Measures of preoperative anxiety: Part two.

The current literature indicates that routine evaluation of preoperative anxiety, its determinants, and patient-specific concerns is universally advocated. This aligns with the increasingly acknowledged importance of prehabilitation - a comprehensive process preparing patients for surgery. A crucial component of prehabilitation is assessing patients' mental health.

Computationally restoring the potency of a clinical antibody against Omicron.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs and revealed how quickly viral escape can curtail effective options. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination and is challenging to replace with existing approaches.

Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-Based Featurization Method.

Protein-ligand interactions are essential to drug discovery and drug development efforts. Desirable on-target or multitarget interactions are the first step in finding an effective therapeutic, while undesirable off-target interactions are the first step in assessing safety. In this work, we introduce a novel ligand-based featurization and mapping of human protein pockets to identify closely related protein targets and to project novel drugs into a hybrid protein-ligand feature space to identify their likely protein interactions.

A Computational Pipeline to Identify and Characterize Binding Sites and Interacting Chemotypes in SARS-CoV-2.

Minimizing the human and economic costs of the COVID-19 pandemic and future pandemics requires the ability to develop and deploy effective treatments for novel pathogens as soon as possible after they emerge. To this end, we introduce a new computational pipeline for the rapid identification and characterization of binding sites in viral proteins along with the key chemical features, which we call chemotypes, of the compounds predicted to interact with those same sites. The composition of source organisms for the structural models associated with an individual binding site is used to assess the site's degree of structural conservation across different species, including other viruses and humans.

Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs, but also revealed how quickly viral escape can curtail effective options. With the emergence of the SARS-CoV-2 Omicron variant in late 2021, many clinically used antibody drug products lost potency, including Evusheld and its constituent, cilgavimab. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination and is challenging to replace with existing approaches.

PDBspheres: a method for finding 3D similarities in local regions in proteins.

We present a structure-based method for finding and evaluating structural similarities in protein regions relevant to ligand binding. PDBspheres comprises an exhaustive library of protein structure regions ('spheres') adjacent to complexed ligands derived from the Protein Data Bank (PDB), along with methods to find and evaluate structural matches between a protein of interest and spheres in the library. PDBspheres uses the LGA (Local-Global Alignment) structure alignment algorithm as the main engine for detecting structural similarities between the protein of interest and template spheres from the library, which currently contains >2 million spheres.

Large-scale application of free energy perturbation calculations for antibody design.

Alchemical free energy perturbation (FEP) is a rigorous and powerful technique to calculate the free energy difference between distinct chemical systems. Here we report our implementation of automated large-scale FEP calculations, using the Amber software package, to facilitate antibody design and evaluation. In combination with Hamiltonian replica exchange, our FEP simulations aim to predict the effect of mutations on both the binding affinity and the structural stability.

Discovery of Small-Molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline.

A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 in Wuhan, China and reached most corners of the globe in less than two months. In just over a year since the initial infections, COVID-19 infected almost 100 million people worldwide.

Improved Protein-Ligand Binding Affinity Prediction with Structure-Based Deep Fusion Inference.

Predicting accurate protein-ligand binding affinities is an important task in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite the recent advances in the application of deep convolutional and graph neural network-based approaches, it remains unclear what the relative advantages of each approach are and how they compare with physics-based methodologies that have found more mainstream success in virtual screening pipelines. We present fusion models that combine features and inference from complementary representations to improve binding affinity prediction.

Single Amino Acid Mutations Affect Zika Virus Replication In Vitro and Virulence In Vivo.

The 2014-2016 Zika virus (ZIKV) epidemic in the Americas resulted in large deposits of next-generation sequencing data from clinical samples. This resource was mined to identify emerging mutations and trends in mutations as the outbreak progressed over time. Information on transmission dynamics, prevalence, and persistence of intra-host mutants, and the position of a mutation on a protein were then used to prioritize 544 reported mutations based on their ability to impact ZIKV phenotype.

Factors Associated with High Preoperative Anxiety: Results from Cluster Analysis.

Background: Preoperative anxiety is a common patients' reaction related to serious adverse events post-operatively. The aim was to explore the characteristics of cardiac surgery patients experiencing high preoperative anxiety.

Methods: A total of 127 patients (mean age 64.

