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In neurodevelopmental research, within-diagnosis heterogeneity and across-diagnosis overlap necessitate a shift from case-control designs to data-driven clustering approaches. However, our understanding of the replicability of these clustering structures across independent datasets remains limited. Our objective was to examine the replicability of clustering structure in measures of brain morphology in neurodiverse children across two independent datasets, namely the Province of Ontario...

Internalizing problems (e.g., anxiety and depression) are associated with a wide range of adverse outcomes. While some predictors of internalizing problems are known (e.g., their frequent co-occurrence with neurodevelopmental (ND) conditions), the biological markers of internalizing problems are not well understood. Here, we used deep learning, a powerful tool for identifying complex and multi-dimensional brain-behaviour relationships, to predict cross-sectional and worsening longitudinal...

CONCLUSION: Mixed biology toddlers have lower EFS and OS compared to those whose tumors have favorable biologic features. Inclusion in high-risk NBL trials should be considered for this rare subgroup.

Sperm gigantism has evolved multiple times independently, raising the question of whether intracellular allocation strategies evolved in concert with cell size. Allocation to intracellular components might evolve from direct selection on specific subcellular constituents that affect cell size indirectly, or instead as a byproduct of selection on cell size per se. We used transmission electron microscopy of nematode spermatozoa to quantify investment in pseudopods, mitochondria, and membranous...

CONCLUSIONS: This study defined a MTD and recommended phase II dose of 200mg twice daily olaparib with concurrent low-dose TRT, and the combination appeared safe without unexpected toxicities.

CONCLUSIONS: Hypertension prevalence in China has risen, while awareness, treatment, and control rates remain relatively low. These findings underscore the urgent need for tailored policies to enhance hypertension management.

SUMOylation is essential in plant and animal cells, but it remains unknown how small ubiquitin-like modifier (SUMO) components act in concert to modify specific targets in response to environmental stresses. In this study, we characterize every SUMO component in the Arabidopsis root to create a complete SUMO Cell Atlas in eukaryotes. This unique resource reveals wide spatial variation, where SUMO proteins and proteases have subfunctionalized in both their expression and subcellular localization....

SUMMARY: EnrichmentMap: RNASeq (enrichmentmap.org) is an intuitive, web-based app for gene-set enrichment analysis and visualization, specifically supporting two-case RNA-Seq experiments for Homo sapiens. The web app introduces a simplified user interface, faster processing times, and eliminates the need for software installation compared to running similar workflows in the Cytoscape desktop software, catering to biologists with minimal computational experience. EnrichmentMap: RNASeq is a new...

CONCLUSIONS: While the institution of a publicly funded genetic testing program was associated with rising utilization, increasing age at testing and decreasing testing of unaffected women suggest limitations in identifying high-risk individuals eligible for risk-reduction.

CONCLUSIONS: These findings suggest that in utero HIV and ART exposure have broad neuroanatomic developmental impacts, particularly in boys, with significant differences in brain regions critical for motor function, expressive language, memory, and emotion. These structural differences align with previously reported motor and language deficits and highlight the importance of early intervention and tailored support strategies for CHEU.

Li-Fraumeni syndrome (LFS) confers high lifetime cancer risk due to germline TP53 pathogenic variants (PV). A comprehensive surveillance regimen termed the 'Toronto Protocol', has been adopted for early tumor detection, demonstrating improved survival among TP53 PV carriers. However, the protocol's "one-size-fits-all" approach fails to consider individual cancer risk. To personalize screening, we developed a support vector machine model to predict early onset of primary tumors (age < 6) using...

CONCLUSIONS: Our results uncover a functional role of CLDN1 in the pathogenesis of PSC and biliary fibrosis. Completed in vivo proof-of-concept studies combined with expression analyses in PSC patients pave the way for the clinical development of CLDN1-specific mAbs to treat PSC.

The unfolded protein response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to endoplasmic reticulum (ER) stressors. Although the UPR is not thought to be necessary for cellular fitness of wild-type cells in the absence of stress, we found that UPR deficiency led to poor growth in cycling mitotic yeast cells. This led to pervasive adaptive aneuploidy of specific chromosomes that was seen in divergent strain backgrounds, indicating an important basal role for...

Mowat‒Wilson syndrome (MWS), a rare genetic disorder caused by heterozygous loss-of-function mutations in ZEB2, is characterised by significant growth retardation with unclear mechanisms. In this study, we developed a Zeb2 haploinsufficient (Zeb2^(+/-)) mouse model that recapitulates key features of MWS, including reduced body weight, impaired intestinal development and skeletal hypoplasia. RNA sequencing revealed significant downregulation of nutrient digestion and absorption pathways in the...

In genome-wide association studies (GWAS), it is often desirable to test for interactions, such as gene-environment (G x E) or gene-gene (G x G) interactions, between single-nucleotide polymorphisms (SNPs, G's) and environmental variables (E's). However, directly accounting for interaction is often infeasible, because the interacting variable is latent or the computational burden is too large. For quantitative traits (Y) that are approximately normally distributed, it has been shown that...

ImportanceOral cavity squamous cell carcinoma (OCSCC) is rare in patients ≤40 years, and their risk factors, presentation, and outcomes may differ from older patients.ObjectiveTo assess the epidemiology, risk factors, and oncologic outcomes of young patients (≤40 years) with OCSCC compared to those >40 years.DesignA multi-institutional retrospective cohort study.SettingNine Canadian institutions from 2005 to 2019.ParticipantsIn total, 4506 adults with OCSCC, of whom 205 (4.55%) were young and...

CONCLUSIONS: These findings provide valuable insights into the mental health burdens facing families living with 22q11DS. Interventions focusing on 22q11DS should integrate techniques to foster social and other supports to improve the mental health of caregivers and children.

The contamination of soil and groundwater by amino-, nitro-, and chloroaromatics, which are compounds extensively used in chemical manufacturing, including pesticide production, poses significant risks due to their toxicity and mutagenicity. This study presents a proof-of-concept blended bacterial culture, developed by combining individual contaminant-degrading enrichments. The culture was tested for bioremediation of three contaminated environmental matrices from a former agrochemical site in...

CONCLUSIONS: In this phase II, prematurely stopped randomized placebo-controlled trial of peginterferon lambda for individuals hospitalized with COVID-19 infection, no apparent benefit was identified.

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