bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Data Visualization for Scalable and Generalizable Single Cell Analysis
Authors: Cho Hyunghoon , Berger Bonnie , Peng Jian 
Published: March 2018

SummarySingle-cell RNA sequencing is becoming effective and accessible as emerging technologies push its scale to millions of cells and beyond. Visualizing the landscape of single cell expression has been a fundamental tool in single cell analysis. However, standard methods for visualization, such as t-stochastic neighbor embedding (t-SNE), not only lack scalability to data sets with millions of cells, but also are unable to generalize to new cells, an important ability for transferring knowledge across fast-accumulating data sets. We introduce net-SNE, which trains a neural network to learn a high quality visualization of single cells that newly generalizes to unseen data. While matching the visualization quality of t-SNE on 14 benchmark data sets of varying sizes, from hundreds to 1.3 million cells, net-SNE also effectively positions previously unseen cells, even when an entire subtype is missing from the initial data set or when the new cells are from a different sequencing experiment. Furthermore, given a “reference” visualization, net-SNE can vastly reduce the computational burden of visualizing millions of single cells from multiple days to just a few minutes of runtime. Our work provides a general framework for newly bootstrapping single cell analysis from existing data sets.
Cortical thickness in right frontal and left lingual gyri differentially mediate episodic memory for spatial contextual details across the adult lifespan
Authors: Swierkot A. , Rajah M. N. 
Published: March 2018

AbstractHealthy aging is associated with declines in episodic memory and with widespread cortical thinning. These parallel declines suggest that age-related changes in cortical thickness may contribute to episodic memory decline with age. The current study uses a cross-sectional study design to examine whether regional cortical thickness mediates the relationship between age and episodic memory, as measured by a context memory task for faces. Mediation and conditional mediation models were tested using bootstrapping in order to determine how age-associated changes in regional cortical thickness mediated age-associated changes in performance on the context memory task. We observed that right superior frontal cortical thickness conditionally mediated spatial context memory only in middle-aged and older adults; and right caudal middle frontal cortical thickness conditionally mediated context memory only in older adults. Left lingual cortical thickness mediated spatial context memory across the adult lifespan, but this effect was most evident at midlife. Right parahippocampal cortical thickness mediated context memory, independent of age. We conclude that our cortical thickness results were generally consistent with the posterior-to-anterior shift in aging hypothesis (Davis et al., 2008) for episodic memory.
USP9X regulates DVL2 ubiquitylation to determine WNT pathway specification
Authors: Nielsen Casey P. , Jernigan Kristin K. , Diggins Nicole L. , Webb Donna J. , MacGurn Jason A. 
Published: March 2018

SummaryThe WNT signaling network is comprised of multiple receptors that relay various input signals via distinct transduction pathways to execute multiple complex and context-specific output processes. Integrity of the WNT signaling network relies on proper specification between canonical and non-canonical pathways, which presents a regulatory challenge given that several signal transducing elements are shared between pathways. Here, we report that USP9X, a deubiquitylase, and WWP1, an E3 ubiquitin ligase, interact physically to regulate a ubiquitin switch on DVL2, a WNT signaling protein. Our findings indicate that USP9X-mediated deubiquitylation of DVL2 is required for canonical WNT activation, while DVL2 ubiquitylation promotes its localization to actin-rich projections and increased cellular motility. We propose that a WWP1-USP9X axis regulates a ubiquitin switch on DVL2 that specifies its participation in either canonical WNT or WNT-PCP pathways. These findings have important implications for therapeutic targeting of USP9X in human cancer.
Microstate EEGlab toolbox: An introductory guide
Authors: Poulsen Andreas Trier , Pedroni Andreas , Langer Nicolas , Hansen Lars Kai 
Published: March 2018

AbstractEEG microstate analysis offers a sparse characterisation of the spatio-temporal features of large-scale brain network activity. However, despite the concept of microstates is straight-forward and offers various quantifications of the EEG signal with a relatively clear neurophysiological interpretation, a few important aspects about the currently applied methods are not readily comprehensible. Here we aim to increase the transparency about the methods to facilitate widespread application and reproducibility of EEG microstate analysis by introducing a new EEGlab toolbox for Matlab. EEGlab and the Microstate toolbox are open source, allowing the user to keep track of all details in every analysis step. The toolbox is specifically designed to facilitate the development of new methods. While the toolbox can be controlled with a graphical user interface (GUI), making it easier for newcomers to take their first steps in exploring the possibilities of microstate analysis, the Matlab framework allows advanced users to create scripts to automatise analysis for multiple subjects to avoid tediously repeating steps for every subject. This manuscript provides an overview of the most commonly applied microstate methods as well as a tutorial consisting of a comprehensive walk-through of the analysis of a small, publicly available dataset.
Onset of differentiation is posttranscriptionally controlled in adult neural stem cells
Authors: Baser Avni , Dang Yonglong , Skabkin Maxim , Gülcüler Balta Gülce S. , Kalamakis Georgios , Kleber Susanne , Göpferich Manuel , Schefzik Roman , Santos Lopez Alejandro , Llorens Bobadilla Enric , Schultz Carsten , Fischer Bernd , Martin-Villalba Ana 
Published: March 2018

SUMMARYThe contribution of posttranscriptional regulation of gene expression to neural stem cell differentiation during tissue homeostasis remains elusive. Here we show highly dynamic changes in protein synthesis along differentiation of stem cells to neurons in vivo. Examination of individual transcripts using RiboTag mouse models reveals that neural stem cells efficiently translate abundant transcripts, whereas translation becomes increasingly controlled with the onset of differentiation. Stem cell generation of early neuroblasts involves translational repression of a subset of mRNAs including the stem cell-identity factors Sox2 and Pax6 as well as translation machinery components. In silico motif analysis identifies a pyrimidine-rich motif (PRM) in this repressed subset. A drop in mTORC1 activity at the onset of differentiation selectively blocks translation of PRM-containing transcripts. Our data uncovers how a drop in mTORC1 allows robust simultaneous posttranscriptional repression of key stem cell identity-factors and translation-components and thereby stemness exit and migration.
Genomic characterization of six virus-associated cancers identifies changes in the tumor microenvironment and altered genetic programming
Authors: Varn Frederick S. , Wang Yue , Cheng Chao 
Published: March 2018

AbstractViruses affect approximately 20% of all human cancers and express immunogenic proteins that make these tumor types potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas and other datasets to define how virus infection shapes the tumor microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the tumor microenvironment varied based on viral status, with infected tumors often exhibiting increased infiltration of cytolytic cell types. Analyses of the infiltrating T cell receptor repertoire revealed that Epstein-Barr virus was associated with decreased diversity in multiple cancers, suggesting an antigen-driven immune response. Tissue-specific gene expression signatures capturing these virus-induced transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of prognosis. The analyses presented suggest viruses have distinct effects in different tumors with implications for immunotherapy.
A novel, biologically-informed polygenic score reveals role of mesocorticolimbic insulin receptor gene network on impulsivity and addiction
Authors: McCracken Kathryn , Hari Dass Shantala A. , Pokhvisneva Irina , Chen Lawrence M. , Garg Elika , Nguyen Thao T. T. , Yaqubi Moein , McEwen Lisa M. , MacIsaac Julie L. , Diorio Josie , Kobor Michael S. , O’Donnell Kieran J. , Meaney Michael J. , Silveira Patricia P. 
Published: March 2018

AbstractImportanceActivation of brain insulin receptors occurs on mesocorticolimbic regions, modulating reward sensitivity and inhibitory control. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related psychopathologies (attention-deficit hyperactivity disorder, addiction), an idea that agrees with the high comorbidity between insulin resistant states and psychiatric conditions. While genetic studies comprise an interesting tool to explore neurobiological mechanisms in community samples, the conventional genome-wide association studies and polygenic risk score methodologies completely ignore the fact that genes operate in networks, and code for precise biological functions in specific tissues.ObjectiveWe propose a novel, biologically informed genetic score reflecting the mesocorticolimbic insulin receptor-related gene network, and investigate if it predicts dopamine-related psychopathology (impulsivity and addiction) in community samples.DesignBirth cohort (Maternal Adversity, Vulnerability and Neurodevelopment, MAVAN) and adult cohort (Study of Addiction, Genes and Environment, SAGE).SettingGeneral community.Participants212 4-year-old children (MAVAN), and 1626 adults (SAGE).ExposureThe biologically informed, mesocorticolimbic specific, insulin receptor polygenic score was created based on levels of co-expression with the insulin receptor in striatum and prefrontal cortex, and calculated in the two samples using the genotype data (Psychip/Psycharray).Main outcomechildhood impulsivity in the Information Sampling task, and risk for early addiction onset.ResultsThe insulin receptor polygenic score showed improved prediction of childhood impulsivity in boys and risk for early addiction onset in males in comparison to conventional polygenic risk scores for attention-deficit hyperactivity disorder or addiction.Conclusions and relevanceThis novel genomic approach reveals insulin action as a relevant biological process involved in the risk for dopamine-related psychopathology.Key pointsQuestionConsidering the modulation of mesocorticolimbic dopaminergic pathways by insulin through the action on its receptors (IR), we investigated if a novel, region specific polygenic score on the IR-related gene network (ePRS-IR) is associated with dopamine-related behaviors (impulsivity and addiction).FindingsThe ePRS-IR showed improved prediction of childhood impulsivity and risk for early addiction onset in comparison to conventional polygenic risk scores for ADHD or addiction.MeaningThis novel genomic approach reveals insulin action as a biological process involved in the risk for dopamine-related psychopathology.
Addressing operational constraints through Contextual Leadership at a KZN Public Hospital
Authors: Zungu Sibongile , Mathu Kenneth M. , Scheepers Caren 
Published: March 2018

Subject area
Organizational Development; Change Management; Leadership; Healthcare Management Operations; Supply Chain.

Study level/applicability
MBA; Masters in Healthcare Management; Post-graduate Diploma in Leadership; MPhil in Strategic Leadership.

Case overview
On April 16, 2016, the CEO of Prince Mshiyeni Memorial hospital, Kwa-Zulu Natal, South Africa, Dr Sandile Tshabalala reflected as he drove through the winding hills of the Cato range. In recent years, the hospital had been a subject of negative publicity with horror stories about patients collapsing while waiting for their medication at one of Durban’s largest hospitals. The case features a number of stakeholders and their demands and even threats. Contextual leadership intelligence requires accurate identification of relevant stakeholders and then involvement in solutions. The case illustrates how these demands had been listened to and how the stakeholders had been involved in finding solutions. A remarkable solution was to realize that the bottleneck at the pharmacy was actually caused by a problem early on in the process, for example, the late start of administrative staff who had to submit patients. A further solution was to utilize the primary health care clinics and even churches for dispensing chronic medicine.

Expected learning outcomes
Gaining insight and foresight into the operations and supply chain dilemmas in public health care. Developing understanding of the impact of various stakeholders in the healthcare sector. Understanding buy-in when leading change. Acquiring contextual leadership intelligence in the public health environment.

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.
Pacari Chocolate: preserving biodiversity, living without regret
Authors: Lupton Nathaniel C. , Sánchez Angélica , Kerpel Annette 
Published: March 2018

Subject area
Emerging Markets.

Study level/applicability
Undergraduate, Masters.

Case overview
Pacari Chocolate is the flagship brand of SKS Farms CIA Ltda., located in Quito, Ecuador. The company specializes in organic chocolate production which it sells in Ecuador and exports to other Latin American, European and North American markets. The company began operation in 2002, founded by Carla Barbotó and her husband Santiago Peralta. Carla is the Director of SKS and Santiago is General Manager. The case is set just after Santiago negotiated a deal to supply Emirates Airlines with mini bars to be distributed to flight passengers. Santiago is excited about this new deal, which will provide a new revenue stream, enhance brand image and potentially create new customers. Carla and Santiago pursue excellence with their products, as evidenced by over 160 awards, many globally recognized. However, their mission is also very much social in that they seek to improve the lives of Andean farmers, indigenous peoples and broader Ecuadorean society. The principle author uses this case in a course on innovative approaches to engaging emerging market opportunities, in which shared (social + economic) value and the formation of strong national industries are key outcomes, to be addressed through complementary market and non-market entrepreneurship strategies.

Expected learning outcomes
Expected learning outcomes are as follows: to identify the contextual challenges faced by an emerging market firm, and explain what must be done to overcome them; to identify the role of a firm in developing a national competency in an agricultural product industry; to demonstrate the creation of “shared value” and examine how the social mission of a company can reinforce and sustain its economic value creating activities; and to generate and evaluate options for developing international markets when a firm has limited resources to invest in marketing activities.

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 3: Entrepreneurship.
Macro-economic index effect on house prices in China
Authors: Li Zheyu , Razali Muhammad Najib , Gholipour Fereidouni Hassan , Mohd. Adnan Yasmin 
Published: March 2018

Purpose
The purpose of this study is to estimate different data models on house prices using statistical models and the variables which are controlled by real estate policy.

Design/methodology/approach
This study used several statistical techniques, such as Vector auto-regression (VAR), Johansen co-integration and variance decomposition, which aim to assess the significant effect of macroeconomic factors on Chinese house prices.

Findings
The results show that land supply and other variables have negative effects on house prices. The results also indicate that financial mortgages for real estate have positive effects on house prices and the area of vacant houses as well as the area of housing sold.

Research limitations/implications
This study only covers three cities in China because of limitations of data for other cities.

