Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions.

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain.

Thiosulfate sulfurtransferase (TST, EC 2.8.1.

Transcriptomic changes in autophagy-related genes are inversely correlated with inflammation and are associated with multiple sclerosis lesion pathology.

Autophagy is a lysosomal degradative pathway essential for maintaining cellular homeostasis and is also implicated in multiple aspects of both innate and adaptive immunity. Neuroinflammation, along with demyelination and axonal loss, is an important component of multiple sclerosis (MS). Induction of autophagy ameliorated disease progression in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, underlying a possible link between autophagy and MS pathology.

Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter.

Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM).

Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors.

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.

Healthcare Professionals' Acceptance of Digital Cognitive Rehabilitation.

With technological possibilities in healthcare steadily increasing, more tools for digital cognitive rehabilitation become available. Acceptance of such technological advances is crucial for successful implementation. Therefore, we examined technology acceptance specifically for this form of rehabilitation in a sample of healthcare providers involved in cognitive rehabilitation.

High-Resolution Transcriptomic and Proteomic Profiling of Heterogeneity of Brain-Derived Microglia in Multiple Sclerosis.

Microglia are important for central nervous system (CNS) homeostasis and first to respond to tissue damage and perturbations. Microglia are heterogeneous cells; in case of pathology, microglia adopt a range of phenotypes with altered functions. However, how these different microglia subtypes are implicated in CNS disease is largely unresolved.

Profiling Microglia From Alzheimer's Disease Donors and Non-demented Elderly in Acute Human Postmortem Cortical Tissue.

Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer's disease (AD). Here, we investigated microglia transcriptomes at bulk and single-cell levels in non-demented elderly and AD donors using acute human postmortem cortical brain samples.

Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients.

Circulating cell-free DNA (ccfDNA) may contain DNA originating from the tumor in plasma of cancer patients (ctDNA) and enables noninvasive cancer diagnosis, treatment predictive testing, and response monitoring. A recent multicenter evaluation of workflows by the CANCER-ID consortium using artificial spiked-in plasma showed significant differences and consequently the importance of carefully selecting ccfDNA extraction methods. Here, the quantity and integrity of extracted ccfDNA from the plasma of cancer patients were assessed.

Driving sleep slow oscillations by auditory closed-loop stimulation-a self-limiting process.

The <1 Hz EEG slow oscillation (SO) is a hallmark of slow-wave sleep (SWS) and is critically involved in sleep-associated memory formation. Previous studies showed that SOs and associated memory function can be effectively enhanced by closed-loop auditory stimulation, when clicks are presented in synchrony with upcoming SO up states. However, increasing SOs and synchronized excitability also bear the risk of emerging seizure activity, suggesting the presence of mechanisms in the healthy brain that counter developing hypersynchronicity during SOs.

Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

Objectives: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis.

Design: Observational study.

Setting: Two tertiary academic children hospital PICUs.

Improving outcome in meningococcal disease: don't forget compartment syndrome!

Objective: To advocate a surgical intervention that can prevent the loss of limbs in patients with meningococcal disease.

Design: Case report.

Setting: Pediatric intensive care unit.

Sympathetic control of the cardiovascular response to acute hypoxemia in the chick embryo.

In response to an acute hypoxemic insult, the mammalian fetus shows a redistribution of the cardiac output in favor of the heart and brain. Peripheral vasoconstriction contributes to this response and is partly mediated by the release of catecholamines. Two mechanisms of catecholamine release in the fetus are reported: 1) neurogenic sympathetic stimulation and 2) a nonneurogenic mechanism via a direct effect of hypoxemia on chromaffin tissues.

Indium-111-DTPA-octreotide uptake measured in normal and abnormal pituitary glands.

Unlabelled: Pituitary uptake of [111In-DTPA]-octreotide is highly variable, and no formal methods for quantification have been described. Conflicting results have therefore been published as to the presence of somatostatin receptors in nonsecreting adenoma of the pituitary gland. The aim of the present study was to define the most accurate method for the analysis of [111In-DTPA]-octreotide SPECT studies of the pituitary gland.