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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...

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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...

CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow...

Pathogenic variants in the autoimmune regulator (AIRE) cause autoimmune polyendocrine syndrome type 1 (APS-1), a rare primary immunodeficiency disease with symptoms including hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis. AIRE increases the expression and presentation of tissue-specific genes expressing "self" antigens in the developing T cell niche, thus triggering the elimination of self-reactive T cells and preventing autoimmunity. Earlier diagnoses can...

Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assay 284 mostly uncharacterized putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 74 new DNA binding motifs. To investigate whether TFs lacking detectable motifs preferably bind epigenetically modified DNA, we develop methylation-sensitive SMiLE-seq (meSMiLE-seq), a microfluidic assay...

The functional impact of a large portion of the human genome known as "dark matter DNA", which is composed mainly of repeat sequences, remains unknown. The genome also encodes many putative and poorly characterized transcription factors. Here, we determine genomic binding locations of 166 poorly characterized human transcription factors in living cells. Nearly half of them associate strongly with known regulatory regions such as promoters and enhancers, frequently co-localizing with each other...

Gene expression is regulated by transcription factors (TFs), which recognize specific DNA sequence motifs. Several hundred putative human TFs, identified mainly by an apparent DNA-binding domain, lack known binding motifs¹. Furthermore, even for well-characterized TFs, it remains controversial the degree to which motifs accurately reflect binding sites in living cells². Here we describe a systematic effort ('Codebook') to determine the sequence specificity of 332 putative and poorly...

There is ongoing debate regarding the degree to which transcription factors (TFs) independently specify genomic binding: TF binding motifs are typically short and degenerate, yielding many more binding site predictions than observed in cells. Here we present genomic high-throughput SELEX (GHT-SELEX)-a scalable method that surveys intrinsic binding of purified TFs to the fragmented, naked and unmodified genome. GHT-SELEX peaks for 179 diverse human TFs display surprisingly high overlap with...