Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome.

Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis.

Theory of Defect-Induced Crystal Field Perturbations in Rare-Earth Magnets.

We present a theory describing the single-ion anisotropy of rare-earth (RE) magnets in the presence of point defects. Taking the RE-lean 1∶12 magnet class as a prototype, we use first-principles calculations to show how the introduction of Ti substitutions into SmFe_{12} perturbs the crystal field, generating new coefficients due to the lower symmetry of the RE environment. We then demonstrate that these perturbations can be described extremely efficiently using a screened point charge model.

Macrophage mediated mesoscale brain mechanical homeostasis mechanically imaged via optical tweezers and Brillouin microscopy .

Tissues are active materials where epithelial turnover, immune surveillance, and remodeling of stromal cells such as macrophages all regulate form and function. Scattering modalities such as Brillouin microscopy (BM) can non-invasively access mechanical signatures at GHz. However, our traditional understanding of tissue material properties is derived mainly from modalities which probe mechanical properties at different frequencies.

Dynamic Monitoring of Probiotics Effect in Parkinson's Disease Patients via Swarm Decomposition and Bispectral Analysis of Electrogastrograms.

People with Parkinson's Disease (PwP) experience a significant deterioration of their daily life quality due to non-motor symptoms, with gastrointestinal dysfunctions manifesting as a vanguard of the latter. Electrogastrography (EGG) is a noninvasive diagnostic tool that can potentially provide biomarkers for the monitoring of dynamic gastric alterations that are related to daily lifestyle and treatment regimens. In this work, a robust analysis of EGG dynamics is introduced to evaluate the effect of probiotic treatment on PwP.

Musculoskeletal pain in Parkinson's disease: Association with dopaminergic deficiency in the caudate nucleus.

Background: Musculoskeletal (MSK) pain affects over 80% of People with Parkinson's (PD, PwP) and may, in part, be dopaminergic in origin, as dopaminergic medication often leads to its relief.

Methods: PwP who underwent striatal dopamine transporter visualization with a radiopharmaceutical DaTscan™ ( I-Ioflupane Injection) using a single-photon emission computed tomography (SPECT) as a part of their clinical-diagnostic work up were enrolled in the "Non-motor International Longitudinal Study" (NILS; UK National Institute for Health Research Clinical Research Network Number 10084) and included in this cross-sectional analysis. The association between specific DaTscan binding ratios for each striatum, the caudate nucleus and putamen and clinical ratings for MSK pain (assessed using the King's Parkinson's Disease Pain Scale (KPPS)) were analysed.

Fermi-Surface Origin of Skyrmion Lattices in Centrosymmetric Rare-Earth Intermetallics.

We show from first principles that barrel-shaped structures within the Fermi surface of the centrosymmetric intermetallic compounds GdRu_{2}Si_{2} and Gd_{2}PdSi_{3} give rise to Fermi surface nesting, which determines the strength and sign of quasi-two-dimensional Ruderman-Kittel-Kasuya-Yosida pairwise exchange interactions between the Gd moments. This is the principal mechanism leading to their helical single-q spin-spiral ground states, providing transition temperatures and magnetic periods in good agreement with experiment. Using atomistic spin-dynamic simulations, we draw a direct line between the subtleties of the three-dimensional Fermi surface topology and the stabilization of a square skyrmion lattice in GdRu_{2}Si_{2} at applied magnetic fields as observed in experiment.

Self-reported periodontitis and C-reactive protein in Parkinson's disease: a cross-sectional study of two American cohorts.

Periodontitis triggers systemic repercussions, such as elevated levels of high-sensitive C-reactive protein (hs-CRP). This has never been studied within Parkinson's Disease (PD). The aim of this study is to compare hs-CRP levels of self-reported periodontitis cases versus cases without periodontitis in PD patients.

The impact of nonmotor symptom burden on sexual function.

Sexual dysfunction (SD) is defined as a combination of reduction in libido, and problems with a person's ability to have sex. It is a frequent but neglected and poorly recognized nonmotor symptom (NMS) in Parkinson's disease (PD) which correlates with reduced quality of life (QoL). Hypersexuality forms another spectrum of SD and is an impulse control disorder (ICD) of behavior, which also affects the sexual desires of people with Parkinson's (PwP) and impacts their partner, family, and QoL.

Ethnic Disparities in Treatment of Chronic Pain in Individuals with Parkinson's Disease Living in the United Kingdom.

Background: Over 80% people with Parkinson's disease (PD; PwP) live with chronic pain.

Objective: Whether ethnic disparities in receipt of appropriate analgesia exist among PwP with chronic pain living in the United Kingdom (UK).

Methods: A retrospective datamining of an existing King's PD Pain Questionnaire validation study dataset enrolling 300 PwP.

Zotatifin, an eIF4A-Selective Inhibitor, Blocks Tumor Growth in Receptor Tyrosine Kinase Driven Tumors.

