1. Berry-Kravis E, Abbeduto L, Hagerman R, Coffey CS, Cudkowicz M, Erickson CA, McDuffie A, Hessl D, Ethridge LE, Tassone F, Kaufmann WE, Friedmann K, Bullard L, Hoffmann A, Veenstra-VanderWeele J, Staley K, Klements D, Moshinsky M, Harkey B, Long JD, Fedler J, Klingner E, Ecklund DJ, Costigan M, Huff T, Pearson B. Effects of AFQ056 on language learning in fragile X syndrome. The Journal of clinical investigation. 2023.

BACKGROUND: FXLEARN, the first-ever large multi-site trial of effects of disease-targeted pharmacotherapy on learning, was designed to explore a new paradigm for measuring effects of mechanism-targeted treatment in fragile X syndrome (FXS). In FXLEARN, the effects of mGluR5 negative allosteric modulator (NAM) AFQ056 on language learning were evaluated in 3-6 year-old children with FXS, expected to have more learning plasticity than adults, where prior trials of mGluR5 NAMs have failed. METHODS: After a 4-month single-blind placebo lead-in, participants were randomized 1:1 to AFQ056 or placebo, with 2 months of dose optimization to the maximum tolerated dose, then 6 months of treatment during which a language learning intervention was implemented for both groups. The primary outcome was a centrally scored videotaped communication measure, the Weighted Communication Scale (WCS). Secondary outcomes were objective performance-based and parent-report cognitive and language measures. RESULTS: FXLEARN enrolled 110 participants, randomized 99, and 91 completed the placebo-controlled period. Although both groups made language progress and there were no safety issues, the change in WCS score during the placebo-controlled period was not significantly different between the AFQ056 and placebo-treated groups, nor were there any significant between-group differences in change in any secondary measures. CONCLUSION: Despite the large body of evidence supporting use of mGluR5 NAMs in animal models of FXS, this study suggests that this mechanism of action does not translate into benefit for the human FXS population and that better strategies are needed to determine which mechanisms will translate from pre-clinical models to humans in genetic neurodevelopmental disorders. TRIAL REGISTRATION: ClincalTrials.gov NCT02920892 FUNDING. This study was supported by NeuroNEXT network NIH grants U01NS096767, U24NS107200, U24NS107209, U01NS077323, U24NS107183, U24NS107168, U24NS107128, U24NS107199, U24NS107198, U24NS107166, U10NS077368, U01NS077366, U24NS107205, U01NS077179, and U01NS077352, NIH grant P50HD103526 and Novartis IIT grant AFQ056X2201T for provision of AFQ056.

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2. Biosca-Brull J, Basaure P, Guardia-Escote L, Cabré M, Blanco J, Morales-Navas M, Sánchez-Santed F, Colomina MT. Environmental exposure to chlorpyrifos during gestation, APOE polymorphism and the risk on autistic-like behaviors. Environmental research. 2023; 237(Pt 2): 116969.

Autism spectrum disorder (ASD) encompasses several neurodevelopmental conditions characterized by communication and social impairment, as well as repetitive patterns of behavior. However, it can co-occur with other mental conditions such as anxiety. The massive use of chlorpyrifos (CPF) has been linked to the increased prevalence of developmental disorders. Likewise, ASD has also been closely linked to a wide variety of genetic factors. The aims of the present investigation are to study how gestational CPF exposure and APOE polymorphism affects communication skills, early development and mid-term anxiety-like behaviors, as well as, changes in gene expression related to the cholinergic system. C57BL/6J and humanized apoE3 and apoE4 homozygous mice were exposed to 0 or 1 mg/kg/day of CPF through the diet, from gestational day (GD) 12-18. In addition, a group of C57BL/6J females were injected subcutaneously with 300 mg/kg/day of valproic acid (VPA) on GD 12 and 13. This group was used as a positive control for studying some core and associated autism-like behaviors. Communication skills by means of ultrasonic vocalizations and physical/motor development were assessed during the preweaning period, whereas locomotor activity, anxiety-like behaviors and the gene expression of cholinergic elements were evaluated during adolescence. Our results showed that C57BL/6J mice prenatally exposed to CPF or VPA showed a decrease in body weight and a delay in eye opening. Communication and anxiety behavior were affected differently depending on treatment, while gene expression was altered by sex and treatment. In addition, none of the parameters evaluated in apoE transgenic mice exposed to CPF were affected, but there were differences between genotypes. Therefore, we suggest that prenatal CPF exposure and VPA produce divergent effects on communication and anxiety.

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3. Blaine RE, Blaine KP, Cheng K, Banuelos C, Leal A. Priorities, barriers, and facilitators for nutrition-related care for autistic children: a qualitative study comparing interdisciplinary health professional and parent perspectives. Frontiers in pediatrics. 2023; 11: 1198177.

INTRODUCTION: Children with autism spectrum disorder often face nutrition-related challenges, such as food selectivity, gastrointestinal issues, overweight and obesity, and inadequate nutrient intake. However, the role of routine nutrition-related screening or care by interdisciplinary health professionals is not well understood. This study aimed to compare the beliefs of health professionals with those of parents of autistic children regarding high-priority nutrition-related challenges, barriers and facilitators to care, and desired education and resources related to nutrition for autistic children. PARTICIPANTS: Interdisciplinary health professionals (n = 25) (i.e., pediatricians, occupational therapists, speech-language pathologists, board certified behavior analysts, registered dietitians) and parents of autistic children (n = 22). METHODS: The study used semi-structured phone interviews, which were recorded, transcribed, verified, and double-coded using the Framework Method. RESULTS: Thematic analysis of transcripts revealed that while health professionals and parents of autistic children shared some perspectives on nutrition-related challenges and care, they also had distinct viewpoints. Parents emphasized the importance of addressing food selectivity, behavioral eating challenges, sensory issues, and sleep disturbances affecting appetite. Both groups acknowledged the need for tailored support, access to an interdisciplinary care team, and reasonable expectations. Some health professionals perceived parents as lacking motivation or the ability to make changes. In contrast, many parents felt that health professionals lacked the knowledge and motivation to take nutrition or growth concerns seriously. Health professionals acknowledged that their lack of knowledge or capacity to provide nutrition education or referrals was a common barrier to care, particularly given limited community resources. DISCUSSION: Health professionals who serve autistic children are motivated to address nutrition-related challenges but lack resources related to nutrition. To promote better health outcomes for autistic children, professionals should identify and support parent motivations around nutrition-related care. Both groups expressed interest in accessing autism-specific resources for education, referral, and screening guidance. Future research could explore the development of healthcare training models that improve the competency of health professionals in providing nutrition care and referral for autistic children.

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4. Bődi CB, Ortega DP, Hawkins LB, James TG, Bright MA. Parents’ and professionals’ perspectives on school-based maltreatment prevention education for children with intellectual and developmental disabilities. Child abuse & neglect. 2023; 145: 106428.

BACKGROUND: Youth with intellectual and developmental disabilities (IDD) are at a significantly increased risk of experiencing maltreatment and abuse. Child maltreatment prevention education programs are effective at improving safety of children and youth, generally. OBJECTIVE: The goal of this study was to understand challenges, benefits, and important considerations of developing an IDD-tailored prevention program. PARTICIPANTS AND SETTING: In total, we recruited 21 professionals and parents who have experience with a child with IDD from New York, Indiana, and Florida. METHODS: Participants were segmented into three focus groups, which were conducted through web-based videoconferencing. Focus groups were moderated by experts in child maltreatment prevention and recorded for data collection. Recordings were transcribed and subsequently coded using a qualitative content analysis approach. RESULTS: The analysis identified several challenges to implementing child maltreatment prevention to students with IDD and pedagogical strategies to overcome those, such as the use of visuals, standardized vocabulary, and relatable examples. Benefits of a prevention program were also mentioned, including feelings of empowerment that can be cultivated by providing opportunities where children with IDD practice being assertive. Considerations for program developers and staff were discussed to ensure that prevention programs are easily adaptable to suit the needs of students with IDD across the continuum. CONCLUSIONS: Previous research has indicated an unmet need for child maltreatment programs among children with IDD. Implementation of an IDD-tailored program must be preceded by gaining invaluable insight from professionals and parents. Findings provide insight into implementation challenges and methods to inform prevention programs.

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5. Dong H, Wang T, Feng J, Xue Y, Jia F. The relationship between screen time before bedtime and behaviors of preschoolers with autism spectrum disorder and the mediating effects of sleep. BMC psychiatry. 2023; 23(1): 635.

BACKGROUND: There are overlapping effects of screen time and sleep on children’s behavior. The purpose of this study was to explore the relationship of screen time with behavior problems in children with autism spectrum disorder (ASD) and the probable mediating effects of sleep, in order to provide evidence for the need for clinical identification and intervention. METHODS: A sample of 358 preschoolers with ASD were included. We investigated the children’s basic characteristics of sex and age, ASD symptoms (ABC, CARS, and ADOS-2), neurodevelopment (GDS-C), sleep habits (CSHQ), and behavior (CBCL). Pearson correlation tests were used to determine the direct correlations among children’s screen time, CBCL, and CSHQ. Linear regression analysis was used to explore whether screen time predicted total score of CBCL. Multi-step linear regression analysis was used to investigate the mediating effect of sleep on the relationship between screen time and total score of CBCL. RESULTS: Screen time before bedtime was correlated with CBCL and CSHQ, which indicated that screen time before bedtime was correlated with sleep and behavior in children with ASD. Screen time before bedtime was a predictor of CBCL total score (indicating children’s behavior), and CSHQ total score (indicating children’s sleep habits) played a partial mediating role between screen time before bedtime and children’s behavior. CONCLUSION: Clinicians should support and educate parents of children with ASD, which should focus on managing screen time, especially screen time before bedtime.

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6. Heraty S, Lautarescu A, Belton D, Boyle A, Cirrincione P, Doherty M, Douglas S, Plas JRD, Van Den Bosch K, Violland P, Tercon J, Ruigrok A, Murphy DGM, Bourgeron T, Chatham C, Loth E, Oakley B, McAlonan GM, Charman T, Puts N, Gallagher L, Jones EJH. Bridge-building between communities: Imagining the future of biomedical autism research. Cell. 2023; 186(18): 3747-52.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

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7. Hu HT, Lin YJ, Wang UT, Lee SP, Liou YH, Chen BC, Hsueh YP. Autism-related KLHL17 and SYNPO act in concert to control activity-dependent dendritic spine enlargement and the spine apparatus. PLoS biology. 2023; 21(8): e3002274.

Dendritic spines, the tiny and actin-rich protrusions emerging from dendrites, are the subcellular locations of excitatory synapses in the mammalian brain that control synaptic activity and plasticity. Dendritic spines contain a specialized form of endoplasmic reticulum (ER), i.e., the spine apparatus, required for local calcium signaling and that is involved in regulating dendritic spine enlargement and synaptic plasticity. Many autism-linked genes have been shown to play critical roles in synaptic formation and plasticity. Among them, KLHL17 is known to control dendritic spine enlargement during development. As a brain-specific disease-associated gene, KLHL17 is expected to play a critical role in the brain, but it has not yet been well characterized. In this study, we report that KLHL17 expression in mice is strongly regulated by neuronal activity and KLHL17 modulates the synaptic distribution of synaptopodin (SYNPO), a marker of the spine apparatus. Both KLHL17 and SYNPO are F-actin-binding proteins linked to autism. SYNPO is known to maintain the structure of the spine apparatus in mature spines and contributes to synaptic plasticity. Our super-resolution imaging using expansion microscopy demonstrates that SYNPO is indeed embedded into the ER network of dendritic spines and that KLHL17 is closely adjacent to the ER/SYNPO complex. Using mouse genetic models, we further show that Klhl17 haploinsufficiency and knockout result in fewer dendritic spines containing ER clusters and an alteration of calcium events at dendritic spines. Accordingly, activity-dependent dendritic spine enlargement and neuronal activation (reflected by extracellular signal-regulated kinase (ERK) phosphorylation and C-FOS expression) are impaired. In addition, we show that the effect of disrupting the KLHL17 and SYNPO association is similar to the results of Klhl17 haploinsufficiency and knockout, further strengthening the evidence that KLHL17 and SYNPO act together to regulate synaptic plasticity. In conclusion, our findings unravel a role for KLHL17 in controlling synaptic plasticity via its regulation of SYNPO and synaptic ER clustering and imply that impaired synaptic plasticity contributes to the etiology of KLHL17-related disorders.

