Associations Among Optimal Lung Cancer Treatment, Clinical Outcomes, and Health Care Utilization in Patients Who Underwent Comprehensive Genomic Profiling.

Background: Although immune checkpoint inhibitor immunotherapies are contraindicated as first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients with ALK rearrangement and EGFR mutation, many receive them. The purpose of this study was to examine the association between optimal first-line treatment in this population and clinical outcomes.

Methods: Claims and genomic data from patients with advanced or metastatic NSCLC were extracted from a nationally representative GuardantINFORM dataset.

A Case Report of Congenital Afibrinogenemia and Literature Review of Management of Post-circumcision Bleeding.

We present a case of bleeding from circumcision in a full-term newborn male resulting from a rare coagulopathy, congenital afibrinogenemia, and a review of the literature regarding the management of bleeding after circumcision. Bleeding was managed with silver nitrate, suturing, thrombin powder, Arista AH (absorbable hemostatic particles; Becton, Dickinson and Company, Franklin Lakes, USA), FFP (fresh frozen plasma), and cryoprecipitate. The Fibrinogen level was less than 30 mg/dl (ref 150-430 mg/dl).

Alluvial connectivity in multi-channel networks in rivers and estuaries.

Channels in rivers and estuaries are the main paths of fluvial and tidal currents that transport sediment through the system. While network representations of multi-channel systems and their connectivity are quite useful for characterisation of braiding patterns and dynamics, the recognition of channels and their properties is complicated because of the large bed elevation variations, such as shallow shoals and bed steps that render channels visually disconnected. We present and analyse two mathematically rigorous methods to identify channel networks from a terrain model of the river bed.

Geometry and Topology of Estuary and Braided River Channel Networks Automatically Extracted From Topographic Data.

Automatic extraction of channel networks from topography in systems with multiple interconnected channels, like braided rivers and estuaries, remains a major challenge in hydrology and geomorphology. Representing channelized systems as networks provides a mathematical framework for analyzing transport and geomorphology. In this paper, we introduce a mathematically rigorous methodology and software for extracting channel network topology and geometry from digital elevation models (DEMs) and analyze such channel networks in estuaries and braided rivers.

Vascular endothelial growth factor levels and bronchopulmonary dysplasia in preterm infants.

Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) regulate both vasculogenesis, the development of blood vessels from precursor cells, and angiogenesis, the formation of blood vessels from preexisting vessels. In the fetal lung, high-affinity receptors for VEGF are expressed mainly in alveolar epithelial cells and myocytes, suggesting a paracrine role for VEGF in modulating activities in adjacent vascular endothelium. Previous studies have shown that vascular growth is impaired in bronchopulmonary dysplasia (BPD).

Effects of Shoal Margin Collapses on the Morphodynamics of a Sandy Estuary.

Shoal margin collapses of several million cubic meters have occurred in the Western Scheldt estuary, the Netherlands, on average five times a year over the last decades. While these collapses involve significant volumes of material, their effect on the channel-shoal morphology is unknown. We hypothesize that collapses dynamicize the channel-shoal interactions, which could impact the ecological functioning, flood safety, and navigation in the estuary.

High-Deductible Health Plans and the Challenges They Pose to Radiologists.

Patients with high-deductible health plans will increasingly be motivated to contact their hospitals or various websites to try to obtain information about the costs of expensive services like advanced imaging. Unfortunately, they will not find price transparency but rather confusion and opaqueness. Hospital personnel and commercial websites often unwittingly provide erroneous pricing information.

Efficacy of proximal colectomy for surgical management of right-sided first colorectal cancer in Lynch Syndrome mutation carriers.

Background: This study analyzes the occurrence of colorectal cancer (CRC) in Lynch syndrome (LS) mutation carriers, interval until diagnosis of metachronous CRC, and survival after proximal colectomy (PC) compared with total (TC) and subtotal colectomy (STC) for right-sided first CRC in LS mutation carriers.

Methods: Sixty-four LS mutation carriers with right-sided first CRC treated with PC or TC + STC were confirmed by clinical records. Bivariate analyses were examined for significance and life tables were generated for risk of metachronous CRC and survival estimates following surgery.

Serum surfactant protein D as a marker for bronchopulmonary dysplasia.

Background: Lung epithelial cells express surfactant protein D (SP-D), a calcium-dependent lectin that plays an important role in antibody-independent pulmonary host defense. Previous studies have shown that it is found in the peripheral circulation in patients with pulmonary disease, likely because of translocation into the blood when lung epithelial barriers are disrupted by inflammation or acute injury. In adults, serum SP-D levels are biomarkers for the progression and severity of chronic lung disease.

