Impact of enzyme replacement therapy on clinical manifestations in females with Fabry disease.

Background: The aim of our multicenter study was to investigate the implementation of the European Fabry guidelines on therapeutic recommendations in female patients with Fabry disease (FD) and to analyze the impact of enzyme replacement therapy (ERT) in treated and untreated females.

Results: Data from 3 consecutive visits of 159 female FD patients from 6 Fabry centers were retrospectively analyzed. According to their treatment, patients were separated in 3 groups (untreated, n = 71; newly ERT-treated, n = 47; long-term ERT-treated, n = 41).

Targeted pre-conditioning and cell transplantation in the murine lower respiratory tract.

Transplantation of airway basal stem cells could achieve a durable cure for genetic diseases of the airway, such as cystic fibrosis and primary ciliary dyskinesia. Recent work demonstrated the potential of primary- and pluripotent stem cell (PSC)-derived basal cells to efficiently engrai into the mouse trachea aier injury. However, there are many hurdles to overcome in translating these approaches to humans including developing safe and efficient methods for delivery in larger animal models.

Dexmedetomidine for Less Invasive Surfactant Administration: A Pilot Study.

Introduction: Less invasive surfactant administration (LISA) involves delivering surfactant to a spontaneously breathing infant by passing a thin catheter through the vocal cords and has become the preferred method for surfactant delivery. However, the role of pre-LISA sedation remains unclear.

Objective: The aim of this study was to describe the use of dexmedetomidine for LISA in preterm and early-term infants.

Accurate Thermochemistry with Multireference Methods: A Stress Test for Internally Contracted Multireference Coupled-Cluster Theory.

The internally contracted multireference coupled-cluster method with single, double and perturbative triple excitations, icMRCCSD(T), was tested for its performance in the context of computational high-accuracy thermochemistry. The results were gauged against the standard single-reference coupled-cluster hierarchy with up to 5-fold excitations. The test set comprised of a selection of first-row dinuclear compounds and the three 3d-transition metal compounds MnH, FeH, and CoH.

The representational geometry for naturalistic textures in macaque V1 and V2.

Our understanding of visual cortical processing has relied primarily on studying the selectivity of individual neurons in different areas. A complementary approach is to study how the representational geometry of neuronal populations differs across areas. Though the geometry is derived from individual neuronal selectivity, it can reveal encoding strategies difficult to infer from single neuron responses.

Circuit-motivated generalized affine models characterize stimulus-dependent visual cortical shared variability.

Correlated variability in the visual cortex is modulated by stimulus properties. The stimulus dependence of correlated variability impacts stimulus coding and is indicative of circuit structure. An affine model combining a multiplicative factor and an additive offset has been proposed to explain how correlated variability in primary visual cortex (V1) depends on stimulus orientations.

Cyclohepta[]fluorene as a bistable molecule: first principles studies on its electronic structure and the effects of benzo-extension, substitution and solvation.

Cyclohepta[]fluorene 1 and its derivatives have received considerable attention due to possible technological applications as molecular devices. Despite efforts from both theory and experiment, the electronic structure of 1 has remained unclear. Herein, we report advanced first-principles calculations on 1 using a multireference and a coupled-cluster method.

Noncanonical Amino Acids in Biocatalysis.

In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. In this review, we will illustrate how the availability of an expanded set of amino acid building blocks has opened a wealth of new opportunities in enzymology and biocatalysis research. Genetic code reprogramming has provided new insights into enzyme mechanisms by allowing introduction of new spectroscopic probes and the targeted replacement of individual atoms or functional groups.

Cooperative AI training for cardiothoracic segmentation in computed tomography: An iterative multi-center annotation approach.

Purpose: Radiological reporting is transitioning to quantitative analysis, requiring large-scale multi-center validation of biomarkers. A major prerequisite and bottleneck for this task is the voxelwise annotation of image data, which is time-consuming for large cohorts. In this study, we propose an iterative training workflow to support and facilitate such segmentation tasks, specifically for high-resolution thoracic CT data.

chARpack: The Chemistry Augmented Reality Package.

Off-loading visualization and interaction into virtual reality (VR) using head-mounted displays (HMDs) has gained considerable popularity in simulation sciences, particularly in chemical modeling. Because of its unique way of immersion, augmented reality (AR) HMD technology has even more potential to be integrated into the everyday workflow of computational chemists. In this work, we present our environment to explore the prospects of AR in chemistry and general molecular sciences: The (chARpack).

POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with V600-mutant melanoma with brain metastasis.

Background: POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with V600-mutant melanoma with asymptomatic brain metastases.

Methods: The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID).

Spectral characterization of human leg EMG signals from an open access dataset for the development of computational models.

Large-scale neuromusculoskeletal models have been used for predicting mechanisms underlying neuromuscular functions in humans. Simulations of such models provide several types of signals of practical interest, such as surface electromyographic signals (EMG), which are compared with experimental data for interpretations of neurophysiological phenomena under study. Specifically, realistic characterization of spectral properties of simulated EMG signals is important for achieving powerful inferences, whereas considerations should be taken for myoelectric signals of different muscles.

DNA Methylation in Ctenophores.