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8. Li Y, Huang WC, Song PH. A face image classification method of autistic children based on the two-phase transfer learning. Frontiers in psychology. 2023; 14: 1226470.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which seriously affects children’s normal life. Screening potential autistic children before professional diagnose is helpful to early detection and early intervention. Autistic children have some different facial features from non-autistic children, so the potential autistic children can be screened by taking children’s facial images and analyzing them with a mobile phone. The area under curve (AUC) is a more robust metrics than accuracy in evaluating the performance of a model used to carry out the two-category classification, and the AUC of the deep learning model suitable for the mobile terminal in the existing research can be further improved. Moreover, the size of an input image is large, which is not fit for a mobile phone. A deep transfer learning method is proposed in this research, which can use images with smaller size and improve the AUC of existing studies. The proposed transfer method uses the two-phase transfer learning mode and the multi-classifier integration mode. For MobileNetV2 and MobileNetV3-Large that are suitable for a mobile phone, the two-phase transfer learning mode is used to improve their classification performance, and then the multi-classifier integration mode is used to integrate them to further improve the classification performance. A multi-classifier integrating calculation method is also proposed to calculate the final classification results according to the classifying results of the participating models. The experimental results show that compared with the one-phase transfer learning, the two-phase transfer learning can significantly improve the classification performance of MobileNetV2 and MobileNetV3-Large, and the classification performance of the integrated classifier is better than that of any participating classifiers. The accuracy of the integrated classifier in this research is 90.5%, and the AUC is 96.32%, which is 3.51% greater than the AUC (92.81%) of the previous studies.

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9. Lo A, Lowery LA, Kuhlthau K, Parker RA, Chan J, Haddad F, Radom-Aizik S, Gehricke JG. Effects of physical exercise, LEGO, and Minecraft activities on anxiety in underserved children with autism: Study design and methodological strategies. MethodsX. 2023; 11: 102332.

Anxiety is a common comorbidity for individuals with ASD, and there is some preliminary data about the efficacy of physical exercise to alleviate anxiety. However, we are not aware of any studies that have compared the effects of a physical exercise program on anxiety in underserved children with ASD using a randomized controlled research design. This paper describes a method to evaluate and compare the efficacy of an 8-week physical exercise intervention with a sedentary play intervention to alleviate anxiety in young children with autism spectrum disorders (ASD) from underserved backgrounds. We assessed anxiety and its physical symptoms using the parent-rated Child Behavior Checklist DSM-5 anxiety (CBCL DSM-5) subscale, the child-rated Screen for Childhood Anxiety Related Emotional Disorder (SCARED), the parent-rated Child’s Sleep Habits Questionnaire (CSHQ), and salivary cortisol. We also utilized the Physical Activity Questionnaire for Older Children (PAQ-C) to assess physical activity level and identify compounds. Unique components of this study include: •Implementation of novel physical exercise and sedentary play interventions that have been designed for children with ASD.•Recruitment of predominantly underserved and non-English speaking families.

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10. McVey AJ, Jones DR, Waisman TC, Raymaker DM, Nicolaidis C, Maddox BB. Mindshift in autism: a call to professionals in research, clinical, and educational settings. Frontiers in psychiatry. 2023; 14: 1251058.

Autistic people often have poor outcomes over the life course, including in health, education, employment, and community inclusion. Many professionals working with Autistic adults in research, clinical, and educational settings devote their careers to trying to improve such outcomes. However, we maintain that real progress cannot happen without a fundamental mindshift. The status quo for professionals is to view autism as an illness. Instead, the neurodiversity movement encourages us to value and embrace autism as an aspect of human diversity and asks us to view Autistic people as a marginalized group that experiences significant disparities. While some professionals may be adopting language and concepts from the neurodiversity movement, we argue that making this mindshift fundamentally changes our practice across research, clinical, and educational settings. In this perspective, we call on professionals to embrace this mindshift to reduce discrimination and stigma, halt the spread of harmful ideologies, and help Autistic adults live fulfilling lives.

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11. Oblong LM, Llera A, Mei T, Haak K, Isakoglou C, Floris DL, Durston S, Moessnang C, Banaschewski T, Baron-Cohen S, Loth E, Dell’Acqua F, Charman T, Murphy DGM, Ecker C, Buitelaar JK, Beckmann CF, Forde NJ. Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study. Molecular autism. 2023; 14(1): 32.

Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, p(adj) = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation.

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12. Salloum-Asfar S. Editorial: Molecular advances and applications of machine learning in understanding autism and comorbid psychiatric disorders. Frontiers in molecular neuroscience. 2023; 16: 1277814.

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13. Tahmazian I, Watts A, Chen O, Ferrara HJ, McCrimmon A, Hu B, Chomiak T. A wearable device-enabled therapeutic approach to improve joint attention in autism spectrum disorder: a prospective pilot study. Journal of neural transmission (Vienna, Austria : 1996). 2023.

It has been previously proposed that interventions aimed at integrating and co-activating music processing and motor control systems could have therapeutic potential for priming social skill development in children with autism spectrum disorder (ASD). In this study, we assessed this hypothesis through a wearable sensor platform called Ambulosono (« Ambulo »-walk; « sono »-sound) in which pleasurable children’s musical stimuli are contingently linked to effortful motor action (locomotor step size), thus creating a motivational state proposed to be conducive to joint attention (JA) operation. Five participants were recruited from a community-based partner and were assessed by scoring responses following therapist-directed bids for JA. Multiple assessment sessions through a repeated time-series design were conducted to determine baseline and post-intervention scores. The intervention session consisted of approximately 15 min of Ambulosono exposure. Baseline and post-intervention data were aggregated and analyzed using a linear mixed-effect model. The wearable sensor and wireless headphones of the Ambulosono system were tolerated by the participants, and there were no adverse effects associated with the use of the device. We found an increase in the average responses to bids for JA during the Ambulosono intervention phase compared to baseline across participants. This increase did not appear to result from enhanced general arousal. Our pilot data support feasibility and further testing of Ambulosono as a therapeutic aid for integration into community-based ASD programs to augment shared child-therapist social interactions.

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14. Wang J, Li W, Li Z, Xue Z, Zhang Y, Yuan Y, Shi Y, Shan S, Han W, Li F, Qiu Z. Taok1 haploinsufficiency leads to autistic-like behaviors in mice via the dorsal raphe nucleus. Cell reports. 2023; 42(9): 113078.

Strong evidence from human genetic studies associates the thousand and one amino acid kinase 1 (TAOK1) gene with autism spectrum disorder (ASD). In this work, we discovered a de novo frameshifting mutation in TAOK1 within a Chinese ASD cohort. We found that Taok1 haploinsufficiency induces autistic-like behaviors in mice. Importantly, we observed a significant enrichment of Taok1 in the dorsal raphe nucleus (DRN). The haploinsufficiency of Taok1 considerably restrained the activation of DRN neurons during social interactions, leading to the aberrant phosphorylation of numerous proteins. Intriguingly, the genetic deletion of Taok1 in VGlut3-positive neurons of DRN resulted in mice exhibiting autistic-like behaviors. Ultimately, reintroducing wild-type Taok1, but not its kinase-dead variant, into the DRN of adult mice effectively mitigated the autistic-like behaviors associated with Taok1 haploinsufficiency. This work suggests that Taok1, through its influence in the DRN, regulates social interaction behaviors, providing critical insights into the etiology of ASD.

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15. Wang X, Sun Z, Yang T, Lin F, Ye S, Yan J, Li T, Chen J. Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition. mSystems. 2023; 8(4): e0041523.

