Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review.

Introduction:  Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra®/Beriplex® P/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data.

Magnetic anisotropy and GGG substrate stray field in YIG films down to millikelvin temperatures.

Quantum magnonics investigates the quantum-mechanical properties of magnons, such as quantum coherence or entanglement for solid-state quantum information technologies at the nanoscale. The most promising material for quantum magnonics is the ferrimagnetic yttrium iron garnet (YIG), which hosts magnons with the longest lifetimes. YIG films of the highest quality are grown on a paramagnetic gadolinium gallium garnet (GGG) substrate.

QSARtuna: An Automated QSAR Modeling Platform for Molecular Property Prediction in Drug Design.

Machine-learning (ML) and deep-learning (DL) approaches to predict the molecular properties of small molecules are increasingly deployed within the design-make-test-analyze (DMTA) drug design cycle to predict molecular properties of interest. Despite this uptake, there are only a few automated packages to aid their development and deployment that also support uncertainty estimation, model explainability, and other key aspects of model usage. This represents a key unmet need within the field, and the large number of molecular representations and algorithms (and associated parameters) means it is nontrivial to robustly optimize, evaluate, reproduce, and deploy models.

Pediatric Consent on FHIR.

Background:  Standardizing and formalizing consent processes and forms can prevent ambiguities, convey a more precise meaning, and support machine interpretation of consent terms.

Objectives:  Our goal was to introduce a systematic approach to standardizing and digitizing pediatric consent forms, which are complex due to legal requirements for child and legal guardian involvement.

Methods:  First, we reviewed the consent requirements from the Arizona regulation, and we used 21 pediatric treatment consents from five Arizona health care organizations to propose and evaluate an implementation-agnostic Consent for Treatment Framework.

Reinvent 4: Modern AI-driven generative molecule design.

REINVENT 4 is a modern open-source generative AI framework for the design of small molecules. The software utilizes recurrent neural networks and transformer architectures to drive molecule generation. These generators are seamlessly embedded within the general machine learning optimization algorithms, transfer learning, reinforcement learning and curriculum learning.

Frontal sinus approach in complicated chronic rhinosinusitis with nasal polyps: Our experience.

Background: Hyperostosis is a common consequence of chronic rhinosinusitis with nasal polyps (CRSwNP) and other chronic rhinosinusitis, affecting mainly structures of the ethmoid labyrinth, frontal and maxillary sinuses. These neo-bones are found in advanced stages of rhinosinusitis causes exacerbation because of ostia outflow blockage. Frequent relapses of the disease due to hyperostosis restenosis, represent a problem in the treatment of chronic frontal sinusitis.

Tough Bioplastics from Babassu Oil-Based Acrylic Monomer, Hemicellulose Xylan, and Carnauba Wax.

We describe here the fabrication, characterization, and properties of tough bioplastics made of a babassu oil-based acrylic polymer (PBBM), hemicellulose xylan grafted with PBBM chains, and carnauba wax (CW). The plastic was primarily designed to obtain bioderived materials that can replace low-density polyethylene (LDPE) in certain food packaging applications. To obtain plastic, the radical polymerization of an original babassu oil-based acrylic monomer (BBM) in the presence of xylan macromolecules modified with maleic anhydride (X-MA) was conducted.

Closing the Cycle as It Begins: Synthesis of ortho-Iodobiaryls via Catellani Reaction.

Despite the advances in the field of carbon-halogen bond formation, the straightforward catalytic access to selectively functionalized iodoaryls remains a challenge. Here, we report a one-pot synthesis of ortho-iodobiaryls from aryl iodides and bromides by palladium/norbornene catalysis. This new example of Catellani reaction features the initial cleavage of a C(sp )-I bond, followed by the key formation of a palladacycle through ortho C-H activation, the oxidative addition of an aryl bromide and the ultimate restoration of the C(sp )-I bond.

