bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germ cell tumour subtypes display differential expression of microRNA371a-3p
Authors: Vilela-Salgueiro Bárbara , Barros-Silva Daniela , Lobo João , Costa Ana Laura , Guimarães Rita , Cantante Mariana , Lopes Paula , Braga Isaac , Oliveira Jorge , Henrique Rui , Jerónimo Carmen 
Published: April 2018

Testicular germ cell tumours (TGCTs) are a heterogeneous group of neoplasms, mostly affecting young men. Curability rates are high and adequate treatment relies on careful and accurate pathological and clinical assessment. Indeed, TGCTs' histopathological subtyping is critical for adequate therapeutic decision. Considering the limitation of currently available serum biomarkers, novel candidates have been proposed, most notably miR-371a-3p, which outperformed classical serum markers, but no detailed information concerning TGCT subtype was available. Thus, we carried out evaluation of miR-371a-3p expression levels among TGCT subtypes using a consecutive cohort of tissue samples. MiR-371a-3p discriminated TGCTs from control tissues with high sensitivity and specificity (AUC = 0.99). Furthermore, seminomas displayed higher miR-371a-3p expression levels compared to non-seminomatous TGCTs, which also showed significant differences among them. Nonetheless, prepubertal TGCTs depicted lower miR-371a-3p expression levels than postpubertal TGCTs. Globally, miR-371a-3p expression levels decreased in parallel with progressive cell differentiation. We concluded that miR-371a-3p is TGCTs-specific and it might be clinically useful for early detection and disease monitoring.
This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
Genetic patterning in Central Eurasia: population history and pigmentation
Authors: Røyrvik Ellen C. , Yuldasheva Nadira , Tonks Susan , Winney Bruce , Ruzibakiev Ruslan , Wells R. Spencer , Bodmer Walter F. 
Published: April 2018

AbstractCentral-western Asia has often been underrepresented in population genetic studies, but it is important for the clarification of the peopling of Eurasia and the relationship between its western and eastern extremities. We genotyped individuals from over 40 population groups, mostly central Eurasian, for mitochondrial HVR1,CCR5del32and five functionalMC1Rvariants (p.Val60Leu, p.Val92Met, p.Arg151Cys, p.Arg160Trp, p.Arg163Gln), and collected published genotype data for comparison. Mitochondrial profiles confirm both the higher heterozygosity in Central Asia than in surrounding areas, and the broadly northern European distribution ofCCR5del32. TheMC1Rvariants profile alone is a good determinant of the longitudinal position of a population group, and combined FSTvalues divide Eurasia into seven broad geographic divisions. We can conclude that Central Asia shares genetic features with both eastern and western Eurasia, compatible with both a scenario where the former acted as a source for the latter two’s genetic diversity, or one where Central Asia is a ‘hybrid zone’ where eastern and western peoples met. Furthermore, the overall high FSTvalues for functionalMC1Rvariants combined with presumed selection pressures on skin pigmentation in low-UV areas lead us to conclude that different variants were selected for in east and west Eurasia, an example of convergent evolution.
Diversity of feature selectivity in macaque visual cortex arising from limited number of broadly-tuned input channels
Authors: Mohan Yamni S. , Jayakumar Jaikishan , Lloyd Errol K.J. , Levichkina Ekaterina , Vidyasagar Trichur R. 
Published: April 2018

AbstractSpikes (action potential) responses of most primary visual cortical cells in the macaque are sharply tuned for the orientation of a line or an edge and neurons preferring similar orientations are clustered together in cortical columns. The preferred stimulus orientation of these columns span the full range of orientations, as observed in recordings of spikes, which represent the outputs of cortical neurons. However, when we imaged also the thalamic input to these cells that occur on a larger spatial scale, we found that the orientation domain map of the primary visual cortex did not show the diversity of orientations exhibited by signals representing outputs of the cells. This map was dominated by just the one orientation that is most commonly represented in subcortical responses. This supports cortical feature selectivity and columnar architecture being built upon feed-forward signals transmitted from the thalamus in a very limited number of broadly-tuned input channels.
Population genomic and evolutionary modelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode, Haemonchus contortus
Authors: Doyle Stephen R. , Illingworth Christopher J. R. , Laing Roz , Bartley David J. , Redman Elizabeth , Martinelli Axel , Holroyd Nancy , Morrison Alison A. , Rezansoff Andrew , Tracey Alan , Devaney Eileen , Berriman Matthew , Sargison Neil , Cotton James A. , Gilleard John S. 
Published: April 2018

AbstractBackgroundInfections with helminths cause an enormous disease burden in billions of animals and plants worldwide. Large scale use of anthelmintics has driven the evolution of resistance in a number of species that infect livestock and companion animals, and there are growing concerns regarding the reduced efficacy in some human-infective helminths. Understanding the mechanisms by which resistance evolves is the focus of increasing interest; robust genetic analysis of helminths is challenging, and although many candidate genes have been proposed, the genetic basis of resistance remains poorly resolved.ResultsHere, we present a genome-wide analysis of two genetic crosses between ivermectin resistant and sensitive isolates of the parasitic nematode Haemonchus contortus, an economically important gastrointestinal parasite of small ruminants and a model for anthelmintic research. Whole genome sequencing of parental populations, and key stages throughout the crosses, identified extensive genomic diversity that differentiates populations, but after backcrossing and selection, a single genomic quantitative trait locus (QTL) localised on chromosome V was revealed to be associated with ivermectin resistance. This QTL was common between the two geographically and genetically divergent resistant populations and did not include any leading candidate genes, suggestive of a previously uncharacterised mechanism and/or driver of resistance. Despite limited resolution due to low recombination in this region, population genetic analyses and novel evolutionary models supported strong selection at this Q.TL, driven by at least partial dominance of the resistant allele, and that large resistance-associated haplotype blocks were enriched in response to selection.ConclusionsWe have described the genetic architecture and mode of ivermectin selection, revealing a major genomic locus associated with ivermectin resistance, the most conclusive evidence to date in any parasitic nematode. This study highlights a novel genome-wide approach to the analysis of a genetic cross in non-model organisms with extreme genetic diversity, and the importance of a high quality reference genome in interpreting the signals of selection so identified.
q2-sample-classifier: machine-learning tools for microbiome classification and regression
Authors: Bokulich Nicholas A. , Dillon Matthew , Bolyen Evan , Kaehler Benjamin D. , Huttley Gavin A. , Caporaso J. Gregory 
Published: April 2018

AbstractMicrobiome studies often aim to predict outcomes or differentiate samples based on their microbial compositions, tasks that can be efficiently performed by supervised learning methods. Here we present a benchmark comparison of supervised learning classifiers and regressors implemented in scikit-learn, a Python-based machine-learning library. We additionally present q2-sample-classifier, a plugin for the QIIME 2 microbiome bioinformatics framework, that facilitates application of the scikit-learn classifiers to microbiome data.Random forest, extra trees, andgradient boostingmodels demonstrate the highest performance for both supervised classification and regression of microbiome data. Automated feature selection and hyperparameter tuning enhance performance of most methods but may not be necessary under all circumstances. The q2-sample-classifier plugin makes these methods more accessible and interpretable to a broad audience of microbiologists, clinicians, and others who wish to utilize supervised learning methods for predicting sample characteristics based on microbiome composition. The q2-sample-classifier source code is available athttps://github.com/qiime2/q2-sample-classifier. It is released under a BSD-3-Clause license, and is freely available including for commercial use.
Identification and Quantification of Paclitaxel and its Metabolites in Human Meconium from Newborns with Gestational Chemotherapeutic Exposure
Authors: Cardonick Elyce , Broadrup Robert , Xu Peining , Doan Mary T. , Jiang Helen , Snyder Nathaniel W. 
Published: April 2018

AbstractObjectiveCancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.Study DesignMeconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.ResultsMean levels of paclitaxel were 399.9 pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3’-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel mean levels were 105.2 and 113.4 pg/mg meconium, respectively.ConclusionIntact paclitaxel, and at least two of its major metabolites were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an efficient approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.
Hif-1alpha induced expression of Il-1beta protects against mycobacterial infection in zebrafish
Authors: Ogryzko Nikolay V. , Lewis Amy , Wilson Heather L. , Meijer Annemarie H. , Renshaw Stephen A. , Elks Philip M. 
Published: April 2018

