The role of blood platelets in tumor angiogenesis

AbstractCoagulation abnormalities occur frequently in cancer patients. It is becoming evident that blood platelets have an important function in this process. However, understanding of the underlying mechanisms is still very modest. In this review, we discuss the role of platelets in tumor angiogenesis and growth and suggest their potential significance in malignancies. Platelets contain various pro-and antiangiogenic molecules, which seem to be endocytosed and sequestered in different populations of α-granules. Furthermore, tumor endothelial cells are phenotypically and functionally different from endothelial cells in healthy tissue, stimulating local platelet adhesion and subsequent activation. As a consequence, platelets are able to secrete their angiogenic and angiostatic content, most likely in a regulated manner. The overall effect of these platelet–endothelium interactions appears to be proangiogenic, stimulating tumor angiogenesis. We favor the view that local adhesion and activation of blood platelets and dysregulation of coagulation represent underestimated pathways in the progression of cancer

Platelets as messengers of early-stage cancer

Platelets have an important role in tumor angiogenesis, growth, and metastasis. The reciprocal interaction between cancer and platelets results in changes of several platelet characteristics. It is becoming clear that analysis of these platelet features could offer a new strategy in the search for biomarkers of cancer. Here, we review the human studies in which platelet characteristics (e.g., count, volume, protein, and mRNA content) are investigated in early-stage cancer. The main focus of this paper is to evaluate which platelet features are suitable for the development of a blood test that could detect cancer in its early stages

Understanding effort regulation: Comparing 'Pomodoro' breaks and self-regulated breaks

BackgroundDuring self-study, students need to monitor and regulate mental effort to replete working memory resources and optimize learning results. Taking breaks during self-study could be an effective effort regulation strategy. However, little is known about how breaktaking relates to self-regulated learning. AimsWe investigated the effects of taking systematic or self-regulated breaks on mental effort, task experiences and task completion in real-life study sessions for 1 day. SampleEighty-seven bachelor's and master's students from a Dutch University. MethodsStudents participated in an online intervention during their self-study. In the self-regulated-break condition (n = 35), students self-decided when to take a break; in the systematic break conditions, students took either a 6-min break after every 24-min study block (systematic-long or 'Pomodoro technique', n = 25) or a 3-min break after every 12-min study block (systematic-short, n = 27). ResultsStudents had longer study sessions and breaks when self-regulating. This was associated with higher levels of fatigue and distractedness, and lower levels of concentration and motivation compared to those in the systematic conditions. We found no difference between groups in invested mental effort or task completion. ConclusionsTaking pre-determined, systematic breaks during a study session had mood benefits and appeared to have efficiency benefits (i.e., similar task completion in shorter time) over taking self-regulated breaks. Measuring how mental effort dynamically fluctuates over time and how effort spent on the learning task differs from effort spent on regulating break-taking requires further research

Robust, defensible, and fair: The AMEE guide to selection into medical school: AMEE Guide No. 153

Selection is the first assessment of medical education and training. Medical schools must select from a pool of academically successful applicants and ensure that the way in which they choose future clinicians is robust, defensible, fair to all who apply and cost-effective. However, there is no comprehensive and evidence-informed guide to help those tasked with setting up or rejuvenating their local selection process. To address this gap, our guide draws on the latest research, international case studies and consideration of common dilemmas to provide practical guidance for designing, implementing and evaluating an effective medical school selection system. We draw on a model from the field of instructional design to frame the many different activities involved in doing so: the ADDIE model. ADDIE provides a systematic framework of Analysis (of the outcomes to be achieved by the selection process, and the barriers and facilitators to achieving these), Design (what tools and content are needed so the goals of selection are achieved), Development (what materials and resources are needed and available), Implementation (plan [including piloting], do study and adjust) and Evaluation (quality assurance is embedded throughout but the last step involves extensive evaluation of the entire process and its outcomes)

Enhancing Team Learning through Leader Inclusiveness: A One-Year Ethnographic Case Study of an Interdisciplinary Teacher Team

Phenomenon: Developing modern medical curricula requires collaboration between different scientific and clinical disciplines. Consequently, institutions face the daunting task to engage colleagues from different disciplines in effective team collaboration. Two aspects that are vital to the success of such teamwork are "team learning behavior" by all team members and "leader inclusiveness behavior" by the team leader. Team members display team learning behavior when they share information, build upon and integrate each other's viewpoints. The team leader can promote such team learning by exhibiting inclusiveness behavior, which aims to encourage diversity and preserve individual differences for an inclusive workplace, nurturing engagement in teamwork. There is a paucity of in-depth research on leader inclusiveness behavior in the field of medical education. This case study aimed to offer unique insight into how leader inclusiveness behavior manifests itself in a successful interdisciplinary teacher team, demonstrating team learning behavior in undergraduate medical education. Approach: We conducted a qualitative, ethnographic case study using different but complementary methods, including observations, interviews and a documentary analysis of email communication. By means of purposive sampling, we selected an existing interdisciplinary teacher team that was responsible for an undergraduate medical course at Maastricht University, the Netherlands, and that was known to be successful. Chaired by a physician, the team included planning group members and tutors with medical, biomedical, and social sciences backgrounds as well as student-representatives. In the course of one academic year, 23 meetings were observed and recorded, informal interviews were conducted, and over 100 email conversations were collected. All data were submitted to a directed content analysis based on team learning and leader inclusiveness concepts. Findings: Leader inclusiveness behavior became evident from verbal and non-verbal interactions between the team leader and team members. Leader inclusiveness behavior that facilitated team learning behavior manifested itself in five actions undertaken by the team leader: coordinating, explicating, inviting, connecting, and reflecting. Similarly, team members facilitated team learning behavior by participating actively, speaking up behavior, and mimicking leader inclusiveness behavior. These behaviors demonstrated engagement and feelings of inclusion, and reinforced leader inclusiveness behavior by creating additional opportunities for the leader to exhibit such behavior. Insights: This case study responds to the need for inclusive leadership approaches in medical education. Our findings build upon theoretical knowledge on team learning and leader inclusiveness concepts. By studying behaviors, interactions and documents we obtained in-depth information on leader inclusiveness. Our findings are unique in that they demonstrate how leader inclusiveness behavior manifests itself when leaders interact with their team members. This study provides health professionals who are active in education with practical suggestions on how to act as a successful and inclusive leader. Finally, the behaviors identified open up avenues for future professional development initiatives and future research on team leadership

