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In this crossover experiment, we investigated the impact of a statement bank, enabling the reuse of previously written feedback (SA condition), on 45 math teachers' feedback for 60 completed linear equation tests, compared to traditional pen-and-paper feedback (PP condition). In the SA condition, teachers were encouraged to use atomic feedback, a set of formulation requirements that makes feedback items significantly more reusable. A previous study found that significantly more feedback was written in the SA condition but did not investigate the content of the feedback. To address this gap, we employed a novel approach of combining text mining with qualitative methods. Results indicate similar wording and sentiments in both conditions. However, SA feedback was more elaborate yet general, focusing on major and minor strengths and deficits, while PP feedback was shorter but more concrete, emphasising main issues. Despite low feedback quality in both conditions, the statement bank led to less effective diagnostic activities, implying that teachers' careless use of statement banks, although convenient, might lead to lower-quality feedback.

Handwritten tasks are better suited than digital ones to assess higher-order mathematics skills, as students can express themselves more freely. However, maintaining reliability and providing feedback can be challenging when assessing high-stakes, handwritten mathematics exams involving multiple assessors. This paper discusses a new semi-automated grading approach called 'checkbox grading'. Checkbox grading gives each assessor a list of checkboxes consisting of feedback items for each task. The assessor then ticks those feedback items which apply to the student's solution. Dependencies between the checkboxes can be set to ensure all assessors take the same route on the grading scheme. The system then automatically calculates the grade and provides atomic feedback to the student, giving a detailed insight into what went wrong and how the grade was obtained. Atomic feedback consists of a set of format requirements for mathematical feedback items, which has been shown to increase feedback's reusability. Checkbox grading was tested during the final high school mathematics exam (grade 12) organised by the Flemish Exam Commission, with 60 students and 10 assessors. This paper focuses on students' perceptions of the received checkbox grading feedback and how easily they interpreted it. After the exam was graded, all students were sent an online questionnaire, including their personalised exam feedback. The questionnaire was filled in by 36 students, and 4 of them participated in semi-structured interviews. Findings suggest that students could interpret the feedback from checkbox grading well, with no correlation between students' exam scores and feedback understanding. Therefore, we suggest that checkbox grading is an effective way to provide feedback, also for students with shaky subject matter knowledge.

Laboratory e-learning support tools can assist students' learning while preparing for laboratory classes. To successfully work in such virtual experimental environments (VEEs) outside class, students require self-regulated learning (SRL) skills. A deeper understanding of the continuous reciprocal interactions between SRL, satisfaction, and online engagement is needed to develop more effective online learning experiences. This study therefore aimed to explore the interconnection between students' satisfaction with, effort/importance and engagement in an exemplary VEE, and to relate this to their perceived SRL and learning outcomes. Based on surveys in 79 university students, SRL was related to VEE engagement, effort/importance, and satisfaction. VEE engagement and satisfaction were not related to learning outcomes, while SRL and effort were. Students with different SRL also tended to interact differently with the VEE and experienced differing degrees of procedural and feedback support by the e-environment. We conclude that, for optimal learning experience and outcomes, students' effort regulation and SRL need to be supported while interacting with the VEE, preferably by interventions that integrate personalized and adaptive features. This study has implications for designing and optimizing VEEs and indicates that future research should focus on VEEs taking students' SRL and effort regulation into account to support individual learners effectively.

Abstract Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1 ∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS.

Abstract Background Poor subjective sleep quality, depressive symptoms and fatigue occur frequently in postpartum. However, the dynamics of their respective associations from prepartum throughout the maternity period in function of baby feeding method have not been fully elucidated. Methods Prospective, longitudinal study using validated questionnaires probing for sleep quality, insomnia, fatigue and depressive symptoms at 35–37 weeks of gestation and at 2, 8 and 12 weeks postpartum in the obstetric departments of two Flemish hospitals. Somers’d ordinal correlation was used for correlations between the results of questionnaires (ratio variables) and the feeding method variable (an ordinal variable); T tests (normal data) or Mann Whitney (non normal data) tests for equality of means; ordinal regression (‘Proportional odds model’) to investigate the predictive value of parameters at one moment on the feeding method choice at a later moment; logistic regression to investigate the predictive value of parameters on later change of feeding method. Results 188 women indicating a choice for either bottle or breastfeeding in prepartum (27–35 weeks’ gestation) were included. Higher fatigue assessed through the Fatigue Severity Scale within late pregnancy was moderately associated with primary bottle feeding choice. Fatigue decreased at early and late postpartum in bottle feeding (-0.38 ± 1.04; p = .110 and − 0.31 ± 1.01; p = .642 respectively), but remained unchanged from late pregnancy through early and late postpartum in breastfeeding (0.04 ± 1.21; p = .110 and − 0.27 ± 0.96; p = .642 respectively), resulting in similar fatigue in both feeding methods in early through late postpartum. There were no differences in sleep quality or insomnia symptoms at all time points. Presence of postpartum depressive symptoms were associated with early switching to bottle feeding (Somers’ d correlation 0.11 (p = .021). Conclusions Fatigue and depressive symptoms are inversely associated with breastfeeding initiation or maintenance and influence feeding method dynamics.

