bluuebunny/crossref_metadata_2025 huggingface dataset:
Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition
Authors: Chen Wu , Cai Zhao-Lin , Chao Eugene S. , Chen Hongmei , Hao Shuang , Chao Hsiao-Tuan , Kim Joo Hyun , Messier Jessica E. , Zoghbi Huda Y. , Tang Jianrong , Swann John W. , Xue Mingshan
Published: April 2019

Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease pathogenesis.
Snail induces epithelial cell extrusion through transcriptional control of RhoA contractile signaling and cell matrix adhesion
Authors: Wee Kenneth , Zadeh Suroor , Verma Suzie , Daly Roger J. , Yap Alpha S. , Davis Melissa J. , Budnar Srikanth
Published: April 2019

Cell extrusion is a morphogenetic process that is implicated in epithelial homeostasis and highly dependent on the cellular insult and context. Minorities of cells expressing HRasV12or undergoing apoptosis are typically extruded apically in vertebrate cells. However, basal extrusion (delamination) predominates when mammalian cells express oncogenic KRas and during development in Drosophila. To explore if the morphogenetic transcription factor, Snail, induces extrusion, we inducibly expressed a metabolically stabilized Snail6SAtransgene mosaically in confluent MCF-7 monolayers. We found that the morphogenetic impact of Snail6SAwas critically influenced by the proportion of cells in which it was expressed. When expressed in small clusters (<3 cells) within confluent monolayers, Snail6SAexpression induced apical cell extrusion. In contrast, confluent cultures of Snail6SAexpressing cells were retained in the monolayer to eventually undergo basal extrusion (delamination). Transcriptomic profiling revealed that Snail6SAdid not substantively alter the balance of epithelial:mesenchymal genes. However, we identified a gene transcriptional network that led to the upregulation of RhoA signalling, actomyosin contractility and reduced basal adhesion in Snail6SAexpressing cells. We show that this was necessary to drive both apical extrusion and basal delamination. Thus, contractile upregulation by RhoA along with weakened basal adhesion provides a pathway for Snail to influence epithelial morphogenesis independently of classic Epithelial to Mesenchymal Transition (EMT).
Single-Cell Signature Explorer for comprehensive visualization of single cell signatures across scRNA-seq data sets
Authors: Pont Frédéric , Tosolini Marie , Fournié Jean Jacques
Published: April 2019

The momentum of scRNA-seq data sets prompts for simple and powerful tools exploring their meaningful signatures. Here we present Single-Cell_Signature_Explorer (https://sites.google.com/site/fredsoftwares/products/single-cell-signature-explorer), the first method for high throughput scoring at single cell level of any gene set-based signature and visualization across t-SNE. By scanning data sets for single or combined signatures, it quantitatively and qualitatively maps any multi-gene feature, exemplified here with signatures of cell lineages, biological hallmarks and metabolic pathways in large scRNAseq datasets of human PBMC, lung cancer and adult testis.
Germline-encoded TCR-MHC contacts promote TCR V gene bias in umbilical cord blood T cell repertoire
Authors: Gao Kai , Chen Lingyan , Zhang Yuanwei , Zhao Yi , Wan Ziyun , Wu Jinghua , Lin Liya , Kuang Yashu , Lu Jinhua , Zhang Xiuqing , Tian Lei , Liu Xiao , Qiu Xiu
Published: April 2019

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the “net” genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR β chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.
Theory of cyborg: a new approach to fish locomotion control
Authors: Jamali Mohammad , Jamali Yousef , Golshani Mehdi
Published: April 2019

Cyborg in the brain-machine interface field has attracted more attention in recent years. To control a creature via a machine called cyborg method, three stages are considerable: stimulation of neurons, neural response, and the behavioral reaction of the subject. Our main concern was to know how electrical stimulation induces neural activity and leads to a behavioral response. Additionally, we were interested to explore which type of electrical stimulation is optimal from different aspects such as maximum response with minimum induction stimulus field, minimum damage of the tissue and the electrode, reduction of the noxiousness of stimuli or pain in the living creature. In this article, we proposed a new model for the induction of neural activity led to locomotion responses through an electrical stimulation. Furthermore, based on this model, we developed a new approach of electrical neural stimulation to provide a better locomotion control of living beings. This approach was verified through the empirical data of fish cyborg. We stimulated the fish brain by use of an ultra-high frequency signal which careered by a random low frequency. According to our model, we could control the locomotion of fish in a novel and innovative way. In this study, we categorized the different cyborg methods based on the nervous system areas and the stimulation signal properties to reach the better and optimal behavioral control of creature. According to this, we proposed a new stimulation method theoretically and confirmed it experimentally.
Super resolution imaging of a distinct chromatin loop in human lymphoblastoid cells
Authors: Zhu Jacqueline Jufen , Parteka Zofia , Lee Byoungkoo , Szalaj Przemyslaw , Wang Ping , Jodkowska Karolina , Aaron Jesse , Chew Teng-Leong , Plewczynski Dariusz , Ruan Yijun
Published: April 2019

The three-dimensional genome structure plays a fundamental role in gene regulation and cellular functions. Recent studies in genomics based on sequencing technologies inferred the very basic functional chromatin folding structures of the genome known as chromatin loops, the long-range chromatin interactions that are often mediated by protein factors. To visualize the looping structure of chromatin we applied super-resolution microscopy iPALM to image a specific chromatin loop in GM12878 cells. Totally, we have generated six images of the target chromatin region at the single molecule resolution. To infer the chromatin structures from the captured images, we modeled them as looping conformations using different computational algorithms and then evaluated the models by comparing with Hi-C data to examine the concordance. The results showed a good correlation between the imaging data and sequencing data, suggesting the visualization of higher-order chromatin structures for the very short genomic segments can be realized by microscopic imaging.
Synthetic lethality targeting LKB1 mutant and EGFR wild type human non-small cell lung cancer cells by glucose starvation and SGLT2 inhibition
Authors: Ren Yi , Chen Jiaqing , Mo Xiaofan , Yang Qiqi , Chen Peishi , Lu Guang , Tan Hayden Weng-Siong , Yi Juan , Yu Qiang , Kim You-Sun , Mallilankaraman Karthik , Shen Han-Ming
Published: April 2019

In this study, we aimed to discover novel therapeutic approaches targeting non-small cell lung cancer (NSCLC) patients without EGFR mutation. First, we found that mutations of EGFR and LKB1 are mutually exclusive in NSCLC. EGFR-WT/LKB1-mutant cells are resistant to EGFR inhibitor erlotinib but are highly susceptible to glucose starvation or SGLT2 inhibitor canagliflozin. Mechanistically, in these cells, glucose starvation causes suppression of AMPK and induction of oxidative stress, leading to cell death. Finally, canagliflozin effectively reduces tumor growth of EGFR-WT/LKB1-mutant NSCLC cells in the mice xenograft model. Our data thus demonstrate that synthetic lethality can be achieved by glucose starvation or SGLT2 inhibition in EGFR-WT/LKB1-mutant NSCLC.

SIGNIFICANCE

At present, EGFR inhibitor-based targeted therapy can only benefit those non-small cell lung cancer (NSCLC) patients with EGFR mutation. Therefore, there is an urgent need to develop alternate targeted therapy for NSCLC with WT EGFR. In this study, we found that mutations of EGFR and LKB1 are mutually exclusive in NSCLC, and more importantly, synthetic lethality can be achieved in EGFR-WT/LKB1-mutant NSCLC cells with glucose starvation or SGLT2 inhibition. Since SGLT2 inhibitors such as canagliflozin are FDA-approved drugs for type II diabetes, our study thus points out a possibility of developing SGLT2 inhibitors as a targeted therapy for NSCLC patients with WT EGFR and mutant LKB1, which will benefit about 15-30% of NSCLC patients.

HIGHLIGHTS

EGFR and LKB1 mutations are mutually exclusive in NSCLC

EGFR-WT/LKB1-mutant NSCLC cells are sensitive to cell death induced by glucose starvation and SGLT2 inhibition

Glucose starvation suppresses AMPK activity in LKB1-mutant NSCLC cells

SGLT2 inhibitor canagliflozin causes synthetic lethality in LKB1-mutant NSCLC cells
Phanerochaete chrysosporium strain B-22, a parasitic fungus infecting Meloidogyne incognita
Authors: Du Bin , Xu Yumei , Dong Hailong , Yan Li , Wang Jianming
Published: April 2019

We characterized the parasitism by strain B-22 of Phanerochaete chrysosporium on the eggs, second stage juveniles (J2), and adult females of the root-knot nematode (Meloidogyne Incognita). Strain B-22 had a strong lethal effect against M. incognita J2. The highest corrected mortality was 71.9% at 3 × 108 conidia mL−1. The estimated LC50 value was 0.96 × 108 conidia mL−1. Strain B-22 parasitized M. incognita eggs 2 days after treatment, causing the depression and dissolution of egg shells. The fungal spores parasitized J2 by gathering in the body wall, germinating to develop hyphae, and crossing the juvenile cuticle to dissolve it, thereby causing the shrinkage and deformation of the juvenile body wall. The spores and hyphae also attacked adult females, causing the shrinkage and dissolution of their bodies and leakage of contents in 5 days. Results of greenhouse experiments showed that different concentrations of P. chrysosporium effectively controlled different life stages of M. incognita and root knot symptoms in tomato plants. Moreover, the control efficacy increased with increasing conidial concentration; the best results were achieved with 3 × 108 cfu mL−1. In the roots, the highest inhibition rate was 84.61% for adult females, 78.91% for juveniles, 84.25% for the egg mass, and 79.48% for the gall index. The highest juvenile inhibition rate was 89.18% in the soil. Meanwhile, strain B-22 improved the plant growth. Thus, P. chrysosporium strain B-22 is safe for tomato plants while effectively parasitizing M. incognita, making it a promising biocontrol agent against M. incognita.
An innovative non-invasive technique for subcutaneous tumour measurements
Authors: Delgado-SanMartin Juan , Ehrhardt Beate , Paczkowski Marcin , Hackett Sean , Smith Andrew , Waraich Wajahat , Klatzow James , Zabair Adeala , Chabokdast Anna , Rubio-Navarro Leonardo , Rahi Amar , Wilson Zena
Published: April 2019

In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. Tumour volume is currently estimated by measuring length and width with callipers and then estimating the volume of the tumour as if it were a regular spheroid. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours frequently are irregular.

This paper explores the extent of inconsistencies in calliper measurements by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. We also explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume – BioVolume™, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour. It detects the tumour region automatically and estimates the tumour volume in under a second. BioVolume has been tested on a dataset of 297 scans from over 120 mice collected by four different operators.

This work demonstrates that it is possible to record tumour measurements in a rapid, minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.
Plant A20/AN1 proteins coordinate different immune responses including RNAi pathway for antiviral immunity
Authors: Chang Li , Chang Ho-Hsiung , Chiu Yi-Shu , Chang Jui-Che , Hsu Duen-Wei , Tzean Yuh , Cheng An-Po , Lu Hsiang-Chia , Yeh Hsin-Hung
Published: April 2019

Salicylic acid (SA)-mediated immunity plays important roles in combating virus in plants. Two plant stress associated protein (SAPs) containing dual A20/AN1 zinc-finger domain were found to play important roles in SA-mediated immunity; however, detailed mechanisms remain elusive. In this study, another orchid homolog gene of Pha13, Pha21, was analyzed. Pha21 confers antiviral immunity in both transgenic orchid and Arabidopsis overexpressing Pha21. Expression of Pha21 is early-induced by SA treatment, and is involved in the expression of the orchid homolog of the master regulator NPR1. Pha21 but not Pha13 is involved in the expression of key RNAi-related genes, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1) in orchids. The involvement of SAPs in expression of orchid DCL4 and AGO1 is not limited to orchid, as AtSAP5 also plays essential role in the expression of Arabidopsis DCL4 and AGO1. However, unlike Pha13 and AtSAP5, Pha21 does not play positive role in the expression of orchid homolog gene of RNA-dependent RNA polymerase 1 (RdR1), an important gene in RNAi pathway. Pha21 can be found localized in the nucleus, and confers self-E3 ligase and ubiquitin binding activities. Functional domain analysis revealed that both A20 and AN1 domains of Pha21 are required for decreasing virus accumulation, and the AN1 domain plays a more important role in the expression of orchid DCL4. Collectively, our data suggests SA regulated SAPs play important roles in antiviral immunity and is involved in delicate regulation of key genes in RNAi-mediated pathway.

IMPORTANCE

Salicylic acid (SA)-mediated antiviral immunity plays an important role to protect plants from virus infection; however, the detailed mechanisms remain elusive. We previously demonstrated that two plant A20/AN1 proteins, orchid Pha13 and Arabidopsis AtSAP5, function similarly and serve as an important hub to regulate SA-mediated antiviral immunity. In this study, we identified another orchid A20/AN1 protein, Pha21, which is involved in SA-mediated antiviral immunity. In contrast to Pha13 and AtSAP5, Pha21 plays minor negative roles in the expression of PhaRdR1 (orchid homolog of RNA-dependent RNA polymerase 1). However, Pha21 and AtSAP5, but not Pha13, are involved in the expression of important players in RNAi pathway, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1), in orchid and Arabidopsis. Our data demonstrates that plant A20/AN1 proteins are conserved players in SA-mediated antiviral resistance among plants, and provide links between the A20/AN1 proteins and the RNAi pathway.
Kinematic calibration of serial robot using dual quaternions
Authors: Li Guozhi , Zhang Fuhai , Fu Yili , Wang Shuguo
Published: April 2019

Purpose

The purpose of this paper is to propose an error model for serial robot kinematic calibration based on dual quaternions.

Design/methodology/approach

The dual quaternions are the combination of dual-number theory and quaternion algebra, which means that they can represent spatial transformation. The dual quaternions can represent the screw displacement in a compact and efficient way, so that they are used for the kinematic analysis of serial robot. The error model proposed in this paper is derived from the forward kinematic equations via using dual quaternion algebra. The full pose measurements are considered to apply the error model to the serial robot by using Leica Geosystems Absolute Tracker (AT960) and tracker machine control (T-MAC) probe.

Findings

Two kinematic-parameter identification algorithms are derived from the proposed error model based on dual quaternions, and they can be used for serial robot calibration. The error model uses Denavit–Hartenberg (DH) notation in the kinematic analysis, so that it gives the intuitive geometrical meaning of the kinematic parameters. The absolute tracker system can measure the position and orientation of the end-effector (EE) simultaneously via using T-MAC.

Originality/value

The error model formulated by dual quaternion algebra contains all the basic geometrical parameters of serial robot during the kinematic calibration process. The vector of dual quaternion error can be used as an indicator to represent the trend of error change of robot’s EE between the nominal value and the actual value. The accuracy of the EE is improved after nearly 20 measurements in the experiment conduct on robot SDA5F. The simulation and experiment verify the effectiveness of the error model and the calibration algorithms.
Intellectual capital for exploratory and exploitative innovation
Authors: Duodu Bismark , Rowlinson Steve
Published: April 2019

Purpose

Intellectual capital (IC) has been suggested to be a means by which firms develop capabilities that enhance competitive advantage. There is, however, a paucity of empirical research linking IC with innovation in construction firms, leaving the IC–innovation link in such environments unclear. The purpose of this paper is to advance understanding of the relationships between IC components and strategic exploratory and exploitative innovation in construction contractor firms.

Design/methodology/approach

The sample comprised 135 management personnel from construction contractor firms in Hong Kong. Data were collected through a questionnaire survey using validated scales in the literature which were subjected to confirmatory factor analysis. Hierarchical linear regression was used to test the hypotheses while partial least squares structural equation modelling was used forpost hocanalysis.

Findings

Social capital (SC) and organisational capital (OC) each have significant positive linear effects on exploratory and exploitative innovation, while human capital (HC) has no direct linear effect on either innovation type. HC, however, affects both exploratory and exploitative innovation through SC or OC. None of the three IC dimensions has a significant quadratic effect on exploratory or exploitative innovation. The findings suggest that in construction contractor firms increases in the accumulation of SC and OC are associated with proportional increases in exploratory and exploitative innovation.

Originality/value

Despite the growth of studies connecting IC to innovation, the link between IC and exploratory and exploitative innovation has focussed on linear effects in units or on radical innovation outcomes. This study makes a novel contextual contribution by exploring both linear and quadratic effects of IC dimensions on strategic exploratory and exploitative innovation processes in construction contractor firms. The insights contribute to advance knowledge on the relationship between IC and innovation categories in different industrial settings.
Mediating effect of organizational learning and moderating role of environmental dynamism on the relationship between strategic change and firm performance
Authors: Mohammad Haruna Isa
Published: April 2019

Purpose

With the materialization of literature on strategic change, it is clear that organizational learning and organizational dynamism have been among the most notable areas of study. The purpose of this paper is to extend the literature on strategic management by examining the mediating effects of organizational learning and the moderating role of environmental dynamism on the relationship between strategic change and firm performance.

Design/methodology/approach

A survey questionnaire was administered to 650 respondents who were both corporate and business-level managers of 22 main deposit money banks (commercial banks) and their branches across the country. In total, 630 questionnaires were returned and 587 were used after following all the processes of data preparation. Path analysis was employed to test the hypotheses in this study using Smart PLS 3.

Findings

The study found a significant mediating effect of organizational learning on the relationship between strategic change and firm performance. Although no significant moderating role of environmental dynamism was found, the directions of the path coefficients are consistent with the hypothesis. All the relationships between the constructs are significant.

Research limitations/implications

It is paramount for managers to understand the type of environment and learning that fits diverse kinds of strategic changes in order to improve firm performance. It is evident that changes that are not proactive and generative organizational learning may seem dangerous for a firm. However, organizations should learn to incorporate the change to be able to compete in a dynamic competitive environment.

Originality/value

Prior studies on strategic change, environmental dynamism and organizational learning have mainly focused on manufacturing and construction industries in the developed countries, but less has been done in the service sector, particularly the banking organizations in developing countries. Nigeria is one of those countries. Therefore, this study focuses on the links between strategic change and firm performance, moderating role of environmental dynamism and the mediating effect of organizational learning within the context of the Nigerian deposit money banks.
Density‐dependent population dynamics of a high Arctic capital breeder, the barnacle goose
Authors: Layton‐Matthews Kate , Loonen Maarten J. J. E. , Hansen Brage Bremset , Coste Christophe F. D. , Sæther Bernt‐Erik , Grøtan Vidar
Published: April 2019

Density regulation of the population growth rate occurs through negative feedbacks on underlying vital rates, in response to increasing population size. Here, we examine in a capital breeder how vital rates of different life‐history stages, their elasticities and population growth rates are affected by changes in population size.

We developed an integrated population model for a local population of Svalbard barnacle geese, Branta leucopsis, using counts, reproductive data and individual‐based mark–recapture data (1990–2017) to model age class‐specific survival, reproduction and number of individuals. Based on these estimates, we quantified the changes in demographic structure and the effect of population size on age class‐specific vital rates and elasticities, as well as the population growth rate.

Local density regulation at the breeding grounds acted to reduce population growth through negative effects on reproduction; however, population size could not explain substantial variation in survival rates, although there was some support for density‐dependent first‐year survival.

With the use of prospective perturbation analysis of the density‐dependent projection matrix, we show that the elasticities to different vital rates changed as population size increased. As population size approached carrying capacity, the influence of reproductive rates and early‐life survival on the population growth rate was reduced, whereas the influence of adult survival increased. A retrospective perturbation analysis revealed that density dependence resulted in a positive contribution of reproductive rates, and a negative contribution of the numbers of individuals in the adult age class, to the realised population growth rate.

The patterns of density dependence in this population of barnacle geese were different from those recorded in income breeding birds, where density regulation mainly occurs through an effect on early‐life survival. This indicates that the population dynamics of capital breeders, such as the barnacle goose, are likely to be more reproduction‐driven than is the case for income breeders.
A Method for Stabilizing the Proportion of the Reduced Form of Albumin During Cell‐Free and Concentrated Ascites Reinfusion Therapy in Patients with Malignant Ascites
Authors: Ohashi Atsushi , Nakai Shigeru , Yamada Sachie , Kato Masao , Hasegawa Midori
Published: April 2019

Cell‐free and concentrated ascites reinfusion therapy (CART) is used to treat malignant ascites. However, the qualities of albumin in malignant ascites, such as antioxidative activity, may decrease owing to oxidative stress caused by cancer cells and inflammatory reactions. We investigated the fraction percentages of mercaptalbumin (HMA%, reduced form) and non‐mercaptalbumin (HNA%, oxidized form) in malignant ascites from 21 patients who received CART and compared the HMA% in the malignant ascites and human serum albumin (HSA) preparations. HMA% of albumin in malignant ascites (22.5%) was significantly lower than that in HSA preparation (42.2%). To ensure a high HMA%, we added L‐cysteine to the paracentesis‐treated ascites followed by dialysis 1 h later. As a result, the HMA% of albumin in malignant ascites was increased to 59.1%. Our results suggest that using this method in CART will improve patient's albumin quality.
Protocolised thromboelastometric‐guided haemostatic management in patients with traumatic brain injury: a pilot study
Authors: Gratz J. , Güting H. , Thorn S. , Brazinova A. , Görlinger K. , Schäfer N. , Schöchl H. , Stanworth S. , Maegele M.
Published: April 2019

Coagulopathy in patients with traumatic brain injury is associated with an increase in morbidity and mortality. Although timely and aggressive treatment of coagulopathy is of paramount importance, excessive transfusion of blood products has been linked with poor long‐term outcomes in patients with traumatic brain injury. A point‐of‐care thromboelastometric‐guided algorithm could assist in creating a more individually tailored approach to each patient. The aim of this study was to evaluate the feasibility of implementing a thromboelastometric‐guided algorithm in centres that were formerly naïve to thromboelastometry. Hence, we developed such an algorithm and provided training to four centres across Europe to direct the haemostatic management of patients with severe traumatic brain injury. The primary outcome was adherence to the algorithm and timing of the availability of relevant results. Thirty‐two patients were included in the study. Complete adherence to the algorithm was observed in 20 out of 32 cases. The availability of thromboelastometric results after hospital admission was reported significantly earlier than conventional coagulation tests (median (IQR [range]) 33 (20–40 [14–250]) min vs. 71 (51–101 [32–290]) min; p = 0.037). Although only 5 out of 32 patients had abnormalities of conventional coagulation tests, 21 out of 32 patients had a coagulopathic baseline thromboelastometric trace. Implementing a thromboelastometric‐guided algorithm for the haemostatic therapy of traumatic brain injury is feasible in centres formerly naïve to this technology and may lead to more rapid and precise coagulation management. Further large‐scale studies are warranted to confirm the results of this pilot trial and evaluate clinical outcomes.
Child outcomes after placement of a cervical pessary in women with a multiple pregnancy: A 4‐year follow‐up of the ProTWIN trial
Authors: Simons Noor E. , van de Beek Cornelieke , van der Lee Johanna H. , Opmeer Brent C. , van Wassenaer‐Leemhuis Aleid G. , van Baar Anneloes L. , Steenis Leonie , Liem Sophie , Schuit Ewoud , Bekedam Dick , Mol Ben W. J. , van‘t Hooft Janneke
Published: April 2019

Introduction

The ProTWIN trial previously showed no beneficial effect of treatment with a cervical pessary vs usual care to prevent preterm birth in women with a multiple pregnancy. However, in women with a midtrimester short cervix (<38 mm), pessary did reduce the composite outcome of neonatal morbidity and mortality. This follow‐up study evaluates the long‐term outcomes of all children born to mothers who participated in the ProTWIN trial at 4 years of age.

Material and methods

Parents received the Ages and Stages Questionnaire, Strength and Difficulties Questionnaire and a health questionnaire. All questionnaires were reported separately and as a combined outcome (abnormal child outcome). A linear mixed effects model was used to adjust for correlated data in twins and correction for confounders was performed. In exploratory analysis, a composite outcome of death or survival with abnormal child outcome was used by combining extrapolated data on child outcome with survival data. All data were analyzed for the total group and the subgroup of women with midtrimester short cervix.

Results

Of the original 813 women of the ProTWIN trial, we approached 579, of whom 258 participated (45%) in follow‐up. We received questionnaires of 514 children (281 pessary vs 233 control), with 119 children in the subgroup of women with midtrimester short cervix. An abnormal child outcome was found in 23% in the pessary group vs 16% in the control group (odds ratio 1.58; 95% confidence interval 0.94‐2.65). In exploratory analysis with extrapolated data on child outcome (n = 815), no difference in abnormal child outcome was seen between the pessary and control group. In the subgroup of women with a short cervix (n = 268), this composite outcome indicated a favorable outcome for children born to mothers with pessary.

Conclusions

In women with a multiple pregnancy, the use of a cervical pessary did not improve development, behavior or physical outcomes of the surviving children at age 4.
Levels of glial cell line‐derived neurotrophic factor are decreased, but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in Parkinson’s disease
Authors: Virachit Sophie , Mathews Kathryn J. , Cottam Veronica , Werry Eryn , Galli Emilia , Rappou Elisabeth , Lindholm Pӓivi , Saarma Mart , Halliday Glenda M. , Shannon Weickert Cynthia , Double Kay L.
Published: April 2019

Growth factors can facilitate hippocampus‐based learning and memory and are potential targets for treatment of cognitive dysfunction via their neuroprotective and neurorestorative effects. Dementia is common in Parkinson’s disease (PD), but treatment options are limited. We aimed to determine if levels of growth factors are altered in the hippocampus of patients with PD, and if such alterations are associated with PD pathology. Enzyme‐linked immunosorbent assays were used to quantify seven growth factors in fresh frozen hippocampus from 10 PD and nine age‐matched control brains. Western blotting and immunohistochemistry were used to explore cellular and inflammatory changes that may be associated with growth factor alterations. In the PD hippocampus, protein levels of glial cell line‐derived neurotrophic factor were significantly decreased, despite no evidence of neuronal loss. In contrast, protein levels of fibroblast growth factor 2 and cerebral dopamine neurotrophic factor were significantly increased in PD compared to controls. Levels of the growth factors epidermal growth factor, heparin‐binding epidermal growth factor, brain‐derived neurotrophic factor and mesencephalic astrocyte‐derived neurotrophic factor did not differ between groups. Our data demonstrate changes in specific growth factors in the hippocampus of the PD brain, which potentially represent targets for modification to help attenuate cognitive decline in PD. These data also suggest that multiple growth factors and direction of change needs to be considered when approaching growth factors as a potential treatment for cognitive decline.
Abdominal aortic aneurysm as an IgG4-related disease
Authors: Prucha M , Sedivy P , Stadler P , Zdrahal P , Prokopova P , Voska L , Sedlackova L
Published: April 2019

The objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4-related disease (IgG4-RD). IgG4-RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4-positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4-RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4-RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4-RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high-power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.
Partial nomadism in large‐bodied bream (Abramis brama)
Authors: Brodersen Jakob , Hansen Joan H. , Skov Christian
Published: April 2019

The recent focus on a common movement ecology paradigm has increased awareness about the importance of distinguishing different movement patterns for understanding their specific impact on animal ecology and evolution. One specific form of movement is nomadism, where animals move between habitats in an arrhythmic fashion. Although not yet described in detail for freshwater fish, nomadism between lakes within drainage systems could affect local lake food webs in an otherwise unpredictable fashion. In this study, we used passive telemetry to describe inter‐lake movements of 1,280 individually tagged adult benthivorous bream (Abramis brama) over nine contiguous years in a drainage system with two paired lakes. The movements can best be described as partial nomadism, where a part of the population is neither resident nor migratory, but instead moves between lakes in a variable, arrhythmic fashion, often with long residency in one lake before moving to the other. We found extensive between‐year variation in the proportion and direction of bream moving, with higher movement propensity being partly associated with lower somatic condition. Notably, movements out of lakes were significantly more in direction of the neighbouring lake than away from the paired lakes, suggesting that at least direction was not random. Since bream are important ecosystem engineers, fluctuating densities of adult bream could affect ecological stability in lakes. Our study suggests that fish populations in interconnected lakes within drainages should not be treated as isolated units, and we discuss this in relation to lake ecology and the importance for lake ecosystem management.
Vertical movements of coastal pike (Esox lucius)—On the role of sun basking
Authors: Nordahl Oscar , Koch‐Schmidt Per , Tibblin Petter , Forsman Anders , Larsson Per
Published: April 2019

Knowledge of patterns and drivers of the spatiotemporal distribution of top predatory fish is key to understand ecological dynamics and to successful management. Here, we integrated field and laboratory approaches to study vertical movements of pike (Esox lucius) in relation to season, light regimes and body temperature. We tagged pike from the Baltic Sea with data storage tags during spawning migration and retrieved them during migration the following years to obtain high‐resolution data from full year of movements. The results showed seasonal and diel patterns of activity and body temperature that conformed to distinct patterns of crepuscular activity and diel vertical migrations. The latter manifested as two different patterns, either a stationary phase in the surface water during day followed by night‐time in deeper water or vice versa. The occurrence of these two behaviours varied among individuals and within individuals among seasons. Diel vertical migration has previously not been described for this shallow‐dwelling species, but was a common and consistent behaviour among individuals in this study. We suggest that the function of the daytime surface behaviour in pike is to increase body temperature through sun basking. This thermoregulatory role of surfacing was supported by the laboratory study where individuals sought the surface layer, exposed themselves to infrared light and thereby attained body temperatures in excess of ambient water. These results support sun basking as a mechanism for heat gain and further suggest that access to sunlight in the surface layer could be an important driver of vertical migrations.
Do behavior and emotions improve after pediatric epilepsy surgery? A systematic review
Authors: Reilly Colin , Baldeweg Torsten , Stewart Neil , Wadhwani Suresh , Jones Chloe , Helen Cross J. , Heyman Isobel
Published: April 2019

Objective

The objective was to systematically review studies that have focused on behavioral and emotional functioning before (baseline) and after (follow‐up) pediatric epilepsy surgery.

Methods

The systematic review was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. PubMed and EMBASE were searched from inception. Findings are described with respect to (1) changes in behavior and emotions between baseline and follow‐up, (2) factors associated with changes in behavior and emotions, and (3) impact of study quality on findings.

Results

Fifteen studies met inclusion criteria. The majority of studies employed parent report screening checklists. In these studies, scores were reported to have significantly improved at follow‐up on at least one domain in seven studies and not to have changed significantly in two studies. In no studies was a deterioration in behavior noted. In studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) clinical diagnoses, no significant change was noted in the numbers of children diagnosed at baseline and at follow‐up. In total, 21 children lost diagnoses, whereas 16 children developed new diagnoses. A better seizure outcome was associated with improvements in behavioral‐emotional functioning at follow‐up in three of the four studies where it was considered. In terms of study quality, none of the studies was rated as strong (ie, had no weak ratings on a quality assessment tool).

Significance

There is some evidence of improvement in emotional and behavioral functioning after epilepsy surgery. However, this is confined to scores on parent‐reported screening measures of emotional and behavioral symptoms and not clinical diagnoses. Future research should focus on including responses from multiple respondents (child, parent, teacher) when using screening instruments, but also diagnostic interviews. There is a need for long‐term follow‐up (beyond 2 years) with sufficiently large sample sizes including data from nonsurgery controls to understand factors associated with changes in functioning postsurgery.
Episodic and Chronic Migraine in Primary Care
Authors: Young Nathan P. , Philpot Lindsey M. , Vierkant Robert A. , Rosedahl Jordan K. , Upadhyaya Sudhindra G. , Harris Ann , Ebbert Jon O.
Published: April 2019

Objective

To inform migraine care model development by assessing differences between patients with chronic migraine (CM) and episodic migraine (EM) in the current state of treatment, disability, patient satisfaction, and quality improvement opportunities.

Background

Efficient and focused use of scarce resources will be needed to address challenges within large populations of migraine patients.

Methods

We deployed a cross‐sectional survey study of randomly selected migraine patients within a community primary care practice.

Results

There were 516 survey respondents (516/1804 [30%] response rate). CM patients were more likely than EM patients to report care from a neurologist (76/110 [69%] vs 229/406 [56%]; P = .0026), and higher disability according to the Migraine Disability Assessment and Headache Impact Test – 6 questionnaires (P < .0001). CM patients were less likely than EM patients to report overall satisfaction with care (16/110 [38%] vs 156/406 [66%], P = .0002), satisfaction with access to care (17/110 [33%] vs 176/406 [68%], P < .0001), and advice they needed (16/110 [31%] vs 160/406 [62%], P < .0001). Most patients with migraine had been offered triptan medications 377/516 (78%). Overall, 156/516 (31%) of individuals were currently taking any medication for migraine prevention, and 208/516 (40%) including botulinum toxin injections. CM patients were more likely to be taking preventive medication (39/110 [36%] vs 117/406 [29%], P = .0191) and report familiarity with the diagnosis of medication‐overuse headache than patients with EM (80/110 [81%] vs 256/406 [69%], P = .0178).

Conclusions

We observed differences between patients with chronic and EM and expected care delivery improvement opportunities for migraine patients in primary care. CM patients report higher levels of disability and less satisfaction with access to perceived needed medical advice and care. These findings support the need to further develop and study novel care models to efficiently and effectively deliver high‐quality care and expertise in limited supply to a diverse migraine population.
Association between overweight or obesity and the risk for childhood asthma and wheeze: An updated meta‐analysis on 18 articles and 73 252 children
Authors: Deng Xiangling , Ma Jia , Yuan Yuan , Zhang Zhixin , Niu Wenquan
Published: April 2019

Background

Overweight or obesity is increasingly recognized as a possible risk factor for childhood asthma.

Objectives

We aimed to meta‐analyse the association between overweight or obesity and the risk for childhood asthma and wheeze and meanwhile explore potential causes of between‐study heterogeneity.

Methods

Literature search, study selection, and data extraction were performed independently and in duplicate. Data were analysed by STATA software.

Results

Eighteen articles and 73 252 children were analysed. In overall analyses, there was a significant association between overweight or obesity and the risk for childhood asthma (odds ratio [OR] = 1.30; 95% confidence interval [CI], 1.23‐1.39; P < 0.001) and wheeze (OR = 1.90; 95% CI, 1.38‐2.63; P < 0.001), with none/marginal publication bias as revealed by the Egger test (P = 0.938/0.038), respectively. Subgroup analyses showed that children with obesity (OR = 1.40; 95% CI, 1.29‐1.52) were more likely to have asthma than children with overweight (OR = 1.22; 95% CI, 1.14‐1.31), and in children with overweight or obesity, girls (OR = 1.34; 95% CI, 1.16‐1.56) were more likely to have asthma than boys (OR = 1.27; 95% CI, 1.15‐1.40).

Conclusions

Our findings indicate that overweight or obesity is a significant risk factor for childhood asthma and wheeze and in children with overweight or obesity, the risk is more evident in girls than in boys.
A cash‐constrained dynamic lot‐sizing problem with loss of goodwill and credit‐based loan
Authors: Chen Zhen , Zhang Ren‐qian
Published: April 2019

We consider a small retailer that manages its inventory under a strict cash constraint. At each period, the retailer's available cash restricts the maximum inventory level that it can replenish. These retailers are nanostores, which are widely present in emerging markets, or small online retailers in some Chinese e‐commerce platforms. We assume that the retailer can decide the satisfied demand quantity even if it has enough inventory, but unsatisfied demand in one period may cause customer demand to decrease in the next period considering the loss of goodwill. The retailer could adopt a credit‐based loan provided by its suppliers or e‐commerce platforms to alleviate cash shortages. A profit maximization single‐item lot‐sizing model is constructed for this problem. Numerical tests demonstrate that cash‐flow constraint is different from traditional capacity constraint, and that cash availability, as well as loan interest rate, can substantially affect a retailer's optimal lot‐sizing decisions. Our model can help a retailer decide at the beginning of the planning horizon whether it is worth applying for a credit‐based loan with a given loan policy. We prove that the zero‐inventory‐ordering property still holds for certain situations, and propose a polynomial algorithm with heuristic adjustments to solve this problem when customers' payment delay length can be neglected. If unit variable ordering costs are equal and the loss of goodwill rate is zero, the algorithm can obtain optimal solutions. Under other situations, comparisons with CPLEX 12.6.2 show that our algorithm can reach optimal performance in most cases, and it has a computation time advantage for large‐sized problems.