1. Abeasi DA, Nkosi NG, Badoe E, Adjeman J. Caring by default: experiences of caregivers of children with developmental disabilities in Ghana mirrored in the context of the stress process model. BMC Nurs;2024 (Jul 15);23(1):482.

BACKGROUND: Caring for a child with developmental disabilities (DD) is associated with significant stress and burden. Caregivers’ experiences are influenced by factors such as poverty, stigma, and the lack of accessibility to services, equipment, and assistive devices. These factors are prevalent in a low-resource setting like Ghana which ultimately influences the experiences of caregivers. The aim of the study was to explore the experiences of caregivers of children with DD in the context of the Stress Process Model. METHODS: The study employed a descriptive phenomenological design Caregivers of children with DD attending the Neurodevelopmental Clinic of a Teaching Hospital were purposively sampled. Data collection involved semi-structured interviews, reaching saturation with 14 participants. The interviews were audio-recorded transcribed verbatim and analysed using thematic analysis. RESULTS: Four main themes emerged: perception of caregiving, stressors faced by caregivers, negative health outcomes and coping strategies. Perception of caregiving had two sub-themes as stressful nature of caregiving and time-consuming. Six sub-themes were linked to stressors faced by caregivers: the child’s ADL needs, communication barrier, managing challenging behaviour, child’s health needs, unmet educational needs, and economic burden. Negative health outcomes had three sub-themes: decline in physical, mental and social well-being. While some caregivers used maladaptive coping strategies like blaming, others employed adaptive coping strategies like religious coping through prayer, self-encouragement and support from other family members. CONCLUSION: The study highlights the complex interaction between caregivers’ perception of their caregiving situation, the stressors they experience, their coping resources, and the negative health outcomes associated with caregiving. These findings underscore the need for context-specific caregiver programmes to mitigate the negative impacts of caregiving.

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2. Annunziata S, Santos L, Caglio A, Geminiani A, Brazzoli E, Piazza E, Olivieri I, Pedrocchi A, Cavallini A. Interactive mirrOring Games wIth sOCial rObot (IOGIOCO): a pilot study on the use of intransitive gestures in a sample of Italian preschool children with autism spectrum disorder. Front Psychiatry;2024;15:1356331.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication, social interaction, and restricted behaviors. The importance of early intervention has been widely demonstrated, and developmental trajectories in ASD emphasize the importance of nonverbal communication, such as intransitive gesture production, as a possible positive prognostic factor for language development. The use of technological tools in the therapy of individuals with ASD has also become increasingly important due to their higher engagement and responsiveness to technological objects, such as robots. MATERIALS AND METHODS: We developed a training protocol using the humanoid robot NAO, called IOGIOCO (Interactive mirroring Games wIth sOCial rObot), based on the use of intransitive gestures embedded in naturalistic dialogues, stimulating a triadic interaction between child, robot and therapist. The training was divided into six levels; the first 2 levels were called « familiarization levels, » and the other 4 were « training levels ». The technological setup includes different complexity levels, from mirroring tasks to building spontaneous interactions. We tested the protocol on 10 preschool children with ASD (aged 2-6 years) for 14 weeks. We assessed them at recruitment (T0), at the end of training (T1), and after 6 months (T2). RESULTS: We demonstrated the tolerability of the protocol. We found that one group (n=4, males and 2 females) reached the training level, while another and group (n=6 males) remained at a familiarization level (mirroring), we analyzed the results for the two groups. In the group that reached the training levels, we found promising results, such as an improvement in the Social Adaptive Domain of the ABAS-II questionnaire between T0 and T2. CONCLUSION: While current results will need a Randomized Controlled Trial to be confirmed, the present work sets an important milestone in using social robots for ASD treatment, aimed at impacting social and communication skills in everyday life.

