1. Chardon FM, McDiarmid TA, Page NF, Daza RM, Martin BK, Domcke S, Regalado SG, Lalanne JB, Calderon D, Li X, Starita LM, Sanders SJ, Ahituv N, Shendure J. Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements. Nat Commun;2024 (Sep 18);15(1):8209.

CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis-regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes. Applying this method to a library of 493 gRNAs targeting candidate cis-regulatory elements in both K562 cells and iPSC-derived excitatory neurons, we identify gRNAs capable of specifically upregulating intended target genes and no other neighboring genes within 1 Mb, including gRNAs yielding upregulation of six autism spectrum disorder (ASD) and neurodevelopmental disorder (NDD) risk genes in neurons. A consistent pattern is that the responsiveness of individual enhancers to CRISPRa is restricted by cell type, implying a dependency on either chromatin landscape and/or additional trans-acting factors for successful gene activation. The approach outlined here may facilitate large-scale screens for gRNAs that activate genes in a cell type-specific manner.

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2. Chen Y, Powers J, McDougle CJ, Zürcher NR, Thom RP. Cervical Cancer Screening and Prevention Uptake in Females with Autism Spectrum Disorder. J Autism Dev Disord;2024 (Sep 18)

This study reports on uptake rates of cervical cancer prevention and screening in a clinically-referred cohort of adolescent and adult females with autism spectrum disorder (ASD). Females with ASD (11-65 years) were invited to participate in an online survey to report on uptake of the human papillomavirus (HPV) vaccination and cervical cancer screening. Participants also provided demographic and clinical information. Chi-square statistical analysis was utilized to examine the relationship between categorical variables and receipt of cervical cancer prevention and screening. Forty-one out of 73 (56%) of adolescent (11-17 years) and 51/108 (47%) of adult (≥ 18 years) females with ASD reported having received at least one dose of the HPV vaccine. Only 30/73 (41%) and 37/108 (34%) of adolescents and adults respectively, were fully vaccinated (≥ 2 doses). Language impairment was the only clinical factor found to be associated with non-receipt of the HPV vaccine. Thirty-one out of 82 (38%) adult females (≥ 21 years) with ASD had received at least one pap smear. Language impairment, intellectual disability, non-independent living, and lower level of education were all associated with not receiving a pap smear. Females with ASD are vulnerable to invasive cervical cancer disease due to low uptake rates of the HPV vaccine and routine pap smear screening.

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3. Dwyer P, Gurba AN, Kapp SK, Kilgallon E, Hersh LH, Chang DS, Rivera SM, Gillespie-Lynch K. Community views of neurodiversity, models of disability and autism intervention: Mixed methods reveal shared goals and key tensions. Autism;2024 (Sep 18):13623613241273029.

What is already known about the topic? Some people support the neurodiversity movement and other people criticize it. They often disagree about what the neurodiversity movement means. Confusion about what the neurodiversity movement is makes it hard for people to agree about how best to support autistic or disabled people.What does this article add? We studied autistic and autism community members’ views on the neurodiversity movement and autism interventions. Most participants supported the neurodiversity movement. Support for the neurodiversity movement was related to wanting to change society and make places more comfortable for autistic people. Neurodiversity supporters felt autistic children should choose their own intervention goals and that autistic adults should help children choose goals. Neurodiversity supporters did not think autistic people should be taught to act less autistic. Both those agreeing and disagreeing with the neurodiversity movement said that it is important to help autistic people be well. Many participants said that society causes all the difficulties disabled people experience. Yet they were somewhat open to helping people grow by teaching them useful skills and trying to cure depression and epilepsy.Implications for practice, research or policy. To better help autistic people, we should listen to participants in this study. They called for improving society, building more spaces where autistic people feel comfortable and helping autistic people lead change. They warned against teaching autistic people to hide their autism. Critics of the neurodiversity movement should read this article to better understand what neurodiversity movement supporters believe. By taking time to learn from one another, we can work together to better support autistic people.

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4. Kavitha V, Siva R. HCBiLSTM-WOA: hybrid convolutional bidirectional long short-term memory with water optimization algorithm for autism spectrum disorder. Comput Methods Biomech Biomed Engin;2024 (Sep 18):1-23.

