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Diffuse intrinsic pontine glioma (DIPG) is an aggressive brainstem tumor affecting children, with median survival under 12 months and no curative treatments. Current therapeutic development centers on ONC201, an imipridone that exhibits clinical activity by selectively activating human caseinolytic protease P (hClpP). X-ray analysis of the hClpP:ONC201 complex offers insights into optimizing the chemical structure of ONC201. Based on this, we designed and synthesized simplified piperazine-based...

Anisotropic flow and radial flow are two key probes of the expansion dynamics and properties of the quark-gluon plasma (QGP). While anisotropic flow has been extensively studied, radial flow, which governs the system's radial expansion, has received less attention. Notably, direct experimental evidence for the global and collective nature of radial flow fluctuations has been lacking. This Letter presents the first measurement of transverse momentum (p_{T}) dependence of radial flow fluctuations...

Multi-omics cancer data provides complementary views of tumorigenesis and progression. Technical challenges exist in integrating these heterogeneous data into deep learning models to better understand tumorigenesis and predict cancer recurrence. We herein propose a novel end-to-end deep learning method (MULGONET) for cancer recurrence prediction and biomarker discovery. First, MULGONET can effectively solve the curse of dimensionality and the lack of model interpretability in multi-omics data...

Captured CO(2) can either be stored or converted into a carbon-containing product. Both processes require energy to liberate CO(2) from the CO(2) capture solution. One way to bypass the energy-intensive recovery of CO(2) is to integrate CO(2) capture and conversion. For example, OH^(-)-based capture solutions react with CO(2) to form (bi)carbonate-rich liquids, which can then be electrochemically converted into upgraded carbon-containing products while regenerating OH^(-) for further CO(2)...

Single-cell RNA sequencing (scRNA-seq) enables detailed comparisons of gene expression across cells and conditions. Single-cell differential expression analysis faces challenges like sample correlation, individual variation, and scalability. We develop a fast and scalable linear mixed-effects model (LMM) estimation algorithm, FLASH-MM, to address these issues. We reformulate aspects of the linear mixed model estimation procedure to make it faster, by reducing computational complexity and memory...

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess...

Bacteria have evolved a wide array of defence systems to combat phage infection, many of which rely on complex signalling systems and large protein complexes to function¹. Here we describe a 164-residue prophage-encoded protein that defends bacteria by sensing conserved oligomeric components of phage assembly. This protein, called ring interacting pore 1 (Rip1), is activated by the portal or small terminase proteins of infecting phages-oligomeric ring-shaped complexes that are essential for...

Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O(2)), we sought to determine whether the modality of HIF-1 activation directs its function. Through...

CONCLUSIONS: DHTs are feasible and can capture clinically meaningful psychological and physiological data in high-risk pediatric and family populations with LFS. They enable timely detection of distress and facilitate targeted interventions. Our findings can inform best practices for patient-centered DHT integration into clinical care, with relevance to pediatric oncology and broader digital health contexts.

B-cell lymphoma 6 (BCL6) is a transcriptional repressor protein central to the development and maintenance of germinal centers (GCs) during the humoral immune response. BCL6 is often deregulated in diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin's lymphoma, and inhibition of the protein-protein interaction between BCL6 and corepressors has been implicated as a therapeutic strategy. Based on a previously identified small molecule binding site on the BCL6 BTB domain, we carried out a...