bluuebunny/crossref_metadata_2025 huggingface dataset:
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program
Authors: Eckersley-Maslin Mélanie , Alda-Catalinas Celia , Blotenburg Marloes , Kreibich Elisa , Krueger Christel , Reik Wolf
Published: January 2019

The molecular regulation of zygotic genome activation (ZGA) in mammals remains an exciting area of research. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two-cell embryo and thus represent an in vitro approximation for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA in either a Dux-dependent or Dux-independent manner. Here we performed a candidate-based overexpression screen, identifying, among others, developmental pluripotency-associated 2 (Dppa2) and Dppa4 as positive regulators of 2C-like cells and transcription of ZGA genes. In the germline, promoter DNA demethylation coincides with expression of Dppa2 and Dppa4, which remain expressed until embryonic day 7.5 (E7.5), when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during induced pluripotent stem cell (iPSC) reprogramming at the time that 2C-like transcription transiently peaks. Through a combination of overexpression, knockdown, knockout, and rescue experiments together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we teased apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilized. Dppa2 and Dppa4 require Dux to initiate 2C-like transcription, suggesting that they act upstream by directly regulating Dux. Supporting this, ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) analysis revealed that Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild-type cells but, in contrast to Dux, can no longer do so in Dppa2/4 double-knockout cells, suggesting that it may act to stabilize rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux up-regulation and activation of the 2C-like transcriptional program, which is subsequently reinforced by Zscan4c.
The circular RNome of primary breast cancer
Authors: Smid Marcel , Wilting Saskia M. , Uhr Katharina , Rodríguez-González F. Germán , de Weerd Vanja , Prager-Van der Smissen Wendy J.C. , van der Vlugt-Daane Michelle , van Galen Anne , Nik-Zainal Serena , Butler Adam , Martin Sancha , Davies Helen R. , Staaf Johan , van de Vijver Marc J. , Richardson Andrea L. , MacGrogan Gaëten , Salgado Roberto , van den Eynden Gert G.G.M. , Purdie Colin A. , Thompson Alastair M. , Caldas Carlos , Span Paul N. , Sweep Fred C.G.J. , Simpson Peter T. , Lakhani Sunil R. , Van Laere Steven , Desmedt Christine , Paradiso Angelo , Eyfjord Jorunn , Broeks Annegien , Vincent-Salomon Anne , Futreal Andrew P. , Knappskog Stian , King Tari , Viari Alain , Børresen-Dale Anne-Lise , Stunnenberg Hendrik G. , Stratton Mike , Foekens John A. , Sieuwerts Anieta M. , Martens John W.M.
Published: January 2019

Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer.
Radiation damage in protein crystallography at X-ray free-electron lasers
Authors: Nass Karol
Published: January 2019

Radiation damage is still the most limiting factor in obtaining high-resolution structures of macromolecules in crystallographic experiments at synchrotrons. With the advent of X-ray free-electron lasers (XFELs) that produce ultrashort and highly intense X-ray pulses, it became possible to outrun most of the radiation-damage processes occurring in the sample during exposure to XFEL radiation. Although this is generally the case, several experimental and theoretical studies have indicated that structures from XFELs may not always be radiation-damage free. This is especially true when higher intensity pulses are used and protein molecules that contain heavy elements in their structures are studied. Here, the radiation-damage mechanisms that occur in samples exposed to XFEL pulses are summarized, results that show indications of radiation damage are reviewed and methods that can partially overcome it are discussed.
A review of machine efficiency in mass customization
Authors: James C.D. , Mondal Sandeep
Published: January 2019

Purpose

The purpose of this paper is to address the gap between definition and practical aspects of production efficiency in mass customization (MC). The paper summarizes all major issues impacting efficiency in MC. Also, the paper reviews metrics, relationship between various parameters and provides a best practices benchmark toolkit to achieve higher machine efficiencies.

Design/methodology/approach

The paper identified and categorized multiple challenges impacting machine efficiency in MC through a literature review spanning over three decades, and also ranked the identified issue-based parameters. Top issues were found varying across different types of industries identified through the review. Metrics pertaining to efficiency and degree of MC are reviewed in the paper. A chronological review of issues is presented, and a chain diagram is built in the paper. Toolkit of best practices created with solution strategies and tools are summarized through the review.

Findings

The paper found that MC reasonably impacts machine efficiency which needs to be addressed. Major issues through literature review-based ranking are uncovered, and worldwide research trend and comparison are presented. Active research in this area is observed to be at its peak since 2010. The extensive use of strategies and benchmark toolkit for improving efficiency are summarized.

Research limitations/implications

Ranking of issues has been done through a literature review; hence, there can be skewness depending on the frequency of issues researched by various authors in various areas of industries.

Practical implications

This paper is useful for manufacturing managers and companies willing to increase the size of their product portfolio and choices within their available resources without compromising machine efficiencies and, thereby, the cost. The identified issues help in providing a comprehensive issue list to the academia.

Originality/value

This paper describes what is believed to be the first study that explicitly examines the issues faced in achieving machine efficiency while manufacturing in an MC environment.
Employee optimism in India: validation of the POSO-E
Authors: Bharti Teena , Rangnekar Santosh
Published: January 2019

Purpose

The purpose of this paper was to validate the short version of personal optimism and self-efficacy optimism scale developed by Gavrilov-Jerkovicet al.(2014) on a sample of 398 employees working in private and public sector organizations in India.

Design/methodology/approach

The study needs to test the psychometric properties of the Indian version of scale by using exploratory factor analysis, convergent validity, discriminant validity and confirmatory factor analysis.

Findings

The results supported for the two-dimensional factor-structure of optimism in consonance with Gavrilov-Jerkovicet al.(2014).

Research limitations/implications

The findings will benefit both the management and the employees. Also, the study expands the existing literature on the variable in the Indian context.

Originality/value

The work validates and provides a unique instrument to measure the employee optimism that can help the management and the employees to focus on themselves to increase the positivity to provide an innovative and creative environment. Also, the work supplements the existing literature on positive attitude or outcome expectancies and helps in establishing the bi-dimensional nature of the construct of optimism.
Antecedents, mediators and consequences of sustainable operations
Authors: De Guimarães Julio Cesar Ferro , Dorion Eric Charles Henri , Severo Eliana Andréa
Published: January 2019

Purpose

The purpose of this paper is to propose a framework for analyzing the relationships between the antecedent factors, mediators and consequences of sustainable operations (SO), which can be applied for empirical studies in the manufacturing industry.

Design/methodology/approach

Based on the importance of identifying the determinants of SO, a qualitative and exploratory research was developed through an extensive review of the literature.

Findings

The main theoretical contribution of this research on organizational studies is the SO analysis proposition framework, which allows the elaboration of scales, based on observable variables of each factor, as well as evaluating the influence intensity of the relations between the constructs.

Research limitations/implications

The proposed framework of this research was developed to analyze companies of the manufacturing industry. In order to use the proposed framework in other industries (commerce, services), it will be necessary to make adaptations and adjustments on the observable variables and constructs.

Originality/value

The paper has an important theoretical value in proposing scales for the SO factors and can be useful for future quantitative approach and surveys. Consequently, the researcher will be able to evaluate the scales of the factors and the intensity of the relations between observable variables in the formation of the constructs, as well as the intensity of influence among the constructs.
TQM, games design and the implications of integration in Industry 4.0 systems
Authors: Beard-Gunter Alison , Ellis David Geraint , Found Pauline Anne
Published: January 2019

Purpose

Voluntary participation, feedback loops, rules and goals are key elements of total quality management (TQM). The purpose of this paper is to determine if these four elements which make TQM successful are the same elements that make computer games successful. If this is the case, what are the implications for developers of Human Computer Interfaces (HCI) in Industry 4.0.

Design/methodology/approach

This paper is a systematic literature review of recent literature on engagement in games and user experiences and HCI design for industry followed by interpretation of the literature. The findings from the literature review are analysed and compared to TQM.

Findings

Good game design and TQM share four key components: goals, rules, a feedback system (including rewards) and voluntary participation. There is an opportunity for HCI developers to use a user experience lens inherent in games evolution and to expand on the design and motivational elements that have made games and TQM successful at motivating and engaging. Kuutti’s (1995) proposal of activity theory puts forward a promising framework for making systems engaging. There are positive implications merging good games design and TQM in socio-technic systems which could improve engagement and quality in companies implementing in Industy 4.0.

Research limitations/implications

The implications of achieving increased engagement in HCI systems similar to those seen in companies that have successfully implemented TQM could lead to greater productivity in companies operating in the highly technical environments of Industry 4.0.

Originality/value

The originality of this paper is threefold: first, a description of the origins in industry of voluntary participation, feedback loops, rules and goals and their relationship to TQM; second, a systematic literature review of the same elements in computer games design; and third, the implications for developers of HCI systems in Industry 4.0.
The magnetotelluric impedance tensor through Clifford algebras: part I — theory
Authors: Romero‐Ruiz Ivan , Pous Jaume
Published: January 2019

The magnetotelluric impedance tensor is analysed in the context of Clifford algebras. In this framework, the tensor is broken down into different parts, each one with a particular geometric algebra meaning, the simplicity of which allows us to deduce a number of known properties and opens up many other possibilities. As examples to show its capabilities, some of the algebraic relationships involving the impedance tensor, such as rotations, Mohr diagrams and phase tensor, are shown under this theory. Rotations are analysed in Clifford algebra and Mohr diagrams, and phase tensor are expressed in Clifford algebra . The galvanic distortion matrix and its transformations are also seen in Clifford algebra , where a number of relationships allow us to recognize the galvanic distortion in a measured two‐dimensional/three‐dimensional impedance tensor. These relationships are useful as constraints to determine the galvanic distortion parameters.
Resource overlap and dilution effects shape host plant use in a myrmecophilous butterfly
Authors: Valdés Alicia , Ehrlén Johan
Published: January 2019

The effects of consumers on fitness of resource organisms are a complex function of the spatio‐temporal distribution of the resources, consumer functional responses and trait preferences, and availability of other resources.

The ubiquitous variation in the intensity of species interactions has important consequences for the ecological and evolutionary dynamics of natural populations. Nevertheless, little is known about the processes causing this variation and their operational scales. Here, we examine how variation in the intensity of a consumer–resource interaction is related to resource timing, resource density and abundance of other resources.

Using the butterfly consumer Phengaris alcon and its two sequential resources, the host plant Gentiana pneumonanthe and the host ants Myrmica spp., we investigated how butterfly egg‐laying depended on focal host plant phenology, density and phenology of neighbouring host plants and host ant abundance.

Butterflies preferred plants that simultaneously maximized the availability of both larval resources in time and space, that is, they chose early‐flowering plants that were of higher nutritional quality for larvae where host ants were abundant. Both the probability of oviposition and the number of eggs were lower in plant individuals with a high neighbour density than in more isolated plants, and this dilution effect was stronger when neighbours flowered early.

Our results show that plant–herbivore interactions simultaneously depend on the spatio‐temporal distribution of a focal resource and on the small‐scale spatial variation in the abundance of other herbivore resources. Given that consumers have negative effects on fitness and prefer certain timing of the resource organisms, this implies that processes acting at the levels of individuals, populations and communities simultaneously contribute to variation in consumer‐mediated natural selection.
Tree species diversity promotes litterfall productivity through crown complementarity in subtropical forests
Authors: Zheng Li‐Ting , Chen Han Y. H. , Yan En‐Rong
Published: January 2019

The role of niche complementarity for driving the positive biodiversity–ecosystem productivity relationship has been widely recognized, but there is scant evidence regarding the role of tree canopy structure on this relationship. Litterfall productivity is proportional to forest net primary productivity in natural forests, and we hypothesized that litterfall productivity would increase with tree species diversity via increased tree crown complementarity.

We investigated annual litterfall productivity, species diversity, tree crown architecture, soil moisture content, soil carbon content and stand age across 28 subtropical forest plots in eastern Zhejiang province, China. Simple linear regression was used to examine bivariate relationships among rarified species richness, crown complementarity, total crown volume, soil moisture content, soil carbon content, stand age and litterfall productivity. Structural equation modelling was employed to quantify the direct and indirect effects of species richness on litterfall productivity through tree crown complementarity.

Litterfall productivity increased with rarefied species richness via increasing crown complementarity rather than total crown volume. Species richness, crown complementarity and litterfall productivity increased with soil moisture content, while crown complementarity and litterfall productivity increased with soil carbon content. Neither species richness nor crown complementarity increased with stand age, even though litterfall productivity increased with stand age.

Synthesis. Our study provides evidence for the strong role of tree crown assembly in shaping ecosystem functions in complex natural forests. Our findings suggest that crown spatial complementarity among trees operates mechanistically to drive the positive tree species diversity–litterfall productivity relationship in subtropical forests. We argue that community and/or ecosystem ecology would benefit from more attention to crown variability among coexisting tree species.
A novel method for elimination of aflatoxin M1 in milk using Lactobacillus rhamnosus GG biofilm
Authors: Assaf Jean Claude , Khoury André El , Chokr Ali , Louka Nicolas , Atoui Ali
Published: January 2019

This study aimed to develop a new method for detoxification of milk from aflatoxin M1 (AFM1) by using Lactobacillus rhamnosus GG biofilm. After inoculation of milk contaminated with AFM1 into L. rhamnosus GG biofilm, the unbound AFM1 was extracted and quantified by HPLC. The stability of the formed AFM1/biofilm complex using different AFM1 contamination levels of milk was also studied. We found that the percentages of bound AFM1 by L. rhamnosus GG biofilm reached up to 60.74%. While no significant difference in milk proteins content was observed after AFM1 binding, some changes in total dry matter and fat content were noticed.
CRISPR/Cas9‐mediated ebony knockout results in puparium melanism in Spodoptera litura
Authors: Bi Hong‐Lun , Xu Jun , He Lin , Zhang Yong , Li Kai , Huang Yong‐Ping
Published: January 2019

Insect body pigmentation and coloration are critical to adaption to the environment. To explore the mechanisms that drive pigmentation, we used the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) genome editing system to target the ebony gene in the non‐model insect Spodoptera litura. Ebony is crucial to melanin synthesis in insects. By directly injecting Cas9 messenger RNA and ebony‐specific guide RNAs into S. litura embryos, we successfully induced a typical ebony‐deficient phenotype of deep coloration of the puparium and induction of melanin formation during the pupal stage. Polymerase chain reaction‐based genotype analysis demonstrated that various mutations had occurred at the sites targeted in ebony. Our study clearly demonstrates the function of ebony in the puparium coloration and also provides a potentially useful marker gene for functional studies in S. litura as well as other lepidopteran pests.
Determination of Antifungal Effect of Edible Coatings Containing Williopsis saturnus var. saturnus Against Yeast and Mold Growth on Kashar Cheese
Authors: Civelek Ilknur , Cagri‐Mehmetoglu Arzu
Published: January 2019