The effects of light physical activity on learning in adolescents: a systematic review

The effects of light physical activity (LPA) interventions on adolescents' learning were reviewed. Learning was operationalized as academic performance and academic-performance-related cognitive functions. Using PubMed, Web of Science, ERIC, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, and Cochrane Library, only English-language studies published until 19-07-2021 were included. Of the resulting 49, 34 studies posed a low risk of bias, covering: executive functions (inhibition, updating, and shifting), memory, and academic performance. The quality of evidence of each outcome was very low, mainly due to inconsistencies in results between studies. Nonetheless, most studies found positive (n = 15) or null (n = 14) effects of LPA interventions on adolescents' learning. Negative effects of LPA interventions were only found from studies with on-task procedures (n = 5). Only two studies utilized longitudinal LPA interventions, of which one reported positive effects, and the other reported null effects. Future studies should explore the role of potential moderators, e.g. timing of LPA interventions with regard to the learning and testing phases. Overall, while introducing LPA in the classroom may be effective at breaking up prolonged sedentary behavior, more high-quality research is needed to establish its positive effect on learning

The effects of light physical activity on learning in adolescents: a systematic review

The effects of light physical activity (LPA) interventions on adolescents' learning were reviewed. Learning was operationalized as academic performance and academic-performance-related cognitive functions. Using PubMed, Web of Science, ERIC, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, and Cochrane Library, only English-language studies published until 19-07-2021 were included. Of the resulting 49, 34 studies posed a low risk of bias, covering: executive functions (inhibition, updating, and shifting), memory, and academic performance. The quality of evidence of each outcome was very low, mainly due to inconsistencies in results between studies. Nonetheless, most studies found positive (n = 15) or null (n = 14) effects of LPA interventions on adolescents' learning. Negative effects of LPA interventions were only found from studies with on-task procedures (n = 5). Only two studies utilized longitudinal LPA interventions, of which one reported positive effects, and the other reported null effects. Future studies should explore the role of potential moderators, e.g. timing of LPA interventions with regard to the learning and testing phases. Overall, while introducing LPA in the classroom may be effective at breaking up prolonged sedentary behavior, more high-quality research is needed to establish its positive effect on learning

When Feedback Backfires: Influences of Negative Discrepancies Between Physicians' Self and Assessors' Scores on Their Subsequent Multisource Feedback Ratings

Introduction: With multisource feedback (MSF) physicians might overrate their own performance compared with scores received from assessors. However, there is limited insight into how perceived divergent feedback affects physicians' subsequent performance scores. Methods: During 2012 to 2018, 103 physicians were evaluated twice by 684 peers, 242 residents, 999 coworkers, and themselves in three MSF performance domains. Mixed-effect models quantified associations between the outcome variable "score changes" between first and second MSF evaluations, and the explanatory variable "negative discrepancy score" (number of items that physicians rated themselves higher compared with their assessors' scores) at the first MSF evaluation. Whether associations differed across assessor groups and across a physician's years of experience as a doctor was analyzed too. Results: Forty-nine percent of physicians improved their total MSF score at the second evaluation, as assessed by others. Number of negative discrepancies was negatively associated with score changes in domains "organization and (self)management" (b = -0.02; 95% confidence interval [CI], -0.03 to -0.02; SE = 0.004) and "patient-centeredness" (b = -0.03; 95% CI, -0.03 to -0.02; SE = 0.004). For "professional attitude," only negative associations between score changes and negative discrepancies existed for physicians with more than 6-year experience (b(6-10yearsofexperience) = -0.03; 95% CI, -0.05 to -0.003; SE = 0.01; b(16-20yearsofexperience) = -0.03; 95% CI, -0.06 to -0.004; SE = 0.01). Discussion: The extent of performance improvement was less for physicians confronted with negative discrepancies. Performance scores actually declined when physicians overrated themselves on more than half of the feedback items. PA score changes of more experienced physicians confronted with negative discrepancies and were affected more adversely. These physicians might have discounted feedback due to having more confidence in own performance. Future work should investigate how MSF could improve physicians' performance taking into account physicians' confidence

The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

Simple Summary Interaction between blood platelets and cancer cells play an important role in various steps of cancer development and progression. These interactions lead to changes in the platelets' RNA content, resulting in tumor-mediated "education" of platelets. Tumor-educated platelets (TEPs) can be used as a non-invasive biomarker source for cancer detection and progression monitoring. Our lab has previously identified that spliced mRNA TEP signatures provide specific information on the presence, location, and molecular features of cancers. Next to mRNA, other RNA types are present in platelets, and their repertoire can potentially be subjected to cancer-mediated alterations. Despite the evidence that circRNA could be a promising cancer biomarker, they have not yet been analyzed in blood platelets of cancer patients. In this proof-of-concept study, we aim to evaluate whether platelets' circRNA signature could be used as a biomarker for cancer detection and progression. Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription-quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies