A autoeficácia tem sido estudada em virtude de suas influências nas formas de pensar e agir dos professores e na aprendizagem de estudantes, no entanto, no contexto do Ensino Superior brasileiro, ela tem sido pouco explorada e os estudos existentes utilizaram instrumentos desenvolvidos para professores de Ensino Básico. Considerando-se que as atividades do Ensino Superior são múltiplas e diversas da Educação Básica, isso é inadequado. Neste artigo, os objetivos foram revisar os principais instrumentos de medida utilizados para investigar as crenças de autoeficácia de professores universitários no cenário internacional e apresentar um novo instrumento elaborado pelos autores, a Escala de Autoeficácia de Professores Universitários Brasileiros, composta de 30 itens e quatro dimensões: ensino, pesquisa, extensão e gestão universitária. Apresenta-se os resultados das análises fatorial exploratória (n = 854) e confirmatória (n = 855), além dos seus dados de validade e confiabilidade. Os resultados apontam para um instrumento fidedigno e adequado ao contexto brasileiro, o que possibilita sua utilização em estudos futuros.

Background: Emerging data indicate that BCHE, a gene encoding the enzyme butyrylcholinesterase, is a negative prognostic marker in MYCN-amplified neuroblastoma. Levels of butyrylcholinesterase in children newly diagnosed with neuroblastoma are proportional to MYCN amplification and the response to therapy. To better understand the functions of butyrylcholinesterase in neuroblastoma, we examine interactions of this enzyme with several neuroblastoma-associated kinases and provide in depth review of known associations. Methods: BCHE-deleted cells (KO) were produced from MYCN-amplified BE(2)-C cells (WT) by the CRISPR-Cas9 targeted disruption of the BCHE locus. Activation levels of several oncoproteins and the expression of N-Myc in KO were compared to WT cells. N-Myc protein expression, multiplexed detection of relative protein expression and phosphorylation of 71 tyrosine kinases and 17 proteins in the MAPK pathway were assessed using Western immunoblotting and microarrays in exponentially growing untreated cells and in cells exposed to the genotoxic stress. Results: BCHE locus disruption and butyrylcholinesterase deficiency result in the loss of N-Myc protein and a significant deactivation of several kinases associated with the aggressive neuroblastoma phenotype as well as major changes in the phosphorylation of upstream and downstream partners of these kinases Conclusions: Butyrylcholinesterase appears to contribute to the activation of several pathways in MYCN-amplified cells including FGF-R1, Ltk, TrkB, and Ros1. Deletion of BCHE and ensuing butyrylcholinesterase deficit deactivate these pathways suggesting the role of BChE as a novel druggable target in neuroblastoma therapy.

The physiological functions of butyrylcholinesterase (BChE) and its role in malignancy remain unexplained. Our studies in children newly diagnosed with neuroblastoma indicated that BChE expressions is proportional to MYCN amplification suggesting that pathogenesis of high-risk disease may be related to the persistent expression of abnormally high levels of tumor-associated BChE. BChE-deficient neuroblastoma cells (KO [knockout]) were produced from MYCN -amplified BE(2)-C cells (WT [wild-type]) by the CRISPR-Cas9 targeted disruption of the BCHE locus. KO cells have no detectable BChE activity. The compensatory acetylcholinesterase activity was not detected. The average population doubling time of KO cells is 47.0±2.4 hours, >2× longer than WT cells. Reduced proliferation rates of KO cells were accompanied by the loss of N-Myc protein and a significant deactivation of tyrosine kinase receptors associated with the aggressive neuroblastoma phenotype including Ros1, TrkB, and Ltk. Tumorigenicity of WT and KO cells in male mice was essentially identical. In contrast, KO xenografts in female mice were very small (0.37±0.10 g), ~3× smaller compared with WT xenografts (1.11±0.30 g). Unexpectedly, KO xenografts produced changes in plasma BChE similarly to WT tumors but lesser in magnitude. The disruption of BCHE locus in MYCN -amplified neuroblastoma cells decelerates proliferation and produces neuroblastoma cells that are less aggressive in female mice.

This article reviews available research literature in the field of lecturer self-efficacy beliefs produced between 1988 and 2020. Given the growing interest in lecturer self-efficacy beliefs in recent years, and the global challenges the Higher Education sector will face following the current Covid-19 pandemic, the time to conduct such a review seems appropriate. Fifty-five empirical papers in English, Spanish and Portuguese were identified and examined. Findings show that papers investigated the beliefs of lecturers from 23 countries using mostly quantitative cross-sectional approaches involving questionnaires. Among the eight main themes that emerged, 'teaching self-efficacy' featured prominently and received most attention, while other aspects of the work of lecturers, including research, service-related and other administrative activities, were also considered. Concerning personal variables like gender, there was no consensus over whether different characteristics affected self-efficacy beliefs more than others. Conclusions point to the need for additional mixed-methods and qualitative studies with more refined and contextualised methodological approaches to better understand the field, to identify actual sources of self-efficacy themselves and to more fully inform policy, practice, the distribution of resources and building capacity.

In this article, we explore Brazilian lecturers’ self-efficacy beliefs as a predictor of quality of life and burnout drawing on the concept and theoretical framework of self-efficacy presented by Albert Bandura, the originator of Social Cognitive Theory. The questionnaires adopted for the research included the Brazilian Lecturer Self-Efficacy Scale (BLSES), the Maslach Burnout Inventory (MBI-ES) and the World Health Organization Quality of Life Assessment (WHOQOL-Bref). The participants were 1,709 lecturers from 78 universities in Brazil, most of whom had a doctoral degree. We analyzed the data using descriptive and inferential statistics, performing structural equation modeling (SEM) and cluster analysis using IBM SPSS and Amos. We hypothesized that lecturer self-efficacy would be a positive predictor of quality of life and this, in turn, would be a negative predictor of burnout itself. SEM model fit indices fell within acceptable levels, with the overall model lending support to the stated hypothesis. In addition, lecturer self-efficacy was also a predictor of personal accomplishment in the MBI-ES. Regarding the cluster analysis, participants fell into five groups based on self-efficacy, quality of life and burnout questionnaire scores, each with associated personal, professional and academic characteristics. By way of discussion, we address reflections arising from findings to university life and working conditions, training needs and the need to establish career planning supported by studies that investigate the phenomenon of teaching in higher education in an integrated manner.

For a large number of Higher Education institutions in the UK, the recruitment of international students remains vital for economic, political, cultural and educational benefits. Increasing competition within the international student market has encouraged many Higher Education institutions to pay closer attention to the quality of their educational offer, as well as the expectations and experiences of international students themselves. With an aim to present a more insightful picture of this position, this article examines the 'service quality' of UK Higher Education through the lens of one group of international students at a single Russell Group institution while also engaging the academic perspective in direct comparison. To achieve this, a mixed-methods research study was carried out at a location in the South East of England, with quantitative survey data collected from a convenience sample of 139 Chinese students and 27 academics, with 11 qualitative follow-up interviews. Results show both consistency and inconsistency between participant perceptions and where those consistencies and inconsistencies may exist. The findings suggest caution when assuming, as is currently prevalent in the context of highly marketised UK Higher Education, that 'service quality' of Higher Education can be comprehensively understood and efficiently improved from the student perspective alone.

ABSTRACT In this article, we present details of a new Academic Boredom Survey Instrument (ABSI) incorporating different measures of academic boredom’s trait, state and other characteristic attributes for the exploratory study of student engagement in Higher Education (HE). Developed from a review of international research literature and our own empirical work in the field, validation of the ABSI proceeded in detail from a sample of 408 undergraduates enrolled on 16 arts, humanities and science degree programmes at two universities and two further education colleges in the UK. In terms of the ABSI’s embedded trait and state questionnaires alone, Exploratory and Confirmatory Factor Analysis resulted in the establishment of three scales, with associated subscales, for general use (boredom proneness and class- and study-related boredom). Together with other characteristic attributes (e.g. sites and triggers, boredom frequency, feelings, coping strategies and revision and assignment boredom), additional data obtained from a modified version of the Shortened Experiences of Teaching and Learning Questionnaire (SETLQ) and course grades from student records, correlation and cluster analysis contributed further in terms of determining the robustness and value of the ABSI as an exploratory tool, as well as highlighting the predictive and diagnostic potential afforded when using complementary research instruments in combination. Offering availability for interdisciplinary use and critical comment across the UK HE sector as a whole, the ABSI has particular relevance in terms of designing and delivering courses, the professional development of staff, student profiling and the provision of student support.

