bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning curve and competence for volumetric laser endomicroscopy in Barrett’s esophagus using cumulative sum analysis
Authors: Trindade Arvind , Inamdar Sumant , Smith Michael , Rosen Lisa , Han Dennis , Chang Kenneth , Leggett Cadman , Lightdale Charles , Pleskow Douglas , Sejpal Divyesh , Tearney Guillermo , Thomas Rebecca , Wallace Michael 
Published: November 2017

Abstract
Background and study aims Little is known about the learning curve for image interpretation in volumetric laser endomicroscopy (VLE) in Barrett’s esophagus (BE). The goal of this study was to calculate the learning curve, competence of image interpretation, sensitivity, specificity, and accuracy of VLE among novice users.
Methods 31 novice users viewed 96 VLE images electronically at three academic institutions after a brief training session. There were 24 images of each histologic type: normal gastric cardia, normal esophageal squamous epithelium, non-neoplastic BE, and neoplastic BE. The users were asked to identify the correct tissue type and level of confidence. The cumulative summation (CUSUM) technique was used to construct a learning curve.
Results 22 (71 %) of the physicians achieved VLE interpretation competency during their 96-slide review. Half of the physicians achieved competency at 65 images (95 % confidence interval [CI] 45 – 85). There was a statistically significant association between confidence in diagnosis and selecting the correct histologic tissue type (P < 0.001). The median accuracy for esophageal squamous epithelium, normal gastric cardia, non-neoplastic BE, and neoplastic BE was 96 % (95 %CI 95 % – 96 %), 95 % (95 %CI 94 % – 96 %), 90 % (95 %CI 88 % – 91 %), 96 % (95 %CI 95 % – 96 %). The overall accuracy was 95 % (95 %CI 93 % – 95 %).
Conclusion The majority of novice users achieved competence in image interpretation of VLE for BE, using a pre-selected image set, with a favorable learning curve after a brief training session. An electronic review of VLE images, prior to real-time use of VLE, is encouraged.
Anti-inflammatory Effects of Canthin-6-one Alkaloids from Ailanthus altissima
Authors: Cho Seung-Kye , Jeong Miran , Jang Dae , Choi Jung-Hye 
Published: November 2017

AbstractCanthin-6-one (CO) alkaloids possess various biological activities, including antibacterial, antitumor, antifungal, and antiviral activities. However, their anti-inflammatory effects and underlying molecular mechanisms are poorly characterized. This study aimed to investigate the anti-inflammatory effects of CO and its derivative 5-(1-hydroxyethyl)-canthin-6-one (5-HCO), isolated from the stem barks of Ailanthus altissima in lipopolysaccharide (LPS)-stimulated macrophages. CO (1 and 5 µM) and 5-HCO (7.5 and 15 µM) significantly inhibited the LPS-induced expression of inducible nitric oxide synthase. In addition, CO (1 and 5 µM) and 5-HCO (15 µM) markedly suppressed the production of prostaglandin E2 (PGE2) and expression of cyclooxygenase-2, a key enzyme in PGE2 synthesis, in LPS-stimulated macrophages. Moreover, CO treatment significantly reduced monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) expression, whereas 5-HCO inhibited MCP-1, but not TNF-α expression. Both CO and 5-HCO inhibited the phosphorylation of inhibitor kappa B and transcriptional activation of nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. In addition, CO, but not 5-HCO, markedly reduced Akt phosphorylation. Taken together, these data suggest that CO, but not 5-HCO with a hydroxyethyl moiety on the D ring, has potent anti-inflammatory activity in LPS-stimulated macrophages through the downregulation of both the NF-κB and the Akt pathway.
The future of the impact agenda depends on the revaluation of academic freedom
Authors: Holbrook J. Britt 
Published: November 2017

