Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.

The pathobiont Staphylococcus aureus (Sa) induces nonprotective antibody imprints that underlie ineffective staphylococcal vaccination. However, the mechanism by which Sa modifies antibody activity is not clear. Herein, we demonstrate that IL-10 is the decisive factor that abrogates antibody protection in mice.

Comparison of Race-neutral Versus Race-specific Spirometry Equations for Evaluation of Child Asthma.

Rationale: Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds.

Objectives: To determine if race-neutral (GLI-Global) versus race-specific (GLI-Race-Specific) reference equations differentially impact spirometry evaluation of childhood asthma.

Methods: The analysis included 8,719 children aged 5 to <12 years from 27 cohorts across the United States grouped by parent-reported race and ethnicity.

A GMR enzymatic assay for quantifying nuclease and peptidase activity.

Hydrolytic enzymes play crucial roles in cellular processes, and dysregulation of their activities is implicated in various physiological and pathological conditions. These enzymes cleave substrates such as peptide bonds, phosphodiester bonds, glycosidic bonds, and other esters. Detecting aberrant hydrolase activity is vital for understanding disease mechanisms and developing targeted therapeutic interventions.

Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants.

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection.

Compounding Phages for Therapeutic Applications.

species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced fatal exacerbations. spp.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care.

Race-Specific Spirometry Equations Do Not Improve Models of Dyspnea and Quantitative Chest CT Phenotypes.

Background: Race-specific spirometry reference equations are used globally to interpret lung function for clinical, research, and occupational purposes, but inclusion of race is under scrutiny.

Research Question: Does including self-identified race in spirometry reference equation formation improve the ability of predicted FEV values to explain quantitative chest CT abnormalities, dyspnea, or Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification?

Study Design And Methods: Using data from healthy adults who have never smoked in both the National Health and Nutrition Survey (2007-2012) and COPDGene study cohorts, race-neutral, race-free, and race-specific prediction equations were generated for FEV Using sensitivity/specificity, multivariable logistic regression, and random forest models, these equations were applied in a cross-sectional analysis to populations of individuals who currently smoke and individuals who formerly smoked to determine how they affected GOLD classification and the fit of models predicting quantitative chest CT phenotypes or dyspnea.

Results: Race-specific equations showed no advantage relative to race-neutral or race-free equations in models of quantitative chest CT phenotypes or dyspnea.

Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against pneumonia.

(PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA ΔCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain.

Bacteriophage Therapy of Multidrug-resistant Achromobacter in an 11-Year-old Boy With Cystic Fibrosis Assessed by Metagenome Analysis.

Background: Cystic fibrosis (CF) is a genetic disease associated with lung disease characterized by chronic pulmonary infection, increasingly caused by multiple drug-resistant pathogens after repeated antibiotic exposure, limiting antibiotic treatment options. Bacteriophages can provide a pathogen-specific bactericidal treatment used with antibiotics to improve microbiologic and clinical outcomes in CF.

Methods: Achromobacter species isolates from sputum of a chronically infected person with CF, were assessed for susceptibility to bacteriophages: 2 highly active, purified bacteriophages were administered intravenously every 8 hours, in conjunction with a 14-day piperacillin/tazobactam course for CF exacerbation.

Medicaid Integrated Purchasing for Physical and Behavioral Health: Early Adopters' Perceptions of Payment Reform Implementation in Washington State.

The Centers for Medicare and Medicaid Innovation (CMMI) gave rise to the State Innovation Models (SIMs). Medicaid Integrated Purchasing for Physical and Behavioral Health, referred to as Payment Model 1 (PM1), was a core payment redesign area of the Washington State SIM project under which our research team was contracted to provide an evaluation. In doing so, we leveraged an open systems conceptual model to assess qualitatively Early Adopter stakeholders' perceived effects of implementation.

Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial.

Background: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

Methods: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization.

Cystic Fibrosis Screen Positive, Inconclusive Diagnosis Genotypes in People with Cystic Fibrosis from the U.S. Patient Registry.

Variants within the cystic fibrosis (CF) transmembrane conductance regulator gene, , that are of unknown significance or are categorized as non-CF causing may be observed in persons with CF. These variants are frequently detected in children with inconclusive newborn screen results and, in some cases, may be associated with a benign presentation in early childhood that progresses to a CF phenotype later in life. To analyze data from individuals enrolled in the U.

Integrating specialist palliative care to improve care and reduce suffering: cystic fibrosis (InSPIRe:CF) - study protocol for a multicentre randomised clinical trial.

Introduction: Cystic fibrosis (CF) is a life-limiting genetic disorder estimated to affect more than 160 000 individuals and their families worldwide. People living with CF commonly experience significant physical and emotional symptom burdens, disruptions to social roles and complex treatment decision making. While palliative care (PC) interventions have been shown to relieve many such burdens in other serious illnesses, no rigorous evidence exists for palliative care in CF.

Unsupervised Learning Identifies Computed Tomographic Measurements as Primary Drivers of Progression, Exacerbation, and Mortality in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome with phenotypic manifestations that tend to be distributed along a continuum. Unsupervised machine learning based on broad selection of imaging and clinical phenotypes may be used to identify primary variables that define disease axes and stratify patients with COPD. To identify primary variables driving COPD heterogeneity using principal component analysis and to define disease axes and assess the prognostic value of these axes across three outcomes: progression, exacerbation, and mortality.

Erratum: Automated CT Staging of Chronic Obstructive Pulmonary Disease Severity for Predicting Disease Progression and Mortality with a Deep Learning Convolutional Neural Network.

[This corrects the article DOI: 10.1148/ryct.2021200477.

Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection.

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing.

Stenotrophomonas maltophilia in patients with bronchiectasis: An analysis of the US bronchiectasis and NTM Research Registry.

Introduction: Little information is available about Stenotrophomonas maltophilia in patients with bronchiectasis. We analyzed data from the US Bronchiectasis and NTM Research Registry to determine its prevalence and association with patient characteristics and severity of disease.

Methods: Baseline and follow-up data were entered into a central web-based database.

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice.

Cystic fibrosis (CF) is an inherited life-threatening disease accompanied by repeated lung infections and multiorgan inflammation that affects tens of thousands of people worldwide. The causative gene, cystic fibrosis transmembrane conductance regulator (CFTR), is mutated in CF patients. CFTR functions in epithelial cells have traditionally been thought to cause the disease symptoms.

Multi-Omics Study of Keystone Species in a Cystic Fibrosis Microbiome.

Ecological networking and in vitro studies predict that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes. The metabolic byproducts from these bacteria facilitate the colonization and growth of CF pathogens like . Here, a multi-omics study informed the control of putative anaerobic keystone species during a transition in antibiotic therapy of a CF patient.

Draft Genome Sequence of the Multidrug-Resistant Strain Pseudomonas aeruginosa PA291, Isolated from Cystic Fibrosis Sputum.

Here, we report the genome sequence of PA291, a nonmucoid, multidrug-resistant strain of Pseudomonas aeruginosa isolated from cystic fibrosis sputum. Short reads were assembled into 190 contigs and scaffold assembled to a length of 6.26 Mbp.

Impacts of innovation in dental care delivery and payment in Medicaid managed care for children and adolescents.

Background: We evaluated a 14-county quality improvement program of care delivery and payment of a dental care organization for child and adolescent managed care Medicaid beneficiaries after 2 years of implementation.

Methods: Counties were randomly assigned to either the intervention (PREDICT) or control group. Using Medicaid administrative data, difference-in-difference regression models were used to estimate PREDICT intervention effects (formally, "average marginal effects") on dental care utilization and costs to Medicaid, controlling for patient and county characteristics.