Oncoprotein expression is controlled at the level of mRNA translation and is regulated by the eukaryotic translation initiation factor 4F (eIF4F) complex. eIF4A, a component of eIF4F, catalyzes the unwinding of secondary structure in the 5'-untranslated region (5'-UTR) of mRNA to facilitate ribosome scanning and translation initiation. Zotatifin (eFT226) is a selective eIF4A inhibitor that increases the affinity between eIF4A and specific polypurine sequence motifs and has been reported to inhibit translation of driver oncogenes in models of lymphoma.

Terahertz response of monolayer and few-layer WTe at the nanoscale.

Tungsten ditelluride (WTe) is an atomically layered transition metal dichalcogenide whose physical properties change systematically from monolayer to bilayer and few-layer versions. In this report, we use apertureless scattering-type near-field optical microscopy operating at Terahertz (THz) frequencies and cryogenic temperatures to study the distinct THz range electromagnetic responses of mono-, bi- and trilayer WTe in the same multi-terraced micro-crystal. THz nano-images of monolayer terraces uncovered weakly insulating behavior that is consistent with transport measurements.

Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration.

Torque magnetometry study of the spin reorientation transition and temperature-dependent magnetocrystalline anisotropy in NdCo.

We present the results of torque magnetometry and magnetic susceptibility measurements to study in detail the spin reorientation transition (SRT) and magnetic anisotropy in the permanent magnet NdCo. We further show simulations of the measurements using first-principles calculations based on density-functional theory and the disordered local moment picture of magnetism at finite temperatures. The good agreement between theory and experimental data leads to a detailed description of the physics underpinning the SRT.

Retrospective study of first episode psychosis in the Dublin Southwest Mental Health Service: demographics, clinical profile and service evaluation of treatment.

Objective: In Ireland, National Clinical Programmes are being established to improve and standardise patient care throughout the Health Service Executive. In line with internationally recognised guidelines on the treatment of first episode psychosis the Early Intervention in Psychosis (EIP) programme is being drafted with a view to implementation by mental health services across the country. We undertook a review of patients presenting with a first episode of psychosis to the Dublin Southwest Mental Health Service before the implementation of the EIP.

Tissue Architectural Cues Drive Organ Targeting of Tumor Cells in Zebrafish.

Tumor cells encounter a myriad of physical cues upon arrest and extravasation in capillary beds. Here, we examined the role of physical factors in non-random organ colonization using a zebrafish xenograft model. We observed a two-step process by which mammalian mammary tumor cells showed non-random organ colonization.

High-frequency microrheology in 3D reveals mismatch between cytoskeletal and extracellular matrix mechanics.

Mechanical homeostasis describes how cells sense physical cues from the microenvironment and concomitantly remodel both the cytoskeleton and the surrounding extracellular matrix (ECM). Such feedback is thought to be essential to healthy development and maintenance of tissue. However, the nature of the dynamic coupling between microscale cell and ECM mechanics remains poorly understood.

Crystal field coefficients for yttrium analogues of rare-earth/transition-metal magnets using density-functional theory in the projector-augmented wave formalism.

We present a method of calculating crystal field coefficients of rare-earth/transition-metal (RE-TM) magnets within density-functional theory (DFT). The principal idea of the method is to calculate the crystal field potential of the yttrium analogue ('Y-analogue') of the RE-TM magnet, i.e.

Human macrophages survive and adopt activated genotypes in living zebrafish.

The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer and neurodegenerative disorders. Here, we sought a model to interrogate human immune behavior in vivo. We determined that primary human monocytes and macrophages survive in zebrafish for up to two weeks.

Probing cellular response to topography in three dimensions.

Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using magnetic-field driven assembly of paramagnetic colloidal particles functionalized with three types of human ECM proteins found in vivo.

Field-induced canting of magnetic moments in GdCo at finite temperature: first-principles calculations and high-field measurements.

We present calculations and experimental measurements of the temperature-dependent magnetization of a single crystal of GdCo in magnetic fields of order 60 T. At zero temperature the calculations, based on density-functional theory in the disordered-local-moment picture, predict a field-induced transition from an antiferromagnetic to a canted alignment of Gd and Co moments at 46.1 T.

A comparison of methods to assess cell mechanical properties.

The mechanical properties of cells influence their cellular and subcellular functions, including cell adhesion, migration, polarization, and differentiation, as well as organelle organization and trafficking inside the cytoplasm. Yet reported values of cell stiffness and viscosity vary substantially, which suggests differences in how the results of different methods are obtained or analyzed by different groups. To address this issue and illustrate the complementarity of certain approaches, here we present, analyze, and critically compare measurements obtained by means of some of the most widely used methods for cell mechanics: atomic force microscopy, magnetic twisting cytometry, particle-tracking microrheology, parallel-plate rheometry, cell monolayer rheology, and optical stretching.