Short-chain fatty acids (SCFAs, especially butyric acid) have been demonstrated to play a promising role in the development of autism spectrum disorders (ASD). Recently, the hypothalamic-pituitary-adrenal (HPA) axis is also suggested to increase the risk of ASD. However, the mechanism underlying SCFAs and HPA axis in ASD development remains unknown. Here, we show that children with ASD exhibited lower SCFA concentrations and higher cortisol levels, which were recaptured in prenatal lipopolysaccharide (LPS)-exposed rat model of ASD. These offspring also showed decreased SCFA-producing bacteria and histone acetylation activity as well as impaired corticotropin-releasing hormone receptor 2 (CRHR2) expression. Sodium butyrate (NaB), which can act as histone deacetylases inhibitors, significantly increased histone acetylation at the CRHR2 promoter in vitro and normalized the corticosterone as well as CRHR2 expression level in vivo. Behavioral assays indicated ameliorative effects of NaB on anxiety and social deficit in LPS-exposed offspring. Our results imply that NaB treatment can improve ASD-like symptoms via epigenetic regulation of the HPA axis in offspring; thus, it may provide new insight into the SCFA treatment of neurodevelopmental disorders like ASD. IMPORTANCE Growing evidence suggests that microbiota can affect brain function and behavior through the « microbiome-gut-brain » axis, but its mechanism remains poorly understood. Here, we show that both children with autism and LPS-exposed rat model of autism exhibited lower SCFA concentrations and overactivation of HPA axis. SCFA-producing bacteria, Lactobacillus, might be the key differential microbiota between the control and LPS-exposed offspring. Interestingly, NaB treatment contributed to the regulation of HPA axis (such as corticosterone as well as CRHR2) and improvement of anxiety and social deficit behaviors in LPS-exposed offspring. The potential underlying mechanism of the ameliorative effect of NaB may be mediated via increasing histone acetylation to the CRHR2 promoter. These results enhance our understanding of the relationship between the SCFAs and the HPA axis in the development of ASD. And gut microbiota-derived SCFAs may serve as a potential therapeutic agent to neurodevelopmental disorders like ASD.

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16. Yang J, Wang F, Li Z, Yang Z, Dong X, Han Q. Constructing high-order functional networks based on hypergraph for diagnosis of autism spectrum disorders. Frontiers in neuroscience. 2023; 17: 1257982.

INTRODUCTION: High-order functional connectivity networks (FCNs) that reflect the connection relationships among multiple brain regions have become important tools for exploring the deep workings of the brain and revealing the mechanisms of brain diseases. The traditional high-order FCN constructed based on the « correlation of correlations » strategy, is a representative method for conducting whole-brain connectivity analysis and revealing global network characteristics. However, whole-brain connectivity analysis may be affected by noise carried by less important brain regions, resulting in redundant information and affecting the accuracy and reliability of the analysis. Moreover, this type of analysis has a high computational complexity. METHODS: To address these issues, a new method for constructing high-order FCN based on hypergraphs is proposed in this article, which is used to accurately capture the real interaction relationships among brain regions. Specifically, first, a low-order FCN reflecting the connection relationships between pairs of brain regions based on resting-state functional Magnetic Resonance Imaging (rs-fMRI) time series is constructed, the method first constructs the low-order FCN that reflects the connection relationships between pairs of brain regions based on rs-fMRI time series, and then selects the « good friends » of each brain region from hypergraph perspective, which refers to the local friend circles with closer relationships. Then, the rs-fMRI time series corresponding to the « good friends » in each brain region’s friend circle are averaged to obtain a sequence that reflects the intimacy between brain regions in each friend circle. Finally, hypergraph high-order FCN, which reflects the interaction relationships among multiple brain regions, is obtained by calculating the correlations based on the sequence of friend circles. RESULTS: The experimental results demonstrate that the proposed method outperforms traditional high-order FCN construction methods. Furthermore, integrating the high-order FCN constructed based on hypergraphs and the low-order FCN through feature fusion to achieve complementary information improves the accuracy of assisting in the diagnosis of brain diseases. DISCUSSION: In addition, the effectiveness of our method has only been validated in the diagnosis of ASD. For future work, we plan to extend this method to other brain connectivity patterns.

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