bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmic hazard map for a 3D whole‐ventricle model under multiple ion channel block
Authors: Okada Jun‐ichi , Yoshinaga Takashi , Kurokawa Junko , Washio Takumi , Furukawa Tetsushi , Sawada Kohei , Sugiura Seiryo , Hisada Toshiaki 
Published: May 2018

Background and PurposeTo date, proposed in silico models for preclinical cardiac safety testing are limited in their predictability and usability. We previously reported a multi‐scale heart simulation that accurately predicts arrhythmogenic risk for benchmark drugs.Experimental ApproachWe created a comprehensive hazard map of drug‐induced arrhythmia based on the electrocardiogram (ECG) waveforms simulated under wide range of drug effects using the multi‐scale heart simulator described here, implemented with cell models of human cardiac electrophysiology.Key ResultsA total of 9075 electrocardiograms constitute the five‐dimensional hazard map, with coordinates representing the extent of the block of each of the five ionic currents (rapid delayed rectifier potassium current (IKr), fast (INa) and late (INa,L) components of the sodium current, L‐type calcium current (ICa,L) and slow delayed rectifier current (IKs)), involved in arrhythmogenesis. Results of the evaluation of arrhythmogenic risk based on this hazard map agreed well with the risk assessments reported in the literature. ECG databases also suggested that the interval between the J‐point and the T‐wave peak is a superior index of arrhythmogenicity when compared to the QT interval due to its ability to characterize the multi‐channel effects compared with QT interval.Conclusion and ImplicationsBecause concentration‐dependent effects on electrocardiograms of any drug can be traced on this map based on in vitro current assay data, its arrhythmogenic risk can be evaluated without performing costly and potentially risky human electrophysiological assays. Hence, the map serves as a novel tool for use in pharmaceutical research and development.
New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations
Authors: Leite Débora Inácio , Fontes Fábio de Vasconcellos , Bastos Monica Macedo , Hoelz Lucas Villas Boas , Bianco Maria da Conceição Avelino Dias , de Oliveira Andressa Paula , da Silva Patricia Bernardino , da Silva Cristiane França , Batista Denise da Gama Jean , da Gama Aline Nefertiti Silva , Peres Raiza Brandão , Villar Jose Daniel Figueroa , Soeiro Maria de Nazaré Correia , Boechat Nubia 
Published: May 2018

AbstractChagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3–8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3‐triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3–8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3‐triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas’ disease.
HE4 suppresses the expression of osteopontin in mononuclear cells and compromises their cytotoxicity against ovarian cancer cells
Authors: James N E , Cantillo E , Oliver M T , Rowswell-Turner R B , Ribeiro J R , Kim K-K , Chichester C O , DiSilvestro P A , Moore R G , Singh R K , Yano N , Zhao T C 
Published: May 2018

SummaryOvarian cancers are known to evade immunosurveillance and to orchestrate a suppressive immune microenvironment. Here we examine the role of human epididymis protein 4 (HE4), an ovarian cancer biomarker, in immune evasion. Through modified subtractive hybridization analyses we have characterized the gene targets of HE4 in human peripheral blood mononuclear cells (PBMCs), and established a preliminary mechanism for HE4-mediated immune failure in ovarian tumours. Upon exposure of purified PMBCs to HE4, osteopontin (OPN) and dual-specificity phosphatase 6 (DUSP6) emerged as the most suppressed and up-regulated genes, respectively. SKOV3 and OVCAR8, human ovarian carcinoma cell lines, exhibited enhanced proliferation in conditioned media from HE4-exposed PBMCs, an effect that was attenuated by the addition of recombinant OPN or OPN-inducible cytokines [interleukin (IL)-12 and interferon (IFN)-Ɣ]. Additionally, upon co-culture with PBMCs, HE4-silenced SKOV3 cells were found to be more susceptible to cytotoxic cell death. The relationship between HE4 and OPN was reinforced further through the analysis of serous ovarian cancer patient samples. In these biopsy specimens, the number of OPN+ T cells correlated positively with progression free survival (PFS) and inversely with serum HE4 level. Taken together, these findings show that HE4 enhances ovarian cancer tumorigenesis by compromising OPN-mediated T cell activation.
Congestion and Distribution of Rents in Wheat Export Sector: A Canada–U.S. Cross‐Border Comparison
Authors: Serfas Devin , Gray Richard , Slade Peter 
Published: May 2018

