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Student success is among the most widely researched areas in tertiary education. Generalisability of research in this field is problematic due to cultural and structural differences between countries, institutions and programmes where the research is done. Engineering education in the Netherlands has not been studied in depth. In this paper, outcomes of studies done outside and inside engineering and outside and inside the Netherlands are discussed to help understand the complexity of student retention issues. Although generalisation is an issue, there are a number of concepts and variables that surface in many of these studies, including students' background and disposition variables, education attributes, variables concerning educational climate and student behaviour. How these variables are related and how a university can apply the outcomes of research in this field of study are discussed in this paper. (Contains 1 table, 3 figures and 2 notes.)

This article illustrates the importance of conducting a comprehensive analysis of suicidality through the case study of an adolescent patient dealing with both depressive disorder and obsessive-compulsive disorder. The aim of treating suicidality is to address the underlying psychiatric conditions and factors contributing to the disorder. This necessitates a thorough evaluation of the treatment environment, the establishment of continuous care, and ensuring safety. By utilizing a new model to distinguish various forms of suicidal behavior and examining suicidality as a distinct phenomenon, it becomes possible to create individualized diagnostic and treatment approaches, along with effective risk assessments. In the presented patient, intrusive thoughts significantly impacted her suicidality. The treatment approach for patient A involved employing eye movement dual task (EMDT), exposure therapy and strategies to enhance autonomy. This approach aims to reduce suicidality, facilitate recovery, and alleviate the fear of losing control.

The central dogma of molecular biology is a key concept for undergraduate students in the life sciences as it describes the flow of information in living systems from gene-to-gene product. However, despite often being covered in many introductory life science courses, students may still have misconceptions surrounding the central dogma even as they move on to advanced courses. Active learning strategies such as laboratory activities can be useful in addressing such misconceptions. In the laboratory exercise presented here, senior undergraduate students explore the intricacies of nonsense suppressor mutations to challenge their understanding of the central dogma. The students introduce a plasmid carrying a nonfunctional chromogenic protein gene due to a nonsense mutation in a codon encoding the chromophore to various nonsense suppressor strains of Escherichia coli . Students then observe distinct chromogenic phenotypes, depending on the suppressor strain. Students showed a moderate increase in understanding of the central dogma. While the central dogma remains a challenging concept, active learning strategies like the one presented here can help reduce conceptual errors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 DeWolf et al.)

Background: The relationship between supervisors and residents plays a prominent role in the professional development of general practice (GP) residents. When disruptions occur in the normal course of healthcare, due to effects of e.g. war or emerging epidemics, we need to consider how this may affect the training of the next generation of general practitioners. As both supervisors and residents face new and unprecedented challenges that impact overall quality of the training. In this study, we examined the characteristics of the supervisory relationship in GP training during the disruptions early on during COVID-19. Our aim was to understand better how resident learning is affected in these circumstances, which is a first step in enabling supervisors, residents and faculty to anticipate disruptive situations better in the future., Methods: We conducted a qualitative case study with a constructivist approach. Seven GP residents at the start of their second placement, and their 10 supervisors participated in this study. Participants came from a University Medical Centre in the Netherlands. Semi-structured interviews were held between September 2020 and February 2021. The subjects were (1) interviewed individually about what they had learned regarding COVID-19, and (2) they were interviewed in supervisory pairs about how they had learned. Data were iteratively analysed; thematic analysis for (1) and template analysis in (2)., Results: We identified notable changes in the supervisor-resident relationship attributable to COVID-19. Supervisors and residents were confronted with an all-encompassing uncertainty in the workplace, and disruptive changes in patient care and learning opportunities for residents. Supervisors and residents addressed these emerging workplace challenges through three types of collaboration, (1) getting the job done; (2) residents' learning; and (3) collective learning. Each type had a different focus and distinctive characteristics of the supervisory relationship., Conclusion: With the outbreak of COVID-19, supervisors and residents were faced with disruptive uncertainty. In these circumstances, learning occurred not only between residents and their supervisors, but also with non-supervising GPs and assistants in collective learning. We propose to complement collective learning in the workplace with reflection between residents and supervisors at the training institution., (© 2023. The Author(s).)

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students' credits and student retention - something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology's potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective.

