Conserved helical motifs in the IKZF1 disordered region mediate NuRD interaction and transcriptional repression.

The transcription factor IKZF1 is essential for B cell development, and recurrently mutated in human B-ALL. IKZF1 has been ascribed both activating and repressive functions via interactions with coactivator and corepressor complexes, but the relative abundance of IKZF1-associated coregulators and their contribution to IKZF1-mediated gene regulation are not well understood. To address this, we performed an unbiased identification of IKZF1-interacting proteins in pre-B cells and found that IKZF1 interacts overwhelmingly with corepressors and heterochromatin-associated proteins.

Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.

Background: Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT). Successful implementation of radiosensitization strategies in DMG remains an essential and promising avenue of investigation.

CT-guided online adaptive stereotactic body radiotherapy for pancreas ductal adenocarcinoma: Dosimetric and initial clinical experience.

Purpose/objectives: Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses.

Materials/methods: This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto).

Comprehensive stereotactic radiosurgery platform characterization: A novel end-to-end approach with anthropomorphic 3D dosimetry.

Background: Stereotactic radiosurgery (SRS) is a widely employed strategy for intracranial metastases, utilizing linear accelerators and volumetric modulated arc therapy (VMAT). Ensuring precise linear accelerator performance is crucial, given the small planning target volume (PTV) margins. Rapid dose falloff is vital to minimize brain radiation necrosis.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

Objectives: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C.

Methods: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers.

Enhancing Safety in AI-Driven Cone Beam CT-based Online Adaptive Radiation Therapy: Development and Implementation of an Interdisciplinary Workflow.

Purpose: The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the "black box" adaptation process. This study identifies high-risk failure modes (FMs) associated with AI-driven OART and proposes an interdisciplinary workflow to mitigate potential medical errors from highly automated processes, enhance treatment efficiency, and reduce the burden on clinicians.

Endothelial sensing of AHR ligands regulates intestinal homeostasis.

Endothelial cells line the blood and lymphatic vasculature, and act as an essential physical barrier, control nutrient transport, facilitate tissue immunosurveillance and coordinate angiogenesis and lymphangiogenesis. In the intestine, dietary and microbial cues are particularly important in the regulation of organ homeostasis. However, whether enteric endothelial cells actively sense and integrate such signals is currently unknown.

Adaptive Radiation Therapy: A Review of CT-based Techniques.

Adaptive radiation therapy is a feedback process by which imaging information acquired over the course of treatment, such as changes in patient anatomy, can be used to reoptimize the treatment plan, with the end goal of improving target coverage and reducing treatment toxicity. This review describes different types of adaptive radiation therapy and their clinical implementation with a focus on CT-guided online adaptive radiation therapy. Depending on local anatomic changes and clinical context, different anatomic sites and/or disease stages and presentations benefit from different adaptation strategies.

Orthogonal Glycosylation with Phosphate Acceptors for Expeditious Synthesis of Bacterial Inner Core Oligosaccharides.

We report a practical one-pot glycosylation strategy for synthesis of bacterial inner core oligosaccharides that composed of unavailable L-glycero-D-manno and D-glycero-D-manno-heptopyranose components. The glycosylation method features a new orthogonal glycosylation procedure; whereby a phosphate acceptor is coupled with a thioglycosyl donor producing a disaccharide phosphate, which can be engaged in another orthogonal glycosylation procedure to couple with a thioglycosyl acceptor. The phosphate acceptors used in above one-pot procedure are directly prepared from thioglycosyl acceptors via the in-situ phosphorylation.

Kawasaki disease in children with Bacillus Calmette-Guérin scar reactivity: Focus on coronary outcomes.

Background: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes.

Loss of H3K9 trimethylation alters chromosome compaction and transcription factor retention during mitosis.

Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and polycomb repressor complexes, binds to chromosomes throughout mitosis and their depletion results in increased chromosome size. In the present study, we show that enzymes that catalyze H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly, however, mutants lacking histone 3 lysine 9 trimethylation (H3K9me3) have unusually small and compact mitotic chromosomes associated with increased histone H3 phospho Ser10 (H3S10ph) and H3K27me3 levels.

Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice.

RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein 2 (RBFOX2) in maintaining cholesterol homeostasis in a lipogenic environment in the liver.

Oestrogen enforces the integrity of blood vessels in the bone during pregnancy and menopause.

The mammalian skeletal system shows sex differences in structure, functions, ageing and disease incidences. The role of blood vessels in physiological, regenerative and pathological bone functions indicates the requisite to understanding their sex specificity. Here, we find oestrogen regulates blood vessel physiology during pregnancy and menopause through oestrogen receptor alpha (ERα) and G-protein coupled oestrogen receptor-1 (Gper1) but not ERβ-dependent signalling in mice.

Validation of a High-Throughput Dicentric Chromosome Assay Using Complex Radiation Exposures.

Validation of biodosimetry assays is routinely performed using primarily orthovoltage irradiators at a conventional dose rate of approximately 1 Gy/min. However, incidental/ accidental exposures caused by nuclear weapons can be more complex. The aim of this work was to simulate the DNA damage effects mimicking those caused by the detonation of a several kilotons improvised nuclear device (IND).

Correlation between mumps and meteorological factors in Xiamen City, China: A modelling study.

Objective: Mumps is a seasonal infectious disease, always occurring in winter and spring. In this study, we aim to analyze its epidemiological characteristics, transmissibility, and its correlation with meteorological variables.

Method: A seasonal model and a next-generation matrix method were applied to estimate the ( ).

Dosimetric assessment of patient dose calculation on a deep learning-based synthesized computed tomography image for adaptive radiotherapy.

Purpose: Dose computation using cone beam computed tomography (CBCT) images is inaccurate for the purpose of adaptive treatment planning. The main goal of this study is to assess the dosimetric accuracy of synthetic computed tomography (CT)-based calculation for adaptive planning in the upper abdominal region. We hypothesized that deep learning-based synthetically generated CT images will produce comparable results to a deformed CT (CTdef) in terms of dose calculation, while displaying a more accurate representation of the daily anatomy and therefore superior dosimetric accuracy.

Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease.

Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD).

Weight-Based Assessment of Access Flow Threshold to Predict Arteriovenous Fistula Functional Patency.

Introduction: The 2019 Kidney Disease Outcome Quality Initiative (K/DOQI) guideline recommended evaluating arteriovenous fistula (AVF) malfunction risks primarily based on clinical monitoring, which can be assisted with the value of vascular access flow (Qa). Nevertheless, Qa thresholds recommended by different guidelines vary, ranging from 300 to 500 ml/min. This study investigated the optimal Qa threshold to predict future functional patency in AVFs with Qa <500 ml/min.

Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction.

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage.

Sex-specific chromatin remodelling safeguards transcription in germ cells.

Stability of the epigenetic landscape underpins maintenance of the cell-type-specific transcriptional profile. As one of the main repressive epigenetic systems, DNA methylation has been shown to be important for long-term gene silencing; its loss leads to ectopic and aberrant transcription in differentiated cells and cancer. The developing mouse germ line endures global changes in DNA methylation in the absence of widespread transcriptional activation.

CNOT3 interacts with the Aurora B and MAPK/ERK kinases to promote survival of differentiating mesendodermal progenitor cells.

Mesendoderm cells are key intermediate progenitors that form at the early primitive streak (PrS) and give rise to mesoderm and endoderm in the gastrulating embryo. We have identified an interaction between CNOT3 and the cell cycle kinase Aurora B that requires sequences in the NOT box domain of CNOT3 and regulates MAPK/ERK signaling during mesendoderm differentiation. Aurora B phosphorylates CNOT3 at two sites located close to a nuclear localization signal and promotes localization of CNOT3 to the nuclei of mouse embryonic stem cells (ESCs) and metastatic lung cancer cells.