One of the most important problems of Kashar cheese producers is mold and yeast spoilage during storage. Williopsis saturnus var. saturnus killer yeast has been reported to have an antagonistic effect on mold and yeast reproduction. In this study, the antifungal effect of a whey protein concentrate (WPC) coating containing W. saturnus was investigated in Kashar cheese. WPC with or without W. saturnus (7 log CFU/g) or W. saturnus without coating was applied on the surface of Kashar cheese samples and stored at 4 °C for 56 days. Microbiological, chemical, physical and sensory properties of cheese samples were assessed. After 56 days of storage, the numbers of lactic acid bacteria were not affected by WPC containing W. saturnus; however, the population of W. saturnus increased by 1 log CFU/g. Application of W. saturnus reduced the growth of other yeasts and molds (P < 0.05). Chemical, physical and sensory properties of all coated cheeses remained unchanged. In a conclusion, use of WPC coatings containing W. saturnus can potentially minimize mold and yeast spoilage of cheese during storage.
Ultrasound‐Assisted Extraction of Chitosan from Squid Pen: Molecular Characterization and Fat Binding Capacity
Authors: Singh Avtar , Benjakul Soottawat , Prodpran Thummanoon
Published: January 2019

Chitosan from squid (Loligo formosana) pens were prepared and characterized. First, ultrasonication condition was optimized for deproteinization of squid pens using central composite design (CCD) of response surface methodology (RSM). Squid pens were ultrasonicated at amplitude 69% for 41.46 min at the solid/solvent ratio of 1:18 yielded 34% (w/w) chitin with the lowest remaining protein. Therefore, ultrasonication effectively reduced the extraction time for chitin production from squid pens as compared to traditional method (5 hr). When the resultant chitin was subjected to deacetylation at different temperatures and times, yield and degree of deacetylation (DDA) of chitosan were in the range of 50% to 65% (w/w) and 78% to 90%. Intrinsic viscosity and molecular weight (MW) of chitosan were in the range of 3.2 to 6.52 dL/g and 1.2 × 105 to 3.2 × 105 Da, respectively. All the chitosans with different DDA were able to bind oil droplets under the mimicked pH condition of gastrointestinal tract. Chitosan produced by deacetylation at 130 °C for 2 hr (CH130‐2) showed the optimum yield (54%) and had medium MW (1.5 × 105 Da). DDA of CH130‐2 determined using 1H‐NMR was 89%, which was similar to that (87%) obtained from FTIR. XRD results showed destruction of chitin structure and decreased crystallinity index from 55% to 27% after deacetylation. CH130‐2 stabilized the emulsion under the simulated gastrointestinal conditions. Therefore, it could be used as dietary fiber to control the adsorption of fat/oil in the human digestive tract.

Practical Application

Chitin and chitosan are marketable products manufactured from crustacean shells. However, extraction of chitin is time consuming. Ultrasonication has been used for extraction of various biomolecules from different sources. It effectively lowers the processing time and enhances extraction yield. Therefore, application of ultrasonication with optimized condition using RSM could reduce extraction time and enhance yield of chitin from squid pen. Chitin from squid pen could be further converted to chitosan with high DDA. Chitosan was able to act as a dietary fiber and reduce fat absorption in gastrointestinal tract. Thus, this information is of benefit for squid processing industry to exploit squid pen, a processing byproduct.
Keeping Out Extreme Inequality from the SDG Agenda – The Politics of Indicators
Authors: Fukuda‐Parr Sakiko
Published: January 2019

The SDGs are important because they set consensus norms. At face value, Goal 10 sets a strong norm on reducing inequality within and between countries. Yet this is undermined and distorted by the targets and indicators which are weak and set an agenda for inclusion rather than for reducing inequalities. This paper explains this paradox as a result of an intense contestation over the framing of the inequality agenda as inclusion, focusing on the poor and excluded, rather than on extreme inequality. The paper provides a detailed account of the negotiations and argues that the insertion of the shared prosperity measure in setting the target on vertical economic inequality (rather than distribution measures such as Gini or Palma ratio) was strategic. It concludes that the political choice over the meaning of a norm is made on what is said to be a technical basis. The technical and political considerations cannot be disentangled and greater transparency on the policy strengths and weaknesses of measurement choices is needed.
The IHME in the Shifting Landscape of Global Health Metrics
Authors: Mahajan Manjari
Published: January 2019