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3. Bagheri S, Yu JC, Gallucci J, Tan V, Oliver LD, Dickie EW, Rashidi AG, Foussias G, Lai MC, Buchanan RW, Malhotra AK, Voineskos AN, Ameis SH, Hawco C. Transdiagnostic Neurobiology of Social Cognition and Individual Variability as Measured by Fractional Amplitude of Low-Frequency Fluctuation in Schizophrenia and Autism Spectrum Disorders. bioRxiv;2024 (Jul 3)

Fractional amplitude of low-frequency fluctuation (fALFF) is a validated measure of resting-state spontaneous brain activity. Previous fALFF findings in autism and schizophrenia spectrum disorders (ASDs and SSDs) have been highly heterogeneous. We aimed to use fALFF in a large sample of typically developing control (TDC), ASD and SSD participants to explore group differences and relationships with inter-individual variability of fALFF maps and social cognition. fALFF from 495 participants (185 TDC, 68 ASD, and 242 SSD) was computed using functional magnetic resonance imaging as signal power within two frequency bands (i.e., slow-4 and slow-5), normalized by the power in the remaining frequency spectrum. Permutation analysis of linear models was employed to investigate the relationship of fALFF with diagnostic groups, higher-level social cognition, and lower-level social cognition. Each participant’s average distance of fALFF map to all others was defined as a variability score, with higher scores indicating less typical maps. Lower fALFF in the visual and higher fALFF in the frontal regions were found in both SSD and ASD participants compared with TDCs. Limited differences were observed between ASD and SSD participants in the cuneus regions only. Associations between slow-4 fALFF and higher-level social cognitive scores across the whole sample were observed in the lateral occipitotemporal and temporoparietal junction. Individual variability within the ASD and SSD groups was also significantly higher compared with TDC. Similar patterns of fALFF and individual variability in ASD and SSD suggest some common neurobiological deficits across these related heterogeneous conditions.

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4. Caron C, McCullagh EA, Bertolin G. Sex-specific loss of mitochondrial membrane integrity and mass in the auditory brainstem of a mouse model of Fragile X syndrome. bioRxiv;2024 (Jul 3)

Sound sensitivity is one of the most common sensory complaints for people with autism spectrum disorders (ASDs). How and why sounds are perceived as overwhelming by affected people is unknown. To process sound information properly, the brain requires high activity and fast processing, as seen in areas like the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem. Recent work has shown dysfunction in mitochondria, which are the primary source of energy in cells, in a genetic model of ASD, Fragile X syndrome (FXS). Whether mitochondrial functions are also altered in sound-processing neurons, has not been characterized yet. To address this question, we imaged the MNTB in a mouse model of FXS. We stained MNTB brain slices from wild-type and FXS mice with two mitochondrial markers, TOMM20 and PMPCB, located on the Outer Mitochondrial Membrane and in the matrix, respectively. These markers allow exploration of mitochondrial subcompartments. Our integrated imaging pipeline reveals significant sex-specific differences in the degree of mitochondrial length in FXS. Significant differences are also observable in the overall number of mitochondria in male FXS mice, however, colocalization analyses between TOMM20 and PMPCB reveal that the integrity of these compartments is most disrupted in female FXS mice. We highlight a quantitative fluorescence microscopy pipeline to monitor mitochondrial functions in the MNTB from control or FXS mice and provide four complementary readouts. Our approach paves the way to understanding how cellular mechanisms important to sound encoding are altered in ASDs.

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5. Erdogan MA, Nesil P, Altuntas I, Sirin C, Uyanikgil Y, Erbas O. Amelioration of propionic acid-induced autism spectrum disorder in rats through dapagliflozin: The role of IGF-1/IGFBP-3 and the Nrf2 antioxidant pathway. Neuroscience;2024 (Jul 14);554:16-25.

The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin’s potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin’s antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin’s potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder.

