bluuebunny/crossref_metadata_2025 huggingface dataset:
KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype
Authors: Zhang Boyi , Long Qilai , Wu Shanshan , Song Shuling , Xu Qixia , Han Liu , Qian Min , Ren Xiaohui , Jiang Jing , Fu Qiang , Guo Jianming , Zhang Xiaoling , Chang Xing , Lam Eric W-F , Campisi Judith , Kirkland James L. , Sun Yu
Published: August 2020

Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation, including epigenetic decoration of chromatin structure and functional modulation of bioactive components. Here we report that expression of the histone H3-specific demethylase KDM4 is upregulated in human stromal cells upon cellular senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation are correlated with adverse survival of cancer patients post-chemotherapy. Global chromatin accessibility mappingviaATAC-seq and expression profiling through RNA-seq reveal extensive reorganization of chromosomes and spatiotemporal reprogramming of the transcriptomic landscape, events responsible for development of the senescence-associated secretory phenotype (SASP). Selectively targeting KDM4 dampens the SASP of senescent stromal cells and enhances the apoptotic index of cancer cells in the treatment-damaged tumor microenvironment (TME), together prolonging overall survival of experimental animals. Our study supports the dynamic change of H3K9/H3K36 methylation marks during cellular senescence, identifies an unusually permissive chromatin state, unmasks KDM4 as a key modulator of the SASP, and presents a novel therapeutic avenue to manipulate cellular senescence and curtail age-related pathologies.
Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice
Authors: Farrell M.R. , Esteban J.S.D. , Faget L. , Floresco S.B. , Hnasko T.S. , Mahler S.V.
Published: August 2020

Pursuing rewards while avoiding danger is an essential function of any nervous system. Here, we examine a new mechanism helping rats negotiate the balance between risk and reward when making high-stakes decisions. Specifically, we focus on GABA neurons within an emerging mesolimbic circuit nexus—the ventral pallidum (VP). These neurons play a distinct role from other VP neurons in simple motivated behaviors in mice, but their roles in more complex motivated behaviors is unknown. Here, we interrogate the behavioral functions of VPGABAneurons in male and female transgenic GAD1:Cre rats (and wildtype littermates), using a reversible chemogenetic inhibition approach. Employing a behavioral assay of risky decision making, and of the food-seeking and shock-avoidance components of this task, we show that engaging inhibitory Gi/osignaling specifically in VPGABAneurons suppresses motivation to pursue highly salient palatable foods, and possibly also motivation to avoid being shocked. In contrast, inhibiting these neurons did not affect seeking of low-value food, free consumption of palatable food, or unconditioned affective responses to shock. Accordingly, when rats considered whether to pursue food despite potential for shock in a risky decision-making task, inhibiting VPGABAneurons caused them to more readily select a small but safe reward over a large but dangerous one—an effect not seen in the absence of shock threat. Together, results indicate that VPGABAneurons are critical for high-stakes adaptive responding that is necessary for survival, but which may also malfunction in psychiatric disorders.

Significance Statement

In a dynamic world, it is essential to implement appropriate behaviors under circumstances involving rewards, threats, or both. Here, we demonstrate a crucial role for VPGABAneurons in high-stakes motivated behavior of several types. We show that this VPGABArole in motivation impacts decision making, as inhibiting these neurons yields a conservative, risk-averse strategy not seen when the task is performed without threat of shock. These new roles for VPGABAneurons in behavior may inform future strategies for treating addiction, and other disorders of maladaptive decision making.
SubFeat: Feature Subspacing Ensemble Classifier for Function Prediction of DNA, RNA and Protein Sequences
Authors: Haque H.M.Fazlul , Arifin Fariha , Adilina Sheikh , Rafsanjani Muhammod , Shatabda Swakkhar
Published: August 2020

The information of a cell is primarily contained in Deoxyribonucleic Acid (DNA). There is a flow of information of DNA to protein sequences via Ribonucleic acids (RNA) through transcription and translation. These entities are vital for the genetic process. Recent developments in epigenetic also show the importance of the genetic material and knowledge of their attributes and functions. However, the growth in known attributes or functionalities of these entities are still in slow progression due to the time consuming and expensivein vitroexperimental methods. In this paper, we have proposed an ensemble classification algorithm calledSubFeatto predict the functionalities of biological entities from different types of datasets. Our model uses a feature subspace based novel ensemble method. It divides the feature space into sub-spaces which are then passed to learn individual classifier models and the ensemble is built on this base classifiers that uses a weighted majority voting mechanism.SubFeattested on four datasets comprising two DNA, one RNA and one protein dataset and it outperformed all the existing single classifiers and as well as the ensemble classifiers.SubFeatis made availalbe as a Python-based tool. We have made the packageSubFeatavailable online along with a user manual. It is freely accessible from here:https://github.com/fazlulhaquejony/SubFeat.
Environmental enrichment reverses memory impairment in B3-ARKO mice
Authors: Ravache Thais Terpins , Nunes Gabriela G. , Batistuzzo Alice , Lorena Fernanda B. , do Nascimento Bruna P. P. , Bernardi Martha , Ribeiro Miriam O.
Published: August 2020