The rise of the Institute for Health Metrics and Evaluation (IHME) has augured profound changes in the landscape of global health metrics. Primarily funded by the Bill and Melinda Gates Foundation, the IHME has offered donors a platform for assessing many health‐related Sustainable Development Goal (SDG) indicators and a toolkit to measure the progress of different countries. The IHME's increasing influence reveals the relative sidelining of international agencies and especially the World Health Organization which has long been central to global health metrics production. This shift reflects a growing conflict between the expertise and norms of national and intergovernmental statistical production on the one hand, and the distinct epistemologies and logics of new non‐state data actors. These transitions – from an international world of statistics to a more plural, global realm of data – have acute implications for the politics and accountability of knowledge production related to the SDGs and development writ large. Even as the SDGs embrace the rubric of ‘no one left behind’, the emerging data politics might be eroding the ability of poorer states to know and act upon their development problems on their own terms.
Pirate Wireless: Revenue Recognition in the Telecommunications Industry
Authors: Henry Theresa F. , Mest David P. , Safar Mona L.
Published: January 2019

Pirate Wireless is a telecommunications company with stores and offices all over the globe. Jim Bayley is an extremely busy professional who enters into a contract with Pirate Wireless for the ultimate purchase of a smartphone with one‐year warranty, voice and data services, Cryptonite encryption software, and an extended warranty. The case requires students to act as Assistant Controller of Pirate Wireless Corporate and determine the appropriate revenue recognition for Pirate Wireless's contract with Jim Bayley. This mandates a thorough review of the five steps of revenue recognition set forth in Revenue from Contracts with Customers, the jointly converged standard issued by the Financial Accounting Standards Board (FASB) and the International Accounting Standards Board (IASB) in May 2014. The FASB's Accounting Standards Codification 606 is effective for all U.S. public entities for fiscal years ending after December 15, 2017. The IASB's International Financial Reporting Standards (IFRS) 15 applies to an entity's first annual IFRS financial statements for a period beginning on or after January 1, 2018. This case is appropriate for an undergraduate or graduate level Intermediate Accounting course.
The global incidence and prevalence of anaphylaxis in children in the general population: A systematic review
Authors: Wang Yichao , Allen Katrina J. , Suaini Noor H. A. , McWilliam Vicki , Peters Rachel L. , Koplin Jennifer J.
Published: January 2019

Background

Despite an increasing number of publications from individual countries and regions, there is still no systematic review of the global epidemiology of anaphylaxis in the general paediatric population.

Methods

We conducted a systematic review, using a protocol registered and published with the international prospective register of systematic reviews (PROSPERO). Results were reported following PRISMA guidelines. The search strategy was designed in Medline (ovid) and modified for Embase (ovid) and PubMed. Papers were screened by two independent reviewers following selection and exclusion criteria. Data extraction and risk of bias assessment were completed by the same two reviewers. Studies in adults only or those that did not report data in children separately were excluded.

Results

A final total of 59 articles were included. Of these, 5 reported cumulative incidence, 39 reported incidence rate and 17 reported prevalence data. The incidence of anaphylaxis in children worldwide varied widely, ranging from 1 to 761 per 100 000 person‐years for total anaphylaxis and 1 to 77 per 100 000 person‐years for food‐induced anaphylaxis. The definition of anaphylaxis from NIAID/FAAN was the most commonly used. Gender and ethnicity were demographic risk factors associated with anaphylaxis in children. Increasing total or food‐induced anaphylaxis incidence over time was reported by 19 studies.

Conclusion

The reported incidence of anaphylaxis in children varied widely. Studies in developing countries are underrepresented. To accurately compare anaphylaxis incidence between countries and investigate the time trends, further studies using a standardized definition across different countries are required.
Prediction of large‐for‐gestational‐age infants in pregnancies complicated by obesity: A population‐based cohort study
Authors: Åmark Hanna , Westgren Magnus , Persson Martina
Published: January 2019

Introduction

Infants born large for gestational age (LGA) have increased risks of adverse perinatal outcomes. Maternal obesity, defined as body mass index (BMI) ≥30 kg/m2, is one of the most prevalent risk factors for LGA and the proportion of pregnancies complicated by obesity is increasing. Early identification of women with BMI ≥30 kg/m2 at increased risk of giving birth to an LGA infant may open possibilities for prevention, aiming at decreasing the incidence of LGA.

Material and methods

A population‐based cohort study using information from the first‐trimester screening database, which was cross‐linked with the Swedish Medical Birth Register. The database included 139 277 full‐term singletons without fetal anomalies born between 2006 and 2015 to mothers without prepregnancy diabetes. Of these, 9.1% (n = 12 704) were infants of mothers with BMI ≥30 kg/m2. For all women with BMI ≥30 kg/m2, a prediction model for LGA to be used in early pregnancy was constructed based on information on biochemical markers and maternal characteristics. A similar model, as well as a prepregnancy prediction model, were constructed for parous women with BMI ≥30 kg/m2. In parous women, data from the previous pregnancy were also used. Receiver operating characteristic curve and area under curve (AUC) were calculated.

Results

The predictive models for LGA in parous women with BMI ≥30 kg/m2 prepregnancy and in early pregnancy had AUCs of 0.80 (95% CI 0.78‐0.82) and 0.81 (95% CI 0.79‐0.82), respectively. For all women with BMI ≥30 kg/m2, the prediction of LGA in early pregnancy had an AUC of 0.66 (95% CI 0.64‐0.67).

