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1.
Front Robot AI ; 8: 768642, 2021.
Article En | MEDLINE | ID: mdl-34881295

Background: Play is critical for children's physical, cognitive, and social development. Technology-based toys like robots are especially of interest to children. This pilot study explores the affordances of the play area provided by developmentally appropriate toys and a mobile socially assistive robot (SAR). The objective of this study is to assess the role of the SAR on physical activity, play behavior, and toy-use behavior of children during free play. Methods: Six children (5 females, Mage = 3.6 ± 1.9 years) participated in the majority of our pilot study's seven 30-minute-long weekly play sessions (4 baseline and 3 intervention). During baseline sessions, the SAR was powered off. During intervention sessions, the SAR was teleoperated to move in the play area and offered rewards of lights, sounds, and bubbles to children. Thirty-minute videos of the play sessions were annotated using a momentary time sampling observation system. Mean percentage of time spent in behaviors of interest in baseline and intervention sessions were calculated. Paired-Wilcoxon signed rank tests were conducted to assess differences between baseline and intervention sessions. Results: There was a significant increase in children's standing (∼15%; Z = -2.09; p = 0.037) and a tendency for less time sitting (∼19%; Z = -1.89; p = 0.059) in the intervention phase as compared to the baseline phase. There was also a significant decrease (∼4.5%, Z = -2.70; p = 0.007) in peer interaction play and a tendency for greater (∼4.5%, Z = -1.89; p = 0.059) interaction with adults in the intervention phase as compared to the baseline phase. There was a significant increase in children's interaction with the robot (∼11.5%, Z = -2.52; p = 0.012) in the intervention phase as compared to the baseline phase. Conclusion: These results may indicate that a mobile SAR provides affordances through rewards that elicit children's interaction with the SAR and more time standing in free play. This pilot study lays a foundation for exploring the role of SARs in inclusive play environments for children with and without mobility disabilities in real-world settings like day-care centers and preschools.

2.
Cell Rep ; 34(1): 108532, 2021 01 05.
Article En | MEDLINE | ID: mdl-33406420

Heterobifunctional proteolysis-targeting chimeric compounds leverage the activity of E3 ligases to induce degradation of target oncoproteins and exhibit potent preclinical antitumor activity. To dissect the mechanisms regulating tumor cell sensitivity to different classes of pharmacological "degraders" of oncoproteins, we performed genome-scale CRISPR-Cas9-based gene editing studies. We observed that myeloma cell resistance to degraders of different targets (BET bromodomain proteins, CDK9) and operating through CRBN (degronimids) or VHL is primarily mediated by prevention of, rather than adaptation to, breakdown of the target oncoprotein; and this involves loss of function of the cognate E3 ligase or interactors/regulators of the respective cullin-RING ligase (CRL) complex. The substantial gene-level differences for resistance mechanisms to CRBN- versus VHL-based degraders explains mechanistically the lack of cross-resistance with sequential administration of these two degrader classes. Development of degraders leveraging more diverse E3 ligases/CRLs may facilitate sequential/alternating versus combined uses of these agents toward potentially delaying or preventing resistance.


Adaptor Proteins, Signal Transducing/metabolism , Antineoplastic Agents/pharmacology , Multiple Myeloma/genetics , Multiple Myeloma/metabolism , Ubiquitin-Protein Ligases/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , Animals , CRISPR-Cas Systems , Cell Line, Tumor , Cyclin-Dependent Kinase 9/metabolism , Drug Resistance, Neoplasm , Gene Editing , Gene Expression Regulation, Neoplastic , Genes, Overlapping , Genome-Wide Association Study , Genomics/methods , Humans , Mice , Multiple Myeloma/drug therapy , Oncogene Proteins/metabolism , Proteins/antagonists & inhibitors , Proteins/metabolism , Proteolysis , Tumor Cells, Cultured
3.
Pediatr Phys Ther ; 32(3): 243-248, 2020 07.
Article En | MEDLINE | ID: mdl-32604369

PURPOSE: The purpose of the study is to examine how perceived barriers change before and after a 3-month period of modified ride-on car use. METHODS: This study used a qualitative content analysis of perceived barriers. Fourteen caregivers (13 mothers; 1 grandmother) responded to a single-question, free-response survey before and after a 3-month period of modified ride-on car use. RESULTS: A total of 11 and 20 perceived barriers were reported before and after the 3-month period. Environmental barriers were the most frequently reported before and after the 3-month period. CONCLUSIONS: Pediatric physical therapists need to be aware of the potential perceived barriers that families may experience in regard to young children with disabilities using modified ride-on cars and determine strategies to support families on an individual basis.


Architectural Accessibility , Disabled Children/rehabilitation , Disabled Children/statistics & numerical data , Physical Therapy Modalities/instrumentation , Physical Therapy Modalities/standards , Practice Guidelines as Topic , Self-Help Devices/standards , Automobiles , Child, Preschool , Female , Humans , Infant , Male , Mobility Limitation , Self-Help Devices/statistics & numerical data , Surveys and Questionnaires , Time Factors
4.
Pediatr Phys Ther ; 32(2): 129-135, 2020 04.
Article En | MEDLINE | ID: mdl-32150029

PURPOSE: Modified ride-on cars have emerged as an early powered mobility option for young children with disabilities. The purpose of this study was to identify, extract, and synthesize perceived barriers of modified ride-on car use reported in previous studies. METHODS: This study was descriptive using a qualitative content analysis of previously published studies identified from a systematic literature search. RESULTS: Categories of perceived barriers were identified: device, environmental, child-related perceived barriers regarding health, tolerance, and abilities, and caregiver-related perceived barriers regarding physical requirements, time, and motivation. Device and environmental perceived barriers were the most reported. CONCLUSIONS: Pediatric physical therapists play a critical role in working with families to promote their self-efficacy for using the modified ride-on car and their capacity for overcoming the inherent difficulties associated with use. Most of the reported perceived barriers are modifiable, at least to some degree, with likely effects on modified ride-on car use.


Automobiles/statistics & numerical data , Disabled Children/statistics & numerical data , Head Protective Devices/statistics & numerical data , Mobility Limitation , Self-Help Devices/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male
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