bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for Developmental Neurotoxicity at the National Toxicology Program: The Future Is Here
Authors: Behl Mamta , Ryan Kristen , Hsieh Jui-Hua , Parham Frederick , Shapiro Andrew J , Collins Bradley J , Sipes Nisha S , Birnbaum Linda S , Bucher John R , Foster Paul M D , Walker Nigel J , Paules Richard S , Tice Raymond R
Published: November 2018

The National Toxicology Program (NTP) receives requests to evaluate chemicals with potential to cause adverse health effects, including developmental neurotoxicity (DNT). Some recent requests have included classes of chemicals such as flame retardants, polycyclic aromatic compounds, perfluoroalkyl substances, and bisphenol A analogs with approximately 20–50 compounds per class, many of which include commercial mixtures. However, all the compounds within a class cannot be tested using traditional DNT animal testing guideline studies due to resource and time limitations. Hence, a rapid and biologically relevant screening approach is required to prioritize compounds for further in vivo testing. Because neurodevelopment is a complex process involving multiple distinct cellular processes, one assay will unlikely address the complexity. Hence, the NTP sought to characterize a battery of in vitro and alternative animal assays to quantify chemical effects on a variety of neurodevelopmental processes. A culmination of this effort resulted in a NTP-hosted collaborative project with approximately 40 participants spanning across domains of academia, industry, government, and regulatory agencies; collaborators presented data on cell-based assays and alternative animal models that was generated using a targeted set of compounds provided by the NTP. The NTP analyzed the assay results using benchmark concentration (BMC) modeling to be able to compare results across the divergent assays. The results were shared with the contributing researchers on a private web application during the workshop, and are now publicly available. This article highlights the overview and goals of the project, and describes the NTP’s approach in creating the chemical library, development of NTPs data analysis strategy, and the structure of the web application. Finally, we discuss key issues with emphasis on the utility of this approach, and knowledge gaps that need to be addressed for its use in regulatory decision making.
Evolution of international collaborative research efforts to develop non-Cochrane systematic reviews
Authors: Viguera-Guerra I. , Ruano Juan , Aguilar-Luque Macarena , Gay-Mimbrera Jesus , Montilla Ana , Fernández-Rueda J. L. , Fernández-Chaichio J. , Sanz-Cabanillas J.L. , Gómez-Arias P. , García-Nieto Antonio Velez , Gómez-Garcia Francisco , Isla-Tejera Beatriz
Published: November 2018

This research-on-research study describes effortsto develop non-Cochrane systematic reviews (SRs) by analysing demographical and time-course collaborations between international institutions using protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO) or published in scientific journals. We have published an a priori protocol to develop this study. Protocols published in scientific journals were searched in MEDLINE/PubMed and Embase databases using the query terms ‘systematic review’[Title] AND ‘protocol’[Title] from February 2011 to December 2017. Protocols registered at PROSPERO during the same period were obtained by web scraping all non-Cochrane records with a Python script. After excluding protocols with less than 90% fulfilled or duplicated, they were classified as published ‘only in PROSPERO’, ‘only in journals’, or in both ‘journals and PROSPERO’. Results of data and metadata extraction using text-mining processes were curated by two reviewers. Datasets and R scripts are freely available to facilitate reproducibility. We obtained 20,814 protocols of non-Cochrane SRs. While ‘unique protocols’ by re-viewers’ institutions from 60 countries were the most frequent, to prepare ‘collaborative protocols’ a median of 6 (2-150) institutions were involved from 130 different countries. Ranked list of countries involved in overall protocol production were the UK, the U.S., Australia, Brazil, China, Canada, the Netherlands, Germany, and Italy. Most protocols were registered only in PROSPERO. However, the number of protocols published in scientific journals (924) or in both PROSPERO and journals (807) has progressively increased over the last three years. Syst Rev and BMJ Open published more than half of the total protocols. While most productive countries were involved in ‘unique’ and ‘collaborative’ protocols, less productive countries only participated in ‘collaborative’ protocols that were mainly published only in PROSPERO. Our results suggest that although most countries were involved in producing in solitary protocols of non-Cochrane SRs during the study period, it would be desirable to develop new strategies to promote international collaborations, especially with less productive countries.
Interpreting coronary artery disease risk through gene-environment interactions in gene regulation
Authors: Findley Anthony S , Richards Allison L , Petrini Cristiano , Alazizi Adnan , Doman Elizabeth , Shanku Alexander G , Davis Omar , Hauff Nancy , Sorokin Yoram , Wen Xiaoquan , Pique-Regi Roger , Luca Francesca
Published: November 2018

GWAS and eQTL studies identified thousands of genetic variants associated with complex traits and gene expression. Despite the important role of environmental exposures in complex traits, only a limited number of environmental factors are measured in these studies. Measuring molecular phenotypes in tightly controlled cellular environments provides a more tractable setting to study gene-environment interactions in the absence of other confounding variables.

We performed RNA-seq and ATAC-seq in endothelial cells exposed to retinoic acid, dexamethasone, caffeine, and selenium to model genetic and environmental effects on gene regulation in the vascular endothelium, a common site of pathology in cardiovascular disease. We found that genes near regions of differentially accessible chromatin were more likely to be differentially expressed (OR = [3.41, 6.52], p < 10−16). Furthermore, we confirmed that environment-specific changes in transcription factor binding are a key mechanism for cellular response to environmental stimuli. SNPs in these transcription response factor footprints for dexamethasone, caffeine, and retinoic acid were enriched in GTEx eQTLs from artery tissues indicating that these environmental conditions are latently present in GTEx samples. Additionally, SNPs in footprints for response factors in caffeine are enriched in colocalized eQTLs for coronary artery disease (CAD), suggesting a role for caffeine in CAD risk. Interestingly, each treatment may amplify or buffer genetic risk for CAD, depending on the particular SNP considered.
Accounting for healthcare-seeking behaviours and testing practices in real-time influenza forecasts
Authors: Moss Robert , Zarebski Alexander E , Carlson Sandra J , McCaw James M
Published: November 2018

For diseases such as influenza, where the majority of infected persons experience mild (if any) symptoms, surveillance systems are sensitive to changes in healthcare-seeking and clinical decision-making behaviours. This presents a challenge when trying to interpret surveillance data in near-real-time (e.g., in order to provide public health decision-support). Australia experienced a particularly large and severe influenza season in 2017, perhaps in part due to (a) mild cases being more likely to seek healthcare; and (b) clinicians being more likely to collect specimens for RT-PCR influenza tests. In this study we used weekly Flutracking surveillance data to estimate the probability that a person with influenza-like illness (ILI) would seek healthcare and have a specimen collected. We then used this estimated probability to calibrate near-real-time seasonal influenza forecasts at each week of the 2017 season, to see whether predictive skill could be improved. While the number of self-reported influenza tests in the weekly surveys are typically very low, we were able to detect a substantial change in healthcare seeking behaviour and clinician testing behaviour prior to the high epidemic peak. Adjusting for these changes in behaviour in the forecasting framework improved predictive skill. Our analysis demonstrates a unique value of community-level surveillance systems, such as Flutracking, when interpreting traditional surveillance data.
An unusual and physiologically vital protein with guanylate cyclase and P-type ATPase like domain in a pathogenic protist
Authors: Günay-Esiyok Özlem , Scheib Ulrike , Noll Matthias , Gupta Nishith
Published: November 2018

Cyclic GMP is considered as one of the master regulators of diverse functions in eukaryotes; its architecture and functioning in protozoans remain poorly understood however. We characterized an unusual and extra-large guanylate cyclase (477-kDa) containing at least 4 putative P-type ATPase motifs and 21 transmembrane helices in a common parasitic protist, Toxoplasma gondii. This protein, termed as TgATPaseP-GC due to its anticipated multi-functionality, localizes in the plasma membrane at the apical pole, while the corresponding cGMP-dependent protein kinase (TgPKG) is distributed in cytomembranes. Both proteins are expressed constitutively during the entire lytic cycle of the parasite in human cells, which suggests a post-translational control of cGMP signaling. Homology modeling indicated an activation of guanylate cyclase by heterodimerization of its two cyclase domains. TgATPaseP-GC is refractory to genetic deletion, and its CRISPR/Cas9-mediated disruption aborts the lytic cycle. Likewise, Cre/loxP-regulated knockdown of the TgATPaseP-GC by 3’ UTR excision inhibited the parasite growth due to impairments in motility-dependent egress and invasion events. Consistently, cGMP-specific phosphodiesterase inhibitors restored the gliding motility of the mutant. A genetic repression of TgPKG, or its pharmacological inhibition phenocopied the defects observed in the TgATPaseP-GC mutant. Our data show a vital function of cGMP signaling, which is inducted by an alveolate-specific guanylate cyclase coupled to P-type like ATPase, and transduced by a dedicated PKG in T. gondii. The presence of TgATPaseP-GC orthologs in many other alveolates with contrasting habitats implies a divergent functional repurposing of cGMP signaling in protozoans. The work also lays an avenue to systematically dissect the cascade and understand its evolution in a model protist.
Gene erosion and genome expansion in a group of highly host-specialized fungal phytopathogens
Authors: Frantzeskakis Lamprinos , Németh Márk Z. , Barsoum Mirna , Kusch Stefan , Kiss Levente , Takamatsu Susumu , Panstruga Ralph
Published: November 2018

