bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Sulf2-dependant astrocyte subtype that stands out through the expression of Olig2 in the ventral spinal cord
Authors: Ohayon David , Escalas Nathalie , Cochard Philippe , Glise Bruno , Danesin Cathy , Soula Cathy 
Published: September 2018

SummaryDuring spinal cord development, both spatial and temporal mechanisms operate to generate glial cell diversity. Here, we addressed the role of the Heparan Sulfate-editing enzyme Sulf2 in the control of gliogenesis in the mouse developing spinal cord and found an unanticipated function for this enzyme. Sulf2 is expressed in ventral spinal progenitors at initiation of gliogenesis, including in Olig2-expressing cells of the pMN domain known to generate most spinal cord oligodendrocyte precursor cells (OPCs). We found that Sulf2 is dispensable for OPC development but required for proper generation of an as-yet-unidentified astrocyte precursor cell (AP) subtype. These cells, like OPCs, express Olig2 while populating the spinal parenchyma at embryonic stages but also retain Olig2 expression as they differentiate into mature astrocytes. We therefore identify a spinal Olig2-expressing AP subtype that segregates early under the influence of the extracellular enzyme Sulf2.
Comparative evidence for the independent evolution of hair and sweat gland traits in primates
Authors: Kamberov Yana G. , Guhan Samantha M. , DeMarchis Alessandra , Jiang Judy , Wright Sara Sherwood , Morgan Bruce A. , Sabeti Pardis C. , Tabin Clifford J. , Lieberman Daniel E. 
Published: September 2018

AbstractHumans differ in many respects from other primates, but perhaps no derived human feature is more striking than our naked skin. Long purported to be adaptive, humans’ unique external appearance is characterized by changes in both the patterning of hair follicles and eccrine sweat glands, producing decreased hair cover and increased sweat gland density. Despite the conspicuousness of these features and their potential evolutionary importance, there is a lack of clarity regarding how they evolved within the primate lineage. We thus collected and quantified the density of hair follicles and eccrine sweat glands from five regions of the skin in three species of primates: macaque, chimpanzee and human. Although human hair cover is greatly attenuated relative to that of our close relatives, we find that humans have a chimpanzee-like hair density that is significantly lower than that of macaques. In contrast, eccrine gland density is on average 10-fold higher in humans compared to chimpanzees and macaques, whose density is strikingly similar. Our findings suggest that a decrease in hair density in the ancestors of humans and apes was followed by an increase in eccrine gland density and a reduction in fur cover in humans. This work answers longstanding questions about the traits that make human skin unique and substantiates a model in which the evolution of expanded eccrine gland density was exclusive to the human lineage.
Nitrogen recycling in coupled green and brown food webs: Weak effects of herbivory and detritivory when nitrogen passes through soil
Authors: Buchkowski Robert W. , Schmitz Oswald J. , Bradford Mark A. 
Published: September 2018

Abstract

The study of coupled green and brown food webs has improved our ability to understand how nutrient cycling and plant communities respond to perturbations. Yet, it is still difficult to predict how rapidly and consistently changes in one food web propagate to the other. An area of particular uncertainty is the response of plants to the changes in leaf litter nitrogen release caused by herbivores and detritivores.

We combined a field experiment and theoretical analysis to assess how herbivory, fertilization, and detritivory changed leaf litter nitrogen release and plant growth. We produced leaf litter in greenhouse cages with a factorial combination of grasshopper herbivory and additional nitrogen fertilizer. Our experiment used the resulting 15N‐labelled leaf litter to measure isopod litter consumption, litter nitrogen release, and plant nitrogen uptake in the field. We then used a dynamical systems model to distinguish whether plant growth relied (a) directly on litter nitrogen release or (b) on other nitrogen pathways so that changes in litter nitrogen release have little immediate impact.

Our empirical results show that the effect of nitrogen fertilization on isopod processing of leaf litter was stronger than the effect of herbivory. Regardless, the available soil nitrogen and plant growth were independent of litter nitrogen release. Our dynamical model attributes the independence to other nitrogen sources and sinks, which buffer the plant‐available nitrogen pool. Isopods and litter with a history of herbivory reduced above‐ground plant growth when we accounted for initial field mesocosm conditions, especially the abundance of the competitively dominant goldenrods. Consequently, the impact of isopods and litter traits do propagate to influence plant growth, but do not have a large enough effect to overcome initial differences in plant biomass and community composition in one year.

Synthesis. Our results indicate animals in green and brown food webs can alter plant litter nitrogen release without any significant nutrient recycling effect on plant growth. Considering the availability of external and soil‐based nitrogen sources, as well as the current plant community and microbial biomass, may be critical to determining when plant growth will respond to animal‐mediated changes in litter decomposition.
What can deliberative mini‐publics contribute to democratic systems?
Authors: BEAUVAIS EDANA , WARREN MARK E. 
Published: September 2018

AbstractCan deliberative mini‐publics contribute to deepening the democratic dimensions of electoral democracies? The question is framed in this article using a problem‐based approach to democratic theory–to count as democratic, political systems must accomplish three basic functions related to inclusion, communication and deliberation, and decision making. This approach is elaborated with an analysis of a real‐world case: a deliberative mini‐public with a citizens’ assembly design, focused on urban planning convened in Vancouver, Canada. This example was chosen because the context was one in which the city's legacy institutions of representative democracy had significant democratic deficits in all three areas, and the mini‐public was a direct response to these deficits. It was found that Vancouver's deliberative mini‐public helped policy makers, activists and affected residents move a stalemated planning process forward, and did do so in ways that improved the democratic performance of the political system. Depending on when and how they are sequenced into democratic processes, deliberative mini‐publics can supplement existing legacy institutions and practices to deepen their democratic performance.
Efficacy of Surgicel® (Fibrillar) for preventing bleeding after endoscopic submucosal dissection for gastric epithelial tumors
Authors: Hwang Jae Jin , Hong Su Jin , Han Jae Pil , Ko Bong Min , Lee Tae Hee , Lee Joon Seong 
Published: September 2018

ObjectiveSurgicel (Fibrillar), i.e. oxidized regenerated cellulose, is used to control oozing bleeding after surgery, but few studies have assessed its effect on complications after endoscopic treatment. The aim of this study was to evaluate the efficacy of Surgicel for preventing bleeding after endoscopic submucosal dissection (ESD) for gastric epithelial tumors.MethodsFrom November 2012 to December 2013 patients scheduled for ESD of gastric epithelial tumors were prospectively enrolled in this study. Patients were assigned randomly to monotherapy with a proton pump inhibitor (PPI) (the MT group) or combination therapy with Surgicel and histamine‐2 receptor antagonist (H2RA) (the CT group) for preventing bleeding after ESD. Major bleeding rates and changes in hemoglobin at 1 and 7 days after ESD were evaluated.ResultsAmong the 157 patients enrolled (111 men, 46 women), 78 were assigned to the MT group and 79 to the CT group; finally, 72 and 74 patients were included in the MT and CT groups. The major bleeding rate was lower in the CT group (6/74, 8.1%) than in the MT group (12/72, 16.7%), but the difference was not significant (P = 0.354). The change in hemoglobin was significantly less marked in the CT group than the MT group 1 day after ESD ([−6.2 ± 9.0] g/L vs [−8.9 ± 6.2] g/L, P = 0.045).ConclusionsCombination therapy with Surgicel and an H2RA decreased the rate of bleeding similarly to PPI. Adding Surgicel to H2RA could be considered for patients with bleeding tendencies, or who require continuous antiplatelet therapy to prevent bleeding after ESD.
Leveraging a Participatory Process for Restoration Return on Investment: The Nature Conservancy's Floodplain Investment Tool
Authors: Lyon Steve W. , Cunha Luciana , DiBlasio Michelle , Creveling Ellen 
Published: September 2018

AbstractIn this study, we develop the Floodplain Investment Tool (FPIT) to help stakeholders prioritize conservation efforts to maximize return on investments (e.g., ensure the most “bang for the buck”). We applied the FPIT for the 177 mi2 (458 km2) Paulins Kill watershed located in northwestern New Jersey, as a case study focusing on nutrient loading. The resultant FPIT reflected independently assessed habitat and ecosystem impairment scores across the watershed. Nutrient load (both total phosphorus [TP] and total nitrogen [TN]) estimates made with the FPIT were in relative agreement across scales with a more robust modeling approach and allowed for development of several application scenarios. For example, we estimated a well‐targeted budget of $2 million could reduce annual nutrient load to be approximately 530 lbs (240 kg) of TP and 5,835 lbs (2,647 kg) of TN for the watershed. Where the clear value for the FPIT can be seen is in the process by which it was pilot‐tested for application and stakeholder voices were integrated into its development. This allows for a level of transparency not available from more top‐down approaches where stakeholders are involved only at the end of the development process.
Contouring consensus guidelines in breast cancer radiotherapy: Comparison and systematic review of patterns of failure
Authors: Gee Harriet E , Moses Lauren , Stuart Kirsty , Nahar Najmun , Tiver Ken , Wang Tim , Ward Rachel , Ahern Verity 
Published: September 2018

SummaryAdequate coverage of sites harbouring potential microscopic disease is paramount, where the clinical decision has been made to include regional lymph node radiotherapy for patients with breast cancer. This must be achieved in balance with minimising dose to normal tissues. Several international consensus guidelines detailing clinical target volumes (CTVs) are available, but there is currently no agreement as to which is most appropriate for a given clinical situation. Contouring guidelines are beneficial for routine practice and essential for clinical trial quality assurance. The aims of this study were as follows: to provide a single point of comparison of four commonly used contouring guidelines, including one used in a current Trans‐Tasman Radiation Oncology Group trial; and to undertake a systematic review of existing studies which map sites of breast cancer recurrence against contouring guidelines. Two international consensus guidelines (European Society for Radiotherapy and Oncology, and Radiation Therapy Oncology Group) were compared with two clinical trial guidelines (TROG 12.02 PET LABRADOR and the Proton/Photon trial NCT02603341 RADCOMP). Comprehensive literature search for patterns of failure studies was undertaken using Embase and Pubmed. We detail the small but significant differences between the breast consensus guidelines, particularly the supraclavicular (SCF) and internal mammary chain CTVs. Seven series were found mapping recurrence patterns. These results are discussed in the context of the contouring guidelines. Several studies found the SCF CTV is the area at greatest risk of geographical ‘miss’. This review will facilitate further discussion about guideline selection and modification, particularly for future clinical trials in Australia and New Zealand.
Inconsistent use of multiple comparison corrections in studies of population genetic structure: Are some type I errors more tolerable than others?
Authors: Hauser Samantha , Wakeland Kristin , Leberg Paul 
Published: September 2018

AbstractStudies of genetic population structure often involve numerous tests of Hardy–Weinberg equilibrium (HWE), linkage disequilibrium (LD) and genetic differentiation. Tests of HWE or LD are important precursors to population structure assessments. When conducting multiple related statistical tests, type I error increases, e.g., familywise error rate (FWER) inflation. FWER inflation can alter the results of statistical tests and thus the conclusions. We surveyed literature from 2011 to 2013 to determine if studies of population structure assess LD and HWE and if FWER corrections were applied consistently across different types of tests. We found significantly inconsistent FWER corrections, with a bias towards less restrictive correction on genetic differentiation and more restrictive corrections with LD and HWE. While varied adjustments of FWER for different types of analyses might be justified, papers with inconsistent usage across tests of HWE, LD and genetic differentiation did not present rationale for their FWER corrections. We also found a lack of documentation of HWE, LD and FWER corrections in studies. We encourage the authors to report statistical tests and related FWER corrections, use FWER corrections consistently or justify their different methods in the same study.
Pollen metabarcoding as a tool for tracking long‐distance insect migrations
Authors: Suchan Tomasz , Talavera Gerard , Sáez Llorenç , Ronikier Michał , Vila Roger 
Published: September 2018

