The role of the PTEN tumor suppressor gene and its anti-angiogenic activity in melanoma and other cancers

Human malignant melanoma and other solid cancers are largely driven by the inactivation of tumor suppressor genes and angiogenesis. Conventional treatments for cancer (surgery, radiation therapy, and chemotherapy) are employed as first-line treatments for solid cancers but are often ineffective as monotherapies due to resistance and toxicity. Thus, targeted therapies, such as bevacizumab, which targets vascular endothelial growth factor, have been approved by the US Food and Drug Administration (FDA) as angiogenesis inhibitors. The downregulation of the tumor suppressor, phosphatase tensin homolog (PTEN), occurs in 30–40% of human malignant melanomas, thereby elucidating the importance of the upregulation of PTEN activity. Phosphatase tensin homolog (PTEN) is modulated at the transcriptional, translational, and post-translational levels and regulates key signaling pathways such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways, which also drive angiogenesis. This review discusses the inhibition of angiogenesis through the upregulation of PTEN and the inhibition of hypoxia-inducible factor 1 alpha (HIF-1-α) in human malignant melanoma, as no targeted therapies have been approved by the FDA for the inhibition of angiogenesis in human malignant melanoma. The emergence of nanocarrier formulations to enhance the pharmacokinetic profile of phytochemicals that upregulate PTEN activity and improve the upregulation of PTEN has also been discussed.https://www.mdpi.com/journal/moleculeshj2024Plant Production and Soil ScienceSDG-03:Good heatlh and well-bein

A hybrid convolutional neural network-transformer method for received signal strength indicator fingerprinting localization in long range wide area network

DATA AVAILABILTY : The dataset used in this work is a publicly available dataset.In recent years, low-power wide area networks (LPWANs), particularly Long-Range Wide Area Network (LoRaWAN) technology, are increasingly being adopted into large-scale Internet of Things (IoT) applications thanks to having the ability to offer cost-effective long-range wireless communication at low-power. The need to provide location-stamped communications to IoT applications for meaningful interpretation of physical measurements from IoT devices has increased demand to incorporate location estimation capabilities into LoRaWAN networks. Fingerprint-based localization methods are increasingly becoming popular in LoRaWAN networks because of their relatively high accuracy compared to range-based localization methods. This work proposes hybrid convolutional neural networks (CNNs)-transformer fingerprinting method to localize a node in a LoRaWAN network. CNNs are adopted to complement the strengths of the Transformer by adding the ability to capture local features from input data and consequently allow the Transformer, through the attention mechanism, to effectively learn global dependencies from the input data. Specifically, the proposed method works by first learning the local location features from the input data using the CNNs and passing the resulting information to the transformer encoder to learn global features from the input data. The output of the transformer encoder is then concatenated with information learned at the local level and then passed through the regressor for the final location estimation. With a localization performance of 290.71 m mean error achieved, the proposed method outperformed similar state-of-the-art works in the literature evaluated on the same publicly available LoRaWAN dataset.http://www.elsevier.com/locate/engappaihj2024Electrical, Electronic and Computer EngineeringSDG-09: Industry, innovation and infrastructur