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6. Hamoud AF, Al-Saadi NH. The Assessment of Selenium, Aluminum, and Zinc in Children with Autism Spectrum Disorder. Biol Trace Elem Res;2024 (Jul 15)

ASD is a complex condition defined by many causes, one of them being excessive concentrations of necessary and harmful chemicals in children. The serum, hair, and nails of children with ASD have lower levels of critical trace elements, according to studies. It is quite obvious that bio elements are involved in physiology and pathophysiology. Thus, this study examined trace element contents in serum samples from children with autism spectrum disorder (ASD), specifically zinc (Zn), aluminum (Al), and selenium (Se). The study also looked for links between trace element levels and autistic severity. The study included 47 children with autism spectrum disorder, and the Gilliam’s Scale was used for severity. The study also included 53 healthy kids with age and gender-matched with those of ASD. For serum trace element analysis, graphite furnace atomic absorption spectrophotometry was used. The study found significant decreases in selenium and zinc concentration (OR, 5.25; CI, 1.96 ~ 14.08; p < 0.001) and increases in aluminum level (OR, 39.34; CI, 8.20 ~ 89.45; p < 0.001) in children with ASD compared to the control group. The area under the curve (AUC) values of 0.85 for Se, 0.98 for Al, and 0.7 for Zn showed high sensitivity and specificity for all parameters. Results indicate a strong positive connection between ASD and their levels of selenium (Se) and zinc (Zn) (β, 0.48; CI, 0.280 ~ 0.679; p < 0.001 and β, 0.31; CI, 0.10 ~ 0.52; p = 0.005). There is a negative correlation between ASD and aluminum (Al) (β 0.83; CI, 0.71 ~ 0.95; p < 0.001). This element may be a biomarker for autism in youngsters. High odds ratio (OR) values indicate trace element risk in autistic children.

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7. King C, Rogers LG, Jansen J, Sivayokan B, Neyhard J, Warnes E, Hall SE, Plakke B. Adolescent Treadmill Exercise Enhances Hippocampal Brain-Derived Neurotrophic Factor (BDNF) Expression and Improves Cognition in Autism-Modeled Rats. Physiol Behav;2024 (Jul 12):114638.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by repetitive behaviors and altered communication abilities. Exercise is a low-cost intervention that could improve cognitive function and improve brain plasticity mechanisms. Here, the valproic acid (VPA) model was utilized to induce ASD-like phenotypes in rodents. Animals were exercised on a treadmill and performance was evaluated on a cognitive flexibility task. Biomarkers related to exercise and plasticity regulation were quantified from the prefrontal cortex, hippocampus, and skeletal muscle. Exercised VPA animals had higher levels of hippocampal BDNF compared to sedentary VPA animals and upregulated antioxidant enzyme expression in skeletal muscle. Cognitive improvements were demonstrated in both sexes, but in different domains of cognitive flexibility. This research demonstrates the benefits of exercise and provides evidence that molecular responses to exercise occur in both the central nervous system and in the periphery. These results suggest that improving regulation of BDNF via exercise, even at low intensity, could provide better synaptic regulation and cognitive benefits for individuals with ASD.

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8. Kosidou K, Karlsson H, Arver S, Bhasin S, Dalman C, Gardner RM. Maternal Steroid Hormone Levels in Early Pregnancy and Autism in the Offspring: A Population-Based, Nested Case-Control Study. Biol Psychiatry;2024 (Jul 15);96(2):147-158.

BACKGROUND: A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. METHODS: Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child’s sex and maternal health, demographic, and socioeconomic factors. RESULTS: We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24-2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36-0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11-1.99). We observed no evidence for interaction with sex of the child. CONCLUSIONS: These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism.

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9. Lyvers M, Luarca A, Priestly G, Thorberg FA. Adult symptoms of ASD in relation to excessive internet use: The roles of ADHD symptoms and negative mood. Int J Psychol;2024 (Jul 15)

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have been reportedly associated with excessive internet use, also known as internet addiction. As ADHD is the most common comorbidity in ASD, the present study examined the possibility that ADHD symptoms, and/or trait and mood factors linked to ASD, ADHD and internet addiction, could account for the association of ASD with internet addiction symptoms. A nonclinical young adult sample of 248 internet using men and women completed self-report measures of ASD and ADHD symptoms, alexithymia, impulsivity, negative moods and internet addiction symptoms. Scores on the ASD and ADHD symptom measures were normally distributed, consistent with the notion that the corresponding disorders represent extreme, impairing ends of population distributions of their symptoms. Hierarchical regression followed by path analysis indicated that the relationship between ASD and internet addiction symptoms was fully mediated by ADHD symptoms and negative moods. Further, the relationship between ADHD and internet addiction symptoms was partially mediated by impulsivity and negative moods. Present findings point to the mediating roles of ADHD symptoms and negative moods in the association of ASD with internet addiction symptoms.

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10. Martins PLB, Torquato GCP, Dias G, Leite IB, Gaspar TM, Pinto JP, Macedo DS. Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Jul 14);134:111089.

OBJECTIVES: This systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs. METHODS: We searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction. RESULTS: Twenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data’s quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies. CONCLUSION: Our results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.

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11. Mathews L, Schafer EC, Gopal KV, Lam B, Miller S. Speech-in-Noise and Dichotic Auditory Training Students With Autism Spectrum Disorder. Lang Speech Hear Serv Sch;2024 (Jul 15):1-14.

PURPOSE: Individuals diagnosed with autism spectrum disorder (ASD) often exhibit auditory processing issues, including poor speech recognition in background noise and dichotic processing (integration of different stimuli presented to the two ears). Auditory training could mitigate these auditory difficulties. However, few auditory training programs have been designed to target specific listening deficits for students with ASD. The present study summarizes the development of an innovative, one-on-one, clinician-developed speech-in-noise (SIN) training program that has not been previously described and an existing dichotic auditory training program to address common auditory processing deficits in students with ASD. METHOD: Twenty verbal students with ASD, ages 7-17 years, completed a one-on-one, clinician-developed SIN training program and a commercially available dichotic training program 2-3 times a week (30-45 min per session) for 12 weeks. Maximum and minimum training levels from the SIN and dichotic training programs were analyzed statistically to document changes in training level over the training period. RESULTS: Analyses of the pre- and posttraining data revealed significant improvements in training level for both the SIN and dichotic training programs. CONCLUSIONS: Overall, the proposed SIN training resulted in significant improvements in training level and may be used along with dichotic training to improve some of the most common auditory processing issues documented in verbal individuals with ASD requiring minimal support. Both types of auditory training may be implemented in one-on-one therapy in clinics and in the schools.

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12. Misiunaite I, Davidson D, Sawyer B. Code- and Meaning-related Emergent Literacy Skills and Joint Attention in Autistic and Non-Autistic Children. J Autism Dev Disord;2024 (Jul 15)

Code- and meaning-related emergent literacy skills of autistic children were compared to those of non-autistic children who did not differ on age and full-scale IQ (FSIQ). The associations between joint attention skills and early literacy abilities were of interest. Seventeen autistic and 20 non-autistic children (48 to 72 months) participated. Parents completed a joint attention measure and children completed code- and meaning-related emergent literacy skills measures. Findings showed that autistic and non-autistic children did not differ on code-related emergent literacy skills, letter knowledge and phonological awareness, but autistic children scored lower on print conceptsand name writing. Autistic children also scored lower on meaning-related skills assessing the comprehensive and quality of oral narratives. FSIQ predicted print concept knowledge in all children. Receptive vocabulary was a significant predictor of meaning-related skills in autistic children and the quality of oral narratives in non-autisticchildren. Joint attention was also a significant predictor of oral narrative quality in autistic children. Recommendations for promoting emergent literacy skills using a strength-based approach are discussed.

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13. Radhakrishnan M, Ramamurthy K, Shanmugam S, Prasanna G, S V, Y S, Won D. A hybrid model for the classification of Autism Spectrum Disorder using Mu rhythm in EEG. Technol Health Care;2024 (Jul 15)

BACKGROUND: Autism Spectrum Disorder (ASD) is a condition with social interaction, communication, and behavioral difficulties. Diagnostic methods mostly rely on subjective evaluations and can lack objectivity. In this research Machine learning (ML) and deep learning (DL) techniques are used to enhance ASD classification. OBJECTIVE: This study focuses on improving ASD and TD classification accuracy with a minimal number of EEG channels. ML and DL models are used with EEG data, including Mu Rhythm from the Sensory Motor Cortex (SMC) for classification. METHODS: Non-linear features in time and frequency domains are extracted and ML models are applied for classification. The EEG 1D data is transformed into images using Independent Component Analysis-Second Order Blind Identification (ICA-SOBI), Spectrogram, and Continuous Wavelet Transform (CWT). RESULTS: Stacking Classifier employed with non-linear features yields precision, recall, F1-score, and accuracy rates of 78%, 79%, 78%, and 78% respectively. Including entropy and fuzzy entropy features further improves accuracy to 81.4%. In addition, DL models, employing SOBI, CWT, and spectrogram plots, achieve precision, recall, F1-score, and accuracy of 75%, 75%, 74%, and 75% respectively. The hybrid model, which combined deep learning features from spectrogram and CWT with machine learning, exhibits prominent improvement, attained precision, recall, F1-score, and accuracy of 94%, 94%, 94%, and 94% respectively. Incorporating entropy and fuzzy entropy features further improved the accuracy to 96.9%. CONCLUSIONS: This study underscores the potential of ML and DL techniques in improving the classification of ASD and TD individuals, particularly when utilizing a minimal set of EEG channels.

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14. Sha M, Parveen Rahamathulla M. Splice site recognition – deciphering Exon-Intron transitions for genetic insights using Enhanced integrated Block-Level gated LSTM model. Gene;2024 (Jul 15);915:148429.

Bioinformatics is a contemporary interdisciplinary area focused on analyzing the growing number of genome sequences. Gene variants are differences in DNA sequences among individuals within a population. Splice site recognition is a crucial step in the process of gene expression, where the coding sequences of genes are joined together to form mature messenger RNA (mRNA). These genetic variants that disrupt genes are believed to be the primary reason for neuro-developmental disorders like ASD (Autism Spectrum Disorder) is a neuro-developmental disorder that is diagnosed in individuals, families, and society and occurs as the developmental delay in one among the hundred genes that are associated with these disorders. Missense variants, premature stop codons, or deletions alter both the quality and quantity of encoded proteins. Predicting genes within exons and introns presents main challenges, such as dealing with sequencing errors, short reads, incomplete genes, overlapping, and more. Although many traditional techniques have been utilized in creating an exon prediction system, the primary challenge lies in accurately identifying the length and spliced strand location classification of exons in conjunction with introns. From now on, the suggested approach utilizes a Deep Learning algorithm to analyze intricate and extensive genomic datasets. M-LSTM is utilized to categorize three binary combinations (EI as 1, IE as 2, and none as 3) using spliced DNA strands. The M-LSTM system is able to sequence extensive datasets, ensuring that long information can be stored without any impact on the current input or output. This enables it to recognize and address long-term connections and problems with rapidly increasing gradients. The proposed model is compared internally with Naïve Bayes and Random Forest to assess its efficacy. Additionally, the proposed model’s performance is forecasted by utilizing probabilistic parameters like recall, F1-score, precision, and accuracy to assess the effectiveness of the proposed system.

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15. Smith SS, Benanni S, Jones Q, Kenney L, Evrard MR. Manipulation of α4βδ GABA(A) receptors alters synaptic pruning in layer 3 prelimbic prefrontal cortex and impairs temporal order recognition: Implications for schizophrenia and autism. Brain Res;2024 (Jul 15);1835:148929.

Temporal order memory is impaired in autism spectrum disorder (ASD) and schizophrenia (SCZ). These disorders, more prevalent in males, result in abnormal dendritic spine pruning during adolescence in layer 3 (L3) medial prefrontal cortex (mPFC), yielding either too many (ASD) or too few (SCZ) spines. Here we tested whether altering spine density in neural circuits including the mPFC could be associated with impaired temporal order memory in male mice. We have shown that α4βδ GABA(A) receptors (GABARs) emerge at puberty on spines of L5 prelimbic mPFC (PL) where they trigger pruning. We show here that α4βδ receptors also increase at puberty in L3 PL (P < 0.0001) and used these receptors as a target to manipulate spine density here. Pubertal injection (14 d) of the GABA agonist gaboxadol, at a dose (3 mg/kg) selective for α4βδ, reduced L3 spine density by half (P < 0.0001), while α4 knock-out increased spine density ∼ 40 % (P < 0.0001), mimicking spine densities in SCZ and ASD, respectively. In both cases, performance on the mPFC-dependent temporal order recognition task was impaired, resulting in decreases in the discrimination ratio which assesses preference for the novel object: -0.39 ± 0.15, gaboxadol versus 0.52 ± 0.09, vehicle; P = 0.0002; -0.048 ± 0.10, α4 KO versus 0.49 ± 0.04, wild-type; P < 0.0001. In contrast, the number of approaches was unaltered, reflecting unchanged locomotion. These data suggest that altering α4βδ GABAR expression/activity alters spine density in L3 mPFC and impairs temporal order memory to mimic changes in ASD and SCZ. These findings may provide insight into these disorders.

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16. Soni V, LoTurco JJ. KATNAL2 mutations link ciliary dysfunction to hydrocephalus and autism. Proc Natl Acad Sci U S A;2024 (Jul 23);121(30):e2410761121.

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17. Torenvliet C, Groenman AP, Van der Burg E, Charlton RC, Hamilton CJ, Geurts HM. Memory strategies in autistic and older adults. Autism Res;2024 (Jul 15)

Memory strategies in autistic adults seem to mimic strategies at older age, as both younger autistic and older non-autistic individuals use fewer semantic features in visual memory tasks. Therefore, the current study aims to investigate whether early differences in memory strategies lead to altered age-related effects in autism, particularly whether initial difficulties in strategy use become advantageous at older age (i.e., « protective aging »). A total of 147 participants across four groups (autistic younger/older, non-autistic younger/older) completed an online assessment. This assessment included a recognition version of the Visual Patterns Test (VPT) to evaluate semantic strategy use in visual memory, the Just Noticeable Difference (JND) size task for assessing visual processing, and the Multifactorial Memory Questionnaire to evaluate subjective memory functioning and strategy use (MMQ). Unexpectedly, all groups benefited from semantic features on the VPT, although the older groups performed less accurately and slower than the younger groups. The JND Size task showed no group differences. Autistic adults rated their MMQ memory as worse than non-autistic adults, despite reporting greater strategy use. These results indicate that cognitive strategies might be more similar between younger/older and autistic/non-autistic people than previously expected, although notable discrepancies between objective and subjective measures were present. They also substantiate previously reported parallel (i.e., similar) age-related effects between autistic and non-autistic people.

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18. Yan J, Zhang Y, Wang J, Zhu G, Fang K. Effects of transcranial magnetic stimulation on sleep structure and quality in children with autism. Front Psychiatry;2024;15:1413961.

INTRODUCTION: Sleep disorders are common in children with autism spectrum disorder (ASD). Transcranial magnetic stimulation (TMS) can influence the excitability of neuronal cells in stimulated areas, leading to improvements in sleep and other autistic symptoms. However, studies on clinical mechanisms of TMS in treating sleep disorders associated with ASD are limited. Therefore, we aimed to explore the effects of TMS on sleep structure and quality in children with ASD. METHODS: Between January 2020 and December 2021, recruitment was advertised through child and adolescent outpatient clinics and online platforms by the Hangzhou Seventh People’s Hospital and Lishui Second People’s Hospital. Sixty children with ASD who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were selected and randomly divided into the active TMS and sham TMS treatment groups. Thirty healthy children of the same age were recruited as controls. The active TMS group received bilateral low-frequency (0.5 Hz) TMS targeting the dorsolateral prefrontal cortex on both sides in children with ASD, whereas the sham TMS group received sham stimulation with the same stimulation time and location as the experimental group. Both groups were treated for 6 weeks, and the participants were assessed using the Sleep Disturbance Scale for Children (SDSC) before treatment, at 3 weeks, and at 6 weeks of intervention. Independent sample t-tests and difference t-tests were used for statistical analysis of the data. RESULTS: No significant differences were observed in general demographic variables, such as age and sex, between the ASD and control groups (P>0.05). Independent sample t-test analysis showed that the total SDSC score, difficulty falling asleep, sleep maintenance, awakening disorders, sleep-wake transition disorders, excessive daytime sleepiness, and nocturnal hyperhidrosis scores were significantly higher in the ASD group than in the control group (P<0.05). Before treatment, no significant differences were observed in the factor or total SDSC scores between the sham TMS group and the active TMS group (P>0.05). After 15 and 30 treatment sessions, the total SDSC score, difficulty falling asleep, sleep maintenance, sleep-wake transition disorders, and excessive daytime sleepiness scores were significantly higher in the sham TMS group than in the active TMS group (P<0.05). The difference t-test analysis showed that after 30 treatment sessions, the reduction rates of the total SDSC score, difficulty falling asleep, sleep maintenance, awakening disorders, sleep-wake transition disorders, excessive daytime sleepiness, and nocturnal hyperhidrosis dimensions were significantly higher in the active TMS group than in the sham TMS group (P<0.05). CONCLUSION: Low-frequency TMS targeting the dorsolateral prefrontal cortex in children with ASD can effectively improve their sleep status, and significant improvement can be achieved after 6 weeks (30 sessions) of treatment.