AbstractDrug resistant mycobacteria are a rising problem worldwide. There is an urgent need to understand the immune response to TB to identify host targets that, if targeted therapeutically, could be used to tackle these currently untreatable infections. Here, we use an Il-1β fluorescent transgenic line to show that there is an early innate immune pro-inflammatory response to well-established zebrafish models of inflammation andMycobacterium marinum(Mm) infection. We demonstrate that host-derived hypoxia signalling, mediated by the Hif-1α transcription factor, can prime macrophages with increased levels of Il-1β in the absence of infection, upregulating neutrophil antimicrobial nitric oxide production, leading to greater protection against infection. Our data link Hif-1α to proinflammatory macrophage Il-1β transcriptionin vivoduring early mycobacterial infection and importantly highlight a host protective mechanism, via antimicrobial nitric oxide, that decreases disease outcomes and that could be targeted therapeutically to stimulate the innate immune response to better deal with infections.
Intrinsic Excitability Increase in Cerebellar Purkinje Cells Following Delay Eyeblink Conditioning in Mice
Authors: Titley Heather K. , Watkins Gabrielle V. , Lin Carmen , Weiss Craig , McCarthy Michael , Disterhoft John F. , Hansel Christian 
Published: April 2018

AbstractCerebellar learning is canonically thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the down-regulation of calcium-dependent SK-type K channels, which is associated with an increase in neuronal excitability. In the hippocampus, SK-mediated intrinsic plasticity has been shown to play a role in trace eyeblink conditioning; however, it is not yet known how intrinsic plasticity contributes to a cerebellar learning task such as delay eyeblink conditioning. Whole cell recordings were obtained from acute cerebellar slices from mice ~48 hours after learning a delay eyeblink conditioning task. Over a period of repeated training sessions mice received either distinctly paired trials of a tone co-terminating with a periorbital shock (conditioned mice) or trials in which these stimuli were presented in an unpaired manner (pseudoconditioned mice). Conditioned mice show a significantly reduced afterhyperpolarization (AHP) following trains of parallel fiber stimuli. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eyeblink conditioning and point toward a downregulation of SK channels as a potential underlying mechanism.
Joint Modeling of Reaction Times and Choice Improves Parameter Identifiability in Reinforcement Learning Models
Authors: Ballard Ian C. , McClure Samuel M. 
Published: April 2018

AbstractBackgroundReinforcement learning models provide excellent descriptions of learning in multiple species across a variety of tasks. Many researchers are interested in relating parameters of reinforcement learning models to neural measures, psychological variables or experimental manipulations. We demonstrate that parameter identification is difficult because a range of parameter values provide approximately equal quality fits to data. This identification problem has a large impact on power: we show that a researcher who wants to detect a medium sized correlation (r= .3) with 80% power between a variable and learning rate must collect 60% more subjects than specified by a typical power analysis in order to account for the noise introduced by model fitting.New MethodWe derive a Bayesian optimal model fitting technique that takes advantage of information contained in choices and reaction times to constrain parameter estimates.ResultsWe show using simulation and empirical data that this method substantially improves the ability to recover learning rates.Comparison with Existing MethodsWe compare this method against the use of Bayesian priors. We show in simulations that the combined use of Bayesian priors and reaction times confers the highest parameter identifiability. However, in real data where the priors may have been misspecified, the use of Bayesian priors interferes with the ability of reaction time data to improve parameter identifiability.ConclusionsWe present a simple technique that takes advantage of readily available data to substantially improve the quality of inferences that can be drawn from parameters of reinforcement learning models.Highlights–Parameters of reinforcement learning models are particularly difficult to estimate–Incorporating reaction times into model fitting improves parameter identifiability–Bayesian weighting of choice and reaction times improves the power of analyses assessing learning rate
Neural network model reference decoupling control for single leg joint of hydraulic quadruped robot
Authors: Gao Bingwei , Han Wenlong 
Published: April 2018

Purpose
To control one of the joints during the actual movement of the hydraulically driven quadruped robot, all the other joints in the leg need to be locked. Once the joints are unlocked, there is a coupling effect among the joints. Therefore, during the normal exercise of the robot, the movement of each joint is affected by the coupling of other joints. This brings great difficulties to the coordinated motion control of the multi-joints of the robot. Therefore, it is necessary to reduce the influence of the coupling of the hydraulically driven quadruped robot.

Design/methodology/approach
To solve the coupling problem with the joints of the hydraulic quadruped robot, based on the principle of mechanism dynamics and hydraulic control, the dynamic mathematical model of the single leg mechanism of the hydraulic quadruped robot is established. On this basis, the coupling dynamics model of the two joints of the thigh and the calf is derived. On the basis of the multivariable decoupling theory, a neural network (NN) model reference decoupling controller is designed.

Findings
The simulation and prototype experiment are carried out between the thigh joint and the calf joint of the hydraulic quadruped robot, and the results show that the proposed NN model reference decoupling control method is effective, and this method can reduce the cross-coupling between the thigh and the calf and improve the dynamic characteristics of the single joint of the leg.