Looking to the past to travel in the future : post pandemic tourism

Dissertation (MSocSci (Historical and Heritage Studies))--University of Pretoria, 2024.Considering the historical background of pandemics, global pandemics have played an enormous role in shaping the tourism landscape. This dissertation intends to improve understanding of the impact of pandemics on tourism by bringing together crisis responses from stakeholders in the 20th and 21st centuries. It examines historical pandemics from the Spanish influenza (1918), till COVID-19 (2019) to compare and identify policy effectiveness trends. Emphasis is placed on the importance of tourism in global economies and post-disaster recovery. In considering the global impact of pandemics on tourism international travel, especially nowadays, are severely restricted during pandemics. Tourism-dependent countries are concerned about these disturbances as it leads to a fall in international travel that exacerbated economic problems, especially in developing nations. The research adopts a forward-looking approach which tries to illuminate historical policy triumphs and failures to inform future efforts. It draws together aspects from policymakers and stakeholders and strives to build a more resilient and adaptable economy that emphasises a need for post-COVID-19 landscape analysis, particularly in severely affected countries. Various government interventions are looked at and conclusions are drawn from both successful and failing methods that could highlight key indicators to assist government with economic recovery. Finally, the research critiques government responses and suggests ways to improve them to help policymakers prepare for future crises and to make global tourism resilient and adaptable post-COVID-19.Historical and Heritage StudiesMSocSci (Historical and Heritage Studies)UnrestrictedFaculty of HumanitiesSDG-11: Sustainable cities and communitie

Effects of digital onboarding on newcomer proactivity behaviours and its impact on socialisation outcomes

Dissertation (MBA)--University of Pretoria, 2023Purpose – The paper aims to firstly investigate whether digital onboarding impacts newcomer proactive behaviours. Secondly to investigate whether newcomer proactive behaviours remain positively related to socialisation outcomes despite the evolving workforce and work environment. The study aims to extend the literature on organisational socialisation through understanding the impact of digital onboarding. Design/methodology/approach – The paper used an exploratory study, based on interviews held with new employees, comprising both digitally onboarded and face to face onboarded employees. Findings – Based on a sample of 14 employees, the results indicated that digital onboarding has no notable effect on newcomer proactive behaviours, specifically information seeking, feedback seeking and general socialising. The study also found that newcomer proactivity remains positively related to socialisation outcomes. Specifically the findings show how information seeking, feedback seeking, and general socialising is related to role clarity, task mastery and social integration, respectively. Research limitations/implications – It may take time for proactive behaviours to become evident, therefore, researchers are encouraged to investigate the research questions by introducing a time lag between the behaviours and cognitions. Practical implications – The paper includes implication for organisational socialisation processes to test for newcomer proactivity during the recruitment process to ensure effective socialisation. Originality/value – This paper identifies an opportunity for organisations to leverage digital onboarding processes as part of their socialisation tactics and confirms that the change in workforce and environment has not displace existent knowledge of effectiveness of socialisation processes.pagibs202

Improved survival of children and adolescents with classical Hodgkin lymphoma treated on a harmonised protocol in South Africa

DATA AVAILABILITY STATEMENT : The dataset for this study is available on request.BACKGROUND : Historic South African 5-year overall survival (OS) rates for Hodgkin lymphoma (HL) from 2000 to 2010 were 46% and 84% for human immunodeficiency virus (HIV)-positive and HIV-negative children, respectively. We investigated whether a harmonised treatment protocol using risk stratification and response-adapted therapy could increase the OS of childhood and adolescent HL. METHODS : Seventeen units prospectively enrolled patients less than 18 years, newly diagnosed with classical HL onto a risk-stratified, response-adapted treatment protocol from July 2016 to December 2022. Low- and intermediate-risk patients received four and six courses of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), respectively. High-risk patients received two courses of ABVD, followed by four courses of cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDac). Those with a slow early response and bulky disease received consolidation radiotherapy. HIV-positive patients could receive granulocyte colony-stimulating factor and less intensive therapy if stratified as high risk, at the treating clinician's discretion. Kaplan–Meier survival analysis was performed to determine 2-year OS and Cox regression to elucidate prognostic factors. RESULTS : The cohort comprised 132 patients (19 HIV-positive, 113 HIV-negative), median age of 9.7 years, with a median follow-up of 2.2 years. Risk grouping comprised nine (7%) low risk, 36 (27%) intermediate risk and 87 (66%) high risk, with 71 (54%) rapid early responders and 45 (34%) slow early responders, and 16 (12%) undocumented. Two-year OS was 100% for low-risk, 93% for intermediate-risk, and 91% for high-risk patients. OS for HIV-negative (93%) and HIV-positive (89%) patients were similar (p = .53). Absolute lymphocyte count greater than 0.6 × 109 predicted survival (94% vs. 83%, p = .02). CONCLUSION : In the first South African harmonised HL treatment protocol, risk stratification correlated with prognosis. Two-year OS of HIV-positive and HIV-negative patients improved since 2010, partially ascribed to standardised treatment and increased supportive care. This improved survival strengthens the harmonisation movement and gives hope that South Africa will achieve the WHO Global Initiative for Childhood Cancer goals.Carnegie Corporation Research Funding; Wits Faculty Research Committee; Crowdfunding; Doit4Charity; Ride Joburg Cycle Race.https://wileyonlinelibrary.com/journal/pbchj2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Organisational culture and organisational performance: A study of the South African public sector