Abstract Background Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. Methods Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. Results Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. Conclusion Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.

Background Young people with congenital heart disease (CHD) are frequently affected by discontinued follow-up when transferring from paediatric to adult care. Identified predictors for discontinuation include mostly patient-related factors, and further knowledge of hospital and healthcare system factors is needed.Aim This study aims to explore patient-related, hospital-related and healthcare system-related factors affecting continued follow-up care after transfer, as perceived and experienced by paediatric cardiology and adult CHD (ACHD) healthcare providers (HCPs) in Sweden and Belgium.Methods This descriptive qualitative study included individual interviews with cardiologists, nurses and administrative staff, subjected to qualitative content analysis. A total of 30 HCPs from 13 specialist care outpatient clinics at 8 different centres in Sweden and Belgium were interviewed. HCPs were included if they had direct contact with patients and had at least 1 year of work experience.Findings The findings illuminate three main categories of factors perceived by HCPs to affect continued follow-up care after transfer, including ‘care structure’, ‘care processes’ and ‘patient characteristics and circumstances’. Success was described as multifactorial, emphasising processes and structures of care, with a focus on collaboration, organisation, joint responsibility, resources, care relationships and transitional care interventions. Few differences appeared between paediatric and ACHD HCPs and between Swedish and Belgian HCPs.Conclusion HCPs perceived factors on patient, hospital and healthcare system levels to influence continued follow-up. Process-related and structure-related aspects of care were perceived as more influential than individual patient characteristics. Hence, future research on discontinued follow-up care should focus on process-related and structure-related aspects of care delivery.

Abstract Attaining complete anomeric control is still one of the biggest challenges in carbohydrate chemistry. Glycosyl cations such as oxocarbenium and dioxanium ions are key intermediates of glycosylation reactions. Characterizing these highly-reactive intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Although C-2 acyl neighbouring-group participation has been well-studied, the reactive intermediates in more remote participation remain elusive and are challenging to study. Herein, we report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors. First, we use a combination of quantum-chemical calculations and infrared ion spectroscopy to determine the structure of the cationic glycosylation intermediate in the gas-phase. In addition, we establish the structure and exchange kinetics of highly-reactive, low-abundance species in the solution-phase using chemical exchange saturation transfer, exchange spectroscopy, correlation spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple-bond correlation nuclear magnetic resonance spectroscopy. Finally, we apply C-3 acyl neighbouring-group participation to the synthesis of complex bacterial oligosaccharides. This combined approach of finding answers to fundamental physical-chemical questions and their application in organic synthesis provides a robust basis for elucidating highly-reactive intermediates in glycosylation reactions.

Abstract The greatest burden of sickle cell anemia (SCA) globally occurs in sub‐Saharan Africa, where significant morbidity and mortality occur secondary to SCA‐induced vasculopathy and stroke. Transcranial Doppler ultrasound (TCD) can grade the severity of vasculopathy, with disease modifying therapy resulting in stroke reduction in high‐risk children. However, TCD utilization for vasculopathy detection in African children with SCA remains understudied. The objective was to perform a prospective, observational study of TCD findings in a cohort of children with SCA from the Democratic Republic of the Congo, Zambia, and Malawi. A total of 770 children aged 2–17 years without prior stroke underwent screening TCD. A study was scored as low risk when the time‐averaged maximum of the mean (TAMMX) in the middle cerebral artery or terminal internal carotid artery was 50 cm/s, conditional risk when 170–200 cm/s, and high risk when >200 cm/s. Low‐risk studies were identified in 604 children (78%), conditional risk in 129 children (17%), and high risk in three children (0.4%). Additionally, 34 (4%) were scored as having an unknown risk study (TAMMX

AbstractThe present paper is a systematic review that brings together and systematizes the articles on luxury marketing based on the target segment’s religion. Religion is believed to guide consumers’ judgments and decisions toward luxury. The mainstream marketing literature has not focused properly on Muslims who make a growing potential market niche that is agreed to require a customized approach. To the best of our knowledge, it is the first attempt undertaken to systematize existing research in this field. A review protocol is designed and implemented. A total of 46 articles on consumer behavior toward luxury sourced from 2011 in peer-reviewed academic journal studies are analyzed. A novel model has been developed which identifies four luxury purchase predictors and offers comprehensive dimensions of each. Based on the identified literature gaps, the study offers suggestions for future researchers as well as luxury marketing practitioners to advance their marketing strategies. This paper theoretically contributes to the existing literature on luxury marketing by proposing a novel framework that can be tested in different marketplaces and used for comparative purposes. The review adds structure and integrates the different findings to enable wider dissemination of the results to audiences interested in marketing luxury considering consumers’ personal, social, cultural, religious, and global factors.