Conclusions

Performance of the prepregnancy and early pregnancy prediction models for LGA in parous women with BMI ≥30 kg/m2 was good. The predictive capacity was largely driven by previous child's birthweight. First‐trimester measurements of fetal size did not improve the predictive capacity in parous women. Predictions of LGA in all women with BMI ≥30 kg/m2 in early pregnancy, without taking previous child's birthweight into account, remain difficult.
Systematic review: epidemiology and response to direct‐acting antiviral therapy in genotype 6 chronic hepatitis C virus infection
Authors: Mettikanont Panita , Bunchorntavakul Chalermrat , Reddy K. Rajender
Published: January 2019

Background

Hepatitis C virus (HCV) genotype 6 (GT6) is predominantly encountered in Southeast Asia and data on GT6 response to direct‐acting antiviral (DAA) therapy are relatively limited.

Aim

To review the epidemiology and virologic outcome of DAA regimens in HCV GT6 patients.

Methods

Electronic literature search of PubMed, EMBASE, and The Cochrane Library databases were conducted.

Results

Hepatitis C virus genotype 6 is the most genetically diverse, has a prevalence of 19.9%‐95.6% in HCV infected patients in Southeast Asia and has been associated with a higher risk of HCC in those with cirrhosis. After an extensive literature review, a total of 20 studies were selected to assess study population and treatment outcomes (total of 938 GT6 patients were included); 12 were clinical trials and eight were observational studies. Sustained virologic response at week 12 (SVR 12) following glecaprevir/pibrentasvir (n = 4; 108 patients), ledipasvir/sofosbuvir (n = 8; 427 patients), sofosbuvir/velpatasvir with or without voxilaprevir (n = 5; 171 patients), sofosbuvir/daclatasvir (n = 3; 172 patients) and sofosbuvir with ribavirin (n = 3; 60 patients) was 98%‐100%, 64%‐100%, 100%, 88%‐94% and 100%, respectively. Failure was mostly in those with cirrhosis and prior treatment experience. DAA therapy was well tolerated and with a serious adverse event rate of <5%.

Conclusions

Hepatitis C virus genotype 6 is genetically diverse and is highly prevalent in Asia. While SVR rates have been high, cirrhosis and prior treatment experience marginally compromise response to DAAs. Large scale and exclusive studies in HCV genotype 6 prevalent areas are needed, while the current evidence suggests that DAAs are highly effective and safe.
Editorial: liver transplantation for primary biliary cholangitis—the need for timely and more effective treatments. Authors' reply
Authors: Harms Maren H. , van Buuren Henk R. , Hansen Bettina E. , Metselaar Herold J.
Published: January 2019

Linked Content

This article is linked to Harms et al and Gerussi et al papers. To view these articles, visit https://doi.org/10.1111/apt.15060 and https://doi.org/10.1111/apt.15095.
Longitudinal analysis of CA19‐9 reveals individualised normal range and early changes before development of biliary tract cancer in patients with primary sclerosing cholangitis
Authors: Wannhoff Andreas , Brune Maik , Knierim Johannes , Weiss Karl Heinz , Rupp Christian , Gotthardt Daniel N.
Published: January 2019

Background

Primary sclerosing cholangitis is associated with an increased risk of biliary tract cancer. Carbohydrate antigen 19‐9 (CA19‐9) can be used to screen for these malignancies.

Aim

To perform a longitudinal analysis of CA19‐9 in patients with primary sclerosing cholangitis.

Methods

We conducted a retrospective analysis of CA19‐9 values in patients who had primary sclerosing cholangitis, with and without biliary malignancy. We calculated the index of individuality and reference change value in patients who were cancer‐free. Long‐term analysis of CA19‐9 in cancer‐free patients was performed and we assessed the change of CA19‐9 prior to diagnosis of cancer.

Results

We obtained 1818 CA19‐9 values from 247 patients, including 32 with malignancy. Median CA19‐9 in cancer‐free individuals was 15.6 U/mL. The index of individuality was 0.37 and the reference change value was 46.23%. In cancer‐free patients, no significant change in CA19‐9 was observed at 1, 2, 5, 7, 10, 15, and 20 years after initial diagnosis of primary sclerosing cholangitis. In patients with biliary tract cancer, CA19‐9 was higher at 3 months prior to diagnosis (P < 0.05) than at 6 months before diagnosis and was also higher than at 3 months prior to last follow‐up in cancer‐free patients (P < 0.05). In 92.9% of patients with biliary cancer, we found an increase in CA19‐9 of >46.23% in the year prior to cancer diagnosis.

Conclusions

CA19‐9 in patients with primary sclerosing cholangitis is highly individual, and the reference change value should be preferred to reference intervals. In this study, CA19‐9 remained stable in patients who were cancer‐free but increased early in those who developed biliary tract cancer. Regular CA19‐9 measurement might improve early detection of these malignancies.
Two‐dimensional mental health and related predictors among adolescents in Korea
Authors: Yoo Changmin , Kahng Sang Kyoung
Published: January 2019

This study examined whether the factor structure of mental health consists of two dimensions (positive and negative mental health) and whether the two dimensions are associated with different predictors. For this purpose, data from the 471 adolescents who participated in the 2012 Children Supplementary Survey of Korean Welfare Panel Study were used. Confirmatory factor analysis indicated that the two‐factor correlated model fits the data significantly better than the one‐factor model. Multivariate analyses revealed that factors associated with positive mental health differ from factors associated with negative mental health. These findings suggest that mental health professionals should consider the dual structure of subjective well‐being and suicidal ideation in the process of assessment and intervention.
Associations among cervical dilatation at admission, intrapartum care, and birth mode in low‐risk, nulliparous women
Authors: Iobst Stacey E. , Breman Rachel B. , Bingham Debra , Storr Carla L. , Zhu Shijun , Johantgen Meg
Published: January 2019

Background

Admission in early labor is associated with increased likelihood of cesarean birth, but the context in which this occurs is unclear. Previous research has explored the relationship between dilatation at admission and the use of single intrapartum interventions; however, the majority of women in the United States receive multiple intrapartum interventions. The objective of this study was to examine the associations among cervical dilatation at admission, intrapartum care, and birth mode in low‐risk, nulliparous women with spontaneous onset of labor.

Methods

This was a cross‐sectional, observational study of 21 858 nulliparous, singleton, term vertex births that occurred from 2002 to 2007 across nine hospitals in the Consortium on Safe Labor. Outcome measures included the individual and combined use of intrapartum interventions (amniotomy, epidural anesthesia, oxytocin augmentation) and birth mode.

Results

In this sample, 92.0% of women received at least one intrapartum intervention and 22.7% received all three interventions. After propensity score adjustment, women were more than twice as likely to receive the combination of amniotomy‐epidural‐oxytocin when admitted at 0‐3 cm (RR 2.83 [95% CI 2.45‐3.27]) and 4‐5 cm (2.49 [2.15‐2.89]) compared to 6‐10 cm. Adjusted likelihood of cesarean birth was five times greater for women admitted at 0‐3 cm (5.26 [4.36‐6.34]) and two times greater for women admitted at 4‐5 cm (2.27 [1.86‐2.77]) compared to 6‐10 cm.

Conclusions

To promote normal physiologic birth, low‐risk, nulliparous women should be engaged in shared decision‐making about timing of admission after spontaneous onset of labor.
Debate: Looking forward: choose data over opinions to best serve youth with bipolar spectrum disorders – commentary on Parry et al. (2018)
Authors: Van Meter Anna R. , Moreira Ana Lúcia R. , Youngstrom Eric A.
Published: January 2019

Over the past two decades, research on pediatric bipolar disorder has grown geometrically. The diagnosis of pediatric bipolar disorder was met with enthusiasm, which in healthy doses catalyzed change, and skepticism, which in good measure pushes for rigor. Skepticism led to productive questions about the phenomenology of pediatric bipolar disorder and how best to diagnose and treat it. With regard to prevalence, key questions included whether it was increasing over time, and whether it was limited to the United States. In 2011, we published a meta‐analysis addressing the prevalence questions; results indicated that bipolar disorder manifested at statistically indistinguishable rates in youth community samples across the world. In their recent paper, Parry et al. examine the studies included in the 2011 meta‐analysis using a qualitative approach. Their opinion piece represents a step backwards; every study has shortcomings, but in focusing on a dozen individual studies, Parry et al. fail to take into account the preponderance of evidence – literally thousands of articles across countries, cohorts and methodologies – that support the existence of bipolar disorder in both prepubescent youth and adolescents. This commentary addresses misperceptions regarding the diagnosis of bipolar disorder in youth, particularly with regard to cross‐informant agreement, to present converging data from international sources regarding the onset of bipolar disorder in childhood, and to correct the false claim that pediatric bipolar disorder is controversial. As clinicians and researchers, we have an obligation to do what we can to improve the lives of youth affected by mental illness. Denying the existence of a serious mood disorder will not serve the best interests of young people and will perpetuate the long delays many experience before getting an accurate diagnosis, appropriate treatment, and a fair chance at a good quality of life.
Exploring binding mechanisms of VEGFR2 with three drugs lenvatinib, sorafenib, and sunitinib by molecular dynamics simulation and free energy calculation
Authors: Wang Yu , Peng Cheng , Wang Guimin , Xu Zhijian , Luo Yongfeng , Wang Jinan , Zhu Weiliang
Published: January 2019

