bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Decline of Intergenerational Income Mobility in Denmark: Returns to Education, Demographic Change, and Labor Market Experience☆
Authors: Harding David J , Munk Martin D 
Published: June 2019

AbstractAlthough there is some evidence of declining intergenerational mobility in wealthy countries, the sources of these changes are not well understood. This paper examines the changes in intergenerational mobility in Denmark, which has one of the highest levels of intergenerational mobility in the world. We show that mobility has been declining for both men and women since the late 1950s across the most recent cohorts who are now old enough to measure permanent adult income, and that these changes were concentrated among children born into the middle three-fifths of the income distribution. We examine the sources of this decline by testing hypotheses related to demographic processes, returns to education, and work experience. Our results highlight the importance of both parent and child work experience and family structure in the family of origin among both men and women as well as, to a lesser degree, marital status, assortative mating, and childbearing among women. Although education was an important driver of parent-child income rank associations (IRA) in each cohort, it played little role in accounting for increases in those associations across cohorts.
Determination of true patient origin through motorcycle mapping: design and implementation of a community-defined geographic infrastructure surveillance tool in rural Sierra Leone
Authors: Monk Edward J M , Yee Ka-Ping , Allan Rupert , Gayton Ivan B 
Published: June 2019

Abstract

Background
Village-level geographic infrastructure data are often insufficient in low-resource settings, despite accurate patient origin determination being essential for surveillance and outbreak management. We detail a novel and seemingly reliable method for the determination of true patient origin with proof of concept in rural Sierra Leone.

Methods
Potential villages (n=2263), identified within a 7800 km2 hospital catchment area from satellite imagery, were accessed by motorcycle and surveyed in person, capturing village name and community-defined section/chiefdom/district.

Results
A survey established 1740 inhabited villages and a village of origin determination tool (gazetteer) was produced. Recording the district/chiefdom/section/village at hospital registration allowed Global Positioning System patient origin determination in 2277/2344 (97.1%) attendances.

Conclusions
Our proof of concept reports a substantial and sustained record of true patient origin in a low-resource setting.
Small-molecule control of super-Mendelian inheritance in gene drives
Authors: López Del Amo Víctor , Leger Brittany S. , Cox Kurt J. , Gill Shubhroz , Bishop Alena L. , Scanlon Garrett D. , Walker James A. , Gantz Valentino M. , Choudhary Amit 
Published: June 2019

ABSTRACTBy surpassing the 50% inheritance limit of Mendel’s law of independent assortment, CRISPR-based gene drives have the potential to fight vector-borne diseases or suppress crop pests. However, contemporary gene drives could spread unchecked, posing safety concerns that limit their use in both laboratory and field settings. Current technologies also lack chemical control strategies, which could be applied in the field for dose, spatial and temporal control of gene drives. We describe in Drosophila the first gene-drive system controlled by an engineered Cas9 and a synthetic, orally-available small molecule.Graphical Abstract
Comparative genomic analyses reveal diverse virulence factors and antimicrobial resistance mechanisms in clinical Elizabethkingia meningoseptica strains
Authors: Chen Shicheng , Soehnlen Marty , Blom Jochen , Terrapon Nicolas , Henrissat Bernard , Walker Edward D. 
Published: June 2019

AbstractThree human clinical isolates of bacteria (designated strains Em1, Em2 and Em3) had high average nucleotide identity (ANI) to Elizabethkingia meningoseptica. Their genome sizes (3.89, 4.04 and 4.04 Mb) were comparable to those of other Elizabethkingia species and strains, and exhibited open pan-genome characteristics, with two strains being nearly identical and the third divergent. These strains were susceptible only to trimethoprim/sulfamethoxazole and ciprofloxacin amongst 16 antibiotics in minimum inhibitory tests. The resistome exhibited a high diversity of resistance genes, including 5 different lactamase- and 18 efflux protein-encoding genes. Forty-four genes encoding virulence factors were conserved among the strains. Sialic acid transporters and curli synthesis genes were well conserved in E. meningoseptica but absent in E. anophelis and E. miricola. E. meningoseptica carried several genes contributing to biofilm formation. 58 glycoside hydrolases (GH) and 25 putative polysaccharide utilization loci (PULs) were found. The strains carried numerous genes encoding two-component system proteins (56), transcription factor proteins (187~191), and DNA-binding proteins (6~7). Several prophages and CRISPR/Cas elements were uniquely present in the genomes.
In vivo screen identifies LXR agonism potentiates sorafenib killing of hepatocellular carcinoma
Authors: Preziosi Morgan E. , Zahm Adam M. , Vázquez-Salgado Alexandra M. , Ackerman Daniel , Gade Terence P. , Kaestner Klaus H. , Wangensteen Kirk J. 
Published: June 2019

ABSTRACTExisting drug therapies for hepatocellular carcinoma (HCC), including sorafenib, extend patient survival by only three months. We sought to identify novel druggable targets for use in combination with sorafenib to increase its efficacy. We implemented an in vivo genetic screening paradigm utilizing a library of 43 genes-of-interest expressed in the context of repopulation of the injured livers of Fumarylacetoacetate Hydrolase-deficient (Fah−/−) mice, which led to highly penetrant HCC. We then treated mice with vehicle or sorafenib to discover genetic determinants of sensitivity and resistance. Liver X Receptor alpha (LXRα) emerged as a potential target. To examine LXRα agonism in combination with sorafenib treatment, we added varying concentrations of sorafenib and LXRα agonist drugs to HCC cell lines. We performed transcriptomic analysis to elucidate the mechanisms of HCC death. Fah−/− mice injected with the screening library developed HCC tumor clones containing Myc cDNA plus various other cDNAs. Treatment with sorafenib resulted in sorafenib-resistant HCCs that were significantly depleted in Nr1h3 cDNA, encoding LXRα, suggesting that LXRα activation is incompatible with tumor growth in the presence of sorafenib treatment in vivo. The combination of sorafenib and LXR agonism led to enhanced cell death as compared to monotherapy in multiple HCC cell lines, due to reduced expression of cell cycle regulators and increased expression of genes associated with apoptosis. Combination therapy also enhanced cell death in a sorafenib-resistant primary human HCC cell line. Our novel in vivo screen led to the discovery that LXR agonist drugs potentiate the efficacy of sorafenib in treating HCC.
The glucocorticoid receptor in the nucleus accumbens plays a crucial role in social rank attainment in rodents
Authors: Papilloud Aurélie , Weger Meltem , Bacq Alexandre , Zalachoras Ioannis , Hollis Fiona , Larrieu Thomas , Battivelli Dorian , Grosse Jocelyn , Zanoletti Olivia , Parnaudeau Sébastien , Tronche François , Sandi Carmen 
Published: June 2019

AbstractSocial hierarchy in social species is usually established through competitive encounters with conspecifics. It determines the access to limited resources and, thus, leads to reduced fights among individuals within a group. Despite the known importance of social rank for health and well-being, the knowledge about the processes underlying rank attainment remains limited. Previous studies have highlighted the nucleus accumbens (NAc) as a key brain region in the attainment of social hierarchies in rodents. In addition, glucocorticoids and the glucocorticoid receptor (GR) have been implicated in the establishment of social hierarchies and social aversion. However, whether GR in the NAc is involved in social dominance is not yet known. To address this question, we first established that expression levels of GR in the NAc of high anxious, submissive-prone rats are lower than that of their low anxious, dominant-prone counterparts. Furthermore, virally-induced downregulation of GR expression in the NAc in rats led to an improvement of social dominance rank. We found a similar result in a cell-specific mouse model lacking GR in dopaminoceptive neurons (i.e., neurons containing dopamine receptors). Indeed, when cohabitating in dyads of mixed genotypes, mice deficient for GR in dopaminoceptive neurons had a higher probability to become dominant than wild-type mice. Overall, our results highlight GR in the NAc and in dopaminoceptive neurons as an important regulator of social rank attainment.
BTLA and PD-1 employ distinct phosphatases to differentially repress T cell signaling
Authors: Xu Xiaozheng , Fulzele Amitkumar , Zhao Yunlong , Wu Zijun , Hu Yanyan , Jiang Yong , Ma Yanzhe , Wang Haopeng , Fu Guo , Bennett Eric , Hui Enfu 
Published: June 2019

ABSTRACTT cell-mediated destruction of tumors and virus-infected cells is restricted by co-inhibitory receptors such as programmed cell death protein 1 (PD-1). Monoclonal antibodies blocking PD-1 have produced impressive clinical activity against human cancers, but durable response is limited to a minority of patients. Previous results suggest that B and T lymphocyte attenuator (BTLA), a co-inhibitory receptor structurally related to PD-1, may contribute to the resistance to PD-1 targeted therapy and co-blockade of BTLA can enhance the efficacy of anti-PD-1 immunotherapy. However, the biochemical mechanism by which BTLA represses T cell activity and to what extent the mechanism differs from that of PD-1 is unknown. Here we examine differences in the ability of BTLA and PD-1 to recruit effector molecules and regulate T cell signaling. We show that PD-1 and BTLA recruit different tyrosine phosphatases to regulate either CD28 or T cell antigen receptor (TCR)-signaling cascades. Our data reveal unexpected disparities between two structurally related immune checkpoints and two phosphatase paralogs.
Machine learning identifies large-scale reward-related activity modulated by dopaminergic enhancement in major depression
Authors: Liu Yuelu , Admon Roee , Belleau Emily L. , Kaiser Roselinde H. , Clegg Rachel , Beltzer Miranda , Goer Franziska , Vitaliano Gordana , Ahammad Parvez , Pizzagalli Diego A. 
Published: June 2019

AbstractBackgroundTheoretical models have emphasized systems-level abnormalities in Major Depressive Disorder (MDD). For unbiased yet rigorous evaluations of pathophysiological mechanisms underlying MDD, it is critically important to develop data-driven approaches that harness whole-brain data to classify MDD and evaluate possible normalizing effects of targeted interventions. Here, using an experimental therapeutics approach coupled with machine-learning we investigated the effect of a pharmacological challenge aiming to enhance dopaminergic signaling on whole-brain’s response to reward-related stimuli in MDD.MethodsUsing a double-blind placebo-controlled design, functional magnetic resonance imaging (fMRI) data from 31 unmedicated MDD participants receiving a single dose of 50 mg amisulpride (MDDAmisulpride), 26 MDD participants receiving placebo (MDDPlacebo), and 28 healthy controls receiving placebo (HCPlacebo) were analyzed. An importance-guided machine learning technique for model selection was used on whole-brain fMRI data probing reward anticipation and consumption to identify features linked to MDD (MDDPlacebo vs. HCPlacebo) and dopaminergic enhancement (MDDAmisulpride vs. MDDPlacebo).ResultsHighly predictive classification models emerged that distinguished MDDPlacebo from HCPlacebo (AUC=0.87) and MDDPlacebo from MDDAmisulpride (AUC=0.89). Although reward-related striatal activation and connectivity were among the most predictive features, the best truncated models based on whole-brain features were significantly better relative to models trained using striatal features only.ConclusionsResults indicate that, in MDD, enhanced dopaminergic signaling restores abnormal activation and connectivity in a widespread network of regions. These findings provide new insights into the pathophysiology of MDD and pharmacological mechanism of antidepressants at the system level in addressing reward processing deficits among depressed individuals.ClinicalTrials.gov identifierNCT01253421 and NCT01701258
DEFORMATION BASED MORPHOMETRY STUDY OF LONGITUDINAL MRI CHANGES IN BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA
Authors: Manera Ana L. , Dadar Mahsa , Collins D. Louis , Ducharme Simon ,   Frontotemporal Lobar Degeneration Neuroimaging Initiative
Published: June 2019

ABSTRACTObjectiveTo objectively quantify how cerebral volume loss could assist with clinical diagnosis and clinical trial design in the behavioural variant of frontotemporal dementia (bvFTD).MethodsWe applied deformation-based morphometric analyses with robust registration to precisely quantify the magnitude and pattern of atrophy in patients with bvFTD as compared to cognitively normal controls (CNCs), to assess the progression of atrophy over one year follow up and to generate clinical trial sample size estimates to detect differences for the structures most sensitive to change. This study included 203 subjects - 70 bvFTD and 133 CNCs - with a total of 482 timepoints from the Frontotemporal Lobar Degeneration Neuroimaging Initiative.ResultsDeformation based morphometry (DBM) revealed significant atrophy in the frontal lobes, insula, medial and anterior temporal regions bilaterally in bvFTD subjects compared to controls with outstanding subcortical involvement. We provide detailed information on regional changes per year. In both cross-sectional analysis and over a one-year follow-up period, ventricle expansion was the most prominent differentiator of bvFTD from controls and a sensitive marker of disease progression.ConclusionsAutomated measurement of ventricular expansion is a sensitive and reliable marker of disease progression in bvFTD to be used in clinical trials for potential disease modifying drugs, as well as possibly to implement in clinical practice. Ventricular expansion measured with DBM provides the lowest published estimated sample size for clinical trial design to detect significant differences over one and two years.
Conjunctival microbiome-host responses are associated with impaired epithelial cell health in both early and late stages of trachoma
Authors: Pickering Harry , Palmer Christine D , Houghton Joanna , Makalo Pateh , Joof Hassan , Derrick Tamsyn , Goncalves Adriana , Mabey David CW , Bailey Robin L , Burton Matthew J , Roberts Chrissy h , Burr Sarah E , Holland Martin J 
Published: June 2019

AbstractBackgroundTrachoma, a neglected tropical disease, is the leading infectious cause of blindness and visual impairment worldwide. Host responses to ocular chlamydial infection resulting in chronic inflammation and expansion of non-chlamydial bacteria are hypothesised risk factors for development of active trachoma and conjunctival scarringMethodsOcular swabs from trachoma endemic populations in The Gambia were selected from archived samples for 16S sequencing and host conjunctival gene expression. We recruited children with active trachoma and adults with conjunctival scarring, alongside corresponding matched controls.FindingsIn children, active trachoma was not associated with significant changes in the ocular microbiome.Haemophilusenrichment was associated with antimicrobial responses but not linked to active trachoma. Adults with scarring trachoma had a reduced ocular bacterial diversity compared to controls, with increased relative abundance ofCorynebacterium. Increased abundance ofCorynebacteriumin scarring disease was associated with innate immune responses to the microbiota, dominated by altered mucin expression and increased matrix adhesion.InterpretationIn the absence of currentC. trachomatisinfection, changes in the ocular microbiome associate with antimicrobial and inflammatory responses that impair epithelial cell health. In scarring trachoma, expansion of ‘non-pathogenic’ bacteria such asCorynebacteriumand innate responses are coincident, warranting further investigation of this relationship. Comparisons between active and scarring trachoma supported the relative absence of type-1 interferon responses in scarring, whilst highlighting a common suppression of re-epithelialisation with altered epithelial and bacterial adhesion, likely contributing to development of scarring pathology.
Islet vascularization is regulated by primary endothelial cilia via VEGF-A dependent signaling
Authors: Xiong Yan , Scerbo M. Julia , Seelig Anett , Volta Francesco , O’Brien Nils , Dicker Andrea , Padula Daniela , Lickert Heiko , Gerdes Jantje M. , Berggren Per-Olof 
Published: June 2019