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19. Yang C, Huang YT, Yao YF, Fu JY, Long YS. Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density. J Proteomics;2024 (Jul 15);303:105202.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1(-/y) mice and 306 DEPs of P90 Fmr1(-/y) mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1(-/y) mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

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20. Yıldız N, Serdaroğlu E, Kart P, Besen S, Kanmaz S, Toprak DE, Kilic B, Ersoy O, Gencpinar P, Dundar NO, Okuyaz C, Serdaroglu A, Carman KB, Yarar C, Ekici B, Tatlı B, Erol İ, Aydın K, Tekgül H, Cansu A. Evaluation of seizure semiology, genetics, magnetic resonance imaging, and electroencephalogram findings in children with Rett syndrome: A multicenter retrospective study. Epilepsy Res;2024 (Jul 6);205:107399.

OBJECTIVES: This study aimed to evaluate seizure semiology, electroencephalogram (EEG), magnetic resonance imaging (MRI), and genetic findings, as well as treatment choices in Rett syndrome (RTT). METHODS: A retrospective analysis was conducted on one hundred and twenty cases diagnosed with RTT with a genetic mutation. Data were obtained from nine participating centers. RESULTS: In this study, 93.3 % of patients were female, with typical RTT found in 70 % of cases. Genetic etiology revealed MECP2, FoxG1, and CDKL5 in 93.8 %, 2.7 %, and 1.8 % of cases, respectively. Atypical RTT clinics were observed in 50 % of male cases, with the first EEG being normal in atypical RTT cases (p = 0.01). Generalized tonic-clonic and myoclonic epilepsy were the most common seizure semiologies, while absence and focal epilepsy were less prevalent. Valproate, levetiracetam, lamotrigine, and clobazam were the most commonly used antiepileptic drugs, affecting the severity and frequency of seizures (p = 0.015, p=<0.001, p = 0.022, and p=<0.001, respectively). No significant differences were observed in EEG findings. The initiation of anti-seizure medications significantly altered seizure characteristics (Table 4). A ketogenic diet and vagal nerve stimulation (VNS) correlated with a 50 % improvement in cognitive function, while steroid treatment showed a 60 % improvement. Remarkably, seizures were substantially reduced after VNS application. CONCLUSION: This study underscores the importance of genetic diagnosis in RTT cases with a clinical diagnosis. These preliminary results will be further validated with the inclusion of clinically diagnosed RTT cases in our ongoing study.

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21. Yu WH, Chu CH, Chen LW, Lin YC, Koh CL, Huang CC. The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe. J Neurodev Disord;2024 (Jul 15);16(1):38.

BACKGROUND: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. METHODS: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. RESULTS: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean - 4.9 cm(3), 95% confidence interval - 9.4 to - 0.3) at TEA and lower motor composite scores (- 8.7, - 14.2 to - 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect - 8.7, - 14.8 to - 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect - 1.8, - 4.9 to - 0.01), suggesting a mediating effect of 20%. CONCLUSIONS: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population.

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