AbstractIn Canada, average grain freight rates are regulated via the Maximum Revenue Entitlement (MRE), while on the US side of the border grain rates are subject to very little oversight. We use this natural experiment to explore how the MRE regulation has impacted freight rates and the distribution of rents in the wheat supply chain since 2012. On both sides of the border, when large crops have exceeded the short‐term capacity of grain export channels to move the crop, export basis has increased and reduced producer prices. In locations not subject to barge competition, US grain freight rates are higher than Canadian rates and are bid up further during periods of congestion. In Canada, MRE regulation redistributes rents away from railways toward grain companies and producers. These higher grain handling margins have increased the incentives to build additional port terminal capacity in the post‐CWB single desk environment.Au Canada, les tarifs marchandises moyens des céréales sont règlementés par le Revenu admissible maximal (RAM), tandis qu'aux États‐Unis, les tarifs céréaliers font l'objet de très peu de suivi. Au moyen de cette expérience naturelle, nous explorons l'impact du RAM sur les tarifs marchandises et sur la distribution des rentes dans la chaine d'approvisionnement du blé depuis 2012. Des deux côtés de la frontière, lorsque de vastes cultures ont excédé la capacité à court terme des voies d'exportation céréalières pour distribuer leurs récoltes, le seuil d'exportation augmente et réduit les prix des producteurs. Là où ils ne sont pas assujettis à la compétition de barges, les tarifs marchandises céréaliers américains s'avèrent plus élevés que les tarifs canadiens et se voient encore surenchéris lors de période de congestion. Au Canada, la règlementation du RAM redirige les rentes des compagnies ferroviaires aux entreprises et producteurs céréaliers. Ces marges de manutention plus élevées ont augmenté les incitatifs pour accroître la capacité des ports‐terminaux dans un environnement à pupitre unique, post Commission canadienne du blé.
When predator odour makes groups stronger: effects on behavioural and chemical adaptations in two termite species
Authors: Lucas Christophe , Brossette Lou , Lefloch Lauriane , Dupont Simon , Christidès Jean‐Philippe , Bagnères Anne‐Geneviève 
Published: May 2018

1. Being able to detect a predator before any physical contact is crucial for individual survival. Predator presence can be detected thanks to several types of signal, such as chemical cues. Chemical signals are produced by predators for their protection against desiccation, for their communication, or possibly as a side‐effect of their activity. In insects, chemical communication plays a key role in diverse biological processes, including prey‐predator or plant‐insect interactions, courtship behaviour, and kin or species recognition.2. Cuticular hydrocarbons (CHCs) are specifically involved in recognition processes and social organisation (division of labour, caste ratios) in social insects. Here, the questions raised are whether termites can detect a predator with their cuticular compounds and whether the predator‐produced compounds can influence their prey.3. The responses of termites Reticulitermes grassei (Clément, 1978) and Reticulitermes flavipes (Kollar, 1837) to the presence of the cuticular compounds produced by a predator, the ant species Lasius niger (Linnaeus, 1758), were investigated. More specifically, the study quantified termite traits such as caste ratios, mortality rates, CHC profile homogeneity and aggressiveness of workers after 2 months' exposure to predator‐produced compounds.4. The results show that the predator odour did affect the aggressiveness of the native species R. grassei but not of the invasive R. flavipes. The caste ratios and the mortality rates were not affected for both species.5. Differences between species are discussed around the native or invasive status of each species, along with the role played by chemical cues on behavioural and chemical adaptations.
Beyond the fast–slow continuum: demographic dimensions structuring a tropical tree community
Authors: Rüger Nadja , Comita Liza S. , Condit Richard , Purves Drew , Rosenbaum Benjamin , Visser Marco D. , Wright S.J , Wirth Christian 
Published: May 2018

AbstractLife‐history theory posits that trade‐offs between demographic rates constrain the range of viable life‐history strategies. For coexisting tropical tree species, the best established demographic trade‐off is the growth‐survival trade‐off. However, we know surprisingly little about co‐variation of growth and survival with measures of reproduction. We analysed demographic rates from seed to adult of 282 co‐occurring tropical tree and shrub species, including measures of reproduction and accounting for ontogeny. Besides the well‐established fast–slow continuum, we identified a second major dimension of demographic variation: a trade‐off between recruitment and seedling performance vs. growth and survival of larger individuals (≥ 1 cm dbh) corresponding to a ‘stature–recruitment’ axis. The two demographic dimensions were almost perfectly aligned with two independent trait dimensions (shade tolerance and size). Our results complement recent analyses of plant life‐history variation at the global scale and reveal that demographic trade‐offs along multiple axes act to structure local communities.
The control of risk hypothesis: reactive vs. proactive antipredator responses and stress‐mediated vs. food‐mediated costs of response
Authors: Creel Scott 
Published: May 2018

AbstractInducible defences against predators evolve because they reduce the rate of direct predation, but this benefit is offset by the cost (if any) of defence. If antipredator responses carry costs, the effect of predators on their prey is partitioned into two components, direct killing and risk effects. There is considerable uncertainty about the strength of risk effects, the factors that affect their strength, and the mechanisms that underlie them. In some cases, antipredator responses are associated with a glucocorticoid stress response, and in other cases they are associated with trade‐offs between food and safety, but there is no general theory to explain this variation. Here, I develop the control of risk (COR) hypothesis, predicting that proactive responses to predictable and controllable aspects of risk will generally have food‐mediated costs, while reactive responses to unpredictable or uncontrollable aspects of predation risk will generally have stress‐mediated costs. The hypothesis is grounded in laboratory studies of neuroendocrine stressors and field studies of food‐safety trade‐offs. Strong tests of the COR hypothesis will require more studies of responses to natural variation in predation risk and the physiological consequences of these responses, but its explanatory power can be illustrated with existing case studies.
Ecological genomics predicts climate vulnerability in an endangered southwestern songbird
Authors: Ruegg Kristen , Bay Rachael A. , Anderson Eric C. , Saracco James F. , Harrigan Ryan J. , Whitfield Mary , Paxton Eben H. , Smith Thomas B. 
Published: May 2018

AbstractFew regions have been more severely impacted by climate change in the USA than the Desert Southwest. Here, we use ecological genomics to assess the potential for adaptation to rising global temperatures in a widespread songbird, the willow flycatcher (Empidonax traillii), and find the endangered desert southwestern subspecies (E. t. extimus) most vulnerable to future climate change. Highly significant correlations between present abundance and estimates of genomic vulnerability – the mismatch between current and predicted future genotype–environment relationships – indicate small, fragmented populations of the southwestern willow flycatcher will have to adapt most to keep pace with climate change. Links between climate‐associated genotypes and genes important to thermal tolerance in birds provide a potential mechanism for adaptation to temperature extremes. Our results demonstrate that the incorporation of genotype–environment relationships into landscape‐scale models of climate vulnerability can facilitate more precise predictions of climate impacts and help guide conservation in threatened and endangered groups.
Non‐invasive brain stimulation for fine motor improvement after stroke: a meta‐analysis
Authors: O'Brien A. T. , Bertolucci F. , Torrealba‐Acosta G. , Huerta R. , Fregni F. , Thibaut A. 
Published: May 2018

