1. Cano S, Díaz-Arancibia J, Arango-López J, Libreros JE, García M. Design Path for a Social Robot for Emotional Communication for Children with Autism Spectrum Disorder (ASD). Sensors (Basel);2023 (Jun 2);23(11)

Children with autism spectrum disorder (ASD) have deficits in social interaction and expressing and understanding emotions. Based on this, robots for children with ASD have been proposed. However, few studies have been conducted about how to design a social robot for children with ASD. Non-experimental studies have been carried out to evaluate social robots; however, the general methodology that should be used to design a social robot is not clear. This study proposes a design path for a social robot for emotional communication for children with ASD following a user-centered design approach. This design path was applied to a case study and evaluated by a group of experts in psychology, human-robot interaction, and human-computer interaction from Chile and Colombia, as well as parents of children with ASD. Our results show that following the proposed design path for a social robot to communicate emotions for children with ASD is favorable.

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2. Celora L, Jaudon F, Vitale C, Cingolani LA. Regulation of dendritic spine length in corticopontine layer V pyramidal neurons by autism risk gene β3 integrin. Mol Brain;2023 (Jun 9);16(1):49.

The relationship between autism spectrum disorder (ASD) and dendritic spine abnormalities is well known, but it is unclear whether the deficits relate to specific neuron types and brain regions most relevant to ASD. Recent genetic studies have identified a convergence of ASD risk genes in deep layer pyramidal neurons of the prefrontal cortex. Here, we use retrograde recombinant adeno-associated viruses to label specifically two major layer V pyramidal neuron types of the medial prefrontal cortex: the commissural neurons, which put the two cerebral hemispheres in direct communication, and the corticopontine neurons, which transmit information outside the cortex. We compare the basal dendritic spines on commissural and corticopontine neurons in WT and KO mice for the ASD risk gene Itgb3, which encodes for the cell adhesion molecule β3 integrin selectively enriched in layer V pyramidal neurons. Regardless of the genotype, corticopontine neurons had a higher ratio of stubby to mushroom spines than commissural neurons. β3 integrin affected selectively spine length in corticopontine neurons. Ablation of β3 integrin resulted in corticopontine neurons lacking long (> 2 μm) thin dendritic spines. These findings suggest that a deficiency in β3 integrin expression compromises specifically immature spines on corticopontine neurons, thereby reducing the cortical territory they can sample. Because corticopontine neurons receive extensive local and long-range excitatory inputs before relaying information outside the cortex, specific alterations in dendritic spines of corticopontine neurons may compromise the computational output of the full cortex, thereby contributing to ASD pathophysiology.

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3. Ciobanu CG, Nucă I, Popescu R, Antoci LM, Caba L, Ivanov AV, Cojocaru KA, Rusu C, Mihai CT, Pânzaru MC. Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome. Int J Mol Sci;2023 (May 24);24(11)

The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice.

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4. Howlin P. Increased risk of physical health problems among older autistic adults. Lancet Healthy Longev;2023 (Jun 6)

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5. Koceski A, Smith CJ, Syed YA, Trajkovski V. Understanding the Relationship between Distress Behaviour and Health Status of People with Autism Spectrum Disorder. Healthcare (Basel);2023 (May 26);11(11)

Autism Spectrum Disorder (ASD) is associated with complex distress and challenging behaviours that have a negative impact on the everyday life of those with ASD, as well as their parents and carers. These challenging behaviours include negative emotional behaviours, motor behaviours, and changes in routines. Even though challenging behaviours occur in most subjects with ASD, the cause of these largely remains unknown. It has been implicated that these challenging behaviours are associated with a change in the health of those with ASD. More research needs to be conducted that can establish a direct association. Towards this goal, the present study aimed to explore whether health status had an impact on the distressing behaviour in the subjects diagnosed with ASD. We analysed the response from the parents/carers in a Macedonian population of those with ASD, to determine which challenging behaviours were most likely to be observed during a change in health. Based on a scoring system, the manifestation of challenging behaviour was evaluated and compared with the changes in health. Changes in appetite or dietary preferences, irritability and low mood, and loss of previously acquired skills had the greatest association with a change in health. These findings provide early insight into types of challenging behaviours that are directly associated with a change in health. Our results demonstrate a relationship between health status and challenging behaviour in the subject with autism, suggesting that caregivers may need to consider this when choosing strategies for managing challenging behaviour.

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6. Lei Y, Peng X, Wang X, Cao H. [Identification of a NONO gene variant in a child with congenital heart disease and global developmental delay]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2023 (Jun 10);40(6):691-695.

OBJECTIVE: To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). METHODS: A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children’s Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. CONCLUSION: The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.

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7. Liu S, Larsson H, Kuja-Halkola R, Lichtenstein P, Butwicka A, Taylor MJ. Age-related physical health of older autistic adults in Sweden: a longitudinal, retrospective, population-based cohort study. Lancet Healthy Longev;2023 (Jun 6)

BACKGROUND: Research of health outcomes in older autistic adults (≥45 years) is concerningly scarce, and little is known about whether intellectual disability and sex affect the health outcomes of this population. The aim of this study was to investigate the association between autism and physical health conditions in older adults and to examine these associations by intellectual disability and sex. METHODS: We conducted a longitudinal, retrospective, population-based cohort study of the Swedish population born between Jan 1, 1932, and Dec 31, 1967, using linked data from the nationwide Total Population Register and the National Patient Register. We excluded individuals who died or emigrated before the age of 45 years, or with any chromosomal abnormalities. Follow-up started at age 45 years for all individuals, and ended at emigration, death, or Dec 31, 2013 (the latest date of available follow-up), whichever was soonest. Diagnoses of autism, intellectual disability, 39 age-related physical conditions, and five types of injury (outcomes) were obtained from the National Patient Register. For each outcome, we calculated 25-year cumulative incidence and used Cox models to estimate hazard ratios (HRs). All analyses were repeated separately by intellectual disability and sex. FINDINGS: Of 4 200 887 older adults (2 063 718 women [49•1%] and 2 137 169 men [50•9%]) in the study cohort, 5291 (0•1%) had a diagnosis of autism recorded in the National Patient Register. Older autistic adults (median follow-up 8•4 years [IQR 4•2-14•6]) had higher cumulative incidence and HRs of various physical conditions and injuries than their non-autistic counterparts (median follow-up 16•4 years [8•2-24•4]). In autistic individuals, the highest cumulative incidence was observed for bodily injuries (50•0% [95% CI 47•6-52•4]). Conditions that autistic adults were at higher risk of than were non-autistic adults included heart failure (HR 1•89 [95% CI 1•61-2•22]), cystitis (2•03 [1•66-2•49]), glucose dysregulation (2•96 [2•04-4•29]), iron deficiency anaemia (3•12 [2•65-3•68]), poisoning (4•63 [4•13-5•18]), and self-harm (7•08 [6•24-8•03]). These increased risks mainly persisted regardless of intellectual disability or sex. INTERPRETATION: Our data indicate that older autistic adults are at substantially increased risk of age-related physical conditions and injuries compared with non-autistic adults. These findings highlight the need for collaborative efforts from researchers, health services, and policy makers to provide older autistic individuals with the necessary support to attain healthy longevity and a high quality of life. FUNDING: Swedish Research Council, Servier Affaires Medicales. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.

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8. Loo BRY, Teo TJY, Liang MJ, Leong DJ, Tan DW, Zhuang S, Hull L, Livingston LA, Mandy W, Happé F, Magiati I. Exploring autistic adults’ psychosocial experiences affecting beginnings, continuity and change in camouflaging over time: A qualitative study in Singapore. Autism;2023 (Jun 10):13623613231180075.

Over their lifetimes, many autistic people learn to camouflage (hide or mask) their autism-related differences to forge relationships, find work and live independently in largely non-autistic societies. Autistic adults have described camouflaging as a ‘lifetime of conditioning . . . to act normal’ involving ‘years of effort’, suggesting that camouflaging develops over an autistic person’s lifetime and may start early on, in childhood or adolescence. Yet, we know very little about why and how autistic people start to camouflage, or why and how their camouflaging behaviours continue or change over time. We interviewed 11 Singaporean autistic adults (9 male, 2 female, 22-45 years old) who shared their camouflaging experiences. We found that autistic adults’ earliest motivations to camouflage were largely related to the desire to fit in and connect with others. They also camouflaged to avoid difficult social experiences (such as being teased or bullied). Autistic adults shared that their camouflaging behaviours became more complex and that, for some, camouflaging became a part of their self-identity over time. Our findings suggest that society should not pathologise autistic differences, but instead accept and include autistic people, to reduce the pressure on autistic people to hide who they truly are.

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9. Mattson JT, Thorne JC, Kover ST. Parental scaffolding in play: A comparison of fetal alcohol spectrum disorders and autism spectrum disorder. Res Dev Disabil;2023 (Jun 7);139:104553.

BACKGROUND: Parental support of child play varies based on child needs; however, how parental play level differs from child play level remains an understudied area of research, especially in relation to specific developmental disabilities. AIMS: To preliminarily explore differences in child and parent play levels in age- and IQ-matched children with fetal alcohol spectrum disorders (FASD) and autism spectrum disorder (ASD). METHODS: and Procedures: Parent-child dyads were recorded during free-play sessions. Parent/child play levels were coded for highest level achieved during each minute of play. Mean play level and dPlay (difference in parent versus child play level) were calculated across play sessions for each dyad. OUTCOMES AND RESULTS: On average, parents of children with FASD demonstrated higher levels of play than other parents. Children with FASD demonstrated higher levels of play than their own parents. In contrast, the play level of parents of children with ASD did not differ from their child’s. There were no between-group differences in dPlay. CONCLUSIONS AND IMPLICATIONS: This preliminary exploratory study suggests that parents of children with developmental disabilities may differentially ‘match’ their child’s play level. Further research on developmental play levels during parent-child play is warranted.

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10. Sotelo-Orozco J, Schmidt RJ, Slupsky CM, Hertz-Picciotto I. Investigating the Urinary Metabolome in the First Year of Life and Its Association with Later Diagnosis of Autism Spectrum Disorder or Non-Typical Neurodevelopment in the MARBLES Study. Int J Mol Sci;2023 (May 29);24(11)

Developmental disabilities are often associated with alterations in metabolism. However, it remains unknown how early these metabolic issues may arise. This study included a subset of children from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) prospective cohort study. In this analysis, 109 urine samples collected at 3, 6, and/or 12 months of age from 70 children with a family history of ASD who went on to develop autism spectrum disorder (ASD n = 17), non-typical development (Non-TD n = 11), or typical development (TD n = 42) were investigated by nuclear magnetic resonance (NMR) spectroscopy to measure urinary metabolites. Multivariate principal component analysis and a generalized estimating equation were performed with the objective of exploring the associations between urinary metabolite levels in the first year of life and later adverse neurodevelopment. We found that children who were later diagnosed with ASD tended to have decreased urinary dimethylamine, guanidoacetate, hippurate, and serine, while children who were later diagnosed with Non-TD tended to have elevated urinary ethanolamine and hypoxanthine but lower methionine and homovanillate. Children later diagnosed with ASD or Non-TD both tended to have decreased urinary 3-aminoisobutyrate. Our results suggest subtle alterations in one-carbon metabolism, gut-microbial co-metabolism, and neurotransmitter precursors observed in the first year of life may be associated with later adverse neurodevelopment.

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11. Stoccoro A, Conti E, Scaffei E, Calderoni S, Coppedè F, Migliore L, Battini R. DNA Methylation Biomarkers for Young Children with Idiopathic Autism Spectrum Disorder: A Systematic Review. Int J Mol Sci;2023 (May 23);24(11)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, the underlying pathological mechanisms of which are not yet completely understood. Although several genetic and genomic alterations have been linked to ASD, for the majority of ASD patients, the cause remains unknown, and the condition likely arises due to complex interactions between low-risk genes and environmental factors. There is increasing evidence that epigenetic mechanisms that are highly sensitive to environmental factors and influence gene function without altering the DNA sequence, particularly aberrant DNA methylation, are involved in ASD pathogenesis. This systematic review aimed to update the clinical application of DNA methylation investigations in children with idiopathic ASD, investigating its potential application in clinical settings. To this end, a literature search was performed on different scientific databases using a combination of terms related to the association between peripheral DNA methylation and young children with idiopathic ASD; this search led to the identification of 18 articles. In the selected studies, DNA methylation is investigated in peripheral blood or saliva samples, at both gene-specific and genome-wide levels. The results obtained suggest that peripheral DNA methylation could represent a promising methodology in ASD biomarker research, although further studies are needed to develop DNA-methylation-based clinical applications.

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12. Tang Y, Li X, Wu W, Shi Z, Chen W, Tian Y. [Clinical and genetic analysis of a child with Mental retardation autosomal dominant 51]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2023 (Jun 10);40(6):696-700.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). METHODS: A child with MRD51 who was hospitalized at Guangzhou Women and Children’s Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. CONCLUSION: The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.

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13. Wilkinson E, Farmer C, Kleiman E, Bal VH. Factor structure of the VABS-3 Comprehensive Parent/Caregiver form in autistic individuals: Poor fit of three-factor and unidimensional models. Autism;2023 (Jun 10):13623613231179288.

Adaptive behavior is a broad set of skills needed to function in everyday life. The Vineland Adaptive Behavior Scales (VABS-3) is commonly used to measure adaptive behavior. It divides adaptive behavior into three domains, Communication, Daily Living Skills, and Socialization, each of which are split into subdomains. Analyses of this three-part structure of the first version of VABS used the instrument as an interview, but now it is done as a questionnaire as well. The structure has not been well supported in samples of autistic people, who often have different strengths and challenges in adaptive behavior compared with non-autistic people. Because adaptive behavior is an important concept in autism research and online-administered questionnaires are increasingly common, it is important to ensure the structure of the VABS-3 Comprehensive Parent/Caregiver Form (VABS-3:CPCF; a questionnaire) works well for autistic individuals across a range of abilities. This study aimed to investigate whether VABS-3:CPCF measures adaptive behavior similarly in verbal and minimally verbal autistic people. However, the data didn’t fit the structure in the first step of the analysis, so this could not be investigated. The next analyses also found the three-domain structure didn’t fit in different age and language groups. In addition, the data didn’t fit a structure combining all the domains into 1 (unidimensional). These results suggest that neither the three-factor or unidimensional structure fit the VABS-3:CPCF, cautioning against interpretation of domain or overall adaptive behavior composite scores in autistic individuals and further encouraging careful consideration of administration format.

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14. Yin H, Qiu Z, Li T, Chen Y, Xia J, Huang G, Xu W, Xie J. [Analysis of NSD1 gene variant in a child with autism spectrum disorder in conjunct with congenital heart disease]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2023 (Jun 10);40(6):701-705.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People’s Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION: The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.

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15. Zhu Y, Xu L, Yu J. Classification of autism based on short-term spontaneous hemodynamic fluctuations using an adaptive graph neural network. J Neurosci Methods;2023 (Jun 7):109901.

BACKGROUND: Short-term spontaneous hemodynamic fluctuations were collected by the functional near-infrared spectroscopy (fNIRS) system to classify children with autism spectrum disorder (ASD) and typical development (TD), and to explore abnormalities in the left inferior frontal gyrus in ASD. METHODS: Using the fNIRS data of 25 children with ASD and 22 children with TD, a graph neural network combined with the temporal convolution module and the graph convolution module was used, to extract the spatio-temporal features of the data and achieve accurate classification of ASD. RESULTS: The graph neural network was used to obtain a good classification result in the left inferior frontal gyrus, with an accuracy of 97.1%, precision of 95.1%, and specificity of 93.4%. It was found that the 5th channel (which is located in BA 10) and the 8th channel (which is located in BA 47) in the left inferior frontal gyrus were closely correlated with ASD. COMPARISON WITH PREVIOUSLY USED METHOD(S): Compared with the previous deep learning model using the same input, the accuracy of our model has increased by up to 13%, and the correlation between channels in the left inferior frontal gyrus area with the best classification effect was explored through the graph neural network. CONCLUSION: The adaptive graph neural network (AGNN) model may be able to mine more valuable information to distinguish ASD from TD and in addition, the left inferior frontal gyrus may have greater investigative value.

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