Autism Spectrum Disorder (ASD) is a type of brain developmental disability that cannot be completely treated, but its impact can be reduced through early interventions. Early identification of neurological disorders will better assist in preserving the subjects’ physical and mental health. Although numerous research works exist for detecting autism spectrum disorder, they are cumbersome and insufficient for dealing with real-time datasets. Therefore, to address these issues, this paper proposes an ASD detection mechanism using a novel Hybrid Convolutional Bidirectional Long Short-Term Memory based Water Optimization Algorithm (HCBiLSTM-WOA). The prediction efficiency of the proposed HCBiLSTM-WOA method is investigated using real-time ASD datasets containing both ASD and non-ASD data from toddlers, children, adolescents, and adults. The inconsistent and incomplete representations of the raw ASD dataset are modified using preprocessing procedures such as handling missing values, predicting outliers, data discretization, and data reduction. The preprocessed data obtained is then fed into the proposed HCBiLSTM-WOA classification model to effectively predict the non-ASD and ASD classes. The initially randomly initialized hyperparameters of the HCBiLSTM model are adjusted and tuned using the water optimization algorithm (WOA) to increase the prediction accuracy of ASD. After detecting non-ASD and ASD classes, the HCBiLSTM-WOA method further classifies the ASD cases into respective stages based on the autistic traits observed in toddlers, children, adolescents, and adults. Also, the ethical considerations that should be taken into account when campaign ASD risk communication are complex due to the data privacy and unpredictability surrounding ASD risk factors. The fusion of sophisticated deep learning techniques with an optimization algorithm presents a promising framework for ASD diagnosis. This innovative approach shows potential in effectively managing intricate ASD data, enhancing diagnostic precision, and improving result interpretation. Consequently, it offers clinicians a tool for early and precise detection, allowing for timely intervention in ASD cases. Moreover, the performance of the proposed HCBiLSTM-WOA method is evaluated using various performance indicators such as accuracy, kappa statistics, sensitivity, specificity, log loss, and Area Under the Receiver Operating Characteristics (AUROC). The simulation results reveal the superiority of the proposed HCBiLSTM-WOA method in detecting ASD compared to other existing methods. The proposed method achieves a higher ASD prediction accuracy of about 98.53% than the other methods being compared.

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5. Kimmig AS, Burger L, Schall M, Derntl B, Wildgruber D. Impairment of affective and cognitive empathy in high functioning autism is mediated by alterations in emotional reactivity. Sci Rep;2024 (Sep 17);14(1):21662.

Empathy impairments are considered a key aspect of autism-spectrum disorders (ASD). Previous research consistently shows reduced cognitive empathy, but findings on affective empathy vary, possibly due to experimental design variations (e.g., stimulus modality, social distance) and individual psychological factors (e.g., perceptual abilities, emotional reactivity). This study aims to clarify deficits in affective and cognitive empathy in ASD by addressing these contributing factors. Empathy was examined in 34 autistic individuals and 33 typically developed controls (TDCs) through the Textual Empathy Test (TET). The TET was developed to assess emotional responses when imagining oneself (emotional reactivity) as compared to a target person (friend, stranger) in emotional situations presented via short verbal descriptions. Participants rated emotional states of the target person (cognitive empathy) as well as their own emotional responses when imagining the target person in that situation (affective empathy). Ratings were interpreted relative to normative mean values through standardized regression coefficients. Results showed that high-functioning autism was associated with lower cognitive and affective empathy irrespective of social distance as well as with decreased emotional reactivity compared to controls. Moreover, emotional reactivity mediated the impact of ASD on both empathic components. In summary, altered emotional reactivity may underlie impaired empathy in autistic individuals.

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6. Leadbitter K, Harrison L, Langhorne S, Ellis C, Smallman R, Pearson A, Hackett L, Kroll L, Dunkerley A, Beach H, Gilbert J, van Gils A, Hutton T, Green J, Bee P. The development, feasibility and acceptability of Empower-Autism: A new psychoeducational and psychotherapeutic programme for caregivers of children recently diagnosed with autism. Autism;2024 (Sep 18):13623613241274566.

What is already known about the topic?Parents and carers face many challenges following their child’s autism diagnosis. They often look for information, and social and emotional support. There has been relatively little research into how best to provide this support and this means that there is no evidence to guide the delivery of services. Studies have suggested that an approach called Acceptance and Commitment Therapy can help parents and carers with their adjustment and emotional wellbeing.What does this article add?This article describes the development of a new group-based programme to address the diverse needs of caregivers after their child’s autism diagnosis. The new programme was developed with caregivers, autistic people and professionals. It was called Empower-Autism and contained lots of information about autism and strategies to support autistic children, alongside therapeutic aspects based on Acceptance and Commitment Therapy. The programme was delivered to 29 parents/carers in three groups. Attendance at the groups was satisfactory. Both parents/carers and facilitators liked and valued the programme and found it accessible. They made suggestions for improvements. After the programme, parents and carers described improved wellbeing. They felt more positive and more connected to other people. They also described parenting their child in a more informed and sensitive way.Implications for practice, research or policyThe new programme is being tested within a large clinical trial. If there are positive results, the programme could be recommended for delivery and this would address an important gap in evidence-based practice.

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7. Lin CH, Zeng T, Lu CW, Li DY, Liu YY, Li BM, Chen SQ, Deng YH. Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial. Front Nutr;2024;11:1447059.

BACKGROUND: The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. METHODS: We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥10(6) CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. RESULTS: Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. CONCLUSION: BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

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8. Maddalon L, Minissi ME, Parsons T, Hervas A, Alcaniz M. Exploring Adaptive Virtual Reality Systems Used in Interventions for Children With Autism Spectrum Disorder: Systematic Review. J Med Internet Res;2024 (Sep 18);26:e57093.

BACKGROUND: Adaptive systems serve to personalize interventions or training based on the user’s needs and performance. The adaptation techniques rely on an underlying engine responsible for processing incoming data and generating tailored responses. Adaptive virtual reality (VR) systems have proven to be efficient in data monitoring and manipulation, as well as in their ability to transfer learning outcomes to the real world. In recent years, there has been significant interest in applying these systems to improve deficits associated with autism spectrum disorder (ASD). This is driven by the heterogeneity of symptoms among the population affected, highlighting the need for early customized interventions that target each individual’s specific symptom configuration. OBJECTIVE: Recognizing these technology-driven therapeutic tools as efficient solutions, this systematic review aims to explore the application of adaptive VR systems in interventions for young individuals with ASD. METHODS: An extensive search was conducted across 3 different databases-PubMed Central, Scopus, and Web of Science-to identify relevant studies from approximately the past decade. Each author independently screened the included studies to assess the risk of bias. Studies satisfying the following inclusion criteria were selected: (1) the experimental tasks were delivered via a VR system, (2) system adaptation was automated, (3) the VR system was designed for intervention or training of ASD symptoms, (4) participants’ ages ranged from 6 to 19 years, (5) the sample included at least 1 group with ASD, and (6) the adaptation strategy was thoroughly explained. Relevant information extracted from the studies included the sample size and mean age, the study’s objectives, the skill trained, the implemented device, the adaptive strategy used, the engine techniques, and the signal used to adapt the systems. RESULTS: Overall, a total of 10 articles were included, involving 129 participants, 76% of whom had ASD. The studies included level switching (7/10, 70%), adaptive feedback strategies (9/10, 90%), and weighing the choice between a machine learning (ML) adaptive engine (3/10, 30%) and a non-ML adaptive engine (8/10, 80%). Adaptation signals ranged from explicit behavioral indicators (6/10, 60%), such as task performance, to implicit biosignals, such as motor movements, eye gaze, speech, and peripheral physiological responses (7/10, 70%). CONCLUSIONS: The findings reveal promising trends in the field, suggesting that automated VR systems leveraging real-time progression level switching and verbal feedback driven by non-ML techniques using explicit or, better yet, implicit signal processing have the potential to enhance interventions for young individuals with ASD. The limitations discussed mainly stem from the fact that no technological or automated tools were used to handle data, potentially introducing bias due to human error.

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9. Mbachu CNP, Hagerman R, Eseigbe E, Odita A, Mbachu I, Ilikanu S, Akowundu K, Ndukwu C, Echezona M, Okereke O, Echendu S, Udigwe I. Knowledge and perceptions about fragile X syndrome and fragile X-premutation-associated conditions among medical doctors in Nigeria. Clin Genet;2024 (Sep 18)

Fragile X syndrome (FXS) is a significant cause of intellectual disability and autism, while Fragile X Premutation -Associated Conditions (FXPAC) are a significant cause of morbidity and mortality globally. This study assessed the level of knowledge and perceptions about FXS and FXPAC among doctors in Nigeria. It was a web-based, cross-sectional study conducted among a cohort of doctors in Nigeria. Socio-demographic profile, knowledge of FXS, perceptions about FXS, knowledge of FXPAC, experience of doctors, and suggested ways of improving knowledge and management of FXS were obtained. Data were analyzed using STATA 16.0. Chi-square and Fisher’s exact tests of association were used to determine the association between variables, with the significance level set at p < 0.05. A total of 274 doctors participated in the study. A significant proportion of respondents had limited knowledge about the clinical features of FXS. Nine of ten (90.0%) participants with good knowledge of FXS had good perceptions of FXS management. This was statistically significant (p < 0.001). There was a high nonresponse rate to what FXPAC is (164/274, 59.9%) among the respondents because of insufficient knowledge. Suboptimal knowledge of FXS which influenced perception was noted among doctors. More strategies should be considered to improve doctors' knowledge and management of FXS and FXPAC in Nigeria.

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10. Nowell S, Steinbrenner JR, Wallisch A, Salley B, McGovern J, McGauley S, Watson LR, Irvin D, Buzhardt J, Boyd B. Adapting the Early Communication Indicator as a Social Communication Outcome Measure for Young Autistic Children: A Pilot Study. Am J Speech Lang Pathol;2024 (Sep 18);33(5):2610-2617.

PURPOSE: We sought to conduct a pilot investigation of the reliability and administration fidelity of a new play-based measure of social communication for infants and toddlers with an autism diagnosis. METHOD: Our team adapted an existing measure, the Early Communication Indicator (ECI), for use with young autistic children in clinical and research contexts. In this brief report, we detail our adaptation process including administration and scoring of the final adapted measure based on data from a two-phase pilot study with young autistic children (N = 17). RESULTS: This adapted measure, the Early Communication Indicator-Autism (ECI-A), captured a range of scores for the ECI, Initiation of Joint Attention, and Directed Communication in pilot testing. Interrater reliability was moderate to strong across the scored behaviors. Finally, parents were able to administer the ECI-A with high fidelity with support from the research staff. CONCLUSIONS: This two-phase pilot study demonstrated promise for the ECI-A as a brief measure of social communication that can be administered by parents and reliably scored by trained staff with limited background in autism assessments. Validation of the ECI-A is presently underway. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26042077.

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11. Schultz PV, Brambila-Manso B, Couto-Rosa L, Rocha KSS, de Araújo D, Ayres LR, Dos Santos Júnior GA. Validation of Autism Stigma Knowledge – Questionnaire (ASK-Q) for Brazilian Portuguese. Explor Res Clin Soc Pharm;2024 (Sep);15:100495.

BACKGROUND: Low levels of knowledge among health professionals about autism spectrum disorders (ASD) can impair the care provided to people with autism. In Brazil, there are still no validated instruments that assess the knowledge of pharmacy students and pharmacists regarding ASD. OBJECTIVE: This study aimed to carry out the cross-cultural adaptation of the Autism Stigma Knowledge Questionnaire (ASK-Q) into Brazilian Portuguese and to evaluate the evidence of content validity. METHODS: This study was conducted in two stages, as recommended in the literature. Stage 1 corresponded to cross-cultural adaptation carried out in six phases (translation of the ASK-Q, synthesis of the translations, evaluation by a committee of experts, evaluation by the target audience of pharmacy students and pharmacists, reverse translation, and evaluation by the author of the original instrument). Step 2 corresponds to the assessment of content validity evidence. RESULTS: The instrument presented semantic, idiomatic, conceptual, and cultural equivalences, and the author considered the adaptation adequate. Content validity had an adequate coefficient (0.89). The ASK-Q was cross-culturally adapted to the Brazilian context according to the main theoretical framework. CONCLUSIONS: Future studies will be conducted to evaluate other evidence for the validity of the ASK-Q-Brasil. These studies will be fundamental in assessing knowledge about ASD.

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12. Sung C, Okyere C, Connor A, Chen J. Lived Experiences and Perceptions of Autistic Young Adults Participating in Employment Readiness Skills Training. J Autism Dev Disord;2024 (Sep 18)

This study aimed to examine the experiences and perceptions of participants engaged in an employment readiness program, Employment Preparation And Skills Support (EPASS), which is a manualized group-based training program designed to improve employment readiness among autistic young adults. A qualitative descriptive design was utilized to generate thick descriptions through semi-structured interviews with 22 transition-age autistic individuals (Mage = 20; 6 females; 16 males). Thematic analysis was employed to understand the experiences and career outcomes of transition-age autistic individuals pre- and post-participation in the EPASS program. Five main themes were identified: (1) More Negative Than Positive Employment-related Experiences; (2) Insight about Training Needs despite Hesitation to Participate; (3) Improved Perception and Confidence of Employment readiness through Experiential Learning; (4) Emerging Career Goals and Plans in Future Application of Knowledge and Skills; and (5) Learning Preference for More Interactive and Practice Experience. Participants reported a better understanding of job preparation skills, work-related social skills and interview etiquette. They also reported that what they learned in EPASS helped them improve their skills and confidence in obtaining and maintaining employment. Overall, participants expressed satisfaction with participating in EPASS and anticipated potential long-term impacts on their employability. This study sheds light on the training needs for transition-age autistic individuals and informs future employment readiness program development. Future studies should focus on collaborating with stakeholders to address training gaps and support needs that foster improved employment outcomes for this population.

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13. Wenneborg K, Pettersson Roll L, Bölte S, Odom S, Bejnö H. The Autism Program Environment Rating Scale in Swedish Primary School: Cultural Adaptation and Content Validation. J Autism Dev Disord;2024 (Sep 18)

There is a recognized need to improve inclusive learning environments for autistic children in primary school settings in Sweden. This study aimed to translate, cross-culturally adapt, and assess the content validity of the Swedish primary school version of the Autism Program Environment Scale (APERS), originally developed to evaluate autism program quality in educational settings in the United States. Following the translation into Swedish and the first cultural adaptation of the APERS, a content panel group of 14 professionals rated its content validity. Four of the content panel members also participated in individual interviews that provided a qualitative evaluation of the instrument’s content validity. Finally, the authors piloted the APERS in 10 Swedish primary school classrooms to assess its feasibility. The ratings and qualitative information from the content panel members indicated a substantial need for the Swedish APERS in primary school, resulting in the culturally adapted APERS-Primary-Sweden (SE). The instrument demonstrated a high level of cross-cultural content validity for assessing the quality of the learning environment for students with autism in Swedish primary school settings. The pilot testing of the instrument resulted in further cultural adaptations. In conclusion, APERS-Primary-SE is a comprehensive scale that can be used to assess the quality of primary school learning environments for children with autism in Sweden. Further research is needed to evaluate the adapted instrument’s effectiveness in improving the learning environment in Swedish primary school classrooms.

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14. Wilson KP, Valazza E, Price C. Video Modeling to Support Social Communication Goals of Autistic Adults: A Tutorial. Am J Speech Lang Pathol;2024 (Sep 18);33(5):2249-2265.

PURPOSE: Decades of research have shown video modeling to be an effective tool for teaching and supporting a variety of skills in autistic children. More recently, video modeling has emerged as an effective support for autistic adults, with much of the literature focused on vocational success through support of language skills. The purpose of this tutorial is to provide speech-language pathologists, autistic adults, and other team members with evidence-based guidelines for use of video modeling to support success with social communication across settings. METHOD: This evidence-based tutorial draws from the literature on video modeling for autistic adults in the area of social communication, presenting empirically supported guidelines for speech-language pathologists considering video modeling as a tool to support social communication within this population and their interaction partners. This tutorial presents an evidence-based, step-by-step guide to the planning, creation, and use of video models with and by autistic adults, along with important additional considerations based on relevant literature. CONCLUSIONS: Video modeling is a social communication support that is backed by the scientific literature as an efficacious tool for use by autistic adults. This tutorial will guide speech-language pathologists’ use of this evidence-based tool as they work alongside autistic adults and others to help meet social communication goals across settings.

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15. Xu D, Sun Z, Yang Y, Cai K, Zhu L, Qi K, Liu Z, Shi Y, Liu Y, Qiao Z, Jiang L, Chen A. Effects of Ball Combination Exercise Combined with cTBS Intervention on Sleep Problems in Children with Autism. J Autism Dev Disord;2024 (Sep 18)

Sleep problems significantly affect the quality of life of autism spectrum disorder (ASD) children. This study aimed to evaluate the effects of a 12-week ball combination exercise, continuous theta burst stimulation (cTBS) stimulation, and combined intervention on sleep problems in children with ASD. Forty-five ASD children were divided into three intervention groups (ball combination exercise(n = 12), cTBS stimulation(n = 10), combined (n = 12) and a control group (n = 11). The intervention groups underwent intervention, while the control group maintained daily activities. The effects were assessed using the Children’s Sleep Habits Questionnaire (CSHQ) scale. The results revealed that after 12 weeks of intervention, three programs reduced sleep problems in children with ASD. The post-test scores of the cTBS group (p = 0.002) and the combined group (p < 0.001) were significantly lower than the baseline scores on the CSHQ scale. The exercise group (p = 0.002) and the combined group (p < 0.001) showed significant improvement in sleep anxiety, while there was no statistically significant difference in the effectiveness of the three interventions for sleep-onset delay. The combined group outperformed the single intervention groups in the CSHQ score and sleep anxiety sub-dimensions. The combined intervention group showed slightly superior performance in sleep onset latency, however, there was no significant difference. Three interventions alleviated sleep issues in ASD children, with the combined method proving more effective. This study validates non-pharmacologic and combined approaches for ASD sleep problems. Future research should delve deeper into the mechanisms of these interventions in ASD children's sleep improvement.

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