Effects of a Nonwearable Digital Therapeutic Intervention on Preschoolers With Autism Spectrum Disorder in China: Open-Label Randomized Controlled Trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause difficulty with communication and social interactions as well as complicated family dynamics. Digital health interventions can reduce treatment costs and promote healthy lifestyle changes. These therapies can be adjunctive or replace traditional treatments. However, issues with cooperation and compliance prevent preschool patients with ASD from applying these tools. In this open-label, randomized controlled trial, we developed a nonwearable digital therapy called virtual reality-incorporated cognitive behavioral therapy (VR-CBT). OBJECTIVE: The aim of this study was to assess the adjunctive function of VR-CBT by comparing the effects of VR-CBT plus learning style profile (LSP) intervention with those of LSP-only intervention in preschool children with ASD. METHODS: This trial was performed in China on 78 preschool children (age 3-6 years, IQ>70) diagnosed with ASD who were randomized to receive a 20-week VR-CBT plus LSP intervention (intervention group, 39/78, 50%) or LSP intervention only (control group, 39/78, 50%). The primary outcome was the change of scores from baseline to week 20, assessed by using the parent-rated Autism Behavior Checklist (ABC). Secondary outcomes included the Childhood Autism Rating Scale (CARS), Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV), and behavioral performance data (accuracy and reaction time) in go/no-go tasks. All primary and secondary outcomes were analyzed in the intention-to-treat population. RESULTS: After the intervention, there was an intervention effect on total ABC (ß=-5.528; P<.001) and CARS scores (ß=-1.365; P=.02). A similar trend was observed in the ABC subscales: sensory (ß=-1.133; P=.047), relating (ß=-1.512; P=.03), body and object use (ß=-1.211; P=.03), and social and self-help (ß=-1.593; P=.03). The intervention also showed statistically significant effects in improving behavioral performance (go/no-go task, accuracy, ß=2.923; P=.04). Moreover, a significant improvement of ADHD hyperactivity-impulsivity symptoms was observed in 53 children with comorbid ADHD based on ADHD-RS-IV (ß=-1.269; P=.02). No statistically significant intervention effect was detected in the language subscale of ABC (ß=-.080; P=.83). Intervention group girls had larger improvements in ABC subscales, that is, sensory and body and object use and in the CARS score and accuracy of go/no-go task (all P<.05) than the control group girls. Statistically significant intervention effects could be observed in hyperactivity-impulsivity symptoms in the intervention group boys with comorbid ADHD compared with those in the control group boys (ß=-1.333; P=.03). CONCLUSIONS: We found potentially positive effects of nonwearable digital therapy plus LSP on core symptoms associated with ASD, leading to a modest improvement in the function of sensory, motor, and response inhibition, while reducing impulsivity and hyperactivity in preschoolers with both ASD and ADHD. VR-CBT was found to be an effective and feasible adjunctive digital tool. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053165; http://www.chictr.org.cn/showproj.aspx?proj=137016.

Effects of Combing Group Executive Functioning and Online Parent Training on School-Aged Children With ADHD: A Randomized Controlled Trial.

OBJECTIVE: The acceptance of drug treatment for younger children with attention-deficit/hyperactivity disorder (ADHD) in China remains low. Here, we explored the clinical benefits of a non-pharmaceutical intervention method combining a group and executive function training and an online parent training program, termed group executive functioning and online parent training (GEF-OPT), for school-aged students with ADHD through a randomized controlled trial. METHOD: A total of 145 children (aged 6-8 years) were formally registered and randomized to the intervention group (n = 73) and waitlist group (n = 72). The enrolled children received eight sessions of GEF-OPT treatment, which consists of a hospital-based children executive function (EF) training program and an online parent training program. Treatment outcome was assessed by a parent/teacher report questionnaire and neurophysiological experiment. RESULTS: After eight sessions of intervention, children in the intervention group showed a significant improvement in inattentive symptom compared to the waitlist group (14.70 ± 4.35 vs. 16.03 ± 2.93; p = 0.024), but an insignificant difference in hyperactive-impulsivity (9.85 ± 5.30 vs. 10.69 ± 5.10; p = 0.913). Comorbid oppositional defiant disorder was significantly reduced in the intervention group (7.03 ± 4.39 vs. 8.53 ± 4.41; p = 0.035). Children in the intervention group had greater reduction in the scores of behavioral regulation index (inhibition, emotional control) and metacognition index (working memory, planning/organization, monitoring) in executive function than those in the waitlist group (p < 0.05). Significant effects were also found in learning problem of Weiss Functional Impairment Scale-Parent form and parental distress between two groups at post-treatment (p < 0.05). In line with this, the result of go/no-go task showed significant improvements in accuracy change (4.45 ± 5.50% vs. 1.76 ± 3.35%; p = 0.001) and reaction time change (47.45 ± 62.25 s vs. 16.19 ± 72.22 s; p = 0.007) in the intervention group compared with the waitlist group. CONCLUSION: We conclude that participants in the GEF-OPT program improved outcomes for inattentive symptom, executive function, learning problems, and parental distress. GEF-OPT is a promising non-pharmaceutical therapeutic option for younger children. TRIAL REGISTRATION: ChiCTR2100052803.

Identification of fruit size associated quantitative trait loci featuring SLAF based high-density linkage map of goji berry (Lycium spp.).

BACKGROUND: Goji (Lycium spp., 2n = 24) is a fruit bearing woody plant popular as a superfood for extensive medicinal and nutritional advantages. Fruit size associated attributes are important for evaluating small-fruited goji berry and plant architecture. The domestication traits are regulated quantitatively in crop plants but few studies have attempted on genomic regions corresponding to fruit traits. RESULTS: In this study, we established high-resolution map using specific locus amplified fragment (SLAF) sequencing for de novo SNPs detection based on 305 F1 individuals derived from L. chinense and L. barbarum and performed quantitative trait loci (QTL) analysis of fruit size related traits in goji berry. The genetic map contained 3495 SLAF markers on 12 LGs, spanning 1649.03 cM with 0.47 cM average interval. Female and male parents and F1 individuals` sequencing depth was 111.85-fold and 168.72-fold and 35.80-fold, respectively. The phenotype data were collected for 2 successive years (2018-2019); however, two-year mean data were combined in an extra year (1819). Total 117 QTLs were detected corresponding to multiple traits, of which 78 QTLs in 2 individual years and 36 QTLs in extra year. Six Promising QTLs (qFW10-6.1, qFL10-2.1, qLL10-2.1, qLD10-2.1, qLD12-4.1, qLA10-2.1) were discovered influencing fruit weight, fruit length and leaf related attributes covering an interval ranged from 27.32-71.59 cM on LG10 with peak LOD of 10.48 and 14.6% PVE. Three QTLs targeting fruit sweetness (qFS3-1, qFS5-2) and fruit firmness (qFF10-1) were also identified. Strikingly, various traits QTLs were overlapped on LG10, in particular, qFL10-2.1 was co-located with qLL10-2.1, qLD10-2.1 and qLA10-2.1 among stable QTLs, harbored tightly linked markers, while qLL10-1 was one major QTL with 14.21 highest LOD and 19.3% variance. As LG10 harbored important traits QTLs, we might speculate that it could be hotspot region regulating fruit size and plant architectures. CONCLUSIONS: This report highlights the extremely saturated linkage map using SLAF-seq and novel loci contributing fruit size-related attributes in goji berry. Our results will shed light on domestication traits and further strengthen molecular and genetic underpinnings of goji berry; moreover, these findings would better facilitate to assemble the reference genome, determining potential candidate genes and marker-assisted breeding.

Identification and characterization of miRNAs in ripening fruit of Lycium barbarum L. using high-throughput sequencing.

MicroRNAs (miRNAs) are master regulators of gene activity documented to play central roles in fruit ripening in model plant species, yet little is known of their roles in Lycium barbarum L. fruits. In this study, miRNA levels in L. barbarum fruit samples at four developmental stages, were assayed using Illumina HiSeqTM2000. This revealed the presence of 50 novel miRNAs and 38 known miRNAs in L. barbarum fruits. Of the novel miRNAs, 36 were specific to L. barbarum fruits compared with L. chinense. A number of stage-specific miRNAs were identified and GO terms were assigned to 194 unigenes targeted by miRNAs. The majority of GO terms of unigenes targeted by differentially expressed miRNAs are "intracellular organelle," "binding," "metabolic process," "pigmentation," and "biological regulation." Enriched KEGG analysis indicated that nucleotide excision repair and ubiquitin mediated proteolysis were over-represented during the initial stage of ripening, with ABC transporters and sulfur metabolism pathways active during the middle stages and ABC transporters and spliceosome enriched in the final stages of ripening. Several miRNAs and their targets serving as potential regulators in L. barbarum fruit ripening were identified using quantitative reverse transcription polymerase chain reaction. The miRNA-target interactions were predicted for L. barbarum ripening regulators including miR156/157 with LbCNR and LbWRKY8, and miR171 with LbGRAS. Additionally, regulatory interactions potentially controlling fruit quality and nutritional value via sugar and secondary metabolite accumulation were identified. These include miR156 targeting of fructokinase and 1-deoxy-D-xylulose-5-phosphate synthase and miR164 targeting of beta-fructofuranosidase. In sum, valuable information revealed by small RNA sequencing in this study will provide a solid foundation for uncovering the miRNA-mediated mechanism of fruit ripening and quality in this nutritional food.