bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-invasive detection of bladder cancer through the analysis of driver gene mutations and aneuploidy
Authors: Springer Simeon , Rodriguez Pena Maria Del Carmen , Li Lu , Douville Christopher , Wang Yuxuan , Cohen Josh , Taheri Diana , Afsari Bahman , Silliman Natalie , Schaeffer Joy , Ptak Janine , Dobbyn Lisa , Papoli Maria , Kinde Isaac , Afsari Bahman , Tregnago Aline C. , Bezerra Stephania M. , VandenBussche Christopher , Fujita Kazutoshi , Ertoy Dilek , Cunha Isabela W. , Yu Lijia , Schoenberg Mark , Bivalacqua Trinity J. , Dickman Kathleen G. , Grollman Arthur P. , Diaz Luis A. , Karchin Rachel , Hruban Ralph , Tomasetti Cristian , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Netto George J. 
Published: October 2017

AbstractCurrent non-invasive approaches for bladder cancer (BC) detection are suboptimal. We report the development of non-invasive molecular test for BC using DNA recovered from cells shed into urine. This “UroSEEK” test incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. We first evaluated 570 urine samples from patients at risk for BC (microscopic hematuria or dysuria). UroSEEK was positive in 83% of patients that developed BC, but in only 7% of patients who did not develop BC. Combined with cytology, 95% of patients that developed BC were positive. We then evaluated 322 urine samples from patients soon after their BCs had been surgically resected. UroSEEK detected abnormalities in 66% of the urine samples from these patients, sometimes up to 4 years prior to clinical evidence of residual neoplasia, while cytology was positive in only 25% of such urine samples. The advantages of UroSEEK over cytology were particularly evident in low-grade tumors, wherein cytology detected none while UroSEEK detected 67% of 49 cases. These results establish the foundation for a new, non-invasive approach to the detection of BC in patients at risk for initial or recurrent disease.
Combining CRISPR/Cas9 mutagenesis and a small-molecule inhibitor to probe the function of MELK in cancer
Authors: Giuliano Christopher J. , Lin Ann , Smith Joan C. , Palladino Ann C. , Sheltzer Jason M. 
Published: October 2017

AbstractThe Maternal Embryonic Leucine Zipper Kinase (MELK) has been identified as a promising therapeutic target in multiple cancer types. MELK over-expression is associated with aggressive disease, and MELK has been implicated in numerous cancer-related processes, including chemotherapy resistance, stem cell renewal, and tumor growth. On the basis of these findings, a MELK inhibitor is currently being tested in several clinical trials. Here, we report that cancer cell lines harboring CRISPR/Cas9-induced null mutations in MELK exhibit wild-type growthin vitro, under environmental stress, in the presence of multiple chemotherapy agents, andin vivo. By combining our MELK-knockout clones with a recently-described, highly-specific MELK inhibitor, we further demonstrate that the acute inhibition of MELK results in no specific anti-proliferative phenotype. Analysis of gene expression data from cohorts of cancer patients identifies MELK expression as a correlate of tumor mitotic activity, explaining its association with poor clinical prognosis. In total, our results demonstrate the power of CRISPR/Cas9-based genetic approaches to investigate cancer drug targets, and call into question the rationale for treating patients with anti-MELK monotherapies.
The Phonetics-Phonology Relationship in the Neurobiology of Language
Authors: Grimaldi Mirko 
Published: October 2017

AbstractIn this work, I address the connection of phonetic structure with phonological representations. This classical issue is discussed in the light of recent neurophysiological data which – thanks to direct measurements of temporal and spatial brain activation – provide new avenues to investigate the biological substrate of human language. After describing principal techniques and methods, I critically discuss magnetoencephalographic and electroencephalographic findings of speech processing based on event-related potentials and event-related oscillatory rhythms. The available data do not permit us to clearly disambiguate between neural evidence suggesting pure acoustic patterns and those indicating abstract phonological features. Starting from this evidence, which only at the surface represents a limit, I develop a preliminary proposal where discretization and phonological abstraction are the result of a continuous process that converts spectro-temporal (acoustic) states into neurophysiological states such that some properties of the former undergo changes interacting with the latter until a new equilibrium is reached. I assume that – at the end of the process – phonological segments (and the related categorical processes) take the form of continuous neural states represented by nested cortical oscillatory rhythms spatially distributed in the auditory cortex. Within this perspective, distinctive features (i.e., the relevant representational linguistic primitives) are represented by both spatially local and distributed neural selectivity. I suggest that this hypothesis is suitable to explain hierarchical layout of auditory cortex highly specialized in analyzing different aspects of the speech signal and to explain learning and memory processes during the acquisition of phonological systems.
Cellular reprogramming of human monocytes is regulated by time-dependent IL4 signalling and NCOR2
Authors: Sander Jil , Schmidt Susanne V. , Cirovic Branko , McGovern Naomi , Papantonopoulou Olympia , Hardt Anna-Lena , Aschenbrenner Anna C. , Kreer Christoph , Quast Kreer , Xu Alexander M. , Schmidleithner Lisa M. , Theis Heidi , Lan Do Thi Huong , Bin Sumatoh Hermi Rizal , Lauterbach Mario A. R. , Schulte-Schrepping Jonas , Gunther Patrick , Xue Jia , Baßler Kevin , Ulas Thomas , Klee Kathrin , Herresthal Stefanie , Krebs Wolfgang , Martin Bianca , Latz Eicke , Händler Kristian , Kraut Michael , Kolanus Waldemar , Beyer Marc , Falk Christine S. , Wiegmann Bettina , Burgdorf Sven , Melosh Nicholas A. , Newell Evan W. , Ginhoux Florent , Schlitzer Andreas , Schultze Joachim L. 
Published: October 2017

AbstractThe clinical and therapeutic value of humanin vitrogenerated monocyte-derived dendritic cell (moDC) and macrophages is well established. However, in line with recent findings regarding myeloid cell ontogeny and due to our limited understanding of their physiological counterparts, transcriptional regulation and heterogeneity, the full potential of these important cellular systems is still underestimated.In this study, we use cutting edge high-dimensional analysis methods to better understand the transcriptional organization, phenotypic heterogeneity and functional differences between humanex vivoisolated andin vitrogenerated mononuclear phagocytes with the aim to better realize their full potential in the clinic.We demonstrate that human monocytes activated by MCSF or GMCSF most closely resemble inflammatory macrophages identifiedin vivo, while IL4 signalling in the presence of GMCSF generates moDCs resembling inflammatory DCsin vivo, but not steady state cDC1 or cDC2. Moreover, these reprogramming regimes lead to activated monocytes that present with profoundly different transcriptomic, metabolic, phenotypic and functional profiles. Furthermore, we demonstrate that CD14+monocytes are integrating multiple exogenous activation signals such as GMCSF and IL4 in a combinatorial and temporal fashion, resulting in a high-dimensional cellular continuum of reprogrammed monocytes dependent on the mode and timing of cytokine exposure. Utilizing nanostraw-based knockdown technology, we demonstrate that the IL4-dependent generation of moDCs relies on the induction, nuclear localization and function of the transcriptional regulator NCOR2.Finally, we unravel unappreciated heterogeneity within the clinically moDCs population and propose a novel high-dimensional phenotyping strategy to better tailor clinical quality control strategies for patient need and culture conditions to enhance therapeutic outcome.
Rats optimally accumulate and discount evidence in a dynamic environment
Authors: Piet Alex T. , El Hady Ahmed , Brody Carlos D. 
Published: October 2017

