Simulating paired and longitudinal single-cell RNA sequencing data with rescueSim.

Motivation: As single-cell RNA-sequencing (scRNA-seq) becomes more widely used in transcriptomic research, complex experimental designs, such as paired or longitudinal studies, become increasingly feasible. Paired/longitudinal scRNA-seq enables the study of transcriptomic changes over time within specific cell types, yet guidance on analytical approaches and resources for study planning, such as power analysis, remains limited. Data simulation is a valuable tool for evaluating analysis method performance and informing study design decisions, including sample size selection.

The common cold is associated with protection from SARS-CoV-2 Infections.

Background: Adults and children often respond differently to SARS-CoV-2 infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

Methods: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved.

Genomic and epidemiologic investigation of Mycobacterium abscessus isolates in a cystic fibrosis center to determine potential routes of transmission.

Background: Cystic Fibrosis (CF) Centers worldwide have reported healthcare-associated outbreaks of nontuberculous mycobacteria (NTM). We report a retrospective investigation of shared Mycobacterium abscessus strains among people with cystic fibrosis (pwCF) receiving care at Dell Children's/Ascension combined Pediatric and Adult CF Program (DCMC).

Methods: Whole genome sequencing (WGS) was used to identify genetically similar isolates among 167 NTM isolates from 57 pwCF.

Oscillometry Measures the Response to Acute Asthma Therapy in the Pediatric Emergency Department.

Rationale: Oscillometry is a feasible and safe method to measure pulmonary function in children with asthma exacerbations in the emergency department (ED), but its utility to measure respiratory impedance as an objective marker of response to initial acute asthma treatments is unknown.

Objectives: To determine the associations between respiratory impedance-derived metrics and asthma exacerbation severity and treatment response in the pediatric ED.

Methods: Prospective study of children 4-18 years presenting to a tertiary-care pediatric ED for asthma exacerbations.

Impact of nasal and inhaled corticosteroids on SARS-CoV-2 infection susceptibility.

Background: It is unknown whether nasal corticosteroid (NCS) or inhaled corticosteroid (ICS) use impacts the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objectives: We sought to examine the associations of NCS and ICS use with the risk of SARS-CoV-2 infection among individuals with allergic rhinitis or asthma.

Methods: This is a prospective, multicenter, SARS-CoV-2 surveillance study of households with children.

Antennal RNAseq reveals odorant receptors with sex-biased expression in the common eastern firefly, Photinus pyralis.

Background: With their charismatic nighttime flashes, fireflies are a classic organismal system for studying the evolution of visual mating signals. However, across their diversity, fireflies employ a variety of mating strategies that include both chemical and visual signals. While phylogenetic evidence points to a common ancestor that relied on long-range pheromones, behavioral evidence suggests that light-dependent flashing fireflies do not use smell for mating.

The MUC5B promoter variant results in proteomic changes in the nonfibrotic lung.

The gain-of-function MUC5B promoter variant is the dominant risk factor for the development of idiopathic pulmonary fibrosis (IPF). However, its impact on protein expression in both nonfibrotic control and IPF lung specimens has not been well characterized. Utilizing laser capture microdissection coupled to mass spectrometry, we investigated the proteomic profiles of airway and alveolar epithelium in nonfibrotic controls (n = 12) and IPF specimens (n = 12), stratified by the MUC5B promoter variant.

The PRIMERO birth cohort: Design and baseline characteristics.

Background: Although early-life respiratory illnesses (RIs) are linked to childhood asthma, it is unclear whether children are predisposed to both conditions or if RIs induce alterations that lead to asthma. Puerto Rican children, who bear a disproportionate burden of early-life RIs and asthma, are an important population for studying this relationship.

Objective: We sought to describe the design and baseline characteristics of the Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO) birth cohort.

Trial design of bacteriophage therapy for nontuberculous mycobacteria pulmonary disease in cystic fibrosis: The POSTSTAMP study.

Bacteriophages (phages) are viruses that selectively infect bacteria and have been utilized to treat Mycobacterium abscessus (Mab) with varying success. The POSTSTAMP study is an ongoing, multi-site phage therapy protocol for treatment-refractory pulmonary Mab disease in people with cystic fibrosis (pwCF). Participants (n = 10) are prospectively assessed while utilizing FDA investigational new drug (IND) approval for compassionate use.

Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.

Introduction: Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors, but they also commonly cause immune-related adverse events (irAEs). The predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Given the similarities between irAEs and autoimmune diseases, we sought to investigate the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.

Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis.

Background: Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design.

Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma.

Background: A subset of asthma patients have airway pathology characterized by a thickened subepithelial basement membrane zone ("BMZ-thick asthma").

Objectives: To characterize the clinical features of BMZ-thick asthma and to determine if BMZ thickness accompanies specific patterns of inflammation in the airway epithelium.

Methods: Design-based stereology was used to quantify BMZ thickness in endobronchial biopsy tissue sections from 109 asthma patients and 41 healthy controls from the Severe Asthma Research Program-3 whose participants had undergone spirometry and gene expression profiling in airway epithelial brushings.

Comparative analysis of ambient, in-home, and personal exposures reveals associations between breathing zone pollutant levels and asthma exacerbations in high-risk children.

Background: Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes.

Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiology of (), which may enable the pathogen to withstand treatment. While antibiotic-treated has been evaluated in experiments it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affects physiologic processes differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4 weeks of treatment with three sterilizing and three non-sterilizing antibiotics.

Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma.

Corticosteroid-responsive type 2 (T2) inflammation underlies the T2-high asthma endotype. However, we hypothesized that type 1 (T1) inflammation, possibly related to viral infection, may also influence corticosteroid response. To determine the frequency and within-patient variability of T1-high, T2-high, and T1/T2-high asthma endotypes and whether virally influenced T1-high disease influences corticosteroid response in asthma.

Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma.

Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. Surfactant protein A (SP-A) plays a critical role in regulating pulmonary innate immunity by binding to numerous respiratory pathogens. Mature SP-A consists of multiple isoforms that form the hetero-oligomers of SP-A1 and SP-A2, organized in 18-mers.

Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung.

Macrophages are required for healthy repair of the lungs following injury, but they are also implicated in driving dysregulated repair with fibrosis. How these 2 distinct outcomes of lung injury are mediated by different macrophage subsets is unknown. To assess this, single-cell RNA-Seq was performed on lung macrophages isolated from mice treated with LPS or bleomycin.

Evaluation of the GenoType NTM-DR line probe assay for nontuberculous mycobacteria using whole genome sequences as reference standard.

Pulmonary nontuberculous mycobacteria (NTM) disease is an emerging public health challenge that is especially problematic in people with cystic fibrosis (CF). Effective treatment depends on accurate species and subspecies identification and antimicrobial susceptibility status. We evaluated the GenoType NTM-DR VER 1.

Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiologic state of () which may enable the pathogen to withstand treatment. While antibiotic-treated have been evaluated in short-term experiments, it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affect physiologic states differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4-week treatment with three sterilizing and three non-sterilizing antibiotics.

Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis.

Background: Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design.