Due to their comparatively small genome size and short generation time, fungi are exquisite model systems to study eukaryotic genome evolution. Powdery mildew (PM) fungi present an exceptional case where their strict host dependency (a lifestyle termed obligate biotrophy) is associated with some of the largest fungal genomes sequenced so far (>100 Mbp). This size expansion is largely due to the pervasiveness of transposable elements (TEs), which can cover more than 70% of these genomes, and is associated with the loss of multiple conserved ascomycete genes (CAGs) required for a free-living lifestyle. To date, little is known about the mechanisms that drove this expansion, and information on ancestral PM genomes is lacking. We report the genome analysis of the early-diverged PM speciesParauncinula polysporathat in contrast to most other PMs reproduces exclusively sexually. TheP. polysporagenome is surprisingly small (<30 Mb) and sparsely equipped with TEs (<10%), despite the conserved absence of a common defense mechanism (RIP) involved in constraining repetitive elements. The genome still harbors the majority of the CAGs that are absent in the genomes of the recently evolved PMs. We speculate that TE spread might have been limited by its unique reproduction strategy and host features and further hypothesize that the loss of CAGs may promote the evolutionary isolation and host niche specialization of PM fungi. Limitations associated with this evolutionary trajectory might have been in part counteracted by the evolution of plastic, TE-rich genomes and/or the expansion of gene families encoding secreted virulence proteins.
Genome-wide screens in accelerated human stem cell-derived neural progenitor cells identify Zika virus host factors and drivers of proliferation
Authors: Wells Michael F. , Salick Max R. , Piccioni Federica , Hill Ellen J. , Mitchell Jana M. , Worringer Kathleen A. , Raymond Joseph J. , Kommineni Sravya , Chan Karrie , Ho Daniel , Peterson Brant K. , Siekmann Marco T. , Pietilainen Olli , Nehme Ralda , Kaykas Ajamete , Eggan Kevin
Published: November 2018

Neural progenitor cells (NPCs) are essential to brain development and their dysfunction is linked to several disorders, including autism, Zika Virus Congenital Syndrome, and cancer. Understanding of these conditions has been improved by advancements with stem cell-derived NPC models. However, current differentiation methods require many days or weeks to generate NPCs and show variability in efficacy among cell lines. Here, we describe humanStem cell-derivedNGN2-acceleratedProgenitor cells (SNaPs), which are produced in only 48 hours. SNaPs express canonical forebrain NPC protein markers, are proliferative, multipotent, and like other human NPCs, are susceptible to Zika-mediated death. We further demonstrate SNaPs are valuable for large-scale investigations of genetic and environmental influencers of neurodevelopment by deploying them for genome-wide CRISPR-Cas9 screens. Our studies expand knowledge of NPCs by identifying known and novel Zika host factors, as well as new regulators of NPC proliferation validated by re-identification of the autism spectrum genePTEN.
Macarthurs 1955 Stability Function is Related to Formal Dynamic Measures of Food Web Stability
Authors: Keegan S. P. , Townsend S. E. , Haydon D.T.
Published: November 2018

Community complexity-stability relationships have been at the centre of ecological thinking for many decades. MacArthur (1955) proposed a measure of stability that reflected the diversity in the number of pathways energy can flow up through a food web but how this index correlates with more formal ideas of dynamical stability remains unexplored. Here, we examine the relationship between MacArthurs proposed index and measures of local and global stability in Lotka-Volterra food web models. Our results provide support for MacArthurs intuitive hypothesis that increasing the diversity of energy pathways through food webs endows them with greater stability, as measured by both the probability of local and global point stabilities, and the return time to stable equilibria following perturbation.
Homework compliance among substance using male offenders of IPV
Authors: Berbary Cassandra , Fernandes Camila , Crane Cory A. , Easton Caroline J.
Published: November 2018

Purpose

Research suggests that homework compliance within cognitive behavioral therapy is associated with treatment adherence and positive treatment outcomes through generalization of learned skills. The purpose of this paper is to determine whether there were differences in aggression and substance use between participants who did and did not complete therapy homework assignments.

Design/methodology/approach

Secondary analyses were conducted using data from Easton et al.’s (2017) randomized controlled trial of substance abuse domestic violence (SADV) treatment among substance dependent intimate partner violence (IPV) offenders. Analyses of covariance were conducted in order to determine whether homework completion had a significant effect on aggression and substance use. Correlational analyses were conducted to determine the association between quality of homework and outcomes.

Findings

Participants (n=63) who completed at least two homework assignments had fewer days of alcohol use during treatment compared to those who did not complete any assignments, p=0.03. There was not a difference in the number of days participants engaged in violence based on homework completion. Analyses indicated that those who displayed aggression proximal to alcohol use during treatment completed significantly fewer homework assignments compared to those who did not display aggression proximal to alcohol use (p=0.04).

Research limitations/implications

This research was limited to a sample of male substance using offenders of IPV within the US additional research utilizing a larger sample size in order to investigate differences in homework completion across treatment groups is needed. Further analysis of the barriers to and predictors of homework compliance among this population is recommended.

Originality/value

This research highlights the need for incorporation of homework and further exploration of methods and treatment modalities to ensure homework compliance among substance using male offenders of IPV.
Multinational companies and the corporate social responsibility at home: the stakeholder approach
Authors: Kim Eun Woo , Choe Soonkyoo , Kwak Jooyoung
Published: November 2018

Purpose

The purpose of this paper is to integrate stakeholder and international business (IB) theories to explore the relationship between the international diversification of emerging-market multinational corporations (EMNCs) and corporate social performance (CSP) in their home markets. While the IB literature generally assumes a positive effect from international diversification on CSP as a result of global learning, the study aims at investigating the complicated effects in the link to the stakeholder theory.

Design/methodology/approach

This paper used combined sources of public survey data (corporate social responsibility (CSR) of the Korean firms) and archival data (foreign direct investment and corporate data). A truncated regression is used for statistical model.

Findings

International diversification helps MNCs to enhance CSP in their home countries. Thus, EMNCs can develop CSR capabilities at the global level, thereby benefiting domestic stakeholders. Also, significant investment in domestic research and development (R&D) and advertising negatively moderates the relationship between international diversification and domestic CSP. In this regard, expanding R&D and advertising facilitates global competitiveness. Moreover, as international diversification increases, EMNCs may redirect resources and re-orient CSR policies toward foreign stakeholders. Consequently, the relationship between international diversification and domestic CSP weaken.

Practical implications

Acceleration in international diversification may weaken domestic CSP, which arises from transformation into the global enterprises.

Originality/value

The study highlights the difficulties of EMNCs in serving domestic stakeholders effectively when their businesses are increasingly internationalized.
The entrepreneurial breaking point: undergoing moments of crisis
Authors: Gonzalez Katerina , Winkler Christoph
Published: November 2018

Purpose

The purpose of this paper is to provide a process view into moments of entrepreneurial crisis within the venture formation process caused by environmental stressors. A new construct is conceptualized, the entrepreneurial breaking point (EBP), as a critical and potentially insurmountable moment of crisis caused by an entrepreneur’s appraisal of environmental threats during a new venture’s formation.

Design/methodology/approach

To develop the EBP within a process model, this study builds upon previous environmental frameworks by expanding upon and infusing a situated social cognitive approach with a stress perspective.

Findings

The theoretical framework developed sheds light on the complex person-environment interaction that can create an EBP, the process of experiencing an EBP, how individuals vary in their activation of coping resources to respond to an EBP and how an EBP can ultimately result in new venture exit, sustained performance or growth.

Practical implications

The paper discusses implications for entrepreneurs during these moments of crises, including suggesting the use of trusted, impartial third-parties to overcome individual weaknesses, increasing awareness of the various environmental threats and finding a balance between goal-related commitment and adaptation.

Originality/value

This paper contributes to the existing literature by operationalizing and contextualizing a special case of socio-cognition under duress, filling an identified need for process work, exploring some reasons for EBP response variation across different entrepreneurs and elaborating on how the behavioral outcomes of an EBP may affect venture performance.
Structural, electronic, and mechanical properties of anatase titanium dioxide
Authors: Dash Debashish , Pandey Chandan Kumar , Chaudhary Saurabh , Tripathy Susanta Kumar
Published: November 2018

Purpose

The purpose of this paper is to analyze various properties of anatase titanium dioxide (TiO2) nanoparticles. Further, it proposes to implement Linear Combinations of Atomic Orbitals (LCAO) basis set under the framework of density functional theory and outline how LCAO is able to provide improved results in terms of various mechanical properties rather than plane wave and other theoretical results.

Design/methodology/approach

This paper provides an exploratory study on anatase TiO2by implementing OLCAO–DFT–LDA–LBFGS–EOS–PZ algorithms to find out various ground-level properties. The data so obtained are complemented by various analysis using mathematical expressions, description of internal processes occurred and comparison to others’ analytical results.

Findings

The paper provides some empirical insights on how mechanical properties of anatase TiO2improved by implementing LCAO methodology. From the analysis of electronic properties, it is seen that the anatase TiO2supports the inter band indirect transition from O-2p in valence region to Ti-3d in the conduction region.

Research limitations/implications

Most of the electronic properties are underestimated because a single exchange-correlation potential is not continuous across the gap. This gap can be enhanced by implementing Green’s function in place of DFT and the other way is to implement self-interaction correction.

Practical implications

The use of anatase TiO2is primarily used for catalytic applications. This is also used to enhance the quality of paper in the paper industry. Additionally, this is used as a prime ingredient in cosmetic industry.

Originality/value

This paper fulfills an identified need to study how LCAO, another basis set, plays an important role in improving material properties.
Re-modified quintic B-spline collocation method for the solution of Kuramoto–Sivashinsky type equations
Authors: Dhiman Neeraj , Tamsir Mohammad
Published: November 2018

Purpose

The purpose of this paper is to present a new method, namely, “Re-modified quintic B-spline collocation method” to solve the Kuramoto–Sivashinsky (KS) type equations. In this method, re-modified quintic B-spline functions and the Crank–Nicolson formulation is used for space and time integration, respectively. Five examples are considered to test out the efficiency and accuracy of the method. The main objective is to develop a method which gives more accurate results and reduces the computational cost so that the authors require less memory storage.

Design/methodology/approach

A new collocation technique is developed to solve the KS type equations. In this technique, quintic B-spline basis functions are re-modified and used to integrate the space derivatives while time derivative is discretized by using Crank–Nicolson formulation. The discretization yields systems of linear equations, which are solved by using Gauss elimination method with partial pivoting.

Findings

Five examples are considered to test out the efficiency and accuracy of the method. Finally, the present study summarizes the following outcomes: first, the computational cost of the proposed method is the less than quintic B-spline collocation method. Second, the present method produces better results than those obtained by Lattice Boltzmann method (Lai and Ma, 2009), quintic B-spline collocation method (Mittal and Arora, 2010), quintic B-spline differential quadrature method (DQM) (Mittal and Dahiya, 2017), extended modified cubic B-spline DQM (Tamsir et al., 2016) and modified cubic B-splines collocation method (Mittal and Jain, 2012).

Originality/value

The method presented in this paper is new to best of the authors’ knowledge. This work is the original work of authors and the manuscript is not submitted anywhere else for publication.
Discrimination of the Sicilian Prickly Pear (Opuntia Ficus‐Indica L., CV. Muscaredda) According to the Provenance by Testing Unsupervised and Supervised Chemometrics
Authors: Albergamo Ambrogina , Mottese Antonio F. , Bua Giuseppe D. , Caridi Francesco , Sabatino Giuseppe , Barrega Luna , Costa Rosaria , Dugo Giacomo
Published: November 2018

Different multivariate techniques were tested in an attempt to build up a statistical model for predicting the origin of prickly pears (Opuntia ficus‐indica L., cv. Muscaredda) from several localities within the Sicilian region. Specifically, two areas known for producing fruits marked respectively by TAP (traditional agri‐food product) and PDO (protected designation of origin) brands, and three sites producing non‐branded fruits, were considered. A validated inductively coupled plasma mass spectrometry (ICP‐MS) method allowed to obtain elemental fingerprints of prickly pears, which were subsequently elaborated by unsupervised tools, such as hierarchical clustering analysis (HCA) and principal component analysis (PCA), and supervised techniques, such as stepwise‐canonical discriminant analysis (CDA) and partial least squares—discriminant analysis (PLS‐DA). With the exception of HCA, which was not enough powerful to correctly cluster all selected samples, PCA successfully investigated the effect of subregional provenance on prickly pears, thus, differentiating labeled products from the non‐labeled counterpart. Also, stepwise CDA and PLS‐DA allowed to build up reliable models able to correctly classify 100% of fruits on the basis of the production areas, by exploiting a restricted pool of metals. Both statistical models, including unsupervised (PCA) and supervised techniques (stepwise CDA or PLS‐DA), may guarantee the provenance of prickly pears protected by quality labels and safeguard producers and consumers.

Practical Application

Based on elemental analysis and chemometrics, the reliable traceability models herein proposed, could be applied to commercial Sicilian prickly pears protected by TAP and PDO logos to guarantee their provenance and, at the same time, to safeguard producers and consumers.
Prevalence of ROS1 fusion in Chinese patients with non‐small cell lung cancer
Authors: Zhang Qing , Wu Chunyan , Ding Wei , Zhang Zhihong , Qiu Xueshan , Mu Dianbin , Zhang Haiqing , Xi Yanfeng , Zhou Jianhua , Ma Liheng , Fu Shijun , Gao Min , Wang Bo , Deng Juan , Lin Dongmei , Zhang Jie
Published: November 2018

Background

The study was conducted to investigate the clinicopathological features and prevalence of ROS1 gene fusion in Chinese patients with non‐small cell lung cancer (NSCLC).

Methods

The presence of ROS1 fusion was assessed by quantitative real‐time PCR. Associations between ROS1 fusion and clinical characteristics were analyzed.

Results

In total, 6066 patients with pathologically confirmed NSCLC and ROS1 fusion test results were enrolled. The average age was 60.89 ± 10.60 years and fusion was detected in 157 (2.59%) patients. Fusion frequency was significantly correlated with age, gender, smoking status (all P < 0.001), pathology type (P = 0.017), and lymph node metastasis stage (P = 0.027). ROS1 fusion‐positive patients were significantly younger (55.68 ± 11.34 vs. negative 61.02 ± 10.44 years; P < 0.01). Fusion frequency was higher in women (3.71% vs. men 1.81%), never‐smokers (3.33% vs. smokers 1.21%), and patients with adenocarcinoma (2.77% vs. squamous lung cancer 0.93%) and at advanced node stages (1.31%, 1.40%, 2.07%, and 3.23% for N0, N1, N2, and N3, respectively). No significant correlation between ROS1 fusion status and pathological stage was found in subgroups classified by pathological, tumor, or metastasis stage (P > 0.05). Age, smoking status, and lymph node stage were statistically significantly correlated with ROS1 fusion frequency (all P < 0.05); gender and pathology type were not significantly correlated with ROS1 fusion status after adjusting for smoking status.

