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Oral squamous cell carcinoma (OSCC) often arises from oral epithelial dysplasia (OED); however, the gene expression changes during OED progression and its microenvironment are not fully understood. This study used spatial transcriptomics to identify differentially expressed genes and microenvironmental alterations associated with malignant transformation of OED. A retrospective analysis of paired OSCC and OED samples was conducted at the Faculty of Dentistry, University of Toronto. A total of 24...

During the Drosophila maternal-to-zygotic transition, maternally deposited RNAs are cleared in a temporally controlled manner. The RNA-binding protein Smaug is a major regulator of maternal mRNA decay and its expression at both the RNA and protein level is limited to a narrow temporal window during the MZT. Here we show that the Pumilio RNA-binding protein promotes degradation of smaug mRNA at the end of the MZT through Pumilio-binding cis-elements in the smaug 3´ untranslated region, and that...

Cancer genomics and precision oncology are increasingly central to cancer care, but many health systems struggle to implement them equitably, effectively, and sustainably. This Commission defines the current global precision oncology landscape and analyses the scientific, structural, and health-system challenges shaping its delivery and impact. Findings indicate that access to cancer genomics and precision oncology remains profoundly unequal across and within countries, leaving millions of...

Cancer genomic data sharing is a core pillar of precision oncology, underpinning reproducibility, scalability, and equity. The ability to discover, access, integrate, interpret, and reuse cancer 'omics data is a key determinant of precision oncology's value and benefit at scale. This work has been conducted as part of The Lancet Oncology Commission on Cancer Genomics and Precision Oncology to examine the practical data architecture required to support cancer genomics in research, clinical care,...

The integration of copy number variant (CNV) workflows into genome sequencing (GS) analysis pipelines allows for the identification of CNVs implicated in disease. Here, we generated a novel resource of CNVs identified in the HostSeq population cohort from Canada, identified the prevalence of recurrent CNVs associated with neurodevelopmental disorders, and determined CNVs of potential clinical relevance for reproductive planning and personal disease risk. GS data and CNV calls were generated for...

Entanglement is a key property of quantum systems. In this Letter the first measurements of quantum entanglement between spins in pairs of Z bosons are reported, using proton-proton collision data from the Large Hadron Collider (LHC) at center-of-mass energies of 13 and 13.6 TeV, recorded with the ATLAS detector. Measurements of angular observables sensitive to ZZ^{*} spin-density-matrix elements in the H→ZZ^{*}→ℓ^{+}ℓ^{-}ℓ^{+}ℓ^{-} process yield coefficients C_{2,1,2,-1}=-0.71±0.45 and...

The microbial utilization of carbohydrates produces metabolic byproducts that are associated with health benefits, such as short-chain fatty acids (SCFAs). The rapid absorption of SCFAs by intestinal epithelial cells makes them challenging to study in vivo. Culturing methods address this limitation by providing controlled conditions that allow for monitoring substrate utilization and the production of fermentation byproducts. In this paper, we describe an easily implemented, cost-effective...

SUMMARY: FAIDR-Desi is a non-technical user interface for design of intrinsically disordered regions (IDRs) based on greedy optimization of sequence features (simple sequence statistics correlated with IDR function, including amino acid composition, residue patterning and short linear interaction motifs), using more features (127) than other IDR design approaches. FAIDR-Desi can be used to design synthetic IDR mimics to establish feature sufficiency for function, or to knock out features to show...

CONCLUSIONS: The findings support cortical myoclonus as a relatively common and clinically actionable movement disorder in 22q11.2DS. As for Parkinson's disease, the results provide preliminary evidence supporting the chromosome 22q11.2 microdeletion as a potential risk-conferring CNV for cortical myoclonus, adding to the genetic heterogeneity associated with this movement disorder.

CONCLUSIONS: PF ependymoma comprises two biologically and clinically distinct entities. Maximal safe resection and focal radiotherapy remain the backbone of treatment, but integrating molecular subgrouping, imaging biomarkers, and modern radiotherapeutic techniques into surgical and adjuvant planning offers the clearest path to improved outcomes, particularly for high-risk PFA tumors.

Next-generation sequencing has transformed diagnosis, prognosis, and treatment across rare disease, cancer, immunology, and infectious disease. As variant interpretation may evolve with emerging evidence, sharing genetic data is essential to improve diagnostic accuracy and advance genomic medicine. However, practical guidance for implementing clinical genetic data sharing remains limited. The Canadian College of Medical Geneticists (CCMG), therefore, developed national guidance to support...

The microbial degradation of synthetic polyesters such as polyethylene terephthalate (PET) is mediated by diverse α/β-hydrolases, many of which remain poorly characterized. In this study, we investigated SM0281, an uncharacterized α/β-hydrolase from the symbiotic legume-associated rhizobacterium Sinorhizobium meliloti. Sequence analysis revealed that SM0281 shares low similarity with known polyester-degrading enzymes. Biochemical characterization of purified SM0281 demonstrated that it is a...

CONCLUSIONS: This study will provide initial evidence on the feasibility and utility of wearable-based digital phenotyping in individuals receiving rTMS for TRD. Our findings will inform the design of future large-scale studies aimed at wearable-supported relapse prevention and precision monitoring in depression care.

Primitive hematopoietic stem cells (pHSCs) sustain lifelong hematopoiesis through tightly regulated transitions between quiescence and activation. Circadian oscillations influence hematopoiesis; however, the mechanisms coordinating metabolic state and stem cell function daily remain incompletely defined. Here, we show that circadian cues coordinated a program of mitochondrial remodeling, metabolic reprogramming, and structural adaptation in pHSCs. At night, peak melatonin levels were associated...

Tuning protein expression in non-model organisms is often constrained by the lack of validated genetic parts and predictive design tools. Translational tuning through the modulation of upstream untranslated regions (5'-UTRs) offers a potentially organism-agnostic route, but existing methods typically rely on mechanistic assumptions, prior knowledge that may not be available in non-model contexts, or the screening of sequence libraries. Here, we present a simple generative approach for creating...

Triple-negative breast cancer is an aggressive and heterogeneous breast cancer subtype with few effective targeted therapies and frequent resistance to chemotherapy. Here, we integrate transcriptional regulatory network inference with chromatin accessibility across a large-scale multi-system collection of primary tumors, patient-derived xenografts and model cell lines to quantify transcription factor activity and identify regulators that underpin triple-negative breast cancer identity. This...

CONCLUSIONS: In addition to shedding light on the molecular events underpinning its pathogenesis, our data will serve as a valuable resource to help accelerate the discovery of improved diagnostics and therapeutics for DKD.

BACKGROUND: Determining the early immune response against SARS-CoV-2 in individuals who are vaccinated is essential for better understanding immune memory and informing COVID-19 vaccine design and use. We aimed to evaluate antibody and T-cell immune markers against SARS-CoV-2 infection among household contacts of index patients infected with SARS-CoV-2.

Adseverin is a Ca^(2+)-dependent, actin severing protein that promotes fusion of osteoclast precursors in osteoclast formation. Currently it is not understood how actin severing activity is regulated in osteoclastogenesis. Mass spectrometry of adseverin immunoprecipitates from osteoclasts showed that adseverin associated with Serpin D1. Purified Serpin D1 interacted with adseverin in vitro in a Ca^(2+)-dependent manner. Ca^(2+) increased actin severing by ~2-fold. Cells that differentiated into...

Pleiotropic and monotonic effects of gene dosage are central to understanding comorbidities in developmental pediatric and psychiatric disorders, yet the underlying biological processes are not well characterized. Here we develop a functional burden analysis to investigate the association of all protein-coding copy-number variants, genome-wide, with 43 complex traits in approximately 500,000 UK Biobank participants. We test variant associations disrupting 172 tissue or cell-type gene sets,...