This paper details a small-scale research project that explores the student transition into higher education (HE), delivered in a further education college (FE), and considers whether the requirements of transition at this level impacts on emotional wellbeing. As such, it aims to contribute to the growing body of research on HE-in-FE from the perspective of student transition and emotional wellbeing. The data drawn on in this paper were collected by a questionnaire, administered at two points in the first semester, to measure levels of anxiety in students, alongside a further questionnaire designed to evaluate the effectiveness of bespoke academic skills input aimed at supporting the transition into HE. From quantitative and qualitative data, key findings identify factors that influence students' emotional responses to HE, including those that exacerbate an those that mitigate negative emotional responses. Significantly, the research identifies academic factors, rather than personal or social issues, as being critical to students' emotional experiences during the transitionary period.

This article describes the development and validation of the Brazilian Lecturer SelfEfficacy Scale (BLSES). The BLSES is a self-report questionnaire assessing four dimensions of Brazilian lecturers’ self-efficacy: teaching self-efficacy, research selfefficacy, extension self-efficacy and management self-efficacy. Following the online distribution and return of 1709 usable 44-item questionnaires, construct validity was studied through exploratory and confirmatory factor analyses using a randomised split sample approach. Exploratory analysis of the first split (n=854 responses) revealed a 30-item four-factor structure subsequently confirmed in the second split (N=855). A hierarchical model with a second-order factor underlying the four firstorder factors was also tested and found acceptable. The psychometric characteristics of the BLSES justify the use of this questionnaire in future research.

Modifying implant surfaces to improve their biocompatibility by enhancing osteoblast activation, growth, differentiation, and induction of greater bone formation with stronger attachments should result in improved outcomes for total joint replacement surgeries. This study tested the hypothesis that nano-structured surfaces, produced by the ion beam-assisted deposition method, enhance osteoblast adhesion, growth, differentiation, bone formation, and maturation. The ion beam-assisted deposition technique was employed to deposit zirconium oxide films on glass substrates. The effects of the ion beam-assisted deposition technique on cellular functions were investigated by comparing adhesion, proliferation, differentiation, and apoptosis of the human osteosarcoma cell line SAOS-2 on coated versus uncoated surfaces. Ion beam-assisted deposition nano-coatings enhanced initial cell adhesion assessed by the number of 4′,6-diamidino-2-phenylindole–stained nuclei on zirconium oxide nano-coated surfaces compared to glass surfaces. This nano-modification also increased cell proliferation as measured by mitochondrial dehydrogenase activity. Moreover, the ion beam-assisted deposition technique improved cell differentiation as determined by the formation of mineralized bone nodules and by the rate of calcium deposition, both of which are in vitro indicators of the successful bone formation. However, programmed cell death assessed by Annexin V staining and flow cytometry was not statistically significantly different between nano-surfaces and glass surfaces. Overall, the results indicate that nano-crystalline zirconium oxide surfaces produced by the ion beam-assisted deposition technique are superior to uncoated surfaces in supporting bone cell adhesion, proliferation, and differentiation. Thus, surface properties altered by the ion beam-assisted deposition technique enhanced bone formation and may increase the biocompatibility of bone cell–associated surfaces.

