Quantitative Relaxometry Assessment of Brain Microstructural Abnormality of Preschool Children With Autism Spectrum Disorder With Synthetic Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to perform an assessment of brain microstructure in children with autism aged 2 to 5 years using relaxation times acquired by synthetic magnetic resonance imaging. MATERIALS AND METHODS: Thirty-four children with autism spectrum disorder (ASD) (ASD group) and 17 children with global developmental delay (GDD) (GDD group) were enrolled, and synthetic magnetic resonance imaging was performed to obtain T1 and T2 relaxation times. The differences in brain relaxation times between the 2 groups of children were compared, and the correlation between significantly changed T1/T2 and clinical neuropsychological scores in the ASD group was analyzed. RESULTS: Compared with the GDD group, shortened T1 relaxation times in the ASD group were distributed in the genu of corpus callosum (GCC) ( P = 0.003), splenium of corpus callosum ( P = 0.002), and right thalamus (TH) ( P = 0.014), whereas shortened T2 relaxation times in the ASD group were distributed in GCC ( P = 0.011), left parietal white matter ( P = 0.035), and bilateral TH (right, P = 0.014; left, P = 0.016). In the ASD group, the T2 of the left parietal white matter is positively correlated with gross motor (developmental quotient [DQ] 2) and personal-social behavior (DQ5), respectively ( r = 0.377, P = 0.028; r = 0.392, P = 0.022); the T2 of the GCC was positively correlated with DQ5 ( r = 0.404, P = 0.018); and the T2 of the left TH is positively correlated with DQ2 and DQ5, respectively ( r = 0.433, P = 0.009; r = 0.377, P = 0.028). All significantly changed relaxation values were not significantly correlated with Childhood Autism Rating Scale scores. CONCLUSIONS: The shortened relaxometry times in the brain of children with ASD may be associated with the increased myelin content and decreased water content in the brain of children with ASD in comparison with GDD, contributing the understanding of the pathophysiology of ASD. Therefore, the T1 and T2 relaxometry may be used as promising imaging markers for ASD diagnosis.

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins.

Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism in S. paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression in S. paraplesia flowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.

When the Loss Costs Too Much: A Systematic Review and Meta-Analysis of Sarcopenia in Head and Neck Cancer.

Purpose: Whether or not skeletal muscle mass (SMM) depletion, known as sarcopenia, has significant negative effects on the prognosis of patients with head and neck cancer (HNC) is both new and controversial. In this meta-analysis, we aimed to determine the prognostic significance of sarcopenia in HNC. Methods: We searched PubMed, the Cochrane Library, Embase, and Web of Science, which contain trial registries and meeting proceedings, to identify related published or unpublished studies. We used the Newcastle-Ottawa Scale (NOS) to appraise the risk of bias of the included retrospective studies. Pooled hazard ratios (HR) and the I 2 statistic were estimated for the impact of sarcopenia on overall survival (OS) and relapse-free survival (RFS). Results: We analyzed data from 11 studies involving 2,483 patients (39.4% on average of whom had sarcopenia). Based on the univariate analysis data, the sarcopenia group had significantly poorer OS compared to the non-sarcopenia group [HR = 1.97, 95% confidence interval (CI): 1.71-2.26, I 2 = 0%]. In the cutoff value subgroup, group 1, defined as skeletal muscle index (SMI) of 38.5 cm2/m2 for women and 52.4 cm2/m2 for men (HR = 2.41, 95% CI: 1.72-3.38, I 2 = 0%), had much poorer OS. In the race subgroup, the results were consistent between the Asia (HR = 2.11, 95% CI: 1.59-2.81) and non-Asia group (HR = 1.92, 95% CI: 1.64-2.25). The sarcopenia group also had significantly poorer RFS (HR = 1.74, 95% CI: 1.43-2.12, I 2 = 0%). Conclusions: Presence of pre-treatment sarcopenia has a significant negative impact on OS and RFS in HNC compared with its absence. Further well-conducted studies with detailed stratification are needed to complement our findings.

InstantScope: a low-cost whole slide imaging system with instant focal plane detection.

We report the development of a high-throughput whole slide imaging (WSI) system by adapting a cost-effective optomechanical add-on kit to existing microscopes. Inspired by the phase detection concept in professional photography, we attached two pinhole-modulated cameras at the eyepiece ports for instant focal plane detection. By adjusting the positions of the pinholes, we can effectively change the view angle for the sample, and as such, we can use the translation shift of the two pinhole-modulated images to identify the optimal focal position. By using a small pinhole size, the focal-plane-detection range is on the order of millimeter, orders of magnitude longer than the objective's depth of field. We also show that, by analyzing the phase correlation of the pinhole-modulated images, we can determine whether the sample contains one thin section, folded sections, or multiple layers separated by certain distances - an important piece of information prior to a detailed z scan. In order to achieve system automation, we deployed a low-cost programmable robotic arm to perform sample loading and $14 stepper motors to drive the microscope stage to perform x-y scanning. Using a 20X objective lens, we can acquire a 2 gigapixel image with 14 mm by 8 mm field of view in 90 seconds. The reported platform may find applications in biomedical research, telemedicine, and digital pathology. It may also provide new insights for the development of high-content screening instruments.

A comparative study of less invasive stabilization system and titanium elastic nailing for subtrochanteric femur fractures in older children.

The objective of this study was to compare prospectively the complications and the radiographic and clinical outcomes of reverse less invasive stabilization system (LISS) and titanium elastic nailing (TEN) for the treatment of subtrochanteric femur fractures in older children. From April 2004 to February 2012, 52 children aged from 10 to 15 years old with subtrochanteric fractures were included in this study. 26 patients were treated with reverse LISS (LISS group) and 26 children treated with titanium elastic nails (TEN group) respectively. Perioperative care was standardized. Surgical time, blood loss, length of hospitalization, hospital costs, fracture union time, full weight-bearing time and complications were analyzed. The radiologic results as well as hip functional outcomes were evaluated. The average follow-up time of LISS group was 36.5±9.3 months and TEN group was 40.2±10.6 months. No significant difference between these two groups was found in union time, full weight-bearing time and average length of hospitalization. However, the patients of LISS group had longer operation time (60.0±10.6 min vs. 40.5±7.4 min, p<0.01), more blood loss (130.0±45.0 ml vs. 15.5±10.2 ml, p<0.01), and more hospital costs (25000±700 RMB vs. 10800±500 RMB, p<0.01). The overall complication rate was significantly higher in the LISS group than in the TEN group (12/26 vs. 5/26, p=0.039). There was no significant difference between the two groups in terms of early and late radiological results. Using the Sanders score system, there were 13 excellent, 6 good and 7 fair results in the LISS group compared with 22 excellent and 4 good results in the TEN group. The excellent and good rate was significantly different between the two groups (p=0.010). Our results indicated that TEN fixation of subtrochanteric femur fractures in older children was associated with better function scores and a lower overall complication rate when compared with reverse LISS.