bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organophosphate insecticide exposure: A clinical consideration of chlorpyrifos regulation
Authors: Curtis Alexa Colgrove , Sattler Barbara 
Published: May 2018

ABSTRACT

Background and purpose:
In March 2017, the Environmental Protection Agency (EPA) reversed course on a proposal to ban the agricultural use of the organophosphate (OP) insecticide chlorpyrifos (CPF). The purpose of this article is to examine the evidence leading to this controversial decision and provide clinically applicable health promotion guidance for nurse practitioners on CPF exposure and risk reduction measures.

Methods:
Environmental Protection Agency documents on CPF regulation and corresponding research referenced within the EPA reports are reviewed. Evidence-based health promotion strategies obtained through PubMed, CINAHL, Center for Disease Control and Prevention, and National Institutes of Health sources are summarized.

Conclusions:
Available data suggest a potential association between CPF exposure and adverse neurodevelopmental outcomes. Particularly vulnerable populations are pregnant women, children younger than two years, and agricultural workers. There may be genetic variability in susceptibility to environmental toxins.

Implications for practice:
Because of the extensive use of the OP CPF in agriculture and other community-based settings throughout the United States, nurse practitioners should be knowledgeable of the evidence regarding CPF exposure and be prepared to provide health promotion guidance to patients in clinical practice. Nurse practitioners should also consider their role in advocacy for healthy environments and the protection of vulnerable populations as it relates to agricultural insecticide exposure.
Impact of the acute care nurse practitioner in reducing the number of unwarranted daily laboratory tests in the intensive care unit
Authors: Jefferson Brian K. , King Joan E. 
Published: May 2018

ABSTRACT

Background:
Frequent laboratory testing may be necessary at times for critically ill patients. However, the practice of indiscriminate laboratory test ordering is common.

Purpose:
The purpose of this quality improvement project was to assess the effectiveness of the acute care nurse practitioner (ACNP) in reducing the number of unwarranted laboratory tests ordered for ICU patients. To determine whether the presence of an ACNP would make a difference, an ACNP was present on daily ICU multidisciplinary rounds to facilitate the discussion of the laboratory testing needs for each patient for the following 24-hour period.

Conclusions:
Eighty-one patients were enrolled in the project, 41 in the comparison and 40 in the intervention group. No significant differences were noted between the two groups. The project demonstrated that although there was an increase in tests ordered for the intervention group, the increase was brought about by an increase in specific individual tests rather than an increase in panels of laboratory tests. A reduction in patient cost was observed for the number of tests ordered. No increase in adverse events was noted.

Implications for Practice:
Acute care nurse practitioner presence on multidisciplinary rounds may be an effective method to change the practice toward the ordering of tests based on clinical indication.
Improving aesthetic outcomes after head and neck reconstruction
Authors: Al Afif Ayham , Uys H. Kendal , Taylor S. Mark 
Published: May 2018

Purpose of review
Tremendous advancements have been made in head and neck reconstruction following oncologic resection. Despite this, many patients are left with disfiguring postoperative changes. The focus of this review highlights various techniques aimed at improving aesthetic outcomes following head and neck cancer therapy, with a focus on liposuction and fat augmentation.

Recent findings
Over the past decade, the use of liposuction in treating lymphedema after head and neck cancer therapy has showed promising results. Owing to great improvements in harvesting and purification techniques, fat augmentation has been effectively utilized in correcting a wide array of defects. Although free tissue transfer is frequently used in head and neck reconstruction, there is a scarcity of literature on the indications for flap revision procedures.

Summary
Head and neck reconstructive surgery can lead to significant cosmetic and functional morbidity. Several tools are available to help improve aesthetic outcomes in this patient population. A thorough understanding of the various techniques and their indications is essential for achieving optimal results.

Video abstract available: See the Video Supplementary Digital Content 1, http://links.lww.com/COOH/A34
Differences Between Subtalar Instability and Lateral Ankle Instability Focusing on Subtalar Ligaments Based on Three Dimensional Isotropic Magnetic Resonance Imaging
Authors: Yoon Deuk Young , Moon Sung Gyu , Jung Hong-Geun , Kim Na Ra 
Published: May 2018

ObjectiveThe purpose of this study was to assess the differences between subtalar instability (STI) and lateral ankle instability (LAI) focusing on subtalar ligaments using 3-dimensional (3D) isotropic magnetic resonance imaging (MRI).MethodsPreoperative MRIs of 10 patients with STI who failed nonoperative treatment and consequently underwent arthroscopic subtalar reconstruction were compared with preoperative MRIs of 23 patients with LAI who underwent ligament repair or reconstruction. Dimensions of anterior capsular ligament (ACL), interosseous talocalcaneal ligament (ITCL), calcaneofibular ligament (CFL), and anterior talofibular ligament (ATFL) were measured. Tears of ACL, ITCL, CFL, ATFL, cervical ligament, and inferior extensor retinaculum were analyzed.ResultsPatients with subtalar instability had significantly lower ACL thickness and width than patients with LAI (thickness: 1.48 vs 2.12 mm,P= 0.045; width: 7.30 vs 8.64 mm,P= 0.029). An ACL thickness of 1.8 mm or less had sensitivity and specificity both at 75.0%, and an ACL width of 8 mm or less had sensitivity of 75.0% and specificity of 85.0% for discriminating STI from LAI. Absence or complete tear of ACL was more frequent in patients with STI than in patients with LAI (60.0% vs 13.0%,P= 0.010). The ATFL thickness was significantly greater in patients with LAI (P= 0.001). Complete tear of ATFL was more common in patients with LAI (P= 0.008). Complete tear of CFL was common in both the STI and LAI groups without significant difference (20.0% vs 21.7%). There was no significant difference in thickness and width of ITCL and in CFL thickness. Complete tear of ITCL, cervical ligament, and inferior extensor retinaculum were rare without significant difference.ConclusionIn patients with STI, the ACL is thin and narrow and more commonly absent or torn compared with patients with LAI. Complete tear of ATFL was more common in patients with LAI. Complete tear of CFL was commonly encountered in both the STI and LAI groups.
Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer
Authors: Choi Yoon Young , Kim Hyunki , Shin Su-Jin , Kim Ha Yan , Lee Jinae , Yang Han-Kwang , Kim Woo Ho , Kim Young-Woo , Kook Myeong-Cherl , Park Young Kyu , Kim Hyung-Ho , Lee Hye Seung , Lee Kyung Hee , Gu Mi Jin , Choi Seung Ho , Hong SoonWon , Kim Jong Won , Hyung Woo Jin , Noh Sung Hoon , Cheong Jae-Ho 
Published: May 2018

Objective:
We investigated microsatellite instability (MSI) status and programed cell death ligand 1 (PD-L1) expression as predictors of prognosis and responsiveness to chemotherapy for stage II/III gastric cancer.

Background:
The clinical implications of MSI status and PD-L1 expression in gastric cancer have not been well-elucidated.

Methods:
Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial—a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five quasi-monomorphic mononucleotide markers were used to assess tumor MSI status. PD-L1 expressions of tumor and stromal immune cells were evaluated using immunohistochemistry.

Results:
Of 592 patients, 40 (6.8%) had MSI-high (MSI-H) tumors. Among 582 patients available for immunohistochemistry evaluation, PD-L1 was positive in tumor cells (tPD-L1) of 16 patients (2.7%) and stromal immune cells (sPD-L1) of 165 patients (28.4%). Multivariable analysis of disease-free survival (DFS) showed that MSI-H and sPD-L1-positivity were independent prognostic factors [hazard ratio 0.301 (0.123–0.736), 0.714 (0.514–0.991); P = 0.008, 0.044), as were receiving chemotherapy, age, tumor grade, and TNM stage. Although adjuvant chemotherapy improved DFS in the microsatellite-stable (MSS) group (5-year DFS: 66.8% vs 54.1%; P = 0.002); no benefit was observed in the MSI-H group (5-year DFS: 83.9% vs 85.7%; P = 0.931). In the MSS group, sPD-L1-negative patients, but not sPD-L1-positive patients, had significant survival benefit from adjuvant chemotherapy compared with surgery only (5-year DFS: 66.1% vs 50.7%; P = 0.001).

Conclusion:
MSI status and PD-L1 expression are clinically actionable biomarkers for stratifying patients and predicting benefit from adjuvant chemotherapy after D2 gastrectomy for stage II/III gastric cancer.
Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Authors: Dentro Stefan C. , Leshchiner Ignaty , Haase Kerstin , Tarabichi Maxime , Wintersinger Jeff , Deshwar Amit G. , Yu Kaixian , Rubanova Yulia , Macintyre Geoff , Demeulemeester Jonas , Vázquez-García Ignacio , Kleinheinz Kortine , Livitz Dimitri G. , Malikic Salem , Donmez Nilgun , Sengupta Subhajit , Anur Pavana , Jolly Clemency , Cmero Marek , Rosebrock Daniel , Schumacher Steven , Fan Yu , Fittall Matthew , Drews Ruben M. , Yao Xiaotong , Lee Juhee , Schlesner Matthias , Zhu Hongtu , Adams David J. , Getz Gad , Boutros Paul C. , Imielinski Marcin , Beroukhim Rameen , Sahinalp S. Cenk , Ji Yuan , Peifer Martin , Martincorena Inigo , Markowetz Florian , Mustonen Ville , Yuan Ke , Gerstung Moritz , Spellman Paul T. , Wang Wenyi , Morris Quaid D. , Wedge David C. , Van Loo Peter ,   on behalf of the PCAWG Evolution and Heterogeneity Working Groupthe PCAWG consortium.,   the PCAWG consortium
Published: May 2018

SUMMARYIntra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin and drivers of ITH across cancer types are poorly understood. To address this question, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples, spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions, with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types, and identify cancer type specific subclonal patterns of driver gene mutations, fusions, structural variants and copy-number alterations, as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution, and provide an unprecedented pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.
Combinatorial quorum sensing in Pseudomonas aeruginosa allows for novel cheating strategies
Authors: Gurney James , Azimi Sheyda , Brown Sam P. , Diggle Stephen P. 
Published: May 2018

ABSTRACTIn the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) is a social trait that is exploitable by non-cooperating cheats. Previously it has been shown that by linking QS to the production of both public and private goods, cheats can be prevented from invading populations of cooperators and this has been termed ‘a metabolic incentive to cooperate’. We hypothesized P. aeruginosa could evolve novel cheating strategies to circumvent private goods metabolism by rewiring its combinatorial response to two QS signals (3O-C12-HSL and C4-HSL). We performed a selection experiment that cycled P. aeruginosa between public and private goods growth media and evolved an isolate which rewired its control of cooperative protease expression from a synergistic (AND-gate) response to dual signal input, to a 3O-C12-HSL only response. We show that this isolate circumvents metabolic incentives to cooperate and acts as a combinatorial signaling cheat, with a higher fitness in competition with its ancestor. Our results show three important principles; first, combinatorial QS allows for diverse social strategies to emerge; second, that restrictions levied by private goods are not sufficient to explain the maintenance of cooperation in natural populations and third that modifying combinatorial QS responses could result in important physiological outcomes in bacterial populations.
Targeting comorbid diseases via network endopharmacology
Authors: Aguirre-Plans Juaquim , Piñero Janet , Menche Jörg , Sanz Ferran , Furlong Laura I , Schmidt Harald H. H. W. , Oliva Baldo , Guney Emre 
Published: May 2018

AbstractThe traditional drug discovery paradigm has shaped around the idea of “one target, one disease”. Recently, it has become clear that not only it is hard to achieve single target specificity but also it is often more desirable to tinker the complex cellular network by targeting multiple proteins, causing a paradigm shift towards polypharmacology (multiple targets, one disease). Given the lack of clear-cut boundaries across disease (endo)phenotypes and genetic heterogeneity across patients, a natural extension to the current polypharmacology paradigm is targeting common biological pathways involved in diseases, giving rise to “endopharmacology” (multiple targets, multiple diseases). In this study, leveraging powerful network medicine tools, we describe a recipe for first, identifying common pathways pertaining to diseases and then, prioritizing drugs that target these pathways towards endopharmacology. We present proximal pathway enrichment analysis (PxEA) that uses the topology information of the network of interactions between disease genes, pathway genes, drug targets and other proteins to rank drugs for their interactome-based proximity to pathways shared across multiple diseases, providing unprecedented drug repurposing opportunities. As a proof of principle, we focus on nine autoimmune disorders and using PxEA, we show that many drugs indicated for these conditions are not necessarily specific to the condition of interest, but rather target the common biological pathways across these diseases. Finally, we provide the high scoring drug repurposing candidates that can target common mechanisms involved in type 2 diabetes and Alzheimer’s disease, two phenotypes that have recently gained attention due to the increased comorbidity among patients.
isiKnock: in silico knockouts in biochemical pathways
Authors: Scheidel Jennifer , Giese Heiko , Schweizer Börje , Amstein Leonie , Ackermann Jörg , Koch Ina 
Published: May 2018

AbstractSummaryisiKnock is a new software that automatically conducts in silico knockouts for mathematical models of biochemical pathways. The software allows for the prediction of the behavior of biological systems after single or multiple knockout. The implemented algorithm applies transition invariants and the novel concept of Manatee invariants. A knockout matrix visualizes the results. The tool enables the analysis of dependencies, for example, in signal flows from the receptor activation to the cell response at steady state.Availability and ImplementationisiKnock is an open-source tool, freely available at http://www.bioinformatik.uni-frankfurt.de/tools/isiKnock/index.php. It requires at least Java 8 and runs under Microsoft Windows, Linux, and Mac OS.Contactina.koch@bioinformatik.uni-frankfurt.de
Cryptic adaptor protein interactions regulate DNA replication initiation
Authors: Matthews Lindsay A. , Simmons Lyle A. 
Published: May 2018

AbstractDNA replication is a fundamental biological process that is tightly regulated in all living cells. In bacteria, the master regulator DnaA controls when and where replication begins by building a step-wise complex that loads the replicative helicase onto chromosomal DNA. In many bacteria, DnaA requires the adaptor proteins DnaD and DnaB to aid DnaA during helicase loading. How DnaA, its adaptors, and the helicase form a complex at the origin is largely unknown. In this study, we addressed this long-standing question by disassembling the initiation proteins into their individual domains and testing all possible pair-wise combinations in a bacterial two-hybrid assay. Here we report a full description of the cryptic interaction sites used by the helicase loading machinery fromBacillus subtilis. In addition, we investigated how complex formation of the helicase loading machinery is regulated by the checkpoint protein SirA, which is a potent replication inhibitor in sporulating cells. We found that SirA and the DnaD adaptor bind overlapping sites on DnaA, and therefore SirA acts as a competitive inhibitor to block initiation. The interaction between DnaA and DnaD was also mapped to the same DnaA surface in the human pathogenStaphylococcus aureus, demonstrating the broad conservation of this interface. Therefore, our approach has unveiled key protein interactions essential for initiation and is widely applicable for mapping interactions in other signaling pathways that are governed by cryptic binding surfaces.Author SummaryIn order to proliferate, bacteria must first build a step-wise protein complex on their chromosomes that determines when and where DNA replication begins. This protein complex is assembled through dynamic interactions that have been difficult to study and remain largely uncharacterized. Here we show that by deconstructing the proteins into their constituent domains, the interactions used to build the initiation complex can be readily detected and mapped to single amino acid resolution. Using this approach, we demonstrate that DNA replication is controlled through conformational changes that dictate the availability of interaction surfaces. In addition, negative regulators can also block DNA replication by influencing complex formation so that cells survive inhospitable conditions. Initiation proteins from the model organismB. subtilisand the human pathogenS. aureuswere both used to underscore the general applicability of the results to different bacterial systems. Furthermore, our general strategy for mapping dynamic protein interactions is suitable for many different signaling pathways that are controlled through cryptic interaction surfaces.
A putative human infertility allele of the meiotic recombinase DMC1 does not affect fertility in mice
Authors: Tran Tina N. , Schimenti John C. 
Published: May 2018

ABSTRACTWhole exome or genome sequencing is becoming routine in clinical situations for identifying mutations underlying presumed genetic causes of disease, including infertility. While this is a powerful approach for implicating polymorphisms or de novo mutations in genes plausibly related to the phenotype, a greater challenge is to definitively prove causality. This is a crucial requisite for treatment, especially for infertility, in which validation options are limited. In this study, we created a mouse model of a putative infertility allele,DMC1M200V.DMC1encodes a RecA homolog essential for meiotic recombination and fertility in mice. This allele was originally implicated as being responsible for sterility of a homozygous African woman, a conclusion supported by subsequent biochemical analyses of the mutant protein and by studies of yeast with the orthologous amino acid change. Here, we found thatDmc1M200V/M200Vmale and female mice are fully fertile and do not exhibit any gonadal abnormalities. Detailed immunocytological analysis of meiosis revealed no defects suggestive of compromised fertility. This study serves as a cautionary tale for making conclusions about consequences of genetic variants, especially with respect to infertility, and emphasizes the importance of conducting relevant biological assays for making accurate diagnoses in the era of genomic medicine.
Nonparametric analysis of contributions to variance in genomics and epigenomics data
Authors: Moskowitz David M. , Greenleaf William J. 
Published: May 2018

AbstractFunctional genomics studies, despite increasingly varied assay types and complex experimental designs, are typically analyzed by methods that are unable to identify confounding effects and that incorporate parametric assumptions particular to gene expression data. We present MAVRIC, a nonparametric method to quantify variance explained by experimental covariates and perform differential analysis on arbitrary data types. We demonstrate that MAVRIC can accurately associate covariates with underlying data variance, deliver sensitive and specific identification of genomic loci with differential counts, and provide effective noise reduction of large-scale consortium data sets.
Comparison of antioxidant activity between cyanidin-3-O-glucoside (C3G) liposome and cyanidin-3-O-glucoside (C3G) in 2D and 3D cell cultures
Authors: Liang Tisong , Guan Rongfa , Cao Guozhou , Shen Haitao , Liu Zhenfeng , Xia Qile , Wang Zhe 
Published: May 2018

ABSTRACTThe 2D cell culture is the predominant in vitro model for numerous studies. However, 2D cell cultures may not accurately reflect the functions of three-dimensional (3D) tissues, which have extensive cell–cell and cell–matrix interactions; thus, using 2D cell cultures may lead to inaccurate experimental results. Therefore, to obtain adequate and detailed information about the antioxidant activity of cyanidin-3-O-glucoside (C3G) and C3G liposomes in the 2D and 3D cell culture models, we used in this study H2O2to construct the cell damage model and assess the antioxidant activity of C3G and C3G liposomes on Caco-2 cells cultured in the 3D model. We also measured the cell viability, cell morphology, and activity of glutathione (GSH), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content of Caco-2 cells treated with H2O2, C3G, and C3G liposomes. Results showed that cells cultured in the 3D culture model formed a 3D structure and tight spheroids and showed increased cell activity and IC50. The C3G and C3G liposomes can enhance the activity of GSH, SOD, and T-AOC but decrease the MDA content. At the same time, the effect was more obvious in the 3D cell culture model than in the cells cultured in the 2D model. This study revealed that the results obtained from the 2D cell model may be inaccurate compared with the results obtained from the 3D cell model. A realistic mechanism study of antioxidant activity of C3G and C3G liposomes in the 3D cell model, which acts as an intermediate stage bridging the in vitro 2D and in vivo models, was observed.