bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoform-selective NADPH oxidase inhibitor panel for pharmacological target validation
Authors: Dao V.T. , Elbatreek Mahmoud H. , Altenhöfer S. , Casas Ana I. , Pachado M.P. , Neullens C.T. , Knaus U. , Schmidt H.H.H.W. 
Published: August 2018

AbstractUnphysiological reactive oxygen species (ROS) formation is considered an important pathomechanism for several disease phenotypes with high unmet medical need. Therapeutically, antioxidants have failed multiple times. Instead, focusing on only disease-relevant, enzymatic sources of ROS appears to be a more promising and highly validated approach. Here the family of five NADPH oxidases (NOX) stands out as drug targets. Validation has been restricted, however, mainly to genetically modified rodents and is lacking in other species including human. It is thus unclear whether the different NOX isoforms are sufficiently distinct to allow selective pharmacological modulation. Here we show for five of the most advanced NOX inhibitors that indeed isoform selectivity can be achieved. NOX1 was most potently (IC50) targeted by ML171 (0.1 μM); NOX2, by VAS2870 (0.7 μM); NOX4, by M13 (0.01 μM) and NOX5, by ML090 (0.01 μM). Conditions need to be carefully controlled though as previously unrecognized non-specific antioxidant and assay artefacts may limit the interpretation of data and this included, surprisingly, one of the most advanced NOX inhibitors, GKT136901. As proof-of-principle that now also pharmacological and non-rodent target validation of different NOX isoforms is possible, we used a human blood-brain barrier model and NOX inhibitor panel at IC50 concentrations. The protective efficacy pattern of this panel confirmed the predominant role of NOX4 in stroke from previous genetic models. Our findings strongly encourage further lead optimization efforts for isoform-selective NOX inhibitors and clinical development and provide an experimental alternative when genetic validation of a NOX isoform is not an option.
Graphical abstract
Desiccation-induced changes in recombination rate and crossover interference inDrosophila melanogaster: evidence for fitness-dependent plasticity
Authors: Aggarwal Dau Dayal , Rybnikov Sviatoslav R. , Cohen Irit , Frenkel Zeev , Rashkovetsky Eugenia , Michalak Pawel , Korol Abraham B. 
Published: August 2018

ABSTRACTMeiotic recombination is evolutionarily ambiguous, as being associated with both benefits and costs to its bearers, with the resultant dependent on a variety of conditions. While existing theoretical models explain the emergence and maintenance of recombination, some of its essential features remain underexplored. Here we focus on one such feature, recombination plasticity, and test whether recombination response to stress is fitness-dependent. We compare desiccation stress effects on recombination rate and crossover interference in chromosome 3 between desiccation-sensitive and desiccation-tolerantDrosophilalines. We show that relative to desiccation-tolerant genotypes, desiccation-sensitive genotypes exhibit a significant segment-specific increase in single- and double-crossover frequencies across the pericentromeric region of chromosome 3. Significant changes (relaxation) in crossover interference were found for the interval pairs flanking the centromere and extending to the left arm of the chromosome. These results indicate that desiccation is a recombinogenic factor and that desiccation-induced changes in both recombination rate and crossover interference are fitness-dependent, with a tendency of less fitted individuals to produce more variable progeny. Such a dependence may play an important role in the regulation of genetic variation in populations experiencing environmental challenges.
Machine learning identifies the immunological signature of Juvenile Idiopathic Arthritis
Authors: Van Nieuwenhove Erika , Lagou Vasiliki , Van Eyck Lien , Dooley James , Bodenhofer Ulrich , Goris An , Humblet-Baron Stephanie , Wouters Carine , Liston Adrian 
Published: August 2018

AbstractJuvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, with a strongly debated pathophysiological origin. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. Here we profiled the adaptive immune system of 85 JIA patients and 43 age-matched controls, identifying immunological changes unique to JIA and others common across a broad spectrum of childhood inflammatory diseases. The JIA immune signature was shared between clinically distinct subsets, but was accentuated in the systemic JIA patients and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and JIA patients, machine learning analysis of the dataset proved capable of diagnosis of JIA patients with ~90% accuracy. These results pave the way for large-scale longitudinal studies of JIA, where machine learning could be used to predict immune signatures that correspond to treatment response group.
Skin Lesion Segmentation with Improved C-UNet Networks
Authors: Jiang Hongda , Rong Ruichen , Wu Junyan , Li Xiaoxiao , Dong Xu , Chen Eric Z 
Published: August 2018

Abstract—This paper proposes an innovative method for Part1, skin lesion segmentation of the ISIC 2018 Challenge. Our network C-UNet is based on UNet network, we combined several methods on this basic network which made some improvements on Jaccard Index ultimately, our method yield an average Jaccard Index of 0.77 on the On-line validation dataset.
Synapse-selective control of cortical maturation and plasticity engages an interneuron-autonomous synaptic switch
Authors: Ribic Adema , Crair Michael C. , Biederer Thomas 
Published: August 2018

HighlightsThe synaptogenic molecule SynCAM 1 is selectively regulated by visual experienceSynCAM 1 controls thalamic input onto cortical Parvalbumin (PV+) interneuronsPV+-specific knockdown of SynCAM 1 arrests maturation of cortical inhibitionThalamic excitation onto PV+ interneurons is essential for critical period closureeTOC BlurbRibic et al. show that network plasticity in both young and adult cortex is restricted by the synapse organizing molecule SynCAM 1. On a cellular level, it functions in Parvalbumin-positive interneurons to recruit thalamocortical terminals. This controls the maturation of inhibitory drive and restricts plasticity in the cortex. These results reveal the synaptic locus of cortical plasticity and identify the first cell-autonomous synaptic factor for closure of cortical critical periods.SummaryBrain plasticity peaks early in life and tapers in adulthood. This is exemplified in the primary visual cortex, where brief loss of vision to one eye abrogates cortical responses to inputs from that eye during the critical period, but not in adulthood. The synaptic locus of critical period plasticity and the cell-autonomous synaptic factors timing these periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits visual cortex plasticity. SynCAM 1 selectively controls the number of excitatory thalamocortical (TC) inputs onto Parvalbumin (PV+) interneurons and loss of SynCAM 1 in turn impairs the maturation of TC-driven feed-forward inhibition. SynCAM 1 acts in cortical PV+ interneurons to perform these functions and its PV+-specific knockdown prevents the age-related plasticity decline. These results identify a synapse type-specific, cell-autonomous mechanism that governs circuit maturation and closes the visual critical period.
The allergic response mediated by fire ant venom proteins
Authors: Daniel Zamith-Miranda , Fox Eduardo G. P. , Monteiro Ana Paula , Gama Diogo , Poublan Luiz E. , de Araujo Almair Ferreira , Araujo Maria F. C. , Atella Georgia C. , Machado Ednildo A. , Diaz Bruno L. 
Published: August 2018

AbstractFire ants are widely studied, invasive and venomous arthropod pests. There is significant biomedical interest in immunotherapy against fire ant stings. However, mainly due to practical reasons, the physiological effects of envenomation has remained poorly characterized. The present study takes advantage of a recently-described venom protein extract to delineate the immunological pathways underlying the allergic reaction to fire ant venom toxins. Mice were injected with controlled doses of venom protein extract. Following sensitization and a second exposure, a marked footpad swelling was observed. Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteinsper secan lead to an allergic response, which casts a new light into the mechanism of action of these toxins.
Ancestry-dependent Enrichment of Deleterious Homozygotes in Runs of Homozygosity
Authors: Szpiech Zachary A. , Mak Angel C.Y. , White Marquitta J. , Hu Donglei , Eng Celeste , Burchard Esteban G. , Hernandez Ryan D. 
Published: August 2018

AbstractRuns of homozygosity (ROH) are important genomic features that manifest when an individual inherits two haplotypes that are identical-by-descent. Their length distributions are informative about population history, and their genomic locations are useful for mapping recessive loci contributing to both Mendelian and complex disease risk. We have previously shown that ROH, and especially long ROH that are likely the result of recent parental relatedness, are enriched for homozygous deleterious coding variation in a worldwide sample of outbred individuals. However, the distribution of ROH in admixed populations and their relationship to deleterious homozygous genotypes is understudied. Here we analyze whole genome sequencing data from 1,441 individuals from self-identified African American, Puerto Rican, and Mexican American populations. These populations are three-way admixed between European, African, and Native American ancestries and provide an opportunity to study the distribution of deleterious alleles partitioned by local ancestry and ROH. We re-capitulate previous findings that long ROH are enriched for deleterious variation genome-wide. We then partition by local ancestry and show that deleterious homozygotes arise at a higher rate when ROH overlap African ancestry segments than when they overlap European or Native American ancestry segments of the genome. These results suggest that, while ROH on any haplotype background are associated with an inflation of deleterious homozygous variation, African haplotype backgrounds may play a particularly important role in the genetic architecture of complex diseases for admixed individuals, highlighting the need for further study of these populations.
Women’s roles in women’s career advancement: what do women expect of each other?
Authors: O’Neil Deborah A. , Brooks Margaret E. , Hopkins Margaret M. 
Published: August 2018

