Evaluation of elexacaftor-tezacaftor-ivacaftor treatment in individuals with cystic fibrosis and CFTR in the USA: a prospective, multicentre, open-label, single-arm trial.

Background: CFTR modulators are approved for approximately 90% of people with cystic fibrosis in the USA and provide substantial clinical benefit. N1303K (Asn1303Lys), one of the most common class 2 CFTR defects, has not been approved for these therapies by any regulatory agency. Preclinical investigation by our laboratories showed N1303K CFTR activation with elexacaftor-tezacaftor-ivacaftor (ETI).

Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarized Xe diffusion MRI.

Rationale: Cystic Fibrosis (CF) progresses through recurrent infection and inflammation, causing permanent lung function loss and airway remodeling. CT scans reveal abnormally low-density lung parenchyma in CF, but its microstructural nature remains insufficiently explored due to clinical CT limitations. To this end, diffusion-weighted Xe MRI is a non-invasive and validated measure of lung microstructure.

A framework for transforming the professional identity and brand image of All Nurses as Leaders.

Background: The professional identity and brand image of nurses as leaders have not kept pace with the roles and scope of contemporary nursing practice.

Purpose: To provide a framework to transform the professional identity and brand image of nursing from a caring discipline to one of leaders.

Methods: A Consensus Development Workgroup (CDW) design was used between the International Society for Professional Identity in Nursing (ISPIN) and the Institute for Brand Image of Nursing (IBIN) to advance the concept of All Nurses as Leaders across all settings and the public domain.

Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis.

Promoting health equity with HBCUs: Breaking away from structural racism.

Background: The United States continues to be plagued with pervasive health disparities. Leading health and professional organizations acknowledge structural racism as a contributing factor for the lack of a racially diverse nursing workforce particularly those serving in leadership roles which could help to mitigate health disparities among historically stigmatized populations.

Purpose: Purpose Lack of funding for Historically Black Colleges and Universities (HBCUs) and lack of meaningful partnerships, stymie efforts that can be made by nursing programs at HBCUs.

Phenotypic Alteration of an Established Human Airway Cell Line by Media Selection.

Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride/bicarbonate channel. Many studies utilize human airway cell models (cell lines and primary cells) to study different aspects of CFTR biology. Media selection can alter the growth and differentiation of primary cells, yet the impact on stable airway cell lines is unclear.

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification.

Objectives: Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen-positive, inconclusive diagnosis (CFSPID), with limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are not well established. We investigated whether clinical characteristics are associated with the risk of reclassification from CFSPID to a CF diagnosis.

Novel Applications of Biomarkers and Personalized Medicine in Cystic Fibrosis.

As routine care in cystic fibrosis (CF) becomes increasingly personalized, new opportunities to further focus care on the individual have emerged. These opportunities are increasingly filled through research in tools aiding drug selection, drug monitoring and titration, disease-relevant biomarkers, and evaluation of therapeutic benefits. Herein, we will discuss such research tools presently being translated into the clinic to improve the personalization of care in CF.

CRISPRi links COVID-19 GWAS loci to LZTFL1 and RAVER1.

Background: To identify host genetic variants (SNPs) associated with COVID-19 disease severity, a number of genome-wide association studies (GWAS) have been conducted. Since most of the identified variants are located at non-coding regions, such variants are presumed to affect the expression of neighbouring genes, thereby influencing COVID-19 disease severity. However, it remains largely unknown which genes are influenced by such COVID-19 GWAS loci.

When CFSPID becomes CF.

There has been a growing number of infants identified as CRMS/CFSPID in countries applying genetic testing as part of cystic fibrosis (CF) newborn screening. Currently there are neither standardized protocols for follow up beyond infancy, nor established predictors to stratify this population as high or low risk of reclassification to CF or CFTR-related disorder. We report a series of 10 children who reclassified, including eight carrying CFTR variants of varying clinical consequence and seven with initial sweat chloride measurements <30 mmol/L.

National Study of Nursing Faculty and Administrators' Perceptions of Professional Identity in Nursing.

Background: Establishing a professional identity in nursing is integral to professional development, yet this area of inquiry remains understudied.

Purpose: This segment of a multiphased national study measured nursing faculty's perceived level of importance regarding key components of professional identity in nursing using the newly developed Professional Identity in Nursing Survey (PINS).

Methods: Fifty subject matter experts from nursing education, practice, and regulation utilized the DeVellis scale development process to develop the PINS over the course of 2 years.

Patient personalized translational tools in cystic fibrosis to transform data from bench to bed-side and back.

Cystic fibrosis is a deadly multiorgan disorder caused by loss of function mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride/bicarbonate ion channel. More than 1,700 genetic variants exist that can cause CF, and majority of these are extremely rare. Because of genetic and environmental influences, CF patients exhibit large phenotypic variation.

Nasal Epithelial Cell-Based Models for Individualized Study in Cystic Fibrosis.

The emergence of highly effective CFTR modulator therapy has led to significant improvements in health care for most patients with cystic fibrosis (CF). For some, however, these therapies remain inaccessible due to the rarity of their individual variants, or due to a lack of biologic activity of the available therapies for certain variants. One proposed method of addressing this gap is the use of primary human cell-based models, which allow preclinical therapeutic testing and physiologic assessment of relevant tissue at the individual level.

The Journey: Nurses on Boards Coalition Preparation and Support Work Group.

Nurses have the knowledge, skills, and expertise to bring value and leadership to a myriad of boards throughout the United States, with nursing leadership critical to the transformation of complex health care systems. The 2011 Institute of Medicine Future of Nursing report calls on nurses to lead at all levels in systems as well as in board rooms. In 2014, the Nurses on Boards Coalition (NOBC) aligned its mission with this charge, creating a goal, as stated on its Web site, to "improve the health of communities and the nation through the service of nurses on boards and other bodies.

CRISPRi-mediated functional analysis of lung disease-associated loci at non-coding regions.

Genome-wide association studies have identified lung disease-associated loci; however, the functions of such loci are not well understood in part because the majority of such loci are located at non-coding regions. Hi-C, ChIP-seq and eQTL data predict potential roles (e.g.

Neutrophil extracellular traps activate IL-8 and IL-1 expression in human bronchial epithelia.

Neutrophil extracellular traps (NETs) provide host defense but can contribute to the pathobiology of diverse human diseases. We sought to determine the extent and mechanism by which NETs contribute to human airway cell inflammation. Primary normal human bronchial epithelial cells (HBEs) grown at air-liquid interface and wild-type (wt)CFBE41o- cells (expressing wtCFTR) were exposed to cell-free NETs from unrelated healthy volunteers for 18 h in vitro.