The case for wearable proximity devices to inform physical distancing among healthcare workers.

Objective: Despite the importance of physical distancing in reducing SARS-CoV-2 transmission, this practice is challenging in healthcare. We piloted use of wearable proximity beacons among healthcare workers (HCWs) in an inpatient unit to highlight considerations for future use of trackable technologies in healthcare settings.

Materials And Methods: We performed a feasibility pilot study in a non-COVID adult medical unit from September 28 to October 28, 2020.

Improving physical distancing among healthcare workers in a pediatric intensive care unit.

Background: Healthcare workers (HCWs) not adhering to physical distancing recommendations is a risk factor for acquisition of severe acute respiratory coronavirus virus 2 (SARS-CoV-2). The study objective was to assess the impact of interventions to improve HCW physical distancing on actual distance between HCWs in a real-life setting.

Methods: HCWs voluntarily wore proximity beacons to measure the number and intensity of physical distancing interactions between each other in a pediatric intensive care unit.

Barriers to physical distancing among healthcare workers on an academic hospital unit during the coronavirus disease 2019 (COVID-19) pandemic.

Background: Physical distancing among healthcare workers (HCWs) is an essential strategy in preventing HCW-to-HCWs transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

Objective: To understand barriers to physical distancing among HCWs on an inpatient unit and identify strategies for improvement.

Design: Qualitative study including observations and semistructured interviews conducted over 3 months.

SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR.

Background: The CFTR modulator ivacaftor has been variably effective in treating individuals with cystic fibrosis (CF) who harbor CFTR gating variants such as G551D, as well as other classes of CFTR variants when used with other modulators. Because CFTR genotype does not fully explain this variability, defining genetic modifiers of response to modulator therapy is of particular interest to the field of individualized CF drug therapy. Previous studies have proposed that a variant in SLC26A9 (rs7512462) is associated with lung disease severity and with response to treatment with ivacaftor in individuals with CF who carry G551D or gating variants.

Genetic Modifiers of Cystic Fibrosis-Related Diabetes Have Extensive Overlap With Type 2 Diabetes and Related Traits.

Context: Individuals with cystic fibrosis (CF) develop a distinct form of diabetes characterized by β-cell dysfunction and islet amyloid accumulation similar to type 2 diabetes (T2D), but generally have normal insulin sensitivity. CF-related diabetes (CFRD) risk is determined by both CFTR, the gene responsible for CF, and other genetic variants.

Objective: To identify genetic modifiers of CFRD and determine the genetic overlap with other types of diabetes.

Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis.

Diabetes is a common complication of cystic fibrosis (CF) that affects approximately 20% of adolescents and 40%-50% of adults with CF. The age at onset of CF-related diabetes (CFRD) (marked by clinical diagnosis and treatment initiation) is an important measure of the disease process. DNA variants associated with age at onset of CFRD reside in and near SLC26A9.

Detecting interaction networks in the human microbiome with conditional Granger causality.

Human microbiome research is rife with studies attempting to deduce microbial correlation networks from sequencing data. Standard correlation and/or network analyses may be misleading when taken as an indication of taxon interactions because "correlation is neither necessary nor sufficient to establish causation"; environmental filtering can lead to correlation between non-interacting taxa. Unfortunately, microbial ecologists have generally used correlation as a proxy for causality although there is a general consensus about what constitutes a causal relationship: causes both precede and predict effects.

A Stoichioproteomic Analysis of Samples from the Human Microbiome Project.

Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals.

Codon bias and the folding dynamics of the cystic fibrosis transmembrane conductance regulator.

Synonymous or silent mutations are often overlooked in genetic analyses for disease-causing mutations unless they are directly associated with potential splicing defects. More recent studies, however, indicate that some synonymous single polynucleotide polymorphisms (sSNPs) are associated with changes in protein expression, and in some cases, protein folding and function. The impact of codon usage and mRNA structural changes on protein translation rates and how they can affect protein structure and function is just beginning to be appreciated.

Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.

We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.

Deep resequencing of in 762 F508del homozygotes reveals clusters of non-coding variants associated with cystic fibrosis disease traits.

Extensive phenotypic variability is commonly observed in individuals with Mendelian disorders, even among those with identical genotypes in the disease-causing gene. To determine whether variants within and surrounding contribute to phenotypic variability in cystic fibrosis (CF), we performed deep sequencing of in 762 patients homozygous for the common CF-causing variant, F508del. In phase 1, ~200 kb encompassing and extending 10 kb 5' and 5 kb 3' of the gene was sequenced in 486 F508del homozygotes selected from the extremes of sweat chloride concentration.

Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.

Creation and characterization of an airway epithelial cell line for stable expression of CFTR variants.

Background: Analysis of the functional consequences and treatment response of rare CFTR variants is challenging due to the limited availability of primary airways cells.

Methods: A Flp recombination target (FRT) site for stable expression of CFTR was incorporated into an immortalized CF bronchial epithelial cell line (CFBE41o-). CFTR cDNA was integrated into the FRT site.

Experimental assessment of splicing variants using expression minigenes and comparison with in silico predictions.

Assessment of the functional consequences of variants near splice sites is a major challenge in the diagnostic laboratory. To address this issue, we created expression minigenes (EMGs) to determine the RNA and protein products generated by splice site variants (n = 10) implicated in cystic fibrosis (CF). Experimental results were compared with the splicing predictions of eight in silico tools.

Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells.

Background: Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic mammary epithelial cells and breast cancer cells using in vitro and in vivo models of chronic cigarette smoke exposure.