Comparisons of Risk Scores for Infective Endocarditis Surgery: A Meta-Analysis.

While multiple scoring systems exist to predict mortality in cardiac surgery, their utility in infective endocarditis (IE) remains uncertain, prompting this study to compare their prognostic accuracy. We conducted a comprehensive review using Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials. Data were pooled using Open-Meta[Analyst] software, and calibration analysis was performed with Review Manager 5.

Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy.

Ionizable lipids are a key component of lipid nanoparticles, the leading nonviral messenger RNA delivery technology. Here, to advance the identification of ionizable lipids beyond current methods, which rely on experimental screening and/or rational design, we introduce lipid optimization using neural networks, a deep-learning strategy for ionizable lipid design. We created a dataset of >9,000 lipid nanoparticle activity measurements and used it to train a directed message-passing neural network for prediction of nucleic acid delivery with diverse lipid structures.

Zwitterionic Polymer-Functionalized Lipid Nanoparticles for the Nebulized Delivery of mRNA.

Lipid nanoparticles (LNPs) have great potential to enable inhaled delivery of mRNA to treat pulmonary diseases. However, this potential has been limited by the challenge of nebulizing the LNPs. Nebulization of LNPs can cause LNPs to aggregate and release encapsulated mRNA, limiting their delivery efficacy.

Sub-cone visual resolution by active, adaptive sampling in the human foveola.

The foveated architecture of the human retina and the eye's mobility enables prime spatial vision, yet the interplay between photoreceptor cell topography and the constant motion of the eye during fixation remains unexplored. With in vivo foveal cone-resolved imaging and simultaneous microscopic photo stimulation, we examined visual acuity in both eyes of 16 participants while precisely recording the stimulus path on the retina. We find that resolution thresholds were correlated with the individual retina's sampling capacity, and exceeded what static sampling limits would predict by 18%, on average.

Inhalable Dry Powders for Lung mRNA Delivery.

Despite great promise, application of mRNA therapeutics in the lung has proven challenging. Many groups have reported success instilling liquid mRNA formulations in animal models, but direct intratracheal administration of large liquid quantities to the human lung presents significant safety and distribution concerns. To accomplish safe and effective mRNA delivery to the lung, formulations must be prepared for dosing via inhalation.

Recent advances in nanoparticulate RNA delivery systems.

Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression.

Cone Density Is Correlated to Outer Segment Length and Retinal Thickness in the Human Foveola.

Purpose: Assessment of the relationship between in vivo foveolar cone density, cone outer segment length (OSL), and foveal retinal thickness (RT).

Methods: Foveolar cone density maps covering the central ±300 µm of the retina were derived from adaptive optics scanning laser ophthalmoscopy images. The corresponding maps of foveal cone OSL and RT were derived from high-resolution optical coherence tomography volume scans.

Combinatorial development of nebulized mRNA delivery formulations for the lungs.

Inhaled delivery of mRNA has the potential to treat a wide variety of diseases. However, nebulized mRNA lipid nanoparticles (LNPs) face several unique challenges including stability during nebulization and penetration through both cellular and extracellular barriers. Here we develop a combinatorial approach addressing these barriers.

Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA.

To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. Here we report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses. We optimized the vaccine by screening a library of 480 biodegradable ionizable lipids with headgroups adjuvanted with cyclic amines and by adjuvanting the mRNA-encoded antigen by fusing it with a natural adjuvant derived from the C3 complement protein.

"Talk and Chalk": An emotion regulation intervention for anger after acquired brain injury.

Uncontrollable anger is a debilitating consequence of acquired brain injury (ABI). This proof-of-concept study investigated the preliminary efficacy of an emotion regulation intervention for managing post-ABI anger. A secondary objective was to determine which participant characteristics were related to intervention gains.

Comparison of Physicochemical Properties of Native Mucus and Reconstituted Mucin Gels.

Simulating native mucus with model systems such as gels made from reconstituted mucin or commercially available polymers presents experimental advantages including greater sample availability and reduced inter- and intradonor heterogeneity. Understanding whether these gels reproduce the complex physical and biochemical properties of native mucus at multiple length scales is critical to building relevant experimental models, but few systematic comparisons have been reported. Here, we compared bulk mechanical properties, microstructure, and biochemical responses of mucus from different niches, reconstituted mucin gels (with similar pH and polymer concentrations as native tissues), and commonly used commercially available polymers.

Cognitive and Behavioral Contributions to Depression Severity, Quality of Life, and Functioning Among People Living With HIV in South Africa.

Cognitive-behavioral treatments for depression typically address both behavioral (e.g., activation) and cognitive (e.

Tailorable Tetrahelical Bundles as a Toolkit for Redox Studies.

Oxidoreductases have evolved over millions of years to perform a variety of metabolic tasks crucial for life. Understanding how these tasks are engineered relies on delivering external electron donors or acceptors to initiate electron transfer reactions. This is a challenge.

Outcomes after resection of primary cardiac sarcoma.

Objective: To evaluate the outcomes of surgical resection of malignant primary cardiovascular tumors.

Methods: From 1983 to 2018, 32 patients underwent surgical resection of malignant primary cardiovascular sarcoma at Cleveland Clinic. Mean age was 48 ± 15 years, and 19 (59%) were women.

Isolated mitral valve endocarditis: Patient, disease, and surgical factors that influence outcomes.

Objective: The objectives of this study were to investigate patient characteristics, valve pathology, bacteriology, and surgical techniques related to outcome of patients who underwent surgery for isolated native (NVE) or prosthetic (PVE) mitral valve endocarditis.

Methods: From January 2002 to January 2020, 447 isolated mitral endocarditis operations were performed, 326 for NVE and 121 for PVE. Multivariable analysis of time-related outcomes used random forest machine learning.

Visualizing Staphylococcus aureus pathogenic membrane modification within the host infection environment by multimodal imaging mass spectrometry.

Bacterial pathogens have evolved virulence factors to colonize, replicate, and disseminate within the vertebrate host. Although there is an expanding body of literature describing how bacterial pathogens regulate their virulence repertoire in response to environmental signals, it is challenging to directly visualize virulence response within the host tissue microenvironment. Multimodal imaging approaches enable visualization of host-pathogen molecular interactions.

Shades of Rage: Applying the Process Model of Emotion Regulation to Managing Anger After Brain Injury.

Uncontrollable anger is common following an acquired brain injury (ABI), with impaired emotion regulation (ER) being one of the main contributors. Existing psychological interventions appear moderately effective, though studies typically include limitations such as small sample sizes, issues of long-term efficacy, and standardization of content. While ER has been a popular research field, the study of ER for anger management after ABI is less well investigated, and contains few interventions based on the widely used Process Model of ER.

Spatial configuration of charge and hydrophobicity tune particle transport through mucus.

Mucus is a selectively permeable hydrogel that protects wet epithelia from pathogen invasion and poses a barrier to drug delivery. Determining the parameters of a particle that promote or prevent passage through mucus is critical, as it will enable predictions about the mucosal passage of pathogens and inform the design of therapeutics. The effect of particle net charge and size on mucosal transport has been characterized using simple model particles; however, predictions of mucosal passage remain challenging.