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Attention to shaping the direction of one's career according to personal needs and preferences is growing. However, there is limited understanding how contextual antecedents affect career authenticity. Moreover, little is known about whether antecedents of career authenticity operate in the same way for men compared to women and if the impact of these antecedents differs per position. In this study, we contribute to these gaps in the literature by analysing the role of five antecedents of career authenticity in the academic context. Our analysis is based on a cross-sectional survey collected among a sample of 398 academics working in The Netherlands. It shows that justice in promotion practices is the most important contextual antecedent in explaining career authenticity in academia. After analysing the data using multi-group Structural Equation Modelling (SEM), we found that some antecedents relate differently to career authenticity for men compared to women. Our data also showed how most antecedents operate differently per academic rank. These insights show that higher education institutes can boost their academics' career authenticity but should tailor such actions to academics of different genders and in different positions.

Summary: Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA+ prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA+ PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8+ T cells. Vγ9Vδ2 T cell expressed NKG2D and DNAM-1 contributed to Vγ9Vδ2 T cell activation and tumor lysis at low PSMA-Vδ2 bsTCE concentrations. In vivo models confirmed the antitumor efficacy of the bsTCE and demonstrated a half-life of 6–7 days. Tissue-cross reactivity analysis was in line with known tissue distribution of PSMA and Vγ9Vδ2 T cells. Together these data show the PSMA-Vδ2 bsTCE to represent a promising anti-tumor strategy and supports its ongoing evaluation in a phase 1/2a clinical trial in therapy refractory metastatic castration-resistant PCa.

This article systematically reviews 35 empirical articles on the topic of networks and career advancement into academic leadership positions. Our objectives in this systematic review are to clarify: (1) the functions that networks fulfil; (2) the outcomes of these functions in terms of career advancement; and (3) whether networks are likely to result in more or less career advancement for women compared to men. Four databases were searched using the PRISMA (preferred reporting items for systematic reviews and meta-analyses) approach to select eligible studies published between 1990 and 2019. We distinguish three different functions that networks may fulfil: operational, developmental and strategic. Mixed results are found for the operational and developmental network functions, while the results suggest that the strategic function contributes to career advancement, particularly for men. The reason for this can be found in the masculine academic context. Our findings implicate that a solution involving equal network opportunities needs to be taken up by the academic community as a whole. To further develop the research field, we call for: (1) more consistent conceptualisation; (2) more attention to the multiple functions of networks and networking behaviour; and (3) more advanced study designs.

BackgroundVγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease. MethodsWe evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH. ResultsBivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice.ConclusionBy enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells.

Introduction: Patients' adherence is essential for COPD self-management, as beneficial effects can only be expected in adherent patients. We explored associations between patients’ adherence to COPD exacerbation action plans and health outcomes. Materials and methods: Pooled COPD self-treatment intervention group data from two RCTs were analysed, only including patients who had ≥1 COPD exacerbation or started ≥1 course of oral corticosteroids over one-year follow-up. Optimal adherence was defined as ‘self-treatment initiated ≤1 day before or after exacerbation start’, suboptimal adherence as ‘self-treatment initiated 2 days before or after exacerbation start or no self-treatment initiated for a short (1–3 days) exacerbation’, and significant delay or no treatment as ‘self-treatment initiated >2 days after exacerbation start or no self-treatment initiated for a longer (>3 days) exacerbation’. Regression models were built for several health outcomes, with the number of COPD exacerbation days/patient/year being the primary outcome. Results: Patients with significant delay or no treatment (n = 46) had more exacerbation days/patient/year (33.3 (95 % CI 10.9; 55.6)) than optimal adherent patients (n = 38) (23.7 (95 % CI 1.7; 45.7)). The duration per COPD exacerbation was longer for patients with significant delay or no treatment (15.5 days) compared to optimal adherent patients (7.8 days). No differences in health outcomes were observed between optimal and suboptimal adherent patients. Conclusions: Being adherent to action plans is associated with better health outcomes than significant delayed treatment or no treatment at all. Interestingly, suboptimal adherence demonstrated health benefits comparable to optimal adherence. COPD self-management interventions should prioritise strategies to optimise patients’ adherence to action plans.

Contribution: This article presents a comprehensive overview of characteristics of educational designs of collaborative engineering design activities found in literature and how these characteristics mediate students' collaboration. Background: Engineers have to solve complex problems that require collaboration. In education, various collaborative engineering design activities have been implemented to prepare students for these professional practices. According to cultural historical activity theory (CHAT), educational activities can be described in terms of interrelated elements, i.e., subject, object, tools, rules, division of labor, and community, that influence learning outcomes. A key issue is how these elements mediate students' collaborative efforts and how they contribute to learning. Research Questions: 1) How is collaborative learning implemented in engineering design education? 2) How do the elements of CHAT and their interrelations mediate collaborative learning? and 3) What is the evidence that the implementation of collaborative learning contributed to the achievement of desired learning outcomes? Methodology: A systematic literature review following preferred reporting items for systematic review and meta-analyses protocols guidelines was conducted, including 111 articles published between 2011 and 2021. CHAT was used as analytical framework. Findings: Collaborative learning was implemented in engineering design activities to develop technical as well as nontechnical skills. For the CHAT elements, it was found that establishing a common object, rules for collaboration, and division of labor are essential for effective collaboration and can be enhanced through digital technologies (tools) and support from a community, for example, educators. Finally, results showed that there is evidence that described implementations contribute to learning. However, this evidence needs to be interpreted with care, due to methodological issues in some included articles.

Educational technologies develop quickly. Which functions of face-to-face education can be substituted by technology for distance learning? One of the risks of online education is the lack of embodied interactions. We investigate what embodied interactive technologies might offer for teaching trigonometry when learning at a distance. In a multiple case study, we analyze the potential of embodied action-based design for fostering conceptual understanding of a sine graph. It appears that independent learning with tablet-based activities leads to acquiring new sensory-motor coordinations. Some students include these new embodied experiences into mathematical discourse and trigonometry problem solving themselves, while others still need some support from a teacher. However, distantly acquired embodied experiences can be easily recalled in a few days after learning and serve well as a substrate for further conceptualization and problem-solving. The results speak for a clear contribution that embodied design might provide for grounding conceptual understanding in distance learning. However, we expect embodied design to be particularly helpful in a blended learning format.

Abstract Arm cycling is used for cardiorespiratory rehabilitation but its therapeutic effects on the neural control of the trunk after spinal cord injury (SCI) remain unclear. We investigated the effects of single session of arm cycling on corticospinal excitability, and the feasibility of home-based arm cycling exercise training on volitional control of the erector spinae (ES) in individuals with incomplete SCI. Using transcranial magnetic stimulation, we assessed motor evoked potentials (MEPs) in the ES before and after 30 min of arm cycling in 15 individuals with SCI and 15 able-bodied controls (Experiment 1). Both groups showed increased ES MEP size after the arm cycling. The participants with SCI subsequently underwent a 6-week home-based arm cycling exercise training (Experiment 2). MEP amplitudes and activity of the ES, and movements of the trunk during reaching, self-initiated rapid shoulder flexion, and predicted external perturbation tasks were measured. After the training, individuals with SCI reached further and improved trajectory of the trunk during the rapid shoulder flexion task, accompanied by increased ES activity and MEP amplitudes. Exercise adherence was excellent. We demonstrate preserved corticospinal drive after a single arm cycling session and the effects of home-based arm cycling exercise training on trunk function in individuals with SCI.

Abstract Bacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25 cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14 Streptococcus pneumoniae or 5 Streptococcus agalactiae serotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM+) memory B cells and vaccine-inefficient S. pneumoniae serotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence of S. agalactiae invasive disease, compared to Dutch donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy.

Background Regional/national SARS-CoV-2 genomic data platforms (DP) have played a key role during the Covid-19 pandemic to centralize data, curate, process and re-share them in a consistent form and pseudonymized/anonymized to international repositories. In Europe, several countries were able to establish such infrastructures rapidly and put them in production over the course of 2021, some earlier. Methods This survey aimed to estimate the effort that was needed to establish and run these DPs during the sequencing peak of the pandemic in 2021, including activities from data curation to data brokering, and what it would take to expand these DPs to other pathogens and antimicrobial resistance from 2023 onwards. Results Overall, a median of 10 person-months (PM) were used by each DP over 2021 and a median of 18 PM (per year) would be needed to expand activities from 2023 onwards. This survey shows that short-term funding remains commonplace and a struggle for the majority of DPs. Key supporters and arguments (e.g. centered around efficiency and cost-savings) for public health authorities and research funding bodies have also been identified to help individual data platforms in strengthening their funding proposals. Conclusions Ultimately, we propose that DPs get connected into a supra-national entity to build a stronger case and get access to major infrastructure funding grants at the European and global levels.

BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched death receptor and EIF2 signalling pathways whereas Anaerostipes positively correlated with enriched interferon signalling, Nur77 signalling and inflammasome pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiotas role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases.

Despite enormous progress in understanding the fundamentals of bacterial gene regulation, our knowledge remains limited when compared with the number of bacterial genomes and regulatory systems to be discovered. Derived from a small number of initial studies, classic definitions for concepts of gene regulation have evolved as the number of characterized promoters has increased. Together with discoveries made using new technologies, this knowledge has led to revised generalizations and principles. In this Expert Recommendation, we suggest precise, updated definitions that support a logical, consistent conceptual framework of bacterial gene regulation, focusing on transcription initiation. The resulting concepts can be formalized by ontologies for computational modelling, laying the foundation for improved bioinformatics tools, knowledge-based resources and scientific communication. Thus, this work will help researchers construct better predictive models, with different formalisms, that will be useful in engineering, synthetic biology, microbiology and genetics.

A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols (≤10 µm) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions.