Insight into the potential candidate genes and signaling pathways involved in lymphoma disease in dogs using a comprehensive whole blood transcriptome analysis.

Lymphoma is one of the most prevalent hematological cancers, accounting for 15-20 % of new cancer diagnoses in dogs. Therefore, this study aims to explore the important genes and pathways involved in canine lymphoma progression and understand the underlying molecular mechanisms using RNA sequencing. In this study, RNAs acquired from seven pairs of lymphoma and non-lymphoma blood samples were sequenced from different breeds of dogs. Sequencing reads were preprocessed, aligned with the reference genome, assembled and expressions were estimated through bioinformatics approaches. At a false discovery rate (FDR) < 0.05 and fold change (FC) ≥ 1.5, a total of 625 differentially expressed genes (DEGs) were identified between lymphoma and non-lymphoma samples, including 347 up-regulated DEGs such as SLC38A11, SCN3A, ZIC5 etc. and 278 down-regulated DEGs such as LOC475937, CSMD1, KRT14 etc. GO enrichment analysis showed that these DEGs were highly enriched for molecular function of ATP binding and calcium ion binding, cellular process of focal adhesion, and biological process of immune response, and defense response to virus. Similarly, KEGG pathways analysis revealed 11 significantly enriched pathways such as ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, ABC transporters etc. In the protein-protein interaction (PPI) network, CDK1 was found to be a top hub gene with highest degree of connectivity. Three modules selected from the PPI network showed that canine lymphoma was highly associated with cell cycle, ECM-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy and RIG-I-like receptor signaling pathway. Overall, our findings highlighted new candidate therapeutic targets for further testing in canine lymphoma and facilitate the understanding of molecular mechanism of lymphoma's progression in dogs.

A Serious Game-Derived Index for Detecting Children With Heterogeneous Developmental Disabilities: Randomized Controlled Trial.

BACKGROUND: Developmental disabilities are a set of heterogeneous delays or difficulties in one or more areas of neuropsychological development. Considering that childhood is an essential stage of brain development and developmental delays lead to personal or social burdens, the early detection of childhood developmental disabilities is important. However, early screening for developmental disabilities has been a challenge because of the fear of positive results, expensive tests, differences in diagnosis depending on examiners' abilities, and difficulty in diagnosis arising from the need for long-term follow-up observation. OBJECTIVE: This study aimed to assess the feasibility of using a serious game-derived index to identify heterogeneous developmental disabilities. This study also examines the correlation between the game-derived index and existing neuropsychological test results. METHODS: The randomized controlled trial involved 48 children with either normal development or developmental disabilities. In this clinical trial, we used 19 features (6 from the Korean-Wechsler Preschool and Primary Scale of Intelligence, 8 from the Psychoeducational Profile Revised, 2 from the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and 3 from the Pediatric Evaluation of Disability Inventory) from neuropsychological tests and 9 (7 game scores, path accuracy, and completion rate) from the serious game, DoBrain. The following analysis was conducted based on participants' baseline information and neuropsychological test and game-derived index data for one week: (1) we compared the baseline information between the normal development and developmental disabilities groups; (2) then we measured the correlation between the game-derived index and the neuropsychological test scores for each group; and (3) we built a classifier based on the game-derived index with a Gaussian process method and then compared the area under the curve (AUC) with a model based on neuropsychological test results. RESULTS: A total of 16 children (normal development=9; developmental disabilities=7) were analyzed after selection. Their developmental abilities were assessed before they started to play the serious games, and statistically significant differences were found in both groups. Specifically, the normal development group was more developed than the developmental disabilities group in terms of social function, gross motor function, full-scale IQ, and visual motor imitation, in that order. Similarly, the normal development group obtained a higher score on the game-derived index than the developmental disabilities group. In the correlation analysis between the game-derived index and the neuropsychological tests, the normal development group showed greater correlation with more variables than the developmental disabilities group. The game-derived index-based model had an AUC=0.9, a similar detection value as the neuropsychological test-based model's AUC=0.86. CONCLUSIONS: A game-derived index based on serious games can detect children with heterogenous developmental disabilities. This suggests that serious games can be used as a potential screening tool for developmental disabilities. TRIAL REGISTRATION: Clinical Research Information Service KCT0003247; https://cris.nih.go.kr/cris/en/search/search_result_st01 .jsp?seq=12365.