A Computational Framework to Identify Biomarkers for Glioma Recurrence and Potential Drugs Targeting Them

Background: Recurrence is still a major obstacle to the successful treatment of gliomas. Understanding the underlying mechanisms of recurrence may help for developing new drugs to combat gliomas recurrence. This study provides a strategy to discover new drugs for recurrent gliomas based on drug perturbation induced gene expression changes.Methods: The RNA-seq data of 511 low grade gliomas primary tumor samples (LGG-P), 18 low grade gliomas recurrent tumor samples (LGG-R), 155 glioblastoma multiforme primary tumor samples (GBM-P), and 13 glioblastoma multiforme recurrent tumor samples (GBM-R) were downloaded from TCGA database. DESeq2, key driver analysis and weighted gene correlation network analysis (WGCNA) were conducted to identify differentially expressed genes (DEGs), key driver genes and coexpression networks between LGG-P vs LGG-R, GBM-P vs GBM-R pairs. Then, the CREEDS database was used to find potential drugs that could reverse the DEGs and key drivers.Results: We identified 75 upregulated and 130 downregulated genes between LGG-P and LGG-R samples, which were mainly enriched in human papillomavirus (HPV) infection, PI3K-Akt signaling pathway, Wnt signaling pathway, and ECM-receptor interaction. A total of 262 key driver genes were obtained with frizzled class receptor 8 (FZD8), guanine nucleotide-binding protein subunit gamma-12 (GNG12), and G protein subunit β2 (GNB2) as the top hub genes. By screening the CREEDS database, we got 4 drugs (Paclitaxel, 6-benzyladenine, Erlotinib, Cidofovir) that could downregulate the expression of up-regulated genes and 5 drugs (Fenofibrate, Oxaliplatin, Bilirubin, Nutlins, Valproic acid) that could upregulate the expression of down-regulated genes. These drugs may have a potential in combating recurrence of gliomas.Conclusion: We proposed a time-saving strategy based on drug perturbation induced gene expression changes to find new drugs that may have a potential to treat recurrent gliomas.

Demonstration of targeted crossovers in hybrid maize using CRISPR technology

Naturally occurring chromosomal crossovers (CO) during meiosis are a key driver of genetic diversity. The ability to target CO at specific allelic loci in hybrid plants would provide an advantage to the plant breeding process by facilitating trait introgression, and potentially increasing the rate of genetic gain. We present the first demonstration of targeted CO in hybrid maize utilizing the CRISPR Cas12a system. Our experiments showed that stable and heritable targeted CO can be produced in F1 somatic cells using Cas12a at a significantly higher rate than the natural CO in the same interval. Molecular characterization of the recombinant plants demonstrated that the targeted CO were driven by the non-homologous end joining (NHEJ) or HDR repair pathways, presumably during the mitotic cell cycle. These results are a step towards the use of RNA-guided nuclease technology to simplify the creation of targeted genome combinations in progeny and accelerate breeding.

Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. In early stages of AD, increased concentration of soluble CSF p-tau was the main driver of accumulation of insoluble tau aggregates across the brain, and mediated the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations were mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations were associated with cognitive decline, which was mediated by faster increase of tau aggregates. In AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline was driven by the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD.

Equipping Property Graduates for the Digital Age

Bridging the gaps between property graduates’ attributes and industry expectations has been touted to be the key driver of sustainable development for the next generation of the workforce. This study investigated property-related knowledge and skills from the perspective of property employers and graduates in Australia in the digital age by (1) identifying the most and least important knowledge and skillsets in the property sector; (2) examining the strategies used to develop the required knowledge and skillsets; and (3) ascertaining if there are differences in the knowledge and skillsets perceived to be necessary between employers and graduates. A questionnaire survey was undertaken across property employers affiliated with the Royal Institution of Chartered Surveyors (RICS) and graduates of an Australian university. The results showed that problem solving and time management are the most important knowledge and skills for property employers and graduates, respectively. Notably, there were statistically significant differences in the perceived importance of course directors maintaining close communication with employers, real-life case study-based school assessment, the use of various course delivery methods, inviting guest speakers, and internship training while studying between employers and graduates. This finding implies that Australian property professionals are yet to fully embrace technology in the digital age.

Creativity in the South Korean Workplace: Procedural Justice, Abusive Supervision, and Competence

Innovation is now a feature of daily life. In a rapidly changing market environment and amid fierce competition, organizations pursue survival and growth through innovation, and the key driver of innovation is the creativity of employees. Because the value of creativity has been emphasized, many organizations are looking for effective ways to encourage employees to be creative at work. From a resource perspective, creativity at work can be viewed as a high-intensity job demand, and organizations should encourage it by providing and managing employee resources. This study is an attempt to empirically investigate how competence and abusive supervision affect the relationship between procedural justice and creativity from the conservation of resources perspective. Findings from two-wave time-lagged survey data from 377 South Korean employees indicate that procedural justice increases creativity through the mediation of competence. Furthermore, abusive supervision has a negative moderating effect on the relationship between procedural justice and competence. The findings show that competence moderates the relationship between procedural justice and creativity and that the lower the level of abusive supervision, the greater the effect of procedural justice on competence and creativity.