PurposeThe purpose of this paper is to better understand women’s working relationships and career support behaviors, by investigating expectations women have of other women regarding senior women’s roles in (and motivations for) helping junior women succeed, and junior women’s engagement in their own career advancement behaviors.Design/methodology/approachThe authors surveyed self- and other-reports of senior women’s engagement in career assistance behaviors on behalf of junior women colleagues, and junior women’s engagement in their own career advancement behaviors. One sample of respondents indicated to what extent they believed senior women did engage in career assistance toward junior women, and to what extent they believed junior women did engage in career advancement. Another sample indicated to what extent they believed senior women should engage in career assistance, and to what extent they believed junior women should engage in their own career advancement.FindingsResults suggest a disconnect between the expectations and perceptions junior and senior women have of each other. Junior women expect senior women to engage in career assistance behaviors to a greater degree than they believe senior women are engaging in such behaviors, and junior women think they are doing more to advance their careers than senior women are expecting them to do. The authors examine individual and organizational implications of these unmet expectations and perception mismatches.Originality/valueWomen-to-women working relationships are under-studied, and typically viewed in either/or terms – good or bad. The findings provide a more nuanced understanding of women’s perceptions and expectations and offer suggestions for how women can influence female career advancement.
Car model reconstruction from images through character line recognition
Authors: Wang Bo , Giannini Franca , Monti Marina , Li BaoJun , Hu Ping , Liang JiCai 
Published: August 2018

Purpose
This paper aims to automatically derive a 2D parametric model of the main characteristic lines of a car from images, blueprints or hand-made sketches of its side view. Then this model can be used for the further computer-aided design manipulation starting from images of the side view of a car.

Design/methodology/approach
The method combines different image edge detection techniques and edge removal processes with optimization techniques according to local and global constraints specific of the single curves to automatically construct a precise parametric model of the main character lines of a car from images. First, process the car image to compute the most important curves and then warp a car template model to match its feature points and curves with the ones detected in the image.

Findings
The paper provides method to construct parametric model from an image using maximum cover ratio to the edge points obtained by state-of-the-art edge detection algorithms. A feature points’ organization mechanism produces quadric curves to express feature curves of a product.

Research limitations/implications
The robustness of the presented method depends on the completeness of edge detection results and the accuracy of some key points’ registration result, so if the image is not good, the result cannot be trusted. Only side-view is considered in this paper. Additional limits in the process regard the side view verification: pictures of the front or rear view can be wrongly classified as lateral ones when they contain round lights.

Practical implications
This program enables designers to convert the image to geometric parametric model directly.

Originality/value
The method is applicable to shaded pictures, sketches and blue prints of the side view of a car. It can process a database of car images in a batch mode or a specific picture on user demand. The method classifies the cars to different categories: SUV/Wagon/Hatchback, sedan, city and coupe. The authors obtain good results for every category.
Hospital service quality – patient preferences – a discrete choice experiment
Authors: Bahrampour Mina , Bahrampour Abbas , Amiresmaili Mohammadreza , Barouni Mohsen 
Published: August 2018

PurposeHigh quality healthcare is important to all patients. If healthcare is felt to be high quality, then patients will be satisfied, and the relationship between patients and healthcare providers will improve. Patient satisfaction is among the most commonly used service quality indicators; however, it is not fully known which factors influence satisfaction. Therefore, it is necessary to pay attention to the elements that affect both healthcare quality and patient satisfaction. Nowadays, several methods are used in health economics to assess patient preferences, prioritize them and help health policy makers improve services. Discrete choice experiment (DCE) is one method that is useful to elicit patient preferences regarding healthcare services. The purpose of this paper is to apply DCE and elicit patient preferences in medical centers to rank certain healthcare quality factors.Design/methodology/approachThe descriptive, analytical study used a cross-sectional questionnaire that the authors developed. In total, 12 scenarios were chosen after applying fractional factorials. The questionnaire was completed by patients who were admitted to Kerman General Teaching Hospitals, South-East Iran in 2015. Patient preferences were identified by calculating the characteristics’ marginal effects and prioritizing them. The generalized estimation equation (GEE) model was used to determine attribute effects on patient preferences.FindingsIn total, 167 patients completed the questionnaire. Prioritizing the attributes showed that “physical examination” was the most important attribute. Other key features included “cleanliness,” “training after discharging,” “medical staff attention,” “waiting for admission” and “staff attitude.” All attributes were statistically significant (p<0.05) except staff behavior. No demographic characteristic was significant.Practical implicationsTo increase hospital patient satisfaction, health policy makers should develop programs to enhance healthcare quality and hospital safety by increasing physical examination quality and other services.Originality/valueTo estimate DCE independent variables, logistic regression models are usually used. The authors used the GEE model to estimate discrete choice experiment owing the explanatory variables’ dependency.
High-cost sharing policies and non-urgent emergency department visits
Authors: Xin Haichang 
Published: August 2018

Purpose
The purpose of this paper is to examine whether high-cost-sharing ambulatory care policies affect non-urgent emergency department (ED) care utilization differently among individuals with and without chronic conditions.

Design/methodology/approach
This retrospective cohort study used 2010–2011 US Medical Expenditure Panel Survey data. Difference-in-difference methods, multivariate logit model and survey procedures were employed. Time lag effect was used to address endogeneity concerns.

Findings
The sample included 4,347 individuals. Difference in non-urgent ED visits log odds between high- and low-cost-sharing policies was not significantly different between chronically ill and non-chronically ill individuals (β=−0.48, p=0.42). Sensitivity analysis with 15 and 25 percent cost-sharing levels also generated consistent insignificant results (p=0.33 and p=0.31, respectively). Ambulatory care incidence rates were not significantly different between high- and low-cost-sharing groups among chronically ill people (incidence rate ratio=0.849, p=0.069).

Practical implications
High-cost-sharing ambulatory care policies were not associated with increased non-urgent ED care utilization among chronically ill and healthy people. The chronically ill patients may have retained sizable ambulatory care that was necessary to maintain their health. Health plans or employers may consider low-level cost-sharing policies for ambulatory care among chronically ill enrollees or employees.

Originality/value
Findings contribute to insurance benefit design; i.e., whether high-cost-sharing ambulatory care policies should be implemented among chronically ill enrollees to maintain their health and save costs for health plans.
Case study illustrations of a psychological treatment pathway in a secure intellectual disability service
Authors: Hickman Gareth , Thrift Su , Taylor Chénelle 
Published: August 2018

Purpose
The purpose of this paper is to describe in detail the treatment pathway utilised in a male medium and low secure intellectual disability (ID) service. Over the preceding five years, service users have followed the outlined treatment pathway. The current paper offers case study material to illustrate the care pathway.

Design/methodology/approach
The treatment pathway is described and two case examples are provided, illustrating participation in the pathway. Evaluative data are provided on length of hospitalisation, direction of pathway at discharge and risk reduction as assessed by the HCR-20, SVR-20 and HONOS Secure measures.

Findings
The case examples provided document the assessment and treatment of two male offenders with ID, outlining their treatment pathways, subsequent reductions in assessed risk and their successful community discharge.

Originality/value
A comprehensive treatment pathway is outlined together with the theoretical rationale, with illustrative case examples.
Age-based maintenance for a fleet of haul trucks
Authors: Chaowasakoo Patarawan , Seppälä Heikki , Koivo Heikki 
Published: August 2018

Purpose
The most costly part in an open-pit mine is the transportation of material out of the mine. The efficiency of the truck-and-shovel fleet plays a major role in cost control. The paper aims to discuss these issues.

Design/methodology/approach
The truck dispatching simulation model with consideration of age-based maintenance is proposed.

Findings
This paper underlines an impact of truck dispatching decisions and reveals remarkable differences in the total production under different approaches of operational availability. Additionally, the simulated results introduce an effective scheduled maintenance for different truck age levels.

Originality/value
The approach is based on a case study taking into account the stochastic equipment behavior and environment in a real open-pit mine. This approach can be used more generally in situations in which truck fleets are used to transport material.
Intra-organizational communication and its consequences
Authors: Suzuki Manami , Ando Naoki , Nishikawa Hidehiko 
Published: August 2018

Purpose
The purpose of this paper is to address intra-organizational communication between parent firms and foreign subsidiaries and examine how such communication effectively facilitates knowledge sharing between parent firms and their subsidiaries.

Design/methodology/approach
This study approaches the relationship between intra-organizational communication and the effectiveness of knowledge sharing from the viewpoint of foreign subsidiaries. The data have been collected from local managers in subsidiaries operating in Japan using a questionnaire survey. The hypotheses are tested by employing a robust regression model.

Findings
This study finds that intra-organizational communication between parent firms and foreign subsidiaries is positively associated with the effectiveness of knowledge sharing. The benefits from intra-organizational communication are greater for service firms than for manufacturing firms. Subsidiaries established through acquisition are found to enjoy a greater positive effect from intra-organizational communication than those established through greenfield investment.

Practical implications
The results of this study suggest that multinational corporations should facilitate intensive intra-organizational communication for knowledge sharing that can lead to the effectiveness of foreign subsidiaries. In particular, service firms should appreciate the value of communication. This study also indicates that foreign subsidiaries established through acquisition should promote communication with their parent firms for successful knowledge sharing.

Originality/value
This study demonstrates that the effect of intra-organizational communication on knowledge sharing differs among industries and among entry modes. This is the initial step to further investigations on the industry and the entry strategy effects of intra-organizational communication.