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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha Center for Medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of Biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely *** presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for *** To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental *** A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy *** in plasma were set as exposures with ASD as the main *** causal relationships were estimated using the inverse variant weight(IVW)*** also performed leave-one-out sensitivity tests to validate the robustness of the *** on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and *** Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and *** Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and *** findings offer perspectives for the discovery of diagnos

关键词： Des-Arg(9)bradykinin autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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Dietary L-proline supplementation ameliorates autism-like behaviors and modulates gut microbiota in the valproic acid-induced mouse model of autism spectrum disorder

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Food Science and Human Wellness 2024年第5期13卷 2889-2905页

作者： Jingjing Fang Ruixuan Geng Seong-Gook Kang Kunlun Huang Tao Tong Key Laboratory of Precision Nutrition and Food Quality Key Laboratory of Functional DairyMinistry of EducationCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China Department of Food Engineering and Solar Salt Research Center Mokpo National UniversityMuangun 58554Korea Key Laboratory of Safety Assessment of Genetically Modified Organism(Food Safety) Ministry of AgricultureBeijing 100083China Beijing Laboratory for Food Quality and Safety Beijing 100083China

The effective intervention strategy for autism spectrum disorder(ASD)are currently ***,we attempted to evaluate the potential of L-proline(Pro),a multifunctional amino acid,in ameliorating autismlike behaviors and clarify the molecular mechanisms involved by using the typical valproic acid(VPA)-induced mouse model of *** significantly attenuates repetitive behaviors and social dysfunction in ASD *** correlation analysis revealed that the beneficial effects of Pro on autism-like behaviors are related to the modulation of gut microbiota structure and *** histological analysis revealed that Pro could reverse the decrease of Nissl-positive cells in the prefrontal cortex(PFC)induced by VPA *** sequencing demonstrated that Pro can also alter the PFC transcriptomic profile distinguished by the regulation of genes involved in Parkinson disease,neuroactive ligand-receptor interaction,oxidative phosphorylation,and mitogen activated protein kinase signaling ***,dietary Pro supplementation may be a promising intervention strategy for ASD.

关键词： L-Proline autism spectrum disorder Gut microbiota Prefrontal cortex Behavior

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autism spectrum disorder Prediction by an Explainable Deep Learning Approach

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Computers, Materials & Continua 2022年第4期71卷 1459-1471页

作者： Anupam Garg Anshu Parashar Dipto Barman Sahil Jain Divya Singhal Mehedi Masud Mohamed Abouhawwash Computer Science and Engineering Department Thapar Institute of Engineering and TechnologyPatialaIndia School of Computer Science and Statistics Trinity College DublinDublinIreland University Institute of Biotechnology Chandigarh UniversityMohaliIndia Department of Computer Science College of Computers and Information TechnologyTaif UniversityTaif21944Saudi Arabia Department of Mathematics Faculty of ScienceMansoura UniversityMansoura35516Egypt Department of Computational Mathematics Scienceand Engineering(CMSE)Michigan State UniversityEast LansingMI48824USA

autism spectrum disorder (ASD) is a developmental disorderwhose symptoms become noticeable in early years of the age though it canbe present in any age group. ASD is a mental disorder which affects the communicational, social and non-verbal behaviors. It cannot be cured completelybut can be reduced if detected early. An early diagnosis is hampered by thevariation and severity of ASD symptoms as well as having symptoms commonly seen in other mental disorders as well. Nowadays, with the emergenceof deep learning approaches in various fields, medical experts can be assistedin early diagnosis of ASD. It is very difficult for a practitioner to identifyand concentrate on the major feature’s leading to the accurate prediction ofthe ASD and this arises the need for having an automated approach. Also,presence of different symptoms of ASD traits amongst toddlers directs tothe creation of a large feature dataset. In this study, we propose a hybridapproach comprising of both, deep learning and Explainable Artificial Intelligence (XAI) to find the most contributing features for the early and preciseprediction of ASD. The proposed framework gives more accurate predictionalong with the recommendations of predicted results which will be a vital aidclinically for better and early prediction of ASD traits amongst toddlers.

