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We study, in this paper, a model for the core of the system of the Glycerophospholipid metabolism in the murine cells. It comprises the simple and enzymatic reactions of PhosphatidylEthanolamine and the PhosphatidylCholine . The model’s general structure is taken from a number of books and articles. We translate this model into a set of ordinary differential equations (ODEs), to propose a quantitative explanation of the experimental experiences and the observed results. In order to make it usable as a basis for simulations and mathematical analysis we need to make precise the various constants present in the equations but which are usually not directly accessible in the literature. In a first step we considered experimental data of rat’s liver cells obtained by NMR spectroscopy: given the values of metabolite concentrations we find appropriate parameter values which allow us to describe the system with ODEs. We have then performed several analyses using the developed model such as stability analysis. A first interesting result is the global stability of the system which was observed by simulation and then proved by mathematical arguments. A second important result is that we observe on the diagrams that the steady state for normal cells is precisely a singular point of order two, whereas tumoral cells present different characteristics; this fact has been proved for PhosphatidylEthanolamine N-Methyl transferase (PEMT), an enzyme which seems to be identified for the first time as a crucial element in the tumoral process. In a second step we applied our model to experimental data of proton HRMAS NMR spectroscopy for solid B16 melanoma and Lewis lung (3LL) 3LL carcinoma cells treated by Chloroethyl Nitrosourea (CENU). We performed a complete comparative analysis of parameters in order to learn the predictive statements to explain increases and decreases which one can observe in concentrations.

Intranasal administration of oxytocin is emerging as a potential pharmacological option for mitigating social difficulties and regulating stress in autism spectrum disorder. However, initial single-dose and multiple-dose trials showed mixed results, with some demonstrating improvements in social and repetitive behavior and others showing no benefit over placebo. This perspective aims to elucidate factors contributing to this variability and to highlight pitfalls and opportunities in the field. We identified two major factors: design-related elements and individual participant characteristics. Pertaining to design-related elements, optimal dosing regimens have yet to be established, but appear to favor moderate intervention durations (i.e., 4–6 weeks) with intermittent and intermediate dosing (i.e., 24–32 IU every other day). Also, the context of the intervention seems crucial, as enhanced outcomes are mainly observed when oxytocin administration is paired with a socially stimulating and supporting environment. In addition, more adequate outcome measures have to be established to effectively assess oxytocin's impact, including behavioral scales and objective biophysiological markers tapping into stress and neurophysiological regulation. Future research should also account for individual participant differences in biological sex, developmental stage and cognitive and adaptive functioning, and incorporate (epi)genetic screening to identify responders. Overall, refining study designs and personalizing intervention protocols are essential for optimizing oxytocin's prosocial and anxiolytic effect in autism. [ABSTRACT FROM AUTHOR]

Purpose: There is a need for valid and reliable clinical assessment tools to assess cardiorespiratory fitness (CRF) levels in adolescents with autism. Therefore, this study aimed to examine the concurrent validity and test-retest reliability of the Astrand-Rhyming Test (ART) in this population. Materials and methods: 45 adolescents with autism aged 12–18 years (n = 32 males, 14.47 ± 1.79 years) performed the ART twice (test-retest reliability) and completed a maximal cardiopulmonary exercise test (CPET) (concurrent validity). Reliability parameters included Pearson correlations, intraclass correlation coefficients (ICCs), standard error of measurements (SEM), minimal detectable changes (MDC), coefficients of variation, paired sample t-tests, linear regressions and Bland-Altman plots. The concurrent validity was evaluated with Pearson correlations, ICCs, paired sample t-tests, linear regressions and Bland-Altman plots. Results: Strong test-retest reliability (r = 0.84–0.85, ICC = 0.84–0.85) was found for the ART, but the wide limits of agreement intervals suggest the presence of substantial variability. The large SEM (4.73–5.08 mL/kg/min) and MDC (13.20-14.07 mL/kg/min) values suggest lower absolute reliability. Moderate to strong levels of association (r = 0.74–0.75) and agreement (ICC = 0.59–0.66) were found between estimated (ART1) and measured (CPET) VO2 max levels, but significant systematic differences (5.71–8.82 mL/kg/min) were observed. Conclusion: The ART is an accessible and promising method to monitor submaximal CRF levels over time but is less appropriate to estimate maximal CRF levels in this population. IMPLICATIONS FOR REHABILITATION: Adolescents with autism are at increased risk of exhibiting low cardiorespiratory fitness (CRF) levels and as a result, placing them at risk for poor physical and mental health outcomes. In clinical practice, the CRF levels of this population should be screened and monitored routinely to identify those at risk and most likely to benefit from a targeted intervention. A submaximal exercise test appears to be feasible in adolescents with autism. The Astrand-Rhyming Test shows good reliability to monitor submaximal CRF levels over time, but is less appropriate to estimate maximal CRF levels in adolescents with autism. The use of the age correction factor of the Astrand-Rhyming Test nomogram is not required to adequately estimate CRF levels in adolescents with autism. [ABSTRACT FROM AUTHOR]

Background & aims: Due to the complexity of early diagnostic decision making, we examined the predictive value of an early diagnostic classification and early abilities on later best estimate diagnosis for 22 clinically referred children with language difficulties. Methods and procedures: Four years after initial evaluation (Time 1), the clinical files of these children were reviewed. A best-estimate (BE) diagnosis of language disorder (LD), intellectual disability (ID), or autism spectrum disorder (ASD) was established, with ASD being most common. Outcomes and results: Early clinical classifications were relatively unstable or difficult to establish at a young age. The magnitude of children's cognitive and receptive language delay was a significant predictor of a later BE diagnosis of ID and LD respectively. A BE diagnosis of ASD, by contrast, could not be predicted from children's early social communication problems nor the presence of restricted and repetitive behaviors and interests. Conclusions: Taken together, the results of this study suggest that language difficulties can be an early marker of a neurodevelopmental disorder which is often not identified at the age of first referral. Implications: Eligibility for treatment should, therefore, be based on biopsychosocial case formulation rather than DSM or ICD diagnostic classification. What this paper adds?: In this study a dimensional approach was used to characterize the abilities of young children referred with mild to profound receptive and/or expressive language difficulties. Later on, a categorical approach was adopted to establish best estimate diagnoses. Our clinical, broadly defined sample reflects the heterogeneous intake of young children referred for diagnostic assessment. Other studies on diagnostic stability often only focus on one diagnostic category (and are explicitly excluding children with specific other diagnoses), not taking into account the difficulties of early differential diagnostic decision making and stability across different categories over time. Investigations of differential diagnosis within a clinical group, instead of only differentiating children with a specific diagnosis from typically developing children, may be more informative for clinicians.

Two semi-structured parental interviews are available with algorithms developed to measure DSM-5 criteria of ASD, namely the Developmental, Dimensional and Diagnostic Interview (3di) and the Diagnostic Interview for Social and Communication Disorders (DISCO-11). The main aim of this study was to examine the agreement between classification according to both interviews, and their convergence with the clinical diagnosis. Therefore, the 3di and DISCO-11 were administered from three groups of parents of a 4-18 year old. Results showed 75% agreement between both instruments, but in the ASD group only 16% of the children scored above threshold on both instruments. Exploratory analyses suggested that the 3di failed to detect rigid and repetitive behaviors, whereas the DISCO-11 was insufficiently sensitive in detecting socio-communicative problems.

We objectively quantified the neural sensitivity of school-aged boys with and without autism spectrum disorder (ASD) to detect briefly presented fearful expressions by combining fast periodic visual stimulation with frequency-tagging electroencephalography. Images of neutral faces were presented at 6 Hz, periodically interleaved with fearful expressions at 1.2 Hz oddball rate. While both groups equally display the face inversion effect and mainly rely on information from the mouth to detect fearful expressions, boys with ASD generally show reduced neural responses to rapid changes in expression. At an individual level, fear discrimination responses predict clinical status with an 83% accuracy. This implicit and straightforward approach identifies subtle deficits that remain concealed in behavioral tasks, thereby opening new perspectives for clinical diagnosis.

Background/Objectives: Prematurely born individuals are at risk for developing socio-emotional difficulties and psychopathologies such as autism spectrum disorder. Particular difficulties processing social information conveyed by the face may underlie these vulnerabilities. Methods: This comprehensive review provides an overview of 27 studies published between 2000 and mid-2022 concerning face processing in individuals born preterm and/or born with low birth weight across different age ranges, paradigms, and outcome measures. The results were interpreted across different developmental stages. Results: Behavioural studies indicated that prematurity is associated with poorer facial identity and expression processing compared to term-born controls, especially for negative emotions. Structural alterations and delayed maturation in key neural face processing structures could explain these findings. Neuroimaging also revealed functional atypicalities, which may either be rooted in the structural alterations or may partly compensate for the delayed maturation. Conclusions: The results suggest that altered face processing may be associated with an increased risk of developing psychopathologies in individuals born prematurely. Future studies should investigate the preterm behavioural phenotype and the potential need for face processing rehabilitation programs. [ABSTRACT FROM AUTHOR]