AbstractOpponents of the impact agenda often base their arguments on the claim that requiring scholarly research to demonstrate broader societal impacts conflicts with academic freedom. This paper argues that this claim entails a narrow interpretation of academic freedom as freedom from interference. A richer interpretation is proposed of academic freedom as freedom to pursue research that may have broader impacts. Adopting a positive view of academic freedom will require disciplines to adjust their standards of academic rigor and universities to amend their criteria for promotion and tenure. It will also provide the foundation for an academic response to the rise of neopopulism.
Hydraulic fracturing near domestic groundwater wells
Authors: Jasechko Scott , Perrone Debra 
Published: November 2017

Significance
Millions of Americans rely on self-supply groundwater wells for drinking water, but the number of these wells that are located near hydraulic fracturing operations is unknown. Here, we show that approximately half of all hydraulically fractured wells stimulated in 2014 exist within 2–3 km of one or more domestic (public and self-supply) groundwater wells. Our finding that many hydraulically fractured and domestic groundwater wells are colocated emphasizes that determining how frequently hydraulic fracturing activities impact groundwater quality is important to maintaining high-quality water in many domestic wells.
Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome
Authors: Reyes Ruiz Valeria M. , Ramirez Jasmine , Naseer Nawar , Palacio Nicole M. , Siddarthan Ingharan J. , Yan Brian M. , Boyer Mark A. , Pensinger Daniel A. , Sauer John-Demian , Shin Sunny 
Published: November 2017

Significance
Inflammasomes are cytosolic multiprotein complexes that initiate innate immune responses to microbial infection. Inflammasome specificity is determined by cytosolic innate immune sensors, including nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs). In mice, which encode seven different NAIPs, individual NAIPs recognize specific components of the structurally related bacterial type III secretion system (T3SS) and flagellar apparatus. Humans encode a single functional NAIP, raising the question of whether human NAIP recognizes the same repertoire of bacterial ligands. Here, we find that, in contrast to the ligand specificity exhibited by the murine NAIPs, the single human NAIP broadly detects multiple T3SS and flagellin proteins. These findings provide a basis for understanding the mechanisms underlying human-specific innate immune responses against bacterial infection.
Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection
Authors: Dharan Adarsh , Opp Silvana , Abdel-Rahim Omar , Keceli Sevnur Komurlu , Imam Sabrina , Diaz-Griffero Felipe , Campbell Edward M. 
Published: November 2017

Significance
Following envelope-mediated fusion, the HIV-1 viral core, which houses the viral RNA and proteins required for virus reverse transcription and integration, must traffic toward the nucleus for subsequent nuclear import of the viral genome. In this study we examined the role of BICD2, a known dynein adaptor protein, for its role during the postentry trafficking of HIV-1 virions. We show that BICD2 binds viral capsid and mediates the postentry trafficking of HIV-1. Moreover, we also show that depletion of BICD2 sensitizes the virus to detection by innate immune sensing, revealing this BICD2 is necessary for the virus to avoid detection by innate sensing mechanisms in macrophages.
Coupled European and Greenland last glacial dust activity driven by North Atlantic climate
Authors: Újvári Gábor , Stevens Thomas , Molnár Mihály , Demény Attila , Lambert Fabrice , Varga György , Jull A. J. Timothy , Páll-Gergely Barna , Buylaert Jan-Pieter , Kovács János 
Published: November 2017

Significance
Atmospheric dust is a major component of climate change. However, the relationship between glacial continental dust activity and abrupt centennial–millennial-scale climate changes of the North Atlantic is poorly known. Recent advances in high-precision radiocarbon dating of small gastropods in continental loess deposits provide an opportunity to gain unprecedented insights into dust variations and its major drivers at centennial–millennial scales from a near-source dust archive. Here, we show that Late Quaternary North Atlantic temperature and dustiness in Greenland and Europe were largely synchronous and suggest that this coupling was driven via precipitation changes and large-scale atmospheric circulation.
Storm, rogue wave, or tsunami origin for megaclast deposits in western Ireland and North Island, New Zealand?
Authors: Dewey John F. , Ryan Paul D. 
Published: November 2017

Significance
The origin of boulderite deposits in the geological record is controversial. Many argue that boulders weighing over 30 tonnes characterize tsunamites. We compare and contrast two such deposits with boulders exceeding this weight: a tsunamite from the Miocene of New Zealand and a present-day boulderite at Annagh Head, western Ireland. Combining field, historical, and oceanographic data, we argue that the latter is a cliff-top storm deposit (CTSD). Numerical modeling shows that the weight of a boulder in such CTSDs does not just reflect storm wave height, which can be over 60 m in western Ireland, but is also a function of its shape. We review the characteristics that distinguish these two deposits.
Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis
Authors: Chang Wen-Hsuan , Choi Si Ho , Moon Byoung-San , Cai Mingyang , Lyu Jungmook , Bai Jinlun , Gao Fan , Hajjali Ibrahim , Zhao Zhongfang , Campbell Daniel B. , Weiner Leslie P. , Lu Wange 
Published: November 2017

Significance
Receptor-like tyrosine kinase (Ryk) is a Wnt receptor and is important for many developmental processes, including cranial facial development, neurogenesis, and axon guidance. However, little is known about the role of the intracellular domain, Ryk-ICD, in signal transduction. Its downstream targets are also unknown. We have previously shown that Ryk-ICD is located in the cytoplasm of neural stem cells whereas it moves into the nucleus upon neuronal differentiation. In this study, we discovered that Smek1/2 function as a chaperone for Ryk-ICD during its nuclear localization and that both Smek and Ryk-ICD associate with chromatin to regulate the transcription of downstream target genes and neural differentiation.
Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2
Authors: Ancona Esselmann Samantha G. , Díaz-Alonso Javier , Levy Jonathan M. , Bemben Michael A. , Nicoll Roger A. 
Published: November 2017

Significance
AMPA-type glutamate receptors are known to play critical roles in both basal synaptic transmission and acute forms of plasticity, such as long-term potentiation and long-term depression, but less is known about their role in neuronal homeostasis. A model for bidirectional synaptic scaling is emerging in which the GluA2 AMPA receptor subunit has a central role. Here we confirm that GluA2, but not GluA1, is necessary for scaling, and we show that GluA2 is also sufficient for mediating this phenomenon. In addition, we find that the membrane-proximal C-terminal domain of GluA2 is required for scaling following chronic pharmacologic silencing of network activity. How the GluA2 membrane-proximal C-terminal domain mediates synaptic insertion of AMPA receptors following chronic silencing remains to be elucidated.
AP-4 mediates export of ATG9A from thetrans-Golgi network to promote autophagosome formation
Authors: Mattera Rafael , Park Sang Yoon , De Pace Raffaella , Guardia Carlos M. , Bonifacino Juan S. 
Published: November 2017

SignificanceA family of adaptor protein (AP) complexes functions to sort transmembrane cargos at different stages of the endomembrane system of eukaryotic cells. AP-4 is one of the most recently described and least well-understood members of this family. Interest in this complex has risen because mutations in any of its four subunits cause a form of hereditary spastic paraplegia (HSP) with intellectual disability. In this study, we demonstrate that AP-4 sorts ATG9A, the only transmembrane component of the core autophagy machinery, from thetrans-Golgi network to peripheral compartments. This sorting is required to promote the early steps of autophagosome formation. Our observations implicate AP-4 as an autophagy regulator and altered autophagy as an underlying defect in AP-4–deficient HSP.
The elusive transpositions
Authors: Lamarche Jean-Baptiste 
Published: November 2017

AbstractFreud’s canonical account portrays the birth of psychoanalysis as the result of an inner observation of oneself located beyond the reach of social requirements. Yet an account of psychoanalytic theory that locates it in the context of the relationships in which it is used shows that the image of the intrapersonal relationship created by this theory, is actuallya transposition of an interpersonal relationship: the portraying of an intrapersonal relationship thus offers a way to define a situation of interaction between social partners. This transposition allows different strategies of actions, which organize interactions by gauging them against norms of modern ‘contractual’ societies. In this way, the situational and dialogical account developed here locates psychoanalysis in its historical and social context.
Enhancing curricula and learning environments using critical realist perspectives and approaches: a case study and critique
Authors: Withell Andrew , Haigh Neil 
Published: November 2017

