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Pediatric brain tumors are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumor types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, and neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumors with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood-brain barrier (BBB), which...

Ex vivo expansion of mobilized peripheral blood (mPB) hematopoietic stem cells (HSCs) represents a promising approach to advance cell and gene therapy strategies yet is hampered by loss of stem cell function when applying commonly used culture protocols. We performed in-depth characterization of mPB expansion cultures by single cell RNA sequencing, which highlighted differentiation trajectories with preservation of lineage fidelity in committed progenitors. Defining a putative HSC cluster...

Antioxidants added to tires to prevent degradation have recently been recognized as emerging environmental contaminants. While their acute aquatic toxicity has raised concern, these compounds are also emitted to the atmosphere and can be associated with particulate matter (PM). On PM they can react heterogeneously with oxidants, producing a range of transformation products (TPs) with unknown impacts to human health via inhalation. Here, we show through laboratory experiments that many previously...

The important role of paternal health in reproductive success, particularly time to pregnancy (TTP) and miscarriage, is gaining recognition. This scoping review aims to identify, consolidate and analyze the literature on paternal preconception health related to TTP and miscarriage. This review was conducted using the Joanna Briggs Institute methodology. The Medline, PsycINFO, Embase, Scopus and CINAHL databases were searched from January 1, 2013-July 26, 2025. Two independent reviewers screened...

Early recognition of patients at risk for deterioration in the emergency department (ED) is critical for patient safety. Traditional early warning scores rely on structured triage data and often perform poorly in the dynamic ED environment. We developed and evaluated two machine learning models integrating structured triage data with transformer-based embeddings of free-text nursing triage notes to predict early clinical deterioration prior to initial physician assessment, designed as a...

CONCLUSIONS: In this single-institution cohort of patients with recurrent ependymoma and long-term follow-up, gross total resection of recurrence was associated with better survival, and locally recurrent patients treated with CSI-RT2 had longer OS. Further work is required to determine the independent effects of CSI-RT2 together with the extent of re-resection.

Introns play a critical role in regulating alternative splicing. However, identifying functional intronic motifs is challenging due to their short and degenerate sequence composition. Massively parallel reporter assays have provided insights into cis-regulatory logic governing alternative splicing, but these approaches are generally performed in cell culture, limiting their ability to capture tissue-specific contexts. Here, we implemented in vivo parallelized reporter assays (PRA) in...

Oncostatin M receptor (OSMR) plays diverse roles in several human malignancies, including brain, breast, and pancreatic cancer. In glioblastoma (GB), OSMR orchestrates a feedforward signaling mechanism with the truncated active mutant of epidermal growth factor receptor (EGFR), the EGFRvIII, and signal transducer and activator of transcription 3 (STAT3) to drive GB progression. Beyond EGFRvIII, OSMR promotes brain tumor stem cell (BTSC) respiration and therapy resistance. The molecular...

Enzymes are adapted to perform optimally in different thermal regimes that would otherwise alter kinetics and stability. Whether adaptive evolution in the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) also compensates for thermal variation remains uncertain. We examined molecular evolution and modelled the change in folding free energy (ΔΔG, where negative values indicate stabilization) of the rubisco large subunit (RbcL) in four phylogenetically distant plant...

Phytopathogenic bacteria rely on type III effectors to suppress host immunity and facilitate colonization. While necessary for virulence, effectors can also trigger effector-triggered immunity (ETI) if hosts have appropriate NLR immune receptors, resulting in a coevolutionary arms races driving high diversity in both the pathogen "effectorome" and the host "NLRome." Here, we synthesize current knowledge of effectoromes into an "interconnected module model", that emphasizes how functional...

Ubiquitin-Specific Protease 18 (USP18) is a deISGylation enzyme and antineoplastic target. To develop USP18 inhibitors, an enzymatically active human recombinant USP18 protein was engineered suitable for high-throughput screening of ~80,000 chemical compounds. Three of them substantially inhibited USP18 enzymatic activity with β-lapachone having prominent antineoplastic activity. Independent β-lapachone treatments of murine and human lung cancer cell lines statistically-significantly reduced...

