Ivacaftor for Chronic Obstructive Pulmonary Disease - Results from a Phase 2, Randomized Controlled Trial.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) exhibit acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. CFTR modulators may improve outcomes in patients with COPD, although recent data regarding magnitude of benefit have been inconclusive and effects on mucociliary clearance are unknown. We conducted a phase 2, randomized, double blind placebo control trial to determine safety and tolerability, and explore the potential mechanism of ivacaftor for the treatment of COPD.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia.

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model.

Pulmonary Fibrosis Ferret Model Demonstrates Sustained Fibrosis, Restrictive Physiology, and Aberrant Repair.

Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans.

Investigating MRI-Associated Biological Aspects of Racial Disparities in Prostate Cancer for African American and White Men.

Background: Understanding the characteristics of multiparametric MRI (mpMRI) in patients from different racial/ethnic backgrounds is important for reducing the observed gaps in clinical outcomes.

Purpose: To investigate the diagnostic performance of mpMRI and quantitative MRI parameters of prostate cancer (PCa) in African American (AA) and matched White (W) men.

Study Type: Retrospective.

nnUNet for Automatic Kidney and Cyst Segmentation in Autosomal Dominant Polycystic Kidney Disease.

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder that causes uncontrolled kidney cyst growth, leading to kidney volume enlargement and renal function loss over time. Total kidney volume (TKV) and cyst burdens have been used as prognostic imaging biomarkers for ADPKD.

Objective: This study aimed to evaluate nnUNet for automatic kidney and cyst segmentation in T2-weighted (T2W) MRI images of ADPKD patients.

Deep learning-based automated kidney and cyst segmentation of autosomal dominant polycystic kidney disease using single vs. multi-institutional data.

Purpose: This study aimed to investigate if a deep learning model trained with a single institution's data has comparable accuracy to that trained with multi-institutional data for segmenting kidney and cyst regions in magnetic resonance (MR) images of patients affected by autosomal dominant polycystic kidney disease (ADPKD).

Methods: We used TensorFlow with a Keras custom UNet on 2D slices of 756 MRI images of kidneys with ADPKD obtained from four institutions in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study. The ground truth was determined via a manual plus global thresholding method.

Understanding basic multicellular unit activity in cortical bone through 3D morphological analysis: New methods to define zones of the remodeling space.

The activity of basic multicellular units (BMU) in cortical bone is classically described as a sequential order of events- resorption, reversal and formation. This simplified portrayal of the remodeling process is pervasive despite the reported variability in remodeling space morphology. These variations may reflect meaningful nuances in BMU activity but methods to quantify 3D remodeling space morphology within the context of the cellular activity are currently lacking.

Technical note: 3D-printed MRI-compatible syringe pump.

Background: A power injector is typically employed to deliver a contrast agent to a subject (e.g., humans, animals, phantoms) during MRI, but it is costly and cannot inject more than one subject at a time.

Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia.

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1-34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER).

Racial Disparities in Quantitative MRI for African American and White Men with Prostate Cancer.

The risk of prostate cancer (PCa) is strongly influenced by race and ethnicity. The purpose of this study is to investigate differences in the diagnostic performance of multiparametric MRI (mpMRI) in African American (AA) and white (W) men. 111 patients (37 AA and 74 W men) were selected from the study's initial cohort of 885 patients after matching age, prostate-specific antigen, and prostate volume.

Mucociliary clearance augmenting drugs block SARS-CoV-2 replication in human airway epithelial cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve the barrier function of the airway epithelium and reduce viral replication and, ultimately, COVID-19 outcomes.

Cutaneous Exposure to Arsenicals Is Associated with Development of Constrictive Bronchiolitis in Mice.

Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome.

Mucociliary Clearance Augmenting Drugs Block SARS-Cov-2 Replication in Human Airway Epithelial Cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve barrier function of the airway epithelium, reduce viral replication and, ultimately, COVID-19 outcomes.

Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection.

Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma.

Conversion of Pulse Protein Foam-Templated Oleogels into Oleofoams for Improved Baking Application.

The food industry has long been searching for an efficient replacement for saturated-fatty-acid-rich fats for baking applications. Although oleogels have been considered a potential alternative for saturated and trans fats, their success in food application has been poor. The present study explored the use of oleofoams obtained by whipping the pulse protein foam-templated oleogels for cake baking.

Direct Assessment of Rabbit Cortical Bone Basic Multicellular Unit Longitudinal Erosion Rate: A 4D Synchrotron-Based Approach.

Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER.

Perfusion Change of Hepatocellular Carcinoma During Atezolizumab plus Bevacizumab Treatment: A Pilot Study.

Purpose: To investigate whether the early perfusion change in hepatocellular carcinoma (HCC) predicts the long-term therapeutic response to atezolizumab plus bevacizumab.

Methods: We retrospectively selected 19 subjects (median age: 62 years, 4 females, and 15 males) having advanced HCC and treated with atezolizumab alone (n = 3) or in combination with bevacizumab (n = 16). The 4-phased CT or MRI imaging was performed for each subject before and at 9 ± 2 and 21 ± 5 weeks after therapy initiation.

Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway.

Simulated microgravity (SMG) inhibits osteoblast differentiation (OBD) and induces bone loss via the inhibition of the Wnt/β-catenin pathway. However, the mechanism by which SMG alters the Wnt/β-catenin pathway is unknown. We previously demonstrated that SMG altered the focal adhesion kinase (FAK)-regulated mTORC1, AMPK and ERK1/2 pathways, leading to the inhibition of tumor cell proliferation/metastasis and promoting cell apoptosis.

Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection.

Substantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both and models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways.

Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction.

Rationale: The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested given limitations to rodent models of COPD.

Disposable point-of-care portable perfusion phantom for quantitative DCE-MRI.

Purpose: To develop a disposable point-of-care portable perfusion phantom (DP4) and validate its clinical utility in a multi-institutional setting for quantitative dynamic contrast-enhanced magnetic resonance imaging (qDCE-MRI).

Methods: The DP4 phantom was designed for single-use and imaged concurrently with a human subject so that the phantom data can be utilized as the reference to detect errors in qDCE-MRI measurement of human tissues. The change of contrast-agent concentration in the phantom was measured using liquid chromatography-mass spectrometry.