AbstractThe aim of this study was to determine whether non‐invasive brain stimulation (NIBS) techniques improve fine motor performance in stroke. We searched PubMed, EMBASE, Web of Science, SciELO and OpenGrey for randomized clinical trials on NIBS for fine motor performance in stroke patients and healthy participants. We computed Hedges’ g for active and sham groups, pooled data as random‐effects models and performed sensitivity analysis on chronicity, montage, frequency of stimulation and risk of bias. Twenty‐nine studies (351 patients and 152 healthy subjects) were reviewed. Effect sizes in stroke populations for transcranial direct current stimulation and repeated transcranial magnetic stimulation were 0.31 [95% confidence interval (CI), 0.08–0.55; P = 0.010; Tau2, 0.09; I2, 34%; Q, 18.23; P = 0.110] and 0.46 (95% CI, 0.00–0.92; P = 0.05; Tau2, 0.38; I2, 67%; Q, 30.45; P = 0.007). The effect size of non‐dominant healthy hemisphere transcranial direct current stimulation on non‐dominant hand function was 1.25 (95% CI, 0.09–2.41; P = 0.04; Tau2, 1.26; I2, 93%; Q, 40.27; P < 0.001). Our results show that NIBS is associated with gains in fine motor performance in chronic stroke patients and healthy subjects. This supports the effects of NIBS on motor learning and encourages investigation to optimize their effects in clinical and research settings.
Medication‐overuse headache detoxification reduces headache disability – the Akershus study of chronic headache
Authors: Kristoffersen E. S. , Grande R. B. , Aaseth K. , Russell M. B. , Lundqvist C. 
Published: May 2018

Background and purposeMedication‐overuse headache (MOH) is a chronic headache (≥15 days/month) associated with overuse of acute headache medication. The objective was to investigate headache‐related disability before and after self‐detoxification from MOH in the general population, as well as possible predictors for successful outcome.MethodsThis was a prospective cohort study. Participants were identified in a cross‐sectional epidemiological sample of 30 000 persons aged 30–44 from the general Norwegian population. People with MOH received short information about the possible role of medication overuse in headache chronification. A total of 108 of the 128 participants (84%) were eligible for follow‐up 1.5 years later.ResultsUsing the Migraine Disability Assessment (MIDAS), people with MOH in the general population were heavily disabled (mean MIDAS score 42.1, 95% confidence interval 31.7–52.6) with a majority in the severe disability class. The MIDAS score was significantly reduced at follow‐up (P < 0.001) for those with successful self‐detoxification. In multivariate analyses, co‐occurrence of migraine (P = 0.044) and lower headache frequency at baseline (P = 0.001) increased the odds for successful self‐detoxification and reversion to episodic headache.ConclusionMedication‐overuse headache causes substantial disability in the general population. Self‐detoxification leads to reduced headache frequency and disability, although 24% of the participants did not complete self‐detoxification. Detoxification should be offered to MOH patients as early as possible with a focus on headache frequency, disability and psychological distress.
DNA replication licensing factor MCM2, geminin, and Ki67 define proliferative state and are linked with survival in oral squamous cell carcinoma
Authors: Al‐Hazmi Nadia , Alhazzazi Turki , Williams Gareth , Stoeber Kai , Al‐Dabbagh Raghad 
Published: May 2018

Oral squamous cell carcinoma (OSCC) is still an unabated global killer with little advancement in its survival rate. DNA replication licensing proteins and Aurora kinase A are biomarkers that play important roles in genomic stability. The expression profile of minichromosomal maintenance protein 2 (MCM2), Ki67, geminin, and Aurora‐A were linked to clinicopathological and outcome parameters, survival, and DNA content in 125 cases of OSCC. Oral fibroepithelial polyps (OFEP) were controls. The OSCC tumour cells were in a rapidly proliferating state, as assessed by the increased expression profile of MCM2, Ki67, geminin, and Aurora‐A and of the geminin/Ki67 ratio, and the decrease of the MCM2/Ki67 ratio, in OSCC compared with OFEP (P < 0.000). There was an association between expression of MCM2, Ki67, and geminin and tumour histologic and invasive front grade (P < 0.05). A total of 82% of the OSCC assessed had aneuploid DNA content, which was associated with increased expression intensity of Aurora‐A (P = 0.01). Geminin and the geminin/Ki67 ratio were associated with TNM staging (P < 0.05), and weak expression of MCM2, Ki67, geminin, and Aurora‐A were predictive of OSCC survival (P < 0.05). Dysregulation of the origin licensing pathway and the mitotic pathway are important events in OSCC, and the combined analysis of these proteins may contribute to improved treatment decisions.
Fatigue prediction for hoist cables over sheaves in large mining shovel application
Authors: Wokem C. , Joseph T. G. , Curley M. 
Published: May 2018

