Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS).

Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed.

CSF neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in FIRES and other infection-triggered encephalopathy syndromes.

Objective: Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes.

Dominant-negative variants in CBX1 cause a neurodevelopmental disorder.

Purpose: This study aimed to establish variants in CBX1, encoding heterochromatin protein 1β (HP1β), as a cause of a novel syndromic neurodevelopmental disorder.

Methods: Patients with CBX1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient.

Dilatation of the bridging cerebral cortical veins in childhood hydrocephalus suggests a malfunction of venous impedance pumping.

Dogs with a naturally occurring form of hydrocephalus have an elevated transmural venous pressure leading to cortical vein dilatation. The purpose of this study is to discover if there is vein dilatation in childhood hydrocephalus and to estimate the pressure required to maintain any enlargement found. Children with hydrocephalus between the ages of 4 and 15 years were compared with a control group.

Thickness of a three-sided coin: A molecular dynamics study.

This Letter presents a numerical study across parameter space to calculate the aspect ratio (ratio of length to diameter) of a fair "three-sided coin": a cylinder that when tossed, has equal probabilities of landing heads, tails, or sideways. The results are cast in the context of previous analytical studies, and the various mechanisms that govern the dynamics of coin tossing are compared and contrasted. After more than 7×10^{8} tosses of coins of various aspect ratios, this study finds the critical aspect ratio to be slightly less than (but not exactly equal to) sqrt[3]/2≈0.

The incidence of obesity, venous sinus stenosis and cerebral hyperaemia in children referred for MRI to rule out idiopathic intracranial hypertension at a tertiary referral hospital: a 10 year review.

Background: Children referred to a tertiary hospital for the indication, "rule out idiopathic intracranial hypertension (IIH)" may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children.

Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study.

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.

Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally.

The incidence of significant venous sinus stenosis and cerebral hyperemia in childhood hydrocephalus: prognostic value with regards to differentiating active from compensated disease.

Background: Symptomatic or active hydrocephalus in children is linked to an elevation in intracranial pressure (ICP), which is likely to be multifactorial in origin. The CSF outflow resistance, venous sinus resistance and total cerebral blood flow are likely factors in the ICP elevation. The purpose of this paper is to define the incidence, site and significance of venous sinus stenosis and/or cerebral hyperemia in a cohort of children diagnosed with hydrocephalus at a tertiary referral hospital.

Expansion of phenotype of DDX3X syndrome: six new cases.

Pathogenic variants in DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder.

Neurologic phenotypes associated with / mutations: Expanding the spectrum of disease.

Objective: To characterize the neurologic phenotypes associated with mutations and to seek genotype-phenotype correlation.

Methods: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with mutations.

Results: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype.

Role of Stone-Wales defects on the interfacial interactions among graphene, carbon nanotubes, and Nylon 6: A first-principles study.

We investigate computationally the role of Stone-Wales (SW) defects on the interfacial interactions among graphene, carbon nanotubes (CNTs), and Nylon 6 using density functional theory (DFT) and the empirical force-field. Our first-principles DFT calculations were performed using the Quantum ESPRESSO electronic structure code with the highly accurate van der Waals functional (vdW-DF2). Both pristine and SW-defected carbon nanomaterials were investigated.

Unique clinical and neurophysiologic profile of a cohort of children with CMTX3.

Objective: To describe in detail the clinical profile of Charcot-Marie-Tooth disease subtype 3 (CMTX3) to aid appropriate genetic testing and rehabilitative therapy.

Methods: We reviewed the clinical and neurophysiologic profile and CMT Pediatric Scale (CMTPedS) assessments of 11 children with CMTX3.

Results: Compared with the more common forms of CMT, CMT1A and CMTX, CMTX3 was characterized by early onset with early and progressive hand weakness.

A mechanochemical study of the effects of compression on a Diels-Alder reaction.

We examine the effects of compressive external forces on the mechanisms of the parent Diels-Alder (DA) reaction between butadiene and ethylene. Reaction pathways and transition states were calculated using the nudged elastic band method within a mechanochemical framework at the CASSCF(6,6)/6-31G**, as well as the B3LYP/6-311++G** levels of theory. Our results suggest that compressive hydrostatic pressure lowers the energy barrier for the parent DA reaction while suppressing the undesirable side reaction, thereby leading to a direct increase in the yield of cyclohexene.

Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3.

With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.

A generalized force-modified potential energy surface for mechanochemical simulations.

We describe the modifications that a spatially varying external load produces on a Born-Oppenheimer potential energy surface (PES) by calculating static quantities of interest. The effects of the external loads are exemplified using electronic structure calculations (at the HF/6-31G(∗∗) level) of two different molecules: ethane and hexahydro-1,3,5-trinitro-s-triazine (RDX). The calculated transition states and Hessian matrices of stationary points show that spatially varying external loads shift the stationary points and modify the curvature of the PES, thereby affecting the harmonic transition rates by altering both the energy barrier as well as the prefactor.

16p13.11 microdeletion in a patient with hemiconvulsion-hemiplegia-epilepsy syndrome: a case report.

We describe a patient with hemiconvulsion-hemiplegia-epilepsy syndrome. The pathophysiology of hemiconvulsion-hemiplegia-epilepsy syndrome remains uncertain and there are probably multiple potential contributing factors. Our patient had a chromosomal 16p13.

The entropy of the rotational conformations of (poly)isoprene molecules and its relationship to rubber elasticity and temperature increase for moderate tensile or compressive strains.

Molecular networks comprised of crosslinked cis-1,4 polyisoprene, often referred to as "natural rubber," are one of the most common systems for the study of rubber elasticity. Under moderate tensile or compressive strain, network chains begin to assume straighter paths, as local molecular kinks are removed. Isoprene units along the chain backbone are mechanically forced from their equilibrium distributions of 18 possible rotational states into a smaller subset of states, restricted to more linear conformations with the greatest end-to-end distances.

Mechanics of three-dimensional, nonbonded random fiber networks.

The mechanical behavior of an ensemble of athermal fibers forming a nonbonded network subjected to triaxial compression is studied using a numerical model. The response exhibits a power law dependence of stress on the dilatation strain and hysteresis upon loading and unloading. A stable hysteresis loop results after the first loading and unloading cycle.

A topology preserving method for generating equilibrated polymer melts in computer simulations.

A new method for generating equilibrated configurations of polymer melts is presented. In this method, the molecular weight of an equilibrated melt of polymers is successively doubled by affinely scaling the simulation box and adding beads along the contour of the chains. At each stage of molecular weight doubling, compressive deformations are produced on all length scales, while the random walk nature of the polymers is preserved, thereby requiring relaxation times significantly smaller than the reptation time to fully equilibrate the melt.

Conformational free energy of melts of ring-linear polymer blends.

The conformational free energy of ring polymers in a blend of ring and linear polymers is investigated using the bond-fluctuation model. Previously established scaling relationships for the free energy of a ring polymer are shown to be valid only in the mean-field sense, and alternative functional forms are investigated. It is shown that it may be difficult to accurately express the total free energy of a ring polymer by a simple scaling argument, or in closed form.

On the relationship between two popular lattice models for polymer melts.

A mapping between two well known lattice bond-fluctuation models for polymers [I. Carmesin and K. Kremer, Macromolecules 21, 2819 (1988); J.

Conformational properties of blends of cyclic and linear polymer melts.

An adapted version of the annealing algorithm to identify primitive paths of a melt of ring polymers is presented. This algorithm ensures that the primitive path length becomes zero for nonconcatenated rings, and that no entanglements are observed. The bond-fluctuation model was used to simulate ring-linear blends with N=150 and 300 monomers.