A Private Tree By-Law’s Contribution to Maintaining a Diverse Urban Forest: Exploring Homeowners’ Replanting Compliance and the Role of Construction Activities in Toronto, Canada

Many municipalities are working to protect and grow their urban forest, including adopting private tree regulations. Such regulations typically require property-owners to apply for a permit to remove trees and, if the permit is granted, plant replacement trees. Even with such regulations, many private trees are removed each year, particularly on residential property. Property-level construction activity, including expanding building footprints, replacing an older home with a new one, and increasing hardscaping, is emerging as a key driver of residential tree loss. This study addresses whether homeowners who receive a permit to remove one or more trees comply with the requirement to plant replacement trees to better understand the effect of private tree regulation. We explore this question through a written survey of homeowners who received a tree removal permit and site visits in Toronto (Ontario, Canada). While 70% of all survey participants planted the required replacement trees 2 to 3 years after receiving the permit, only 54% of homeowners whose permit was associated with construction planted. Additionally, most replacement trees were in good health but were dominated by a few genera. We also found significant differences in replacement planting and tree survival across the city’s 4 management districts. This study highlights that if resources supporting private tree regulations are limited, tree permits associated with construction should be prioritized for follow-up. Additionally, guidance about diverse species to plant should be communicated to ensure that private tree regulations are supporting the long-term protection of the urban forest.

Opportunities to prevent and manage undernutrition to amplify efforts to end TB

The bidirectional relationship between TB and nutrition is well recognized – primary undernutrition is a risk factor for developing TB disease, while TB results in wasting. Although nutrition support is acknowledged as an important intervention in TB programmes, it is seldom afforded commensurate priority for action. TB incidence and deaths worldwide are falling too slowly to meet WHO End TB Strategy milestones, and the number of undernourished people is increasing, likely to be further exacerbated by the ongoing COVID-19 pandemic. Undernutrition needs to be more urgently and intensively addressed. This is especially true for the WHO South-East Asia Region, where the high rates of undernutrition are a key driver of the TB epidemic. The evidence base has been sufficiently robust for clear and workable programmatic guidance to be formulated on assessment, counselling and interventions for TB patients. Many high-burden countries have developed policies addressing TB and nutrition. Gaps in research to date have frustrated the development of more refined programmatic approaches related to addressing TB and malnutrition. Future research can be shaped to inform targeted, actionable policies and programmes delivering dual benefits in terms of undernutrition and TB. There are clear opportunities for policy-makers to amplify efforts to end TB by addressing undernutrition.

Examine the Factors Influencing Effectiveness of HRM Practices Designed to Improve Knowledge Transfer

Software development companies are noted for their innovative IT products. This is due to the focus on knowledge as a key driver for the innovations. Knowledge is a key element to all human resources. The purpose of this research is to investigate the factors influencing the effectiveness of HRM practices designed to improve knowledge transfer within software companies. A theoretical model was developed and empirically tested to test the hypothesis. Software companies were chosen in Sri Lanka with their professionals acting as respondents to survey. A sample includes 203 employees of Sri Lankan software companies. The results show that the order of importance of the HRM practices tested here is selection and recruitment, training and development, performance appraisal, and reward and compensation. The results also indicate that selection and recruitment, training and development, performance appraisal, and reward and compensation showed a positive impact with knowledge transfer improvement, as perceived by the professionals in the Sri Lankan software industry.

Analyzing and Forecasting Tourism Demand in Vietnam with Artificial Neural Networks

Vietnam has experienced a tourism expansion over the last decade, proving itself as one of the top tourist destinations in Southeast Asia. The country received more than 18 million international tourists in 2019, compared to only 1.5 million twenty-five years ago. Tourist spending has translated into rising employment and incomes for Vietnam’s tourism sector, making it the key driver to the socio-economic development of the country. Following the COVID-19 pandemic, only 3.8 million international tourists visited Vietnam in 2020, plummeting by 78.7% year-on-year. The latest outbreak in early summer 2021 made the sector continue to hit bottom. Although Vietnam’s tourism has suffered extreme losses, once the contagion is under control worldwide, the number of international tourists to Vietnam is expected to rise again to reach pre-pandemic levels in the next few years. First, the paper aims to provide a summary of Vietnam’s tourism characteristics with a special focus on international tourists. Next, the predictive capability of artificial neural network (ANN) methodology is examined with the datasets of international tourists to Vietnam from 2008 to 2020. Some ANN architectures are experimented with to predict the monthly number of international tourists to the country, including some lockdown periods due to the COVID-19 pandemic. The results show that, with the correct selection of ANN architectures and data from the previous 12 months, the best ANN models can be forecast for next month with a MAPE between 7.9% and 9.2%. As the method proves its forecasting accuracy, it would serve as a valuable tool for Vietnam’s policymakers and firm managers to make better investment and strategic decisions.