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The advent of massive open online courses (MOOCs) has created opportunities for learning that are clearly in high demand, but the direction in which MOOCs should evolve to best meet the interests and needs of learners is less apparent. Motivated by our interest in whether there are potential and purpose for archived MOOCs to be used as learning resources beyond and between instructor-led live-sessions, we examined the use of a statistics MOOC and a computer science MOOC, both of which were made available as archived-courses after a live-session and for which enrolment continued to grow while archived. Using data collected from surveys of learner demographics and intent, the course database of major learner activity, and the detailed clickstream of all learner actions, we compared the demographics, intent, and behaviour of live- and archived-learners. We found that archived-learners were interested in the live-MOOC and that their patterns of use of course materials, such as the number and sequence of videos they watched, the number of assessments they completed, their demonstration of self-regulatory behaviour, and their rate of participation in the discussion forums, were similar to the live-learners. In addition, we found evidence of learners drawing on an archived-MOOC for use as reference material. Anticipated areas of impact of this work include implications for the future development of MOOCs as resources for self-study and professional development, and in support of learner success in other courses.

Background: Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression. Methods: To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells. Results: Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1. Conclusion: These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis. [ABSTRACT FROM AUTHOR]

Most ecological models are based on the assumption that species interact in pairs. Diverse communities, however, can have higher‐order interactions, in which two or more species jointly impact the growth of a third species. A pitfall of the common pairwise approach is that it misses the higher‐order interactions potentially responsible for maintaining natural diversity. Here, we explore the stability properties of systems where higher‐order interactions guarantee that a specified set of abundances is a feasible equilibrium of the dynamics. Even these higher‐order interactions which lead to equilibria do not necessarily produce stable coexistence. Instead, these systems are more likely to be stable when the pairwise interactions are weak or facilitative. Correlations between the pairwise and higher‐order interactions, however, do permit robust coexistence even in diverse systems. Our work not only reveals the challenges in generating stable coexistence through higher‐order interactions but also uncovers interaction patterns that can enable diversity. [ABSTRACT FROM AUTHOR]

Summary: Contemporary work teams are increasingly faced with external pressures and changing demands that thrust them into stressful conditions that require coping to maintain not only performance but also well‐being. In this paper, we treat the COVID‐19 pandemic as an extreme case of multilevel stressors and coping in teams to investigate how teams and their members simultaneously cope with stressors at both individual and team levels and the impacts this has on their well‐being. We conducted a longitudinal qualitative multi‐case study involving 12 teams, utilizing data from 69 members collected through diaries, interviews, and surveys over a period of 6 months. Our findings illustrate how the needs and coping efforts of teams and individuals can sometimes conflict, resulting in opposing states of well‐being at different levels. We frame this phenomenon as the multilevel well‐being paradox. Our emergent process model of multilevel coping in teams suggests that teams thrive when they establish a shared appraisal of stressors and coping options through active team reflection, and when they adopt coping approaches that align with the specific stressors experienced at both levels. This study advances our understanding of coping in teams by illuminating the intricate interplay between team and individual well‐being and highlighting the paradoxical nature of this relationship. [ABSTRACT FROM AUTHOR]

Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p < 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24–39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) β2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished β2 adrenergic sensitivity. Although IL6R remained elevated, β2 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention. [ABSTRACT FROM AUTHOR]

In this study, we follow students' modeling and covariational reasoning in the context of learning about big data. A three-week unit was designed to allow 12th grade students in a mathematics course to explore big and mid-size data using concepts such as trend and scatter to describe the relationships between variables in multivariate settings. Students' emergent ideas were followed along a varied learning trajectory that included computer-supported collaborative and inquiry-based approaches, using visualization tools and statistical software to explore data and fit a suitable trend, and student presentations of investigations. Findings show progress in some components of students' reasoning and modeling of covariation, and indicate which features of the unit design might contribute to it.

Dental pain, including toothache, is one of the most prevalent types of orofacial pain, causing severe, persistent pain that has a significant negative effect on quality of life, including eating disturbances, mood changes, and sleep disruption. As the primary cause of toothache pain is injury to the uniquely innervated dental pulp, rodent models of this injury provide the opportunity to study neurobiological mechanisms of tissue injury-induced persistent pain. Here we evaluated behavioral changes in mice with a dental pulp injury (DPI) produced by mechanically exposing the pulp to the oral environment. We monitored the daily life behaviors of mice with DPI, including measures of eating, drinking, and movement. During the first 48 hours, the only parameter affected by DPI was locomotion, which was reduced. There was also a significant short-term decrease in the amount of weight gained by DPI animals that was not related to food consumption. As cold allodynia is frequently observed in individuals experiencing toothache pain, we tested whether mice with DPI demonstrate an aversion to drinking cold liquids using a cold-sucrose consumption test. Surprisingly, mice with DPI increased their consumption of sucrose solution, to over 150% of baseline, regardless of temperature. Both the weight loss and increased sucrose intake in the first 2 days of injury were reversed by administration of indomethacin. These findings indicate that enhanced sucrose consumption may be a reliable measure of orofacial pain in rodents, and suggest that alterations in energy expenditure and motivational behaviors are under-recognized outcomes of tooth injury.