Osteosarcoma (OST) is the most common bone tumor in children and adolescents with a second peak of incidence in elderly adults usually diagnosed as secondary tumors in Paget's disease or irradiated bone. Subjects with metastatic disease or whose disease relapses after the initial therapy have a poor prognosis. Moreover, multifocal OST contains tumor-initiating cells that are resistant to chemotherapy. The use of aggressive therapies in an attempt to eradicate these cells can have long-term negative consequences in these vulnerable patient populations. 227Th-labeled molecular probes based on ligands to OST-associated receptors such as IGF-1R (insulin-like growth factor receptor 1), HER2 (human epidermal growth factor receptor 2), and PSMA (prostate-specific membrane antigen) are expected to detect and treat osseous and nonosseous sites of multifocal OST. Published reports indicate that 227Th has limited myelotoxicity, can be stably chelated to its carriers and, as it decays at targeted sites, 227Th produces 223Ra that is subsequently incorporated into the areas of increased osteoblastic activity, that is, osseous metastatic lesions. Linear energy transfer of α particles emitted by 227Th and its daughter 223Ra is within the range of the optimum relative biological effectiveness. The radiotoxicity of α particles is virtually independent of the phase in the cell cycle, oxygenation, and the dose rate. For these reasons, even resistant OST cells remain susceptible to killing by high-energy α particles, which can also kill adjacent quiescent OST cells or cells with low expression of targeted receptors. Systemic side effects are minimized by the limited range of these intense radiations. Quantitative single-photon emission computed tomography of 227Th and 223Ra is feasible. Additionally, the availability of radionuclide pairs, for example, 89Zr for positron emission tomography and 227Th for therapy, establish a strong basis for the theranostic use of 227Th in the individualized treatment of multifocal OST.

This study explored factors that influence academic achievement and hence, future career prospects. The relationships between the factors, academic trait boredom, approach to learning and academic achievement were examined using data collected from university students at a small English university and from their student records. The initial statistical analysis revealed significant effects of gender on learning approach and two of the three academic trait boredom subscales. Female students proved to be less prone to academic trait boredom than their male counterparts. A model was then developed that showed how a student’s choice of learning approach was influenced by academic trait boredom and impinged on academic achievement. This modelling also confirmed that students who are more prone to academic trait boredom are also more likely to adopt a surface approach to learning rather than a deep or strategic one. The results of this investigation have implications for students, lecturers, course designers and learning support staff both here in this one location as well as elsewhere across the higher education sector.

Biomaterials with enhanced biocompatibility are favored in implant studies to improve the outcomes of total joint replacement surgeries. This study tested the hypothesis that nano-structured surfaces for orthopedic applications, produced by the ion beam-assisted deposition method, would enhance osteointegration by altering the expression of bone-associated genes in osteoblasts. The ion beam-assisted deposition technique was employed to deposit nano-films on glass or titanium substrates. The effects of the ion beam-assisted deposition produced surfaces on the human osteosarcoma cell line SAOS-2 at the molecular level were investigated by assays of adhesion, proliferation, differentiation, and apoptosis on coated surfaces versus uncoated cobalt-chrome, as the control. Ion beam-assisted deposition nano-coatings enhanced bone-associated gene expression at initial cell adhesion, proliferation, and differentiation compared to cobalt-chrome surfaces as assessed by polymerase chain reaction techniques. Increased cell proliferation was observed using a nuclear cell proliferation-associated antigen. Moreover, enhanced cell differentiation was determined by alkaline phosphatase activity, an indicator of bone formation. In addition, programmed cell death assessed by annexin V staining and flow cytometry was lower on nano-surfaces compared to cobalt-chrome surfaces. Overall, the results indicate that nano-coated surfaces produced by the ion beam-assisted deposition technique for use on implants were superior to orthopedic grade cobalt-chrome in supporting bone cell adhesion, proliferation, and differentiation and reducing apoptosis. Thus, surface properties altered by the ion beam-assisted deposition technique should enhance bone formation and increase the biocompatibility of bone cell-associated surfaces.

The activity of MP1, a pyrrolomycin, was studied in MYCN amplified neuroblastoma (NB) alone and combined with temsirolimus (TEM). Activity of MP1 was tested in MYCN amplified (BE-2c, IMR) and non amplified (SKN-AS) NB cells. The effect of MP1 on MYCN, MCL-1, cleaved PARP, LC3II/LC3I, bcl-2, BAX, and BRD-4 were determined by western blot and RNAseq. The effect of MP1 on metabolism, mitochondrial morphology, and cell cycle was determined. Toxicology and efficacy of MP1 plus TEM were evaluated. The IC50 of MP1 was 0.096 μM in BE-2c cells compared to 0.89 μM in IMR, and >50 μM in SKN-AS. The IC50 of MP1 plus TEM in BE-2c cells was 0.023 μM. MP1 inhibited metabolism leading to quiescence and produced a decline in cell cycle S-phase. Electron microscopy showed cristae loss and rounding up of mitochondria. Gene and protein expression for MYCN and MCL-1 declined while LCII and cleaved PARP increased. Protein expression of BAX, bcl-2, and BRD-4 were not significantly changed after MP1 treatment. The in-vivo concentrations of MP1 in blood and tumor were sufficient to produce the biologic effects seen in-vitro. MP1 plus TEM produced a complete response in 3 out of 5 tumor bearing mice. In a second mouse study, the combination of MP1 and TEM slowed tumor growth compared to control. MP1 has a potent inhibitory effect on the viability of MYCN amplified NB. Inhibition of metabolism by MP1 induced quiescence and autophagy with a favorable toxicology and drug distribution profile. When combined with TEM anti-tumor activity was potentiated in-vitro and in-vivo.

Abstract Ewing's sarcoma (EWS) is a malignant tumor that primarily develops in children and adolescents. The main driver in EWS tumor progression is the result of a chromosomal translocation, t(11;22)(q24;q12), leading to the EWS-FLI1 fusion protein that functions as an oncogenic transcription factor. EWS is curable if diagnosed early, however, patients presenting with metastasis upon diagnosis have the worst prognosis of all the bone tumors. There is emerging evidence that a low oxygen (hypoxic) microenvironment contributes to increased EWS-FLI1 expression in EWS tumors and induces cellular changes observed in many cancers leading to the selection of clones with tumor initiating cell (TIC) properties. TICs are widely considered to be responsible for relapse, metastasis, and therapeutic resistance in many tumors. The effects of hypoxia are mediated primarily by hypoxia inducible factors HIF-1α and HIF-2α and have been demonstrated to upregulate EWS-FLI1 and stem cell-related factors, but the mechanism by which hypoxia promotes aggressiveness of this normally treatable cancer is unclear. In our study, we hypothesize that exosomes secreted under hypoxic conditions enhance the aggressiveness in Ewing's sarcoma by promoting tumor initiating cells in EWS cells and in stromal cells of the tumor microenvironment. This hypothesis is based on evidence in the literature showing that small vesicles (exosomes) released from cancer cells can reprogram metabolic and cellular function of both tumor cells and cells that compose the tumor microenvironment. In our study, RNAseq and pathway analysis of exosomes secreted from hypoxic EWS cells revealed high levels of the EWS-FLI1 fusion transcripts and stem cell related factors CD133, SOX2, OCT4, NANOG and MYC. Moreover, various co-culturing assays demonstrated that hypoxic EWS exosomes can increase cell motility, anchorage independent growth, chemoresistance and TIC formation in EWS cells, and transform microenvironment cells. Our in vivo model revealed that EWS exosomes injected into developing EWS tumors in mice significantly increased tumor formation. EWS tumors injected with hypoxic exosomes had increased expression of the CD133 TIC marker when analyzed by flow cytometry. These findings suggest that hypoxic EWS exosomes can enhance aggressiveness in EWS by promoting TIC formation, therapy resistance, invasiveness and motility in their target cells. Here, we describe a mechanism where EWS-FLI1 containing exosomes enhance TIC formation and introduce a new pathway that must be considered to effectively treat aggressive EWS tumors. Citation Format: Matthew Kling, Donald Coulter, Nagendra Chaturvedi, Timothy McGuire, John Sharp, Shantaram Joshi. Exosomes secreted under hypoxia enhance aggressiveness in Ewing's sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3183.

