Neuroendocrine cell proliferations in lungs explanted for fibrotic interstitial lung disease and emphysema.

Using recently proposed pathological criteria, we determined the incidence of neuroendocrine cell proliferation in a series of explants with lung disease. Cases were defined as NECH (≥3 bronchioles with ≥5 endocrine cells), borderline diffuse neuroendocrine cell hyperplasia (DPNECH) (1-3 tumourlets with or without NECH), and DPNECH (≥3 tumourlets with NECH). Endocrine cells were identified by immunohistochemical staining for synaptophysin.

Osteosarcoma in a Child Below 2 Years of Age: Case Report and Review of the Literature.

Background: Osteosarcoma in children below the age of 5 is extremely rare.

Observation: We report on a previously well 14-month-old male infant, who presented with a reluctance to weight-bear on his right leg and had an associated limp. Plain imaging and a magnetic resonance imaging scan demonstrated a lytic lesion in the right distal femur.

First principles studies of the interactions between alkali metal elements and oxygen-passivated nanopores in graphene.

We characterize the structure-property relationship of alkali metal elements in oxygen-passivated graphene pores using the density functional theory that accounts for quantum mechanical effects and charge transfer. Our description is based on the structural and electronic properties of the system and shows common trends among the different alkali metals and pores. We find that these nanopores which serve as docking sites for alkali metal elements give the strongest binding when the size of the pore is similar to the element's van der Waals radius.

Early developmental arrest and impaired gastrointestinal homeostasis in U12-dependent splicing-defective -deficient mice.

Splicing is an essential step in eukaryotic gene expression. While the majority of introns is excised by the U2-dependent, or major class, spliceosome, the appropriate expression of a very small subset of genes depends on U12-dependent, or minor class, splicing. The U11/U12 65K protein (hereafter 65K), encoded by , is one of seven proteins that are unique to the U12-dependent spliceosome, and previous studies including our own have established that it plays a role in plant and vertebrate development.

"It's just more personal": Using multiple methods of qualitative data collection to facilitate participation in research focusing on sensitive subjects.

Background: Often researchers use only one interview method within a single study. However, it is increasingly common for a variety of interview methods to be employed within a project. Providing choice to participants may facilitate recruitment, particularly when research focuses on a sensitive subject.

Integrated measurement of intracellular proteins and transcripts in single cells.

Biological function arises from the interplay of proteins, transcripts, and metabolites. An ongoing revolution in miniaturization technologies has created tools to analyze any one of these species in single cells, thus resolving the heterogeneity of tissues previously invisible to bulk measurements. An emerging frontier is single cell multi-omics, which is the measurement of multiple classes of analytes from single cells.

SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice.

DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle.

Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer patients with and without human immunodeficiency virus (HIV) infection.

Objective: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients.

Materials And Methods: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015.

Falling through the gap: Dental treatment experiences of patients affected by cleft lip and/or palate.

Introduction: In the UK, one in 600–700 infants is born with a cleft lip and/or palate (CL/P). Previous research has identified patients with CL/P to be at high risk of long-term oral health issues. Yet, few of these patients are currently accessing community dental care.

Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.

Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function. Among the genes coding for the MYST family of KATs (KAT5-KAT8) are the oncogenes KAT6A (also known as MOZ) and KAT6B (also known as MORF and QKF). KAT6A has essential roles in normal haematopoietic stem cells and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia.

Favourable outcomes for childhood acute lymphoblastic leukaemia in an isolated setting: The Tasmanian experience.

Background: Tasmania is a large, relatively isolated island located south of mainland Australia with limited tertiary level paediatric oncology services.

Aims: To benchmark regional outcomes for childhood acute lymphoblastic leukaemia (ALL) against published international standards.

Methods: We undertook a retrospective cohort study, analysing the clinical characteristics and health outcomes of all children diagnosed with and treated for ALL in Tasmania, Australia between 2006 and 2015.

Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding.

TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding.

Alcohol Contributes to Attraction of Heliothis (= Chloridea) virescens Males to Females.

Female-emitted volatile sex pheromones in most moths are composed of biosynthetically related blends of fatty acid derivatives, such as aldehydes, acetate esters and alcohols. In many moths, as in the noctuid Heliothis (Chloridea) virescens, the pheromone gland contains alcohols (e.g.