AbstractHow choices are made within noisy environments is a central question in the neuroscience of decision making. Previous work has characterized temporal accumulation of evidence for decision-making in static environments. However, real-world decision-making involves environments with statistics that change over time. This requires discounting old evidence that may no longer inform the current state of the world. Here we designed a rat behavioral task with a dynamic environment, to probe whether rodents can optimally discount evidence by adapting the timescale over which they accumulate it. Extending existing results about optimal inference in a dynamic environment, we show that the optimal timescale for evidence discounting depends on both the stimulus statistics and noise in sensory processing. We found that when both of these components were taken into account, rats accumulated and temporally discounted evidence almost optimally. Furthermore, we found that by changing the dynamics of the environment, experimenters could control the rats’ accumulation timescale, switching them from accumulating over short timescales to accumulating over long timescales and back. The theoretical framework also makes quantitative predictions regarding the timing of changes of mind in the dynamic environment. This study establishes a quantitative behavioral framework to control and investigate neural mechanisms underlying the adaptive nature of evidence accumulation timescales and changes of mind.
DirtyGenes: significance testing for gene or bacterial population composition changes using the Dirichlet distribution
Authors: Shaw Laurence M , Blanchard Adam , Chen Qinglin , An Xinli , Tötemeyer Sabine , Zhu Yong-Guan , Stekel Dov J 
Published: October 2017

AbstractHigh throughput sequencing, and quantitative polymerase chain reaction (qPCR), can detect changes in bacterial communities or the genes that they carry, between different environments or treatments. These methods are applied widely to microbiomes in humans, animals, soil and water; an important application is for changes in antimicrobial resistance genes (ARGs). However, at present, there is no statistical method to determine whether observed changes in the overall composition are significant, or result from random variations between samples. Therefore researchers are limited to graphical descriptions. We describe a novel statistical method to determine whether or not observed differences in bacterial populations or their genes are significant. It can be used with data from shotgun metagenomics, 16S characterisation or qPCR. It can also be used for experimental design, to calculate the number of samples needed in future experiments. We show its application to two example data sets. The first is published data on bacterial communities and ARGs in the environment, in which we show that there are significant changes in both ARG and community composition. The second is a new data set on seasonality in bacterial communities and ARGs in hooves from four sheep. While the observed differences are not significant, we show that a minimum group size of eight sheep in a future experiment would provide sufficient power to observe significant changes, should the already observed changes be true. This method has broad uses for statistical testing and experimental design in experiments on changing microbiomes, including for studies on antimicrobial resistance.
South African health decentralisation: requiring contextually intelligent leaders
Authors: Meyer Ellenore , Thomas Leena , Smith Selma , Scheepers Caren 
Published: October 2017

Subject area
Public Health; Leadership; Organisational Development; Organisational Behaviour; Public Administration Management.

Study level/applicability
Postgraduate level for honours or masters programmes in courses on public health; executive leadership and management programmes; MBA level.

Case overview
The case unpacks decentralisation as a means to promote and improve local decision-making and accountability through community participation and engagements. Ayanda Nkele was a programme manager in a health district in South Africa. He was faced with many challenges when trying to implement his programme, most of which were related to local authority, responsibilities and decision-making abilities at his level. This case describes briefly the South African health system. and how it functions. It describes the proposed changes to the health system and its transformation towards Universal Health Coverage. The decision space analysis as discussed in the case illustrates the types of decentralisation in the country and how this also applies to Nkele’s level.

Expected learning outcomes
Understanding the concepts and principles of decentralisation within the context of strengthening district health services, the re-engineering of primary health care (PHC) and rolling out a National Health Insurance in South Africa. Applying the “decision space” approach to analyse the extent of decentralisation. Grasping the requirement of leaders to be “contextually intelligent” and identify the important contextual variables to take into account when analysing public health care.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 7: Management Science.
Resource extractivism, health and climate change in small islands
Authors: Bambrick Hilary 
Published: October 2017

Purpose
The extraction of natural resources has long been part of economic development in small islands. The damage to environment and health is extensive, even rendering once productive islands virtually uninhabitable. Rather than providing long-term benefits to the population or to the environment, the culture of “extractivism” – a nonreciprocal approach where resources are removed and used with little care or regard to consequences – has instead left many in far more fragile circumstances, increasingly dependent on external income. The purpose of this paper is to show how continued extractivism in small islands is contributing to global climate change and increasing climate risks to the local communities.

Design/methodology/approach
Through a series of case studies, this paper examines the history of extractivism in small islands in Oceania, its contribution to environmental degradation locally and its impacts on health.

Findings
It examines how extractivism continues today, with local impacts on environment, health and wellbeing and its much more far-reaching consequences for global climate change and human health. At the same time, these island countries have heightened sensitivity to climate change due to their isolation, poverty and already variable climate, whereas the damage to natural resources, the disruption, economic dependence and adverse health impacts caused by extractivism impart reduced resilience to the new climate hazards in those communities.

Practical implications
This paper proposes alternatives to resource extractivism with options for climate compatible development in small islands that are health-promoting and build community resilience in the face of increasing threats from climate change.

Originality/value
Extractivism is a new concept that has not previously been applied to understanding health implications of resource exploitation thorough the conduit of climate change. Small-island countries are simultaneously exposed to widespread extractivism, including of materials contributing to global climate change, and are among the most vulnerable to the hazards that climate change brings.
Mainstreaming climate change into the EIA procedures: a perspective from China
Authors: Gao Qi 
Published: October 2017

Purpose
In the face of climate change, environmental impact assessment (EIA) and strategic environmental assessment (SEA) are expected to translate global or national mitigation and adaptation targets to project and plan levels of decision-making. This paper aims to examine how to transform China’s EIA procedures to accommodate consideration of climate change and what constraints might be for doing so.

Design/methodology/approach
The main methodology used in this paper is doctrinal research, which is the primary legal methodology to find the law and interpret and analyse the document. Theoretical research is applied to analyse the ideas and assumptions of the mainstreaming approach. Comparative research is done to consider relevant international experiences.

Findings
Despite well-founded rationale for the mainstreaming approach, entrenched institutional, legal and technical obstacles cannot be neglected in the context of China. Urgent needs to fix existing EIA/SEA loopholes and improve the general enabling environment are also highlighted as a fundamental aspect of mainstreaming.

Originality/value
The potential of mainstreaming climate change into China’s EIA procedures remains largely unexplored. As a ground-breaking work from China’s perspective, the findings of this paper can serve as an important foundation for future research from legal and other perspectives.
Towards understanding the effects of time and emotions on the vacation experience
Authors: Torres Edwin N. , Wei Wei , Hua Nan 
Published: October 2017

PurposeThe purpose of this paper is to uncover how emotions change (or remain constant) throughout the course of the vacation experience. Although the importance of affective experiences has been recognized in the literature, the momentary effects of each stage of the vacation on the overall appraisal of the experience deserve more attention.Design/methodology/approachA survey instrument was developed using the PANAS scale. Customers were asked for their emotions at different points of their vacation. Data were analysed using multinomial logistic regression, correlations and path analysis.FindingsThe results indicate that it is possible for guests to experience different affective states at different parts of the vacation experience. Furthermore, it is also likely for each service experience to impact the next service, in spite of the apparent distinction between them. Finally, the researchers noted the tendency of consumers to recall mostly positive emotions, thus raising the possibility of various kinds of memory biases in recalling a vacation experience.Originality/valueEmotions are by their very nature momentary. Consequently, these affective states can change over time, especially over a vacation spanning several days. Therefore, the present research contributes to the literature, in that it measures emotions at various points in time, determines the impact of emotions towards one service provider on the next and ascertains the impact of said emotions on the overall vacation experience.
Herbaceous competition and browsing may induce arrested succession in central European forests
Authors: Thrippleton Timothy , Bugmann Harald , Snell Rebecca S. 
Published: October 2017

AbstractArrested succession, that is, an ecosystem permanently halted in an early successional, typically non‐forested state, has been suggested to result from intense competition by understorey vegetation, high browsing pressure and additional disturbances, but the relative importance of these factors is unclear. In addition, distinguishing between permanently arrested succession or merely delayed succession may be highly challenging, if not impossible, due to the large time‐scales involved.We used the dynamic vegetation model LandClim to systematically explore the effect of multiple factors on delayed and arrested succession over a time span of 1,000 years, starting from an unforested state. We included abiotic and biotic factors as well as large‐scale overstorey disturbance, in four Central European landscapes.Arrested succession occurred in 1%–14% of the simulations. Among the non‐arrested simulations, 95% reached a forested state (defined as ≥10% canopy cover) within 100 years. Large herbaceous biomass was the most important predictor for arrested succession, followed by browsing and large‐scale disturbances. Combinations of factors were important at particular locations in the landscape, where understorey competition and browsing jointly induced a strong establishment filter. Abiotic conditions consistently influenced the probability of arrested succession, with a low probability under mesic conditions and increased likelihood in more xeric parts of the landscapes.Synthesis. We demonstrated that permanently arrested succession has the potential to occur in temperate forests, particularly under a combination of high amounts of herbaceous biomass and ungulate browsing in drought‐constrained landscape positions. We thus conclude that considering environmental heterogeneity at the landscape scale is key for understanding the conditions that lead to delayed and arrested succession.
Effect of androgen deprivation therapy on the contractile properties of type I and type II skeletal muscle fibres in men with non‐metastatic prostate cancer
Authors: Lamboley Cedric R , Xu Hongyang , Dutka Travis L , Hanson Erik D , Hayes Alan , Violet John A , Murphy Robyn M , Lamb Graham D 
Published: October 2017

SummaryThe contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age‐ and activity‐matched healthy male subjects (Control). Mechanically‐skinned muscle fibres were exposed to a sequence of heavily Ca2+‐buffered solutions at progressively higher free [Ca2+] to determine their force‐Ca2+ relationship. Ca2+‐sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by −0.05 and −0.04 pCa units, respectively, P < .02), and specific force was around 13% lower in type I fibres of ADT subjects than in Controls (P = .02), whereas there was no significant difference in type II fibres. Treatment with the reducing agent dithiothreitol slightly increased specific force in type I and type II fibres of ADT subjects (by ~2%‐3%, P < .05) but not in Controls. Pure type IIx fibres were found frequently in muscle from ADT subjects but not in Controls, and the overall percentage of myosin heavy chain IIx in muscle samples was 2.5 times higher in ADT subjects (P < .01). The findings suggest that testosterone suppression can negatively impact the contractile properties by (i) reducing Ca2+‐sensitivity in both type I and type II fibres and (ii) reducing maximum specific force in type I fibres.
Governing Towards ‘One Health’: Establishing Knowledge Integration in Global Health Security Governance
Authors: Connolly John 
Published: October 2017

AbstractRecent global threats (e.g. Ebola, avian influenza, the Zika virus) have demonstrated the need for policy makers to focus on the detection of risks at the animal‐human interface. Yet epistemic knowledge across these domains is not sufficiently joined‐up. The article argues that, despite some progress, in order for the policy agenda for global health security to develop towards a ‘One Health’ model there is a need for integration across public and animal health domains. This article sets out an evaluation framework for establishing knowledge integration across these sectors. The article concludes that although ‘One Health may seem utopian, given there are key challenges when it comes to reaching integration, there are important steps that can be taken the short to medium‐term. These include reforms to education and training programmes and interdisciplinary research collaborations. A key determinant of whether One Health becomes a paradigm which frames public policy, and leads to policy and institutional changes to enable public value creation and sustainability, is the presence of an ‘epistemic community’ that bridges health networks.