A Comprehensive Analysis of Topiramate and Drug Reaction With Eosinophilia and Systemic Symptoms.

Introduction Recent publications have described drug reaction with eosinophilia and systemic symptoms (DRESS) with topiramate. Topiramate has been associated with other severe cutaneous adverse reactions, including Stevens-Johnson syndrome, but a relationship to DRESS has not been established. To determine if there is a causal association between topiramate and DRESS, we conducted a comprehensive review of the data in the Janssen Research & Development Global Safety Database (GSD), signaling databases, and the literature.

T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth.

RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma.

Radiotherapy induces DNA damage, resulting in cell-cycle arrest and activation of cell-intrinsic death pathways. However, the radioresistance of some tumour entities such as malignant melanoma limits its clinical application. The innate immune sensing receptor retinoic acid-inducible gene I (RIG-I) is ubiquitously expressed and upon activation triggers an immunogenic form of cell death in a variety of tumour cell types including melanoma.

Carotid-body modulation through meditation in stage-I hypertensive subjects: Study protocol of a randomized and controlled study.

Adjunctive therapy for hypertension is in high demand for clinical research. Therefore, several meta-analyses have provided sufficient evidence for meditation as an adjunct therapy, without being anchored on reliable physiological grounds. Meditation modulates the autonomic nervous system.

On the atomistic origin of the polymorphism and the dielectric physical properties of beryllium oxide.

Polymorphic beryllium oxide has been theoretically investigated from first principles as regards orbital occupancies, chemical bonding, polarization, as well as dielectric properties. By means of Crystal-Orbital Bond Index (COBI) analysis, the important role of the 2p orbitals on beryllium has been elucidated, in particular in terms of the correlation between polarization and beryllium-atom displacement, including the impact of the latter on the covalency of the BeO bond. In addition, several structural possibilities for a Be Mg O solid solution have been investigated for a Be content between 6% and 22%; for those, dynamically stable structures have been found, displaying large polarization values, more covalent BeO bonds, and a tendency for tetrahedral Be coordination.

Pulmonary function and medication effect in mild-stage subjects with Parkinson's disease.

Background: Parkinson's disease (PD) causes a series of movement disorders, many of them starting in the early stage.

Objective: To analyze the pulmonary function of mild-stage subjects with PD and to investigate the effects of levodopa on it.

Methods: We included 21 patients with idiopathic PD and 20 healthy control subjects.

Neurochemical Profile of BRAFV600E/AktT308D/S473D Mouse Gangliogliomas Reveals Impaired GABAergic System Inhibition.

Gangliogliomas (GGs), composed of dysmorphic neurons and neoplastic astroglia, represent the most frequent tumor entity associated with chronic recurrent epileptic seizures. So far, a systematic analysis of potential differences in neurochemical profiles of dysmorphic tumoral neurons as well as neurons of the peritumoral microenvironment (PTME) was hampered by the inability to unequivocally differentiate between the distinct neuronal components in human GG biopsies. Here, we have applied a novel GG mouse model that allows to clearly resolve the neurochemical profiles of GG-intrinsic versus PTME neurons.

Gastrulation: Nodal signaling controls ordered collective cell migration.

By combining classical embryological experiments, advanced imaging, and active-particle simulations, a new study reveals how the coupling of signaling and active mechanical forces triggers the collective ordered internalization of mesendoderm cells during gastrulation in zebrafish embryos.

Next-generation sequencing of a combinatorial peptide phage library screened against ubiquitin identifies peptide aptamers that can inhibit the ubiquitin transfer cascade.

Defining dynamic protein-protein interactions in the ubiquitin conjugation reaction is a challenging research area. Generating peptide aptamers that target components such as ubiquitin itself, E1, E2, or E3 could provide tools to dissect novel features of the enzymatic cascade. Next-generation deep sequencing platforms were used to identify peptide sequences isolated from phage-peptide libraries screened against Ubiquitin and its ortholog NEDD8.

Management after acute injury of the anterior cruciate ligament (ACL), part 2: management of the ACL-injured patient.

Purpose: The aim of this consensus project was to create a treatment algorithm for the management of the ACL-injured patient which can serve as an aid in a shared decision-making process.

Methods: For this consensus process, a steering and a rating group were formed. In an initial face-to-face meeting, the steering group, together with the expert group, formed various key topic complexes for which various questions were formulated.

Lipid alterations by oxidative stress increase detached acrosomes after cryopreservation of semen in Holstein bulls.

The nearly exclusive use of cryopreserved semen in cattle breeding enables long shipping distances, higher storage times, quarantine to avoid germ transmission and easy dispersal of high genetic value bulls. Spermatozoa from bulls are well freezable and improvement of cryopreservation protocols over decades has led to high semen quality. However, there is still some loss of spermatozoa in each semen dose due to detached acrosomes after thawing.

A Deep Learning Framework for the Detection and Quantification of Reticular Pseudodrusen and Drusen on Optical Coherence Tomography.

Purpose: The purpose of this study was to develop and validate a deep learning (DL) framework for the detection and quantification of reticular pseudodrusen (RPD) and drusen on optical coherence tomography (OCT) scans.

Methods: A DL framework was developed consisting of a classification model and an out-of-distribution (OOD) detection model for the identification of ungradable scans; a classification model to identify scans with drusen or RPD; and an image segmentation model to independently segment lesions as RPD or drusen. Data were obtained from 1284 participants in the UK Biobank (UKBB) with a self-reported diagnosis of age-related macular degeneration (AMD) and 250 UKBB controls.

Mastering the game of Stratego with model-free multiagent reinforcement learning.

We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence (AI) has not yet mastered. It is a game characterized by a twin challenge: It requires long-term strategic thinking as in chess, but it also requires dealing with imperfect information as in poker.

Unbiased retrieval of frequency-dependent mechanical properties from noisy time-dependent signals.

The mechanical response of materials to dynamic loading is often quantified by the frequency-dependent complex modulus. Probing materials directly in the frequency domain faces technical challenges such as a limited range of frequencies, long measurement times, or small sample sizes. Furthermore, many biological samples, such as cells or tissues, can change their properties upon repetitive probing at different frequencies.

Metal-Ligand Role Reversal: Hydride-Transfer Catalysis by a Functional Phosphorus Ligand with a Spectator Metal.

Hydride transfer catalysis is shown to be enabled by the nonspectator reactivity of a transition metal-bound low-symmetry tricoordinate phosphorus ligand. Complex ·[Ru], comprising a nontrigonal phosphorus chelate (, P(N(-N(2-pyridyl)CH)) and an inert metal fragment ([Ru] = (MeC)Ru), reacts with NaBH to give a metallohydridophosphorane (·[Ru]) by P-H bond formation. Complex ·[Ru] is revealed to be a potent hydride donor (Δ° < 41 kcal/mol, Δ° = 38 ± 2 kcal/mol in MeCN).

β-Nuclear-Recoil Correlation from ^{6}He Decay in a Laser Trap.

We report the first precise measurement of a β-recoil correlation from a radioactive noble gas (^{6}He) confined via a magneto-optical trap. The measurement is motivated by the search for exotic tensor-type contributions to the charged weak current. Interpreted as tensor currents with right-handed neutrinos, the measurements yield |C_{T}/C_{A}|^{2}≤0.

Fast absolute 3D CGO-based electrical impedance tomography on experimental tank data.

To present the first 3D CGO-based absolute EIT reconstructions from experimental tank data.CGO-based methods for absolute EIT imaging are compared to traditional TV regularized non-linear least squares reconstruction methods. Additional robustness testing is performed by considering incorrect modeling of domain shape.

Residence times of groundwater along a flow path in the Great Artesian Basin determined by Kr, Cl and He: Implications for palaeo hydrogeology.

Understanding the age distribution of groundwater can provide information on both the recharge history as well as the geochemical evolution of groundwater flow systems. Of the few candidates available that can be used to date old groundwater, Kr shows the most promise because its input function is constant through time and there are less sources and sinks to complicate the dating procedure in comparison to traditional tracers such as Cl and He. In this paper we use Kr in a large groundwater basin to obtain a better understanding of the residence time distribution of an unconfined-confined aquifer system.

Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.

Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways.

Effects of salinity and temperature on seawater dissolution rate of initial detonation agent mercury fulminate.

Mercury fulminate (HgFu) was used as an initial detonator for World War I and II munitions. Its presence in previously discarded and dumped munitions could potentially supply mercury pollution into coastal ecosystems where bygone weaponries reside. There is evidence that historical munitions have already contributed mercury pollution in coastal environments, and millions remain embedded in sediments and subjected to further weakening via corrosion under environmental conditions.

Effect of donor pancreas extraction time on pancreas transplantation-a Swiss tertiary center experience.

We aimed to assess the effect of donor pancreas extraction time (ET) on postoperative complications and graft function after pancreas transplantation (PT). We analyzed all consecutive donor pancreas procurements for the simultaneous pancreas and kidney transplantation (SPK) and the associated PT in a Swiss transplant center over a 20-year period. Pancreas ET was defined as the time from cold flush to static storage of the pancreas on ice.

Effects of the RNA-Polymerase Inhibitors Remdesivir and Favipiravir on the Structure of Lipid Bilayers-An MD Study.

The structure and dynamics of membranes are crucial to ensure the proper functioning of cells. There are some compounds used in therapeutics that show nonspecific interactions with membranes in addition to their specific molecular target. Among them, two compounds recently used in therapeutics against COVID-19, remdesivir and favipiravir, were subjected to molecular dynamics simulation assays.

GOF Mutant p53 in Cancers: A Therapeutic Challenge.

is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential.