bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic identification of the functional surface for RNA binding by Escherichia coli ProQ
Authors: Pandey Smriti , Gravel Chandra M , Stockert Oliver M , Wang Clara D , Hegner Courtney L , LeBlanc Hannah , Berry Katherine E
Published: October 2019

The FinO-domain-protein ProQ is an RNA-binding protein that has been known to play a role in osmoregulation in proteobacteria. Recently, ProQ has been shown to act as a global RNA-binding protein in Salmonella and E. coli, binding to dozens of small RNAs (sRNAs) and messenger RNAs (mRNAs) to regulate mRNA-expression levels through interactions with both 5′ and 3′ untranslated regions (UTRs). Despite excitement around ProQ as a novel global RNA-binding protein interacting with many sRNAs and mRNAs, and its potential to serve as a matchmaking RNA chaperone, significant gaps remain in our understanding of the molecular mechanisms ProQ uses to interact with RNA. In order to apply the tools of molecular genetics to this question, we have adapted a bacterial three-hybrid (B3H) assay to detect ProQ's interactions with target RNAs. Using domain truncations, site-directed mutagenesis and an unbiased forward genetic screen, we have identified a group of highly conserved residues on ProQ's NTD as the primary face for in vivo recognition of two RNAs, and propose that the NTD structure serves as an electrostatic scaffold to recognize the shape of an A-form RNA duplex.
The Longitudinal Assessment of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Alzheimer’s disease and their Association with White Matter Hyperintensities in the National Alzheimer’s Coordinating Center’s Uniform Data Set
Authors: Anor Cassandra J. , Dadar Mahsa , Collins D. Louis , Tartaglia M. Carmela
Published: October 2019

Introduction

Neuropsychiatric symptoms (NPS) are common in all dementias, including those with Alzheimer’s disease (AD). NPS contribute to patients’ distress, caregiver burden, and can lead to institutionalization. White matter hyperintensities (WMH) are a common finding on MRI usually indicative of cerebrovascular disease and have been associated with certain NPS. The aim of this study was two-fold. Firstly, we assessed the relationship between WMH load and NPS severity in MCI due to AD (MCI-AD) and AD. Secondly, we assessed the ability of WMH to predict the development and progression of NPS in these participants. Data was obtained from the National Alzheimer’s Coordinating Center.

Methods

WMH were obtained from baseline MRIs and quantified using an automated segmentation technique. NPS were measured using the Neuropsychiatric Inventory (NPI). Mixed effect models and correlations were used to determine the relationship between WMH load and NPS severity scores.

Results

Cross-sectional analysis showed no significant association between NPS and WMH at baseline. Longitudinal mixed effect models, however, revealed a significant relationship between increase in NPI total scores and baseline WMH load (p=0.014). There was also a significant relationship between increase in irritability severity scores over time and baseline WMH load (p= 0.009). Trends were observed for a relationship between increase in agitation severity scores and baseline WMH load (p=0.058). No other NPS severity scores were significantly associated with baseline WMH load. The correlation plot analysis showed that baseline whole brain WMH predicted change in future NPI total scores (r=0.169, p=0.008). Baseline whole brain WMH also predicted change in future agitation severity scores (r= 0.165, p= 0.009). The temporal lobe WMH (r=0.169, p=0.008) and frontal lobe WMH (r=0.153, p=0.016) contributed most to this this change.

Conclusion

Irritability and agitation are common NPS and very distressful to patients and caregivers. Our findings of an increase in irritability severity over time as well as higher agitation severity scores at follow-up in participants with MCI-AD and AD with increased WMH loads have important implications for treatment, arguing for aggressive treatment of vascular risk factors in patients with MCI-AD and AD.
Dopaminergic signals for reward, performance and social outcomes are dynamically gated during courtship
Authors: Roeser Andrea , Gadagkar Vikram , Das Anindita , Puzerey Pavel A. , Kardon Brian , Goldberg Jesse H.
Published: October 2019

How does courtship affect dopaminergic (DA) responses to reward and motor performance outcomes? We used electrophysiology and fiber photometry to record DA signals in two mesostriatal pathways as thirsty male songbirds sang alone and to females. When alone, water reward signals were observed globally but singing-related performance error signals were restricted to a song-specialized mesostriatal pathway. During courtship singing, DA responses to both water-predicting cues and song performance outcomes diminished, and DA signals in the song pathway were instead driven by female calls timed with the male song. Thus DA signals are dynamically gated and routed through distinct pathways as animals change their priorities in response to a courtship opportunity.
Combining whole genome shotgun sequencing and rDNA amplicon analyses to improve detection of microbe-microbe interaction networks in plant leaves
Authors: Regalado Julian , Lundberg Derek S. , Deusch Oliver , Kersten Sonja , Karasov Talia , Poersch Karin , Shirsekar Gautam , Weigel Detlef
Published: October 2019

Microorganisms from all domains of life establish associations with plants. Although some harm the plant, others antagonize pathogens or prime the plant immune system, acquire nutrients, tune plant hormone levels, or perform additional services. Most culture-independent plant microbiome research has focused on amplicon sequencing of 16S rDNA and/or the internal transcribed spacer (ITS) of rDNA loci, but the decreasing cost of high-throughput sequencing has made shotgun metagenome sequencing increasingly accessible. Here, we describe shotgun sequencing of 275 wild Arabidopsis thaliana leaf microbiomes from southwest Germany, with additional bacterial 16S rDNA and eukaryotic ITS1 amplicon data from 176 of these samples. The shotgun data were dominated by bacterial sequences, with eukaryotes contributing only a minority of reads. For shotgun and amplicon data, microbial membership showed weak associations with both site of origin and plant genotype, both of which were highly confounded in this dataset. There was large variation among microbiomes, with one extreme comprising samples of low complexity and a high load of microorganisms typical of infected plants, and the other extreme being samples of high complexity and a low microbial load. We use the metagenome data, which captures the ratio of bacterial to plant DNA in leaves of wild plants, to scale the 16S rDNA amplicon data such that they reflect absolute bacterial abundance. We show that this cost-effective hybrid strategy overcomes compositionality problems in amplicon data and leads to fundamentally different conclusions about microbiome community assembly.
Pan-transcriptome-based Candidate Therapeutic Discovery for Idiopathic Pulmonary Fibrosis
Authors: Wang Yunguan , Yella Jaswanth K. , Ghandikota Sudhir , Cherukuri Tejaswini C. , Ediga Harshavardhana H. , Madala Satish K. , Jegga Anil G.
Published: October 2019

BACKGROUND

Although the advent of two FDA-approved therapies for idiopathic pulmonary fibrosis (IPF) has energized the field, their effects are largely suppressive than pulmonary fibrosis remission- or reversion-inducing. Hence, the pursuit for newer IPF therapeutics continues. Recent studies show that joint analysis of systems biology level information with drug-disease connectivity are effective in discovery of biologically relevant candidate therapeutics.

METHODS

Publicly available gene expression signatures from IPF patients are used to query large scale perturbagen signature library to discover compounds that can potentially reverse dysregulated gene expression in IPF. Two methods are used to calculate IPF-compound connectivity: gene expression-based connectivity and feature-based connectivity. Identified compounds are further prioritized based on their shared mechanism(s) of action.

RESULTS

We identified 77 compounds as potential candidate therapeutics for IPF. Of these 39 compounds are either FDA-approved for other diseases or are currently in phase 2/3 clinical trials suggesting their repurposing potential for IPF. Among these compounds are multiple receptor kinase inhibitors (e.g., nintedanib, currently approved for IPF, and sunitinib), aurora kinase inhibitor (barasertib), EGFR inhibitors (erlotinib, gefitinib), calcium channel blocker (verapamil), phosphodiesterase inhibitors (roflumilast, sildenafil), PPAR agonists (pioglitazone), HDAC inhibitors (entinostat), and opioid receptor antagonists (nalbuphine). As a proof-of-concept, we performed in vitro validations with verapamil using lung fibroblasts from IPF and show its potential benefits in pulmonary fibrosis.

CONCLUSIONS

Since about half of the candidates discovered in this study are either FDA-approved or are currently in clinical trials for other diseases, rapid translation of these compounds as potential IPF therapeutics is feasible. Further, the generalizable, integrative connectivity analysis framework in this study can be readily adapted in early phase drug discovery for other common and rare diseases with transcriptomic profiles.
Polymorphic forms of bendamustine hydrochloride: crystal structure, thermal properties and stability at ambient conditions
Authors: Gaztañaga Pablo , Baggio Ricardo , Vega Daniel Roberto
Published: October 2019

Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydrochloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the `heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979).Mikrochim. Acta,72, 259–271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linkedviaa monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.
Experimental and theoretical charge density, intermolecular interactions and electrostatic properties of metronidazole
Authors: Kalaiarasi Chinnasamy , George Christy , Gonnade Rajesh G. , Hathwar Venkatesha R. , Poomani Kumaradhas
Published: October 2019

Metronidazole is a radiosensitizer; it crystallizes in the monoclinic system with space groupP21/c. The crystal structure of metronidazole has been determined from high-resolution X-ray diffraction measurements at 90 K with a resolution of (sin θ/λ)max= 1.12 Å−1. To understand the charge-density distribution and the electrostatic properties of metronidazole, a multipole model refinement was carried out using the Hansen–Coppens multipole formalism. The topological analysis of the electron density of metronidazole was performed using Bader's quantum theory of atoms in molecules to determine the electron density and the Laplacian of the electron density at the bond critical point of the molecule. The experimental results have been compared with the corresponding periodic theoretical calculation performed at the B3LYP/6-31G** level usingCRYSTAL09. The topological analysis reveals that the N—O and C—NO2exhibit less electron density as well as negative Laplacian of electron density. The molecular packing of crystal is stabilized by weak and strong inter- and intramolecular hydrogen bonding and H...H interactions. The topological analysis of O—H...N, C—H...O and H...H intra- and intermolecular interactions was also carried out. The electrostatic potential of metronidazole, calculated from the experiment, predicts the possible electrophilic and nucleophilic sites of the molecule; notably, the hydroxyl and the nitro groups exhibit large electronegative regions. The results have been compared with the corresponding theoretical results.
Making up ideal recruits
Authors: Gebreiter Florian
Published: October 2019

Purpose

The purpose of this paper is to examine the role of graduate recruitment in the professional socialisation and subjectification of Big Four professionals.

Design/methodology/approach

The paper draws on documentary data and interviews conducted at one British university. It adopts an interpretive perspective and is informed by Foucault’s work on technologies of power and technologies of the self.

Findings

The paper argues that the graduate recruitment practices of Big Four firms represent a series of examinations which produce the category of ideal recruits. It moreover suggests that this category serves as the ultimate objective of an ethical process whereby aspiring accountants consciously and deliberately seek to transform themselves into the type of subjects they aspire to be – ideal recruits.

Research limitations/implications

The findings of the paper are primarily based on interviews conducted at one university. Future research could explore if students at other universities experience graduate recruitment in similar or different ways.

Originality/value

The paper highlights the constitutive role of graduate recruitment practices and shows that they can construct ideal recruits as much as they select them. It also shows that graduate recruitment is an important anticipatory socialisation mechanism that can compel aspiring accountants to learn how to look, sound and behave like Big Four professionals long before they join such organisations. Finally, the paper discusses its implications for the future of the profession, social mobility and the use of Foucault’s work on technologies of power and the self in studying subjectivity at elite professional service firms.
The tax gap as a public management instrument: application to wealth taxes
Authors: Durán-Cabré José M. , Esteller Moré Alejandro , Mas-Montserrat Mariona , Salvadori Luca
Published: October 2019

Purpose

The purpose of this paper is to study the concept of tax gap, that is the difference between the total amount of taxes collected and the total tax revenues that would be collected under full tax compliance.

Design/methodology/approach

The authors also present the methodology to estimate the gap for two taxes levied on wealth: the wealth tax and the inheritance and gift tax; both are administered in Spain by the regional tax authorities.

Findings

The authors point out that its estimation offers useful information about the relative size and nature of non-compliance, as well as its evolution over time. Likewise, the tax gap is a valuable instrument not only to define enforcement strategies of the tax administration but also to enhance its accountability. Nonetheless, the methodology used to estimate the tax gap and, consequently, the interpretation of the results is subject to limitations that are discussed in the paper.

Originality/value

Finally, the paper provides the results of the estimations obtained from using microdata: 44.34 per cent gap in the wealth tax and 41.26 per cent in the inheritance and gift tax.
Managing environmental building performance through IT systems
Authors: Maslesa Esmir , Jensen Per Anker
Published: October 2019

Purpose

This paper aims to disclose the role and features of various IT systems for environmental building performance (EBP) in facilities management.

Design/methodology/approach

The study focuses on IT systems used for facilities management in four organisations. The study is based on a maximum variance case study in which the selected organisations have different organisation type and portfolio size. Three organisations are from Denmark and one is from the UK.

Findings

Several IT systems can be used for managing EBP. EBP in IT systems is primarily reflected through energy management, with specific focus on monitoring and reporting electricity, heating and water consumption. Furthermore, greenhouse gas emissions related to energy consumption can be calculated in some IT systems, while other environmental categories like building materials and recycling potentials are not adequately supported by the systems covered in this study. Some IT systems offer additional features relating to EBP, such as waste management and space management, but the study shows that these features are not demanded at the current point.

Practical implications

The results can be used to support decision-making in organisations to improve EBP in facilities management by IT systems.