ABSTRACTWhile critical realist (CR) ontological and epistemological perspectives and research approaches are becoming more widely adopted by higher education researchers, the scope of research is relatively limited, and novice researchers in the area still struggle to create rich, in‐depth, and critical accounts of these approaches ‘in action’. This article provides an account of teacher‐researchers’ exploration of these perspectives in the context of an important aspect their everyday teaching practice – the design of effective curricula and learning environments. The context is research that focused on the design, evaluation, and enhancement of learning environments intended to facilitate students’ development of design thinking expertise. The article outlines the researchers’ CR paradigm positioning and implications for methodologies used to gather, analyse, and theorise data about the response of design and business students to three iterations of a design thinking learning environment. The research involved action research that integrated survey, case study, and theorising methodologies. Examples of data, analyses, and explanatory theory are provided to give insights into specific research tasks and their outcomes. Possible explanations for the findings and their implications for attempts to enhance the learning environment are considered from a CR perspective along with challenges that deploying these approaches may entail.
RecoverY: k-mer-based read classification for Y-chromosome-specific sequencing and assembly
Authors: Rangavittal Samarth , Harris Robert S , Cechova Monika , Tomaszkiewicz Marta , Chikhi Rayan , Makova Kateryna D , Medvedev Paul 
Published: November 2017

Abstract

Motivation
The haploid mammalian Y chromosome is usually under-represented in genome assemblies due to high repeat content and low depth due to its haploid nature. One strategy to ameliorate the low coverage of Y sequences is to experimentally enrich Y-specific material before assembly. As the enrichment process is imperfect, algorithms are needed to identify putative Y-specific reads prior to downstream assembly. A strategy that uses k-mer abundances to identify such reads was used to assemble the gorilla Y. However, the strategy required the manual setting of key parameters, a time-consuming process leading to sub-optimal assemblies.

Results
We develop a method, RecoverY, that selects Y-specific reads by automatically choosing the abundance level at which a k-mer is deemed to originate from the Y. This algorithm uses prior knowledge about the Y chromosome of a related species or known Y transcript sequences. We evaluate RecoverY on both simulated and real data, for human and gorilla, and investigate its robustness to important parameters. We show that RecoverY leads to a vastly superior assembly compared to alternate strategies of filtering the reads or contigs. Compared to the preliminary strategy used by Tomaszkiewicz et al., we achieve a 33% improvement in assembly size and a 20% improvement in the NG50, demonstrating the power of automatic parameter selection.

Availability and implementation
Our tool RecoverY is freely available at https://github.com/makovalab-psu/RecoverY.

Supplementary information
Supplementary data are available at Bioinformatics online.
Depression symptoms as mediators of inequalities in self-reported health: the case of Southern European elderly
Authors: Leão T , Perelman J 
Published: November 2017

Abstract

Background
Inequalities in the distribution of self-reported health (SRH) have been widely reported. Its higher expressivity among women, elderly and least educated groups has been partly attributed to differences in their health perceptions. However, this subjectivity may be masking the burden of mental illness in these groups. Thus, we sought to understand if depression symptoms mediate inequalities in SRH.

Methods
SHARE waves 4 and 6, pertaining to Spain, Italy and Portugal, were used (n2011 = 8517, n2015 = 11 046). Inequalities in SRH were calculated, comparing the risk amongst education level, gender and age groups, adjusting for chronic diseases, functional limitations and country fixed effects. We then tested depression symptoms as mediators.

Results
Depression symptoms were associated with poor SRH (odds ratio (OR)2011 = 1.379, OR2015 = 1.384, P < 0.001). Their inclusion reduced the magnitude of the association between SRH and education, annulled the statistical significance for age, and reversed the gender effect. As expected, chronic diseases and functional limitations remained significant predictors of poor SRH.

