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1.
BackgroundConsidering the potential cumulative effects of repetitive head impact (HI) exposure, we need sensitive biomarkers to track short- and long-term effects. Circulating small extracellular vesicles (sEVs) (<200 nm) traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease. The purpose of this study was to identify the microRNA (miRNA) profile in circulating sEVs derived from human plasma following repetitive HI exposure.MethodsHealthy adult (aged 18–35 years) soccer players were randomly assigned to one of 3 groups: the HI group performed 10 standing headers, the leg impact group performed 10 soccer ball trapping maneuvers over 10 min, and the control group did not participate in any soccer drills. Plasma was collected before testing and 24 h afterward, and sEVs were isolated and characterized via nanoparticle tracking analysis. Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs, and candidate microRNAs were analyzed via quantitative polymerase chain reaction. In silico target prediction was performed using TargetScan (Version 7.0; targetscan.org) and miRWalk (http://mirwalk.umm.uni-heidelberg.de/) programs, and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney (HEK) 293T/17 cells.ResultsPlasma sEV concentration and size were not affected across time and group following repetitive HI exposure. After 24 h, the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p, miR-423-5p, and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p, miR-144-5p, miR-221-5p, and miR-22-3p. Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels. To our knowledge, miR-7844-5p is a previously unknown miRNA. We identified 8 miR-7844-5p mRNA targets: protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B), LIM and senescent cell antigen-like domains 1 (LIMS1), autophagy-related 12 (ATG12), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), integrin subunit alpha-1 (ITGA1), mitogen-activated protein kinase 1 (MAPK1), glycogen synthase kinase 3β (GSK3β), and mitogen-activated protein kinase 8 (MAPK8).ConclusionCollectively, these data indicate repetitive HI exposure alters plasma sEV miRNA content, but not sEV size or number. Furthermore, for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis, autophagy regulation, mood disorders, and neurodegenerative disease.  相似文献   
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Background:Osteoarthritis is one of the leading causes of pain and disability worldwide,and a large percentage of patients with osteoarthritis are individuals who are also obese.In recent years,a series of animal models have demonstrated that obesity-inducing diets can result in synovial joint damage(both with and without the superimposition of trauma),which may be related to changes in percentage of body fat and a series of low-level systemic inflammatory mediators.Of note,there is a disparity between whether the dietary challenges commence at weaning,representing a weanling onset,or at skeletal maturity,representing an adult onset of obesity.We wished to evaluate the effect ofthe dietary exposure time and the age at which animals are exposed to a high-fat and high-sucrose(HFS) diet to determine whether these factors may result in disparate outcomes,as there is evidence suggesting that these factors result in differential metabolic disturbances.Based on dietary exposure time,we hypothesized that rats fed an HFS diet for 14 weeks from weaning(HFS Weanling) would demonstrate an increase in knee joint damage scores,whereas rats exposed to the HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult) and rats exposed to a standard chow diet(Chow)would not display an increase in knee joint damage scores.Methods:Male Sprague-Dawley rats were fed either an HFS diet for 14 weeks from weaning(HFS Weanling) or an HFS diet for 4 weeks,starting at 12 weeks of age(HFS Adult).At sacrifice,joints were scored using the modified Mankin Criteria,and serum was analyzed for a defined subset of inflammatory markers(Interleukin-6,leptin,monocyte chemoattractant protein-1,and tumor necrosis factorα).Results:When the HFS Weanling and HFS Adult groups were compared,both groups had a similar percent of body fat,although the HFS Weanling group had a significantly greater body mass than the HFS Adult group.The HFS Weanling and HFS Adult animals had a significant increase in body mass and percentage of body fat when compared to the Chow group.Although knee joint damage scores were low in all 3 groups,we found,contrary to our hypothesis,that the HFS Adult group had statistically significant greater knee joint damage scores than the Chow and HFS Weanling groups.Furthermore,we observed that the HFS Weanling group did not have significant differences in knee joint damage scores relative to the Chow group.Conclusion:These findings indicate that the HFS Weanling animals were better able to cope with the dietary challenge of an HFS diet than the HFS Adult group.Interestingly,when assessing various serum proinflammatory markers,no significant differences were detected between the HTS Adult and HFS Weanling groups.Although details regarding the mechanisms underlying an increase in knee joint damage scores in the HFS Adult group remain to be elucidated,these findings indicate that dietary exposure time maybe less important than the age at which an HFS diet is introduced.Moreover,increases in serum proinflammatory mediators do not appear to be directly linked to knee joint damage scores in the HFS Weanling group animals but may be partially responsible for the observed knee joint damage in the adults over the very short time of exposure to the HFS diet.  相似文献   