Lenvatinib (LEN), sorafenib (SOR), and sunitinib (SUN) are drugs targeting vascular endothelial growth factor receptor 2 (VEGFR2). Despite sharing similar chemical structures and bioactivities, LEN and SOR bind to different functional states of VEGFR2, viz. DFG‐in and DFG‐out state, respectively. SUN binds to the DFG‐out state of VEGFR2 just like SOR but with less potency. Thus, detail binding mechanisms between VEGFR2 and these drugs, especially dynamic interaction, are valuable for future drug design. In the present work, molecular dynamics simulation, essential dynamic analysis, and molecular mechanics/generalized born surface area were performed to these VEGFR2–drugs systems. Rank of calculated binding affinities is in accordance with the experimental data. The binding free energy calculation suggests that van der Waals interaction plays a vital role in the binding. Per‐residue free energy decomposition indicates that residues L840, V848, A866, E885, L889, V899, V916, F918, C919, L1035, C1045, D1046, and F1047 play an important role in the binding between VEGFR2 and LEN/SOR. While residues L840, V848, E917, F918, C919, G922, L1035, and F1047 contribute the major hydrophobic interaction for SUN binding to the receptor. Our results also reveal that residue E885/D1046 plays a vital role in binding via forming hydrogen bonds with drugs.
Angiopoietin‐1 haploinsufficiency affects the endothelial barrier and causes hereditary angioedema
Authors: d'Apolito Maria , Santacroce Rosa , Colia Anna Laura , Cordisco Giorgia , Maffione Angela Bruna , Margaglione Maurizio
Published: January 2019

Background

Different mutations of the angiopoietin‐1 gene (ANGPT1) have been associated with the occurrence of hereditary angioedema (HAE).

Objective

The purpose of the study is to clarify whether the ANGPT1 A119S variant plays its role via haploinsufficiency or a dominant negative effect.

Methods

The ability of ANGPT1 A119S variant to affect the endothelial barrier function was assessed by immunocytochemistry. Inter‐endothelial gap formation molecules primarily responsible for cell‐cell adhesions of HUVECs, vascular endothelial (VE)‐cadherin and β‐catenin, and reorganization of the F‐actin cytoskeletal were evaluated.

Results

In in vitro conditions mimicking the heterozygous state, the p.A119S variant significantly reduced the capability to bind its natural receptor (80.7% of normal), less than the homozygous condition (59.1%). After stimulation of VEGF or bradykinin, the addiction to equimolar amounts of wtANGPT1 and ANGPT1 p.A119S clearly reduced the expression of VE‐cadherin on the endothelial cell surface (31% and 24% respectively). Likewise, cell surface expression of β‐catenin was reduced and severe gap formation between adjacent HUVECs developed. In cultured cells, β‐catenin expression was mostly observed along the cell surface. Treatment with equimolar amounts of wtANGPT1 and ANGPT1 p.A119S failed to restore the reorganization of the F‐actin cytoskeletal elements. ANGPT1 p.A119S variant in homozygous condition further diminished VE‐cadherin and β‐catenin expression and failed to reduce stress fibre formation significantly affecting the endothelial barrier functionality.

Conclusions and Clinical Relevance

Present data show that in a heterozygous state the p.A119S substitution results in a pathogenic loss of function of the protein due to a mechanism of haploinsufficiency. The ANGPT1 reduced ability to counteract the increment of endothelial permeability produced by inducers, such as VEGF and bradykinin, stimulate vascular leakage and reorganization of the F‐actin cytoskeletal elements. As a result, a partial impairment of the ANGPT1 functionality, like when dominant mutations occur, represents a pathophysiological cause of HAE.
Dietary fats, olive oil and respiratory diseases in Italian adults: A population‐based study
Authors: Cazzoletti Lucia , Zanolin Maria Elisabetta , Spelta Francesco , Bono Roberto , Chamitava Liliya , Cerveri Isa , Garcia‐Larsen Vanessa , Grosso Amelia , Mattioli Veronica , Pirina Pietro , Ferrari Marcello
Published: January 2019

Background

Fat intake has been associated with respiratory diseases, with conflicting results.

Objective

We studied the association between asthma and rhinitis with dietary fats, and their food sources in an Italian population.

Methods

Clinical and nutritional information was collected for 871 subjects (aged 20‐84) from the population‐based multi‐case‐control study Genes Environment Interaction in Respiratory Diseases (GEIRD): 145 with current asthma (CA), 77 with past asthma (PA), 305 with rhinitis and 344 controls. Food intake was collected using the EPIC (European Investigation into Cancer and Nutrition) Food Frequency Questionnaire. The associations between fats and respiratory diseases were estimated by multinomial models. Fats and their dietary sources were analysed both as continuous variables and as quartiles.

Results

Monounsaturated fatty acids and oleic acid were associated with a reduced risk of CA in both continuous (RRR = 0.68, 95%CI: 0.48; 0.96; RRR = 0.69; 95%CI: 0.49; 0.97, per 10 g, respectively) and per‐quartile analyses (p for trend = 0.028 and 0.024, respectively). Olive oil was associated with a decreased risk of CA (RRR = 0.80; 95%CI: 0.65; 0.98 per 10 g). An increased risk of rhinitis was associated with moderate total fat and SFA intake.

Conclusions

High dietary intakes of oleic acid and of olive oil are associated with a lower risk of asthma but not of rhinitis.