AbstractInsects account for a large portion of Earth's biodiversity and are key players for ecosystems, notably as pollinators. While insect migration is suspected to represent a natural phenomenon of major importance, remarkably little is known about it, except for a few flagship species. The reason for this situation is mainly due to technical limitations in the study of insect movement. Here, we propose using metabarcoding of pollen carried by insects as a method for tracking their migrations. We developed a flexible and simple protocol allowing efficient multiplexing and not requiring DNA extraction, one of the most time‐consuming part of metabarcoding protocols, and apply this method to the study of the long‐distance migration of the butterfly Vanessa cardui, an emerging model for insect migration. We collected 47 butterfly samples along the Mediterranean coast of Spain in spring and performed metabarcoding of pollen collected from their bodies to test for potential arrivals from the African continent. In total, we detected 157 plant species from 23 orders, most of which (82.8%) were insect‐pollinated. Taxa present in Africa–Arabia represented 73.2% of our data set, and 19.1% were endemic to this region, strongly supporting the hypothesis that migratory butterflies colonize southern Europe from Africa in spring. Moreover, our data suggest that a northwards trans‐Saharan migration in spring is plausible for early arrivals (February) into Europe, as shown by the presence of Saharan floristic elements. Our results demonstrate the possibility of regular insect‐mediated transcontinental pollination, with potential implications for ecosystem functioning, agriculture and plant phylogeography.
Blocking FGFR4 exerts distinct anti‐tumorigenic effects in esophageal squamous cell carcinoma
Authors: Xin Zhongwei , Song Xuemin , Jiang Bin , Gongsun Xin , Song Liang , Qin Qiming , Wang Qiang , Shi Mo , Liu Xiangyan 
Published: September 2018

BackgroundThe FGFR family can be activated by FGFs and plays important roles in regulating cell growth, differentiation, migration, and angiogenesis. Recent studies have suggested that FGFR4 could regulate several processes, including tumor progression. Esophageal squamous cell carcinoma (ESCC) is a malignancy with high global occurrence. However, the molecule mechanism and the potential roles of FGFR4 in ESCC remain unknown.MethodsImmunohistochemistry and Western blotting were used to detect FGFR4 expression in ESCC samples and cell lines. Cell counting kit‐8, and clonogenic, transwell, flow cytometric, and tumor xenograft in nude mice assays were utilized to determine the effect of blocking FGFR4 in proliferation, invasion, migration, and apoptosis of ESCC cells.ResultsFGFR4 is frequently overexpressed in ESCC tissue and cell lines. in vitro assays have shown that blocking FGFR4 by a specific blocker, H3B‐6527, significantly decreases proliferation, invasion, and migration, and alters epithelial‐mesenchymal transition markers in ESCC cells. In addition, FGFR4 blockade is associated with the induction of apoptosis and affects PI3K/Akt and MAPK/ERK pathways. Moreover, FGFR4 blockade could significantly inhibit the growth of xenograft tumors in vivo.ConclusionOur findings suggest that blocking FGFR4 significantly suppresses the malignant behaviors of ESCC and indicate that FGFR4 is a potential target for the treatment of ESCC.
Tight junction, mucin, and inflammasome‐related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice
Authors: Tan Hern‐Tze Tina , Hagner Stefanie , Ruchti Fiorella , Radzikowska Urszula , Tan Ge , Altunbulakli Can , Eljaszewicz Andrzej , Moniuszko Marcin , Akdis Mübeccel , Akdis Cezmi A. , Garn Holger , Sokolowska Milena 
Published: September 2018

AbstractBackgroundAsthma is a chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Specific pathways are thought to be involved in the pathomechanisms of different inflammatory phenotypes of asthma; however, direct in vivo comparison has not been performed.MethodsWe developed mouse models representing three different phenotypes of allergic airway inflammation—eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT‐PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air‐liquid interface were used to study the mechanisms revealed in the in vivo models.ResultsBy whole‐genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome‐related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo‐1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome‐related molecules such as Nlrp3, Nlrc4, Casp‐1, and IL‐1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine—IL‐1β—may transiently impair epithelial barrier function, while IL‐1β and IL‐17 increase mucin expressions in primary human bronchial epithelial cells.ConclusionOur findings suggest that differential expression of TJ, mucin, and inflammasome‐related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic.
Using clinical and genetic data to predict pulmonary hypertension in bronchopulmonary dysplasia
Authors: Trittmann J K , Bartenschlag A , Zmuda E J , Frick J , Stewart W C L , Nelin L D 
Published: September 2018

AbstractAimPulmonary hypertension significantly increases morbidity and mortality in infants with bronchopulmonary dysplasia. The frequency of single nucleotide polymorphisms in arginase‐1 (ARG1 rs2781666) and dimethylarginine dimethylaminohydrolase‐1 (DDAH1 rs480414) genes has been found to differ in a cohort of bronchopulmonary dysplasia patients with pulmonary hypertension (cases) and without pulmonary hypertension (controls). Therefore, we tested the hypothesis that combining these genotypes with phenotypic data would better predict pulmonary hypertension in bronchopulmonary dysplasia patients.MethodsBronchopulmonary dysplasia patients (n = 79) born at <35 weeks gestation were studied. Pulmonary hypertension was diagnosed by echocardiographic criteria (n = 20). ROC curves to predict pulmonary hypertension in bronchopulmonary dysplasia were generated from genotype and/or clinical data.ResultsCases were born at an earlier gestation and weighed less at birth than did controls. ROC curves for rs2781666 had an AUC of 0.61, while rs480414 had an AUC of 0.66. Together, the AUC was 0.70. When clinical data were added to the genetic model, AUC was 0.73.ConclusionThese findings demonstrate that ROC predictive modelling of pulmonary hypertension in bronchopulmonary dysplasia improves with inclusion of both genotypic and phenotypic data. Further refinement of these types of models could facilitate the implementation of precision medicine approaches to pulmonary hypertension in bronchopulmonary dysplasia.
Semi-Supervised Validation of Multiple Surrogate Outcomes with Application to Electronic Medical Records Phenotyping
Authors: Hong Chuan , Liao Katherine P. , Cai Tianxi 
Published: September 2018

Abstract
The Electronic Medical Records (EMR) data linked with genomic data have facilitated efficient and large scale translational studies. One major challenge in using EMR for translational research is the difficulty in accurately and efficiently annotating disease phenotypes due to the low accuracy of billing codes and the time involved with manual chart review. Recent efforts such as those by the Electronic Medical Records and Genomics (eMERGE) Network and Informatics for Integrating Biology & the Bedside (i2b2) have led to an increasing number of algorithms available for classifying various disease phenotypes. Investigators can apply such algorithms to obtain predicted phenotypes for their specific EMR study. They typically perform a small validation study within their cohort to assess the algorithm performance and then subsequently treat the algorithm classification as the true phenotype for downstream genetic association analyses. Despite the superior performance compared to simple billing codes, these algorithms may not port well across institutions, leading to bias and low power for association studies. In this paper, we propose a semi-supervised method to make inferences about both the accuracy of multiple available algorithms and the effect of genetic markers on the true phenotype, leveraging information from both a large set of unlabeled data where both genetic markers and algorithm output information and a small validation data where labels are additionally available. The simulation studies show that the proposed method substantially outperforms existing methods from the missing data literature. The proposed methods are applied to an EMR study of how low density lipoprotein risk alleles affect the risk of cardiovascular disease among patients with rheumatoid arthritis.