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As low-stakes testing contexts increase, low test-taking effort may serve as a serious validity threat. One common solution to this problem is to identify noneffortful responses and treat them as missing during parameter estimation via the effort-moderated item response theory (EM-IRT) model. Although this model has been shown to outperform traditional IRT models (e.g., two-parameter logistic [2PL]) in parameter estimation under simulated conditions, prior research has failed to examine its performance under violations to the model’s assumptions. Therefore, the objective of this simulation study was to examine item and mean ability parameter recovery when violating the assumptions that noneffortful responding occurs randomly (Assumption 1) and is unrelated to the underlying ability of examinees (Assumption 2). Results demonstrated that, across conditions, the EM-IRT model provided robust item parameter estimates to violations of Assumption 1. However, bias values greater than 0.20 SDs were observed for the EM-IRT model when violating Assumption 2; nonetheless, these values were still lower than the 2PL model. In terms of mean ability estimates, model results indicated equal performance between the EM-IRT and 2PL models across conditions. Across both models, mean ability estimates were found to be biased by more than 0.25 SDs when violating Assumption 2. However, our accompanying empirical study suggested that this biasing occurred under extreme conditions that may not be present in some operational settings. Overall, these results suggest that the EM-IRT model provides superior item and equal mean ability parameter estimates in the presence of model violations under realistic conditions when compared with the 2PL model.  相似文献   
5.
Reading and Writing - Spelling and handwriting are different processes; however, they are learned simultaneously, and numerous studies have shown that they interact. Besides the commonly reported...  相似文献   
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Battles for technological dominance: an integrative framework   总被引:3,自引:0,他引:3  
This paper proposes an integrative framework for understanding the process by which a technology achieves dominance when “battling” against other technological designs. We focus on describing the different stages of a dominance battle and propose five battle milestones that in turn define five key phases in the process. We review the literature from several disciplines to identify the key firm- and environment-level factors that affect the outcome of a technology battle and posit that the relative importance of each factor will vary depending on the phase considered. Our framework complements and extends existing literature and has implications both for theory and for management practice.  相似文献   
7.
Web‐based e‐learning education research and development now focuses on the inclusion of new technological features and the exploration of software standards. However, far less effort is going into finding solutions to psychopedagogical problems in this new educational category. This paper proposes a psychopedagogical instructional model based on content structure, the latest research into information processing psychology and social contructivism, and defines a blended approach to the learning process. Technologically speaking, the instructional model is supported by learning objects, a concept inherited from the object‐oriented paradigm.  相似文献   
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Purpose: This paper reflects upon the practice of Argentine rural extensionists working in the extension public system through the process of identifying different rural extensionists' types of mindsets and comparing them with transfer of technology extension approach, dialogical processes of horizontal knowledge exchange, participatory perspectives and innovation system approach.

Design/Methodology/approach: A quali-quantitative investigation was conducted. Surveys containing closed and open questions were sent via email to rural extensionists. This allowed the researcher to identify their beliefs about different issues connected to extension practice. The sample was incidental (n = 219; 143 men, 76 women). Qualitative data was categorized and quantified. Finally, a two-steps cluster analysis was implemented.

Findings: Two types of rural extensionists' mindsets were identified, one of which relates to the transfer of technology approach and other to the dialogical/horizontal model, yet neither of them fitting the ideal of the most important extension institution of the country, which supports an innovation system approach.

Practical implications: Extensionists' practices and institutional ideals do not coincide. Reflexive training processes are required to make beliefs about rural extension explicit in order to build a contextually suitable extension proposal. Originality/Value: Through a quali-quantitative approach to the issue of rural extensionists' mindsets, this paper contributes to a better understanding of Argentine rural extensionists' practices.  相似文献   

10.
Tertiary Education and Management - Why is the gender gap so large in researchers’ career progression? Do men and women have different priorities in their academic careers? This study...  相似文献   
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