Practical implications
The proposed method provides technical support for the mechanical–hydraulic cross-coupling among the joints of the hydraulic quadruped robot, achieving coordinated movement of multiple joints of the robot and promoting the performance and automation level of the hydraulic quadruped robot.

Originality/value
On the basis of the theory of multivariable decoupling, a new decoupling control method is proposed, in which the mechanical–hydraulic coupling is taken as the coupling behavior of the hydraulic foot robot. The method reduces the influence of coupling of system, improves the control precision, realizes the coordinated movement among multiple joints and promotes the popularization and use of the hydraulically driven quadruped robot.
Challenges in working with patients with dual diagnosis
Authors: Pinderup Pernille 
Published: April 2018

Purpose
Studies have shown that mental health professionals find working with patients with dual diagnosis challenging, and the purpose of this paper is to examine some of these challenges.

Design/methodology/approach
In total, 85 mental health professionals from 8 different mental health centres in Denmark were interviewed. The data analysis was inspired by a grounded theory approach.

Findings
Different challenges in the dual diagnosis treatment were identified and they suggested that the focus of treatment was mainly on the mental illness rather than the substance use disorder. The single focus of the treatment made it challenging to treat patients with dual diagnosis sufficiently. While several studies explain the single focus by inadequate competencies among professionals, the present study suggests that the single focus is also explained by the way that the treatment is organised. For instance, standardized treatment packages and insufficient guidelines on substance abuse treatment make it challenging to treat patients with dual diagnosis.

Originality/value
This paper suggests that a more flexible, and a longer period of, treatment, together with more sufficient guidelines on dual diagnosis treatment and a more formalized collaboration with the substance abuse treatment centres, will make it a less challenging issue to treat patients with dual diagnosis.
Chaos in a second-order non-autonomous Wien-bridge oscillator without extra nonlinearity
Authors: Xu Quan , Zhang Qinling , Jiang Tao , Bao Bocheng , Chen Mo 
Published: April 2018

Purpose
The purpose of this paper is to develop a simple chaotic circuit. The circuit can be fabricated by less discrete electronic components, within which complex dynamical behaviors can be generated.

Design/methodology/approach
A second-order non-autonomous inductor-free chaotic circuit is presented, which is obtained by introducing a sinusoidal voltage stimulus into the classical Wien-bridge oscillator. The proposed circuit only has two dynamic elements, and its nonlinearity is realized by the saturation characteristic of the operational amplifier in the classical Wien-bridge oscillator. After that, its dynamical behaviors are revealed by means of bifurcation diagram, Lyapunov exponent and phase portrait and further confirmed using the 0-1 test method. Moreover, an analog circuit using less discrete electronic components is implemented, and its experimental results are measured to verify the numerical simulations.

Findings
The equilibrium point located in a line segment varies with time evolution, which leads to the occurrence of periodic, quasi-periodic and chaotic behaviors in the proposed circuit.

Originality/value
Unlike the previously published works, the significant values of the proposed circuit with simple topology are inductor-free realization and without extra nonlinearity, which make the circuit can be used as a paradigm for academic teaching and experimental illustraction for chaos.
Developing new capability: middle managers’ role in corporate entrepreneurship
Authors: Wu Yuanyuan , Ma Zhenzhong , Wang Milo Shaoqing 
Published: April 2018

PurposeThe purpose of this paper is to explore the role of middle managers in the corporate entrepreneurship process that drives new capability development. Middle managers are highlighted as key entrepreneurial agents because of their special position in an organization.Design/methodology/approachThe paper draws on existing capability development and corporate entrepreneurship literature and develops a conceptual model and research propositions that are illustrated through three examples from a Chinese private firm.FindingsThis paper contends the dual role of middle managers, both as change implementers to follow pre-set rules of an existing corporate entrepreneurship system and as change initiators to bring new rules to improve the existing system.Research limitations/implicationsThe paper is conceptual in nature, advancing the understanding of middle managers’ role in corporate entrepreneurship. The paper provides directions for future empirical research.Practical implicationsThe interactions between middle managers and other organizational agents are discussed in the propositions. This paper suggests the importance of empowering middle managers to facilitate changes in complex internal environments.Originality/valueThe paper provides a unique theoretical contribution by introducing the interface-based, multi-level conceptual model of corporate entrepreneurship toward new capability development.