Conclusion

An overall ROS1 fusion frequency of 2.59% was confirmed in this study. ROS1 fusion was more prevalent among younger patients, never‐smokers, and those at advanced node stages.
Rapamycin improves healthspan but not inflammaging in nfκb1−/− mice
Authors: Correia‐Melo Clara , Birch Jodie , Fielder Edward , Rahmatika Dina , Taylor Jennifer , Chapman James , Lagnado Anthony , Carroll Bernadette M. , Miwa Satomi , Richardson Gavin , Jurk Diana , Oakley Fiona , Mann Jelena , Mann Derek A. , Korolchuk Viktor I. , Passos João F.
Published: November 2018

Increased activation of the major pro‐inflammatory NF‐κB pathway leads to numerous age‐related diseases, including chronic liver disease (CLD). Rapamycin, an inhibitor of mTOR, extends lifespan and healthspan, potentially via suppression of inflammaging, a process which is partially dependent on NF‐κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF‐κB signalling, such as that which occurs in several age‐related chronic diseases. In this study, we investigated whether rapamycin could ameliorate age‐associated phenotypes in a mouse model of genetically enhanced NF‐κB activity (nfκb1−/−) characterized by low‐grade chronic inflammation, accelerated aging and CLD. We found that, despite showing no beneficial effects in lifespan and inflammaging, rapamycin reduced frailty and improved long‐term memory, neuromuscular coordination and tissue architecture. Importantly, markers of cellular senescence, a known driver of age‐related pathology, were alleviated in rapamycin‐fed animals. Our results indicate that, in conditions of genetically enhanced NF‐κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.
Spotted wing drosophila (Drosophila suzukii) utilization and dispersal from the wild host Asian bush honeysuckle (Lonicera spp.)
Authors: Leach Heather , Hagler James R. , Machtley Scott A. , Isaacs Rufus
Published: November 2018

Wild host plants in the landscape surrounding fruit farms may significantly influence the movement and population of the polyphagous and invasive pest Drosophila suzukii.

Across 2 years, we sampled wild hosts adjacent to 10 blueberry farms in Michigan, U.S.A. We found five commonly infested wild fruits.

Honeysuckle was a particularly abundant early season reproductive host. Consequently, six blueberry farms with honeysuckle at the margin were evaluated further. At each farm, nonhost plants and honeysuckle were monitored for larval and adult D. suzukii. The season‐long abundance of D. suzukii adults and early‐season infestation was highest near and within honeysuckle.

In 2017, we tracked the movement of D. suzukii between honeysuckle and blueberries in early and late season using a protein immunomarking technique. Of the 1881 flies captured in our study, 7.1% were marked and their distribution pattern was even throughout the farm. Moreover, early season flies were less likely to remain in the marked host compared with late season flies.

The findings of the present study highlight the importance of wild hosts on local pest pressure from D. suzukii and suggest that wild host management should be considered as part of integrated strategies for reducing the economic impacts of this pest.
Prevalence and correlates of growth failure in young African patients with sickle cell disease
Authors: Alexandre‐Heymann Laure , Dubert Marie , Diallo Dapa A. , Diop Saliou , Tolo Aissata , Belinga Suzanne , Sanogo Ibrahima , Diagne Ibrahima , Wamba Guillaume , Boidy Kouakou , Ly Indou Deme , Kamara Ismaël , Traore Youssouf , Offredo Lucile , Jouven Xavier , Ranque Brigitte
Published: November 2018

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high‐income countries, but data are lacking in sub‐Saharan Africa. We performed a cross‐sectional study nested in the CADRE (Cœur, Artères et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5–21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD‐related complications. GF was diagnosed in 51% of HbSS, 58% of HbSβ0, 44% of HbSC, 38% of HbSβ+ patients and 32% of controls. GF in patients was positively associated with parents’ lower education level, male sex, age 12–14 years, lower blood pressure, HbSS or HbSβ0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD‐related complications. In sub‐Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD‐related clinical complications.
Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab
Authors: Tamura Ryota , Tanaka Toshihide , Ohara Kentaro , Miyake Keisuke , Morimoto Yukina , Yamamoto Yohei , Kanai Ryuichi , Akasaki Yasuharu , Murayama Yuichi , Tamiya Takashi , Yoshida Kazunari , Sasaki Hikaru
Published: November 2018

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naïve Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post‐Bev recurrent tumors from 9 patients were included. The expression of programmed cell death‐1 (PD‐1)/PD ligand‐1 (PD‐L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD‐L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The PD‐1+ cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naïve Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor‐associated macrophages significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post‐Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long‐term Bev therapy.
A rapid method for estimation of the efficacy of potential antimicrobials in humans and animals by agar diffusion assay
Authors: Salina Elena G. , Ekins Sean , Makarov Vadim A.
Published: November 2018

Drug resistance continues to challenge traditional antimicrobial drugs and limit their clinical utility. This requires us to continue our search for new drug candidates with novel mechanisms of action against infectious diseases. We now describe a simple agar diffusion assay, which can be used as a general method for the rapid detection of antimicrobial activity of drug candidates in animal or human blood plasma for the ultimate prediction of the efficacy of potential drugs prior to clinical trials. We present an example for a clinical candidate against Mycobacterium tuberculosis.
A general model for fuzzy decision tree and fuzzy random forest
Authors: Zheng Hui , He Jing , Zhang Yanchun , Huang Guangyan , Zhang Zhenjiang , Liu Qing
Published: November 2018

The problem of risk classification and prediction, an essential research direction, aiming to identify and predict risks for various applications, has been researched in this paper. To identify and predict risks, numerous researchers build models on discovering hidden information of a label (positive credit or negative credit). Fuzzy logic is robust in dealing with ambiguous data and, thus, benefits the problem of classification and prediction. However, the way to apply fuzzy logic optimally depends on the characteristics of the data and the objectives, and it is extraordinarily tricky to find such a way. This paper, therefore, proposes a general membership function model for fuzzy sets (GMFMFS) in the fuzzy decision tree and extend it to the fuzzy random forest method. The proposed methods can be applied to identify and predict the credit risks with almost optimal fuzzy sets. In addition, we analyze the feasibility of our GMFMFS and prove our GMFMFS‐based linear membership function can be extended to a nonlinear membership function without a significant increase in computing complex. Our GMFMFS‐based fuzzy decision tree is tested with a real dataset of US credit, Susy dataset of UCI, and synthetic datasets of big data. The results of experiments further demonstrate the effectiveness and potential of our GMFMFS‐based fuzzy decision tree with linear membership function and nonlinear membership function.
Household self‐blame for disasters: responsibilisation and (un)accountability in decentralised participatory risk governance
Authors: Sou Gemma
Published: November 2018

The most important theoretical argument concerning decentralised participatory governance is that it can make a government more accountable for the needs of the governed. Key to this process are participatory spaces that act as mechanisms for dialogue between citizens and local government. However, within Cochabamba, a city in the centre of Bolivia, South America, ‘at‐risk’ citizens engage minimally with disaster risk issues in participatory spaces, despite high levels of civic participation. This is because ‘at‐risk’ populations view disasters as a private/household problem that is symptomatic of household error, rather than seeing them as a broader public problem due to wider structural inequalities. Consequently, they redistribute responsibility for disaster risk reduction towards households, which (re)produces the absolution of government authorities as guarantors of disaster risk reduction. This paper challenges the normative assumption that participatory spaces facilitate democratic deliberation of disaster risk reduction and the downward accountability of local government for disaster risk reduction.
Spatial variability in the somatic growth of pikeperch Sander lucioperca, an invasive piscivorous fish
Authors: Nolan Emma T. , Britton J. Robert
Published: November 2018

Introduced fishes can develop invasive populations that impact native species and ecosystems. Understanding the population ecology of introduced species in their extended ranges and how this compares to their native ranges is therefore important for informing their management. Here, the age and somatic growth rates of the piscivorous freshwater fish pikeperch Sander lucioperca were analysed across their invasive and native ranges to determine their spatial patterns and drivers. Analyses were initially completed in their invaded range in central and western England. Populations varied spatially in their growth rates; being slowest for a population in a narrow and shallow canal and fastest in a large, impounded lowland river. A meta‐analysis of parameters of the von Bertalanffy growth model then revealed that across their native and invasive ranges, their theoretical ultimate lengths (L∞) and growth coefficients (K) were significantly related to latitude, but not longitude. Their relationships with latitude were nonlinear, with higher values of L∞ and lower values of K being evident towards their northerly and southerly range limits. Faster growth rates were evident in the middle of their range (45 to 55°N), suggesting temperatures here were most optimal for growth, but were in a trade‐off with reduced ultimate lengths. These spatial patterns suggest that whilst introduced S. lucioperca can colonise new waters across a wide area, the expression of their life‐history traits will vary spatially, with potential implications for how invasive populations establish and integrate into native fish communities.
Experimental study of unstable crack propagation velocity for X80 pipeline steel
Authors: Dong Shaohua , Zhang Lai bin , Zhang Hewei , Chen Yinuo , Zhang Hang
Published: November 2018

Unstable crack propagation velocity following the failure of pipeline steel has always been a problem. In this study, differences between the existing unstable crack propagation calculation models were analysed, and the deficiencies within the crack propagation velocity models were overcome. The hardening coefficient and hardening index of the ductile material were considered, and a velocity model of unstable crack propagation of pipelines based on the Hutchinson‐Rice‐Rosengren (HRR) theory elastic‐plastic stress‐strain field and the displacement field was established. Consequently, the limit propagation velocity was obtained. In full‐scale burst test, the pipe with diameter of 1422 mm was chosen to simulate the natural gas pipeline transportation environment. Compared with the theoretical result, the error was limited in 13%. The research result solved the problem of quantifying the propagation velocity of the crack in X80 pipeline, which was significant for describing the forecast of velocity and length of unstable propagation and failure characteristics of pipelines.
Methodology for assessment of statistical planning effects on the S‐N curve determination using Monte Carlo simulations
Authors: Goedel Fábio , Chamberlain Pravia Zacarias Martin , Mezzomo Gustavo Prates
Published: November 2018

