Early childhood is an important period of sensory, motor, cognitive and socio-emotional maturation, yet relatively little is known about the brain changes specific to this period. Voxel-based morphometry (VBM) is a technique to estimate regional brain volumes from magnetic resonance (MR) images. The default VBM processing pipeline can be customized to increase accuracy of segmentation and normalization, yet the impact of customizations on analyses in young children are not clear. Here, we assessed the impact of different preprocessing steps on T1-weighted MR images from typically developing children in two separate cohorts. Data were processed with the Computational Anatomy Toolbox (CAT12), using seven different VBM pipelines with distinct combinations of tissue probability maps (TPMs) and DARTEL templates created using the Template-O-Matic, and CerebroMatic. The first cohort comprised female children aged 3.9–7.9 years (N = 62) and the second included boys and girls aged 2.7–8 years (N = 74). We found that pipelines differed significantly in their tendency to classify voxels as grey or white matter and the conclusions about some age effects were pipeline-dependent. Our study helps to both understand age-associations in grey and white matter volume across early childhood and elucidate the impact of VBM customization on brain volumes in this age range.

Approximately 10% of births are preterm (PTB; <37 weeks gestational age; GA), which confers risk for cognitive, behavioral, and mental health challenges. Using the large and relatively diverse (i.e., designed to reflect sociodemographic variation in the US population) Adolescent Brain Cognitive DevelopmentSMStudy (ABCD Study®), we characterized the impact of PTB on brain structure in middle-late childhood (9-10 years). The ABCD sample covers the GA spectrum, and the large sample size (∼11,500) permits consideration of how associations between PTB and brain structure are impacted by GA, sex, birthweight, and analytic choices such as controlling for total brain size. We found a pattern of relative cortical thinning in temporoparietal and dorsal prefrontal regions and thickening of medial prefrontal and occipital regions in PTB compared to children born full term (≥37 weeks GA). This pattern was apparent when controlling for mean thickness and when considering moderate (>32 and <37 weeks GA) and very PTB (≤32 weeks GA) separately, relative to full term birth. Surface area and subcortical volumes showed reductions in PTB children that were largely attenuated when controlling for brain size. Effects on cortical thickness and surface area were partially mediated by birthweight. Although boys are at increased risk for adverse outcomes following PTB, there was limited evidence of sex differences of PTB effects. Finally, cortical thickness effects estimated in a ‘discovery’ sample (N=7528) predicted GA in a holdout ‘replication’ sample (N=2139). Our findings help to clarify the effects of PTB on brain structure into late childhood across the GA spectrum.SignificancePreterm birth (PTB) affects ∼10% of children and increases the risk of neurodevelopmental and mental health challenges. Here we examined long-term effects of PTB on brain structure in middle-late childhood in the large and relatively diverse ABCD sample. We further assessed the influence of gestational age, sex, birthweight, controlling for brain size and data quality. Our findings replicate a pattern of occipitotemporal and dorsal prefrontal cortical thinning in PTB that was seen in both moderate preterm and very preterm relative to full-term birth. Effects were similar in males and females and partially mediated by birthweight. Our findings suggest that community-recruited children born preterm show a pattern of structural alterations on a continuum that relates to gestational age and birthweight.

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.

Background: Tactile processing plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. An understanding of how tactile processing changes with age from early childhood to adulthood is fundamental in understanding altered tactile experiences in neurodevelopmental disorders, such as autism spectrum disorder. Methods:In this cross-sectional study, 142 children and adults aged 3-23 years completed a vibrotactile testing battery consisting of 5 tasks, which rely on different cortical and cognitive mechanisms. The battery was designed to be suitable for testing in young children to investigate how tactile processing changes from early childhood to adulthood. Results:Our results suggest a pattern of rapid, age-related changes in tactile processing toward lower discrimination thresholds (lower discrimination thresholds = greater sensitivity) across early childhood, though we acknowledge limitations with cross-sectional data. Differences in the rate of change across tasks were observed, with tactile performance reaching adult-like levels at a younger age on some tasks compared to others. Conclusions:While it is known that early childhood is a period of profound development including tactile processing, our data provides evidence for subtle differences in the developmental rate of the various underlying cortical, physical, and cognitiveThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV- OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease specific survival, and progression free interval in an in-house cohort of HPV(-) OSCC patients. Finally, due to lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behavior. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV- OSCC.

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