Aggregator

Advances in sequencing technology have enabled population-level Whole Genome Sequencing (WGS) efforts to be undertaken in many countries. Often, this requires collaboration across a distributed network of sequencing centres to allow efficient use of existing resources. Previously we tested the robustness of short-read sequencing technology and analysis pipelines across three established sequencing centres located in Montreal, Toronto, and Vancouver, constituting CGEn, Canada's national platform...

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD.

Cells undergoing division mount a unique response to DNA damage that ensures accurate chromosome segregation. The CIP2A-TOPBP1 complex has emerged as an important mitotic genome maintenance factor, but its function remains unclear. Here, we report that DDIAS is a DNA-binding effector of the CIP2A pathway in human cells. DDIAS physically interacts with TOPBP1, and its inactivation causes synthetic lethality with BRCA1 and BRCA2 deficiency. Homologous recombination (HR)-deficient tumors upregulate...

No abstract

CONCLUSIONS: This benchmark demonstrated the utility of CoW segmentation algorithms for some downstream clinical applications with explainability. The annotated datasets and top-performing algorithms are published alongside this benchmark to foster methodological advances and clinical tool development. (Funded by the Digitalization Initiative of the Zurich Higher Education Institutions and the Helmut Horten Foundation.).

INTRODUCTION: Subclinical cardiovascular remodeling may impair cerebral hemodynamics and contribute to dementia, but the perfusion features linking subclinical cardiovascular dysfunction to cerebrovascular injury remain unclear.

MYC-driven (MYC^(+)) cancers are highly aggressive and often fatal. MYC dysregulation is a key event in these cancers, yet MYC overexpression alone is often insufficient to initiate or sustain tumorigenesis. Plasmocytoma variant translocation 1 (PVT1), a long noncoding RNA (lncRNA) adjacent to MYC on chromosome 8q24, is frequently co-amplified with MYC in many of these cancers. Our prior work showed that PVT1 potentiates MYC function, although the underlying mechanism has remained unclear. Here...

Genomic rearrangements can drive cancer through mechanisms that extend beyond classical oncogenic fusions such as BCR-ABL A substantial fraction of these events involve long noncoding RNAs (lncRNAs), yet their functional impact on tumorigenesis has remained largely opaque. The lncRNA plasmacytoma variant translocation 1 (PVT1), positioned adjacent to MYC at chromosome 8q24, is among the most frequently altered loci in MYC-driven (MYC^(+)) cancers. We recently showed that PVT1 translocations...

Condensed aromatic carbon (ConAC) is widely recognized as a chemically recalcitrant component of soil organic matter. However, its stock and potential transformation into dissolved condensed aromatic carbon (dConAC) in forest soils may be altered in response to environmental changes that alter forest litter production. Using three decades of detrital input and removal treatments in a temperate forest, we investigated bulk ConAC and dConAC in soil profiles with the benzene polycarboxylic acid...

The sharing of data generated by clinical genetic and genomic testing without explicit consent is important for timely diagnosis and treatment. While many jurisdictions permit the sharing of identifiable data for direct clinical care, institutional policies vary in how clearly they specify key elements, including when sharing is permitted, what data are covered, and what safeguards apply. Greater clarity around these elements may support responsible data sharing while balancing timely care with...

Heterozygous loss-of-function variants in Neurabin I (PPP1R9A), responsible for encoding a cytoskeletal scaffolding protein essential for synaptic plasticity, are recurrently associated with neurodevelopmental and neuropsychiatric disorders, yet their direct effects on human neuronal maturation remain unclear. Here, we establish the first comprehensive human mechanistic model of PPP1R9A haploinsufficiency using an isogenic CRISPR/Cas9-engineered iPSC system differentiated into cortical neurons...

CONCLUSIONS: Children and adolescents develop recurrent AVMs at a higher rate than adult patients despite angiographic cure after initial resection. On multivariable analysis, deep venous drainage was independently associated with recurrence. Further work can help elucidate clinical and radiographic predictors of disease recurrence.

CONCLUSIONS: AMR and graft loss following kidney transplantation were defined by compartment-specific disruptions in complement and mitochondrial proteins.

CONCLUSION: The mis-localization and altered post-translational modification of p.(Ala2Val) DKC1 provides functional evidence to clinical laboratories to reclassify p.(Ala2Val) variant as "pathogenic" as per American College of Medical Genetics (ACMG) variant interpretation guidelines.

Endogenous retrotransposable elements (EREs) can modulate immune responses. We explored ERE transcription in relation to response to immune checkpoint inhibition in advanced solid tumors. ERE expression was measured in pre and on-treatment samples from patients treated in a clinical trial with pembrolizumab. We evaluated immune cell infiltration and correlated ERE expression with interferon-stimulated gene profiles and cytolytic activity. Two independent datasets were retrospectively analyzed as...

Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity, revealing how shared or lineage-specific processes influence their evolutionary trajectories. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, complex trait mappings, and evolution. Following massive collection efforts by the...

No abstract

IntroductionWhile there has been a rapid uptake of virtual care in recent years, understanding of its impact on the quality of cancer care remains fragmented due to the heterogeneity of evaluation measures used to date and the lack of a framework to guide the work. We aimed to develop a comprehensive evaluation framework for virtual care in routine oncology practice.MethodsWe conducted separate nominal consensus groups with key informants (knowledge users, policy makers, clinicians, patients,...

Per and polyfluoroalkyl substances (PFAS) have emerged as ubiquitous contaminants in municipal solid waste (MSW) landfill leachates due to their widespread industrial applications, environmental persistence, and the disposal of PFAS-containing waste in landfill. This study presents a multi-regional investigation of PFAS occurrence, influencing factors, and treatment performance in 17 landfill leachates and 9 corresponding effluents across China. Sum PFAS concentrations in raw leachates ranged...

Inflammatory diseases of connective tissues such as periodontitis and rheumatoid arthritis exhibit localized destruction of matrix collagen and loss of tissue function. These diseases are driven by interconnected signaling pathways that determine disease progression and severity. Both periodontitis and rheumatoid arthritis involve the release of extracellular Vimentin (ECV) from stromal and immune cells at diseased sites, but the processes by which ECV binds to cells and promotes inflammatory...