1. Bastan E, Beck SR, Surtees AD. Autistic people differ from non-autistic people subjectively, but not objectively in their reasoning. Autism. 2024: 13623613241277055.

Autistic people often experience challenges in social contexts, and when decisions need to be made quickly. There is evidence showing that autistic people have a tendency for greater deliberation and lower intuition, compared to non-autistic people. This has led to the researchers’ proposal that autism is associated with an enhanced level of rationality. However, these theories have been mostly explored through the lens of either only non-social domain or only social domain. To address this gap, we recruited autistic adults and carefully matched them with non-autistic adults for comparison. We used a task representing both social and non-social interactions in a comparison structure and asked participants’ moral judgements on scenarios’ main characters. This was complemented by subjective and objective measures of reasoning. Our findings did not reveal meaningful differences between groups in terms of deliberation. However, we did observe that autistic participants self-reported lower levels of intuition, compared to non-autistic participants. Autistic people consistently rate themselves as less intuitive than their counterparts. Nevertheless, objective evidence supporting this across tasks and studies is inconsistent.

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2. Bleimeister IH, Avni I, Granovetter MC, Meiri G, Ilan M, Michaelovski A, Menashe I, Behrmann M, Dinstein I. Idiosyncratic pupil regulation in autistic children. Autism Res. 2024.

Recent neuroimaging and eye-tracking studies have suggested that children with autism exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here, we extended this research to pupillometry recordings. We successfully acquired pupillometry recordings from 111 children (74 with autism), 4.5-years-old on average, who viewed three 90 s movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group as well as between each autistic child and all children in the TD group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group or the comparison group. Children with autism exhibited significantly weaker inter-subject correlations than TD children in all comparisons. These differences were independent of previously reported differences in gaze inter-subject correlations and were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. The results demonstrate the utility of measuring the idiosyncrasy of pupil regulation, which can be performed with passive viewing of movies even by young children with co-occurring intellectual disability. These findings reveal that a considerable number of children with autism have significantly less stable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

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3. Borie AM, Dromard Y, Chakraborty P, Fontanaud P, Andre EM, François A, Colson P, Muscatelli F, Guillon G, Desarménien MG, Jeanneteau F. Neuropeptide therapeutics to repress lateral septum neurons that disable sociability in an autism mouse model. Cell Rep Med. 2024: 101781.

Confronting oxytocin and vasopressin deficits in autism spectrum disorders and rare syndromes brought promises and disappointments for the treatment of social disabilities. We searched downstream of oxytocin and vasopressin for targets alleviating social deficits in a mouse model of Prader-Willi syndrome and Schaaf-Yang syndrome, both associated with high prevalence of autism. We found a population of neurons in the lateral septum-activated on termination of social contacts-which oxytocin and vasopressin inhibit as per degree of peer affiliation. These are somatostatin neurons expressing oxytocin receptors coupled to GABA-B signaling, which are inhibited via GABA-A channels by vasopressin-excited GABA neurons. Loss of oxytocin or vasopressin signaling recapitulated the disease phenotype. By contrast, deactivation of somatostatin neurons or receptor signaling alleviated social deficits of disease models by increasing the duration of contacts with mates and strangers. These findings provide new insights into the treatment framework of social disabilities in neuropsychiatric disorders.

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4. Chettle J, Louie RJ, Larner O, Best R, Chen K, Morris J, Dedeic Z, Childers A, Rogers RC, DuPont BR, Skinner C, Küry S, Uguen K, Planes M, Monteil D, Li M, Eliyahu A, Greenbaum L, Mor N, Besnard T, Isidor B, Cogné B, Blesson A, Comi A, Wentzensen IM, Vuocolo B, Lalani SR, Sierra R, Berry L, Carter K, Sanders SJ, Blagden SP. LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder. HGG Adv. 2024; 5(4): 100345.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.

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5. Davis AM, Telfer NA, Artis J, Abubakare O, Keller-Bell YD, Caruthers C, Jones DR, Pierce NP. Resilience and strengths in the Black autism community in the United States: A scoping review. Autism Res. 2024.

Gaps in research knowledge pertaining to resiliency factors and strengths among the Black autism community, inclusive of autistic persons and their support system exist. A scoping review was conducted to further explore quantitative, qualitative, and mixed methods studies that investigate resiliency factors and related strengths in the Black autism community in the United States. A total of 436 articles were identified, with 28 studies included in the final review. Results demonstrated that (1) strengths of Black autistic persons across the life course have been disregarded in research; (2) Black caregiver advocacy, while common, is also a developmental process that can be supported by community-based interventions; (3) informal supports including family and friends play an instrumental role in supporting the well-under investigated being of Black parents of autistic children; and (4) spirituality is often endorsed by Black caregivers of autistic children, such as playing a role in acceptance of the autism diagnosis and with coping with difficult life situations. Research and practice implications are discussed.

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6. Giofrè D, Lievore R, Allen K, Tonizzi I, Mammarella IC, Toffalini E. Understanding sex/gender differences in intelligence profiles of children with Autism: A comprehensive WISC meta-analysis. Res Dev Disabil. 2024; 154: 104854.

BACKGROUND: Intelligence assessment in children with autism spectrum disorders (ASD) often sparks debates about sex/gender differences. Specifically, the question arises whether girls exhibit lower performance on intelligence scales compared to boys. This meta-analysis examines nine studies (N=1105; 809 boys and 296 girls) to quantify sex/gender differences on the Wechsler Intelligence Scale for Children (WISC) in children with ASD, comparing their results to typically developing children. METHOD AND PROCEDURES: Random-effects meta-analyses on WISC indices and subtests were conducted to address the heterogeneity across effect sizes. Results for children with ASD were compared to those of typically developing children. OUTCOMES AND RESULTS: Findings revealed no significant differences in general intellectual functioning (full-scale IQ), verbal comprehension, working memory, or processing speed between boys and girls in children with ASD. Boys showed an advantage only in the perceptual reasoning index. At the subtest level, boys outperformed on certain tasks, while girls excelled in others. CONCLUSIONS AND IMPLICATIONS: The observed pattern of differences in the ASD population aligns quantitatively with those in typically developing populations. Differences, if present, are specific to certain indices rather than general intelligence. These insights contribute to a nuanced understanding of gender-related cognitive variations in the context of ASD.

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7. Huang Y, Chen W, Gan Y, Liu X, Tian Y, Zhang J, Li F. Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits: Evidence from the Shanghai birth cohort. J Hazard Mater. 2024; 480: 135857.

The epidemiological evidence regarding prenatal PFAS exposure and its interaction with genetic factors on the autistic traits risk is unclear. This study included 1610 mother-child pairs from the Shanghai Birth Cohort (SBC). Ten PFAS were quantified in blood serum collected in the first trimester. Child autistic traits were evaluated at age 4 using a Chinese version of the social responsiveness scale-short form (SRS-SF). We calculated the polygenic risk score (PRS) to evaluate the cumulative genetic effects of autism. Additive interaction models were established to explore whether genetic susceptibility modified the effects of prenatal PFAS exposure. After adjusting for confounders, we found prenatal PFOA exposure was associated with an increased risk of autistic traits in children (OR, 3.05; 95 % CI, 1.14-7.58), and the increased risk associated with PFOA was mitigated among women who reported pre-pregnancy folic acid supplementation. Additionally, an increased risk of autistic traits was observed in children with higher levels of prenatal PFHxS exposure and a high PRS (p for interaction = 0.021). Our findings suggest prenatal PFAS exposure may increase the risk of autistic traits in children, especially in those with a high genetic risk. Further research is warranted to confirm this association and explore the underlying mechanisms.

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8. Jia Z, Zhang H, Lv Y, Yu L, Cui Y, Zhang L, Yang C, Liu H, Zheng T, Xia W, Xu S, Li Y. Intrauterine chromium exposure and cognitive developmental delay: The modifying effect of genetic predisposition. Sci Total Environ. 2024; 946: 174350.

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children’s cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child’s cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one’s adverse genetic background jointly contribute to an increased risk of CDD in children.

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9. Kumar M, Mehan S, Kumar A, Sharma T, Khan Z, Tiwari A, Das Gupta G, Narula AS. Therapeutic efficacy of Genistein in activation of neuronal AC/cAMP/CREB/PKA and mitochondrial ETC-Complex pathways in experimental model of autism: Evidence from CSF, blood plasma and brain analysis. Brain Res. 2024: 149251.

Autism is a complex neurodevelopmental condition characterized by repetitive behaviors, impaired social communication, and various associated conditions such as depression and anxiety. Its multifactorial etiology includes genetic, environmental, dietary, and gastrointestinal contributions. Pathologically, Autism is linked to mitochondrial dysfunction, oxidative stress, neuroinflammation, and neurotransmitter imbalances involving GABA, glutamate, dopamine, and oxytocin. Propionic acid (PRPA) is a short-chain fatty acid produced by gut bacteria, influencing central nervous system functions. Elevated PRPA levels can exacerbate Autism-related symptoms by disrupting metabolic processes and crossing the blood-brain barrier. Our research investigates the neuroprotective potential of Genistein (GNT), an isoflavone compound with known benefits in neuropsychiatric and neurodegenerative disorders, through modulation of the AC/cAMP/CREB/PKA signaling pathway and mitochondrial ETC complex (I-IV) function. In silico analyses revealed GNT’s high affinity for these targets. Subsequent in vitro and in vivo experiments using a PRPA-induced rat model of autism demonstrated that GNT (40 and 80 mg/kg., orally) significantly improves locomotion, neuromuscular coordination, and cognitive functions in PRPA-treated rodents. Behavioral assessments showed reduced immobility in the forced swim test, enhanced Morris water maze performance, and restored regular locomotor activity. On a molecular level, GNT restored levels of key signaling molecules (AC, cAMP, CREB, PKA) and mitochondrial complexes (I-V), disrupted by PRPA exposure. Additionally, GNT reduced neuroinflammation and apoptosis, normalized neurotransmitter levels, and improved the complete blood count profile. Histopathological analyses confirmed that GNT ameliorated PRPA-induced brain injuries, restored normal brain morphology, reduced demyelination, and promoted neurogenesis. The study supports GNT’s potential in autism treatment by modulating neural pathways, reducing inflammation, and restoring neurotransmitter balance.

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10. Langhorne S, Uglik-Marucha N, Broadhurst C, Lieven E, Pearson A, Vitoratou S, Leadbitter K. Correction: The Knowledge of Autism Questionnaire-UK: Development and Initial Psychometric Evaluation. J Autism Dev Disord. 2024.

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11. Liu X, Cherepanov S, Abouzari M, Zuko A, Yang S, Sayadi J, Jia X, Terao C, Sasaki T, Yokoyama S. R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder. Peptides. 2024; 182: 171301.

This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (OXTR) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca(2+) mobilization in vitro. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in OXTR on functional activity and highlight the necessity for population-specific genetic study and in vitro analysis to elucidate genetic susceptibilities to neuropsychiatric conditions.

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12. Nayak NN, Shakya S, Gudi N, Khurana S, Gopalakrishnan S, Rao V, Rao BK. Clothing design solutions for children with developmental disabilities: A scoping review protocol. MethodsX. 2024; 13: 102974.

Children with Developmental Disabilities (DD) often face significant challenges in performing dressing task, fundamental activities of daily living. Inability to accomplish this task independently significantly impacts participation in social and recreational activities, affecting Quality of Life (QoL). Additionally, burden on caregivers increases which in turn leads to stress and burnout. Addressing dressing-related challenges through innovative clothing designs enhances self-independence, alleviate caregiver burden, and improve QoL. However, studies published in this focused area are quite heterogeneous resulting in lack of comprehensive understanding of different clothing solutions that exist for children with DD. Therefore, this scoping review is undertaken to map clothing design solutions available for children with DD between 0 and 18 years. Arksey and O’Malley’s framework will be followed, database-specific search strategy and grey literature searches will be conducted to retrieve articles published in English from January 2000 to May 2024. All selected articles will be screened independently by two reviewers, and data will be extracted. The purpose of this scoping review is to map clothing design solutions available for children with DD from scientific literature. Adaptive clothing being an emerging area, evidence from this study may encourage designers to bring innovation in clothing industry for a wider range of disabilities.

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13. Ponce Rodriguez L, Fuentes Rueda CM, Rojo Franconetti M, Esteban L, Ibáñez-Alfonso JA. Influence of temperament on early neurodevelopmental disorders: a systematic review protocol. BMJ Open. 2024; 14(10): e083266.

INTRODUCTION: Several studies have highlighted the role of temperament as a relevant construct to understand the wide variability observed in neurodevelopmental disorders (NDDs) such as autism spectrum disorder and attention deficit hyperactivity disorder. Some studies have pointed to temperamental traits such as strained control as possible precursors to the development of these disorders. In addition, how temperament influences high-risk populations, as well as intervention programmes aimed at families, has been investigated. METHODS AND ANALYSIS: This paper presents the protocol that will be followed to carry out a systematic review, the objective of which is to know how child temperament is related to the different domains of development in children with NDD or the risk of suffering from it. The search strategy will be implemented in Web of Science (WoS Core Collection), PubMed, ERIC, PsycINFO and Cochrane databases. The risk of bias will be measured by the Newcastle-Ottawa Scale to carry out the integration of the results obtained to synthesis without meta-analysis will be used. This systematic review aims to improve scientific evidence for institutions and professionals and enhance the effectiveness of early care programmes for children with NDD and their families. ETHICS AND DISSEMINATION: No express approval has been sought from any ethics committee because there is no primary data involved and no access to confidential patient information. PROSPERO REGISTRATION NUMBER: CRD42023445173.

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14. Prillinger K, Amador de Lara G, Klöbl M, Lanzenberger R, Plener PL, Poustka L, Konicar L, Radev ST. Multisession tDCS combined with intrastimulation training improves emotion recognition in adolescents with autism spectrum disorder. Neurotherapeutics. 2024: e00460.

Previous studies indicate that transcranial direct current stimulation (tDCS) is a promising emerging treatment option for autism spectrum disorder (ASD) and its efficacy could be augmented using concurrent training. However, no intrastimulation social cognition training for ASD has been developed so far. The objective of this two-armed, double-blind, randomized, sham-controlled clinical trial is to investigate the effects of tDCS combined with a newly developed intrastimulation social cognition training on adolescents with ASD. Twenty-two male adolescents with ASD were randomly assigned to receive 10 sessions of either anodal or sham tDCS at F3/right supraorbital region together with online intrastimulation training comprising basic and complex emotion recognition tasks. Using baseline magnetic resonance imaging data, individual electric field distributions were simulated, and brain activation patterns of the training tasks were analyzed. Additionally, questionnaires were administered at baseline and following the intervention. Compared to sham tDCS, anodal tDCS significantly improved dynamic emotion recognition over the course of the sessions. This task also showed the highest activations in face processing regions. Moreover, the improvement was associated with electric field density at the medial prefrontal cortex and social awareness in exploratory analyses. Both groups showed high tolerability and acceptability of tDCS, and significant improvement in overall ASD symptoms. Taken together, multisession tDCS improved dynamic emotion recognition in adolescents with ASD using a task that activates brain regions associated with the social brain network. The variability in the electric field might diminish tDCS effects and future studies should investigate individualized approaches.

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15. Rizvi A, Husain K, Ashraf S, Trivedi C, Jain SB, Safwi SR. Trend in Emergency Department Visits Among Children and Youth With Autism Spectrum Disorder: A Cross-Sectional Analysis of the National Hospital Ambulatory Medical Care Survey, 2016-2021. Prim Care Companion CNS Disord. 2024; 26(5).

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16. Schultz LM, Knighton A, Huguet G, Saci Z, Jean-Louis M, Mollon J, Knowles EEM, Glahn DC, Jacquemont S, Almasy L. Copy-number variants differ in frequency across genetic ancestry groups. HGG Adv. 2024; 5(4): 100340.

Copy-number variants (CNVs) have been implicated in a variety of neuropsychiatric and cognitive phenotypes. We found that deleterious CNVs are less prevalent in non-European ancestry groups than they are in European ancestry groups of both the UK Biobank (UKBB) and a US replication cohort (SPARK). We also identified specific recurrent CNVs that consistently differ in frequency across ancestry groups in both the UKBB and SPARK. These ancestry-related differences in CNV prevalence present in both an unselected community population and a family cohort enriched with individuals diagnosed with autism spectrum disorder (ASD) strongly suggest that genetic ancestry should be considered when probing associations between CNVs and health outcomes.

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17. Sharifi O, Haghani V, Neier KE, Fraga KJ, Korf I, Hakam SM, Quon G, Johansen N, Yasui DH, LaSalle JM. Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression. Commun Biol. 2024; 7(1): 1292.

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment.

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18. Wang X, Lalli M, Thopte U, Buxbaum JD. A scalable, high-throughput neural development platform identifies shared impact of ASD genes on cell fate and differentiation. bioRxiv. 2024.

BACKGROUND: Deleterious mutations in hundreds of genes confer high risk for neurodevelopmental disorders (NDDs), posing significant challenges for therapeutic development. Identifying convergent pathways shared across NDD genes could reveal high-impact therapeutic targets. METHODS: To identity convergent pathways in NDD genes, we optimized Perturb-seq, a method combining CRISPR perturbation with single-cell RNA sequencing (scRNA-seq), and applied structural topic modeling (STM) to simultaneously assess impact on cell fate and developmental stage. We then studied a subset of autism spectrum disorder (ASD) genes implicated in regulation of gene expression using these improved molecular and analytical approaches. RESULTS: Results from targeting 60 high-confidence ASD risk genes revealed significant effects on neural development. As expected, ASD risk genes impacted both progenitor fate and/or neuronal differentiation. Using STM, we could identify latent topics jointly capturing cell types, cell fate, and differentiation stages. Repression of ASD risk genes led to changes in topic proportions and effects of four genes ( DEAF1 , KMT2A , MED13L , and MYT1L) were validated in an independent dataset. CONCLUSIONS: Our optimized Perturb-seq method, combined with a novel analytical approach, provides a powerful, cost-effective framework for uncovering convergent mechanisms among genes involved in complex neurodevelopmental processes. Application of these methods advanced understanding of the impact of ASD mutations on multiple dimensions of neural development, and provides a framework for a broader examination of the function of NDD risk genes.

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