AbstractCables are used in many engineering applications, whether considered as stationary or running cables. In the latter, ropes are subjected to repeated tension and bending as they run over a sheave wheel. Such loading scenarios are seen for large mining equipment such as draglines and shovel hoist ropes. Fretting fatigue failure often occurs after several cycles of loading because of wires rubbing against each other and external wires rubbing against sheave wheels. It is also pertinent to understand the behaviour of cables subjected to bending over sheaves, to be able to predict fretting fatigue life, so as to set preventive maintenance activities to avoid catastrophic failure in such systems. In this paper, the behaviour of 2 specific configuration strands, composing either 7 or 19 wires, bent over a sheave is investigated numerically. To aid preventive maintenance inspection, critical locations of stress concentrations are identified as a function of applied load or tensile stress. The investigation also considers the impact of groove size, diameter of sheave to diameter of cable ratio, and contact length, enabling the application to infer fatigue life.
Influence of land use on the trophic niche overlap of dung beetles in the semideciduous Atlantic forest of Argentina
Authors: Giménez Gómez Victoria C. , Verdú José R. , Gómez‐Cifuentes Andrés , Vaz‐de‐Mello Fernando Z. , Zurita Gustavo A. 
Published: May 2018

AbstractThe degradation and replacement of natural ecosystems affect species abundance, diversity and interspecific interaction through the modification of resource availability and environmental conditions. Land uses preserving the forest canopy show higher species richness and similarity to the native forest.In this study, we explored changes in the trophic niche overlap of dung beetles between the native forest and different land uses in the semideciduous Atlantic forest, under the hypothesis that trophic niche overlap increases with species richness.We sampled dung beetles in protected native forests and four land uses (pine plantations, agroforestry parklands, silvo‐pastoral systems and open pastures), using seven potential food sources (monkey, feline, tapir and deer dung, decomposing fruit, decomposing fungi and carrion). The species richness of each habitat, the trophic niche overlap and the relation between both measures were analysed. Also, we explored species trophic preferences in each habitat to explain and discuss the results obtained in trophic niche overlap measures.As expected, our results showed a positive relation between species richness and trophic niche overlap. Moreover, the addition of different resources in open habitats did not increase species richness, suggesting that resource availability may not be the main mechanism explaining the empoverished dung beetle community observed in open habitats. Other mechanisms, such as physiological restrictions, may play a role in limiting the use of these habitats. Studies on the mechanisms leading to the patterns of species abundance and diversity observed in land uses are necessary to propose management recommendations that increase the sustainability of open habitats.
Tepid massage for febrile children: A systematic review and meta‐analysis
Authors: Lim Junghee , Kim Juyoung , Moon Bora , Kim Gaeun 
Published: May 2018

AbstractAimThis study aimed to examine the effect of tepid massage in febrile children comparing with other fever management.MethodsExperimental studies published in English were included; quasi‐experimental research studies were also included in consideration of rare experimental studies in Korean. The search strategy sought to identify published research reports in the English language and covered all major databases up to 2016. The methodological quality of each study was assessed by 2 independent reviewers using a Scottish Intercollegiate Guidelines Network's Methodology Checklist. Means and standard deviations were used for continuous variables, and standardized mean difference was used for variables of different scales. Heterogeneity was assessed using the I2 statistics after visual reviewing with forest plots.ResultsThis study reviewed mainly the effect of tepid massage on temperature compared with the use of antipyretics, along with other adverse effects in relation with fever management. The results revealed no significant effect of tepid massage on temperature in febrile children. In addition, incidence rates of adverse effects including chills, goose pimples, and discomfort were higher in tepid massage groups.ConclusionThis meta‐analysis showed the need for re‐verification of commonly used practice including the use of tepid massage and proper body temperature measurement.