One of the most important input data in fatigue analysis is the material fatigue properties. This research aims to present a methodology for assessment of statistical planning of fatigue experiments through a MatLab algorithm developed based on Monte Carlo simulations, which enables to simulate statistically the effects of main parameters used for defining the fatigue test setting and to verify their impact on the relative percentage difference (RPD) in fatigue properties estimation comparing to a reference material. The aspects treated here have not been clearly discussed in the standards. Therefore, the proposed recommendations combined with standards procedures is a tool for test engineers, permitting a fatigue test planning with more background and precision, which can help in decisions about which is the better setup, including the sample size, number of stress levels, stress value in each level, and replication. The methodology and good practices presented in this paper were demonstrated by means of actual data from the literature.
Gliomasphere marker combinatorics: multidimensional flow cytometry detects CD44+/CD133+/ITGA6+/CD36+ signature
Authors: Erhart Friedrich , Blauensteiner Bernadette , Zirkovits Gabriel , Printz Dieter , Soukup Klara , Klingenbrunner Simone , Fischhuber Katrin , Reitermaier René , Halfmann Angela , Lötsch Daniela , Spiegl‐Kreinecker Sabine , Berger Walter , Visus Carmen , Dohnal Alexander
Published: November 2018

Glioblastoma is the most dangerous brain cancer. One reason for glioblastoma's aggressiveness are glioblastoma stem‐like cells. To target them, a number of markers have been proposed (CD133, CD44, CD15, A2B5, CD36, CXCR4, IL6R, L1CAM, and ITGA6). A comprehensive study of co‐expression patterns of them has, however, not been performed so far. Here, we mapped the multidimensional co‐expression profile of these stemness‐associated molecules. Gliomaspheres – an established model of glioblastoma stem‐like cells – were used. Seven different gliomasphere systems were subjected to multicolor flow cytometry measuring the nine markers CD133, CD44, CD15, A2B5, CD36, CXCR4, IL6R, L1CAM, and ITGA6 all simultaneously based on a novel 9‐marker multicolor panel developed for this study. The viSNE dimensionality reduction algorithm was applied for analysis. All gliomaspheres were found to express at least five different glioblastoma stem‐like cell markers. Multi‐dimensional analysis showed that all studied gliomaspheres consistently harbored a cell population positive for the molecular signature CD44+/CD133+/ITGA6+/CD36+. Glioblastoma patients with an enrichment of this combination had a significantly worse survival outcome when analyzing the two largest available The Cancer Genome Atlas datasets (MIT/Harvard Affymetrix: P = 0.0015, University of North Carolina Agilent: P = 0.0322). In sum, we detected a previously unknown marker combination – demonstrating feasibility, usefulness, and importance of high‐dimensional gliomasphere marker combinatorics.
Testin protects against cardiac hypertrophy by targeting a calcineurin‐dependent signalling pathway
Authors: Gao Lu , Liu Yuan , Guo Sen , Xiao Lili , Liang Cui , Wang Xiaofang
Published: November 2018

Multiple organs express testin (TES), including the heart. Nevertheless, current understanding of the influence of TES on cardiovascular diseases, especially on cardiac hypertrophy and its etiology, is insufficient. This study investigated the influence of TES on cardiac hypertrophy and its etiology. Murine models with excessive TES expression specific to the heart were constructed with an adeno‐associated virus expression system. Cardiac hypertrophy was stimulated through aortic banding (AB). The severity of cardiac hypertrophy was evaluated through molecular, echocardiographic, pathological, and hemodynamic examination. The findings of our study revealed that TES expression was remarkably suppressed not only in failing human hearts but also in mouse hearts with cardiac hypertrophy. It was discovered that excessive TES expression driven by an adeno‐associated viral vector noticeably inhibited hypertrophy triggered by angiotensin II (Ang II) in cultivated cardiomyocytes from newborn rats. It was also revealed that TES knockdown via AdshTES caused the reverse phenotype in cardiomyocytes. Furthermore, it was proved that excessive TES expression attenuated the ventricular dilation, cardiac hypertrophy, dysfunction, and fibrosis triggered by AB in mice. It was discovered that TES directly interacted with calcineurin and suppressed its downstream signalling pathway. Moreover, the inactivation of calcineurin with cyclosporin A greatly offset the exacerbated hypertrophic response triggered by AB in TES knockdown mice. Overall, the findings of our study suggest that TES serves as a crucial regulator of the hypertrophic reaction by hindering the calcineurin‐dependent pathway in the heart.