Multiscale analysis for patterns of Zika virus genotype emergence, spread, and consequence.

The question of how Zika virus (ZIKV) changed from a seemingly mild virus to a human pathogen capable of microcephaly and sexual transmission remains unanswered. The unexpected emergence of ZIKV's pathogenicity and capacity for sexual transmission may be due to genetic changes, and future changes in phenotype may continue to occur as the virus expands its geographic range. Alternatively, the sheer size of the 2015-16 epidemic may have brought attention to a pre-existing virulent ZIKV phenotype in a highly susceptible population.

Measures of preoperative anxiety.

The evaluation of treatment from the patient's perspective (Patient Reported Outcomes, PROs) currently remains one of the most vibrant and dynamically developing fields of research. Among PROs, patient self-assessment of various symptoms, including one's psychological state, is of great importance. Anxiety is one of the most frequently observed psychological reactions among patients awaiting various surgeries, and may occur even in up to 80% of patients scheduled for high-risk surgical procedures.

Sendai virus intra-host population dynamics and host immunocompetence influence viral virulence during passage.

serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during passage.

Microbial mercury methylation in Antarctic sea ice.

Atmospheric deposition of mercury onto sea ice and circumpolar sea water provides mercury for microbial methylation, and contributes to the bioaccumulation of the potent neurotoxin methylmercury in the marine food web. Little is known about the abiotic and biotic controls on microbial mercury methylation in polar marine systems. However, mercury methylation is known to occur alongside photochemical and microbial mercury reduction and subsequent volatilization.

Identification of Genome-Wide Mutations in Ciprofloxacin-Resistant F. tularensis LVS Using Whole Genome Tiling Arrays and Next Generation Sequencing.

Francisella tularensis is classified as a Class A bioterrorism agent by the U.S. government due to its high virulence and the ease with which it can be spread as an aerosol.

Light Regimes Shape Utilization of Extracellular Organic C and N in a Cyanobacterial Biofilm.

Unlabelled: Although it is becoming clear that many microbial primary producers can also play a role as organic consumers, we know very little about the metabolic regulation of photoautotroph organic matter consumption. Cyanobacteria in phototrophic biofilms can reuse extracellular organic carbon, but the metabolic drivers of extracellular processes are surprisingly complex. We investigated the metabolic foundations of organic matter reuse by comparing exoproteome composition and incorporation of (13)C-labeled and (15)N-labeled cyanobacterial extracellular organic matter (EOM) in a unicyanobacterial biofilm incubated using different light regimes.

Identification of a novel drug lead that inhibits HCV infection and cell-to-cell transmission by targeting the HCV E2 glycoprotein.

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2's interaction with different host factors.

GeneSV - an Approach to Help Characterize Possible Variations in Genomic and Protein Sequences.

A computational approach for identification and assessment of genomic sequence variability (GeneSV) is described. For a given nucleotide sequence, GeneSV collects information about the permissible nucleotide variability (changes that potentially preserve function) observed in corresponding regions in genomic sequences, and combines it with conservation/variability results from protein sequence and structure-based analyses of evaluated protein coding regions. GeneSV was used to predict effects (functional vs.

Rapid countermeasure discovery against Francisella tularensis based on a metabolic network reconstruction.

In the future, we may be faced with the need to provide treatment for an emergent biological threat against which existing vaccines and drugs have limited efficacy or availability. To prepare for this eventuality, our objective was to use a metabolic network-based approach to rapidly identify potential drug targets and prospectively screen and validate novel small-molecule antimicrobials. Our target organism was the fully virulent Francisella tularensis subspecies tularensis Schu S4 strain, a highly infectious intracellular pathogen that is the causative agent of tularemia and is classified as a category A biological agent by the Centers for Disease Control and Prevention.

A strain of Yersinia pestis with a mutator phenotype from the Republic of Georgia.

We describe here a strain of Yersinia pestis, G1670A, which exhibits a baseline mutation rate elevated 250-fold over wild-type Y. pestis. The responsible mutation, a C to T substitution in the mutS gene, results in the transition of a highly conserved leucine at position 689 to arginine (mutS(L689R)).

The role of viral population diversity in adaptation of bovine coronavirus to new host environments.

The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens.