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Providing students with autonomy over their learning process can support the development of their self-regulation skills. This study aimed to examine the effects of autonomy-support interventions on students' self-regulated learning strategies. The participants were 432 students from three secondary schools in the Netherlands. In each school, a one-year field experiment was performed, in which teachers and students shared control over learning processes. At the start and end of the school year, students from both the experimental and control conditions completed a questionnaire on perceived autonomy support and self-regulation strategies used. Univariate analyses of covariance were performed to examine the effects of the interventions on perceived autonomy support and the use of self-regulated learning strategies. The intervention with the highest amount of student control showed positive effects on self-regulated learning strategies 'task orientation', 'planning', and 'process evaluation', although it did show a small decrease in perceived autonomy support. The other two interventions showed an increase in perceived autonomy support and a positive trend in 'monitoring'. The field experiments suggest that different ways of supporting student autonomy can yield different effects on students' self-regulated learning strategies. The tentative conclusion is that a focus on student control is the most effective.

Abstract Background Kidney transplantation (kTx) is by far the most effective method of treating end-stage renal disease, with immunosuppressive therapy being obligatory for all, except identical twins. Despite kTx being the most effective treatment for end-stage renal disease, the patients face significant morbidity. They are often burdened with diabetes, anaemia, lipid disorders, all of which pose heightened risks for cardiovascular disease. Knowing that nutritional status plays a significant role in post-transplant results including graft survival, we conducted this systematic review with the aim to summarise the evidence of nutritional diseases following exposure to immunosuppressive therapy among patients after kTx. Methods This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Our search encompasses observational studies (cohort, case–control, cross-sectional) and randomized controlled trials (RCTs), published and unpublished, completed, and ongoing, written in English from the last 10 years (up to 17th February 2023) in the following databases: MEDLINE (via PubMed), EMBASE (Elsevier), Scopus and Web of Science. Any settings were eligible for inclusion. Quality assessments were done using ROBINS-I and RoB2 tools. Results were summarised in a narrative synthesis. Quantitative analysis was conducted where feasible. The protocol for proposed systematic review was published elsewhere. Results A total of 24 studies were included (participants n = 9,536) in the review. The majority of studies were cohort (n = 16), with moderate or low quality. Most of the studies (n = 16) were conducted in hospital settings. All studies had a higher proportion of male participants compared to female participants, except for one. Diabetes emerged as the most frequent disease assessed (n = 14), while tacrolimus (Tac) was the most commonly evaluated immunosuppressive medication used (n = 16). As a result, Tac presented a higher risk factor for the development of diabetes compared to cyclosporine (CsA). In addition, Tac was linked to weight gain in post-transplant recipients. In contrary, no relationship was found between steroids and weight gain. Regarding other immunosuppressants, everolimus was found to be associated with lipid abnormalities. Though, the relationship between lipid abnormalities and steroid use yielded inconsistent results. Calcineurin inhibitors (CNIs) were studied in various research articles. Consequently, patients who were not using CNIs had a lower prevalence of hypomagnesaemia, hyperkalaemia, and metabolic acidosis compared to those treated with CNIs. Also, CNIs were found to have a negative impact on 25-hydroxyvitamin D (25(OH)D) levels. Another aspect was the use of slow and fast Tacrolimus metabolizers. There was no difference observed in phase angle, visceral fat area, lean body mass index, and the proportion of lean mass as a percentage of total body mass between them. Finally, mammalian target of rapamycin (mTOR) inhibitors was associated with bone status and mycophenolate mofetil was linked to Vitamin B12 deficiencies. Conclusions To the best of our knowledge, this systematic review represents the first comprehensive overview of the evidence regarding immunosuppressive therapy and nutritional diseases in kTx patients. Our findings indicate an association between immunosuppressive therapy and nutritional diseases in this population. However, there is high heterogeneity and suboptimal quality of the included studies. Future researchers should prioritise high-quality, prospective randomized controlled trials to further elucidate these relationships. Trial registration PROSPERO (CRD42023396773), dated 12 April 2023. Protocol publication: https://doi.org/10.3390/jcm12216955 .

Abstract Migraine is a debilitating headache disorder. The disease has neurovascular origin and migraine attacks can be elicited by vasodilative neuropeptides such as alpha calcitonin gene-related peptide (αCGRP). Antagonizing CGRP actions in migraine patients has proven clinically efficient. Here, we present a pipeline for development of a peptide-based hCGRP receptor antagonist with increased half-life capable of antagonising the vasodilatory effect of hαCGRP. A series of hαCGRP8-37 analogues carrying a C18-or C20-diacid lipidation was screened for their antagonism against the hCGRP receptor. hαCGRP8-37 analogues with a C20-diacid were 2-6 fold more potent than analogues conjugated with a C18-diacid. Half-life of hαCGRP8-37 analogues carrying a C20-diacid was estimated in mice in a pilot study (n = 1–2). Half-lives ranged from 7.3 to 13.7 h. An hαCGRP8-37 analogue conjugated with a C20 diacid at position 25 was subjected to an amino acid substitution scan to identify mutations that could further enhance hCGRP receptor antagonism. Substituting alanine with serine at position 36 resulted in a ~ 4 fold gain of potency. Vasodilative actions of hαCGRP were successfully antagonized by hαCGRP8-37 analogues carrying a C20 diacid at position 25. Our findings demonstrate that lipidation can improve hαCGRP8-37 pharmacokinetics while maintaining hαCGRP antagonism, thus demonstrating potential for a peptide-based migraine treatment strategy.

