (86%) and meningothelial (39%) subtypes. Thus, inactivation of NF2, often combined with the presence of macro-mutation on 22q, is likely not as important for the development of the meningothelial subtype, as opposed to the fibroblastic form. Analysis of 40 CpG sites distributed within 750 bp of the promoter region suggests that NF2 promoter methylation does not play a major role in meningioma development

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

First Community-Wide, Comparative Cross-Linking Mass Spectrometry Study

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats. Such consensus formats should become accepted in the field and be shown to lead to reproducible results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. Our study therefore builds the framework for establishing best practice guidelines to conduct cross-linking experiments, perform data analysis, and define reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results

My Brother's Teacher? Siblings and Literacy Development in the Home

Frequency of sibling literacy interactions were examined in 134 families with at least two children, where at least one of the children attended school in grade one to grade four. Parents in the majority of families reported that their children read together on a regular basis without a parent present. This held across various demographic constellations including gender of the older child. However, children from families with three or more children were less likely to read with their siblings. Implications for parents and teachers are discussed

My brother's teacher?: Literacy development and sibling relationships in the home

Frequency of sibling literacy interactions were examined in 134 families with at least two children, where at least one of the children attended school in grade one to grade four. Parents in the majority of families reported that their children read together on a regular basis without a parent present. This held across various demographic constellations including gender of the older child. However, children from families with three or more children were less likely to read with their siblings. Implications for parents and teachers are discussed.https://new.hindawi.com/journals/edri/2011/253896

Challenges in the Accurate Surveillance of Booster Seat and Bicycle Helmet Usage by Children: Lessons from the Field

Motor vehicle collisions and bicycle collisions and falls are a leading cause of death by preventable injury for children. In order to design, implement and evaluate campaigns and programs aimed at improving child safety, accurate surveillance is needed. This paper examined the challenges that confront efforts to collect surveillance data relevant to child traffic safety, including observation, interview, and focus group methods. Strategies to address key challenges in order to improve the efficiency and accuracy of surveillance methods were recommended. The potential for new technology to enhance existing surveillance methods was also explored

Profiles of Adjustment in Children and Adolescents Exposed to Intimate Partner Violence: A Scoping Review Investigating Resilience Processes

Even though the negative sequelae of childhood exposure to intimate partner violence (IPV) have been largely established empirically, recent person-centered investigations have shown that young people who experience IPV at home represent a heterogeneous population including different subgroups of individuals with distinct profiles of adjustment. This comprehensive scoping review synthesizes and critically analyzes research on profiles of adjustment in children and adolescents exposed to IPV, with an emphasis on resilience profiles and the factors that promoted more positive outcomes. We searched for relevant research studies across five major bibliographic citation electronic databases, as well as reference lists of included articles, key printed journals, and the grey literature. A total of 13 research studies met our inclusion criteria and therefore were included in this scoping review. At least one “resilient profile” of adjustment was consistently identified across studies, which included between 13% and 67% of participants. Resilient profiles were typically characterized by the absence of adjustment problems and high functioning (e.g., high self-esteem, self-efficacy, and constructive problem-solving abilities) among children and adolescents exposed to IPV. All included studies also identified a number of individual-level, family-level, and environmental-level factors that were significantly associated with resilient adjustment among study participants. Based on the results of our review, we offered recommendations for practice, policy, and research

Linking a History of Childhood Abuse to Adult Health among Canadians: A Structural Equation Modelling Analysis

A history of childhood abuse has been linked to serious and long-lasting problems in adulthood. We developed two theoretical models concerning how early adverse experiences affect health in adulthood, and we tested the empirical fit of the two models in a population-based representative sample of Canadian adults (N = 25,113) using a structural equation modelling (SEM) technique, path analysis. The first model included direct pathways by which a history of three types of childhood abuse—exposure to intimate partner violence, physical abuse, and sexual abuse—affected adult physical and mental health, as well as indirect pathways by which perceived social support and everyday life stress acted as mediators of these associations. The second model included only indirect pathways and tested mediating effects. Global statistics indicated that both models were a good fit to the data, and local statistics supported the hypothesized associations between independent, dependent, and mediator variables

Validation of the German Normalisation Process Theory Measure G-NoMAD: translation, adaptation, and pilot testing

Abstract Background Implementing evidence-based healthcare practices (EBPs) is a complex endeavour and often lags behind research-informed decision processes. Understanding and systematically improving implementation using implementation theory can help bridge the gap between research findings and practice. This study aims to translate, pilot, and validate a German version of the English NoMAD questionnaire (G-NoMAD), an instrument derived from the Normalisation Process Theory, to explore the implementation of EBPs. Methods Survey data has been collected in four German research projects and subsequently combined into a validation data set. Two versions of the G-NoMAD existed, independently translated from the original English version by two research groups. A measurement invariance analysis was conducted, comparing latent scale structures between groups of respondents to both versions. After determining the baseline model, the questionnaire was tested for different degrees of invariance (configural, metric, scalar, and uniqueness) across samples. A confirmatory factor analysis for three models (a four-factor, a unidimensional, and a hierarchical model) was used to examine the theoretical structure of the G-NoMAD. Finally, psychometric results were discussed in a consensus meeting, and the final instructions, items, and scale format were consented to. Results A total of 539 health care professionals completed the questionnaire. The results of the measurement invariance analysis showed configural, partial metric, and partial scalar invariance indicating that the questionnaire versions are comparable. Internal consistency ranged from acceptable to good (0.79 ≤ α ≤ 0.85) per subscale. Both the four factor and the hierarchical model achieved a better fit than the unidimensional model, with indices from acceptable (SRMR = 0.08) to good (CFI = 0.97; TLI = 0.96). However, the RMSEA values were only close to acceptable (four-factor model: χ2164 = 1029.84, RMSEA = 0.10; hierarchical model: χ2166 = 1073.43, RMSEA = 0.10). Conclusions The G-NoMAD provides a reliable and promising tool to measure the degree of normalisation among individuals involved in implementation activities. Since the fit was similar in the four-factor and the hierarchical model, priority should be given to the practical relevance of the hierarchical model, including a total score and four subscale scores. The findings of this study support the further usage of the G-NoMAD in German implementation settings. Trial registration Both the AdAM project (No. NCT03430336, 06/02/2018) and the EU-project ImpleMentAll (No. NCT03652883, 29/08/2018) were registered on ClinicalTrials.gov. The ImplementIT study was registered at the German Clinical Trial Registration (No. DRKS00017078, 18/04/2019). The G-NoMAD validation study was registered at the Open Science Framework (No7u9ab, 17/04/2023)