bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships among factors affecting advanced practice registered nurses' job satisfaction and intent to leave: A systematic review
Authors: Han Robin M. , Carter Patricia , Champion Jane Dimmitt 
Published: May 2018

Background and purpose:
This systematic review explores relationships between advanced practice registered nurses' (APRN) job satisfaction and intent to leave. There exists a dearth of APRN providers compared with the ever-growing need for their services. Furthermore, the organizational costs associated with the APRN turnover are extremely high. It, therefore, behooves practice administrators to understand what factors most contribute to APRN job satisfaction and retention.

Methods:
A search of research databases CINAHL, PubMed, and PsycINFO, using keywords “Advanced Practice Registered Nurse,” “job satisfaction,” “intent to leave,” “anticipated turnover,” and “Nurse Practitioner” to yield articles included in this review.

Conclusions:
The strength of existing evidence for this topic is weak. Studies have found that extrinsic factors, such as administrative support and salary, significantly contribute to job dissatisfaction, whereas intrinsic factors, such as autonomy and finding work meaningful, most significantly contribute to job satisfaction. Additional research is needed to better understand the factors relating to APRN job satisfaction and dissatisfaction, and how those factors influence practitioners' intent to leave.

Implications for practice:
Efforts to improve APRN job satisfaction will have positive implications for provider retention, practices, and patients. Administrators should consider the job satisfaction factors identified herein when implementing practice improvement and retention efforts.
Surrogates' experiences of engaging in Physician Orders for Life-Sustaining Treatment discussions for persons with advanced dementia
Authors: Kim Hyejin , Bradway Christine , Hickman Susan E. , Ersek Mary 
Published: May 2018

ABSTRACT

Background and purpose:
Little is known about surrogates' experiences of engaging in Physician Orders for Life-Sustaining Treatment (POLST) discussions. This study describes family surrogates' experiences when engaging in POLST discussions with primary care providers.

Methods:
Semistructured interviews were conducted with 10 family surrogates of individuals with advanced dementia who were enrolled in a Program of All-Inclusive Care for the Elderly or resided in a nursing home. Interviews were analyzed using directed content analysis based on the conceptual model of communication and surrogate decision making by Torke et al.

Results and conclusion:
Surrogates reported that clear explanations of clinical information and the opportunity to ask questions and reiterate what they heard were helpful in making treatment decisions. Moreover, surrogates reported feeling respected and understood when providers expressed concern for them or their family member with advanced dementia and asked them about their emotional responses to decision making. Although nine surrogates reported very positive communication with providers, one surrogate expressed discomfort with the interaction and described feeling pressured to make health care decisions.

Implications for practice:
With effective communication, family surrogates feel emotionally supported during communication and decision-making processes. Providers are encouraged to focus on developing expert communication skills for end-of-life care discussions.
Noise Analysis in Biochemical Complex Formation
Authors: Xu Zikai , Ghusinga Khem Raj , Singh Abhyudai 
Published: May 2018

AbstractSeveral biological functions are carried out via complexes that are formed via multimerization of either a single species (homomers) or multiple species (heteromers). Given functional relevance of these complexes, it is arguably desired to maintain their level at a set point and minimize fluctuations around it. Here we consider two simple models of complex formation – one for homomer and another for heteromer of two species – and analyze how important model parameters affect the noise in complex level. In particular, we study effects of (i) sensitivity of the complex formation rate with respect to constituting species’ abundance, and (ii) relative stability of the complex as compared with that of the constituents. By employing an approximate moment analysis, we find that for a given steady state level, there is an optimal sensitivity that minimizes noise (quantified by fano-factor; variance/mean) in the complex level. Furthermore, the noise becomes smaller if the complex is less stable than its constituents. Finally, for the heteromer case, our findings show that noise is enhanced if the complex is comparatively more sensitive to one constituent. We briefly discuss implications of our result for general complex formation processes.
pheno-seq – linking morphological features to gene expression in 3D cell culture systems
Authors: Tirier Stephan M. , Park Jeongbin , Preußer Friedrich , Amrhein Lisa , Gu Zuguang , Steiger Simon , Mallm Jan-Philipp , Waschow Marcel , Eismann Björn , Gut Marta , Gut Ivo G. , Rippe Karsten , Schlesner Matthias , Theis Fabian , Fuchs Christiane , Ball Claudia R. , Glimm Hanno , Eils Roland , Conrad Christian 
Published: May 2018

Abstract3D-culture systems have advanced cancer modeling by reflecting physiological characteristics of in-vivo tissues, but our understanding of functional intratumor heterogeneity including visual phenotypes and underlying gene expression is still limited. Single-cell RNA-sequencing is the method of choice to dissect transcriptional tumor cell heterogeneity in an unbiased way, but this approach is limited in correlating gene expression with contextual cellular phenotypes.To link morphological features and gene expression in 3D-culture systems, we present ‘pheno-seq’ for integrated high-throughput imaging and transcriptomic profiling of clonal tumor spheroids. Specifically, we identify characteristic EMT expression signatures that are associated with invasive growth behavior in a 3D breast cancer model. Additionally, pheno-seq determined transcriptional programs containing lineage-specific markers that can be linked to heterogeneous proliferative capacity in a patient-derived 3D model of colorectal cancer. Finally, we provide evidence that pheno-seq identifies morphology-specific genes that are missed by scRNA-seq and inferred single-cell regulatory states without acquiring additional single cell expression profiles. We anticipate that directly linking molecular features with patho-phenotypes of cancer cells will improve the understanding of intratumor heterogeneity and consequently be useful for translational research.
A crowdsourced analysis to identifyab initiomolecular signatures predictive of susceptibility to viral infection
Authors: Fourati Slim , Talla Aarthi , Mahmoudian Mehrad , Burkhart Joshua G. , Klén Riku , Henao Ricardo , Aydin Zafer , Yeung Ka Yee , Ahsen Mehmet Eren , Almugbel Reem , Jahandideh Samad , Liang Xiao , Nordling Torbjörn E.M. , Shiga Motoki , Stanescu Ana , Vogel Robert ,   The Respiratory Viral DREAM Challenge Consortium, Pandey Gaurav , Chiu Christopher , McClain Micah T. , Woods Chris W. , Ginsburg Geoffrey S. , Elo Laura L. , Tsalik Ephraim L. , Mangravite Lara M. , Sieberts Solveig K. 
Published: May 2018

AbstractRespiratory viruses are highly infectious; however, the variation of individuals’ physiologic responses to viral exposure is poorly understood. Most studies examining molecular predictors of response focus on late stage predictors, typically near the time of peak symptoms. To determine whether pre- or early post-exposure factors could predict response, we conducted a community-based analysis to identify predictors of resilience or susceptibility to several respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV) using peripheral blood gene expression profiles collected from healthy subjects prior to viral exposure, as well as up to 24 hours following exposure. This analysis revealed that it is possible to construct models predictive of symptoms using profiles even prior to viral exposure. Analysis of predictive gene features revealed little overlap among models; however, in aggregate, these genes were enriched for common pathways. Heme Metabolism, the most significantly enriched pathway, was associated with higher risk of developing symptoms following viral exposure.
Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and promotes childhood atopy and asthma
Authors: Levan S.R. , Stamnes K.A. , Lin D.L. , Fujimura K.E. , Ownby D.R. , Zoratti E.M. , Boushey H.A. , Johnson C.C. , Lynch S.V. 
Published: May 2018

AbstractNeonates at risk of childhood atopy and asthma are characterized by gut microbiome perturbation and fecal enrichment of 12,13 DiHOME(1); however, the underlying mechanism and source of this metabolite remain poorly understood. Here we show that 12,13 DiHOME treatment of human dendritic cells altered peroxisome proliferator-activated receptor γ regulated gene expression and decreased immune tolerance. In mice, 12,13 DiHOME treatment prior to airway challenge exacerbated pulmonary inflammation and decreased lung regulatory T cells. Neonatal fecal metagenomic sequencing revealed putative bacterial sources of 12,13 DiHOME. In our cohort, three bacterial genes and their product, 12,13 DiHOME, are associated with increased odds of childhood atopy or asthma, suggesting that early-life gut-microbiome risk factors may shape immune tolerance and identify high-risk neonates years in advance of clinical symptoms.One Sentence SummaryEarly-life gut-microbiome risk factors may shape immune tolerance and identify neonates at high-risk of disease.
Drosophila mef2is essential for normal mushroom body and wing development
Authors: Crittenden Jill R. , Skoulakis Efthimios M. C. , Goldstein Elliott. S. , Davis Ronald L. 
Published: May 2018

ABSTRACTMEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruitflyDrosophila, MEF2 is essential for normal development of wing veins, and for mushroom body formation in the brain. In embryos mutant forD-mef2, there was a striking reduction in the number of mushroom body neurons and their axon bundles were not detectable. D-MEF2 expression coincided with the formation of embryonic mushroom bodies and, in larvae, expression onset was confirmed to be in post-mitotic neurons. With aD-mef2point mutation that disrupts nuclear localization, we find that D-MEF2 is restricted to a subset of Kenyon cells that project to the α/β, and γ axonal lobes of the mushroom bodies, but not to those forming the α’/β’ lobes. Our findings that ancestralmef2is specifically important in dopamine-receptive neurons has broad implications for its function in mammalian neurocircuits.
Enhancer control of miR-155 expression in Epstein-Barr virus infected B cells
Authors: David Wood C. , Carvell Thomas , Gunnell Andrea , Ojeniyi Opeoluwa O. , Osborne Cameron , West Michelle J. 
Published: May 2018

ABSTRACTThe oncogenic microRNA-155 (miR-155) is the most frequently upregulated miRNA in Epstein-Barr virus (EBV)-positive B cell malignancies and is upregulated in other non-viral lymphomas. Both the EBV nuclear antigen 2 (EBNA2), and B cell transcription factor, interferon regulatory factor 4 (IRF4) are known to activate transcription of the host cell gene from which miR-155 is processed (miR-155HG,BIC). EBNA2 also activatesIRF4transcription indicating that EBV may upregulate miR-155 through direct and indirect mechanisms. The mechanism of transcriptional regulation ofIRF4andmiR-155HGby EBNA2 however has not been defined. We demonstrate that EBNA2 can activateIRF4andmiR-155HGexpression through specific upstream enhancers that are dependent on the Notch signaling transcription factor RBPJ, a known binding partner of EBNA2. We demonstrate that in addition to activation of themiR-155HGpromoter, IRF4 can also activatemiR-155HGvia the upstream enhancer also targeted by EBNA2. Gene editing to remove the EBNA2- and IRF4-responsivemiR-155HGenhancer located 60 kb upstream ofmiR-155HGled to reducedmiR155HGexpression in EBV-infected cells. Our data therefore demonstrate that specific RBPJ-dependent enhancers regulate the IRF4-miR-155 expression network and play a key role in the maintenance of miR-155 expression in EBV-infected B cells. These findings provide important insights that will improve our understanding of miR-155 control in B cell malignancies.IMPORTANCEMicroRNA-155 (miR-155) is expressed at high level in many human cancers particularly lymphomas. Epstein-Barr virus (EBV) infects human B cells and drives the development of numerous lymphomas. Two EBV-encoded genes (LMP1 and EBNA2) upregulate miR-155 expression and miR-155 expression is required for the growth of EBV-infected B cells. We show that the EBV transcription factor EBNA2 upregulates miR-155 expression by activating an enhancer upstream from the miR-155 host gene (miR-155HG) from which miR-155 is derived. We show that EBNA2 also indirectly activatesmiR-155expression through enhancer-mediated activation ofIRF4.IRF4 then activates both themiR-155HGpromoter and the upstream enhancer, independently of EBNA2. Gene editing to remove themiR-155HGenhancer leads to a reduction inmiR-155HGexpression. We therefore identify enhancer-mediated activation ofmiR-155HGas a critical step in promoting B cell growth and a likely driver of lymphoma development.
Evaluation of the GenoType MTBDRplusand MTBDRslfor the detection of drug-resistantMycobacterium tuberculosison isolates from Beijing, China
Authors: Jian Jiyong , Yang Xinyu , Yang Jun , Chen Liang 
Published: May 2018

ABSTRACTThe incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR) and extreme drug resistance (XDR-TB) continue to increase alarmingly worldwide and reliable and fast diagnosis of MDR-TB and XDR-TB is essential for the adequate treatment of patients. So molecular line probe assays (LPAs) for detection of MDR-TB and XDR-TB have been endorsed by the World Health Organization (WHO). We analyzed 96 isolates from Beijing comparing culture-based drug susceptibility testing (DST) to LPAs detecting rifampicin (RFP), isoniazid (INH), and levofloxacin (LFX), amikacin (AM), capreomycin (CMP), ethambutol (EMB) resistance. Compared to phenotypic DST, the GenoType MTBDRplusand MTBDRslshowed a sensitivity of 98.7% and a specificity of 88.9% for detection of RFP resistance, 82.1% and 94.4% for INH, 89.7% and 94.4% for LFX, 60.0% and 98.7% for AM/CPM, 57.5% and 98.2% for EMB, respectively. The sensitivity and specificity of LPAs for MDR-TB and XDR-TB were 80.8%, 100% and 50.0%, 97.6%. Mutations in codon S531L of therpoBgene and S315T1 ofKatGgene were dominated in MDR-TB strains. The most frequently observed mutations were in codon A90V of thegyrAgene, A1401G of therrsgene and M306V of theembBgene, according to the MTBDRslresults. Our study showed that, in combination to phenotypic DST, application of the LPAs might be an efficient and reliable supplementary DST assay for rapid susceptibility screening of MDR-TB and XDR-TB. Using LPAs in high MDR/XDR burden countries allows for appropriate and timely treatment, which will reduce transmission rates, morbidity and improve treatment outcomes in patients.
The Biological Evaluation of Fusidic Acid and Its Hydrogenation Derivative as Antimicrobial and Anti-inflammatory Agents
Authors: Wu Pan-Pan , He Hao , Hong W. David , Wu Tong-Rong , Zhao Su-Qing , Cui Xi-Ping , Zhong Ying-Ying , Li Dong-Li , Xu Xue-Tao , Sheng Zhao-Jun , Tu Bo-Rong , Gao Min , Zhou Jun , Ward Stephen A. , O’Neill Paul M. , Zhang Kun 
Published: May 2018

AbstractFusidic acid (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria. Herein, the hydrogenation derivative (WU-FA-01) of fusidic acid was prepared, and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammation properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. The results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed, and the results were in accordance with the MIC and MBC results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced up-regulation of pro-inflammation cytokines IL-1β, TNF-α and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model. Overall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activitiesin vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effectsin vivo. These results provide a scientific basis for developing fusidic acid derivatives as antimicrobial and anti-inflammatory agents.
Restriction of chromatin accessibility is necessary for appropriate enhancer expression
Authors: Hagey Daniel W. , Klum Susanne , Zaouter Cecile , Muhr Jonas 
Published: May 2018

AbstractTissue specific gene expression underpins cell type diversity, and arises from the cooperative activities of transcription factors and the chromatin landscape. It has been previously demonstrated that enhancers with specific arrangements of transcription factor binding motifs can bring together commonly and specifically expressed factors in order to stabilize chromatin accessibility and drive spatially restricted reporter expression within different regions of the CNS. However, when reporters were used to analyse the activity of enhancers bound differentially by a common factor in the endoderm and CNS, several examples of non-tissue specific reporter expression were observed. In order to judge whether or not this may have been due to the unregulated chromatin environment of exogenously delivered enhancer reporters, here we have analysed the chromatin landscape of cells from the CNS and endodermal tissues and find that this reflects neighbouring gene expression to a greater degree than transcription factor binding. This work demonstrates that chromatin accessibility plays an essential role in defining enhancer activity in distantly related cell types.
Studies on the mechanism of membrane mediated general anesthesia
Authors: Pavel Mahmud Arif , Petersen E. Nicholas , Wang Hao , Lerner Richard A. , Hansen Scott B. 
Published: May 2018

ABSTRACTInhaled anesthetics are a chemically diverse collection of hydrophobic molecules that robustly activate TWIK related K+ channels (TREK-1) and reversibly induce loss of consciousness. For a hundred years anesthetics were speculated to target cellular membranes, yet no plausible mechanism emerged to explain a membrane effect on ion channels. Here we show that inhaled anesthetics (chloroform and isoflurane) activate TREK-1 through disruption of palmitate-mediated localization of phospholipase D2 (PLD2) to lipid rafts and subsequent production of signaling lipid phosphatidic acid (PA). Catalytically dead PLD2 robustly blocks anesthetic TREK-1 currents in cell patch-clamp. Localization of PLD2 renders the anesthetic-insensitive TRAAK channel sensitive. General anesthetics chloroform, isoflurane, diethyl ether, xenon, and propofol disrupt lipid rafts and activate PLD2. In the whole brain of flies, anesthesia disrupts rafts and PLDnull flies resist anesthesia. Our results establish a membrane mediated target of inhaled anesthesia and suggest PA helps set anesthetic sensitivity in vivo.
Haplotype-based eQTL mapping finds evidence for complex gene regulatory regions poorly tagged by marginal SNPs
Authors: Brown Robert , Sankararaman Sriram , Pasaniuc Bogdan 
Published: May 2018

AbstractMotivationExpression quantitative trait loci (eQTLs), variations in the genome that impact gene expression, are identified through eQTL studies that test for a relationship between single nucleotide polymorphisms (SNPs) and gene expression levels. These studies typically assume an underlying additive model. Non-additive tests have been proposed, but are limited due to the increase in the multiple testing burden and are potentially biased by filtering criteria that relies on marginal association data. Here we propose using combinations of short haplotypes instead of SNPs as predictors for gene expression. Essentially, this method looks for genomic regions where haplotypes have different effect sizes. The differences in effect can be due to multiple genetic architectures such as a single SNP, a burden of rare SNPs, multiple SNPs with independent effect or multiple SNPs with an interaction effect occurring on the same haplotype.ResultsSimulations show that when haplotypes, rather than SNPs, are assigned non-zero effect sizes, our method has increased power compared to the marginal SNP method. In the GEUVADIS gene expression data, our method finds 101 more eGenes than the marginal method (5,202 vs. 5,101). The methods do not have full overlap in the eGenes that they find. Of the 5,202 eGenes found by our method, 707 are not found by the marginal method—even though it has a lower significance threshold. This indicates that many genes have regulatory architectures that are not well tagged by marginal SNPs and demonstrates the need to better model alternative archi-tectures.
The transnational comparative study on the potential risks and efficiency of commercial banks based on the weight-limited DEA model
Authors: Wang Hao , Wang Yu , Zhao Shuang , Wang Lan-ping , An Hui 
Published: May 2018

Purpose
The purpose of this paper is to calculate the bank efficiency of removing potential risks that are hidden from the extreme portfolio of bank’s assets and further compare the differences and causes of bank’s efficiency and potential risk level between China’s representative banks and OECD representative banks in 2011-2015.

Design/methodology/approach
Based on the weight-limited DEA model, this paper calculates the bank’s efficiency and further compares the differences between China’s representative banks and OECD representative banks by using commercial banks’ transnational data.

Findings
By analyzing US representative banks’ data, the authors find that the excessive expansion of the scale of banks’ investment for the non-real economy shrinks after the bubble burst and would not improve the efficiency of banks immediately. The OECD representative banks rather prefer to extreme asset portfolio so that the potential risks gradually increase, while there is a diminishing effect on investments in non-real economies to improve bank efficiency. On the other hand, China’s representative banks have the signs of reducing investment in the real estate market, but the existence of the bubble in the market led to a lagged effect on the impact of adjustment of bank asset portfolio on efficiency.

Research limitations/implications
This paper has practical significance for commercial banks to improve efficiency and reduce credit risks. This is conducive to the implementation of targeted supervision by the banking supervision department.

Practical implications
Based on the lesson that the financial crisis created by the real estate bubble burst in the USA in 2008 and the financial market active guidance of the developed economies, faced with the reality of Chinese real estate market bubble rising and the continuous improvement of Chinese financial market, this paper compares the differences between representative banks in China and OECD, and explores the causes by using the cross-country data of commercial banks.

Originality/value
By adjusting the weight of the input variables in the efficiency measurement, quantifying the risk is often overlooked by the changes in bank efficiency. This potential risk is caused by the bank’s investment preferences in the non-real economy represented by real estate and tradable financial assets.