关键词： Deep learning explainable artificial intelligence autism spectrum disorder machine learning

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autism spectrum disorder and personality disorders: Comorbidity and differential diagnosis

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World Journal of Psychiatry 2021年第12期11卷 1366-1386页

作者： Camilla Rinaldi Margherita Attanasio Marco Valenti Monica Mazza Roberto Keller Adult autism Center Department of Mental HealthASL Cittàdi TorinoTurin 10138Italy Department of Applied Clinical Sciences and Biotechnology University of L’AquilaL’Aquila 67100Italy Regional Centre for autism Abruzzo Region Health SystemL’Aquila 67100Italy

BACKGROUND Differential diagnosis,comorbidities and overlaps with other psychiatric disorders are common among adults with autism spectrum disorder(ASD),but clinical assessments often omit screening for personality disorders(PD),which are especially common in individuals with high-functioning ASD where there is less need for *** To summarize the research findings on PD in adults with ASD and without intellectual disability,focusing on comorbidity and differential *** PubMed searches were performed using the key words“Asperger’s Syndrome”,“autism”,“Personality”,“Personality disorder”and“comorbidity”in order to identify relevant articles published in *** literature was identified through searching Google *** literature reviews and reference sections of selected papers were also examined for additional potential *** search was restricted to studies published up to April *** review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses *** The search found 22 studies carried out on ASD adults without intellectual disability that met the inclusion criteria:16 evaluated personality profiles or PD in ASD(comorbidity),five compared ASD and PD(differential diagnosis)and one performed both *** were significant differences in the methodological Cluster A and cluster C PD are the most frequent co-occurring PD,but overlapping features should be *** on differential diagnosis were only found with cluster A and cluster B *** ASD in high-functioning adults is associated with a distinct personality profile even if variability *** studies are needed to explore the complex relationship between ASD and PD.

关键词： autism spectrum disorder Asperger’s Syndrome Personality disorder Adulthood Comorbidity Differential diagnosis

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Designing and deploying a mixed-reality aquarium for cognitive training of young children with autism spectrum disorder

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Science China(Information Sciences) 2021年第5期64卷 209-211页

作者： Juan LIU Yulong BIAN Yanran YUAN Yuting XI Wenxiu GENG Xinpei JIN Wei GAI Xiangmin FAN Feng TIAN Xiangxu MENG Chenglei YANG Software College Shandong University Jining No.1 People's Hospital Institute of Software Chinese Academy of Sciences

autism spectrum disorder (ASD), a developmental disorder severely affecting cognition and social behavior, is increasing in prevalence [1]. This increasing trend is especially severe in children, making the early intervention crucial to ASD treatment. Children with ASD have been found impairments in several aspects of cognition functions.

关键词： autism spectrum disorder Mixed reality, Cognitive training Young ASD children User study Quantitative research

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Efficacy and moderating factors of the Early Start Denver Model in Chinese toddlers with autism spectrum disorder:a longitudinal study

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世界儿科杂志:英文版 2023年第8期19卷 741-752页

作者： Shi-Huan Wang Hai-Tao Zhang Yuan-Yuan Zou San-Mei Cheng Xiao-Bing Zou Kai-Yun Chen Child Developmental and Behavioral Center The Third Affiliated Hospital of Sun Yat-sen UniversityNo.600Tianhe RoadGuangzhou510630China

Background Several studies have shown the effectiveness of the Early Start Denver Model(ESDM),but few studies have explored the long-term efficacy of *** study aimed to explore the efficacy and moderating factors of ESDM in Chinese toddlers with autism spectrum disorder(ASD)in a longitudinal *** A total of 60 toddlers with ASD were recruited and randomly divided into two groups:ESDM group all received 24 weeks intervention;Control group were waiting for *** assessment(T0)was conducted before intervention,including Gesell Developmental Scale(GDS)and Psycho-educational Profile-3rd Edition(PEP-3).All toddlers with ASD were examined in the first assessment(T1)at 6 months and in the second assessment(T2)at 12 *** In T1 assessment,the increments in speech and personal communication development quotient in GDS were significantly larger in the ESDM group than in the control group(P=0.010,0.047).In T2 assessment,the ESDM group had higher elevation in cognitive verbal/preverbal(CVP),social reciprocity and characteristic verbal behaviors assessed by PEP-3(P=0.021,0.046,0.014).In addition,the severity of stereotyped behavior was negatively associated with improvement in *** income was positively associated with improvement in speech and CVP(all P<0.05).Conclusions ESDM can effectively improve speech and communication in toddlers with ASD after 24-week *** importantly,ESDM can promote cognition and social interaction and can reduce stereotyped verbal behavior in toddlers with ASD in longitudinal *** severity of stereotyped behavior and family ecological factors may be considered as affecting the efficacy of ESDM.

