Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone.

Background: Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required.

Objectives: The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy.

Serum response factor mediates nociceptor inflammatory pain plasticity.

Introduction: Chronic metabotropic glutamate receptor activation in nociceptive afferents may upregulate A-Kinase Anchoring Protein 150 (AKAP150) expression and/or function.

Objectives: To quantify transcriptional changes in AKAP150 expression and/or function after long-term mGluR5 agonist exposure, and identify transcriptional elements responsible.

Methods: Dorsal root ganglia (DRG) were dissected from Sprague-Dawley rats and cultured for biochemical analysis of AKAP150 expression after prolonged mGluR5 agonist exposure.

Subproteomic profiling of sarcolemma from dystrophic skeletal muscle.

The proteomic data presented in this article provide supporting information to the related research article "Proteomic analysis of the sarcolemma-enriched fraction from dystrophic skeletal muscle" (Murphy et al., 2018) [1]. In the associated research article, the sarcolemma from normal versus dystrophic skeletal muscle was analyzed by mass spectrometry-based proteomics.

Clonal variation in productivity and proteolytic clipping of an Fc-fusion protein in CHO cells: Proteomic analysis suggests a role for defective protein folding and the UPR.

Product degradation, such as clipping, is a common quality issue in the production of Fc-fusion proteins from Chinese hamster ovary (CHO) cells. Degradation of proteins is mainly due to the action of either intracellular or extracellular host cell proteases. This study was carried out to understand more fundamentally the intracellular events that may play a role in determining why cell lines from the same cell line development project can vary with regards to the extent of Fc-fusion protein clipping.

Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic.

Background: In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC).

Methods: Initially, a chart review was performed on all patients with hemoptysis (2011-2012) and thereafter a prospective analysis was performed (2013-2016).

Accuracy of Endoscopic Ultrasound Imaging in Distinguishing Celiac Ganglia From Celiac Lymph Nodes.

Background & Aims: Endoscopic ultrasound (EUS) allows visualization of celiac lymph nodes (CLNs) and celiac ganglia (CG). Reliably distinguishing these structures is important for tumor staging and CG ablative therapies. We aimed to evaluate the accuracy of EUS in distinguishing CLNs from CG using a strict cytopathology reference standard.

Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis.

Patients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of MAP2K1/MEK1 in 50% and 25% of cases, respectively. We evaluated a patient with treatment-refractory LCH for mutations in the RAS-RAF-MEK-ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto-activating.

Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling.

The hyaluronidase Hyal1 is clinically and functionally implicated in prostate cancer progression and metastasis. Elevated Hyal1 accelerates vesicular trafficking in prostate tumor cells, thereby enhancing their metastatic potential in an autocrine manner through increased motility and proliferation. In this report, we found Hyal1 protein is a component of exosomes produced by prostate tumor cell lines overexpressing Hyal1.

MDA-5 associated rapidly progressive interstitial lung disease with recurrent Pneumothoraces: a case report.

Background: Clinically hypomyopathic dermatomyositis is a rare disease that is important to recognize, investigate and treat early as it is associated with poor prognosis. In a proportion of patients, myositis specific antibodies could be negative, but with high clinical suspicion, myositis associated antibodies should be ordered. Anti-MDA-5 antibodies was reported in literature to be associated with severe and rapidly progressive interstitial lung disease, with few case reports of pneumothorax and/or pneumomediastinum.

The effects of red tide (Karenia brevis) on reflex impairment and mortality of sublegal Florida stone crabs, Menippe mercenaria.

The Florida stone crab, Menippe mercenaria, is a major commercial fishery that occurs primarily along Florida's west coast, where harmful algal blooms of Karenia brevis frequently develop. To determine sublethal and lethal effects of K. brevis on M.

Analysis of Cell-Free DNA to Assess Risk of Tumoremia Following Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Adenocarcinomas.

