bluuebunny/crossref_metadata_2025_split huggingface dataset:
The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer
Authors: Kandil Sahar , Prencipe Filippo , Jones Samuel , Hiscox Stephen , Westwell Andrew D. 
Published: August 2017

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK‐VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA‐MB‐231, BT474 and T47D). Compound 5c was identified to display an average activity of IC50 = 23.5–31.3 μm, which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series.
Assessing the ideal microwave duration for disinfection of sinus irrigation bottles—A quantitative study
Authors: Nikolaou E. , Mitsi E. , Ferreira D.M. , Bartolo A. , Leong S.C. 
Published: August 2017

ObjectivesSaline irrigation of the nasal cavity and paranasal sinuses has a recognised role in the management of chronic rhinosinusitis. However, bacterial recontamination of irrigation bottles through backflow from the sinonasal cavity is a concern in recurrent sinus cavity infections. While patients are encouraged to clean the irrigation bottles regularly, there remains significant concern that the use of contaminated bottles may perpetuate chronic rhinosinusitis. This study assesses the optimal microwave duration to achieve decontamination for each irrigation bottle component part (reservoir, tube and nozzle) using a standard, commercially available microwave. In addition, the irrigation fluid was also tested for contamination after each microwave cycle.Study DesignLaboratory‐based experimental study.ParticipantsNo patients were involved in this study.Main outcome measuresThe percentage in vitro decontamination of the bottles’ components was determined following 30, 60, 90, 120, 150 seconds of microwave cycles.ResultsComplete decontamination of the bottles was not achieved at any of the tested microwave cycles. Levels of decontamination differed for the different bottle components, and the greatest degree of decontamination for all bottle components occurred at 90 seconds. Although higher levels of decontamination were observed at microwave durations exceeding 90 seconds, this was at the expense of thermal degradation and deformation of the reservoir plastic component of the irrigation bottle. Similarly, lowest contamination of irrigation fluid was observed at 120 seconds.ConclusionsThis study highlights the importance of establishing precise decontamination procedures and recommends a microwave cycle of 90 seconds for optimal decontamination.
MicroRNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole miRNome profiling of human hippocampus
Authors: Bencurova Petra , Baloun Jiri , Musilova Katerina , Radova Lenka , Tichy Boris , Pail Martin , Zeman Martin , Brichtova Eva , Hermanova Marketa , Pospisilova Sarka , Mraz Marek , Brazdil Milan 
Published: August 2017

SummaryObjectiveMesial temporal lobe epilepsy (mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis (HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+HS complicates its therapy. The pathological mechanism underlying mTLE+HS may involve abnormal gene expression regulation, including posttranscriptional networks involving microRNAs (miRNAs). miRNA expression deregulation has been reported in various disorders, including epilepsy. However, the miRNA profile of mTLE+HS is not completely known and needs to be addressed.MethodsHere, we have focused on hippocampal miRNA profiling in 33 mTLE+HS patients and nine postmortem controls to reveal abnormally expressed miRNAs. In this study, we significantly reduced technology‐related bias (the most common source of false positivity in miRNA profiling data) by combining two different miRNA profiling methods, namely next generation sequencing and miRNA‐specific quantitative real‐time polymerase chain reaction.ResultsThese methods combined have identified and validated 20 miRNAs with altered expression in the human epileptic hippocampus; 19 miRNAs were up‐regulated and one down‐regulated in mTLE+HS patients. Nine of these miRNAs have not been previously associated with epilepsy, and 19 aberrantly expressed miRNAs potentially regulate the targets and pathways linked with epilepsy (such as potassium channels, γ‐aminobutyric acid, neurotrophin signaling, and axon guidance).SignificanceThis study extends current knowledge of miRNA‐mediated gene expression regulation in mTLE+HS by identifying miRNAs with altered expression in mTLE+HS, including nine novel abnormally expressed miRNAs and their putative targets. These observations further encourage the potential of microRNA‐based biomarkers or therapies.
The European Union Post‐Brexit: Static or Dynamic Adaptation?
Authors: Majone Giandomenico 
Published: August 2017

AbstractThe choice facing the leaders of the European Union, after Brexit, is between a static adaptation, leaving the current approach to integration essentially unchanged, and a dynamic adaptation, which recognises the need for radical changes. Dynamic adaptation requires institutional leadership—something apparently incompatible with the basic principle of the equality of all the Member States. The clearest indication of a deficit of leadership is the failure to define the real purpose of the collective activity. This failure is at the root of Brexit, as may be seen from the explicit rejection of the indefinite goal of ‘ever closer union’ by the British prime minister in November 2015. An alternative approach to European integration finds a good theoretical foundation in Buchanan's theory of clubs. The essential principle of a functional organisation at supranational level is that activities would be selected specifically and organised separately. A strictly functional approach to integration could revive an interest in political union in the form of a confederation. As Tocqueville had clearly understood long ago, the weakness of confederations increases in direct proportion to the extent of their nominal power. What is most important today is to distinguish between the general idea of European integration and one particular implementation of that idea, such as the European Union.
‘Accountable Independence’ of the European Central Bank: Seeing the Logics of Transparency
Authors: Curtin Deirdre 
Published: August 2017