RationaleAccumulating evidence point to a role for primary cilia in endothelial cell function. Islet vascularization is an important determinant of islet function and glucose homeostasis. We have previously shown that β-cell cilia directly regulate insulin secretion. However, it is unclear whether primary cilia are also implicated in islet vascularization and thus contribute to glucose homeostasis.ObjectiveTo characterize the role of primary cilia in islet vascularization.Methods and ResultsAt four weeks, Bbs4−/− islets show markedly lower intra-islet capillary density with enlarged diameters. We transplanted islets into the anterior chamber (ACE) of mouse eyes for longitudinal and non-invasive in vivo monitoring of vascular morphology. Bbs4−/− islets exhibited significantly delayed re-vascularization and enlarged vessels during engraftment. Similar vascular phenotypes were observed in two other ciliopathy models. By shifting the relative contributions of host versus donor endothelial cells in islet revascularization, we found that primary cilia on endothelial cells is essential for this process. Electron microscopy analysis further revealed a lack of fenestration in engrafted Bbs4−/− islets, partially impairing vascular permeability and glucose delivery to β-cells. Finally, we identified that Vascular endothelial cell growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR2) signalling is involved in islet vascularization, islet function and vascular fenestration. In vitro silencing of two different ciliary genes in endothelial cells disrupts VEGF-A/ VEGFR2 internalization and phospho-activation of downstream signalling components. Consequently, key features of angiogenesis including proliferation, migration and tube formation are attenuated in BBS4 silenced endothelial cells.ConclusionsEndothelial cell primary cilia regulate islet vascularization and vascular barrier function via VEGF-A/ VEGFR2 signaling pathway. Islet vascularization is impaired in four weeks old Bbs4−/− mice. Long-time monitoring of re-vascularization of WT and Bbs4−/− islets recapitulates the phenotype and demonstrates a role for cilia in islet vascularization and vascular barrier function. VEGF-A/ VEGFR2-dependent signalling is regulated by endothelial primary cilia.
Diverse noncanonical PAMs recognized by SpCas9 in human cells
Authors: Hu Ziying , Wang Daqi , Zhang Chengdong , Wang Shuai , Gao Siqi , Hou Linghui , Wang Hongyan , Wang Yongming 
Published: June 2019

AbstractThe CRISPR/Cas9 system derived from Streptococcus pyogenes (SpCas9) provides unprecedented genome editing capabilities, but the potential for off-target mutations limits its application. In addition to NGG protospacer adjacent motif (PAM), off-target mutations are also associated with noncanonical PAMs, which have not yet been systematically evaluated. Here, we developed a highly sensitive approach that allows systematically analyzing PAM sequences in human cells, and identified multiple alternative PAMs recognized by SpCas9.
Legitimizing private legal systems through CSR communication: a Walmart case study
Authors: Harrison Virginia 
Published: June 2019

Purpose
The purpose of this paper is to understand the role of corporate social responsibility (CSR) communications in business by merging previously unconnected lines of thought in communications and law. Using Walmart as an example, the study shows that CSR communication can legitimize a corporation’s autonomous legal system of regulation and governance over its business practices.

Design/methodology/approach
A qualitative case study of all online corporate communications webpages from Walmart was examined. Discourse and qualitative analyses were used to show how language and online communications practices created actional legitimacy for Walmart’s CSR practices.

Findings
Using the UN’s Guiding Principles for Business as a framework for analysis, the study demonstrated how CSR communications helps Walmart to establish its own system of CSR norms, structures and remediation processes for its business outside of the state. These communications also sought to legitimize these actions among stakeholders.

Research limitations/implications
This case study looks at one corporation (Walmart) to illustrate a new connection between CSR communication and legitimacy. Future research in communications can extend this line of inquiry by examining how communications can reinforce autonomous legal systems and public perceptions.

Originality/value
Backer’s (2007) autonomous legal system and the concept of actional legitimacy in communications have not yet been studied systematically. This case study demonstrates how CSR communications can legitimize a multinational corporation’s business practices, which, in turn, raises ethical considerations for the ways this communication serves the greater society.
Grammar checking and relation extraction in text: approaches, techniques and open challenges
Authors: Madi Nora , Al-Matham Rawan , Al-Khalifa Hend 
Published: June 2019

Purpose
The purpose of this paper is to provide an overall review of grammar checking and relation extraction (RE) literature, their techniques and the open challenges associated with them; and, finally, suggest future directions.

Design/methodology/approach
The review on grammar checking and RE was carried out using the following protocol: we prepared research questions, planed for searching strategy, addressed paper selection criteria to distinguish relevant works, extracted data from these works, and finally, analyzed and synthesized the data.

Findings
The output of error detection models could be used for creating a profile of a certain writer. Such profiles can be used for author identification, native language identification or even the level of education, to name a few. The automatic extraction of relations could be used to build or complete electronic lexical thesauri and knowledge bases.

Originality/value
Grammar checking is the process of detecting and sometimes correcting erroneous words in the text, while RE is the process of detecting and categorizing predefined relationships between entities or words that were identified in the text. The authors found that the most obvious challenge is the lack of data sets, especially for low-resource languages. Also, the lack of unified evaluation methods hinders the ability to compare results.