Norepinephrine plays an important role in modulating the processes of memory consolidation and evocation through its beta-adrenergic receptors (Adrβ), which are expressed in the hippocampus and amygdala. Several studies have shown that all three subtypes of Adrβ (β1, β2and β3) play an important role in cognition. Environmental enrichment (EE), a technique initially used to decrease the stress of animals held in captive environments, has also been shown to produce cognitive benefits in both healthy and sick animals. In this study, we hypothesized that EE would reverse the memory impairment induced by the absence or Adrβ3. To test this, 21- and 86-day-old Adrβ3KO mice were exposed to an EE protocol for 8 weeks. The study showed that the EE protocol is able to correct the memory impairment when applied to Adrβ3KO animals immediately after weaning but has no effect when applied to adult animals. We also found that aging worsens the memory of Adrβ3KO mice. Our results suggest that a richer and more diverse environment helps to correct memory impairment in Adrβ3KO animals. They also reinforce the idea that noradrenergic signaling is involved in the cognitive impairment observed late in life, as aging led to a worsening in the memory of the Adrβ3KO animals that was not corrected by the environmental enrichment protocol.
Accurate brain age prediction using recurrent slice-based networks
Authors: Lam Pradeep K. , Santhalingam Vigneshwaran , Suresh Parth , Baboota Rahul , Zhu Alyssa H. , Thomopoulos Sophia I. , Jahanshad Neda , Thompson Paul M.
Published: August 2020

BrainAge (a subject’s apparent age predicted from neuroimaging data) is an important biomarker of brain aging. The deviation of BrainAge from true age has been associated with psychiatric and neurological disease, and has proven effective in predicting conversion from mild cognitive impairment (MCI) to dementia. Conventionally, 3D convolutional neural networks and their variants are used for brain age prediction. However, these networks have a larger number of parameters and take longer to train than their 2D counterparts. Here we propose a 2D slice-based recurrent neural network model, which takes in an ordered sequence of sagittal slices as input to predict the brain age. The model consists of two components: a 2D convolutional neural network (CNN), which encodes the relevant features from the slices, and a recurrent neural network (RNN) that learns the relationship between slices. We compare our method to other recently proposed methods, including 3D deep convolutional regression networks, information theoretic models, and bag-of-features (BoF) models (such as BagNet) - where the classification is based on the occurrences of local features, without taking into consideration their global spatial ordering. In our experiments, our proposed model performs comparably to, or better than, the current state of the art models, with nearly half the number of parameters and a lower convergence time.
Inflammasome- and gasdermin D-independent IL-1β production mobilizes neutrophils to inhibit antitumor immunity
Authors: Kiss Máté , Vande Walle Lieselotte , Lebegge Els , Van Damme Helena , Murgaski Aleksandar , Qian Junbin , Ehling Manuel , Pretto Samantha , Bolli Evangelia , Keirsse Jiri , Elkrim Yvon , Martins Maria Solange , Fossoul Amelie , Lambrechts Diether , Mazzone Massimiliano , Wullaert Andy , Lamkanfi Mohamed , Van Ginderachter Jo A. , Laoui Damya
Published: August 2020

Interleukin-1β (IL-1β) is a central mediator of inflammation whose secretion typically requires proteolytic maturation by the inflammasome and formation of membrane pores by gasdermin D (GSDMD). Emerging evidence suggests an important role for IL-1β in promoting cancer progression in patients, but the underlying mechanisms are little understood. Here, we show a key role for IL-1β in driving tumor progression in two distinct mouse tumor models. Notably, inflammasome activation and GSDMD were dispensable for the production of intratumoral bioactive IL-1β, which promoted systemic mobilization and infiltration of neutrophils into tumors. Neutrophils recruited via IL-1β suppressed the acquisition of an effector T-cell phenotype and subsequent antitumor immune response. Moreover, IL-1β was essential for neutrophil accumulation upon antiangiogenic therapy, thereby contributing to therapy-induced immunosuppression. Antitumor immunity in the absence of IL-1β-dependent neutrophil recruitment relied on immunostimulatory macrophages which promoted the infiltration and activation of cytotoxic T-cells. Overall, these results support a tumor-promoting role for IL-1β through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for its release in tumors.
Five patterns of cell signaling pathways associated with cell behavior
Authors: Takeda Yuji , Kawano Kazuharu , Ma Rui , Saitoh Shinichi , Asao Hironobu
Published: August 2020

Cell signaling pathway is complex systems. Here, we present a concept for a new approach to analyze cell signaling pathway associated with cell behavior. In theoretically, cell behavior is recognized by energy and fluctuation. In this study, we measured phosphorylation level of signal transducers in a cell and fluctuation of the phosphorylation level in the cell population using flow cytometry. Flow cytometric data of mean fluorescence intensity (MFI) and coefficient variation (CV) were considered to the energy and the fluctuation, respectively. Topologically, the changes of MFI and CV were categorized into five patterns (we tentatively named as attractive, subsequent, passive, counter, and negative arbiter). In this study, we clarified the relationship between the cell behavior and the five patterns. Furthermore, combining the five patterns can define the signaling pathways, such as simple activated signal, oscillating signal, regulatory signal, robust signal, or homeostatic signal. These observations provide a proof of concept for general strategy to use the five patterns for connection between cell signaling pathway and cell behavior.
Fibre-specific laterality of white matter in left and right language dominant people
Authors: Verhelst Helena , Dhollander Thijs , Gerrits Robin , Vingerhoets Guy
Published: August 2020

Despite the typical symmetrical appearance of the human brain, several functional and structural asymmetries have been reported. Language is the most commonly described lateralised cognitive function, relying relatively more on the left hemisphere in over 90% of the population. This is in line with white matter studies which have revealed leftwards lateralisation of the arcuate fasciculus, a white matter tract that connects important language-related regions. Most research to date examining the structure-function relationship of language lateralisation only included people showing a left language hemisphere dominance. As such, the reported correlations do not allow for inferences of relationships between the directions of functional and structural lateralisation of language.

In this work, we applied a state-of-the-art “fixel-based” analysis approach, which allows to statistically analyse white matter micro- and macrostructure on a fibre-specific level. To study lateralisation using this framework, we defined a bespoke fibre-specific laterality index which allowed us to examine whole-brain white matter asymmetries in samples of participants with left and right language dominance (LLD and RLD respectively). Both groups showed similar extensive and intricate patterns of significant white matter lateralisation. Few group differences were found between both groups, with a similar leftwards lateralisation of the arcuate fasciculus, regardless of functional language lateralisation of the participants. A significant group difference of lateralisation was detected in the forceps minor, with a leftwards lateralisation in LLD and rightwards lateralisation for the RLD group.

In conclusion, we showed that fixel-based analysis of fibre-specific lateralisation indices is an effective approach to study white matter asymmetries. Our results suggest that the lateralisation of language functioning and the arcuate fasciculus are driven by independent biases. The exact relationship between forceps minor asymmetry and language dominance could be an interesting subject of future studies.
Diploid genome architecture revealed by multi-omic data of hybrid mice
Authors: Han Zhijun , Cui Kairong , Placek Katarzyna , Hong Ni , Lin Chengqi , Chen Wei , Zhao Keji , Jin Wenfei
Published: August 2020

Although mammalian genomes are diploid, previous studies extensively investigated the average chromatin architectures without considering the differences between homologous chromosomes. We generated Hi-C, ChIP-seq, and RNA-seq data sets from CD4 T cells of B6, Cast, and hybrid mice, to investigate the diploid chromatin organization and epigenetic regulation. Our data indicate that inter-chromosomal interaction patterns between homologous chromosomes are similar, and the similarity is highly correlated with their allelic coexpression levels. Reconstruction of the 3D nucleus revealed that distances of the homologous chromosomes to the center of nucleus are almost the same. The inter-chromosomal interactions at centromere ends are significantly weaker than those at telomere ends, suggesting that they are located in different regions within the chromosome territories. The majority of A|B compartments or topologically associated domains (TADs) are consistent between B6 and Cast. We found 58% of the haploids in hybrids maintain their parental compartment status at B6/Cast divergent compartments owing to cis effect. About 95% of the trans-effected B6/Cast divergent compartments converge to the same compartment status potentially because of a shared cellular environment. We showed the differentially expressed genes between the two haploids in hybrid were associated with either genetic or epigenetic effects. In summary, our multi-omics data from the hybrid mice provided haploid-specific information on the 3D nuclear architecture and a rich resource for further understanding the epigenetic regulation of haploid-specific gene expression.
Robotic assembly for tight tolerant cascaded peg-in-hole process with incomplete constraints
Authors: Cheng Hongtai , Liu Tianzhuo , Zhang Wei , Hao Lina
Published: August 2020

Purpose

Installing a tight tolerant stepped shaft is not a trivial task for an industrial robot. If all peg-hole constraints are complete, the cascaded peg-in-hole task can be simplified into several independent stages and accomplished one by one. However, if some of the constraints are incomplete, the cross stage interference will bring additional difficulties. This paper aims to discuss the cascaded peg-in-hole problem with incomplete constraints.

Design/methodology/approach

In this paper, the problem is formulated according to geometric parameters of the stepped shaft and completeness of the corresponding hole. The possible jamming type is modeled and analyzed. A contact modeling and control strategy is proposed to compensate the peg postures under incomplete constraints.

Findings

The above methods are implemented on an experiment platform and the results verify the effectiveness of the proposed robotic assembly strategy.

Originality/value

Based on force/torque sensor, a hybrid control strategy for incomplete constraints cascaded peg-in-hole assembly problem is proposed.
Modelling the effect of computation sampling on insight error in computational fluid dynamics scientific simulation
Authors: Masiane Moeti , Jacques Eric , Feng Wuchun , North Chris
Published: August 2020

Purpose

The purpose of this paper is to collect data from humans as they generate insights from the visualised results of computational fluid dynamics (CFD) scientific simulation. The authors hypothesise the behaviour of their insight errors (IEs) and proceed to quantify the IEs provided by the crowd participants. They then use the insight framework to model the behaviours of the errors. Using the crowd responses and models from the framework, they test the hypotheses and use the results to validate the framework for the speedup of CFD applications.

Design/methodology/approach

The authors use a randomised between-subjects experiment with blocking. CFD grid resolution is the independent variable while IE is the dependent variable. The experiment has one treatment factor with five levels. In case varying timestamps has an effect on insight variance levels, the authors block the responses by timestep. In total, 150 participants are randomly assigned to one of five groups and also randomly assigned to one of five blocks within a treatment. Participants are asked to complete a benchmark and open-ended task.

Findings

The authors find that the variances of insight and perception errors have a U-shaped relationship with grid resolution, that similar to the previously studied visualisation applications, the IE framework is valid for insights generated from CFD results and grid resolution can be used to predict the variance of IE resulting from observing CFD post-processing results.

Originality/value

To the best of the authors’ knowledge, no other work has measured IE variance to present it to simulation users so that they can use it as a feedback metric for selecting the ideal grid resolution when using grid resolution to speedup CFD simulation.
Animal infection models using non‐mammals
Authors: Kaito Chikara , Murakami Kanade , Imai Lina , Furuta Kazuyuki
Published: August 2020

The use of non‐human animal models for infection experiments is important for investigating the infectious processes of human pathogenic bacteria at the molecular level. Mammals, such as mice and rabbits, are also utilized as animal infection models, but large numbers of animals are needed for these experiments, which is costly, and fraught with ethical issues. Various non‐mammalian animal infection models have been used to investigate the molecular mechanisms of various human pathogenic bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. This review discusses the desirable characteristics of non‐mammalian infection models and describes recent non‐mammalian infection models that utilize Caenorhabditis elegans, silkworm, fruit fly, zebrafish, two‐spotted cricket, hornworm, and waxworm.
Teenage social behaviour and emotional well‐being: the role of gender and socio‐economic factors
Authors: Hartas Dimitra , Kuscuoglu Ahmet
Published: August 2020

This article draws on the Millennium Cohort Study (MCS) to examine parent ratings of social, emotional and behavioural difficulties and prosocial behaviour in pre‐ and mid‐adolescents. A series of mixed‐design ANOVAs yielded interesting results. Parent ratings of emotional difficulties in girls increased as they moved from pre‐ to mid‐adolescence whereas for boys the reverse was found. Peer problems were found to be on the rise, whereas prosocial skills decreased for 14‐year‐olds. Most importantly, significant associations were found between socio‐economic measures (that is, family income and parent education) and ratings across the domains of the Strengths and Difficulties Questionnaire, highlighting the socio‐economic specificity of behaviour and well‐being in adolescents. These findings have significant implications for understanding trends in young people's social behaviour and emotional well‐being from pre‐ to mid‐adolescence within their socio‐economic context.
Prognostic models versus single risk factor approach in first‐trimester selective screening for gestational diabetes mellitus: a prospective population‐based multicentre cohort study
Authors: van Hoorn F , Koster MPH , Naaktgeboren CA , Groenendaal F , Kwee A , Lamain‐de Ruiter M , Franx A , Bekker MN
Published: August 2020

Objectives

To evaluate whether (1) first‐trimester prognostic models for gestational diabetes mellitus (GDM) outperform the currently used single risk factor approach, and (2) a first‐trimester random venous glucose measurement improves model performance.

Design

Prospective population‐based multicentre cohort.

Setting

Thirty‐one independent midwifery practices and six hospitals in the Netherlands.

Population

Women recruited before 14 weeks of gestation without pre‐existing diabetes.

Methods

The single risk factor approach (presence of at least one risk factor: BMI ≥30 kg/m2, previous macrosomia, history of GDM, positive first‐degree family history of diabetes, non‐western ethnicity) was compared with the four best performing models in our previously published external validation study (Gabbay‐Benziv 2014, Nanda 2011, Teede 2011, van Leeuwen 2010) with and without the addition of glucose.

Main outcome measures

Discrimination was assessed by c‐statistics, calibration by calibration plots, added value of glucose by the likelihood ratio chi‐square test, net benefit by decision curve analysis and reclassification by reclassification plots.

Results

Of the 3723 women included, a total of 181 (4.9%) developed GDM. The c‐statistics of the prognostic models were higher, ranging from 0.74 to 0.78 without glucose and from 0.78 to 0.80 with glucose, compared with the single risk factor approach (0.72). Models showed adequate calibration, and yielded a higher net benefit than the single risk factor approach for most threshold probabilities. Teede 2011 performed best in the reclassification analysis.

Conclusions

First‐trimester prognostic models seem to outperform the currently used single risk factor approach in screening for GDM, particularly when glucose was added as a predictor.

Tweetable abstract

Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes.
Identification of salivary proteins in the whitefly Bemisia tabaci by transcriptomic and LC–MS/MS analyses
Authors: Huang Hai‐Jian , Ye Zhuang‐Xin , Lu Gang , Zhang Chuan‐Xi , Chen Jian‐Ping , Li Jun‐Min
Published: August 2020

The whitefly Bemisia tabaci is a notorious agricultural pest of many crops worldwide. Although it is thought that B. tabaci secretes saliva into the host plant to counter plant defenses, knowledge on the whitefly salivary proteome is limited. Here, we characterized the gene/protein repertoires of B. tabaci salivary glands and secreted saliva by transcriptomic and liquid chromatography tandem mass spectroscopy analyses. A total of 698 salivary gland‐enriched unigenes and 171 salivary proteins were identified. Comparative analysis between the B. tabaci salivary proteins and those of different arthropod species revealed numerous similarities in proteins associated with binding, hydrolysis, and oxidation‐reduction, which demonstrates a degree of conservation across herbivorous saliva. There were 74 proteins only identified in B. tabaci saliva, of which 34 were B. tabaci‐specific. In addition, 13 salivary proteins, of which 11 were B. tabaci‐specific, were differentially regulated when B. tabaci fed on different hosts. Our results provide a good resource for future functional studies of whitefly salivary effectors, and might be useful in pest management.
Infliximab plus azathioprine is more effective than azathioprine alone in achieving mucosal healing in pediatric patients with Crohn's disease
Authors: Melek Jan , Štanclová Markéta , Dědek Petr , Malý Jan , Bayer Milan , Pozler Oldřich , Bureš Jan
Published: August 2020

Objectives

Over the past few years, mucosal healing (MH) has emerged as a promising goal in the treatment of pediatric patients with Crohnʼs disease (CD). We aimed to assess whether combination therapy with infliximab (IFX) + azathioprine (AZA) was more effective than AZA therapy alone in achieving mucosal healing in pediatric patients with CD.

Methods

Newly diagnosed pediatric patients with CD at the Department of Pediatrics in University Hospital in Hradec Králové were retrospectively recruited (2000‐2014). The patients were divided into two groups according to the therapy: (a) IFX + AZA ± corticosteroids ± 5‐aminosalicylic acid (5‐ASA) (n = 16); and (b) AZA ± corticosteroids ± 5‐ASA (n = 40). The patients were also divided into two groups: “MH” and “no MH,” according to their MH status. MH was defined as the complete endoscopic disappearance of all mucosal ulcerations (including aphthous ulcerations) and the absence of any sign of mucosal inflammation in the terminal ileum and the large bowel.

Results

Of 56 patients, MH was observed in 56% (9/16) treated with combined therapy in comparison with 15% (6/40) of patients in the AZA group (P = 0.006). The median dose of AZA in both groups was 2.1 mg/kg per day. We observed eight adverse events in seven patients from the IFX + AZA group. Adverse effects were less common in the AZA group (P = 0.002).

Conclusion

Combined therapy (IFX + AZA) was more effective in achieving MH in pediatric CD than treatment with AZA alone.
The role of WNT1 mutant variant (WNT1c.677C>T) in osteogenesis imperfecta
Authors: Zhang Bashan , Li Rong , Wang Wenfeng , Zhou Xueming , Luo Beijing , Zhu Zinian , Zhang Xibo , Ding Aijiao
Published: August 2020

Osteogenesis imperfecta (OI), also known as “brittle bone disease,” is a rare inherited genetic disorder characterized by bone fragility and often associated with short stature. The mutation in WNT1 causes autosomal recessive OI (AR‐OI) due to the key role of WNT/β‐catenin signaling in bone formation. WNT1 mutations cause phenotypes in OI of varying degrees of clinical severity, ranging from moderate to progressively deforming forms. The nucleotide change c.677C > T is one of the recurrent variants in the WNT1 alleles in Chinese AR‐OI patients. To explore the effects of mutation c.677C > T on WNT1 function, we evaluated the activation of WNT/β‐catenin signaling, cell proliferation, osteoblast differentiation, and osteoclast differentiation in WNT1c.677C>T, WNT1c.884C>A, and wild type WNT1 transfected into MC3T3‐E1 preosteoblasts. Plasmids containing wild type WNT1, WNT1c.677C>T, and WNT1c.884C>A cDNAs were constructed. Protein levels of phosphorylation at serine 9 of GSK‐3β (p‐GSK‐3β), GSK‐3β, nonphosphorylated β‐catenin (non‐p‐β‐catenin), and β‐catenin were detected with western blot. Cell proliferation was determined using MTS. BMP‐2 and RANKL mRNA and protein levels were detected by qPCR and western blot. Our results showed that WNT1c.677C>T failed to activate WNT/β‐catenin signaling and impaired the proliferation of preosteoblasts. Moreover, compared to wild type WNT1, WNT1c.677C>T downregulated BMP‐2 protein expression and was exhibited a diminished capacity to suppress the RANKL protein level. In conclusion, mutation c.677C > T hindered the ability of WNT1 to induce the WNT/β‐catenin signaling pathway and it affected the WNT/β‐catenin pathway which might potentially contribute to hampered bone homeostasis.
A history of canine parvovirus in Australia: what can we learn?
Authors: Kelman M , Norris JM , Barrs VR , Ward MP
Published: August 2020

Canine parvovirus (CPV) has been reported throughout the world since the late 1970s. Published information was reviewed to draw insights into the epidemiology, pathogenesis, diagnosis, treatment and outcomes of CPV disease in Australia and the role of scientific research on CPV occurrence, with key research discoveries and knowledge gaps identified. Australian researchers contributed substantially to early findings, including the first reported cases of parvoviral myocarditis, investigations into disease aetiopathogenesis, host and environmental risk factors and links between CPV and feline panleukopenia. Two of the world's first CPV serological surveys were conducted in Australia and a 1980 national veterinary survey of Australian and New Zealand dogs revealed 6824 suspected CPV cases and 1058 deaths. In 2010, an Australian national disease surveillance system was launched; 4940 CPV cases were reported between 2009 and 2014, although underreporting was likely. A 2017 study estimated national incidence to be 4.12 cases per 1000 dogs, and an annual case load of 20,110 based on 4219 CPV case reports in a survey of all Australian veterinary clinics, with a 23.5% response rate. CPV disease risk factors identified included socioeconomic disadvantage, geographical location (rural/remote), season (summer) and rainfall (recent rain and longer dry periods both increasing risk). Age <16 weeks was identified as a risk factor for vaccination failure. Important knowledge gaps exist regarding national canine and feline demographic and CPV case data, vaccination coverage and population immunity, CPV transmission between owned dogs and other carnivore populations in Australia and the most effective methods to control epizootics.
A Cross‐Cultural Analysis of Early Prelinguistic Gesture Development and Its Relationship to Language Development
Authors: Cameron‐Faulkner Thea , Malik Nivedita , Steele Circle , Coretta Stefano , Serratrice Ludovica , Lieven Elena
Published: August 2020

Many Western industrialized nations have high levels of ethnic diversity but to date there are very few studies which investigate prelinguistic and early language development in infants from ethnic minority backgrounds. This study tracked the development of infant communicative gestures from 10 to 12 months (n = 59) in three culturally distinct groups in the United Kingdom and measured their relationship, along with maternal utterance frequency and responsiveness, to vocabulary development at 12 and 18 months. No significant differences were found in infant gesture development and maternal responsiveness across the groups, but relationships were identified between gesture, maternal responsiveness, and vocabulary development.
Creating a Developmental Scale to Account for Heterotypic Continuity in Development: A Simulation Study
Authors: Petersen Isaac T. , LeBeau Brandon , Choe Daniel Ewon
Published: August 2020

Many psychological constructs show heterotypic continuity—their behavioral manifestations change with development but their meaning remains the same. However, research has paid little attention to how to account for heterotypic continuity. A promising approach to account for heterotypic continuity is creating a developmental scale using vertical scaling. A simulation was conducted to compare creating a developmental scale using vertical scaling to traditional approaches of longitudinal assessment. Traditional approaches that failed to account for heterotypic continuity resulted in less accurate growth estimates, at the person‐ and group level. Findings suggest that ignoring heterotypic continuity may result in faulty developmental inferences. Creating a developmental scale with vertical scaling is recommended to link different measures across time and account for heterotypic continuity.
Family violence and oppositional defiant disorder symptoms in Chinese children: The role of parental alienation and child emotion regulation
Authors: Chen Hui , Lin Xiuyun , Heath Melissa Allen , Ding Wan
Published: August 2020

Oppositional defiant disorder (ODD) is one of the most common developmental disorders during childhood. The current study examined the mediating role of parental alienation and the moderating role of child Emotion Regulation that had been divided into Lability/Negativity and Emotion Regulation when considering the relation between family violence and ODD symptoms. A sample of 409 children (Mage = 9.36, SD = 1.55) and their parent was recruited from 14 primary schools in China. Parents reported on experiences of family violence, Emotion Regulation and ODD symptoms and children reported on experiences of parental alienation. A mediation path from family violence to ODD symptoms via parental alienation was significant, suggesting that family violence was related to parental alienation, which was further associated with ODD symptoms. The moderation analysis showed family violence interacted with Lability/Negativity, such that higher level of family violence was associated with higher levels of ODD symptoms among children with Lability/Negativity. These findings underscore the necessity of adopting a multilevel perspective in understanding the development of ODD symptoms and the importance of paying more attention to family violence in Chinese family.
Subcostal versus transhepatic view to assess the inferior vena cava in critically ill patients
Authors: Valette Xavier , Ribstein Pierre , Ramakers Michel , du Cheyron Damien
Published: August 2020

Background

Evaluation of the inferior vena cava (IVC) is not always possible through the subcostal (SC) window.

Methods

Inferior vena cava diameters measured by transhepatic (TH) and SC views were compared by Bland and Altman analysis.

Results

131 patients were enrolled, including 88 (67%) under mechanical ventilation. The echogenicity was statistically poorer through the TH view in comparison with the SC view (P = .002). The correlation between the SC and TH views was good and better for respiratory variation than for end‐expiratory or end‐inspiratory diameter measurements (r = 0.86). Despite low bias, the limits of agreement were wide (−7.5 and 7.7 mm for end‐expiratory diameter, −8.7 and 8.5 mm for end‐inspiratory diameter, and −5.3 and 5.8 mm for respiratory variation). Complementary analysis showed that the concordance between the SC and the TH views was better when the IVC was distended. However, the limits of agreement remained broad.

Conclusions

Although feasible in almost all patients, the TH view does not provide better echogenicity in comparison with the SC view. Despite a good correlation with the SC view and a low bias, the limits of agreement were wide, especially when the IVC has an ellipsoidal shape, suggesting caution in the interpretation of data obtained by the TH view.
POPULAR SUPPORT FOR TRADE AGREEMENTS AND PARTNER COUNTRY CHARACTERISTICS: EVIDENCE FROM AN UNEXPECTED ELECTION OUTCOME
Authors: Coupé Tom , Shepotylo Oleksandr
Published: August 2020

Using quasi‐experimental data from a survey that was conducted immediately before and after the November 2016 presidential election, we analyze how the election of Donald Trump affected the willingness of Europeans to sign a trade and investment agreement with the United States. We find that the election outcome lead to an immediate and sizable negative effect on Europeans' image of the United States. But we do not find that, at the same time, there was a negative reaction in the willingness of Europeans to sign an agreement with the United States. (JEL F14, F55, C26, F50)
Speedier delivery: coastal shipping times and speeds during the Age of Sail †
Authors: Bogart Dan , Dunn Oliver , Alvarez‐Palau Eduard J. , Shaw‐Taylor Leigh
Published: August 2020

There is a debate about whether coastal shipping experienced substantial productivity growth prior to the advent of steam power. To study changes over the long eighteenth century, this article uses thousands of coastal journey times culled from Board of Trade crew lists between 1835 and 1844 and coastal port books for the mid‐to‐late 1600s, along with a newly digitized coastal network. Comparisons between matched samples show that journey speeds, defined as miles sailed per day, were significantly higher in the crew lists compared to the port books, and that voyage cycle times, defined as days between starting two identical voyages, were substantially lower. The study also shows that voyage times in the east coast coal trade were substantially lower around 1840 than around 1700, but the difference was much smaller when peace years are compared. These new data imply that total factor productivity growth in the east coast coal trade was significant, especially if one accounts for gains from peace after 1815. The findings contribute to the larger literature studying the rate and sources of productivity growth during the industrial revolution.
Impact of interleukin‐6 on drug transporters and permeability in the hCMEC/D3 blood–brain barrier model
Authors: Simon Florian , Guyot Laetitia , Garcia Jessica , Vilchez Gaelle , Bardel Claire , Chenel Marylore , Tod Michel , Payen Léa
Published: August 2020

The blood–brain barrier (BBB) is a highly selective membrane composed predominantly of brain capillary endothelial cells expressing drug efflux transporters that prevent substrates from accessing the brain. Inflammation is associated with central nervous system diseases and can impair BBB permeability via several mechanisms, including altered transporter and cell junction expression. This can modify the brain’s exposure to drugs. However, comprehensive genomic analysis of the impact of interleukin (IL)‐6, which plays a key role in the inflammatory response, on the BBB is lacking. In the present study, we analyzed the effects of exposure of hCMEC/D3 cells to 20 ng/mL IL‐6 for 72 h. We performed RNA sequencing and ABC transporter efflux assays. Physiologically based pharmacokinetics (PBPK) simulations were conducted to evaluate the potential impact of IL‐6 on the digoxin pharmacokinetics profile and brain exposure by decreasing BBB ABCB1 efflux activity. Exposure of hCMEC/D3 cells to IL‐6 triggered the deregulation of numerous genes involved in barrier permeability, such as cell junctions, focal adherens complex, and cell adhesion molecules. We observed mild modification of the mRNA expression and efflux activities of ABC transporters. PBPK simulation showed that, if we only consider the impact of IL‐6 on ABCB1 transporter, the modification of the digoxin pharmacokinetics profile and brain exposure is slight. IL‐6 slightly affected the gene expression levels and activities of ABC transporters on BBB cells, exhibiting a weaker effect than on hepatic cells. However, inflammation may cause other modifications, such as altered BBB permeability, that could modify drug pharmacokinetics.
Structural and rheological properties of medium‐chain triacylglyceride oleogels
Authors: Fayaz Goly , Polenghi Ombretta , Giardina Agata , Cerne Virna , Calligaris Sonia
Published: August 2020

This research studied the effect of gelator molecules on structural properties of oleogels containing medium‐chain triacylglycerides (MCTs). To this aim, a large selection of gelators (rapeseed wax RAW, rice wax RW, sunflower wax SW, beeswax BW, monoglycerides MG, and γ‐oryzanol and β‐sitosterol mixture γ+β) at increasing concentrations (5–15% w/w) was considered. Results showed that RAW was not able to structure MCT at any concentration. However, addition of 5% (w/w) of MG, SW and BW resulted to a self‐standing gel. Regarding γ+β and RW, gel structures were generated at 10% (w/w). By increasing the concentration, a reinforcement of the network strength was highlighted by the progressive increase of the rheological parameters. The strongest oleogel obtained by γ+β at 10% (w/w) and further BW and RW at 15% (w/w) concentration. These findings could provide interesting information in the choice of the best performing MCT structuring agent for intended food applications.
The efficacy of administrating a sweet‐tasting solution for reducing the pain related to dental injections in children: A randomized controlled trial
Authors: Ghaderi Faezeh , Ahmadbeigi Mahboobe , Vossoughi Mehrdad , Sardarian Ahmadreza
Published: August 2020

Background

Anaesthetic injections are an unpleasant experience for children in the dental office. Oral intake of sweet substances by newborns has been shown to be effective in reducing pain.

Aim

The purpose of this study was to determine whether a prior administration of a sweet‐tasting solution has an effect on dental injection pain.

Design

A total of 56 healthy children needing bilateral maxillary primary canine extraction were included in this split‐mouth randomized clinical trial. In the test side, dental injection (local infiltration) was applied after the patient received a sweet‐tasting solution, while in the control side sterile water was administered. The patients’ demographic characteristics, body mass index (BMI), and sweet taste preference were recorded. Pain perception during injection was measured using visual analogue scale (VAS) and sound, eye, body movement (SEM).

Results

Mean VAS (28.30 ± 6.43) and SEM (2.14 ± 0.78) in the test side were lower than the control side (45.80 ± 7.17 and 2.95 ± 1.00). It was shown that higher BMI was associated with reduction in the analgesic effect, while the individual's tendency to sweetness increased pain reduction.

Conclusions

Sweet taste administration before dental injections in children helps to control the associated pain. This effect is influenced by the individual's sweet taste tendency and BMI.
A new surgical approach of direct perineal wound full‐thick closure for perineal wound of abdominoperineal resection for rectal carcinoma: A prospective cohort trial
Authors: Yang Yong‐Ping , Yu Ling‐Yun , Wang Min , Mu Yu , Li Jian‐Nan , Shang Feng‐Jia , Wu Xian‐Feng , Liu Tong‐Jun , Shi Jian
Published: August 2020

Perineal wound complications after APR have high morbidity in the colorectal surgical department. Although some approaches have been figured out to solve this clinical focus, the outcomes are still not satisfied. Herein, this prospective comparative clinical trial has been designed to evaluate a new surgical procedure of direct perineal wound full‐thick closure (DPWC), compared with conventional perineal wound closure (CPWC), with hopes of making wound healing with less complications. In addition, an evaluation of an incision negative wound pressure therapy, as another focus in this field, was also analysed in the DPWC group. A total of 44 participants in our department were recruited from March 2018 to March 2020, divided into two groups randomly, CPWC group and DPWC group. The patients' characteristics, such as age, gender, BMI, smoking, alcohol consumption, comorbidities, CEA level, and high‐risk of invasion, were recorded without statistical significance between the CPWC group and DPWC group. After the same standard abdominal phase, these two groups were performed in different perineal phases. And then, operative and postoperative outcomes were analysed with different statistical methods. Data on wound healing time and length of stay in the DPWC group were shorter than those in the CPWC group (P < .05). Furthermore, cases of wound infection within 30 days in the DPWC group were also less than that in the CPWC group (P < .05). However, no difference was found between the incisional negative pressure wound therapy assisted group (NPA group) and non‐ incisional negative pressure wound therapy assisted group (non‐NPA group). During this study, hypoalbuminemia, as an independent high‐risk factor, impacted perineal wound healing. (P = .0271) In conclusion, DPWC is a new surgical approach, which can lead to a better outcome than DPWC, and it can be another surgical procedure for clinicians. In addition, hypoalbuminemia should be interfered for avoiding perineal wound complications.
Improvement in tricuspid regurgitation following catheter ablation of atrial fibrillation
Authors: Markman Timothy M. , Plappert Theodore , De Feria Alsina Alejandro , Levin Michael , Amankwah Nigel , Sheth Samip , Gertz Zachary M. , Schaller Robert D. , Marchlinski Francis E. , Rame Jesus E. , Frankel David S.
Published: August 2020

Introduction

Functional tricuspid regurgitation (TR) remains a challenging clinical problem with poor outcomes and few effective treatments. Atrial fibrillation (AF) has been associated with functional TR. We sought to determine whether restoring sinus rhythm through catheter ablation of AF can decrease the degree of TR.

Methods and Results

A retrospective cohort study of patients undergoing AF ablation between 2011 and 2017 at a single center was conducted. We included patients with at least moderate TR on echocardiogram within the year preceding ablation, who underwent repeat echocardiogram within the year following ablation. Formal quantitative analysis was performed by an experienced research echocardiographer, blinded to arrhythmia outcomes. Arrhythmia‐free survival was correlated to the extent of improvement in TR. Thirty‐six patients met the inclusion criteria. A baseline echocardiogram was performed 37 ± 68 days before ablation and follow‐up echocardiogram 139 ± 112 days following ablation. Patients were 63.7 ± 11.1 years old with a mean CHA2DS2‐VASc score of 2.7 ± 1.7. The degree of TR improved by at least one grade in 23 patients (64%). TR area decreased from 11.6 ± 3.4 to 7.0 ± 3.5 cm2 (p < .001) following ablation. Freedom from AF postablation was associated with a greater likelihood of improvement in TR by at least one grade (100% vs. 41%, p = .02).

Conclusions

In patients with AF and at least moderate TR, catheter ablation is associated with substantial improvement in TR severity.
MCTR1 enhances the resolution of lipopolysaccharide‐induced lung injury through STAT6‐mediated resident M2 alveolar macrophage polarization in mice
Authors: Wang Qian , Zhang Hua‐Wei , Mei Hong‐Xia , Ye Yang , Xu Hao‐Ran , Xiang Shu‐Yang , Yang Qian , Zheng Sheng‐Xing , Smith Fang‐Gao , Jin Sheng‐Wei
Published: August 2020

Acute respiratory distress syndrome (ARDS) is a fatal disease characterized by excessive infiltration of inflammatory cells. MCTR1 is an endogenously pro‐resolution lipid mediator. We tested the hypothesis that MCTR1 accelerates inflammation resolution through resident M2 alveolar macrophage polarization. The mice received MCTR1 via intraperitoneal administration 3 days after LPS stimulation, and then, the bronchoalveolar lavage (BAL) fluid was collected 24 hours later to measure the neutrophil numbers. Flow cytometry was used to sort the resident and recruited macrophages. Post‐treatment with MCTR1 offered dramatic benefits in the resolution phase of LPS‐induced lung injury, including decreased neutrophil numbers, reduced BAL fluid protein and albumin concentrations and reduced histological injury. In addition, the expression of the M2 markers Arg1, FIZZ1, Remlα, CD206 and Dectin‐1 was increased on resident macrophages in the LPS + MCTR1 group. Resident macrophage depletion abrogated the therapeutic effects of MCTR1, and reinjection of the sorted resident macrophages into the lung decreased neutrophil numbers. Finally, treatment with MCTR1 increased STAT6 phosphorylation. The STAT6 inhibitor AS1517499 abolished the beneficial effects of MCTR1. In conclusion, MCTR1 promotes resident M2 alveolar macrophage polarization via the STAT6 pathway to accelerate resolution of LPS‐induced lung injury.