Intersectional inequities in maternal mortality: Examining the compounded risks for black birthing individuals with physical disabilities.

Background: People who are Black and have physical disabilities likely face a dual burden of risk for maternal mortality due to enduring systemic oppression rooted in racism and ableism.

Objective: To investigate maternal mortality risks among Black birthing individuals with physical disabilities in the United States and assess the potential compounding effect when these marginalized identities intersect.

Methods: We conducted a historical cohort study using the 2004-2021 Healthcare Cost and Utilization Project Nationwide Inpatient Sample.

Identifying Artifacts from Large Library Docking.

While large library docking has discovered potent ligands for multiple targets, as the libraries have grown the hit lists can become dominated by rare artifacts that cheat our scoring functions. Here, we investigate rescoring top-ranked docked molecules with orthogonal methods to identify these artifacts, exploring implicit solvent models and absolute binding free energy perturbation as cross-filters. In retrospective studies, this approach deprioritized high-ranking nonbinders for nine targets while leaving true ligands relatively unaffected.

Identifying Artifacts from Large Library Docking.

While large library docking has discovered potent ligands for multiple targets, as the libraries have grown, the very top of the hit-lists can become populated with artifacts that cheat our scoring functions. Though these cheating molecules are rare, they become ever-more dominant with library growth. Here, we investigate rescoring top-ranked molecules from docking screens with orthogonal methods to identify these artifacts, exploring implicit solvent models and absolute binding free energy perturbation (AB-FEP) as cross-filters.

Shape-Based Virtual Screening of a Billion-Compound Library Identifies Mycobacterial Lipoamide Dehydrogenase Inhibitors.

Lpd (lipoamide dehydrogenase) in (Mtb) is required for virulence and is a genetically validated tuberculosis (TB) target. Numerous screens have been performed over the last decade, yet only two inhibitor series have been identified. Recent advances in large-scale virtual screening methods combined with make-on-demand compound libraries have shown the potential for finding novel hits.

Cardiac Amyloidosis Imaging, Part 3: Interpretation, Diagnosis, and Treatment.

Cardiac amyloidosis was thought to be rare, undiagnosable, and incurable. However, recently it has been discovered to be common, diagnosable, and treatable. This knowledge has led to a resurgence in nuclear imaging with Tc-pyrophosphate-a scan once believed to be extinct-to identify cardiac amyloidosis, particularly in patients with heart failure but preserved ejection fraction.

Cardiac Amyloidosis Imaging, Part 1: Amyloidosis Etiology and Image Acquisition.

Cardiac amyloidosis is a systemic form of amyloidosis in which protein-based infiltrates are deposited in myocardial extracellular space. The accumulation of amyloid fibrils causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Until recently, cardiac amyloidosis was considered rare.

Cardiac Amyloidosis Imaging, Part 2: Quantification and Technical Considerations.

Tc-pyrophosphate imaging has been around for a long time. In the 1970s, it was used to image recent myocardial infarction. However, it has recently been recognized for its value in detecting cardiac amyloidosis, leading to widespread use across the United States.

Enhancing Hit Discovery in Virtual Screening through Absolute Protein-Ligand Binding Free-Energy Calculations.

In the hit identification stage of drug discovery, a diverse chemical space needs to be explored to identify initial hits. Contrary to empirical scoring functions, absolute protein-ligand binding free-energy perturbation (ABFEP) provides a theoretically more rigorous and accurate description of protein-ligand binding thermodynamics and could, in principle, greatly improve the hit rates in virtual screening. In this work, we describe an implementation of an accurate and reliable ABFEP method in FEP+.

A methodology for the systematic identification of naturally occurring radioactive materials (NORM).

Naturally occurring radioactive materials (NORM) are present worldwide and under certain circumstances (e.g., human activities) may give radiation exposure to workers, local public or occasional visitors and non-human biota (NHB) of the surrounding ecosystems.

Epik: p and Protonation State Prediction through Machine Learning.

Epik version 7 is a software program that uses machine learning for predicting the p values and protonation state distribution of complex, druglike molecules. Using an ensemble of atomic graph convolutional neural networks (GCNNs) trained on over 42,000 p values across broad chemical space from both experimental and computed origins, the model predicts p values with 0.42 and 0.

Benchmarking Refined and Unrefined AlphaFold2 Structures for Hit Discovery.

The recently developed AlphaFold2 (AF2) algorithm predicts proteins' 3D structures from amino acid sequences. The open AlphaFold protein structure database covers the complete human proteome. Using an industry-leading molecular docking method (Glide), we investigated the virtual screening performance of 37 common drug targets, each with an AF2 structure and known and structures from the DUD-E data set.

Proficiency test data interpretation and data rejection.

An extension to the interpretation, evaluation and visualisation of radioactivity proficiency test exercises (PTEs) are presented in this paper. In addition to the use of the ζ- and z-tests, a test for acceptance of relative uncertainties is introduced, the R-test, along with an overall performance score and additional data visualisation using modified Naji- and Pom-plots. Additionally, 'improbable deviations' are identified using a simple test.

An Intelligent System to Enhance the Performance of Brain Tumor Diagnosis from MR Images.

In the human body, cancer is caused by aberrant cell proliferation. Brain tumors are created when cells in the human brain proliferate out of control. Brain tumors consist of two types: benign and malignant.

Illness Incidence, Psychological Characteristics, and Sleep in Dogsled Drivers During the Iditarod Trail Sled Dog Race.

Introduction: Every March, dogsled drivers (mushers) compete in a 1569-km race across Alaska, involving physical exertion, mental exertion, and sleep deprivation for up to 2 wk. These factors may increase mushers' vulnerability to illness, making them a relevant study population for acute infection risk factors. Specifically, the influence of psychological factors on illness risk during prolonged physical exertion has rarely been investigated.

Efficient Exploration of Chemical Space with Docking and Deep Learning.

With the advent of make-on-demand commercial libraries, the number of purchasable compounds available for virtual screening and assay has grown explosively in recent years, with several libraries eclipsing one billion compounds. Today's screening libraries are larger and more diverse, enabling the discovery of more-potent hit compounds and unlocking new areas of chemical space, represented by new core scaffolds. Applying physics-based in silico screening methods in an exhaustive manner, where every molecule in the library must be enumerated and evaluated independently, is increasingly cost-prohibitive.

Sled dogs as a model for PM2.5 exposure from wildfires in Alaska.

Particulate matter 2.5 (PM2.5) exposure induces oxidative stress associated with many negative health outcomes such as respiratory disorders, cardiovascular disease and neurodegenerative disease.

Review of COVID-19 Myocarditis in Competitive Athletes: Legitimate Concern or Fake News?

Since the first reported case of COVID-19 in December 2019, the global landscape has shifted toward an unrecognizable paradigm. The sports world has not been immune to these ramifications; all major sports leagues have had abbreviated seasons, fan attendance has been eradicated, and athletes have opted out of entire seasons. For these athletes, cardiovascular complications of COVID-19 are particularly concerning, as myocarditis has been implicated in a significant portion of sudden cardiac death (SCD) in athletes (up to 22%).

Elucidating the structural, anticancer, and antibacterial traits of Punica granatum peel extracts-mediated Ag and Ag/GO nanocomposites.

Ag nanoparticles and Ag/GO nanocomposites have been synthesized by facile, eco-friendly, and cost-effective green approach using the peel extracts of Punica granatum. The synthesized Silver Nanoparticles and Silver Graphene Oxide nanocomposites were characterized by UV-visible spectroscopy, X-ray diffraction, transmission electron microscopy, and Fourier transform infrared analysis. AgNPs revealed spherical morphology with particle size ranging from 30 to 40 nm.

Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding.

We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking, rigid receptor docking, and protein structure prediction with explicit solvent molecular dynamics simulations. This novel methodology in detailed retrospective and prospective testing succeeded to determine protein-ligand binding modes with a root-mean-square deviation within 2.5 Å in over 90% of cross-docking cases.

Worldwide Variation in the Use of Nuclear Cardiology Camera Technology, Reconstruction Software, and Imaging Protocols.

Objectives: This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED).

Background: Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols.

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS.

Objectives: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

Background: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries.

Impact of Different Automated Binding Pose Generation Approaches on Relative Binding Free Energy Simulations.

Relative binding free energy (RBFE) prediction methods such as free energy perturbation (FEP) are important today for estimating protein-ligand binding affinities. Significant hardware and algorithmic improvements now allow for simulating congeneric series within days. Therefore, RBFE calculations have an enormous potential for structure-based drug discovery.

Dual energy CT: a step ahead in brain and spine imaging.

Objective: The purpose of this pictorial essay is to illustrate the utility of dual energy CT as an adjunct or alternative to routine single energy CT (SECT) scan of the brain and spine in emergency neuroradiology practice.

Conclusion: Dual energy CT can be used as a problem-solving tool in brain and spine imaging. It enables one to make a confident and accurate diagnosis for a variety of clinical conditions thereby impacting patient management.

Half-life determination and comparison of activity standards of Pa.

The results of an international comparison of activity measurements of a solution of Pa are reported and analysed. Prior to this, no known standardisation of Pa by activity measurement had been carried out. The comparison was run in 2017-2018 involving eight laboratories, and returned results with no identifiable inconsistencies between methods or laboratories.