Conclusions
Depression symptoms, together with chronic diseases and functional limitations, explain the poorer SRH of the least educated, female and older groups in the Southern European population. Therefore, tackling inequalities in SRH must require focusing on mental health issues, which disproportionately affect the most vulnerable groups.
Tracing cellular heterogeneity in pooled genetic screens via multi-level barcoding
Authors: Boettcher Michael , Covarrubias Sergio , Biton Anne , Blau James A , Wang Haopeng , Zaitlen Noah , McManus Michael T 
Published: November 2017

AbstractWhile pooled loss- and gain-of-function screening approaches have become increasingly popular to systematically investigate mammalian gene function, they have thus far ignored the fact that cell populations are heterogeneous. Here we introduce multi-level barcoded sgRNA libraries to (i) monitor differences in the behavior of multiplexed clonal cell lines, (ii) trace sub-clonal lineages of cells expressing the same sgRNA, (iii) derive in-sample screen replicates and (iv) reduce the number of cells and sequencing read counts required to reach statistical significance. Using our approach, we illustrate how clonal heterogeneity impairs the results of pooled genetic screens and demonstrate the ability of multi-level barcoding to resolve cellular heterogeneity related issues.
Elevated polygenic burden for autism is associated with differential DNA methylation at birth
Authors: Hannon Eilis , Schendel Diana , Ladd-Acosta Christine , Grove Jakob ,   iPSYCH-Broad ASD Group, Hansen Christine Søholm , Andrews Shan V. , Hougaard David Michael , Bresnahan Michaeline , Mors Ole , Hollegaard Mads Vilhelm , Bækvad-Hansen Marie , Hornig Mady , Mortensen Preben Bo , Børglum Anders D. , Werge Thomas , Pedersen Marianne Giørtz , Nordentoft Merete , Buxbaum Joseph , Fallin M Daniele , Bybjerg-Grauholm Jonas , Reichenberg Abraham , Mill Jonathan 
Published: November 2017

ABSTRACTBackgroundAutism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors, interests, or activities. The etiology of ASD involves both inherited and environmental risk factors, with epigenetic processes hypothesized as one mechanism by which both genetic and non-genetic variation influence gene regulation and pathogenesis.MethodsWe quantified neonatal methylomic variation in 1,263 infants - of whom ~50% went on to subsequently develop ASD – using DNA isolated from a unique collection of archived blood spots taken shortly after birth. We used matched genetic data from the same individuals to examine the molecular consequences of ASD genetic risk variants, identifying methylomic variation associated with elevated polygenic burden for ASD. In addition, we performed DNA methylation quantitative trait loci (mQTL) mapping to prioritize target genes from ASD GWAS findings.ResultsAlthough we did not identify specific loci showing consistent changes in neonatal DNA methylation associated with later ASD, we found a significant association between increased polygenic burden for autism and methylomic variation at two CpG sites located proximal to a robust GWAS signal for ASD on chromosome 8.ConclusionsThis study is the largest analysis of DNA methylation in ASD yet undertaken and the first to integrate both genetic and epigenetic variation at birth in ASD. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with disease, and of using mQTL to refine the functional and regulatory variation associated with ASD risk variants.
Cytokine response of acute myeloid leukemia cells has impact on patient prognosis: Insights from mathematical modeling
Authors: Stiehl Thomas , Ho Anthony D , Marciniak-Czochra Anna 
Published: November 2017

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease. One reason for the heterogeneity may originate from inter-individual differences in the responses of leukemic cells to endogenous cytokines. On the basis of mathematical modeling, computer simulations and patient data, we have provided evidence that cytokine-independent leukemic cell proliferation is linked to early relapses and poor overall survival. Depending whether the model of cytokine-dependent or cytokine-independent leukemic cell proliferation fits to the clinical data, patients can be assigned to two groups that differ significantly with respect to overall survival. The modeling approach further enables us to identify parameter constellations that can explain unexpected responses of some patients to external cytokines such as blast crisis or remission without chemotherapy.