Surface Immobilization of Redox-Labile Fluorescent Probes: Enabling Single-Cell Co-Profiling of Aerobic Glycolysis and Oncogenic Protein Signaling Activities.

An analytical method is described for profiling lactate production in single cells via the use of coupled enzyme reactions on surface-grafted resazurin molecules. The immobilization of the redox-labile probes was achieved through chemical modifications on resazurin, followed by bio-orthogonal click reactions. The lactate detection was demonstrated to be sensitive and specific.

Are electronic nicotine delivery systems helping cigarette smokers quit? Evidence from a prospective cohort study of U.S. adult smokers, 2015-2016.

Background: The potential of electronic nicotine delivery systems (ENDS) to reduce the cardiovascular and other disease risks of smoking is of great interest. While many smokers report using ENDS for cessation, their impact under real-world use patterns and conditions on adult smokers' quitting behavior is uncertain. The objective of this study was to generate more recent and comprehensive evidence on the effect of "real world" ENDS use on the population quit rates of adult smokers while taking account of frequency and duration of use, device type, e-liquid flavor, and reasons for use.

Allosteric Inhibitor of KRas Identified Using a Barcoded Assay Microchip Platform.

Protein catalyzed capture agents (PCCs) are synthetic antibody surrogates that can target a wide variety of biologically relevant proteins. As a step toward developing a high-throughput PCC pipeline, we report on the preparation of a barcoded rapid assay platform for the analysis of hits from PCC library screens. The platform is constructed by first surface patterning a micrometer scale barcode composed of orthogonal ssDNA strands onto a glass slide.

An Educational Intervention to Improve Inpatient Documentation of High-risk Diagnoses by Pediatric Residents.

Objectives: Diagnoses extracted from physician notes are used to calculate hospital quality metrics; failure to document high-risk diagnoses may lead to the appearance of worse-than-expected outcomes for complex patients. Academic hospitals often rely on documentation authored by trainees, yet residents receive little training in this regard. In this study, we evaluate inpatient pediatric resident notes to determine which high-risk diagnoses are commonly missed and assess the efficacy of a multitiered intervention to improve the documentation of these diagnoses.

Regulation of the Peptidoglycan Amidase PGLYRP2 in Epithelial Cells by Interleukin-36γ.

Interleukin-36 (IL-36) cytokines are important regulators of mucosal homeostasis and inflammation. We have previously established that oral epithelial cells upregulate IL-36γ expression in response to the bacterial pathogen Here, we have established that IL-36γ can stimulate the gene expression of mechanistically distinct antimicrobial proteins, including the peptidoglycan amidase PGLYRP2, in oral epithelial cells (e.g.

Adaptive Divergence in a Defense Symbiosis Driven from the Top Down.

Most studies of adaptive radiation in animals focus on resource competition as the primary driver of trait divergence. The roles of other ecological interactions in shaping divergent phenotypes during such radiations have received less attention. We evaluate natural enemies as primary agents of diversifying selection on the phenotypes of an actively diverging lineage of gall midges on tall goldenrod.

The TNF receptor family member Fn14 is highly expressed in recurrent glioblastoma and in GBM patient-derived xenografts with acquired temozolomide resistance.

Background: Glioblastoma (GBM) is a difficult to treat brain cancer that nearly uniformly recurs, and recurrent tumors are largely therapy resistant. Our prior work has demonstrated an important role for the tumor necrosis factor-like weak inducer of apoptosis (TWEAK) receptor fibroblast growth factor-inducible 14 (Fn14) in GBM pathobiology. In this study, we investigated Fn14 expression in recurrent GBM and in the setting of temozolomide (TMZ) resistance.

Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL.

After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-γ, IL-17A, IL-8, and macrophage inflammatory protein 1α.

Measuring the Impact of Environment on the Health of Large Cities.

The relative significance of indicators and determinants of health is important for local public health workers and planners. Of similar importance is a method for combining and evaluating such markers. We used a recently developed index, the Urban Health Index (UHI), to examine the impact of environmental variables on the overall health of cities.

Parent-perceived isolation and barriers to psychosocial support: a qualitative study to investigate how peer support might help parents of burn-injured children.

Introduction: Burn injuries can be traumatic and distressing for the affected child and family, with a prolonged period of recovery. This research explores parents' experiences of support following their child's injury and their thoughts on peer support specifically.

Methods: Thirteen semi-structured interviews were conducted with parents/caregivers, a mean of three years after their child's injury, either face-to-face or remotely.