关键词： autism spectrum disorder Efficacy Early Start Denver Model Longitudinal Moderating factors Stereotyped behavior

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Analysis of neurotransmitters validates the importance of the dopaminergic system in autism spectrum disorder

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世界儿科杂志:英文版 2023年第8期19卷 770-781页

作者： Sharmistha Saha Mahasweta Chatterjee Nilanjana Dutta Swagata Sinha Kanchan Mukhopadhyay Manovikas Biomedical Research and Diagnostic Centre Manovikas Kendra482 MadudahPlot I-24Sector-JE.M.BypassKolkataWest Bengal700107India

Background The reasons behind the cardinal symptoms of communication deficits and repetitive,stereotyped behaviors that characterize autism spectrum disorder(ASD)remain *** dopamine(DA)system,which regulates motor activity,goal-directed behaviors,and reward function,is believed to play a crucial role in ASD,although the exact mechanism is still *** have shown an association of the dopamine receptor D4(DRD4)with various neurobehavioral *** We analyzed the association between ASD and four DRD4 genetic polymorphisms,5′flanking 120-bp duplication(rs4646984),rs1800955 in the promoter,exon 112 bp duplication(rs4646983),and exon 348 bp *** also examined plasma DA and its metabolite levels,DRD4 mRNA expression,and correlations of the studied polymorphisms with these parameters by case–control comparative *** expression of DA transporter(DAT),which is important in regulating the circulating DA level,was also *** A significantly higher occurrence of rs1800955“T/TT”was observed in the *** traits were affected by rs1800955“T”and the higher repeat alleles of the exon 348 bp repeats,rs4646983 and *** probands exhibited lower DA and norepinephrine levels together with higher homovanillic acid levels than the control *** and DRD4 mRNA expression were down-regulated in the probands,especially in the presence of DAT rs3836790“6R”and rs27072“CC”and DRD4 rs4646984 higher repeat allele and rs1800955“T”.Conclusion This pioneering investigation revealed a positive correlation between genetic variants,hypodopaminergic state,and impairment in socio-emotional and communication reciprocity in Indian subjects with ASD,warranting further in-depth analysis.

关键词： autism spectrum disorder Dopamine Neurotransmitter

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Assessing the Accuracy of the Modified Chinese autism spectrum Rating Scale and Social Responsiveness Scale for Screening autism spectrum disorder in Chinese Children

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Neuroscience Bulletin 2017年第2期33卷 168-174页

作者： Bingrui Zhou Hao Zhou Lijie Wu Xiaobing Zou Xuerong Luo Eric Fombonne Yi Wang Weili Yan Xiu Xu Department of Child Healthcare Children’s Hospital of Fudan UniversityShanghai 201102China Department of Neurology Children’s Hospital of Fudan UniversityShanghai 201102China School of Public Health Harbin Medical UniversityHarbin 150081China Child Development Center The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Psychiatry The Second Xiangya Hospital of Central South UniversityChangsha 410011China Oregon Health and Science University PortlandOR 97239USA Department of Clinical Epidemiology Children’s Hospital of Fudan UniversityShanghai 201102China

The reported prevalence of autism spectrum disorder（ASD） has been increasing rapidly in many parts of the world. However, data on its prevalence in China are largely missing. Here, we assessed the suitability of the modi？ed Chinese version of a newly-developed ASD screening tool, the Modi？ed Chinese autism spectrum Rating Scales（MC-ASRS） in screening for ASD in Chi nese children aged 6–12 years, through comparison with the Social Responsiveness Scale（SRS） that has been widely used for ASD screening. We recruited the par ents/caregivers of 1588 typically-developing children and190 children with ASD aged 6–12 years to complete the MC-ASRS and SRS, and evaluated the validity of both scales in discriminating children with ASD from those developing typically. The results showed that MC-ASRSperformed as well as SRS in sensitivity, speci？city, and area-under-the-curve（both [0.95） in receiver operating characteristic analysis, with a fair false-negative *** results suggest that MC-ASRS is a promising tool for screening for children with ASD in the general Chinese population.