Originality/value
This study proposes policy suggestions according to the empirical results obtained.
Transcendence/religion to immanence/nonreligion in assisted dying
Authors: Beaman Lori G. , Steele Cory 
Published: March 2018

PurposeThe purpose of this paper is to draw attention to the ways in which the Supreme Court of Canada has shifted away from transcendent/religious to nonreligious conceptualizations of assisted dying.Design/methodology/approachA discourse analysis of a Supreme Court of Canada case on assisted dying and the facta of the 26 associated interveners.FindingsThe research points to a shift away from religious to nonreligious understandings in the way the Court conceptualizes suffering, pain, illness and assisted dying.Originality/valueThis paper contributes to the understanding of nonreligion as a social phenomenon.
The direct and indirect effect of cash transfers: the case of Indonesia
Authors: Yusuf Arief Anshory 
Published: March 2018

Purpose
The purpose of this paper is to analyze the impact of unconditional cash transfers in Indonesia on poverty and inequality while, unlike much of the previous literature on the welfare impact of such transfers, acknowledging that they will have both a direct effect and an economy-wide effect on the national economy.

Design/methodology/approach
The methodology used is a Computable General Equilibrium (CGE) model of the Indonesian economy. The unique feature of this model, which is very relevant in this study, is the disaggregation of households by expenditure classes; this allows for precise estimation of the distributional impact and poverty incidence.

Findings
The results suggest that, despite a large reduction in poverty, particularly in rural areas, such transfers reduce the Indonesian GDP, especially if domestically financed through increasing the value added tax of all commodities. However, the GDP reduction can be reduced by approximately half when cash transfers are financed by reducing the distortionary fuel subsidy. Moreover, cash transfers financed by reducing the fuel subsidy also reduce inequality by much more than otherwise. Various extents of the distribution of the transfers are compared, from giving them to the poorest 10 percent to distributing them equally to all households. The benefit of the transfers, in terms of reduced poverty and inequality, is found to be smaller when the author extends the beneficiaries toward the non-poor, although the economy-wide cost, in terms of the reduced GDP, is smaller.

Research limitations/implications
The CGE model used in this model is a comparative-static model that does not explicitly model the time dimension, i.e. how the impact of the transfers evolves over time. This is important if we want to know the timing of the transfers and how and when they are translated into impacts.

Practical implications
To reduce the contractionary effect of cash transfers program, government/policy makers should carefully look for appropriate financing such as from removing subsidy with pre-existing distortions like fuel subsidies.

Social implications
Government needs to carefully design cash transfers to minimize the negative indirect (economy-wide) implication for the national economy and to make sure that the transfers reach the targeted beneficiaries.

Originality/value
Few previous studies have acknowledged the indirect economy-wide effect in analyzing the impact of cash transfers. To the author’s knowledge, this has never been done before for Indonesia. Unlike previous studies, this paper is unique as it contains sensitivity analysis on how transfers can be mistargeted and reach the non-poor and looks at the implications not only for poverty and inequality but also for the rest of the economy.
Education and teenage childbirth in Uganda
Authors: Makate Marshall , Makate Clifton 
Published: March 2018

Purpose
The role of increased schooling on teenage childbirth has been expansively studied especially in developed countries. However, caveats remain in the case of low-income countries especially Sub-Saharan Africa. The purpose of this paper is to ascertain the impact of increased schooling on the probability of first childbirth at 15 years or younger, 16-17, 18-19, and 20 years or older, in the important context of Uganda – a country with one of the highest adolescent fertility rates in Africa.

Design/methodology/approach
The empirical analysis uses recent data from the nationally representative Demographic and Health Survey for Uganda conducted in 2011. The authors then adopt a fuzzy regression discontinuity design, estimated using instrumental variables techniques that exploit the exogenous change in schooling impelled by the universal primary education policy enacted in 1997 in Uganda. The empirical approach compares the fertility outcomes for women born in 1984-1992 (i.e. exposed to the policy) to those born in 1973-1981 (i.e. non-exposed).

Findings
The authors find that a one-year increase in schooling lowers the probability of first childbirth at age the age of 15 years or younger, 16-17, 18-19, and 20 years or older by nearly 8.2, 9.2, 9.4, and 9.5 percentage points, respectively. Also, pathways through which education impacts teenage motherhood included information access through the media, increased literacy, prenatal care utilization, marital status, and unhealthy sexual behavior.

Originality/value
The paper uses nationally representative survey data to scrutinize the causal influence of schooling on the probability of first childbirth using the 1997 universal primary education in Uganda as a natural experiment to identify the impact of schooling. The study recommends that expanding primary schooling opportunities for girls may be an effective strategy toward accelerated reductions in teenage fertility in Uganda.