AbstractThe European Central Bank (ECB) emerged from the financial crisis not only as the institutional ‘winner’ but also as the most central—and powerful—supranational institution of our times. This article challenges the so‐called ‘accountable independence’ of the ECB across the range of tasks it carries out. Citizens ‘see’ the ECB today especially for its role in promoting austerity and its involvement as part of the troika and otherwise in the economic decision making of troubled Member States. Far from ECB monetary policy heralding a ‘new democratic model’, the ECB today suffers from a clear deficit in democracy. In between the grandiose concept of ECB ‘independence’ and the more performative ECB ‘accountability’ lies ‘transparency’. Across the range of ECB practices there is a need to take the related concepts of ‘transparency’ and of (democratic) ‘accountability’ more seriously, both in conceptual terms and in their relationship to one another.
Streptococcus pneumoniae surface protein PfbA is a versatile multidomain and multiligand‐binding adhesin employing different binding mechanisms
Authors: Beulin Darwin Selvi Jemima , Radhakrishnan Deepthi , Suresh Sharanya C. , Sadasivan Chittalakottu , Yamaguchi Masaya , Kawabata Shigetada , Ponnuraj Karthe 
Published: August 2017

Streptococcus pneumoniae, one of the major human respiratory pathogens, uses its repertoire of surface proteins to adhere to the epithelium of the nasopharynx and lungs leading to colonization. PfbA is a conserved surface protein of S. pneumoniae and helps the bacterium to colonize the host by recognizing the extracellular matrix (ECM) molecule fibronectin, as well as blood proteins like plasminogen and human serum albumin. The crystal structure of rPfbA150–607 revealed it to possess a beta‐helical region similar to those of carbohydrate‐active enzymes as well as a C‐terminal segment that resembles the fibronectin‐binding regions of fibronectin‐binding proteins. To get more insight into the putative carbohydrate‐binding property of PfbA and its binding to various host molecules, we generated three different constructs of PfbA and characterized them by ELISA, isothermal titration calorimetry and bio‐layer interferometry experiments. Importantly, the isothermal titration calorimetry experiments revealed that PfbA binds to different saccharides. Further, ELISA and bio‐layer interferometry experiments identified that (a) apart from fibronectin and plasminogen, the beta helix of PfbA also binds to other ECM molecules (b) lysines are not responsible for PfbA's binding to plasminogen, (c) in comparison with native fibrinogen, deglycosylated‐fibrinogen exhibits reduced binding affinity towards PfbA implying the importance of sugar molecule‐PfbA interaction and (d) the C‐terminal region of PfbA binds exclusively to the N‐terminal F1 modules of fibronectin. Thus, the results of this study show PfbA to be a versatile multidomain and multiligand‐binding protein employing different binding mechanisms. These results could be useful for structure‐based designing of inhibitors against PfbA.
Do adult mental health services identify child abuse and neglect? A systematic review
Authors: Read John , Harper David , Tucker Ian , Kennedy Angela 
Published: August 2017

AbstractChild abuse and neglect play a causal role in many mental health problems. Knowing whether users of mental health services were abused or neglected as children could be considered essential for developing comprehensive formulations and effective treatment plans. In the present study we report the findings of a systematic review, using independent searches of three databases designed to discover how often mental health staff find out whether their clients were abused or neglected as children. Twenty‐one relevant studies were identified. Most people who use mental health services are never asked about child abuse or neglect. The majority of cases of child abuse or neglect are not identified by mental health services. Only 28% of abuse or neglect cases identified by researchers are found in the clients’ files: emotional abuse, 44%; physical abuse, 33%; sexual abuse, 30%; emotional neglect, 17%; and physical neglect, 10%. Between 0% and 22% of mental health service users report being asked about child abuse. Men and people diagnosed with psychotic disorders are asked less than other people. Male staff ask less often than female staff. Some improvement over time was found. Policies compelling routine enquiry, training, and trauma‐informed services are required.
Cost‐effective options for the prevention and management of gastrointestinal and liver disease in the Asia–Pacific region
Authors: Roberts‐Thomson Ian C , Lung Thomas 
Published: August 2017

AbstractThe Asia–Pacific region contains more than half of the world's population and is markedly heterogeneous in relation to income levels and the provision of public and private health services. For low‐income countries, the major health priorities are child and maternal health. In contrast, priorities for high‐income countries include vascular disease, cancer, diabetes, dementia, and mental health disorders as well as chronic inflammatory disorders such as hepatitis B and hepatitis C. Cost‐effectiveness analyses are methods for assessing the gains in health relative to the costs of different health interventions. Methods for measuring health outcomes include years of life saved (or lost), quality‐adjusted life years, and disability‐adjusted life years. The incremental cost‐effectiveness ratio measures the cost (usually in US dollars) per life year saved, quality‐adjusted life year gained, or disability‐adjusted life year averted of one intervention relative to another. In low‐income countries, approximately 50% of infant deaths (< 5 years) are caused by gastroenteritis, the major pathogen being rotavirus infection. Rotavirus vaccines appear to be cost‐effective but, thus far, have not been widely adopted. In contrast, infant vaccination for hepatitis B is promoted in most countries with a striking reduction in the prevalence of infection in vaccinated individuals. Cost‐effectiveness analyses have also been applied to newer and more expensive drugs for hepatitis B and C and to government‐sponsored programs for the early detection of hepatocellular, gastric, and colorectal cancer. Most of these studies reveal that newer drugs and surveillance programs for cancer are only marginally cost‐effective in the setting of a high‐income country.
The signals to trigger the initiation of ovule enlargement are from the pollen tubes: The direct evidence
Authors: Zhong Sheng , Zhang Jun , Qu Li‐Jia 
Published: August 2017

SummaryIn angiosperms, initiation of ovule enlargement represents the start of seed development, the molecular mechanism of which is not yet elucidated. It was previously reported that pollen tube contents, rather than double fertilization, can trigger ovule enlargement. However, it remains unclear whether the signal(s) to trigger the initiation of ovule enlargement are from the sperm cells or from the pollen tubes. Recently, we identified a mutant drop1− drop2−, which produces pollen tubes with no sperm cells. Taking advantage of this special genetic material, we conducted pollination assays, and found that the ovules pollinated with drop1− drop2− pollen could initiate the enlargement and exhibited significant enlarged sizes at 36 h after pollination in comparison with those unpollinated ovules. However, the sizes of the ovules pollinated with drop1− drop2− pollen are significantly smaller than those of the ovules pollinated with wild‐type pollen. These results demonstrate that the pollen tube, rather than the sperm cells, release the signal to trigger the initiation of ovule enlargement, and that double fertilization is required for further enlargement of the seeds.
Loss of chloroplast‐localized protein phosphatase 2Cs in Arabidopsis thaliana leads to enhancement of plant immunity and resistance to Xanthomonas campestris pv. campestris infection
Authors: Akimoto‐Tomiyama Chiharu , Tanabe Shigeru , Kajiwara Hideyuki , Minami Eiichi , Ochiai Hirokazu 
Published: August 2017

SummaryProtein phosphatases (PPs) counteract kinases in reversible phosphorylation events during numerous signal transduction pathways in eukaryotes. PP2Cs, one of the four major classes of the serine/threonine‐specific PP family, are greatly expanded in plants. Thus, PP2Cs are thought to play a specific role in signal transduction pathways. Some rice PP2Cs classified in subgroup K are responsive to infection by the compatible Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight. In Arabidopsis thaliana, orthologous PP2C genes (AtPP2C62 and AtPP2C26) classified to subgroup K are also responsive to Xanthomonas campestris pv. campestris (Xcc, causal agent of black rot) infection. To elucidate the function of these subgroup K PP2Cs, atpp2c62‐ and atpp2c26‐deficient A. thaliana mutants were characterized. A double mutant plant which was inoculated with a compatible Xcc showed reduced lesion development, as well as the suppression of bacterial multiplication. AtPP2C62 and AtPP2C26 localized to the chloroplast. Furthermore, the photosynthesis‐related protein, chaperonin‐60, was indicated as the potential candidate for the dephosphorylated substrate catalysed by AtPP2C62 and AtPP2C26 using two‐dimensional isoelectric focusing sodium dodecylsulfate‐polyacrylamide gel electrophoresis (2D‐IDF‐SDS‐PAGE). Taken together, AtPP2C62 and AtPP2C26 are suggested to be involved in both photosynthesis and suppression of the plant immune system. These results imply the occurrence of crosstalk between photosynthesis and the plant defence system to control productivity under pathogen infection.
The Shifting Border Between Perception and Cognition
Authors: Phillips Ben 
Published: August 2017

AbstractThe distinction between perception and cognition has always had a firm footing in both cognitive science and folk psychology. However, there is little agreement as to how the distinction should be drawn. In fact, a number of theorists have recently argued that, given the ubiquity of top‐down influences (at all levels of the processing hierarchy), we should jettison the distinction altogether. I reject this approach, and defend a pluralist account of the distinction. At the heart of my account is the claim that each legitimate way of marking a border between perception and cognition deploys a notion I call ‘stimulus‐control.’ Thus, rather than being a grab bag of unrelated kinds, the various categories of the perceptual are unified into a superordinate natural kind (mutatis mutandis for the complimentary categories of the cognitive).
Uptake kinetics of nitrate, ammonia and phosphate by the dinoflagellate Heterocapsa circularisquama isolated from Hiroshima Bay, Japan
Authors: Yamamoto Tamiji , Kishigami Tomoko , Nakagawa Hikaru 
Published: August 2017

SUMMARY
Heterocapsa circularisquama is a harmful dinoflagellate whose first bloom in Hiroshima Bay, Japan, appeared in 1992. As suggested by the authors’ group, in the Seto Inland Sea including Hiroshima Bay, oligotrophication particularly the reduction of phosphate starting 1980 is severe. The bloom caused serious damage to the bay's extensive oyster culture. In the present study, the uptake kinetics of nitrate, ammonia, and phosphate by this species were experimentally investigated. The maximum uptake rate (ρmax) and the half‐saturation constant (Ks) were 0.41 pmol cell−1 h−1 and 4.45 μM, respectively, for nitrate, 2.02 pmol cell−1 h−1 and 11.1 μM for ammonium, and 0.079 pmol cell−1 h−1 and 1.79 μM for phosphate. The maximum specific uptake rates (Vmax) for nitrate, ammonia, and phosphate were estimated to be 8.95, 44.1, and 21.3 day−1, respectively. A comparison of Vmax/Ks, which is also an index of affinity to nutrients, between this species and others suggested that H. circularisquama can utilize nitrate and ammonia efficiently, but not phosphate. Considering both reports describing that H. circularisquama has the ability to utilize dissolved organic phosphorus (DOP) and the DOP concentration is higher than phosphate in Hiroshima Bay, it was concluded that H. circularisquama became dominant due to the phosphate reduction measure.
Innovative look at dairy heifer rearing: Effect of prenatal and post‐natal environment on later performance
Authors: Van Eetvelde M , Opsomer G 
Published: August 2017

ContentsAs heifer rearing is a costly investment, dairy farmers have been stimulated to maximize early growth of their calves, mainly by enhanced liquid feeding. However, the long‐term effects of this “accelerated growth” are largely unknown. Studies recently performed at Ghent University indicate that in dairy cattle, certain maternal factors (such as young age and high milk yield) and environmental factors (such as high ambient temperatures) create a suboptimal environment for the developing foetus, altering the phenotype of the newborn calf. According to the “thrifty phenotype hypothesis,” these metabolic alterations prepare the newborn for similar (“matching”) conditions after birth, enhancing its survival during periods of limited feeding. Yet, when an abundance of nutrients is available in post‐natal life (e.g., during periods of enhanced feeding), the “mismatch” between pre‐ and post‐natal environment results in an early catch‐up growth, with potential negative consequences. The aim of the article was to discuss this mismatch between pre‐ and post‐natal environment in dairy calves. Previous studies, especially in human medicine, have shown catch‐up growth to be associated with obesity, fertility problems, metabolic diseases and a reduced lifespan. Hence, we hypothesize that, by applying programs of accelerated growth, our current management system accentuates the mismatch between the pre‐ and post‐natal environment in dairy calves. We can conclude that, although more research is necessary, the current findings point towards a more individual approach when rearing dairy heifers.
Insurance, Public Assistance, and Household Flood Risk Reduction: A Comparative Study of Austria, England, and Romania
Authors: Hanger Susanne , Linnerooth‐Bayer Joanne , Surminski Swenja , Nenciu‐Posner Cristina , Lorant Anna , Ionescu Radu , Patt Anthony 
Published: August 2017

AbstractIn light of increasing losses from floods, many researchers and policymakers are looking for ways to encourage flood risk reduction among communities, business, and households. In this study, we investigate risk‐reduction behavior at the household level in three European Union Member States with fundamentally different insurance and compensation schemes. We try to understand if and how insurance and public assistance influence private risk‐reduction behavior. Data were collected using a telephone survey (n = 1,849) of household decisionmakers in flood‐prone areas. We show that insurance overall is positively associated with private risk‐reduction behavior. Warranties, premium discounts, and information provision with respect to risk reduction may be an explanation for this positive relationship in the case of structural measures. Public incentives for risk‐reduction measures by means of financial and in‐kind support, and particularly through the provision of information, are also associated with enhancing risk reduction. In this study, public compensation is not negatively associated with private risk‐reduction behavior. This does not disprove such a relationship, but the negative effect may be mitigated by factors related to respondents' capacity to implement measures or social norms that were not included in the analysis. The data suggest that large‐scale flood protection infrastructure creates a sense of security that is associated with a lower level of preparedness. Across the board there is ample room to improve both public and private policies to provide effective incentives for household‐level risk reduction.