Establishing Proximal and Distal Regional Identities in Murine and Human Tissue-Engineered Lung and Trachea.

The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks.

Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease.

Rationale: Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions.

A Large State Medicaid Outpatient Advanced Imaging Utilization Management Program: Substantial Savings Without the Need for Denials.

A decade of rapidly rising outpatient advanced imaging utilization ended toward the end of the past decade, with slow growth since. This has been attributed to repetitive reimbursement cuts, medical radiation exposure concerns, increasing deductibles and patient copayments, and the influence of radiology benefit management companies. State Medicaid programs have been reluctant to institute radiology benefit management preauthorization programs since the time burden for obtaining test approval could cause providers to drop out.

Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung Injury Repair.

Type 2 alveolar epithelial cells (AEC2) are regarded as the progenitor population of the alveolus responsible for injury repair and homeostatic maintenance. Depletion of this population is hypothesized to underlie various lung pathologies. Current models of lung injury rely on either uncontrolled, nonspecific destruction of alveolar epithelia or on targeted, nontitratable levels of fixed AEC2 ablation.

Urinary tract obstruction in the mouse: the kinetics of distal nephron injury.

Congenital urinary tract obstruction is the single most important cause of childhood chronic kidney disease. We have previously demonstrated that human and primate fetal obstruction impairs the development, differentiation, and maturation of the kidney. Research using postnatal rodent models has primarily focused upon the role of proximal tubular injury, with few reports of collecting duct system pathology or the suitability of the postnatal models for examining injury to the distal nephron.

Stepwise evolution of essential centromere function in a Drosophila neogene.

Evolutionarily young genes that serve essential functions represent a paradox; they must perform a function that either was not required until after their birth or was redundant with another gene. How young genes rapidly acquire essential function is largely unknown. We traced the evolutionary steps by which the Drosophila gene Umbrea acquired an essential role in chromosome segregation in D.

The effect of a no-denial policy on imaging utilization.

Purpose: Seeking to control advanced diagnostic imaging costs, health insurance plans have instituted broad-based utilization management systems. Most processes ultimately contain denial provisions, meaning that the health plans will refuse to pay for requested studies if performed. The aim of this analysis was to determine whether removal of a denial provision would result in increased utilization of imaging services.

Congenital urinary tract obstruction: defining markers of developmental kidney injury.

Congenital urinary tract obstruction (diagnosed antenatally by ultrasound screening) is one of the main causes of end-stage kidney disease in children. The extent of kidney injury in early gestation and the resultant abnormality in kidney development determine fetal outcome and postnatal renal function. Unfortunately, the current approach to diagnostic evaluation of the severity of injury has inherently poor diagnostic and prognostic value because it is based on the assessment of fetal tubular function from fetal urine samples rather than on estimates of the dysplastic changes in the injured developing kidney.

Urinary biomarkers in obstructive nephropathy.

Background And Objectives: Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging.

Design, Setting, Participants, & Measurements: This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR.

Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1) gene family.

Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA.

CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC).

Internal standards: a source of analytical bias for volatile organic analyte determinations.

The use of internal standards in the determination of volatile organic compounds as described in SW-846 Method 8260C introduces a potential for bias in results once the internal standards (ISTDs) are added to a sample for analysis. The bias is relative to the dissimilarity between the analyte and internal standard physical properties that influence how easily analytes are separated from a matrix and concentrated during analysis. Method 5032 is a vacuum distillation procedure for extracting analytes from a sample for use with Method 8260C.

Ontogeny of CD24 in the human kidney.

The heat-stable antigen, CD24, is a cell-surface sialoglycoprotein expressed on immature cells that disappears after they have reached their final stage of differentiation. In mice, CD24 expression is preferentially upregulated in the developing mouse metanephros as compared with the surrounding intermediate mesoderm, but its role and expression in the developing human kidney has not been well described. Here we found in normal human fetal kidneys (8 to 38 weeks of gestation) that CD24 expression was upregulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape bodies.

Phenotypic transition of the collecting duct epithelium in congenital urinary tract obstruction.

Epithelial-mesenchymal transition (EMT) has emerged in recent years as an important process in the development of organ fibrosis in many human diseases. Our previous experience in a nonhuman primate model of obstructive nephropathy suggested that EMT of collecting duct epithelium contributes to the development of interstitial fibrosis. In this study we demonstrate for the first time in humans that obstructed fetal collecting duct epithelium undergoes transition to mesenchymal phenotype, characterized by decreased expression of epithelial markers, de novo expression of mesenchymal markers with subsequent loss of cell-cell interaction, disruption of the basement membrane, and increased deposition of extracellular matrix into the expanded interstitium of the obstructed kidney.