The Hippo signaling pathway, first identified in Drosophila, is a conserved regulator of organ size and tissue homeostasis that balances proliferation and apoptosis. In mammals, its core kinases mammalian Sterile 20-like kinases 1 and 2 (MST1/2) and large tumor suppressor kinases 1 and 2 (LATS1/2) restrict the transcriptional coactivators Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), whose nuclear translocation drives cell proliferation and...

Polycomb repressive complex 2 (PRC2)-mediated histone H3 K27 trimethylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochromatin. In early development, Polycomb-regulated genes can display long-range three-dimensional interactions, many of which resolve during lineage differentiation. Here we report that Polycomb-anchored looping is controlled by H3K27me3 spreading and regulates target gene silencing to influence cell fate specification. Using glioma-derived H3 Lys27-to-Met...

Intrinsically disordered regions (IDRs) represent at least one-third of the human proteome and defy the established structure-function paradigm. Because IDRs often have limited positional sequence conservation, the functional classification of IDRs using standard bioinformatics is generally not possible. Here, we show that evolutionarily conserved molecular features of IDRs enable clustering of the human disordered proteome (IDRome) into a map with strong functional enrichments. We quantify how...

Anaplastic thyroid cancer (ATC) is highly lethal. Although patients with the BRAF^(V600E) alteration respond to the type I RAF inhibitor (RAFi) dabrafenib with trametinib, most rapidly develop adaptive or acquired resistance. Here, multi-region whole-genome, high-coverage whole-exome, and single-nuclei RNA sequencing of tumors from ATC patients undergoing type I RAFi and MEKi therapy reveals that reactivation of the mitogen-activated protein kinase (MAPK) pathway, along with immunosuppressive...

The human coronavirus HCoV-OC43 (OC43) is the most widespread of the four common cold-causing seasonal coronaviruses, and tissue culture-adapted strains of it have been used for ~50 years. Nevertheless, clinical isolates of OC43 differ from tissue culture-adapted OC43 in ways that call into question the value of the latter as a model. Among these are differences in their entry mechanisms and the activities of their hemagglutinin-esterases (HE). We now show that the spike proteins of OC43...

CONCLUSIONS: We identified a significant serological benefit of SCV2 vaccination relative to infection, in terms of antibody avidity, level, and durability. These data can support clinicians in making evidence-based vaccine recommendations for children with ALL.

Episignatures are increasingly valuable for variant interpretation in rare neurodevelopmental disorders, especially when optimized to capture the impact of specific variant types and locations across a gene. Here, we generated a next-generation DNA methylation (DNAm) episignature for Kabuki syndrome type 1 (KS1) using the largest cohort studied to date, aiming to clarify the epigenomic and phenotypic effects of diverse KMT2D variant types and positions. Genome-wide DNAm profiles were obtained...

Per- and polyfluoroalkyl substances (PFAS) are persistent contaminants frequently detected in surface waters, yet their behavior in cold-region river basins remains insufficiently characterized. In this study, 26 PFAS were measured in river water and sediments at 27 sites across the Songhua River Basin, Northeast China, during warm and cold seasons. The objectives were to characterize PFAS occurrence, evaluate spatial and seasonal variability at the basin scale, examine sediment-water...

In this study, for the first time, the distribution and fractionation of persistent organic pollutants (POPs) along both latitudinal and longitudinal transects are investigated simultaneously in surface soil. Distributions and fractionations of two isomers of hexachlorocyclohexane (HCH), α- and β-HCH, were analyzed in Chinese rural surface soil using a set of soil samples collected in 2005, 2012, and 2019 to study the lifecycle of the global/latitudinal fractionation of POPs. The primary...