bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is polypharmacy an increasing burden in chronic kidney disease? The German experience
Authors: Parker Kathrine , Wong Joanne 
Published: May 2019

Abstract
This is a commentary article describing the key findings of the German chronic kidney disease (GCKD) study and how these relate to current practice. With the GCKD study showing high levels of polypharmacy, this article discusses ways to ensure that polypharmacy is appropriate and the difficulties faced within a chronic kidney disease population. Suggestions of ways to minimize medication burden in renal patients provide some practical advice for clinicians.
Professional development: life or death after pre-service training?
Authors: Higginbotham Christine 
Published: May 2019

Abstract
Within the ELT profession there has been some discussion regarding the appropriateness of one-month pre-service teacher training courses such as CELTA. These courses are designed on the assumption that graduates will need further support and professional development in their first post. This paper examines the extent to which 115 newly qualified teachers (NQTs) were supported in their first teaching posts and addresses a second concern: do short, intensive courses encourage trainees to develop reflective-practice skills? The findings suggest that generally NQTs are not well supported in their first teaching posts, nor are they provided with adequate continued professional development by the institutions they work for. This is particularly evident in the teaching of young learners. However, most NQTs felt CELTA had sufficiently prepared them to be able to reflect on their classroom teaching in their first posts, despite some obstacles to reflective practice being raised.
Ecological and physiological implications of nitrogen oxide reduction pathways on greenhouse gas emissions in agroecosystems
Authors: Yoon Sukhwan , Song Bongkeun , Phillips Rebecca L , Chang Jin , Song Min Joon 
Published: May 2019

ABSTRACTMicrobial reductive pathways of nitrogen (N) oxides are highly relevant to net emissions of greenhouse gases (GHG) from agroecosystems. Several biotic and abiotic N-oxide reductive pathways influence the N budget and net GHG production in soil. This review summarizes the recent findings of N-oxide reduction pathways and their implications to GHG emissions in agroecosystems and proposes several mitigation strategies. Denitrification is the primary N-oxide reductive pathway that results in direct N2O emissions and fixed N losses, which add to the net carbon footprint. We highlight how dissimilatory nitrate reduction to ammonium (DNRA), an alternative N-oxide reduction pathway, may be used to reduce N2O production and N losses via denitrification. Implications of nosZ abundance and diversity and expressed N2O reductase activity to soil N2O emissions are reviewed with focus on the role of the N2O-reducers as an important N2O sink. Non-prokaryotic N2O sources, e.g. fungal denitrification, codenitrification and chemodenitrification, are also summarized to emphasize their potential significance as modulators of soil N2O emissions. Through the extensive review of these recent scientific advancements, this study posits opportunities for GHG mitigation through manipulation of microbial N-oxide reductive pathways in soil.
Multiplex genome editing of microorganisms using CRISPR-Cas
Authors: Adiego-Pérez Belén , Randazzo Paola , Daran Jean Marc , Verwaal René , Roubos Johannes A , Daran-Lapujade Pascale , van der Oost John 
Published: May 2019

ABSTRACT
Microbial production of chemical compounds often requires highly engineered microbial cell factories. During the last years, CRISPR-Cas nucleases have been repurposed as powerful tools for genome editing. Here, we briefly review the most frequently used CRISPR-Cas tools and describe some of their applications. We describe the progress made with respect to CRISPR-based multiplex genome editing of industrial bacteria and eukaryotic microorganisms. We also review the state of the art in terms of gene expression regulation using CRISPRi and CRISPRa. Finally, we summarize the pillars for efficient multiplexed genome editing and present our view on future developments and applications of CRISPR-Cas tools for multiplex genome editing.
Prevalence of antibiotic-resistant Escherichia coli isolated from urban and agricultural streams in Canterbury, New Zealand
Authors: Van Hamelsveld Sophie , Adewale Muyiwa E , Kurenbach Brigitta , Godsoe William , Harding Jon S , Remus-Emsermann Mitja N P , Heinemann Jack A 
Published: May 2019

Abstract
Baseline studies are needed to identify environmental reservoirs of non-pathogenic but associating microbiota or pathogenic bacteria that are resistant to antibiotics and to inform safe use of freshwater ecosystems in urban and agricultural settings. Mesophilic bacteria and Escherichia coli were quantified and isolated from water and sediments of two rivers, one in an urban and one in an agricultural area near Christchurch, New Zealand. Resistance of E. coli to one or more of nine different antibiotics was determined. Additionally, selected strains were tested for conjugative transfer of resistances. Despite having similar concentrations of mesophilic bacteria and E. coli, the rivers differed in numbers of antibiotic-resistant E. coli isolates. Fully antibiotic-susceptible and -resistant strains coexist in the two freshwater ecosystems. This study was the first phase of antibiotic resistance profiling in an urban setting and an intensifying dairy agroecosystem. Antibiotic-resistant E. coli may pose different ingestion and contact risks than do susceptible E. coli. This difference cannot be seen in population counts alone. This is an important finding for human health assessments of freshwater systems, particularly where recreational uses occur downstream.
Outcomes and characterization of chromosomal self-targeting by native CRISPR-Cas systems in Streptococcus thermophilus
Authors: Cañez Cassandra , Selle Kurt , Goh Yong Jun , Barrangou Rodolphe 
Published: May 2019

ABSTRACT
CRISPR-Cas systems provide adaptive immunity against phages in prokaryotes via DNA-encoded, RNA-mediated, nuclease-dependent targeting and cleavage. Due to inefficient and relatively limited DNA repair pathways in bacteria, CRISPR-Cas systems can be repurposed for lethal DNA targeting that selects for sequence variants. In this study, the relative killing efficiencies of endogenous Type I and Type II CRISPR-Cas systems in the model organism Streptococcus thermophilus DGCC7710 were assessed. Additionally, the genetic and phenotypic outcomes of chromosomal targeting by plasmid-programmed Type I-E or Type II-A systems were analyzed. Efficient killing was observed using both systems, in a dose-dependent manner when delivering 0.4–400 ng of plasmid DNA. Targeted PCR screening and genome sequencing were used to determine the genetic basis enabling survival, showing that evasion of Type I-E self-targeting was primarily the result of low-frequency defective plasmids that excised the targeting spacer. The most notable genotype recovered from Type II-A targeting of genomic locus, lacZ, was a 34 kb-deletion derived from homologous recombination (HR) between identical conserved sequences in two separate galE coding regions, resulting in 2% loss of the genome. Collectively, these results suggest that HR contributes to the plasticity and remodeling of bacterial genomes, leading to evasion of genome targeting by CRISPR-Cas systems.
Managing Fragmented Fire-Threatened Landscapes with Spatial Externalities
Authors: Lauer Christopher J , Montgomery Claire A , Dietterich Thomas G 
Published: May 2019

Abstract
Accounting for externalities generated by fire spread is necessary for managing fire risk on landscapes with multiple owners. In this paper, we determine the optimal management of a synthetic landscape parameterized to represent the ecological conditions of Douglas-fir (Pseudotsuga menziesii) plantations in southwest Oregon. The problem is formulated as a dynamic game, where each agent maximizes their own objective without considering the welfare of the other agents. We demonstrate a method for incorporating spatial information and externalities into a dynamic optimization process. A machine-learning technique, approximate dynamic programming, is applied to determine the optimal timing and location of fuel treatments and timber harvests for each agent. The value functions we estimate explicitly account for the spatial interactions that generate fire risk. They provide a way to model the expected benefits, costs, and externalities associated with management actions that have uncertain consequences in multiple locations. The method we demonstrate is applied to analyze the effect of landscape fragmentation on landowner welfare and ecological outcomes.
Genome-Wide Patterns of Gene Expression in a Wild Primate Indicate Species-Specific Mechanisms Associated with Tolerance to Natural Simian Immunodeficiency Virus Infection
Authors: Simons Noah D , Eick Geeta N , Ruiz-Lopez Maria J , Hyeroba David , Omeja Patrick A , Weny Geoffrey , Zheng HaoQiang , Shankar Anupama , Frost Simon D W , Jones James H , Chapman Colin A , Switzer William M , Goldberg Tony L , Sterner Kirstin N , Ting Nelson 
Published: May 2019

AbstractOver 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to human immunodeficiency virus in humans. Notably, an immunosuppressive gene, CD101, was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus.
Functional Ability in Everyday Life: Are Associations With an Engaged Lifestyle Mediated by Working Memory?
Authors: Guye Sabrina , Röcke Christina , Martin Mike , von Bastian Claudia C 
Published: May 2019

Abstract

Objectives
An engaged lifestyle has been linked to measures of functional ability in everyday life. However, the underlying mechanism of this link is still understudied. We propose working memory as a potential mediator of this relation.

Methods
Modeling data of 158 older adults with a latent-variables approach, we examined whether working memory mediated the relation between an engaged lifestyle, that is, intellectual, social, and physical activities, and functional ability, that is, self-reported everyday failures and test-based everyday performance.

Results
Working memory was found to fully mediate the relation between gaming activities and test-based everyday performance. Furthermore, we found a negative association between sports activities and self-reported everyday failures not mediated through working memory, indicating that individuals who reported high levels of sports activities reported fewer everyday cognitive failures. All other lifestyle activities were, however, neither directly nor indirectly associated with functional ability.

Discussion
Working memory is one pathway by which gaming activities are related to test-based measures of functional ability in everyday life. Given the overlapping cognitive demands of working memory, gaming activities, and the test-based measure of functional ability, the findings suggest that while an engaged lifestyle can benefit functional ability, those benefits may be limited to highly similar domains.
MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy
Authors: Cardoso Ana M S , Sousa Madalena , Morais Catarina M , Oancea-Castillo Liliana R , Régnier-Vigouroux Anne , Rebelo Olinda , Tão Hermínio , Barbosa Marcos , Pedroso Maria C de Lima , Jurado Amália S 
Published: May 2019

Abstract
Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.
Mapping Arctic clam abundance using multiple datasets, models, and a spatially explicit accuracy assessment
Authors: Misiuk Benjamin , Bell Trevor , Aitken Alec , Brown Craig J , Edinger Evan N 
Published: May 2019

Abstract
Species distribution models are commonly used in the marine environment as management tools. The high cost of collecting marine data for modelling makes them finite, especially in remote locations. Underwater image datasets from multiple surveys were leveraged to model the presence–absence and abundance of Arctic soft-shell clam (Mya spp.) to support the management of a local small-scale fishery in Qikiqtarjuaq, Nunavut, Canada. These models were combined to predict Mya abundance, conditional on presence throughout the study area. Results suggested that water depth was the primary environmental factor limiting Mya habitat suitability, yet seabed topography and substrate characteristics influence their abundance within suitable habitat. Ten-fold cross-validation and spatial leave-one-out cross-validation (LOO CV) were used to assess the accuracy of combined predictions and to test whether this was inflated by the spatial autocorrelation of transect sample data. Results demonstrated that four different measures of predictive accuracy were substantially inflated due to spatial autocorrelation, and the spatial LOO CV results were therefore adopted as the best estimates of performance.
Is microwave ablation an alternative to stereotactic ablative body radiotherapy in patients with inoperable early-stage primary lung cancer?
Authors: Watson Robert A , Tol Isabel , Gunawardana Shannon , Tsakok Maria T 
Published: May 2019

Summary
A best evidence topic was written according to a structured protocol. The question addressed was: in patients with inoperable early-stage primary lung cancer does microwave ablation (MWA) or stereotactic ablative body radiotherapy (SBRT) achieve improved outcomes in terms of local control, recurrence, survival and complications? Altogether, more than 550 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. No single study directly compared the effects of MWA with SBRT. However, the best available evidence for MWA (7 studies) was compared to that for SBRT (5 studies). The range of 3-year survival reported for MWA was 29.2–84.7%, compared with 42.7–63.5% for SBRT. The range of median survival was 35–60 months for MWA and 32.6–48 months for SBRT. This suggests similar outcomes between these two 2 techniques. Different side-effect profiles were observed between techniques with MWA associated with pneumothorax and fever and SBRT most commonly causing radiation pneumonitis and rib fractures. The evidence base for MWA is less than that for SBRT and is heterogenous in terms of participants and technical design. However, within these limitations, we conclude that MWA appears comparable with SBRT in terms of local control and survival rates.
Autoimmune hepatitis during preoperative chemotherapy in a patient with thymoma
Authors: Nishimura Tomoki , Tsunezuka Hiroaki , Miyata Naoko , Inoue Masayoshi 
Published: May 2019

Abstract
Autoimmune diseases associated with thymoma are well known, with myasthenia gravis being the most common, while autoimmune hepatitis (AIH) is extremely rare. The case of a 63-year-old woman with AIH that developed during preoperative chemotherapy for invasive type B2 thymoma is presented. Liver dysfunction was improved by steroid treatment using oral prednisolone, 30 mg daily, followed by tapering. The patient underwent a macroscopic complete resection including dissemination, and no evidence of recurrence has been seen for 13 months. Although the serum levels of anti-acetylcholine receptor antibody were elevated, no symptoms of myasthenia gravis appeared during the clinical course. This is a rare case of non-myasthenic thymoma complicated with AIH. AIH should be carefully considered in thymoma patients with liver dysfunction, since multidisciplinary treatment is required for invasive thymoma.
Asylum Seeker Children in Nauru: Australia’s International Human Rights Obligations and Operational Realities
Authors: Dechent Susanna , Tania Sharmin , Mapulanga-Hulston Jackie 
Published: May 2019

Abstract
This article examines if Australia’s policy and law regarding asylum seeker and refugee children in Nauru are consistent with its international legal obligations under the terms of the Convention on the Rights of the Child (CRC). Under article 3 of the CRC, Australia is required to consider the best interests of each child within its jurisdiction. It is also bound by the CRC prohibition on arbitrary detention and obligations derived from Convention rights relating to health, education, and family matters. To assess Australia’s law and policy, the article draws on the findings of recent inquiries and reports that examine how detention and conditions at the processing centre and in the community in Nauru have impacted on the mental and physical well-being of children. The article highlights gaps in the implementation of Convention rights and draws together the findings and recommendations made in recent reports to assist in the development of suitable solutions. It concludes that Australia’s treatment of asylum seeker and refugee children violates key obligations under the CRC and that, accordingly, Australia should remove these children from Nauru and settle them in Australia.
Comparative Functional and Phylogenomic Analyses of Host Association in the Remoras (Echeneidae), a Family of Hitchhiking Fishes
Authors: Kenaley C P , Stote A , Ludt W B , Chakrabarty P 
Published: May 2019

Synopsis
The family Echeneidae consists of eight species of marine fishes that hitchhike by adhering to a wide variety of vertebrate hosts via a sucking disc. While several studies have focused on the interrelationships of the echeneids and the adhesion performance of a single species, no clear phylogenetic hypothesis has emerged and the morphological basis of adhesion remains largely unknown. We first set out to resolve the interrelationships of the Echeneidae by taking a phylogenomic approach using ultraconserved elements. Then, within this framework, we characterized disc morphology through µ-CT analysis, evaluated host specificity through an analysis of host phylogenetic distance, and determined which axes of disc morphological variation are associated with host diversity, skin surface properties, mean pairwise phylogenetic distance (MPD obs.), and swimming regime. We recovered an extremely well-supported topology, found that the specificity of host choice is more variable in a pelagic group and less variable in a reef-generalist group than previously proposed, and that axes of disc morphospace are best explained by models that include host skin surface roughness, host MPD obs., and maximum host Reynolds number. This suggests that ecomorphological diversification was driven by the selection pressures of host skin surface roughness, host specialization, and hydrodynamic regime.
Phosphorylation by protein kinase C stabilizes ABCG1 and increases cholesterol efflux
Authors: Watanabe Taro , Kioka Noriyuki , Ueda Kazumitsu , Matsuo Michinori 
Published: May 2019

AbstractATP-binding cassette protein G1 (ABCG1) plays an important role in eliminating excess cholesterol from macrophages and in the formation of high-density lipoprotein (HDL), which contributes to the prevention and regression of atherosclerosis. The post-translational regulation of ABCG1 remains elusive, although phosphorylation by protein kinase A destabilizes ABCG1 proteins. We examined the phosphorylation of ABCG1 using HEK293 and Raw264.7 cells. ABCG1 phosphorylation was enhanced by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator. PKC activation by TPA increased ABCG1 protein levels and promoted ABCG1-dependent cholesterol efflux to HDL. This activity was suppressed by Go6976, a PKCα/βI inhibitor, suggesting that PKC activation stabilizes ABCG1. To confirm this, the degradation rate of ABCG1 was analysed; ABCG1 degradation was suppressed upon PKC activation, suggesting that PKC phosphorylation regulates ABCG1 levels. To confirm this involvement, we co-expressed ABCG1 and a constitutively active form of PKCα in HEK cells. ABCG1 was increased upon co-expression. These results suggest that PKC-mediated phosphorylation, probably PKCα, stabilizes ABCG1, consequently increasing ABCG1-mediated cholesterol efflux, by suppressing ABCG1 degradation. PKC activation could thus be a therapeutic target to suppress the development of atherosclerosis.