Dissertation (MBA)--University of Pretoria, 2023Despite initiated reforms, public sector organisations in developing countries often grapple with performance and service delivery issues. This study seeks to enrich existing literature by examining the influence of organisational cultural dimensions (i.e., involvement, consistency, adaptability, and mission) on organisational performance as a measure of effectiveness and efficiency within South Africa's public sector. Considering its importance, the impact of organisational culture on performance remains unexplored in this context. Using quantitative methodology and descriptive and causal designs, data was collected from 174 participants, including both management and non-management roles, across various public organisations in South Africa. Data was analysed using both Statistical Package for Social Sciences (SPSS) and SmartPLS. Results indicate that dimensions like involvement and adaptability have a significant correlation with organisational performance, while the relationship between mission culture and performance is only partially significant. The study provides a foundational framework for generalising findings related to public sector organisations in developing countries, specifically within the South African context. Furthermore, the practical implications for managers are that they should respond to internal and external changes and empower employees in decision-making processes. These insights demonstrate the critical role of organisational culture in the execution of performance improvement plans.pagibs202

Price effects after one-day abnormal returns and crises in the stock markets

DATA AVAILABILITY: Data will be made available on request.We investigate price effects after one-day abnormal returns during crises in US, Japanese, Chinese, Russian and Brazilian stock markets, using the ANOVA, Mann–Whitney, t-tests, the modified cumulative abnormal return approach, regression analysis with dummy variables, and the trading simulation approach. The results suggest that the momentum effect is the most typical case of price behaviour after the days with positive abnormal returns, especially in emerging markets in pre and post crisis periods. Interestingly the momentum effect in developed markets changes into contrarian during crisis periods. However, in emerging markets the momentum effect prevails even in crisis periods. However, the power of the detected effects is weak. These effects do not provide opportunities to beat the market and might result from prevailing positive returns in these stock markets.http://www.elsevier.com/locate/ribafhj2024EconomicsSDG-08:Decent work and economic growt

Broad-scale genetic assessment of southern ground-hornbills (Bucorvus leadbeateri) to inform population management

DATA AVAILABILITY : Bucorvus leadbeateri sequences are available on GenBank, accession numbers: OP046521-OP046574, and OP122231 - OP122407.The Southern Ground-hornbill (SGH) (Bucorvus leadbeateri) is considered an umbrella species for biodiversity conservation in savannah biomes since they require large territories and significant protection measures that help to conserve a wide range of biodiversity with similar savanna and grassland requirements. Declines of the species are attributed to low reproductive rates coupled with multiple anthropogenic threats, including secondary poisoning, and persecution. Little is known about connectivity and population structure of SGH populations in Africa, south of the equator. Knowledge of population differentiation is needed to ensure that targeted conservation management plans can be implemented to slow population declines and ensure survival of the species. To inform a long-term conservation strategy, we investigated the broad-scale population structure of Southern Ground-hornbill across their sub-equatorial range. Our study based on 16 microsatellite loci identified moderate variation (average of 5.889 alleles per locus and a mean observed heterozygosity of 0.546) similar to other long-lived avian species. In contrast, mitochondrial DNA sequences analysis identified low diversity (Hd = 0.3313, π = 0.0015). A Bayesian assignment approach, principal component analysis, analysis of molecular variance and phylogenetic analysis identified weak to moderate population structuring across long distances and mitochondrial data showed a shallow phylogeny. Restriction to long-distance dispersal was detected that could not be attributed to isolation by distance, suggesting that other factors, such as their dispersal biology, are shaping the observed genetic differentiation. Although our study does not support the designation of populations as independent conservation units, we advocate that population management should continue to follow the Precautionary Principle (mixing founders from the same range state, rather than allowing mixing of founders from the extremes of the range) until there is scientific certainty. Following further research, if no independent conservation units are detected, then the global captive population can contribute to reintroductions across the range. In the wild, populations at the edge of the species range may need additional management strategies and gene flow should be promoted between neighbouring populations.https://www.elsevier.com/locate/geccohj2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-15:Life on lan

Activities as the critical link between motivation and destination choice in cultural tourism

PURPOSE : This study aimed to determine the motivations of a select group of South Africans in terms of their potential engagement with cultural tourism; more specifically, the study set out to show whether these motivations influence the cultural activities that the tourists want to participate in and whether their interest in specific cultural activities determines their destination choices. Furthermore, the mediating role of activities in the relationship between cultural motivations and destination choice was also assessed. DESIGN/METHODOLOGY/APPROACH : An online panel survey collected responses from 1,530 potential cultural tourists across South Africa. Hypotheses were tested, using structural equation modelling. FINDINGS : The results show that tourists' motivations for cultural tourism influence their likelihood of participating in specific cultural activities. Cultural tourism is shown to be influenced by more than learning and includes entertainment, relaxation, novelty and escape dimensions. There also seems to be a difference in the activities engaged in by destination type. For example, tourists likely to take part in indigenous cultural tourism activities are more likely to do so at hedonic destinations. PRACTICAL IMPLICATIONS : This paper contributes to the understanding of cultural tourism activities, aiding destinations in attracting cultural tourists. Destinations need to develop activities that match visitor motivations, increase satisfaction and encourage visitors to return. ORIGINALITY/VALUE : The paper increases the understanding of cultural tourism in South Africa and underlines the importance of communities in providing distinctive tourism activities. The study also has an important social dimension, highlighting the role of social status in cultural tourism consumption and destination selection.https://www.emerald.com/insight/publication/issn/2514-9792hj2024Tourism ManagementSDG-11:Sustainable cities and communitie

Adopting technology in favour of human labour: A managerial perspective on the impact of Fourth Industrial Revolution technologies in South Africa

Dissertation (MPhil)--University of Pretoria, 2023The unemployment rate in South Africa has reached unsustainable levels and the advancements in the capabilities of technologies associated with the fourth industrial revolution are such that what was once considered science fiction is now becoming a reality. Making use of an exploratory qualitative research design, this study sets out to explore what would be the driving forces behind business leaders wanting to adopt fourth industrial technologies in South Africa and where does the responsibility for a solution reside to the unemployment challenges which South Africa faces. A total of fourteen semi-structured, in-depth interviews with senior business leaders across ten different industries took place to gather the required data. The findings of this study showed that there is an awareness amongst business leaders when it comes to the technologies of the fourth industrial revolution, their capabilities, as well as the impact these technologies can potentially have in exacerbating levels of unemployment. The findings show however that business leaders do not believe that South Africa’s current unemployment challenge has been caused by the adoption of technologies of the fourth industrial revolution primarily due to limited adoption rates. Business leaders see competitive advantage as a strong enough driver to adopt technologies even at the expense of human labour, and concerningly they see South Africa’s education system as inadequate when it comes to arming humans with the skills required to succeed in a world which is continuing to integrate with technologies of the fourth industrial revolution. This research and its findings contribute to the extant literature on Technological Unemployment.pagibs202