Human-in-the-loop assisted de novo molecular design.

A de novo molecular design workflow can be used together with technologies such as reinforcement learning to navigate the chemical space. A bottleneck in the workflow that remains to be solved is how to integrate human feedback in the exploration of the chemical space to optimize molecules. A human drug designer still needs to design the goal, expressed as a scoring function for the molecules that captures the designer's implicit knowledge about the optimization task.

Plant Oil-Based Acrylic Latexes towards Multisubstrate Bonding Adhesives Applications.

To investigate the utility of acrylic monomers from various plant oils in adhesives manufacturing, 25-45 wt. % of high oleic soybean oil-based monomer (HOSBM) was copolymerized in a miniemulsion with commercially applied butyl acrylate (BA), methyl methacrylate (MMA), or styrene (St). The compositions of the resulting ternary latex copolymers were varied in terms of both "soft" (HOSBM, BA) and "rigid" (MMA or St) macromolecular fragments, while total monomer conversion and molecular weight of copolymers were determined after synthesis.

Implications of Additivity and Nonadditivity for Machine Learning and Deep Learning Models in Drug Design.

Matched molecular pairs (MMPs) are nowadays a commonly applied concept in drug design. They are used in many computational tools for structure-activity relationship analysis, biological activity prediction, or optimization of physicochemical properties. However, until now it has not been shown in a rigorous way that MMPs, that is, changing only one substituent between two molecules, can be predicted with higher accuracy and precision in contrast to any other chemical compound pair.

Tubular electrosynthesis of silica-coated magnetite and evaluation of magnetic nanobiocatalyst efficacy during biomass hydrolysis.

Magnetic nanobiocatalysts (MNBCs) are a promising immobilization approach to ease enzyme recovery during bioprocessing. However, industrial adoption of MNBCs is unfeasible because MNBC-synthesis involves complex and potentially expensive processing steps including synthesis of silica-coated superparamagnetic iron oxide nanoparticles (Si-SPIONs). We developed a single-step process for Si-SPION synthesis using a tubular electrochemical system (TES) and investigated the effect of concentration of the NaSiO coating agent on Si-SPION properties.

Effect of Fatty Acid Polyunsaturation on Synthesis and Properties of Emulsion Polymers Based on Plant Oil-Based Acrylic Monomers.

This study demonstrated that polymerization behavior of plant oil-based acrylic monomers (POBMs) synthesized in one-step transesterification reaction from naturally rich in oleic acid olive, canola, and high-oleic soybean oils is associated with a varying mass fraction of polyunsaturated fatty acid fragments (linoleic (C18:2) and linolenic (C18:3) acid esters) in plant oil. Using miniemulsion polymerization, a range of stable copolymer latexes was synthesized from 60 wt.% of each POBM and styrene to determine the impact of POBM chemical composition (polyunsaturation) on thermal and mechanical properties of the resulted polymeric materials.

Synergistic Behavior of Plant Proteins and Biobased Latexes in Bioplastic Food Packaging Materials: Experimental and Machine Learning Study.

Plant-based proteins are attractive components which may serve as sustainable alternatives to current petrochemical products. Both soy protein and major corn protein, zein, are of interest in food packaging applications due to their sustainability, biodegradation properties, and inherent physicochemical properties. This study discusses the development of bioplastic materials, where it explores the effects of combining zein, soy protein, and plasticizing latexes derived from plant oil-based monomers (POBMs) on properties of resulting bioplastic films.

Hybrid Metal-Dielectric-Metal Sandwiches for SERS Applications.

The development of efficient plasmonic nanostructures with controlled and reproducible surface-enhanced Raman spectroscopy (SERS) signals is an important task for the evolution of ultrasensitive sensor-related methods. One of the methods to improving the characteristics of nanostructures is the development of hybrid structures that include several types of materials. Here, we experimentally investigate ultrathin gold films (3-9 nm) near the percolation threshold on Si/Au/SiO and Si/Au/SiO/graphene multilayer structures.

Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions.

The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.

DockStream: a docking wrapper to enhance de novo molecular design.

Recently, we have released the de novo design platform REINVENT in version 2.0. This improved and extended iteration supports far more features and scoring function components, which allows bespoke and tailor-made protocols to maximize impact in small molecule drug discovery projects.

Two-dimensional array of iron-garnet nanocylinders supporting localized and lattice modes for the broadband boosted magneto-optics.

We demonstrate a novel all-dielectric magnetophotonic structure that consists of two-dimensional arrays of bismuth substituted iron-garnet nanocylinders supporting both localized (Fabry-Perot-like) and lattice (guided-like) optical modes. Simultaneous excitation of the two kinds of modes provides a significant enhancement of the Faraday effect by 3 times and transverse magneto-optical Kerr effect by an order of magnitude compared to the smooth magnetic film of the same effective thickness. Both magneto-optical effects are boosted in wide spectral and angular ranges making the nanocylinder array magnetic dielectric structures promising for applications with short and tightly focused laser pulses.

Optical Constants and Structural Properties of Epitaxial MoS Monolayers.

Two-dimensional layers of transition-metal dichalcogenides (TMDs) have been widely studied owing to their exciting potential for applications in advanced electronic and optoelectronic devices. Typically, monolayers of TMDs are produced either by mechanical exfoliation or chemical vapor deposition (CVD). While the former produces high-quality flakes with a size limited to a few micrometers, the latter gives large-area layers but with a nonuniform surface resulting from multiple defects and randomly oriented domains.

Optical Constants of Chemical Vapor Deposited Graphene for Photonic Applications.

Graphene is a promising building block material for developing novel photonic and optoelectronic devices. Here, we report a comprehensive experimental study of chemical-vapor deposited (CVD) monolayer graphene's optical properties on three different substrates for ultraviolet, visible, and near-infrared spectral ranges (from 240 to 1000 nm). Importantly, our ellipsometric measurements are free from the assumptions of additional nanometer-thick layers of water or other media.

Glucan Conversion and Membrane Recovery of Biomimetic Cellulosomes During Lignocellulosic Biomass Hydrolysis.

Enzyme immobilization has been identified as one way to recycle enzymes and reduce processing costs during enzymatic hydrolysis of lignocellulosic materials. However, most immobilization methods have not been attractive to lignocellulosic processing plants. In this study, cellulase enzymes were attached to a copolymer of glycidyl methacrylate (GMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) to make polymer-enzyme conjugates (PECs) and facilitate recovery using a 50-kDa molecular weight cutoff membrane.

Article-Level Metrics.

In the era of digitization and Open Access, article-level metrics are increasingly employed to distinguish influential research works and adjust research management strategies. Tagging individual articles with digital object identifiers allows exposing them to numerous channels of scholarly communication and quantifying related activities. The aim of this article was to overview currently available article-level metrics and highlight their advantages and limitations.

Environment-Sensitive Polymeric Micelles Encapsulating SN-38 Potently Suppress Growth of Neuroblastoma Cells Exhibiting Intrinsic and Acquired Drug Resistance.

Conventional treatment approaches fail to provide durable control over aggressive malignancies due to intrinsic or acquired drug resistance characteristic of high-risk disease. SN-38, a potent camptothecin analog specifically targeting DNA topoisomerase I cleavage complexes, has shown promise in preclinical studies against aggressive solid tumors. However, its clinical utility is limited by inadequate solubility in pharmaceutically acceptable vehicles and by poor chemical and metabolic stability.

Human Locomotion Strategies Under Changed Bodyweight Support.

The aim of this study was the analysis of human musculoskeletal system energy costs of normal walking and walking under reduced weight loading. There were 15 subjects who participated in the study. We analyzed the biomechanical parameters of walking under different musculoskeletal system loads.