bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrence of adenoma after curative endoscopic submucosal dissection for a rectal intramucosal adenocarcinoma in adenoma
Authors: Nakano Yoshiko , Toyonaga Takashi , Nishino Eisei , Inoue Taro , Shinjo Isato , Han-no Hajime , Tanaka Shinwa , Morita Yoshinori , Umegaki Eiji , Kodama Yuzo
Published: April 2019

Background and study aims A 71-year-old female underwent endoscopic submucosal dissection (ESD) for a subcircumferential lateral-spreading rectal tumor. Pathological examination showed an intramucosal adenocarcinoma in villous adenoma (size: 155 × 140 mm), which had been curatively resected with negative margins. However, follow-up colonoscopy revealed a tumor at the ulcer scar site, which soon grew into a circumferential lesion. Nineteen months after the first ESD procedure, additional ESD was performed for the recurrent lesion, which was resected en bloc without any adverse events, although severe fibrosis was noted in the submucosa. Pathological examination revealed a villous adenoma similar to the primary lesion with negative margins, but tumor cell nests were also present in the submucosa, which implied that tumor cell implantation had occurred during the first ESD. The post-ESD ulcer bed was subjected to argon plasma coagulation to prevent tumor recurrence after confirmation of the pathological results. There have not been any signs of recurrence during 9 years of follow-up.
Successful outcomes of a new combined solution of hyaluronic acid, chondroitin sulfate and poloxamer 407 for submucosal injection: animal survival study
Authors: Córdova Henry , Cuatrecasas Miriam , García-Rodríguez Ana , Montenegro Andrea , Melo Jordana , Rodríguez-de Miguel Cristina , Martínez-Pallí Graciela , Garcés-Durán Rodrigo , Llach Josep , Fernández-Esparrach Gloria
Published: April 2019

Background and study aims Endoscopic resection requires use of submucosal injection. This study was conducted to assess efficacy and impact on early healing of hyaluronic acid combined with chondroitin sulfate and poloxamer 407 (Ziverel) when used as a solution for submucosal injection.

Materials and methods Prospective and comparative study of gastric endoscopic mucosal resection (EMR) with three groups of two Yorkshire pigs. Six submucosal cushions were created in each animal by injecting 2 mL of Ziverel (Group 1) or succinylated gelatin (SG) (Group 2), enabling 12 EMR in each group. Submucosal cushions were created with Ziverel in Group 3, without resection. Electrosurgery unit settings were the same in all cases. EMR defects and injection sites were marked with clips. The animals were sacrificed 7 days later. EMR specimen size and duration of procedure were recorded. EMR specimens and EMR scars and injection sites were evaluated by a blinded pathologist.

Results We successfully performed 24 EMR (15 en-bloc and 9 piecemeal, without differences between groups 1 and 2). Mean EMR specimen dimensions were significantly larger in Group 1 (median 19 mm, range 6 – 40 vs 16.6 mm, range 5‑25; P = 0.019), without changing the electrocautery unit settings. Blinded histopathologist assessment of EMR specimens showed less fibrosis in the submucosa and a trend to fewer cautery artifacts with Ziverel and did not identify any significant differences in early healing of resection sites.

Conclusion The combination of Ziverel enables EMR and does not negatively affect early healing.
Three-dimensional periodic materials as seismic base isolator for nuclear infrastructure
Authors: Witarto Witarto , Wang S. J. , Yang C. Y. , Wang Jiaji , Mo Y. L. , Chang K. C. , Tang Yu
Published: April 2019

Recent advance of periodic materials from the field of solid-state physics into that of earthquake engineering has resulted in a novel seismic isolation technique. In this study, we developed a new configuration of structural foundation using a three-dimensional (3D) periodic material for seismic isolation of critical infrastructure, particularly nuclear infrastructure. To this aim, we first performed analytical and finite element studies to compare two different types of 3D unit cells, i.e., Bragg Scattering and Locally resonant unit cells, to investigate their characteristics and applicability as a seismic isolator. We then designed a large scale test specimen based on the Bragg-scattering type unit cell using common construction materials: reinforced concrete blocks and polyurethane sheets. The designed test specimen was constructed and tested using a shake table subjected to different types of excitations in the horizontal and vertical directions as well as the torsional mode. The dynamic response of a small modular reactor (SMR) building model protected by the 3D periodic foundation demonstrates that 90% response reduction was achieved within the frequency band gaps. The response attenuation was achieved in all three tested directions. Moreover, the periodic foundation-isolated SMR building exhibited a stable response with negligible rocking on the structural system.
Local photo-mechanical stiffness revealed in gold nanoparticles supracrystals by ultrafast small-angle electron diffraction
Authors: Mancini Giulia Fulvia , Pennacchio Francesco , Latychevskaia Tatiana , Reguera Javier , Stellacci Francesco , Carbone Fabrizio
Published: April 2019

We demonstrate that highly ordered two-dimensional crystals of ligand-capped gold nanoparticles display a local photo-mechanical stiffness as high as that of solids such as graphite. In out-of-equilibrium electron diffraction experiments, a strong temperature jump is induced in a thin film with a femtosecond laser pulse. The initial electronic excitation transfers energy to the underlying structural degrees of freedom, with a rate generally proportional to the stiffness of the material. Using femtosecond small-angle electron diffraction, we observe the temporal evolution of the diffraction feature associated with the nearest-neighbor nanoparticle distance. The Debye-Waller decay for the octanethiol-capped nanoparticle supracrystal, in particular, is found to be unexpectedly fast, almost as fast as the stiffest solid known and observed by the same technique, i.e., graphite. Our observations unravel that local stiffness in a dense supramolecular assembly can be created by van der Waals interactions up to a level comparable to crystalline systems characterized by covalent bonding.
Quantifying the response of aquatic biodiversity to variations in river hydrology and water quality in a healthy water ecology pilot city, China
Authors: Zhao C. S. , Pan T. L. , Yang S. T. , Sun Y. , Zhang Y. , Ge Y. R. , Dong B. E. , Zhang Z. S. , Zhang H. M.
Published: April 2019

Prediction and assessment of the effects of habitat change on aquatic biodiversity remain a hot issue globally. This paper developed a practical methodology based on ecosystem models to comprehensively assess the effects of habitat changes on aquatic biodiversity. The partial least-squares (PLS) method was used to analyse the key hydrological and water quality factors influencing riverine aquatic organisms. The biomass of aquatic organisms under undisturbed conditions was simulated using the food web model Ecosim. Based on the relationship between habitat factors variation and biodiversity variation, a multidimensional river hydrology–water quality–biodiversity response model was established. Application and testing of the methodologies in the first water ecology pilot city in China, namely Jinan City, showed that four water quality factors (total phosphorus, total nitrogen, ammonia nitrogen and dissolved oxygen) significantly affected aquatic biodiversity. For hydrological factors, water depth had a strong effect on fish diversity, whereas flow velocity largely affected fish and algal diversity. The application suggested that response model was practical in modelling the effects of habitat variation on biodiversity. It is anticipated that this model will help assess the effects of changes due to climate- and human-induced stress on aquatic ecosystems and provide a scientific basis for river management decisions.
Lost in the hall of mirrors
Authors: Hutton Christopher
Published: April 2019

The categoryAryanand the paradigm of ideas associated with it remains highly controversial in contemporary India, and the history, status, and impact of this concept are contested at many levels. This paper starts with the assumption that the genesis of this concept lies in Western linguistic theorizing, and analyzes in outline the reception and impact of Aryan Invasion Theory and the postulation of an Aryan-Dravidian divide. Radical Hindu nationalists reject all aspects of the colonial scholarship of India; other Indian scholars see Western scholarship as authoritative to the extent that it falls within the framework of secular modernity. The argument made here is that the entire Aryan paradigm rests on a faulty set of academic presumptions and that its impact has been more long lasting and destructive than even the application of race theory to the understanding of India. In this sense the paper accepts the criticisms made by radical Hindu nationalists of colonial linguistics, and this raises further complex issues about knowledge production and application, scholarly expertise and authority.
Networking engagement in professional practices
Authors: Sancho Guinda Carmen
Published: April 2019

In this chapter I revisit the concept of metadiscursive engagement, track its major courses of research up to date, and discuss the interpersonal and discursive assumptions it entails. In light of these assumptions, I draw connections among the different contributions to this volume, present a networked picture of engagement resulting from their different understandings, and finally pinpoint challenges and emerging issues. The global and open vision of engagement offered here not only intends to bring together the three major theoretical frameworks resorted to in this volume (i.e. the Appraisal System, the Hylandian Metadiscourse Model and Multimodality), but also to suggest relating them with the idea of ‘distance’ between sender and addressee, explored by both the Appraisal System itself and the pragmatic theories of Proximisation and Politeness.
Rebuilding trust in the banking sector
Authors: McLaren-Hankin Yvonne
Published: April 2019

The financial crisis and various international scandals are widely viewed as having eroded trust in the banking sector, leading to calls for banks to act urgently to rebuild trust among stakeholders. This chapter examines one type of stakeholder communication, namely press releases on the subject of customer complaints, and aims to identify mechanisms by which the UK bank Barclays engages with customers as a means of regaining their trust. It shows that, through reader reference and transitivity structures in which readers (and writer) are projected into particular roles, Barclays seeks to demonstrate ability and benevolence, two of the three dimensions of an organisation’s trustworthiness (Mayer et al. 1995), and that the emphasis shifts from one to the other over time.
Verbal and nonverbal engagement devices in business persuasive discourse
Authors: Díez Prados Mercedes
Published: April 2019

The present chapter analyzes verbal and nonverbal engagement devices in four business pitches delivered by entrepreneurs in the British TV program Dragon’s Den. Taken for granted their eminently persuasive character, the purpose is to analyze the expression of engagement in verbal and nonverbal signs aiming at convincing potential investors of the product’s worth. A tridimensional analysis is carried out: firstly, structural features are identified following Daly and Davy’s (2016a and b) proposal. Secondly, verbal engagement devices are examined according to Martin and White’s (2005) Appraisal System and Hyland’s (2005a and b) Engagement Model. Thirdly, persuasive nonverbal signs are identified applying Cestero Mancera’s (2016 and 2017) taxonomy. Results show that while pitches are grossly monoglossic in their verbal realizations, nonverbal persuasive signs seem to acknowledge and guide the audience’s perception.
Engagement of readers/customers in the discourse of e-tourism promotional genres
Authors: Suau-Jiménez Francisca
Published: April 2019

Tourism 2.0 involves direct e-communication between travellers and the tourism industry, and needs websites that attract customers. Recent research in this field (Austin 2009; Brodie, Hollebeek et al. 2011) suggests that they must also include the co-creation of values that align with the customer in some way. Their design must be persuasive yet trustworthy. This is partly achieved through discursive strategies that reflect the voice of the institution or business (author), and others that engage the customer (reader). This study discusses engagement as a key concept in promotional websites (hotels, tourist guides, etc.) from interpersonality, based on the cometval corpus. Its conclusions note significant and controversial differences on how these e-genres are construed in English and Spanish, with societal implications.
Van den vos Reynaerde
Authors: Malfliet Rudi
Published: April 2019

Van den vos Reynaerde is interpreted as the satiric textualization of a particular social discourse. In the first part, the objectives are the three estates: clergy, nobility and peasants. The second part is focussed on the dysfunction of authority, its lack of moral and social legitimation and the relation individual-authority. The medieval society is criticized in a goliardic-inspired manner, where the satiric subject reflects through inversion the satiric objective. It is pointed out that the text contains a parody on the biblical story of Judith and Holofernes, to discern whether opposing a repressive authority allows for ‘just war’. The results of this study challenge the conventional interpretations of Van den vos Reynaerde based on an Arthurian courtly context. The author’s profile and intended public are reviewed with respect to these conclusions.
Typology of Pluractional Constructions in the Languages of the World
Authors: Mattiola Simone
Published: April 2019

The aim of this book is to give the first large-scale typological investigation of pluractionality in the languages of the world. Pluractionality is defined as the morphological modification of the verb to express a plurality of situations that can additionally involve a plurality of participants and/or spaces. Based on a 246-language sample, the main characteristics of pluractionality are described and discussed throughout the book. Firstly, a description of the functions that pluractional markers cross-linguistically express is presented and the relationships occurring among them are explained through the semantic map model. Then, the marking strategies that languages display to express such functions are illustrated and some issues concerning the formal identification are briefly discussed as well. The typological generalizations are corroborated showing how pluractional markers work in three specific languages (Akawaio, Beja, Maa). In conclusion, the theoretical conceptualization of pluractionality is discussed referring to the Radical Construction Grammar approach.
Do generations differ in sports participation and physical activity over the life course? Evidence from multiple datasets
Authors: van Oostrom Sandra H. , Slobbe Lany C. J. , van den Berg Saskia W. , Verschuren W. M. Monique , Picavet H. Susan J.
Published: April 2019

Generational differences in health‐related factors will affect forecasts of future disease patterns and health care needs. We studied whether participation in sports activity and being physically active are different between 10‐year generations over a part of their life course. We used three different datasets on Dutch adults: a cohort study running for 20 years, the Doetinchem Cohort Study (DCS), multiple yearly databases (2001–2015) from the Netherlands health interview study (HIS), and a retrospective cohort study on life time sports careers, the Sports Participation Monitor (SPM). Based on a different questionnaire in each study, frequencies of weekly sport participation and being physically active according to recommended levels were determined by generation and sex. All data sets showed that self‐reported sport participation has been increasing with every 10‐year generation already for many decades. Especially for those generations born in the 1930s up to the 1960s, sport participation is higher compared to their predecessors. For instance at age 50, 43% of those born in the 1940s engaged in sports activities compared to 55% of those born in the 1950s (DCS data). Physical activity according to recommended levels showed no systematic differences by generation.

In conclusion, favourable generation‐specific trends in participation in sports activities are found: recent generations are doing better than the older generations. It is unclear whether this also reflects higher levels of physical activity or lower levels of inactivity. Future research may reveal whether these developments also hold for other countries, and whether these developments continue for the younger generations.
Pro-Fibrotic CD26-Positive Fibroblasts Are Present in Greater Abundance in Breast Capsule Tissue of Irradiated Breasts
Authors: Borrelli Mimi R , Irizzary Dre , Patel Ronak A , Nguyen Dung , Momeni Arash , Longaker Michael T , Wan Derrick C
Published: April 2019

Background

Breast capsular contracture is a major problem following implant-based breast reconstruction, particularly in the setting of radiation therapy. Recent work has identified a fibrogenic fibroblast subpopulation characterized by CD26 surface marker expression.

Objectives

This work aimed to investigate the role of CD26-positive fibroblasts in the formation of breast implant capsules following radiation therapy.

Methods

Breast capsule specimens were obtained from irradiated and nonirradiated breasts of 10 patients following bilateral mastectomy and unilateral irradiation at the time of expander-implant exchange, under institutional review board approval. Specimens were processed for hematoxylin and eosin staining as well as for immunohistochemistry and fluorescence activated cell sorting for CD26-positive fibroblasts. Expression of fibrotic genes and production of collagen were compared between CD26-positive, CD26-negative, and unsorted fibroblasts.

Results

Capsule specimens from irradiated breast tissue were thicker and had greater CD26-postive cells on immunofluorescence imaging and on fluorescence activated cell sorting analysis than did capsule specimens from the nonirradiated breast. Compared with CD26-negative fibroblasts, CD26-positive fibroblasts produced more collagen and had increased expression of the profibrotic genes IL8, TGF-β1, COL1A1, and TIMP4.

Conclusions

CD26-positive fibroblasts were found in a significantly greater abundance in capsules of irradiated compared with nonirradiated breasts and demonstrated greater fibrotic potential. This fibrogenic fibroblast subpopulation may play an important role in the development of capsular contracture following irradiation, and its targeted depletion or moderation may represent a potential therapeutic option.

Level of Evidence: 2
Hybrid analysis of gene dynamics predicts context-specific expression and offers regulatory insights
Authors: Finkle Justin D , Bagheri Neda
Published: April 2019

Motivation

To understand the regulatory pathways underlying diseases, studies often investigate the differential gene expression between genetically or chemically differing cell populations. Differential expression analysis identifies global changes in transcription and enables the inference of functional roles of applied perturbations. This approach has transformed the discovery of genetic drivers of disease and possible therapies. However, differential expression analysis does not provide quantitative predictions of gene expression in untested conditions. We present a hybrid approach, termed Differential Expression in Python (DiffExPy), that uniquely combines discrete, differential expression analysis with in silico differential equation simulations to yield accurate, quantitative predictions of gene expression from time-series data.

Results

To demonstrate the distinct insight provided by DiffExpy, we applied it to published, in vitro, time-series RNA-seq data from several genetic PI3K/PTEN variants of MCF10a cells stimulated with epidermal growth factor. DiffExPy proposed ensembles of several minimal differential equation systems for each differentially expressed gene. These systems provide quantitative models of expression for several previously uncharacterized genes and uncover new regulation by the PI3K/PTEN pathways. We validated model predictions on expression data from conditions that were not used for model training. Our discrete, differential expression analysis also identified SUZ12 and FOXA1 as possible regulators of specific groups of genes that exhibit late changes in expression. Our work reveals how DiffExPy generates quantitatively predictive models with testable, biological hypotheses from time-series expression data.

Availability and implementation

DiffExPy is available on GitHub (https://github.com/bagherilab/diffexpy).

Supplementary information

Supplementary data are available at Bioinformatics online.
Computational identification of prion-like RNA-binding proteins that form liquid phase-separated condensates
Authors: Orlando Gabriele , Raimondi Daniele , Tabaro Francesco , Codicè Francesco , Moreau Yves , Vranken Wim F
Published: April 2019

Motivation

Eukaryotic cells contain different membrane-delimited compartments, which are crucial for the biochemical reactions necessary to sustain cell life. Recent studies showed that cells can also trigger the formation of membraneless organelles composed by phase-separated proteins to respond to various stimuli. These condensates provide new ways to control the reactions and phase-separation proteins (PSPs) are thus revolutionizing how cellular organization is conceived. The small number of experimentally validated proteins, and the difficulty in discovering them, remain bottlenecks in PSPs research.

Results

Here we present PSPer, the first in-silico screening tool for prion-like RNA-binding PSPs. We show that it can prioritize PSPs among proteins containing similar RNA-binding domains, intrinsically disordered regions and prions. PSPer is thus suitable to screen proteomes, identifying the most likely PSPs for further experimental investigation. Moreover, its predictions are fully interpretable in the sense that it assigns specific functional regions to the predicted proteins, providing valuable information for experimental investigation of targeted mutations on these regions. Finally, we show that it can estimate the ability of artificially designed proteins to form condensates (r=−0.87), thus providing an in-silico screening tool for protein design experiments.

Availability and implementation

PSPer is available at bio2byte.com/psp.

Supplementary information

Supplementary data are available at Bioinformatics online.
When Peaceful People Fight: Beyond Neutralization and Subcultural Theory
Authors: Sandberg Sveinung , Copes Heith , Pedersen Willy
Published: April 2019