Background & Aims: Cellular and nuclear material from tumors disseminates into the bloodstream (tumoremia), but it is not clear whether medical procedures cause release of this material or contribute to formation of metastases. We performed a prospective study of blood samples from patients with pancreatic adenocarcinoma (PDAC) to determine whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) associates with markers of tumoremia.

Methods: We obtained peripheral blood from 104 patients (35 with PDAC) before and after EUS-FNA of primary tumors; blood samples from 69 healthy individuals were used as controls.

Proteomic analysis of the sarcolemma-enriched fraction from dystrophic mdx-4cv skeletal muscle.

The highly progressive neuromuscular disorder dystrophinopathy is triggered by primary abnormalities in the Dmd gene, which causes cytoskeletal instability and loss of sarcolemmal integrity. Comparative organellar proteomics was employed to identify sarcolemma-associated proteins with an altered concentration in dystrophic muscle tissue from the mdx-4cv mouse model of dystrophinopathy. A lectin agglutination method was used to prepare a sarcolemma-enriched fraction and resulted in the identification of 190 significantly changed protein species.

Outcomes of Presumed Aseptic Long-Bone Nonunions With Positive Intraoperative Cultures Through a Single-Stage Surgical Protocol.

Objective: To evaluate the outcomes of a single-stage surgical protocol to treat a presumed aseptic long-bone nonunion with positive intraoperative cultures obtained at the time of surgery.

Design: Retrospective comparative series.

Setting: Orthopaedic specialty hospital.

High-risk HPV genotype distribution in HPV co-test specimens: study of a predominantly Midwestern population.

Introduction: High-risk HPV (HR-HPV) genoprevalence was assessed in cytologic specimens co-tested for HR-HPV in a predominantly Midwestern U.S. population, of which there are limited current data.

Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats.

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or -3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O₂ with brief hypoxic episodes (12% O₂); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, -3 PUFAs in fish oil, or olive oil only from P0 to P14.

Targeting epigenetics for treatment of BRAF mutated metastatic melanoma with decitabine in combination with vemurafenib: A phase lb study.

Introduction: Epigenetic modifications play an important role in progression and development of resistance in BRAF positive metastatic melanoma. Therefore, we hypothesized that the action of vemurafenib (BRAF inhibitor) can be made more effective by combining with low dose decitabine (a DNA methyltransferase inhibitor). The primary objective of this phase lb study was to determine the dose limiting toxicity and maximum tolerated dose of combination of subcutaneous decitabine with oral vemurafenib in patients with BRAF positive metastatic melanoma with or without any prior treatment.

Parallel mRNA, proteomics and miRNA expression analysis in cell line models of the intestine.

Aim: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine.

Methods: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.

Purification and Identification of Membrane Proteins from Urinary Extracellular Vesicles using Triton X-114 Phase Partitioning.

Urinary extracellular vesicles (uEVs) have become a promising source for biomarkers accurately reflecting biochemical changes in kidney and urogenital diseases. Characteristically, uEVs are rich in membrane proteins associated with several cellular functions like adhesion, transport, and signaling. Hence, membrane proteins of uEVs should represent an exciting protein class with unique biological properties.

Efficacy and Treatment Response of Intra-articular Corticosteroid Injections in Patients With Symptomatic Knee Osteoarthritis.

Introduction: Intra-articular corticosteroid injections are often used for short-term pain relief in patients with knee osteoarthritis (OA). This study investigates the efficacy of intra-articular corticosteroid injections in patients with symptomatic knee OA and factors that affect treatment response.

Methods: This prospective, multicentered cohort study had 100 participants with radiographic evidence of knee OA enrolled.

A novel inhibitory anti-invasive MAb isolated using phenotypic screening highlights AnxA6 as a functionally relevant target protein in pancreatic cancer.

Background: Discovery and validation of new antibody tractable targets is critical for the development of new antibody therapeutics to address unmet needs in oncology.

Methods: A highly invasive clonal variant of the MDA-MB-435S cell line was used to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry.

A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection.