Navigating COPD in Aging Populations: Insights Into Pathophysiology and Comprehensive Care.

Chronic obstructive pulmonary disease (COPD) poses a significant and growing health burden among aging populations, marked by increasing prevalence and complex management challenges specific to elderly patients. This review explores the multifaceted interplay between COPD and aging, highlighting overlapping pathophysiological processes and comorbidities that complicate diagnosis and treatment. We examine age-specific management strategies, emphasizing the need for tailored approaches that account for the unique physical, cognitive, and health-related quality of life impacts on older adults.

Pulmonary hypertension in chronic obstructive pulmonary disease: current understanding, knowledge gaps and future directions.

Purpose Of Review: Despite the advent of effective and mechanistically diverse treatments for pulmonary arterial hypertension (PAH) and their positive impacts on the functional capacities and outcomes for PAH patients, the much larger population of patients with pulmonary hypertension (PH) in chronic lung diseases like chronic obstructive pulmonary disease (PH-COPD) remain without effective therapies.

Recent Findings: In this review, we will highlight advances in the understanding of PH-COPD pathobiology, the clinical impact comorbid PH has on COPD outcomes, and detail the spectrum of disease and clinical phenotypes that encompass the heterogenous disease manifestations of PH-COPD. Finally, we will examine recent studies exploring the effects of potential treatments for PH-COPD and highlight sub-populations and treatment options that warrant further study.

Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

Research Question: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19?

Background: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections.

Ageing and chronic obstructive pulmonary disease: interrelationships.

Purpose Of Review: As life expectancy increases, the ageing population accrues an increasing burden of chronic conditions and functional compromise. Some conditions that lead to compromise are deemed part of 'natural ageing,' whereas others are considered to represent disease processes. Ageing ('a natural process') and chronic obstructive pulmonary disease ('a disease') share many common features, both pulmonary and systemic.

Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer: Real-World Incidence, Risk Factors, and Management Practices Across Six Health Care Centers in North Carolina.

Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer and have expanded use in small cell lung cancer. Although generally better tolerated than traditional chemotherapy, immune-related adverse events, such as immune checkpoint inhibitor-related pneumonitis (ICI-P), remain poorly understood toxicities that limit ICI treatment and can result in considerable morbidity. In this retrospective case-control study, we assessed a lung cancer cohort to identify ICI-P risk factors.

Treatment with a monoclonal antibody against methamphetamine and amphetamine reduces maternal and fetal rat brain concentrations in late pregnancy.

We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v.

A novel N-terminal domain may dictate the glucose response of Mondo proteins.

Glucose is a fundamental energy source for both prokaryotes and eukaryotes. The balance between glucose utilization and storage is integral for proper energy homeostasis, and defects are associated with several diseases, e.g.

Brain cancer prognosis: independent validation of a clinical bioinformatics approach.

Translational and evidence based medicine can take advantage of biotechnology advances that offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. The clinical information hidden in these data can be clarified with clinical bioinformatics approaches. We have recently proposed a method to analyze different layers of high-throughput (omic) data to preserve the emergent properties that appear in the cellular system when all molecular levels are interacting.

Monoclonal antibodies as pharmacokinetic antagonists for the treatment of (+)-methamphetamine addiction.

Developing specific medications to treat (+)-methamphetamine (METH) addiction is a difficult challenge because METH has multiple sites of action that are intertwined with normal neurological function. As a result, no small molecule medication for the treatment of METH addiction has made it through the FDA clinical trials process. With the invention of a new generation of proteinbased therapies, it is now possible to consider treating drug addiction by an entirely different approach.

Phylogenetic analysis and classification of the fungal bHLH domain.

The basic Helix-Loop-Helix (bHLH) domain is an essential highly conserved DNA-binding domain found in many transcription factors in all eukaryotic organisms. The bHLH domain has been well studied in the Animal and Plant Kingdoms but has yet to be characterized within Fungi. Herein, we obtained and evaluated the phylogenetic relationship of 490 fungal-specific bHLH containing proteins from 55 whole genome projects composed of 49 Ascomycota and 6 Basidiomycota organisms.

Evolution of the Max and Mlx networks in animals.

Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation.

Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems.

Background: Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular levels (genomic, transcriptional, etc.) separately.

Site-specific evolutionary rates in proteins are better modeled as non-independent and strictly relative.

Motivation: In a nucleotide or amino acid sequence, not all sites evolve at the same rate, due to differing selective constraints at each site. Currently in computational molecular evolution, models incorporating rate heterogeneity always share two assumptions. First, the rate of evolution at each site is assumed to be independent of every other site.

Biochemical and functional evidence of p53 homology is inconsistent with molecular phylogenetics for distant sequences.

