Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Localized targeted antiangiogenic drug delivery for glioblastoma

Systemic delivery of antiangiogenic agents has been ineffective in improving the overall survival of patients with both primary and recurrent glioblastoma, in part due to dose-limiting toxicities. With the development of new and efficient localized delivery methods and vehicles, an otherwise lethal dose of antiangiogenic chemotherapy can be used to treat tumors while minimizing systemic side effects. Current in-vitro and in-vivo animal studies have shown promising results that encourage the pursuit towards human clinical trials for localized antiangiogenic treatment in the near future

The pathogenesis of Chiari I malformation and syringomyelia

The pathogeneses of Chiari malformation type I and syringomyelia are incompletely understood. In this article, the authors attempt to review the current theories on the pathogeneses of Chiari I malformation and syringomyelia. A literature review for articles pertaining to Chiari I malformation or syringomyelia before August 2010 was conducted; in addition, the author's own experience in treating Chiari I malformation and syringomyelia is included. Chiari I malformation has been defined radiographically as cerebellar tonsillar herniation or ectopia 5 mm or greater below the foramen magnum. By this narrow definition, Chiari I malformation (i.e. cerebellar tonsillar herniation or ectopia 5 mm or greater below the foramen magnum) likely encompasses a heterogeneous grouping of disorders caused by different mechanisms. Molecular and genetic studies have been helpful in furthering our understanding of Chiari I malformation. A review of the pathogeneses of Chiari I malformation and syringomyelia is reported

Anticipating engagement: pre-service teachers' perceptions of virtual worlds

Engagement has become a significant driver in the choice of resources that teachers utilise at both university and K-12 level. Educators and governments recognise that increasingly, students are being pushed away from school due to a lack of engagement at a time when the need to have a skilled and educated society is ever more pressing. Information communication technologies (ICTs) are often used as a means to provide engagement. With the now ubiquitous presence of ICTs in classrooms, homes and workplaces, the need to develop high quality learning experiences with ICTs is increasingly apparent. Virtual worlds are an ICT that, when first encountered, offer what appears to be a highly engaging environment especially for young adults and children. Many virtual worlds have some level of game features such as multiple paths, user-level control, interaction, visuals, risk-taking, rules and goals (Baranauskas et al. 2001; Crookall et al. 1987; Gredler 1996). Malone (1980) suggests that there are four factors of games that contribute to the level of engagement; challenge, fantasy, complexity and control. However, for students at university, these features can possibly act as a motivator or as a deterrent. Most adult students have expectations about what they believe a learning experience should be. Due to the connection they make with games and having fun, games are not traditionally linked to serious learning