IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples.

Objective: Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics.

Methods And Materials: The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity.

PKCδ regulates integrin αVβ3 expression and transformed growth of K-ras dependent lung cancer cells.

We have previously shown that Protein Kinase C delta (PKCδ) functions as a tumor promoter in non-small cell lung cancer (NSCLC), specifically in the context of K-ras addiction. Here we define a novel PKCδ -> integrin αVβ3 ->Extracellular signal-Regulated Kinase (ERK) pathway that regulates the transformed growth of K-ras dependent NSCLC cells. To explore how PKCδ regulates tumorigenesis, we performed mRNA expression analysis in four KRAS mutant NSCLC cell lines that stably express scrambled shRNA or a PKCδ targeted shRNA.

Plasma QconCATs reveal a gender-specific proteomic signature in apheresis platelet plasma supernatants.

Unlabelled: Clinical translation of proteomic technologies is often hampered by technical limitations, including inter-laboratory inconsistencies of label-free derived relative quantification, time-consuming analytical approaches and the subsequent challenge of performing proteomic analyses on large cohorts of subjects. Here we introduce plasma QconCAT-based targeted proteomics, an approach that allows the simultaneous absolute quantitation down to the picogram level of hundreds of proteins in a single liquid chromatography-selected reaction monitoring mass spectrometry run. We demonstrate the robustness of the approach by analyzing apheresis platelet concentrate supernatants at storage day 1 and the end of the shelf life for this blood-derived therapeutic, day 5.

Metabolomics of AS-5 RBC supernatants following routine storage.

Background And Objectives: The safety and efficacy of stored red blood cells (RBCs) transfusion has been long debated due to retrospective clinical evidence and laboratory results, indicating a potential correlation between increased morbidity and mortality following transfusion of RBC units stored longer than 14 days. We hypothesize that storage in Optisol additive solution-5 leads to a unique metabolomics profile in the supernatant of stored RBCs.

Materials And Methods: Whole blood was drawn from five healthy donors, RBC units were manufactured, and prestorage leucoreduced by filtration.

Natural killer cell-activating receptor NKG2D mediates innate immune targeting of allogeneic neural progenitor cell grafts.

Cell replacement therapy holds promise for a number of untreatable neurological or psychiatric diseases but the immunogenicity of cellular grafts remains controversial. Emerging stem cell and reprogramming technologies can be used to generate autologous grafts that minimize immunological concerns but autologous grafts may carry an underlying genetic vulnerability that reduces graft efficacy or survival. Healthy allogeneic grafts are an attractive and commercially scalable alternative if immunological variables can be controlled.

Improving psychiatric hospital care for pediatric patients with autism spectrum disorders and intellectual disabilities.

Pediatric patients with autism spectrum disorders (ASD) and/or intellectual disabilities (ID) are at greater risk for psychiatric hospitalization compared to children with other disorders. However, general psychiatric hospital environments are not adapted for the unique learning styles, needs, and abilities of this population, and there are few specialized hospital-based psychiatric care programs in the United States. This paper compares patient outcomes from a specialized psychiatric hospital program developed for pediatric patients with an ASD and/or ID to prior outcomes of this patient population in a general psychiatric program at a children's hospital.

Onychomycosis in the Denver pediatrics population, a retrospective study.

Onychomycosis (OM) is a common nail disorder in adults but has been rare in children. Recent international studies have demonstrated a rise in the prevalence of OM in children and adolescents, with Trichophyton rubrum being the most common pathogen. This 5-year retrospective chart review of children (aged <18) found that 66 of 141 patients (46.

Safety and tolerability of antiretrovirals during pregnancy.

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥ 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred.

Transfusion-related acute lung injury (TRALI): a clinical review with emphasis on the critically ill.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality world-wide. Although first described in 1983, it took two decades to develop consensus definitions, which remain controversial. The pathogenesis of TRALI is related to the infusion of donor antibodies that recognize leucocyte antigens in the transfused host or the infusion of lipids and other biological response modifiers that accumulate during the storage or processing of blood components.

Towards inference of a biochemical ontology from a metabolic database.

In order to predict the metabolic fate of an arbitrary compound based solely on structure, it is useful to be able to identify substructural 'functional groups' that are biochemically reactive. These functional groups are the substructural elements that can be removed and replaced to transform one compound into another. This problem of identifying functional groups is related to the problem of classifying compounds.

Solitary chemoreceptor cell survival is independent of intact trigeminal innervation.

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al. [2003] Proc Natl Acad Sci USA 100:8981-8986). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al.

Progesterone receptor transcription and non-transcription signaling mechanisms.

The diverse effects of progesterone on female reproductive tissues are mediated by the progesterone receptor (PR), a member of the nuclear receptor family of ligand-dependent transcription factors. Thus, PR is an important therapeutic target in female reproduction and in certain endocrine dependent cancers. This paper reviews our understanding of the mechanism of action of the most widely used PR antagonist RU486.