bluuebunny/crossref_metadata_2025 huggingface dataset:
MLDSP-GUI: An alignment-free standalone tool with an interactive graphical user interface for DNA sequence comparison and analysis
Authors: Randhawa Gurjit S. , Hill Kathleen A. , Kari Lila
Published: September 2019

MLDSP-GUI (Machine Learning with Digital Signal Processing) is an open-source, alignment-free, ultrafast, computationally lightweight, standalone software tool with an interactive Graphical User Interface (GUI) for comparison and analysis of DNA sequences. MLDSP-GUI is a general-purpose tool that can be used for a variety of applications such as taxonomic classification, disease classification, virus subtype classification, evolutionary analyses, among others.

Availability

MLDSP-GUI is open-source, cross-platform compatible, and is available under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/). The executable and dataset files are available at https://sourceforge.net/projects/mldsp-gui/.

Contact

grandha8@uwo.ca

Supplementary information

Supplementary data are available online.
NIHBA: A Network Interdiction Approach with Hybrid Benders Algorithm for Strain Design
Authors: Jiang Shouyong , Wang Yong , Kaiser Marcus , Krasnogor Natalio
Published: September 2019

Flux balance analysis (FBA) based bilevel optimisation has been a great success in redesigning metabolic networks for biochemical overproduction. To date, many computational approaches have been developed to solve the resulting bilevel optimisation problems. However, most of them are of limited use due to biased optimality principle, poor scalability with the size of metabolic networks, potential numeric issues, or low quantity of design solutions in a single run. In this work, we have employed a network interdiction model free of growth optimality assumptions, a special case of bilevel optimisation, for computational strain design and have developed a hybrid Benders algorithm (HBA) that deals with complicating binary variables in the model, thereby achieving high efficiency without numeric issues in search of best design strategies. More importantly, HBA can list solutions that meet users’ production requirements during the search, making it possible to obtain numerous design strategies at a small runtime overhead (typically ∼1 hour).
Membrane composition influences the conformation and function of the dopamine transporter in vivo
Authors: Fong Wendy M. , Erreger Kevin , Choi Se Joon , Reddy India , Johnson Christopher W. , Mosharov Eugene V. , Javitch Jonathan A. , Yamamoto Ai
Published: September 2019

The biophysical and biochemical properties of membrane lipids can alter the conformation and function of membrane-spanning proteins, yet the specific, physiological consequence in vivo of changing the membrane milieu for a specific protein has been rarely investigated. Using various genetic approaches to eliminate expression of the membrane-associated protein Flotillin-1, we have found that the lipid environment of the dopamine transporter (DAT) is necessary for mice to respond to amphetamine but not cocaine, because the localization of DAT to cholesterol-rich membranes is required for a DAT conformation that is essential for reverse transport of dopamine. Furthermore, a conditional rather than constitutive loss-of-function approach was necessary to reveal this phenotype, indicating a broader role for membrane-protein interactions that are modulated by Flotillin-1. Taken together, these findings demonstrate how interaction of a transmembrane protein with its membrane environment can regulate distinct events in the vertebrate brain that give rise to specific behavioral outcomes.
Uncovering the dynamic mechanisms of thePseudomonas aeruginosaquorum sensing and virulence networks using Boolean modelling
Authors: Banzhaf Manuel , Resendis-Antonio Osbaldo , Zepeda-Mendoza M. Lisandra
Published: September 2019

Introduction

Pseudomonas aeruginosais an opportunistic pathogen with an extraordinary metabolic adaptability and a large repertoire of virulence factors that allow it to cause acute and chronic infections. Treatment ofP. aeruginosainfections often fail due to its antibiotic resistance mechanisms, thus novel strategies aim at targeting virulence factors instead of growth-related features. However, there is currently not a clear understanding of the dynamic nature inherent to the wiring of its virulence networks.

Results

In this study, we manually reconstructed the signalling and transcriptional regulatory networks of 12 acute (incl. pyocin and elastase) and 8 chronic virulence factors (incl. biofilm), and the 4 quorum sensing (QS) systems ofP. aeruginosa.Using Boolean modelling (BM), we unveiled the important roles that stochasticity and node connectivity play in the networks’ inherent dynamicity and robustness. We showed that both the static interactions, as well as the time when the interactions take place, are important features in the QS network. In addition, we found that the virulence factors of the acute networks are under strict repression, or under an activation that is non-strict or oscillatory, while the chronic networks favour the repression of the virulence factor, with only moderate activation under certain conditions.

Conclusion

In conclusion, ourin silico-modelling framework provided us with a system-level view of theP. aeruginosavirulence and QS networks to gain new insights into the various mechanisms that support its pathogenicity and response to stressors targeting these networks. Thus, we suggest that BM provides an invaluable tool to guide the design of new treatments againstP. aeruginosa.
Rapid phylogenetic analysis of African swine fever virus from metagenomic sequences
Authors: Xiong Dongyan , Zhang Xiaoxu , Yu Junping , Wei Hongping
Published: September 2019

African swine fever virus (ASFV) has devastating impacts on swine health and the world economy. Rapid and accurate phylogenetic analysis of ASFV causing outbreaks is important to reveal diversity and evolutionary of ASFV. Because it is time-consuming and needs biosafety laboratories to isolate ASFV, here we present a new way to perform rapid genome-wide phylogenetic analysis of ASFV using an allele calling based on gene by gene approach directly from genome drafts assembled from metagenomic sequences. Using open-accessed chewBBACA software, 41 publicly available ASFV genomes were analyzed to optimize the parameters and find the alleles. Alleles as many as 94 were found for building the phylogenetic trees, which covered more than 56% of the whole genome. Based on the alleles, current ASFV isolates could be divided into two major clades and a few subclades. Then the method is used to analyze two ASFV genome drafts assembled from two metagenomic sequences of a swine whole blood and a swine spleen tissue collected in Wuhan, China. It shows that the two ASFV genomes showed highest similarity to that of Pig/HLJ/2018 strain and DB/LN/2018 strain, which isolated recently in China. This proved that the ASFV in Wuhan originate from the same source causing the earlier outbreaks in Helongjiang and Liaoning province of China. This method makes it possible to analyze phylogenetic analysis of ASFV draft genomes flexibly without the need of ASFV isolation. Furthermore, because it is based on Allele calling, the ASFV-specific genetic markers found could be translated into clinical diagnostics or can be used broadly to identify conserved putative therapeutic candidates.
Resolving sub-clonal heterogeneity within cell-line growths by single cell sequencing genomic DNA
Authors: Velazquez-Villarreal Enrique I. , Maheshwari Shamoni , Sorenson Jon , Fiddes Ian T. , Kumar Vijay , Yin Yifeng , Webb Michelle , Catalanotti Claudia , Grigorova Mira , Edwards Paul A. , Carpten John D. , Craig David W.
Published: September 2019

We performed shallow single-cell sequencing of genomic DNA across 1,475 cells from a well-studied cell-line, COLO829, to resolve overall tumor complexity and clonality. This melanoma tumor-line has been previously characterized by multiple technologies and provides a benchmark for evaluating somatic alterations, though has exhibited conflicting and indeterminate copy number states. We identified at least four major sub-clones by discriminant analysis of principal components (DAPC) of single cell copy number data. Break-point and loss of heterozygosity (LOH) analysis of aggregated data from sub-clones revealed a complex rearrangement of chromosomes 1, 10 and 18 that was maintained in all but two sub-clones. Likewise, two of the sub-clones were distinguished by loss of 1 copy of chromosome 8. Re-analysis of previous spectral karyotyping data and bulk sequencing data recapitulated these sub-clone hallmark features and explains why the original bulk sequencing experiments generated conflicting copy number results. Overall, our results demonstrate how shallow copy number profiling together with clustering analysis of single cell sequencing can uncover significant hidden insights even in well studied cell-lines.
Target Gene Notebook: Connecting genetics and drug discovery
Authors: Reeve Mary Pat , Kirby Andrew , Wierzbowski Jamey , Daly Mark , Hutz Janna
Published: September 2019

Target Gene Notebook was developed to enable more efficient linking of genetic associations to functional biological information. This process is essential to translating genetic insights into therapeutic hypotheses and, eventually, drug discovery. Although many public databases provide access to unfiltered genome annotations and genetic results, there was no existing tool to maintain group curation and integration with proprietary experimental data. We provide Target Gene Notebook freely via the MIT open-source license for the purposes of assisting therapeutic target evaluation and the creation of durable institutional and public knowledge bases. Implemented as a Java backend serving mainly Javascript content derived from gene-specific SQLite databases, Target Gene Notebook enables automated access to the most widely used sources of genetic association, expression and protein QTL data, provides intuitive interfaces to credible set and colocalization information, and enables comprehensive literature review and annotation by multiple users simultaneously to create a consistent target knowledgebase within an organization or across a consortium. TargetGeneNotebook is freely available from GitHub https://github.com/targetgenenotebook/tgn.git under the MIT open-source end-user license agreement and a live version of the interface is provided at http://tgn.broadinstitute.org/.
The nasopalatine ducts of the mouse conserve a functional role in pheromone signaling
Authors: Levy Dana Rubi , Sofer Yizhak , Brumfeld Vlad , Zilkha Noga , Kimchi Tali
Published: September 2019

Social communication in most mammals is mediated by chemosignals, collected by active sniffing and detected mainly by the vomeronasal organ (VNO). In reptiles, however, chemosignals are delivered to the VNO through the oral cavity via the nasopalatine ducts (NPDs) – two direct passageways connecting the nasal and the oral cavities. While the structure of the NPDs is highly conserved across terrestrial vertebrate, it is unclear whether they retain any functional role in mammalian chemosignaling. Here we assess the role of the mouse NPDs in VNO function and associated behavioral responses. By reconstructing the 3D morphological architecture of the mouse snout using micro CT, we identify a net of micro-tunnels forming a direct passageway connecting the NPDs to the nasal cavity and the vomeronasal organ. We further demonstrate that physical obstruction of the NPDs destructs VNO clearance, and reduces chemosignaling-evoked neuronal activation in the medial amygdala. Obstruction of the NPDs also impaired the innate male preference for female chemosignals as well as social approach behavior, indicating the crucial role of the murine nasopalatine ducts in pheromone sensing.
Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation
Authors: Jafari Mehrnoosh , Schumacher Adrian-Minh , Snaidero Nicolas , Neziraj Tradite , Ullrich Gavilanes Emily M. , Jürgens Tanja , Flórez Weidinger Juan Daniel , Schmidt Stephanie S. , Beltrán Eduardo , Hagan Nellwyn , Woodworth Lisa , Ofengeim Dimitry , Gans Joseph , Wolf Fred , Kreutzfeldt Mario , Portugues Ruben , Merkler Doron , Misgeld Thomas , Kerschensteiner Martin
Published: September 2019

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structuralin vivoimaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread but transient loss of dendritic spines. Spines destined for removal show a local calcium accumulation and are subsequently removed by invading macrophages and activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy.

HIGHLIGHTS

Widespread, but transient loss of synapses in inflammatory lesions and beyond

Reversible impairment of neuronal firing and circuit function in the inflamed cortex

Calcium dyshomeostasis of single spines precedes swift synapse loss

Phagocyte-mediated spine pruning as targetable mechanism of synapse loss
Hierarchical structure is employed by humans during visual motion perception
Authors: Bill Johannes , Pailian Hrag , Gershman Samuel J , Drugowitsch Jan
Published: September 2019

In the real world, complex dynamic scenes often arise from the composition of simpler parts. The visual system exploits this structure by hierarchically decomposing dynamic scenes: when we see a person walking on a train or an animal running in a herd, we recognize the individual’s movement as nested within a reference frame that is itself moving. Despite its ubiquity, surprisingly little is understood about the computations underlying hierarchical motion perception. To address this gap, we developed a novel class of stimuli that grant tight control over statistical relations among object velocities in dynamic scenes. We first demonstrate that structured motion stimuli benefit human multiple object tracking performance. Computational analysis revealed that the performance gain is best explained by human participants making use of motion relations during tracking. A second experiment, using a motion prediction task, reinforced this conclusion and provided fine-grained information about how the visual system flexibly exploits motion structure.
The ALBA RNA-binding proteins function redundantly to promote growth and flowering in Arabidopsis
Authors: Wang Naiqi , Jalajakumari Meachery , Miller Thomas , Asadi Mohsen , Millar Anthony A
Published: September 2019

RNA-binding proteins (RBPs) are critical regulators of gene expression, but have been poorly studied relative to other classes of gene regulators. Recently, mRNA-interactome capture identified many Arabidopsis RBPs of unknown function, including a family of ALBA domain containing proteins. Arabidopsis has three short-form ALBA homologues (ALBA1-3) and three long-form ALBA homologues (ALBA4-6), both of which are conserved throughout the plant kingdom. Despite this ancient origin, ALBA-GUS translational fusions of ALBA1, ALBA2, ALBA4, and ALBA5 had indistinguishable expression patterns, all being preferentially expressed in young, rapidly dividing tissues. Likewise, all four ALBA proteins had indistinguishable ALBA-GFP subcellular localizations in roots, all being preferentially located to the cytoplasm, consistent with being mRNA-binding. Genetic analysis demonstrated redundancy within the long-form ALBA family members; in contrast to single alba mutants that all appeared wild-type, a triple alba456 mutant had slower rosette growth and a strong delay in flowering-time. RNA-sequencing found most differentially expressed genes in alba456 were related to metabolism, not development. Additionally, changes to the alba456 transcriptome were subtle, suggesting ALBA4-6 participates in a process that does not strongly affect transcriptome composition. Together, our findings demonstrate that ALBA protein function is highly redundant, and is essential for proper growth and flowering in Arabidopsis.

Highlight

The RNA-binding ALBA proteins have indistinguishable expression patterns and subcellular localizations in Arabidopsis, acting redundantly to promote growth and flowering via a mechanism that does not strongly affect transcriptome composition.
Employment exclusion in Spain: a territorial approach
Authors: Lafuente-Lechuga Matilde , Faura-Martínez Ursula , García-Luque Olga
Published: September 2019

Purpose

This paper studies social inequality in the vital field of employment in Spain during the crisis period 2009-2014.

Design/methodology/approach

Factor analysis is used to build a synthetic index of employment exclusion. The starting information matrix collects data from a wide set of employment variables for all 17 Spanish autonomous communities and the autonomous cities of Ceuta and Melilla. Based on this information, four factors are extracted which explain employment exclusion in different situations of vulnerability, such as unemployment, temporality, poverty or low pay.

Findings

In the territorial ranking, Madrid, Basque Country, Aragon and Catalonia show the lowest risk of employment exclusion, whereas Ceuta, Andalusia, Extremadura and Canary Islands show the highest ones.

Originality/value

The main value of this research is that it confirms the need for coordination of public policies in order to foster social and territorial cohesion in Spain.
In flight again with wings that were once broken; effects of post-traumatic growth and personal resources on burnout recovery
Authors: Semeijn Judith , Van Ruysseveldt Joris , Vonk Greet , van Vuuren Tinka
Published: September 2019

Purpose

Adequate recovery from burnout is important to understand. The purpose of this paper is to investigate whether post-traumatic growth (PTG) contributes to higher engagement and reduced symptoms of burnout and whether this process is mediated by personal resources.

Design/methodology/approach

In a cross-sectional survey, 166 Dutch workers who had fully recovered from burnout were questioned on their level of PTG, their personal resources (optimism, resilience and self-efficacy), and their levels of engagement and burnout.

Findings

Fully recovered workers scored somewhat higher on current burnout level, but did not differ from norm group workers in their engagement level. Moreover, PTG appeared to positively affect both higher engagement and lower burnout levels, which is fully mediated by personal resources.

Research limitations/implications

Post-traumatic growth (PTG) impacts on engagement and burnout levels amongst workers who have recovered from burnout by enhancing personal resources. The role of personal resources and the impact of PTG on engagement and burnout complaints following (recovery from) burnout deserve further investigation.

Practical implications

Management can support workers who have (recovered from a) burnout, by being aware of their (higher) engagement, and facilitate the enhancement of PTG and personal resources.

Originality/value

This study is one of the first to study the role of PTG after (recovery from) burnout and reveals valuable findings for both research and practice.
Skills and knowledge management in higher education: how service learning can contribute to social entrepreneurial competence development
Authors: Halberstadt Jantje , Timm Jana-Michaela , Kraus Sascha , Gundolf Katherine
Published: September 2019

Purpose

The purpose of this paper is to elaborate on how service learning approaches are able to foster social entrepreneurship competences. The aim of the paper is to formulate a framework of key competences for social entrepreneurship and to give first insights in how service learning actually has an impact on change in students’ set of competences.

Design/methodology/approach

This paper uses a mixed-methods approach combining qualitative data collectionmethods of learning diaries of the students and semi-structured interviews, including 40 master’s students studying at a German university in interdisciplinary learning settings and five instructors from the same universities. Analysis was carried out by means of qualitative content analysis.

Findings

This paper provides empirical insights about the competences that are being fostered by service learning. From these, a framework for social entrepreneurship competences is being derived.

Research limitations/implications

The set of competences should be further investigated, as it was derived out of a small data set. Therefore, researchers are encouraged to use the set of competences for social entrepreneurship as a basis for future research and on a longer-term perspective, which lead to substantial implications for educational practice.

Practical implications

This paper includes implications for new perspectives on service learning in the light of the development of a relevant framework for social entrepreneurship competence, having significant implications for educational practice in social entrepreneurship education.

Originality/value

With this paper, the authors fulfill the need of a framework of social entrepreneurship competences that serves as a foundation for educational practice and further research in the context of service learning and beyond.
Mean reversion in corporate leverage: evidence from India
Authors: Chauhan Gaurav S. , Banerjee Pradip
Published: September 2019

Purpose

Recent papers on target capital structure show that debt ratio seems to vary widely in space and time, implying that the functional specifications of target debt ratios are of little empirical use. Further, target behavior cannot be adjudged correctly using debt ratios, as they could revert due to mechanical reasons. The purpose of this paper is to develop an alternative testing strategy to test the target capital structure.

Design/methodology/approach

The authors make use of a major “shock” to the debt ratios as an event and think of a subsequent reversion as a movement toward a mean or target debt ratio. By doing this, the authors no longer need to identify target debt ratios as a function of firm-specific variables or any other rigid functional form.

Findings

Similar to the broad empirical evidence in developed economies, there is no perceptible and systematic mean reversion by Indian firms. However, unlike developed countries, proportionate usage of debt to finance firms’ marginal financing deficits is extensive; equity is used rather sparingly.

Research limitations/implications

The trade-off theory could be convincingly refuted at least for the emerging market of India. The paper here stimulated further research on finding reasons for specific financing behavior of emerging market firms.

Practical implications

The results show that the firms’ financing choices are not only depending on their own firm’s specific variables but also on the financial markets in which they operate.

Originality/value

This study attempts to assess mean reversion in debt ratios in a unique but reassuring manner. The results are confirmed by extensive calibration of the testing strategy using simulated data sets.
Occupational contact dermatitis in a manicurist
Authors: Nakagawa Michiyo , Hanada Miho , Amano Hiroo
Published: September 2019

We report a case of a manicurist who developed an allergic skin reaction to acrylates, manifested by itchy erythema, papules, vesicles and fissures on her hands, fingertips, forearm and eyelids. Patch tests showed positive reactions to three nail products used: ethylene glycol dimethacrylate, 2‐hydroxyethyl methacrylate, ethyl acrylate and 2‐hydroxyethyl acrylate in (meth)acrylate series. By using gel nail products, our patient became sensitized to 2‐hydroxyethyl methacrylate. We assume that this had been the trigger, leading to the occurrence of cross‐reactions between numerous acrylates including ethylene glycol dimethacrylate, ethyl acrylate and 2‐hydroxyethyl acrylate. When handling nail products, it is necessary to prevent airway sensitization, contact sensitization and cross‐reaction between various acrylates.
Association of rs3783641 single‐nucleotide polymorphism in GTP cyclohydrolase 1 gene with post‐herpetic neuralgia
Authors: Zheng Na‐Na , Zhang Ruo‐Chen , Yang Xiao‐Xiao , Zhong Lian‐Sheng
Published: September 2019

Post‐herpetic neuralgia (PHN) is a well‐established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate‐limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single‐nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high‐resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.
Energetics meets sexual conflict: The phenology of hibernation in Tasmanian echidnas
Authors: Nicol Stewart C. , Morrow Gemma E. , Harris Rachel L.
Published: September 2019

Echidnas are egg‐laying mammals found across Australia, and in Tasmania they hibernate, resulting in a most unusual mating system: males enter hibernation in late summer–early autumn and arouse in late autumn–early winter to mate, although females are still hibernating. Groups of males compete for matings and both males and females mate with multiple partners. Females that mate early return to hibernation even when pregnant, and males continue to mate with pregnant females. We asked to what extent can the bizarre combination of behavioural and physiological features that characterize reproduction of Tasmanian echidnas be attributed to their phylogeny, and how much is a consequence of their ecology?

To understand the interaction between energetics and the echidna mating system in determining the timing of echidna hibernation, we analysed data from an 18‐year study of a wild population of Tasmanian echidnas (Tachyglossus aculeatus setosus)

Males in best condition arouse earliest and seek out suitable females, and females that mate early in the mating season re‐enter hibernation while pregnant.

Competition between males drives early mating and while mating with males in the best condition could be advantageous for females and their young, egg‐laying in winter is potentially disadvantageous, and post‐mating hibernation by females is a means of delaying hatching of young until environmental conditions are more favourable. This post‐mating hibernation by females is usually disrupted by males which mate with them although they are already pregnant.

Comparisons with other echidna populations suggest that a decreased activity period due to hibernation has not increased male–male competition.

Similar competition between groups of males for access to females is seen in chlamyphorid armadillos, which occupy a similar ecological niche to echidnas.

A free Plain Language Summary can be found within the Supporting Information of this article.
The Chinese Social Credit System: A Model for Other Countries?
Authors: Mac Síthigh Daithí , Siems Mathias
Published: September 2019

Many countries know financial consumer credit ratings, and recent years have also seen a proliferation of rating systems in relation to online platforms and in the ‘sharing economy’, such as eBay, Uber and Airbnb. In the view of many Western observers, however, the emerging Chinese Social Credit System indicates a paradigm shift compared to these former rating systems as it aims for a comprehensive and uniform social rating based on penalty and award mechanisms. By contrast, this article suggests that the evolving forms of the Chinese system should be seen as a specific instance of a wider phenomenon. Thus, it develops a framework that compares different rating systems by reference to their drafters, users, aims, scoring systems, application, use of algorithms, enforcement and accountability; it identifies shortcomings of both low and high interventionist rating systems; and it discusses a range of regulatory approaches and emerging issues that law makers should consider.
Effect of Lower Third Molar Segmentations on Automated Tooth Development Staging using a Convolutional Neural Network
Authors: Merdietio Boedi Rizky , Banar Nikolay , De Tobel Jannick , Bertels Jeroen , Vandermeulen Dirk , Thevissen Patrick Werner
Published: September 2019

Staging third molar development is commonly used for age estimation in subadults. Automated developmental stage allocation to the mandibular left third molar in panoramic radiographs has been examined in a pilot study. This method used an AlexNet Deep Convolutional Neural Network (CNN) approach to stage lower left third molars, which had been selected by manually drawn bounding boxes around them. This method (bounding box AlexNet = BA) still contained parts of surrounding structures which may have affected the automated stage allocation performance. We hypothesize that segmenting only the third molar could further improve the automated stage allocation performance. Therefore, the current study aimed to determine and validate the effect of lower third molar segmentations on automated tooth development staging. Retrospectively, 400 panoramic radiographs were collected, processed and segmented in three ways: bounding box (BB), rough (RS), and full (FS) tooth segmentation. A DenseNet201 CNN was used for automated stage allocation. Automated staging results were compared with reference stages – allocated by human observers – overall and per stage. FS rendered the best results with a stage allocation accuracy of 0.61, a mean absolute difference of 0.53 stages and a Cohen's linear κ of 0.84. Misallocated stages were mostly neighboring stages, and DenseNet201 rendered better results than AlexNet by increasing the percentage of correctly allocated stages by 3% (BA compared to BB). FS increased the percentage of correctly allocated stages by 7% compared to BB. In conclusion, full tooth segmentation and a DenseNet CNN optimize automated dental stage allocation for age estimation.
Delayed complications following microwave ablation of lung tumours
Authors: Harvey James , Windsor Morgan N , Steinke Karin
Published: September 2019

The majority of complications following microwave ablation (MWA) of lung tumours are immediately evident, however, delayed complications do occasionally occur. The radiologist plays a major role in identifying and in guiding the management of these complications. This pictorial essay explores the imaging appejmironce of several potentially life‐threatening delayed complications of pulmonary MWA.
Leveraging Asia's Financial Hubs for the AIIB: Hong Kong and Singapore
Authors: Li Yu‐wai Vic
Published: September 2019

The Asian Infrastructure Investment Bank (AIIB) appeared at its inception to be a Beijing‐led multilateral development bank that is focused on the financing of mega infrastructure projects. The role for meaningful participation by offshore financial centers such as Hong Kong and Singapore was less defined. This article maps the growing role and influence of these two city‐states within the ongoing development of the AIIB. It analyzes the respective and distinct motivations of Hong Kong and Singapore as members in the AIIB, and assesses how each city is positioning itself to make unique contributions to the new multilateral development bank.
Brown marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae), detections in Western Sydney, New South Wales, Australia
Authors: Horwood Martin , Milnes Joshua M , Cooper W Rodney
Published: September 2019

Brown marmorated stink bug (BMSB), Halyomorpha halys Stål, 1855, is a polyphagous agricultural insect pest which causes serious production losses. BMSB also has human lifestyle impacts which arise from its habit of overwintering in homes. The invasiveness of BMSB and the harm it causes is making it a pest of increasing global importance. Over the past 30 years, the bug has spread from its native range in East Asia to North America and Europe. On November 2017 and January 2018, BMSBs were found at two Western Sydney locations in goods imported from northern Italy. While BMSB detections in imports are common in Australia, these encounters were significant because of sightings of bugs outside the infested premises, indicating possible spread into the local environment. Measures undertaken in Western Sydney to contain and eradicate BMSB included fumigation of infested goods, insecticide treatment of the warehouse site and surroundings and delimiting surveillance. Before commencing widespread surveillance, a vegetation survey was conducted to identify known host and potential BMSB host plants around the infested premises. ESRI Collector for ArcGIS™ was used to compile host plant location data which served as the basis for pheromone trap deployment and physical inspection. Surveillance continued until May 2018. No live BMSBs were detected. DNA analysis of dead BMSBs collected from infested goods discerned the presence of two different haplotypes (H): H1 (previously detected in North America, Europe and China) and H23 (North America and Japan).
A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves
Authors: Jagannathan V. , Drögemüller C. , Leeb T. ,   Dog Biomedical Variant Database Consortium (DBVDC)
Published: September 2019

The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have a minimum coverage of 10× and an average coverage of ~24×. In total, we identified 23 133 692 single‐nucleotide variants (SNVs) and 10 048 038 short indels, including 93% undescribed variants. On average, each individual dog genome carried ∼4.1 million single‐nucleotide and ~1.4 million short‐indel variants with respect to the reference genome assembly. About 2% of the variants were located in coding regions of annotated genes and loci. Variant effect classification showed 247 141 SNVs and 99 562 short indels having moderate or high impact on 11 267 protein‐coding genes. On average, each genome contained heterozygous loss‐of‐function variants in 30 potentially embryonic lethal genes and 97 genes associated with developmental disorders. More than 50 inherited disorders and traits have been unravelled using the DBVDC variant catalogue, enabling genetic testing for breeding and diagnostics. This resource of annotated variants and their corresponding genotype frequencies constitutes a highly useful tool for the identification of potential variants causative for rare inherited disorders in dogs.
Increasing the accuracy of genomic prediction in pure‐bred Limousin beef cattle by including cross‐bred Limousin data and accounting for an F94L variant in MSTN
Authors: Lee J. , Kim J.‐M. , Garrick D. J.
Published: September 2019

Explicitly fitting effects for major genes or QTL that account for a large percentage of variation in a whole genomic prediction model may increase prediction accuracy. This study compared approaches to account for a major effect of an F94L variant in the MSTN gene within the genomic prediction using bovine whole‐genomic SNP markers. Among the beef cattle breeds, Limousin have been known to have an F94L variant that is not present in Angus. The reference population in this study consisted of 3060 beef cattle including pure‐bred Limousin (PL), cross‐bred Limousin with Angus (LF) and pure‐bred Angus, genotyped using a BovineSNP50 BeadChip and directly for the MSTN‐F94L variant. We compared prediction accuracies in PL animals using the three datasets from only the PL population, admixed PL and LF (AL) or multibreed analysis using all of the PL, LF and Angus (MB) population according to four‐fold cross‐validation after K‐means clustering. The MSTN‐F94L variant was the most strongly associated with five traits (birth weight, calving ease direct, milk, weaning weight and yield grade) among the 13 measured traits in PL and AL populations. Fitting the MSTN‐F94L variant as a random effect, the genomic prediction accuracies for birth weight increased by 2.7% in PL, by 2.2% in AL and by 3.2% in MB. Prediction accuracies for five traits increased in the MB analysis. Fitting MSTN‐F94L as a fixed effect in PL, AL and MB analyses resulted in increased prediction accuracy in PL for eight traits. Prediction accuracies can be improved by including a causal variant in genomic evaluation compared with simply using whole‐genome SNP markers. Fitting the causal variant as a fixed effect along with markers fitted as random effects resulted in greater prediction accuracies for most traits. Causal variants should be genotyped along with SNP markers.
Plasma steroid hormone concentrations and their relationships in Suffolk ewes during gestation and parturition
Authors: Miura Hiroshi , Yamazaki Tatsuya , Kikuchi Motohiro , Sakaguchi Minoru
Published: September 2019

In this study, we measured plasma concentrations of progesterone, pregnenolone, estradiol, estrone, estrone sulfate, and cortisol and analyzed the correlations between these hormones during gestation in 13 Suffolk ewes, the main breed in Japan. Progesterone increased during gestation and decreased a few days before parturition; however, this pattern was different in samples with high progesterone concentrations (P4 spike samples). This P4 spike was associated with a high pregnenolone concentration. Apart from the P4 spike, the progesterone change was similar to that in other sheep breeds. Pregnenolone increased during gestation and decreased after parturition. A significant correlation between progesterone and pregnenolone was observed a few days before parturition. Estrone sulfate and estradiol concentrations increased during gestation, but estrone did not. They increased shortly before parturition, and then decreased immediately after parturition. At parturition, the correlation between estrone and estrone sulfate was significantly stronger. Moreover, a strong correlation between estrone sulfate and estradiol was observed after parturition. Cortisol did not change during gestation and increased shortly before parturition. The results showed steroid hormone dynamics in normal pregnant Suffolk ewes, which were mostly in line with those of other sheep breeds. It should be noted that high progesterone concentrations altered the typical patterns.
Corneal refractive surgery combined with simultaneous corneal cross‐linking: Indications, protocols and clinical outcomes—A review
Authors: Ma Jiaonan , Wang Yan , Jhanji Vishal
Published: September 2019

Corneal refractive surgery is one of the most common approaches for correction of refractive errors. Combined corneal refractive surgery and corneal cross‐linking (CXL) has been proposed as a method to achieve better refractive stability and to prevent iatrogenic corneal ectasia. However, there are concerns regarding its indications, surgical safety, standardization of protocols and long‐term effect on corneal tissue. This review article aims to discuss the current knowledge and recent updates on combination of CXL and refractive surgery.
Enhanced gaze‐following behavior in Deaf infants of Deaf parents
Authors: Brooks Rechele , Singleton Jenny L. , Meltzoff Andrew N.
Published: September 2019

Gaze following plays a role in parent–infant communication and is a key mechanism by which infants acquire information about the world from social input. Gaze following in Deaf infants has been understudied. Twelve Deaf infants of Deaf parents (DoD) who had native exposure to American Sign Language (ASL) were gender‐matched and age‐matched (±7 days) to 60 spoken‐language hearing control infants. Results showed that the DoD infants had significantly higher gaze‐following scores than the hearing infants. We hypothesize that in the absence of auditory input, and with support from ASL‐fluent Deaf parents, infants become attuned to visual‐communicative signals from other people, which engenders increased gaze following. These findings underscore the need to revise the ‘deficit model’ of deafness. Deaf infants immersed in natural sign language from birth are better at understanding the signals and identifying the referential meaning of adults’ gaze behavior compared to hearing infants not exposed to sign language. Broader implications for theories of social‐cognitive development are discussed. A video abstract of this article can be viewed at https://youtu.be/QXCDK_CUmAI
Trends in antidiabetic drug utilization and expenditure in Denmark: A 22‐year nationwide study
Authors: Bang Camilla , Mortensen Martin B. , Lauridsen Kasper G. , Bruun Jens M.
Published: September 2019

Aims

To examine the nationwide trends in antidiabetic drug utilization and expenditure in Denmark over the past 22 years.

Methods

Data on antidiabetic use and expenditure from 1996 to 2017 were retrieved from the Register of Medicinal Product Statistics. Antidiabetic drug use is reported as defined daily dose (DDD) in total counts and per 1000 inhabitants/d. Expenditure is reported as volume sold in total counts per 1000 inhabitants and as annual mean expenditure.

Results

Throughout the study period, the total use of antidiabetic drugs increased from 16.4 to 55.8 DDDs per 1000 inhabitants/d, while total expenditure increased from €59 to €286 m. The introduction of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), dipeptidyl peptidase‐4 inhibitors and sodium‐glucose co‐transporter‐2 inhibitors has, since 2005, led to considerable variation in the proportional use of the different drug classes. Use of insulin and insulin analogues accounted for the majority of the cost of antidiabetic drugs, peaking at 75% in 2008; however, its proportional impact on overall antidiabetic drug expenditure decreased to ~44% in 2017. In contrast, a steep increase in GLP‐1RA expenditure was observed from 2010 to 2017, reaching an annual cost of €85 m (~29% of all antidiabetic expenditure).

Conclusion

Antidiabetic drug utilization and cost in Denmark has increased considerably over the last 22 years, in accordance with the increased incidence of type 2 diabetes and changes in treatment guidelines. The release of several novel antidiabetic drugs seems to be responsible for the increase in antidiabetic drug expenditure.
Congenital atresia of the left main coronary artery: Imaging feature in children
Authors: Luo Xianghong , Li Zhaojun
Published: September 2019

Congenital left main coronary atresia (LMCA) is a rare coronary anomaly associated with myocardial ischemia and sudden death. Echocardiography is an important tool for diagnosis of LMCA. The results of echocardiography and relevant clinical signs were retrospectively analyzed in 3 children with LMCA. Echocardiographic examination showed the signs of LMCA: in left coronary sinus no opening of left coronary artery (LCA), retrograded blood flow in LCA, abound blood flow in ventricular wall, and mild widen RCA.
Association of CD204+ macrophages with poor outcomes of malignant lymphomas not in remission treated by allogeneic HCT
Authors: Kawajiri Akihisa , Kitano Shigehisa , Maeshima Akiko Miyagi , Inamoto Yoshihiro , Tajima Kinuko , Takemura Tomonari , Tanaka Takashi , Ito Ayumu , Okinaka Keiji , Kurosawa Saiko , Kim Sung‐Won , Taniguchi Hirokazu , Ogawa Chitose , Izutsu Koji , Yamamoto Noboru , Fukuda Takahiro
Published: September 2019

Objective

CD204+ tumor‐associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT).

Methods

In a total of 81 patients who received allogeneic HCT for non‐remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high‐power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile).

Results

The B‐cell lymphoma proportion was higher in the low group, while T‐cell lymphoma and adult T‐cell leukemia proportions were higher in the high group. The 3‐year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3‐year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse.

Conclusions

CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas.
House dust mite‐treated PAR2 over‐expressor mouse: A novel model of atopic dermatitis
Authors: Smith Leila , Gatault Solene , Casals‐Diaz Laura , Kelly Pamela A. , Camerer Eric , Métais Charles , Knaus Ulla G. , Eissner Günther , Steinhoff Martin
Published: September 2019

Background

Atopic dermatitis (AD) is a complex skin disease involving causative effects from both intrinsic and extrinsic sources. Murine models of the disease often fall short in one of these components and, as a result, do not fully encapsulate these disease mechanisms.

Objective

We aimed to determine whether the protease‐activated receptor 2 over‐expressor mouse (PAR2OE) with topical house dust mite (HDM) application is a more comprehensive and clinically representative AD model.

Methods

Following HDM extract application to PAR2OE mice and controls, AD clinical scoring, itching behaviour, skin morphology and structure, barrier function, immune cell infiltration and inflammatory markers were assessed. Skin morphology was analysed using haematoxylin and eosin staining, and barrier function was assessed by transepidermal water loss measurements. Immune infiltrate was characterised by histological and immunofluorescence staining. Finally, an assessment of AD‐related gene expression was performed using quantitative RT‐PCR.

Results

PAR2OE mice treated with HDM displays all the characteristic clinical symptoms including erythema, dryness and oedema, skin morphology, itch and inflammation typically seen in patients with AD. There is a significant influx of mast cells (P < .01) and eosinophils (P < .0001) into the dermis of these mice. Furthermore, the PAR2OE + HDM mice exhibit similar expression patterns of key differentially expressed genes as seen in human AD.

Conclusion

The PAR2OE + HDM mouse presents with a classic AD pathophysiology and is a valuable model in terms of reproducibility and overall disease representation to study the condition and potential therapeutic approaches.