Bryophyte research is severely underrepresented compared to vascular plant research, even though we know that bryophytes are crucial components of ecosystems and contribute significantly to ecosystem functions and processes, and thus to ecosystem services. This underrepresentation creates many hurdles and barriers that Early Career Researchers (ECRs) must first overcome to establish in this field, which significantly hinders research now and in the future. Therefore, this work deals with the future of bryophyte research, and bryophyte ecology in particular, which is reflected in the perspectives of ECRs in this scientific field. By listing the many barriers that bryophyte researchers and especially ECRs face, including underrepresentation, funding and publishing, but also possible solutions, we want to raise awareness for and advocate to raise the profile of bryophyte research. We here identify multiple barriers that bryophyte-focused ECRs face and what is needed to overcome them. We address different structural and institutional levels, ranging from early education in schools to academia, funding and publishing. Raising the profile of bryophyte research works on many different levels simultaneously. To improve the prospects of bryophytes and thus increase scientific interest in, and ultimately understanding of, this important group of plants, we need to raise awareness now.

Abstract The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo‐kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo‐kept lions under the hypothesis that short QT is unique to zoo‐kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo‐kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights-together with neuroscience, biology and data science-closer.

Background Diagnosing acute disease in older adults is challenged by vague and atypical symptoms. Point-of-care tests (POCTs) at home may improve diagnostics and clinical decision-making. We compared various POCT devices to routine testing in acutely ill older adults to assess their clinical reliability.Methods We enrolled participants aged 65+ years requiring acute in-home assessment with signs of acute conditions. Venous and capillary blood samples were collected and analysed on-site using POCT, while identical samples were transported and analysed in a routine laboratory. Agreement between POCT and laboratory testing was assessed using scatter plots with linear regression, Pearson’s correlation coefficient (PCC), limits of agreement, and Bland-Altman plots. Misclassification rates were calculated based on clinically meaningful cut-offs to assess POCT’s clinical reliability.Results We included 100 participants with a mean age of 81.6 (±8.4 SD) years. Strong correlation was found between POCT and routine measurements (PCC: 0.76–0.94 for capillary samples and 0.85–0.98 for venous samples). Venous samples showed higher PCC than capillary, except for neutrophils (0.93 for capillary, 0.89 for venous). Misclassification occurred in capillary samples for haemoglobin (10/62) and total WBC (6/50), while in venous samples, misclassification was observed for haemoglobin (4/54), total WBC (4/50), K+ (5/47), urea (5/47), and creatinine (3/42). No misclassification was observed for Na+.Conclusion POCT provides acceptable, clinically reliable measurements in acutely ill older adults, potentially enhancing diagnostics and treatments during in-home assessment. Venous blood testing is preferable due to a lower misclassification rate, but capillary blood remains a pragmatic alternative, despite higher variation and inaccuracy.

Summary: Background & aims: Accurate fat mass (FM) and muscle mass (MM) assessment is an informative marker of an individual's health. However, the optimal method for assessing body composition in transgender men remains to be determined. Here, we aim to compare body composition estimates in transgender men by bioimpedance analysis (BIA) using the reference settings for “males” and “females” and by dual x-ray absorptiometry (DXA) scans. Methods: We conducted a cross-sectional pilot study investigating the body composition of 10 transgender men undergoing hormonal therapy using BIA and DXA scans. Results: BIA yielded significantly different estimates of body composition depending on the use of either “female” or “male” settings (P

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well‐characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune‐related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor‐infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Clinical academics experience dual workplaces, namely the clinical and the research environment. However, working in two workplaces leads to difficulties in forming an integrated identity, affecting a person’s work environment and well-being. The aim was to explore how clinical academics experience the psychosocial work environment and their suggestions for improving and changing work well-being. A multicenter qualitative approach with group interviews inspired by participatory action design was used. A purposeful criterion sampling strategy was used, selecting researchers affiliated with the university’s research network (n = 12). Data were analyzed by thematic analysis and the consolidated criteria for reporting qualitative research was applied. The main finding, ‘lack of integration of research in clinical practice’, revealed how clinical academics balanced between the two practices, how their need for belonging in both work environments was established by fellowship, and how motivational factors and role models could be enhanced through a joint commitment of responsibility in research units and clinical practice. This study provides a contemporary understanding of the challenges that mainly Ph.D. students encounter and what solutions they would offer. This study adds to knowledge on well-being in psychological work and provides solutions on how clinical academic Ph.D. students can achieve the integration of research in clinical practice.

Autonomy-supportive activities are understood to promote students' autonomous forms of learning motivation, educational outcomes and well-being. In the current study, two learning labs in one Dutch secondary school have been studied. In these learning labs--each lasting one entire school year--students' autonomy during their learning process have been supported by organisational, procedural and cognitive autonomy support activities. Effects on students' learning motivation and their achievement have been examined. In one learning lab, indicated as the one with the most autonomy-supportive classroom climate, students show relatively high scores on intrinsic motivation for learning and high achievements. In the other learning lab, no effects have been found on students' learning motivation and achievement. The extent to which student were allowed to set the task sequence is found to be an autonomy-supportive activity that positively affected both learning motivational and achievement most. Implications for practice and research are discussed.