Recognizing Mendelian causes is crucial in molecular diagnostics and counseling for patients with autism spectrum disorder (ASD). We explored facial dysmorphism and facial asymmetry in relation to genetic causes in ASD patients and studied the potential of objective facial phenotyping in discriminating between Mendelian and multifactorial ASD. In a cohort of 152 ASD patients, 3D facial images were used to calculate three metrics: a computational dysmorphism score, a computational asymmetry score, and an expert dysmorphism score. High scores for each of the three metrics were associated with Mendelian causes of ASD. The computational dysmorphism score showed a significant correlation with the average expert dysmorphism score. However, in some patients, different dysmorphism aspects were captured making the metrics potentially complementary. The computational dysmorphism and asymmetry scores both enhanced the individual expert dysmorphism scores in differentiating Mendelian from non‐Mendelian cases. Furthermore, the computational asymmetry score enhanced the average expert opinion in predicting a Mendelian cause. By design, our study does not allow to draw conclusions on the actual point‐of‐care use of 3D facial analysis. Nevertheless, 3D morphometric analysis is promising for developing clinical dysmorphology applications in diagnostics and training. [ABSTRACT FROM AUTHOR]

Background: Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross‐frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of "harmonic" cross‐frequency couplings, whereas "nonharmonic" decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings. Methods: Within this exploratory, randomized, placebo‐controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak‐frequencies in the alpha (8–14 Hz) and theta (4–8 Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting‐state electroencephalography was acquired before and after 4 weeks of oxytocin administration (12 IU twice‐daily) in children with autism spectrum disorder (8–12 years, n = 33 oxytocin; n = 34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism (n = 40). Results: Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha‐theta cross‐frequency decoupling, indicating a higher incidence of spurious "noisy" coupling in their resting brain (p =.001). Dimensionally, increased neural coupling was associated with more social difficulties (p =.002) and lower activity of the parasympathetic "rest & digest" branch of the autonomic nervous system (p =.018), indexed with high‐frequency heart‐rate‐variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross‐frequency configurations was increased in the cohort of autistic children (p <.001), indicating a beneficial effect of oxytocin on reducing spurious cross‐frequency‐interactions. Furthermore, parallel epigenetics changes of the oxytocin receptor gene indicated that the neural effects were likely mediated by changes in endogenous oxytocinergic signaling (p =.006). Conclusions: Chronic oxytocin induced important homeostatic changes in the resting‐state intrinsic neural frequency architecture, reflective of reduced noisy oscillatory couplings and improved signal‐to‐noise properties. [ABSTRACT FROM AUTHOR]

Previous research suggested that adolescents with autism spectrum disorder are better than typically developing children in detecting local, non-social details within complex visual scenes. To better understand these differences, we used the image database by Sareen et al., containing the size and on-screen location information of all changes in the images, in a change blindness paradigm. In this task, an original and a modified real-world scene, separated by a gray blank, alternate repeatedly until observers detect the change. Our results indicated that participants with and without autism spectrum disorder performed similarly when scenes were presented upright, but that only the performance of the typically developing adolescents became worse in the inverted scene condition. In this condition, the correlation between performance and both image difficulty and change predictability was significantly weaker in autism spectrum disorder than in typically developing participants. We suggest that these findings result from a more locally biased search strategy in people with autism spectrum disorder, compared to typically developing participants, in tasks in which the rapid processing of global information does not help to improve change detection performance. Finally, although we found change location, change size, and age to influence participant performance, none of these was directly linked to the observed group-level differences.

Local and global visual processing abilities and processing style were investigated in individuals with autism spectrum disorder (ASD) versus typically developing individuals, children versus adolescents and boys versus girls. Individuals with ASD displayed more attention to detail in daily life, while laboratory tasks showed slightly reduced global processing abilities, intact local processing abilities, and a more locally oriented processing style. However, the presence of these group differences depended on particular task and sample (i.e., age and gender) characteristics. Most measures of local and global processing did not correlate with each other and were not associated with processing style. Significant associations between local-global processing and ASD symptom severity were observed, but the causality of these associations remains unclear.

The multiple object tracking (MOT) paradigm has proven its value in targeting a number of aspects of visual cognition. This study used MOT to investigate the effect of object-based grouping, both in children with and without autism spectrum disorder (ASD). A modified MOT task was administered to both groups, who had to track and distinguish four targets that moved randomly amongst four distracters, irrespective of the grouping condition. No group difference was revealed between children with and without ASD: both showed adequate MOT abilities and a similar amount of grouping interference. Implications of the current result are considered for previous MOT studies, the developmental trajectory of perceptual grouping, and the idea of heightened sensitivity to task characteristics in ASD.

While most typically developing (TD) participants have a coarse-to-fine processing style, people with autism spectrum disorder (ASD) seem to be less globally and more locally biased when processing visual information. The stimulus-specific spatial frequency content might be directly relevant to determine this temporal hierarchy of visual information processing in people with and without ASD. We implemented a semantic priming task in which (in)congruent coarse and/or fine spatial information preceded target categorization. Our results indicated that adolescents with ASD made more categorization errors than TD adolescents and needed more time to process the prime stimuli. Simultaneously, however, our findings argued for a processing advantage in ASD, when the prime stimulus contains detailed spatial information and presentation time permits explicit visual processing.