Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cavity tumor. In this study, we examined the basis for the activity of PD-1-based immune checkpoint therapy that is being explored widely in head and neck cancers. Using multispectral imaging, we systematically investigated the OTSCC tumor microenvironment (TME) by evaluating the frequency of PD-1 expression in CD8+, CD4+ and FoxP3+ tumor-infiltrating lymphocytes (TIL). We also defined the cellular sources of PD-L1 to evaluate the utility of PD-1:PD-L1 blocking antibody therapy in this patient population. PD-L1 was expressed in 79% of the OTSCC specimens examined within the TME. Expression of PD-L1 was associated with moderate to high levels of CD4+ and CD8+ TIL. We found that CD4+ TIL were present in equal or greater frequencies than CD8+ TIL in 94% of OTSCC, and that CD4+ FOXP3neg TIL were co-localized with PD-1/PD-L1/CD68 more frequently than CD8+ TIL. However, both CD4+PD1+ and CD8+PD1+ TIL were anergic in the setting of PD-L1 expression. Overall, our results highlight the importance of CD4+ TIL as pivotal regulators of PD-L1 levels and in determining the responsiveness of OTSCC to PD1-based immune checkpoint therapy.
Purpose Our previous work on manipulating typicality of category exemplars during treatment of naming deficits has shown that training atypical examples generalizes to untrained typical examples but not vice versa. In contrast to natural categories that consist of fuzzy boundaries, well-defined categories (e.g., shapes) have rigid category boundaries. Whether these categories illustrate typicality effects similar to natural categories is under debate. The present study addressed this question in the context of treatment for naming deficits in aphasia. Methods Using a single subject experiment design, three participants with aphasia received a semantic feature treatment to improve naming of either typical or atypical items of shapes, while generalization was tested to untrained items of the category. Results For two of the three participants, training naming of atypical examples of shapes resulted in improved naming of untrained typical examples. Training typical examples in one participant did not improve naming of atypical examples. All three participants, however, showed weak acquisition trends. Conclusions Results of the present study show equivocal support for manipulating typicality as a treatment variable within well defined categories. Instead, these results indicate that acquisition and generalization effects within well defined categories such as shapes are overshadowed by their inherent abstractness.
BackgroundTelevision (TV) viewing has been associated with many undesirable outcomes for children, such as increased risk of obesity, but TV viewing can also have benefits. Although restrictive parenting practices are effective in reducing children’s TV viewing, not all parents use them and it is currently unclear why. The current study examined parenting practices related to TV viewing in the context of social- cognitive theory. Specifically, we hypothesized that positive and negative Parental Outcome Expectations for child’s TV Viewing (POETV) would be associated with social co-viewing and restrictive parenting practices, and that POETV and parenting practices influence the amount of TV viewed by child.MethodData were collected from an internet survey of 287 multi-ethnic parents and their 6–12 year old children on participants’ sociodemographic information, parenting practices related to TV use, POETV, and parent and child TV viewing. Path analysis was used to examine the relationship amongst variables in separate models for weekday and weekend TV viewing. controlling for child age, household education, and parental TV viewing.ResultsThe results provided partial support for the hypotheses, with notable differences between weekday and weekend viewing. The models explained 13.6 % and 23.4 % of the variance in children’s TV viewing on weekdays and weekends respectively. Neither positive nor negative POETV were associated with restrictive TV parenting in either model. One subscale each from positive and negative POETV were associated with social co-viewing parenting on both weekends and weekdays in the expected direction. Restrictive parenting practices were directly negatively associated with children’s TV viewing on weekdays, but not weekends. Social co-viewing parenting was directly positively associated with children’s TV viewing on weekends, but not weekdays. The strongest influence on children’s TV viewing was having a TV in the child’s bedroom. Negative POETV was weakly associated with having a TV in the child’s room.ConclusionsThese findings suggest that POETV and parenting may have a greater impact on weekend TV viewing, when children tend to watch more TV, than weekday. The models suggest that POETV, parenting and especially removing the TV from children’s rooms may be promising targets for interventions.
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