This review and synthesis of relevant literature considers the nature of boredom and boredom proneness in general terms before focusing on how the academic boredom experienced by undergraduates at university is sufficiently different from other known types to warrant a unique and important field of study. Derived from within the literature itself, academic boredom is commonly presented as a largely negative and deactivating achievement-related emotion known to impact usually adversely on student engagement and performance. Tracing traditional as well as contemporary views from within psychology, which has tended to dominate the field, findings that remain largely quantitative and highly statistical in nature are exemplified alongside the more exploratory but mixed-methods and educational work recently conducted in the UK. A comparison of the questionnaire-based self-report instruments frequently used in data collection is also included. Rooted largely within Control-Value Theory, the implications associated with academic boredom are far from trivial, particularly with respect to understanding sites and triggers, how students respond and cope and how the overall quality of the student experience might be improved. Limitations in the work undertaken to date draw attention to opportunities for further educational and interdisciplinary research.

Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription‐3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3‐NH2 terminal domain inhibitor (S3‐NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high‐risk SHH‐TP53‐mutated and MYC‐amplified Non‐WNT/SHH tumors. Treatment of MB cells with S3‐NTDi leads to growth inhibition, cell cycle arrest, and apoptosis. S3‐NTDi downregulated expression of STAT3 target genes, delayed migration of MB cells, attenuated epithelial‐mesenchymal transition (EMT) marker expressions and reduced cancer stem‐cell associated protein expressions in MB‐spheres. To elucidate mechanisms, we showed that S3‐NTDi induce expression of pro‐apoptotic gene, C/EBP‐homologous protein (CHOP), and decrease association of STAT3 to the proximal promoter of CCND1 and BCL2. Of note, S3‐NTDi downregulated microRNA‐21, which in turn, de‐repressed Protein Inhibitor of Activated STAT3 (PIAS3), a negative regulator of STAT3 signaling pathway. Furthermore, combination therapy with S3‐NTDi and cisplatin significantly decreased highly aggressive MYC‐amplified MB cell growth and induced apoptosis by downregulating STAT3 regulated proliferation and anti‐apoptotic gene expression. Together, our results revealed an important role of STAT3 in regulating MB pathogenesis. Disruption of this pathway with S3‐NTDi, therefore, may serves as a promising candidate for targeted MB therapy by enhancing chemosensitivity of MB cells and potentially improving outcomes in high‐risk patients.

Academic boredom is a largely negative and disabling achievement-related emotion. In this mixed-methods exploration of 224 students attending a single university in England, academic boredom was found to arise at the point of course delivery, while studying at other times and during the completion of assignments for assessment. Quantitative data from the recently adapted Boredom Proneness Scale for use across the UK higher education sector (the BPS-UKHE) and the Approaches and Study Skills Inventory for Students (ASSIST), enriched with qualitative data from 10 semi-structured research interviews, indicate that those with a higher propensity towards academic boredom than others displayed the deep, strategic and surface profiles of 'less effective learners'. This was reflected in their interest in ideas, their ability to organise resources and manage time, what they had to memorise or do to 'get by', their achievement motivation and their sense of purpose. As part of a greater evolving network of other contributing factors, this translated into lower final degree marks and fewer 'good' degree awards. Recommendations surrounding boredom mitigation and approaches to learning are suggested which warrant serious consideration. The work presented here makes an important contribution to a surprisingly neglected field of UK higher education research and the student engagement agenda.

Medulloblastoma (MB) is the most common childhood brain tumor, which occurs in the posterior fossa. MB tumors are highly heterogeneous and have diverse genetic make-ups, with differential microRNA (miRNA) expression profiles and variable prognoses. MB can be classified into four subgroups, each with different origins, pathogenesis, and potential therapeutic targets. miRNA and small-molecule targeted therapies have emerged as a potential new therapeutic paradigm in MB treatment. However, the development of chemoresistance due to surviving cancer stem cells and dysregulation of miRNAs remains a challenge. Combination therapies using multiple drugs and miRNAs could be effective approaches. In this review we discuss various MB subtypes, barriers, and novel therapeutic options which may be less toxic than current standard treatments.