Epigenomic regulation and dynamic DNA methylation, in particular, are widespread mechanisms orchestrating the genome operation across time and species. Whole-genome bisulfite sequencing (WGBS) is currently the only method for unbiasedly capturing the presence of 5-methylcytosine (5-mC) DNA methylation patterns across an entire genome with single-nucleotide resolution. Bisulfite treatment converts unmethylated cytosines to uracils but leaves methylated cytosines intact, thereby creating a map of all methylated cytosines across a genome also known as a methylome.

Gap Junctions in Ctenophora.

Gap junction proteins form specialized intercellular communication channels, including electrical synapses, that regulate cellular metabolism and signaling. We present a molecular inventory of the gap junction proteins-innexins (INX-like) in ctenophores, focusing on two reference species, Pleurobrachia bachei and Mnemiopsis leidyi. Innexins were identified in more than 15 ctenophore species, including such genera as Euplokamis, Pukia, Hormiphora, Bolinopsis, Cestum, Ocyropsis, Dryodora, Beroe, benthic ctenophores, Coeloplana and Vallicula, and undescribed species of Mertensiidae.

Gene Expression Patterns in the Ctenophore Pleurobrachia bachei: In Situ Hybridization.

In situ hybridization is a powerful and precise tool for revealing cell- and tissue-specific gene expression and a critical approach to validating single-cell RNA-seq (scRNA-seq). However, applying it to highly fragile animals such as ctenophores is challenging. Here, we present an in situ hybridization protocol for adult Pleurobrachia bachei (Cydippida)-a notable reference species representing the earliest-branching metazoan lineage, Ctenophora, sister to the rest of Metazoa.

RNA Isolation from Ctenophores.

RNA-seq or transcriptome analysis of individual cells and small cell populations is essential for virtually any biomedical field. Here, we examine and discuss the different methods of RNA isolation specific to ctenophores. We present a convenient, inexpensive, and reproducible protocol for RNA-seq libraries that are designed for low quantities of samples.

DNA Isolation Long-Read Genomic Sequencing in Ctenophores.

Long-read sequencing has proven the necessity for high-quality genomic assemblies of reference species, including enigmatic ctenophores. Obtaining high-molecular-weight genomic DNA is pivotal to this process and has proven highly problematic for many species. Here, we discuss different methodologies for gDNA isolation and present a protocol for isolating gDNA for several members of the phylum Ctenophora.

Air-Stable Dinuclear Complexes of Four-Coordinate Zn and Ni Ions with a Radical Bridge: A Detailed Look at Redox Activity and Antiferromagnetic Coupling.

Air-stable dinuclear complexes [(bmsab)Ni(tmsab)Ni(bmsab)] and [(bmsab)Zn(tmsab)Zn(bmsab)] (bmsab = bis(methanesulfoneamido)benzene, tmsab = tetra(methanesulfonamido)benzene) were prepared via a synthetic route based on heteroleptic precursor complexes. The new complexes combine a distorted tetrahedral coordination environment with an open-shell bridging ligand. The Zn species was subjected to a detailed investigation of the (spectro-)electrochemical processes.

The reduction behavior of sulfurized polyacrylonitrile (SPAN) in lithium-sulfur batteries using a carbonate electrolyte: a computational study.

Lithium-sulfur batteries (LSBs) have attracted attention due to their high theoretical energy density. This and various other advantages, such as the availability and non-toxicity of sulfur, raise interest in LSBs against the background of the energy revolution. However, a polysulfide shuttle mechanism can adversely affect the electrochemical performance of the cell.

Automated image quality assessment for selecting among multiple magnetic resonance image acquisitions in the German National Cohort study.

In magnetic resonance imaging (MRI), the perception of substandard image quality may prompt repetition of the respective image acquisition protocol. Subsequently selecting the preferred high-quality image data from a series of acquisitions can be challenging. An automated workflow may facilitate and improve this selection.

Performance Tests of the Second-Order Approximate Internally Contracted Multireference Coupled-Cluster Singles and Doubles Method icMRCC2.

Benchmark results are presented for the second-order approximation of the internally contracted multireference coupled-cluster method with single and double excitations, icMRCC2 [Köhn, Bargholz, J. Chem. Phys.

Survival Among Veterans Receiving Steroids for Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy.

Importance: Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy.

Objective: To characterize how systemic steroids and steroid timing for irAEs are associated with survival in patients receiving ICI therapy.

Mean inner potential of elemental crystals from density-functional theory calculations: Efficient computation and trends.

The mean inner potential (V) of crystals plays an important role in electron microscopy. In a few cases, it has been measured experimentally, using mostly electron holography; however, it is not uncommon to find reports that disagree by a few volts regarding the mean inner potential of the same material. Different levels of theory have also been used to estimate its value, often by building the crystal as a superposition of isolated atoms or ions-an independent-atom approximation that does not take bonding into account.

The Mean Inner Potential of Hematite α-Fe2O3 Across the Morin Transition.

We measure the mean inner potential (MIP) of hematite, α-Fe2O3, using electron holography and transmission electron microscopy. Since the MIP is sensitive to valence electrons, we propose its use as a chemical bonding parameter for solids. Hematite can test the sensitivity of the MIP as a bonding parameter because of the Morin magnetic phase transition.