Originality/value

This study contributes with new knowledge on how IT systems are used in different organisations for managing EBP. The paper also shows how various IT systems can add value to real estate organisations and facilities management departments and support their business processes relating to EBP.
Challenges associated with the use of information and communication technologies in information sharing by fish farmers in the Southern highlands of Tanzania
Authors: Benard Ronald , Dulle Frankwell , Lamtane Hieromin
Published: October 2019

Purpose

This paper aims to examine the challenges facing fish farmers in the use of information and communication technology (ICT) in information sharing on fish farming.

Design/methodology/approach

This study used both quantitative and qualitative methods. It involved 240 fish farmers who were randomly selected. Questionnaires, focus group discussions (FGDs), observation and key informant’s interviews were used as methods of data collection. Both descriptive and inferential statistics were used to analyse quantitative data, while content analysis was used for qualitative data.

Findings

It was found that the most frequently used ICTs by fish farmers in sharing agricultural information were mobile phones, radio and television. Also, the study revealed that major challenges facing fish farmers in sharing information include unfavourable radio or television broadcasting time, high cost of acquiring and maintenance of ICT facilities, lack of training on ICT, poor network connectivity and low level of literacy. Moreover, it was further found that there was negative significant relationship (P < 0.05) between challenges associated with the use and degree of ICT usage by fish farmers.

Originality/value

The study is original with the exception of areas where citations have been made. Besides, it provides awareness and understanding of the challenges facing fish farmers in ICT usage in information sharing on fish farming, and this will enable improvement of timely provision and access to relevant information and hence improved fish farming production.
Analysis of barriers in implementation of digital transformation of supply chain using interpretive structural modelling approach
Authors: Agrawal Prakash , Narain Rakesh , Ullah Inayat
Published: October 2019

Purpose

Digital supply chain (DSC) is an agile, customer-driven and productive way to develop different forms of returns for companies and to leverage efficient approaches with emerging techniques and data analytics. Though the advantages of digital supply chain management (DSCM) are many, its implementation is quite slow for several reasons. The purpose of this paper is to identify the major barriers which hinder the adoption of DSC and to analyse the interrelationship among them. The barriers of DSC are explored on the basis of existing literature and experts’ opinion.

Design/methodology/approach

This paper uses the interpretive structural modelling (ISM) approach to develop a hierarchical structural model which shows the mutual dependence among the barriers of DSC. Cross-impact matrix multiplication applied to classification analysis was performed to represent these barriers graphically on the basis of their driving power and dependence.

Findings

The research demonstrates that the barriers “no sense of urgency”, “lack of industry specific guidelines”, “lack of digital skills and talent” and “high implementation and running cost” are the most significant barriers to digital transformation of supply chain. This paper also suggests some managerial implications to overcome the barriers which hinder the implementation of digital transformation of supply chain.

Practical implications

This paper assists managers and policymakers to understand the order in which these barriers must be tackled and adopts a roadmap for successful implementation of DSCM and reap its benefits.

Originality/value

This is one of the initial research studies which has analysed the barriers of DSC using ISM approach.
Effects of processing conditions on mechanical properties of PLA printed parts
Authors: Behzadnasab Morteza , Yousefi Ali Akbar , Ebrahimibagha Dariush , Nasiri Farahnaz
Published: October 2019

Purpose

With recent advances in additive manufacturing (AM), polymer-based three-dimensional (3D) printers are available for relatively low cost and have found their way even in domestic and educational uses. However, the optimum conditions for processing and post-processing of different materials are yet to be determined. The purpose of this paper is to examine the effects of printing temperature, pattern and annealing conditions on tensile strength and modulus of samples printed with polylactic acid (PLA).

Design/methodology/approach

This study focuses on fused deposition modelling according to ISO/ASTM 52900 material extrusion AM. To print parts with maximum mechanical properties, the printing variables must be optimised. To determine the printing and annealing condition on physical and mechanical properties of PLA-based parts, dogbone-shaped tensile samples were printed at four different nozzle temperatures and five different filling patterns embedded in a 3D printing software. The samples were further annealed at three different temperatures for three different time intervals. The mechanical properties were evaluated and the changes in mechanical properties were analysed with the help of rheometrical measurements.

Findings

The results showed that printing condition has a significant influence on final properties, for example, the strain at break value increases with increasing nozzle temperature from 34 to 56 MPa, which is close to the value of the injected sample, namely, 65 MPa. While tensile strength increases with printing temperature, the annealing process has negative effects on the mechanical properties of samples.

Originality/value

The authors observed that traditional findings in polymer science, for example, the relationship between processing and annealing temperature, must be re-evaluated when applied in 3D printing because of major differences in processing conditions resulting from the layer-by-layer manufacturing.
Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp
Authors: van der Velden Jaap J. A. J. , van Geel Michel , Engelhart Jans J. , Jonkman Marcel F. , Steijlen Peter M.
Published: October 2019

Peeling skin disease is a rare genodermatosis characterized by superficial exfoliation or peeling of the skin. Peeling skin disease is caused by biallelic mutations in CDSN as an autosomal recessive trait. Monoallelic mutations in CDSN have also been described in an autosomal dominant inherited genodermatosis: hypotrichosis simplex of the scalp. This disease is characterized by progressive hair loss of the scalp with onset after early childhood. Clinical data were obtained from a patient with lifelong generalized skin peeling and both his parents. The patient's parents did not suffer from skin peeling, but the mother had a history of thin scalp hair since early childhood. Mutation analysis in the patient showed compound heterozygous mutations in exon 2 of CDSN, a nonsense mutation c.598C>T (p.[Gln200*]), previously associated with hypotrichosis simplex of the scalp, and a frame‐shift mutation c.164_167dup (p.[Thr57Profs*6]), previously described in peeling skin disease. The p.(Gln200*) mutation was also found in the mother of the proband. Our study strengthens the previously established link between mutations in CDSN to peeling skin disease and hypotrichosis simplex of the scalp.
Oncolytic viruses: what to expect from their use in cancer treatment
Authors: Terrível Maria , Gromicho Catarina , Matos Ana Miguel
Published: October 2019

Oncolytic viruses are biologic agents able to selectively infect and destroy cancer cells while sparing the normal ones. Furthermore, they also stimulate the host immune system to combat the tumor growth and to promote tumor removal. This review thoroughly describes different types of viruses developed for targeting specific cancers, as well as the strategies to improve the efficacy and safety of oncolytic virotherapy. It also explores how their potential as anticancer agents may be enhanced through combination with other traditional therapies, such as chemotherapy or more recent approaches, such as checkpoint inhibitors. There are many oncolytic viruses currently being tested in clinical trials for the treatment of various types of cancer, suggesting that this approach could become the near future of the oncology field.
Rubber agroforestry in Thailand provides some biodiversity benefits without reducing yields
Authors: Warren‐Thomas Eleanor , Nelson Luke , Juthong Watinee , Bumrungsri Sara , Brattström Oskar , Stroesser Laetitia , Chambon Bénédicte , Penot Éric , Tongkaemkaew Uraiwan , Edwards David P. , Dolman Paul M.
Published: October 2019

Monocultural rubber plantations have replaced tropical forest, causing biodiversity loss. While protecting intact or semi‐intact biodiverse forest is paramount, improving biodiversity value within the 11.4 million hectares of existing rubber plantations could offer important conservation benefits, if yields are also maintained. Some farmers practice agroforestry with high‐yielding clonal rubber varieties to increase and diversify incomes. Here, we ask whether such rubber agroforestry improves biodiversity value or affects rubber yields relative to monoculture.

We surveyed birds, fruit‐feeding butterflies and reptiles in 25 monocultural and 39 agroforest smallholder rubber plots in Thailand, the world's biggest rubber producer. Management and vegetation structure data were collected from each plot, and landscape composition around plots was quantified. Rubber yield data were collected for a separate set of 34 monocultural and 47 agroforest rubber plots in the same region.

Reported rubber yields did not differ between agroforests and monocultures, meaning adoption of agroforestry in this context should not increase land demand for natural rubber. Butterfly richness was greater in agroforests, where richness increased with greater natural forest extent in the landscape. Bird and reptile richness were similar between agroforests and monocultures, but bird richness increased with the height of herbaceous vegetation inside rubber plots.

Species composition of butterflies differed between agroforests and monocultures, and in response to natural forest extent, while bird composition was influenced by herbaceous vegetation height within plots, the density of non‐rubber trees within plots (representing agroforestry complexity) and natural forest extent in the landscape. Reptile composition was influenced by canopy cover and open habitat extent in the landscape. Conservation priority and forest‐dependent birds were not supported within rubber.

Synthesis and applications. Rubber agroforestry using clonal varieties provides modest biodiversity benefits relative to monocultures, without compromising yields. Agroforests may also generate ecosystem service and livelihood benefits. Management of monocultural rubber production to increase inter‐row vegetation height and complexity may further benefit biodiversity. However, biodiversity losses from encroachment of rubber onto forests will not be offset by rubber agroforestry or rubber plot management. This evidence is important for developing guidelines around biodiversity‐friendly rubber and sustainable supply chains, and for farmers interested in diversifying rubber production.
MicroRNA‐147b suppresses the proliferation and invasion of non‐small‐cell lung cancer cells through downregulation of Wnt/β‐catenin signalling via targeting of RPS15A
Authors: Ning Qian , Pang Yamei , Shao Shan , Luo Minna , Zhao Lin , Hu Tinghua , Zhao Xinhan
Published: October 2019

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR‐147b has emerged as one of the cancer‐related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR‐147b in non‐small‐cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR‐147b in NSCLC. Our results demonstrate that miR‐147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR‐147b decreased the proliferative ability, colony‐forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR‐147b. Our results showed that miR‐147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR‐147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR‐147b overexpression downregulated the activation of Wnt/β‐catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR‐147b‐mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR‐147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A‐induced Wnt/β‐catenin signalling and suggest that the miR‐147b/RPS15A/Wnt/β‐catenin axis is an important regulatory mechanism for malignant progression of NSCLC.
miR‐138 mediates sorafenib‐induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells
Authors: Zheng Yingjie , Zhang Jingyu , Ye Bin
Published: October 2019

Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR‐138 in tumor tissues is related to the poor prognosis in patients, and that miR‐138 mediates sorafenib‐induced cell survival in cholangiocarcinoma cells. Moreover, miR‐138 negatively regulates SOX4 expression by specifically targeting its 3′ untranslated region (3′ UTR). As per our results, overexpression of SOX4 reversed sorafenib‐induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR‐138/SOX4 is involved in sorafinib‐mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.
Why information and transparency about electricity matter: Fragmentation of governance and accountability under New Public Management
Authors: Molyneaux Lynette , Head Brian
Published: October 2019

From 1995, Australian governments pursued efficiency benefits arising from significant structural reforms in the Electricity Supply Industry, including corporatisation and regulation of network monopolies, and introduction of competition for generators and for retailers. The restructure was motivated by the ideology of New Public Management and influenced by the field of neoliberal economics. More than two decades later, prices paid for electricity by residential and commercial customers have escalated sharply, resulting in sustained anger from all consumers. The Australian Competition and Consumer Commission Chair has admitted that ‘The National Electricity Market is largely broken’. This article documents the reduction in public access to information about electricity supply, the fragmentation in responsibility and accountability for consumer outcomes, and the consequences of these changes for transparency, industry operation, and retail electricity prices. New research enabled the creation of a database of Queensland energy production, consumption, and prices; this facilitated a fresh analysis of Queensland electricity sector performance since the restructure of electricity supply.
Antioxidative Polyphenols of Canola Meal Extracted by High Pressure: Impact of Temperature and Solvents
Authors: Nandasiri Ruchira , Eskin N. A. Michael , Thiyam‐Höllander Usha
Published: October 2019

Canola meal, a by‐product of oil pressing, is a rich source of phenolic antioxidants. However, its use in the food and feed sector is still limited by the need for greener, sustainable, and more cost‐effective extraction methods. This study used accelerated solvent extraction (ASE) to enhance the extraction efficiency of the phenolic antioxidants. The high selectivity and short extraction time associated with ASE were ideal for obtaining high yields of these antioxidants. The structure‐based activity of phenolic compounds may be influenced by the high pressure and temperature of the greener ASE process. The present study evaluated the effect of temperature (140, 160, and 180 °C) and pressure (1,500 psi) on the extraction and yield of phenolic compounds from canola meal as well as the solvent type (ethanol and methanol) and concentration (30%, 40%, 60%, and 70% v/v). Antioxidant activity was determined by 2,2‐diphenyl‐1‐picrylhydrazyl, ferric reducing/antioxidant power assay, and ion‐chelating activity. The highest yield of phenolic compounds was obtained with 70% methanol (20.72 ± 1.47 mg SAE/g DM [milligrams of sinapic acid equivalents per gram of dry matter]) and 70% ethanol (24.71 ± 2.77 mg SAE/g DM) at 180 °C temperature. A similar trend was observed for the antioxidant activity of the extracts and their total flavonoid content. The structure‐based antioxidant activity of the extracts examined increased with the increase in the percentage of the extracting solvent (P > 0.05). This study established ASE as an efficient green method for extracting phenolic compounds from canola meal, with potential application for the production of natural bioactive compounds from underutilized agricultural by‐products.

Practical Application

ASE is an efficient eco‐friendly method for extracting phenolic compounds from agricultural by‐products such canola meal. Under the conditions of high pressure and temperature, ASE significantly improved the yields of phenolic compounds, sinapine, sinapic acid, and canolol. Under these conditions, water, as an extractant, was not effective in extracting sianpine. Moreover, it was much less effective than both 70% ethanol and 70% methanol in extracting sinapine or canolol. These phenolic compounds are of great interest as natural antioxidants for enhancing the shelf life of food products. They also represent new sources of neutraceuticals for improving human health.
Geriatric Emergency Department Innovations: The Impact of Transitional Care Nurses on 30‐day Readmissions for Older Adults
Authors: Dresden Scott M. , Hwang Ula , Garrido Melissa M. , Sze Jeremy , Kang Raymond , Vargas‐Torres Carmen , Courtney D. Mark , Loo George , Rosenberg Mark , Richardson Lynne
Published: October 2019

Objectives

Transitional care nurse (TCN) care has been associated with decreased hospitalizations for older adults in the emergency department (ED). The objective of this study was to evaluate the association between TCN care and readmission for geriatric patients who visit the ED within 30 days of a prior hospital discharge.

Methods

We studied a prospective cohort of ED patients aged 65 and older with an ED visit within 30 days of inpatient discharge. Patients with an Emergency Severity Index of 1 or prior TCN contact were excluded. Entropy balancing and logistic regression were used to estimate the average incremental effect of the TCN intervention on risk of admission during the index ED visit and within 30 days of prior discharge.

Results

Of 6,838 visits, 608 included TCN care. TCN patients had lower risk of readmission during the index ED visit at Mount Sinai Medical Center (MSMC), −10.1 percentage points (95% confidence interval [CI] = −18.5 to −2.7), and Northwestern Memorial Hospital (NMH), −17.3 percentage points (95% CI = −23.1 to −11.5), but not St. Joseph’s Regional Medical Center (SJRMC), −2.5 percentage points (95% CI = −10.5 to 5.5). TCN patients had fewer readmissions within 30 days of prior hospital discharge at NMH, −16.2 percentage points (95% CI = −22.0 to −10.3), but not at MSMC, −5.6 percentage points (95% CI = −13.1 to 1.8), or at SJRMC, 0.5 percentage points (95% CI = −7.2 to 8.2).

Conclusions

Transitional care nurse care in the ED after a prior hospitalization was associated with decreased readmission of older adults during the index ED visit at two of three hospitals, with sustained reduction for the entire 30‐day readmission window at one hospital. TCN interventions in the ED may decrease readmissions for geriatric patients in the ED; however, these results may be dependent on implementation of the program and availability of ED, hospital, and local resources for older adults.
Trial implementation of CIRCuiTS cognitive remediation therapy for people with schizophrenia in Orange, New South Wales
Authors: Thomas Matt , Rusten Kim
Published: October 2019

Objective

Many people with schizophrenia experience cognitive impairments and current practice guidelines recommend cognitive remediation therapy. This implementation trial examined aspects of feasibility, acceptability and outcomes of the computerised interactive remediation of cognition—interactive training for schizophrenia cognitive remediation therapy program in our local context.

Design

A longitudinal design was utilised with participants providing outcome data at commencement of the computerised interactive remediation of cognition—interactive training for schizophrenia program, completion and at follow‐up 3 months later.

Setting

Our trial was conducted in the inpatient and community mental health contexts within the New South Wales regional city of Orange, between January 2017 and December 2018.

Participants

Fifty‐three adult volunteers commenced the computerised interactive remediation of cognition—interactive training for schizophrenia program and participated in this trial. Forty‐five participants were currently admitted to psychiatric rehabilitation inpatient units at Bloomfield hospital, and eight were referred by Orange Community Mental Health Service.

Main outcome measure(s)

Participants completed measures of cognitive functioning (repeatable battery for the assessment of neuropsychological status), functional independence (Adaptive Behaviour Assessment Scales 3) and Goal attainment scaling.

Results

Most participants reported they liked computerised interactive remediation of cognition—interactive training for schizophrenia therapy and made excellent progress towards their goals. Those who completed the program made significant gains in the domains of attention, memory and independence in key aspects of daily living. Gains in functional independence were sustained for a small sample following program completion.

Conclusion

This implementation trial showed the computerised interactive remediation of cognition—interactive training for schizophrenia cognitive remediation therapy program was feasible, acceptable and contributed to strong outcomes in both the inpatient and community contexts. Efforts are in progress to translate the computerised interactive remediation of cognition—interactive training for schizophrenia program, and future research will focus on longer term outcomes, cost‐benefit analyses and the experiences of participants and therapists.
Primary congenital glaucoma in Denmark, 1977–2016
Authors: Pedersen Karen B. , Kappelgaard Per , Kessel Line , Sandfeld Lisbeth , Zibrandtsen Nathalie , Bach‐Holm Daniella
Published: October 2019

Purpose

To perform an epidemiological survey of all patients in Denmark diagnosed with primary congenital glaucoma (PCG) from 1977 to 2016.

Methods

A retrospective, nationwide study based on a review of medical files of all children with PCG born in Denmark from 1977 to 2016. PCG was defined as glaucoma due to isolated angle dysgenesis affecting children from birth and including late onset/late recognized PCG, excluding glaucoma associated with other congenital abnormalities. Incidence and risk factors of PCG including gender, consanguinity, family history, ethnicity, comorbidity and prematurity were evaluated and stratified by decade (1977–1986, 1987–1996, 1997–2006 and 2007–2016). Age at first symptoms, age at diagnosis, age at time of first surgery and possible diagnostic delay were assessed.

Results

Of 118 patients were identified, annual incidence of PCG was 4.8 per 100 000 live born. 62.3% of cases were bilateral. The relative risk (RR) of PCG was significantly higher in boys (62.7% of patients, RR 1.60 (95% CI 1.10–2.32)). 13.6% had comorbidity. Median age at time of first symptoms was 75 days, median age at time of diagnosis was 150 days and median diagnostic delay was 75 days with no significant difference throughout the decades. Unilateral cases presented symptoms and were diagnosed significantly later than bilateral cases.

Conclusion

We provide unique nation‐based information on the incidence of PCG from a single country covering 40 years. Male gender was a risk factor. Diagnostic delay was unchanged throughout the 4 decades and a high percentage of comorbidity was revealed. Introducing a standardized paediatric screening of all PCG children should be considered.
Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen
Authors: Favié Laurent M.A. , Huitema Alwin D.R. , van den Broek Marcel P.H. , Rademaker Carin M.A. , de Haan Timo R. , van Straaten Henrica L.M. , Simons Sinno H.P. , Rijken Monique , Nuytemans Debbie H.G.M. , Egberts Toine C.G. , Groenendaal Floris ,   on behalf of the PharmaCool study group*
Published: October 2019

Aims

Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed.

Methods

Data from preterm neonates and (near‐)term neonates with and without therapeutic hypothermia receiving lidocaine were included. Pharmacokinetic analyses were performed using non‐linear mixed effects modelling. Simulations were performed to evaluate the proposed dosing regimen. Lidocaine was considered effective if no additional anticonvulsant was required and safe if no cardiac adverse events occurred.

Results

Data were available for 159 neonates; 50 (31.4%) preterm and 109 term neonates, of whom 49 (30.8%) were treated with therapeutic hypothermia. Lidocaine clearance increased with postmenstrual age by 0.69%/day (95% confidence interval 0.54–0.84%). During therapeutic hypothermia (33.5°C), lidocaine clearance was reduced by 21.8% (7.26%/°C, 95% confidence interval 1.63–11.2%) compared to normothermia (36.5°C). Simulations demonstrated that the proposed dosing regimen leads to adequate average lidocaine plasma concentrations. Effectiveness and safety were assessed in 92 neonates. Overall effectiveness was 53.3% (49/92) and 56.5% (13/23) for neonates receiving the proposed dosing regimen. No cardiac toxicity was observed.

Conclusion

Lidocaine pharmacokinetics was adequately described across the entire neonatal age range. With the proposed dosing regimen, lidocaine can provide effective and safe treatment for neonatal seizures.
Formula feeding can help illuminate long‐term consequences of full ectogenesis
Authors: Buturovic Zeljka
Published: October 2019

Breastfeeding is analogous to pregnancy as an experience, in its exclusiveness to women, and in its cost and the effects it has on equitable share of labor. Therefore, the history of formula feeding provides useful insights into the future of full ectogenesis, which could evolve into a more severe version of what formula feeding is today: simplify life for some women and provide couples with a more equitable share of work at the cost of stigma, guilt and a daily diet of studies purporting to show the benefits of natural pregnancy. Making pregnancy an optional route to motherhood would make women's life trajectory more similar to men's and thus put pressure on women to compete with men on the ground shaped by men's preferences. Despite being a treasured experience of many women today, bearing children could become the luxury of the few, the province of the very poor and a choice working women will pay a high price for as women who choose pregnancy become stigmatized as self‐indulgent or unprofessional and penalized for it in the workplace. At the same time, scarce societal resources that could be used to support pregnant women and working mothers would instead be directed toward proving to women or even forcing them to gestate children “the right way.” While not necessarily threatening on its own, when added to formula feeding, IVF, stem‐cell produced ova and sex robots, full ectogenesis could diminish men's stake in women's wellbeing and even existence.