The tumor suppressor p53 is mutated in approximately 50% of all human cancer cases worldwide. It is commonly assumed that the phylogenetic history of this important tumor suppressor has been thoroughly studied; however, few detailed studies of the entire extended p53 protein family have been reported, and none comprehensively and simultaneously consider functional, molecular, and phylogenetic data. Herein we examine a diverse collection of reported p53-like protein sequences, including representatives from the arthropods, nematodes, and protists, with the goal of answering several important questions.

Hepatic endopolyploidy as a cellular consequence of age-specific selection for rate of development in mice.

Endopolyploidy is the generation of polyploid cells by DNA replication without subsequent cell division and is correlated with hypertrophic growth or growth via cell size. Thus, selection that alters growth may also change onset and frequency of endopolyploidy as a correlated response. We search for endopolyploidy in the liver in response to age-specific restricted index selection for the rate of development.

Development and preclinical testing of a high-affinity single-chain antibody against (+)-methamphetamine.

Chronic or excessive (+)-methamphetamine (METH) use often leads to addiction and toxicity to critical organs like the brain. With medical treatment as a goal, a novel single-chain variable fragment (scFv) against METH was engineered from anti-METH monoclonal antibody mAb6H4 (IgG, kappa light chain, K(d) = 11 nM) and found to have similar ligand affinity (K(d) = 10 nM) and specificity as mAb6H4. The anti-METH scFv (scFv6H4) was cloned, expressed in yeast, purified, and formulated as a naturally occurring mixture of monomer ( approximately 75%) and dimer ( approximately 25%).

Application of complex demodulation on bZIP and bHLH-PAS protein domains.

Proteins are built with molecular modular building blocks such as an alpha-helix, beta-sheet, loop region and other structures. This is an economical way of constructing complex molecules. Periodicity analysis of protein sequences has allowed us to obtain meaningful information concerning their structure, function and evolution.

Molecular architecture of the DNA-binding region and its relationship to classification of basic helix-loop-helix proteins.

Multivariate statistical analyses are used to explore the molecular architecture of the DNA-binding and dimerization regions of basic helix-loop-helix (bHLH) proteins. Alphabetic amino acid data are transformed to biologically meaningful quantitative values using a set of 5 multivariate "indices." These multivariate indices summarize variation in a large suite of amino acid physiochemical attributes and reflect variability in polarity-accessibility-hydrophobicity, propensity for secondary structure, molecular size, codon composition, and electrostatic charge.

Gaussian quadrature formulae for arbitrary positive measures.

We present computational methods and subroutines to compute Gaussian quadrature integration formulas for arbitrary positive measures. For expensive integrands that can be factored into well-known forms, Gaussian quadrature schemes allow for efficient evaluation of high-accuracy and -precision numerical integrals, especially compared to general ad hoc schemes. In addition, for certain well-known density measures (the normal, gamma, log-normal, Student's t, inverse-gamma, beta, and Fisher's F) we present exact formulae for computing the respective quadrature scheme.

Spectral analysis of sequence variability in basic-helix-loop-helix (bHLH) protein domains.

The basic helix-loop-helix (bHLH) family of transcription factors is used as a paradigm to explore structural implications of periodicity patterns in amino acid sequence variability. A Boltzmann-Shannon entropy profile represents site-by-site amino acid variation in the bHLH domain. Spectral analysis of almost 200 bHLH sequences documents the periodic nature of the bHLH sequence variation.

Networks of coevolving sites in structural and functional domains of serpin proteins.

Amino acids do not occur randomly in proteins; rather, their occurrence at any given site is strongly influenced by the amino acid composition at other sites, the structural and functional aspects of the region of the protein in which they occur, and the evolutionary history of the protein. The goal of our research study is to identify networks of coevolving sites within the serpin proteins (serine protease inhibitors) and classify them as being caused by structural-functional constraints or by evolutionary history. To address this, a matrix of pairwise normalized mutual information (NMI) values was computed among amino acid sites for the serpin proteins.

Sequence signatures and the probabilistic identification of proteins in the Myc-Max-Mad network.

Accurate identification of specific groups of proteins by their amino acid sequence is an important goal in genome research. Here we combine information theory with fuzzy logic search procedures to identify sequence signatures or predictive motifs for members of the Myc-Max-Mad transcription factor network. Myc is a well known oncoprotein, and this family is involved in cell proliferation, apoptosis, and differentiation.

Solving the protein sequence metric problem.

Biological sequences are composed of long strings of alphabetic letters rather than arrays of numerical values. Lack of a natural underlying metric for comparing such alphabetic data significantly inhibits sophisticated statistical analyses of sequences, modeling structural and functional aspects of proteins, and related problems. Herein, we use multivariate statistical analyses on almost 500 amino acid attributes to produce a small set of highly interpretable numeric patterns of amino acid variability.