The protein kinase pUL97, encoded by human cytomegalovirus (HCMV), is an important determinant of virus replication. Recently, indolocarbazoles were identified as a class of substances that inhibit the pUL97 kinase activity in vitro. In parallel, it was shown that indolocarbazoles interfere with HCMV replication; however, the causal relationship between inhibition of pUL97 kinase activity and virus replication has not been clarified. Here evidence is provided that indolocarbazole-mediated inhibition of virus replication is a direct result of diminished pUL97 protein kinase activity. In cell culture infections, a strong and selective antiviral activity was measured with respect to several strains of HCMV in contrast with other related or non-related viruses. For fine quantification, recombinant HCMVs expressing green fluorescent protein were used, demonstrating the high sensitivity towards compounds NGIC-I and Gö6976. Interestingly, a ganciclovir-resistant virus mutant (UL97-M460I) showed increased sensitivity to both compounds. Supporting this concept, transfection experiments with cloned pUL97 revealed that ganciclovir-resistant mutants were characterized by reduced levels of autophosphorylation compared with wild-type and possessed particularly high sensitivity to indolocarbazoles. Moreover, the Epstein-Barr virus-encoded homologous kinase, BGLF4, which showed a similar pattern of autophosphorylation and ganciclovir phosphorylation activities, was not inhibited. Importantly, a cytomegalovirus deletion mutant, lacking a functional UL97 gene and showing a severe impairment of replication, was completely insensitive to indolocarbazoles. Thus, our findings indicate that a specific block in the activity of pUL97 is the critical step in indolocarbazole-mediated inhibition of virus replication and that pUL97 might be targeted very efficiently by a novel antiviral therapy.

Growth control of African trypanosomes in the mammalian host is coupled to differentiation of a non-dividing life cycle stage, the stumpy bloodstream form. We show that a protein kinase with novel domain architecture is important for growth regulation. Zinc finger kinase (ZFK) has a kinase domain related to RAC and S6 kinases flanked by a FYVE-related zinc finger and a phox (PX) homology domain. To investigate the function of the kinase during cyclical development, a stable transformation procedure for bloodstream forms of differentiation-competent (pleomorphic) Trypanosoma brucei strains was established. Deletion of both allelic copies of ZFK by homologous recombination resulted in reduced growth of bloodstream-form parasites in culture, which was correlated with an increased rate of differentiation to the non-dividing stumpy form. Growth and differentiation rates were returned to wild-type level by ectopic ZFK expression. The phenotype is stage-specific, as growth of procyclic (insect form) trypanosomes was unaffected, and Deltazfk/Deltazfk clones were able to undergo full cyclical development in the tsetse fly vector. Deletion of ZFK in a differentiation-defective (monomorphic) strain of T. brucei did not change its growth rate in the bloodstream stage. This suggests a function of ZFK associated with the trypanosomes' decision between either cell cycle progression, as slender bloodstream form, or differentiation to the non-dividing stumpy form.

The UL97-encoded protein kinase (pUL97) of human cytomegalovirus (HCMV) plays a critical role in the control of virus replication. Deletion of the UL97 gene results in a drastic reduction in the replication efficiency. Although the exact function of pUL97 remains unclear and its sensitivity to specific inhibitors is speculative, protein kinase inhibitors of the indolocarbazole class are effective inhibitors of cytomegalovirus. Based on the phosphorylation of ganciclovir (GCV), a novel quantification system for pUL97 kinase activity was established: the phosphorylated form of GCV exerts an easily quantifiable cytotoxic effect in transfected cells. Importantly, the addition of indolocarbazole compounds, Gö6976 and NGIC-I, which were highly effective at nanomolar concentrations while other protein kinase inhibitors were not, led to a significant reduction of pUL97 kinase activity. It was also demonstrated that a catalytically inactive mutant of pUL97, K355M, and a GCV-resistant mutant, M460I, were both negative for GCV phosphorylation, although protein phosphorylation remained detectable for the latter mutant. In vitro kinase assays were used to confirm the levels of pUL97-mediated phosphorylation recorded. To generate a tool for screening large numbers of putative inhibitors that preferentially interfere with GCV as well as protein phosphorylation, pUL97-expressing cell clones with stable pUL97 kinase activity were selected. This study demonstrates that certain indolocarbazole compounds are potent pUL97 inhibitors and, therefore, represent novel candidates for antiviral drugs that target viral protein kinase functions.