In March 2020, many schools worldwide were closed due to the COVID-19 pandemic. This closure confronted mathematics teachers with the challenging transition to emergency remote teaching (ERT). How did students experience ERT, and how did these experiences relate to context variables and to their teachers' beliefs and practices? In particular, what didactic approaches and formative assessment practices did secondary mathematics students experience, and which beliefs did they hold concerning digital mathematics education? How were these student experiences and beliefs related to student context variables (gender, need to support family, personal home equipment), teacher beliefs, delivery modes, and student appreciation of mathematics? To investigate these issues, we set out online questionnaires for mathematics teachers and their students in Flanders--the Dutch-speaking part of Belgium--, Germany, and the Netherlands. Data consisted of completed questionnaires by 323 mathematics teachers and 2126 of their students. Results show that even though students preferred regular face-to-face teaching, they were content with the quality of their teachers' distance mathematics teaching. Students reported that they were taught new topics often, but did not experience teachers initiating peer feedback. High student appreciation of mathematics, good home environment, and more synchronous delivery of ERT were related to ERT experiences and more positive beliefs concerning digital mathematics education. These findings have implications for ERT teaching strategies in future, as well as for hybrid teaching practices.

Objective To evaluate the content and usability of a new direct observation tool for assessing competency in delivering person-centred care based on the Gothenburg Centre for Person-Centred Care (gPCC) framework.Design This is a qualitative study using think-aloud techniques and retrospective probing interviews and analyzed using deductive content analysis.Setting Sessions were conducted remotely via Zoom with participants in their homes or offices.Participants 11 participants with lengthy experience of receiving, delivering and/or implementing gPCC were recruited using purposeful sampling and selected to represent a broad variety of stakeholders and potential end-users.Results Participants generally considered the content of the four main domains of the tool, that is, person-centred care activities, clinician manner, clinician skills and person-centred care goals, to be comprehensive and relevant for assessing person-centred care in general and gPCC in particular. Some participants pointed to the need to expand person-centred care activities to better reflect the emphasis on eliciting patient resources/capabilities and psychosocial needs in the gPCC framework. Think-aloud analyses revealed some usability issues primarily regarding difficulties or uncertainties in understanding several words and in using the rating scale. Probing interviews indicated that these problems could be mitigated by improving written instructions regarding response options and by replacing some words. Participants generally were satisfied with the layout and structure of the tool, but some suggested enlarging font size and text spacing to improve readability.Conclusion The tool appears to satisfactorily cover major person-centred care activities outlined in the gPCC framework. The inclusion of content concerning clinician manner and skills was seen as a relevant embellishment of the framework and as contributing to a more comprehensive assessment of clinician performance in the delivery of person-centred care. A revised version addressing observed content and usability issues will be tested for inter-rater and intra-rater reliability and for feasibility of use in healthcare education and quality improvement efforts.

Summary: Background: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. Methods: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. Findings: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. Interpretation: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. Funding: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.

Abstract The neuropeptide corticotropin-releasing factor (CRF) exerts a pivotal role in modulating neuronal activity in the mammalian brain. The effects of CRF exhibit notable variations, depending on factors such as duration of exposure, concentration, and anatomical location. In the CA1 region of the hippocampus, the impact of CRF is dichotomous: chronic exposure to CRF impairs synapse formation and dendritic integrity, whereas brief exposure enhances synapse formation and plasticity. In the current study, we demonstrate long-term effects of acute CRF on the density and stability of mature mushroom spines ex vivo. We establish that both CRF receptors are present in this hippocampal region, and we pinpoint their precise subcellular localization within synapses by electron microscopy. Furthermore, both in vivo and ex vivo data collectively demonstrate that a transient surge of CRF in the CA1 activates the cyclin-dependent kinase 5 (Cdk5)-pathway. This activation leads to a notable augmentation in CRF-dependent spine formation. Overall, these data suggest that upon acute release of CRF in the CA1-SR synapse, both CRF-Rs can be activated and promote synaptic plasticity via activating different downstream signaling pathways, such as the Cdk5-pathway.

Abstract Behavioral traits in dogs are assessed for a wide range of purposes such as determining selection for breeding, chance of being adopted or prediction of working aptitude. Most methods for assessing behavioral traits are questionnaire or observation-based, requiring significant amounts of time, effort and expertise. In addition, these methods might be also susceptible to subjectivity and bias, negatively impacting their reliability. In this study, we proposed an automated computational approach that may provide a more objective, robust and resource-efficient alternative to current solutions. Using part of a ‘Stranger Test’ protocol, we tested n = 53 dogs for their response to the presence and neutral actions of a stranger. Dog coping styles were scored by three dog behavior experts. Moreover, data were collected from their owners/trainers using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ). An unsupervised clustering of the dogs’ trajectories revealed two main clusters showing a significant difference in the stranger-directed fear C-BARQ category, as well as a good separation between (sufficiently) relaxed dogs and dogs with excessive behaviors towards strangers based on expert scoring. Based on the clustering, we obtained a machine learning classifier for expert scoring of coping styles towards strangers, which reached an accuracy of 78%. We also obtained a regression model predicting C-BARQ scores with varying performance, the best being Owner-Directed Aggression (with a mean average error of 0.108) and Excitability (with a mean square error of 0.032). This case study demonstrates a novel paradigm of ‘machine-based’ dog behavioral assessment, highlighting the value and great promise of AI in this context.

Abstract Background Shared decision-making has become of increased importance in choosing the most suitable treatment strategy for early rectal cancer, however, clinical decision-making is still primarily based on physicians’ perspectives. Balancing quality of life and oncological outcomes is difficult, and guidance on patients’ involvement in this subject in early rectal cancer is limited. Therefore, this study aimed to explore preferences and priorities of patients as well as physicians’ perspectives in treatment for early rectal cancer. Methods In this qualitative study, semi-structured interviews were performed with early rectal cancer patients (n = 10) and healthcare providers (n = 10). Participants were asked which factors influenced their preferences and how important these factors were. Thematic analyses were performed. In addition, participants were asked to rank the discussed factors according to importance to gain additional insights. Results Patients addressed the following relevant factors: the risk of an ostomy, risk of poor bowel function and treatment related complications. Healthcare providers emphasized oncological outcomes as tumour recurrence, risk of an ostomy and poor bowel function. Patients perceived absolute risks of adverse outcome to be lower than healthcare providers and were quite willing undergo organ preservation to achieve a better prospect of quality of life. Conclusion Patients’ preferences in treatment of early rectal cancer vary between patients and frequently differ from assumptions of preferences by healthcare providers. To optimize future shared decision-making, healthcare providers should be aware of these differences and should invite patients to explore and address their priorities more explicitly during consultation. Factors deemed important by both physicians and patients should be expressed during consultation to decide on a tailored treatment strategy.

Abstract Background During transition to adulthood and transfer to adult healthcare, emerging adults with chronic conditions are at risk of deteriorating disease control, well-being, and acute, as well as long-term complications. Despite an increasing call for person-centred healthcare services attuned to young peoples’ needs, few validated instruments exist pinpointing adolescents’ and emerging adults’ experiences of preparation for transition and transfer. Thus, the overarching purpose of this study was to develop a person-centred, clinically applicable instrument (Transitional care EXPeriences Questionnaire, TEXP-Q) adjustable to different chronic conditions, although the focus in the present study was Type 1 Diabetes. The specific aim was, therefore, to describe the development and psychometric evaluation of TEXP-Q in emerging adults with Type 1 Diabetes. Methods Initial development of the TEXP-Q was inspired by existing research. Items were formulated in accordance with consensus recommendations for developing patient-reported measures, and extra consideration was taken to ensure person-centredness. Psychometric evaluation comprised two phases: In phase I, data from cognitive interviews, content validity indexing, and judgement of an expert panel provided information on face and content validity. In phase II, data from a cross-sectional study conducted at eight adult diabetes outpatient clinics in Sweden (n = 163) allowed for explorative factor analysis (EFA), as well as calculation of content validity, reliability and responsiveness. Results Combining results from cognitive interviews, content validity index values and expert panel judgement, a test version of TEXP-Q was developed, the content and face validity of which were considered good. This version consisted of 17 items answered on a five-point Likert scale, and three open-ended questions answered in free text. During EFA, four items were removed, and a three-factor solution was recognised as most adequate, accounting for 60% cumulative variance and one single cross-loading. After EFA, the instrument comprised 13 questions, divided into three latent factors. Cronbach’s alpha for the complete instrument was 0.866, which indicates good internal consistency. Crohnbach’s alpha approximated to 0.8 for all factors respectively. Conclusion TEXP-Q is a newly developed, person-centred instrument which has proven to be both valid and reliable when applied to youths with T1D. The questionnaire fills a need for instruments focusing on emerging adults’ experiences of preparation for transition and transfer.