关键词： autism spectrum disorder Screening accuracy ROC analysis Modi?ed Chinese autism spectrum Rating Scale Social Responsiveness Scale

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Differential diagnosis between autism spectrum disorder and other developmental disorders with emphasis on the preschool period

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世界儿科杂志:英文版 2023年第8期19卷 715-726页

作者： Taynara Amancio de Lima Patricia Aparecida Zuanetti Marina Estima Neiva Nunes Ana Paula Andrade Hamad Department of Neurosciences and Behavioral Sciences Ribeirão Preto Medical SchoolUniversity of São PauloAv.Bandeirantes3900Monte AlegreRibeirão PretoSP14049-900Brazil University Hospital Ribeirão Preto Medical SchoolUniversity of São Paulo(HCFMRP-USP)Ribeirão PretoSPBrazil

Background Neurodevelopmental disorders are a heterogeneous group of conditions that manifest as delays or deviations in the acquisition of expected developmental milestones and behavioral *** spectrum disorder(ASD)is a neurodevelopmental disorder characterized by deficits in communication and social interaction and by repetitive and restricted patterns of behavior,interests and *** aim of this review is to discuss the clinical features of the differential diagnoses of ASD that are prevalent among preschoolers,focusing on their similarities and *** sources The international medical literature search was conducted using PubMed and was revised regarding the subject using single and/or combined keywords as follows:differential diagnosis,preschoolers,diagnostic challenge,attention deficit hyperactivity disorder,intellectual disability,high abilities/giftedness,childhood apraxia of speech,social communication disorder,Landau–Kleffner syndrome,stereotyped movement disorder and excessive screen *** We describe conditions commonly found in clinical practice,taking ASD as a *** addressed converging and divergent aspects of behavior,cognition,communication,language,speech,socialization,and stereotypes for the diagnosis of ASD and other disorders identified as potential differential or comorbid *** The ranking and characterization of symptoms appear to be essential for better understanding the underlying common ground between children with developmental disorders and children with ASD,thus properly diagnosing and directing social,professional,or medication *** detailed discussion adds to the literature since,although ASD differential diagnoses are frequently mentioned and discussed in textbooks and journal articles,they rarely occupy a prominent place as we aimed herein.

关键词： autism spectrum disorder Clinical features Differential diagnosis Neurodevelopmental disorders Preschool

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Diagnosis of autism spectrum disorder by Imperialistic Competitive Algorithm and Logistic Regression Classifier

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Computers, Materials & Continua 2023年第11期77卷 1515-1534页

作者： Shabana R.Ziyad Liyakathunisa Eman Aljohani I.A.Saeed Department of Computer Science College of Computer Engineering and SciencesPrince Sattam bin Abdulaziz UniversityAl Kharj16274Saudi Arabia Department of Computer Science College of Computer Science and EngineeringTaibah UniversityMadinah41411Saudi Arabia Department of Information Systems College of Computer Engineering and SciencesPrince Sattam bin Abdulaziz UniversityAl Kharj16274Saudi Arabia

autism spectrum disorder(ASD),classified as a developmental disability,is now more common in children than ever.A drastic increase in the rate of autism spectrum disorder in children worldwide demands early detection of autism in *** can seek professional help for a better prognosis of the child’s therapy when ASD is diagnosed under five *** research study aims to develop an automated tool for diagnosing autism in *** computer-aided diagnosis tool for ASD detection is designed and developed by a novel methodology that includes data acquisition,feature selection,and classification *** most deterministic features are selected from the self-acquired dataset by novel feature selection methods before *** Imperialistic competitive algorithm(ICA)based on empires conquering colonies performs feature selection in this *** performance of Logistic Regression(LR),Decision tree,K-Nearest Neighbor(KNN),and Random Forest(RF)classifiers are experimentally studied in this research *** experimental results prove that the Logistic regression classifier exhibits the highest accuracy for the self-acquired *** ASD detection is evaluated experimentally with the Least Absolute Shrinkage and Selection Operator(LASSO)feature selection method and different *** Exploratory Data Analysis(EDA)phase has uncovered crucial facts about the data,like the correlation of the features in the dataset with the class variable.

关键词： autism spectrum disorder feature selection imperialist competitive algorithm LASSO logistic regression random forest

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