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It is challenge to pinpoint the functional variants among numerous genetic variants. Investigating the spatial dynamics of the human brain transcriptome for genes and exploring the expression quantitative trait loci data may provide the potential direction to identify the functional variants among autism spectrum disorders (ASD) patients. In order to explore the association of ITIH3 with ASD, the present study included three components: identifying the spatial-temporal expression of ITIH3 in the developing human brain using the expression data from the Allen Institute for Brain Science; examining the cis-acting regulatory effect of SNPs on the ITIH3 expression using UK Brain Expression Consortium database; validating the effect of identified SNPs using a case-control study with samples of 602 cases and 604 controls. The public expression data showed that ITIH3 may have a role in the development of human brain and suggested a cis-eQTL effect for rs2535629 and rs3617 on ITIH3 in the hippocampus. Genetic analysis of the above two SNPs suggested that the over-dominant model of rs2535629 was significantly associated with decreased risk of ASD. Convergent lines of evidence supported ITIH3 rs25352629 as a susceptibility variant for ASD. [ABSTRACT FROM AUTHOR]

The changing spatiotemporal patterns of the individual susceptible-infected-symptomatic-treated-recovered epidemic process and the interactions of information/material flows between regions, along with the 2002-2003 Severe Acute Respiratory Syndrome (SARS) epidemiological investigation data in mainland China, including three typical locations of individuals (working unit/home address, onset location and reporting unit), are used to define the in-out flow of the SARS epidemic spread. Moreover, the input/output transmission networks of the SARS epidemic are built according to the definition of in-out flow. The spatiotemporal distribution of the SARS in-out flow, spatial distribution and temporal change of node characteristic parameters, and the structural characteristics of the SARS transmission networks are comprehensively and systematically explored. The results show that (1) Beijing and Guangdong had the highest risk of self-spread and output cases, and prevention/control measures directed toward self-spread cases in Beijing should have focused on the later period of the SARS epidemic; (2) the SARS transmission networks in mainland China had significant clustering characteristics, with two clustering areas of output cases centered in Beijing and Guangdong; (3) Guangdong was the original source of the SARS epidemic, and while the infected cases of most other provinces occurred mainly during the early period, there was no significant spread to the surrounding provinces; in contrast, although the input/output interactions between Beijing and the other provinces countrywide began during the mid-late epidemic period, SARS in Beijing showed a significant capacity for spatial spreading; (4) Guangdong had a significant range of spatial spreading throughout the entire epidemic period, while Beijing and its surrounding provinces formed a separate, significant range of high-risk spreading during the mid-late period; especially in late period, the influence range of Beijing's neighboring provinces, such as Hebei, was even slightly larger than that of Beijing; and (5) the input network had a low-intensity spread capacity and middle-level influence range, while the output network had an extensive high-intensity spread capacity and influence range that covered almost the entire country, and this spread and influence indicated that significant clustering characteristics increased gradually. This analysis of the epidemic in-out flow and its corresponding transmission network helps reveal the potential spatiotemporal characteristics and evolvement mechanism of the SARS epidemic and provides more effective theoretical support for prevention and control measures. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) is the most common tumour in children younger than 5 years old and notable for highly heterogeneous. Our aim was to quantify the intra-tumoural metabolic heterogeneity of primary tumour lesions by using 18 F-FDG PET/CT and evaluate the prognostic value of intra-tumoural metabolic heterogeneity in NB patients., Methods: We retrospectively enrolled 38 pretreatment NB patients in our study. 18 F-FDG PET/CT images were reviewed and analyzed using 3D slicer software. The semi-quantitative metabolic parameters of primary tumour were measured, including the maximum standard uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). The areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index) was used to quantify intra-tumoural metabolic heterogeneity. The median follow-up was 21.3 months (range 3.6 - 33.4 months). The outcome endpoint was event-free survival (EFS), including progression-free survival and overall survival. Survival analysis was performed using Cox regression models and Kaplan Meier survival plots., Results: In all 38 newly diagnosed NB patients, 2 patients died, and 17 patients experienced a relapse. The AUC-CSH total (r=0.630, P<0.001) showed moderate correlation with the AUC-CSH 40% . In univariate analysis, chromosome 11q deletion (P=0.033), Children's Oncology Group (COG) risk grouping (P=0.009), bone marrow involvement (BMI, P=0.015), and AUC-CSH total (P=0.007) were associated with EFS. The AUC-CSH total (P=0.036) and BMI (P=0.045) remained significant in multivariate analysis. The Kaplan Meier survival analyses demonstrated that patients with higher intra-tumoural metabolic heterogeneity and BMI had worse outcomes (log-rank P=0.002)., Conclusion: The intra-tumoural metabolic heterogeneity of primary lesions in NB was an independent prognostic factor for EFS. The combined predictive effect of intra-tumoural metabolic heterogeneity and BMI provided prognostic survival information in NB patients., (© 2022. The Author(s).)