Fights are widespread in society, but for most people it happens once or twice and is not part of a consistent pattern or lifestyle. Using a narrative criminological framework, we study the stories of violence among people who otherwise seldom engage in violent behaviour. The young Norwegians we interviewed, emphasized that their fights emerged as a response to insults, was fuelled by drinking and could be exciting. Participants had negative evaluations of their fights, took the blame for them, talked down their importance and self-critically used humour to ridicule their involvement. Our study demonstrates the shortcomings of subcultural and neutralization theories when it comes to understanding violent behaviour among those who rarely engage in it.
The Bayley-III scale may underestimate neurodevelopmental disability after cardiac surgery in infants
Authors: Goldstone Andrew B , Baiocchi Michael , Wypij David , Stopp Christian , Andropoulos Dean B , Atallah Joseph , Atz Andrew M , Beca John , Donofrio Mary T , Duncan Kim , Ghanayem Nancy S , Goldberg Caren S , Hövels-Gürich Hedwig , Ichida Fukiko , Jacobs Jeffrey P , Justo Robert , Latal Beatrice , Li Jennifer S , Mahle William T , McQuillen Patrick S , Menon Shaji C , Pike Nancy A , Pizarro Christian , Shekerdemian Lara S , Synnes Anne , Williams Ismée A , Bellinger David C , Newburger Jane , Gaynor J William
Published: April 2019

OBJECTIVES

Neurodevelopmental disability is the most common complication among congenital heart surgery survivors. The Bayley scales are standardized instruments to assess neurodevelopment. The most recent edition (Bayley Scales of Infant and Toddler Development 3rd Edition, Bayley-III) yields better-than-expected scores in typically developing and high-risk infants than the second edition (Bayley Scales of Infant Development 2nd Edition, BSID-II). We compared BSID-II and Bayley-III scores in infants undergoing cardiac surgery.

METHODS

We evaluated 2198 infants who underwent operations with cardiopulmonary bypass between 1996 and 2009 at 26 institutions. We used propensity score matching to limit confounding by indication in a subset of patients (n = 705).

RESULTS

Overall, unadjusted Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores (90.7 ± 17.2 vs 77.6 ± 18.8, P < 0.001), and unadjusted Bayley-III composite cognitive and language scores were higher than BSID-II Mental Development Index scores (92.0 ± 15.4 vs 88.2 ± 16.7, P < 0.001). In the propensity-matched analysis, Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores [absolute difference 14.1, 95% confidence interval (CI) 11.7–17.6; P < 0.001] and the Bayley-III classified fewer children as having severe [odds ratio (OR) 0.24; 95% CI 0.14–0.42] or mild-to-moderate impairment (OR 0.21; 95% CI 0.14–0.32). The composite of Bayley-III cognitive and language scores was higher than BSID-II Mental Development Index scores (absolute difference 4.0, 95% CI 1.4–6.7; P = 0.003), but there was no difference between Bayley editions in the proportion of children classified as having severe cognitive and language impairment.

CONCLUSIONS

The Bayley-III yielded higher scores than the BSID-II and classified fewer children as severely impaired. The systematic bias towards higher scores with the Bayley-III precludes valid comparisons between early and contemporary cardiac surgery cohorts.
Barriers to health care seeking with bothersome lower urinary tract symptoms among men—a nationwide study
Authors: Rubach Ann , Balasubramaniam Kirubakaran , Elnegaard Sandra , Larsen Stine E , Jarbøl Dorte E
Published: April 2019

Background

The majority of men who report urological symptoms of extreme concern or influence on daily activities do not contact their general practitioner (GP). No previous study on barriers to health care seeking with lower urinary tract symptoms in men has been carried out in a population-based setting.

Objectives

(i) To examine associations between different types of lower urinary tract symptoms and barriers to contact a GP in men with urological symptoms reported to be of concern or influencing daily activity (termed ‘bothersome’); (ii) to examine associations between age and barriers to health care seeking in men with bothersome lower urinary tract symptoms.

Study design

A population-based cross-sectional study design.

Methods

A total of 48 910 men aged 20 or older were randomly selected from the general Danish population. Data was collected in 2012. Logistic regression was used to calculate odds ratios for reporting different barriers to health care seeking with bothersome lower urinary tract symptoms according to age and urological symptom.

Results

A total of 23 240 men participated. Among men aged 20–39 years who reported bothersome lower urinary tract symptoms, the proportion who did not contact their GP ranged from 73.4% (incontinence) to 84.5% (nocturia). Men younger than 60 years of age had significantly higher odds for reporting any barriers to health care seeking compared to older men. The odds for reporting each of the barriers differed significantly according to the different urological symptoms.

Conclusion

Younger men more often report barriers to health care seeking, but the barriers differ between the different urological symptoms.
Viral fitness: history and relevance for viral pathogenesis and antiviral interventions
Authors: Domingo Esteban , de Ávila Ana I , Gallego Isabel , Sheldon Julie , Perales Celia
Published: April 2019

The quasispecies dynamics of viral populations (continuous generation of variant genomes and competition among them) has as one of its frequent consequences variations in overall multiplication capacity, a major component of viral fitness. This parameter has multiple implications for viral pathogenesis and viral disease control, some of them unveiled thanks to deep sequencing of viral populations. Darwinian fitness is an old concept whose quantification dates back to the early developments of population genetics. It was later applied to viruses (mainly to RNA viruses) to quantify relative multiplication capacities of individual mutant clones or complex populations. The present article reviews the fitness concept and its relevance for the understanding of the adaptive dynamics of viruses in constant and changing environments. Many studies have addressed the fitness cost of escape mutations (to antibodies, cytotoxic T cells or inhibitors) as an influence on the efficacy of antiviral interventions. Here, we summarize the evidence that the basal fitness level can be a determinant of inhibitor resistance.
Polygenic risk scores for Alzheimer’s disease, and academic achievement, cognitive and behavioural measures in children from the general population
Authors: Korologou-Linden Roxanna , Anderson Emma L , Jones Hannah J , Davey Smith George , Howe Laura D , Stergiakouli Evie
Published: April 2019

Objective

Several studies report a polygenic component of risk for Alzheimer’s disease. Understanding whether this polygenic signal is associated with educational, cognitive and behavioural outcomes in children could provide an earlier window for intervention.

Methods

We examined whether polygenic risk scores (PRS) at varying P-value thresholds in children from the Avon Longitudinal Study of Parents and Children were associated with academic achievement, cognitive and behavioural measures in childhood and adolescence.

Results

We did not detect any evidence that the genome-wide significant PRS (5x10-8) were associated with these outcomes. PRS at the highest P-value threshold examined (P ≤ 5x10-1) were associated with lower academic achievement in adolescents (Key Stage 3; β: -0.03; 95% confidence interval: -0.05, -0.003) but the effect was attenuated when single nucleotide polymorphisms (SNPs) associated with educational attainment were removed. These PRS were associated with lower IQ (β: -0.04; 95% CI: -0.07, -0.02) at age 8 years with the effect remaining after removing SNPs associated with educational attainment.

Conclusions

SNPs mediating the biological effects of Alzheimer’s disease are unlikely to operate early in life. The evidence of association between PRS for Alzheimer’s disease at liberal thresholds and cognitive measures suggest shared genetic pathways between Alzheimer’s disease, academic achievement and cognition.
Determinants of breastfeeding practices among mothers in Malawi: a population-based survey
Authors: Chipojola Roselyn , Lee Gabrielle T , Chiu Hsiao-Yean , Chang Pi-Chen , Kuo Shu-Yu
Published: April 2019

Background

High rates of early initiation and exclusive breastfeeding have been reported in Malawi, yet the underlying factors are unknown. Our objective is to examine the determinants of breastfeeding practices for mothers of infants less than 24 months old in Malawi.

Methods

A cross-sectional study was conducted using nationally representative data from the 2010 Malawi Demographic and Health Survey. Multivariate logistic regression analysis was used.

Results

Of 7282 women, 95.4% initiated breastfeeding within 1 hour after birth; thereafter 71.3% of women practiced exclusive breastfeeding, 6.1% predominantly breastfed, and 1.9% chose bottle feeding exclusively. The odds of early initiation were higher among women with frequent antenatal care visits and multiparous mothers. Similarly, frequent antenatal care visits and hospital delivery were positive determinants for exclusive breastfeeding. Infants at 6 months of age were more likely to predominantly breastfeed than they were at 1 month. The odds of bottle feeding were higher among women who were educated, who delivered at a hospital.

Conclusions

Optimal breastfeeding practices are highly prevalent in Malawi. Health care practice emphasizing frequent antenatal care visits that provide breastfeeding education and breastfeeding support in hospital care after childbirth are important for sustaining breastfeeding.
Regulation of signaling mediated by nucleic acid sensors for innate interferon-mediated responses during viral infection
Authors: Takaoka Akinori , Yamada Taisho
Published: April 2019

Type I and type III interferons are important anti-viral cytokines that are massively induced during viral infection. This dynamic process is regulated by many executors and regulators for efficient eradication of invading viruses and protection from harmful, excessive responses. An array of innate sensors recognizes virus-derived nucleic acids to activate their downstream signaling to evoke cytokine responses including interferons. In particular, a cytoplasmic RNA sensor RIG-I (retinoic acid-inducible gene I) is involved in the detection of multiple types of not only RNA viruses but also DNA viruses. Accumulating findings have revealed that activation of nucleic acid sensors and the related signaling mediators is regulated on the basis of post-translational modification such as ubiquitination, phosphorylation and ADP-ribosylation. In addition, long non-coding RNAs (lncRNAs) have been implicated as a new class of regulators in innate signaling. A comprehensive understanding of the regulatory mechanisms of innate sensor activation and its signaling in host–virus interaction will provide a better therapeutic strategy to efficiently control viral infection and maintain immune homeostasis.
Slow Larvae Mutant and Its Potential to Improve the Pupal Color-Based Genetic Sexing System in Mexican Fruit Fly, (Diptera: Tephritidae)
Authors: Meza José S , Cáceres Carlos , Bourtzis Kostas
Published: April 2019

For many years, an area-wide fruit fly control campaign against the Mexican fruit fly, Anastrepha ludens (Loew) has been implemented in some regions of Mexico and Texas, using the sterile insect technique (SIT) as its principal component. To improve the efficiency of the SIT, a genetic sexing strain based on black pupae mutation (bp) was developed for A. ludens, namely, ‘Tapachula-7’ (Tap-7 genetic sexing strains [GSSs]). This strain was introduced into the AW-IPM program recently and allows male-only releases for SIT applications. Here, we report the genetic and biological characterization of a new mutation, slow larvae (sl), which was introduced to the original translocation of the Tap-7 GSS resulting in two new GSS (slow-7 and Tap/slow-7). In both GSSs, the translocated wild-type males emerge from brown pupae that develop faster than females. The females are homozygous for sl mutation in the slow-7 GSS and homozygous for sl and bp mutations in the Tap/slow-7 GSS, reaching larval maturity 2 d after most of the wild-type males, allowing the separation of most males during pupariation. The potential use of the slow-7 and Tap/slow-7 GSSs in mass rearing and large-scale population suppression programs is discussed.
Study on the Genetic Differentiation of Geographic Populations of Calliptamus italicus (Orthoptera: Acrididae) in Sino-Kazakh Border Areas Based on Mitochondrial COI and COII Genes
Authors: Xu Ye , Mai Ji-wei , Yu Bing-jie , Hu Hong-xia , Yuan Liang , Jashenko Roman , Ji Rong
Published: April 2019

Calliptamus italicus L. is an important pest on the desert and semidesert steppes along the Sino-Kazakh border. To elucidate the molecular mechanism of its continuous outbreaks, we studied 11 different geographic populations of C. italicus to determine: 1) the complete sequences of the entire mitochondrial cytochrome oxidase subunit I (COI) and mitochondrial cytochrome oxidase subunit II (COII) genes, and 2) performed genetic diversity, differentiation, gene flow, and molecular variation analyses. Of the 11 populations, the Yining County (YNX) population had the highest haplotype diversity and Pi values. There are significant differences in Tajima’s D and Fu’s Fs (P < 0.05). The fixation index Fst values of the total C. italicus population were 0.03352, and its gene flow Nm values of the total C. italicus population were 15.32. Taken together, there were five main findings: 1) the current genetic differentiation of C. italicus arose within populations; 2) genetic exchange levels were high between geographical populations; 3) genetic variation level was low; 4) C. italicus populations likely expanded in recently, and 5) there was no significant correlation between genetic distance and geographic distance for any geographic population. Findings from this study indicate that frequent gene exchange between populations may enhance the adaptability of C. italicus along the Sino-Kazakh border, leading to frequent outbreaks.
Ligand-Binding-Site Structure Shapes Allosteric Signal Transduction and the Evolution of Allostery in Protein Complexes
Authors: Abrusán György , Marsh Joseph A
Published: April 2019

The structure of ligand-binding sites has been shown to profoundly influence the evolution of function in homomeric protein complexes. Complexes with multichain binding sites (MBSs) have more conserved quaternary structure, more similar binding sites and ligands between homologs, and evolve new functions slower than homomers with single-chain binding sites (SBSs). Here, using in silico analyses of protein dynamics, we investigate whether ligand-binding-site structure shapes allosteric signal transduction pathways, and whether the structural similarity of binding sites influences the evolution of allostery. Our analyses show that: 1) allostery is more frequent among MBS complexes than in SBS complexes, particularly in homomers; 2) in MBS homomers, semirigid communities and critical residues frequently connect interfaces and thus they are characterized by signal transduction pathways that cross protein–protein interfaces, whereas SBS homomers usually not; 3) ligand binding alters community structure differently in MBS and SBS homomers; and 4) except MBS homomers, allosteric proteins are more likely to have homologs with similar binding site than nonallosteric proteins, suggesting that binding site similarity is an important factor driving the evolution of allostery.
Is Attentional Filtering Impaired in Schizophrenia?
Authors: Luck Steven J , Leonard Carly J , Hahn Britta , Gold James M
Published: April 2019

Recent evidence suggests that schizophrenia involves hyperfocusing, an unusually narrow but intense focusing of processing resources. This appears to contradict the classic idea that schizophrenia involves an impairment in the ability to focus on relevant information and filter irrelevant information. Here, we review one set of studies suggesting that attentional filtering is impaired in people with schizophrenia and another set of studies suggesting that attentional filtering is unimpaired or even enhanced in these individuals. Considerable evidence supports both conclusions, and we propose 3 potential ways of reconciling the conflicting evidence. First, impaired attentional filtering may occur primarily during periods of active psychosis, with hyperfocusing being a part of the broad pattern of cognitive impairment that persists independent of the level of positive symptoms. Second, schizophrenia may involve hyperfocusing in the visual modality and impaired attentional filtering in the auditory modality. Third, attention may be directed toward irrelevant inputs as a result of impaired executive control, and hyperfocusing on those inputs may be functionally equivalent to a failure of attentional filtering. Given the widespread clinical observations and first-person reports of impaired attentional filtering in schizophrenia, it will be important for future research to test these possibilities.
Reach of a low-intensity, multicomponent childhood overweight and obesity intervention delivered in an integrated primary care setting
Authors: Raynor Hollie A , Barroso Cristina , Propst Sara , Berlin Kristoffer , Robson Shannon , Khatri Parinda
Published: April 2019

Reach (i.e., proportion and representativeness of participants) of low-intensity, multicomponent childhood overweight/obesity interventions delivered in primary care settings with low-income and/or minority families is unknown. The purpose of this research is to describe the reach of a low-intensity, multicomponent childhood overweight/obesity intervention delivered in an integrated primary care setting in a federally qualified health center (FQHC). Eligibility criteria included children aged 4–10 years with a body mass index (BMI) ≥85th percentile, with a female caregiver. Using the electronic health record (EHR) and release forms, families were broadly categorized into groupings from recruitment flow, with differing proportions calculated from these groupings. Representativeness was determined using EHR data from families who were informed about the program (n = 963). Three calculated reach rates ranged from 54.9% to 3.9%. Lower reach rates were calculated using the number of families randomized (n = 73) as the numerator and the children from families who were informed about the program (n = 963) or all eligible children in the FQHC attending appointments (n = 1,864) as denominators. The first two steps in recruitment, informing families about the program and families initiating participation, were where the largest decreases in reach occurred. Children who were randomized were older, had a higher BMI, had a greater number of medical diagnoses indicating overweight or obesity, and were Hispanic. Reach of the intervention was low. Strategies that assist with reducing time for informing families of treatment and increasing families’ awareness of their child’s weight status should assist with enhancing reach.
Apoptosis Resistance in Fibroblasts Precedes Progressive Scarring in Pulmonary Fibrosis and Is Partially Mediated by Toll-Like Receptor 4 Activation
Authors: Hanson Kelly M , Hernady Eric B , Reed Christina K , Johnston Carl J , Groves Angela M , Finkelstein Jacob N
Published: April 2019

Inhalation of environmental toxicants such as cigarette smoke, metal or wood dust, silica, or asbestos is associated with increased risk for idiopathic pulmonary fibrosis (IPF). IPF involves progressive scarring of lung tissue, which interferes with normal respiration and is ultimately fatal; however, the complex cellular mechanisms of IPF pathogenesis remain unclear. Fibroblast apoptosis is essential in normal wound healing but is dysregulated in IPF. Recent studies suggest that Toll-like receptor 4 (TLR4) is key in the onset of IPF. Here, radiation-induced PF was used as a model for IPF because it very closely mimics the progressive and intractable nature of IPF. Female C57BL/6J (C57) and C57BL/6J TLR4−/− mice were exposed to a single dose of 13 Gy whole-thorax ionizing radiation. Although both strains showed similar levels of immediate radiation-induced damage, C57 mice exhibited more extensive fibrosis at 22-week postirradiation (PI) than TLR4−/− mice. Isolated C57 primary 1° MLFs showed decreased apoptosis susceptibility as early as 8-week postirradiation, a phenotype that persisted for the remainder of the radiation response. TLR4−/− 1° mouse lung fibroblasts did not exhibit significant apoptosis resistance at any point. Systemic release of high mobility group box 1, a TLR4 agonist, during the pneumonitis phase of the radiation response may act through TLR4 to contribute to fibroblast apoptosis resistance and thus interfere with wound resolution. These findings demonstrate that apoptosis resistance occurs earlier in pulmonary fibrosis pathogenesis than previously assumed, and that TLR4 signaling is a key mediator in this process.
Reappraisal of the morphology and phylogenetic relationships of the alligatoroid crocodylian Diplocynodon hantoniensis from the late Eocene of the United Kingdom
Authors: Rio Jonathan P , Mannion Philip D , Tschopp Emanuel , Martin Jeremy E , Delfino Massimo
Published: April 2019

Diplocynodon is a genus of basal alligatoroid comprising nine species, which spanned the late Palaeocene to middle Miocene of Europe. Despite recent revisions of most Diplocynodon species, one of the earliest named and most complete, Diplocynodon hantoniensis, has not been re-described for over 150 years. This species is known from the remains of numerous individuals from the Priabonian (late Eocene) Headon Hill Formation, which crops out at Hordle (Hordwell) Cliff in Hampshire, United Kingdom. Here we re-describe and diagnose Diplocynodon hantoniensis, providing the first detailed description of postcranial anatomy in Diplocynodon, and indeed any basal alligatoroid. Diplocynodon hantoniensis is diagnosed by four autapomorphies, including retention of the ectopterygoid–pterygoid flexure through ontogeny and a unique anterior process of the ectopterygoid adjacent to the posteriormost maxillary alveoli. A critical review of previously referred remains from elsewhere in Europe and the USA restricts Diplocynodon hantoniensis to the late Eocene of the UK. Through comparisons with extant crocodylians, the well-preserved postcranial skeleton enables the interpretation of numerous muscle attachments in the forelimbs and hindlimbs, providing a potentially rich source of character data for future phylogenetic analyses. Based on a comparison of humeral morphology between a large sample of crocodylian species, we outline two new morphological characters in the humerus. We include D. hantoniensis in a phylogenetic analysis, including all putative Diplocynodon species (103 taxa scored for 187 characters). We use four different character-weighting schemes: equal weighting, implied weighting (k value = 8) and extended implied weighting with k-values of 4 and 8. In general, these weighted analyses produce congruent results with the equal-weights analysis, and increase the resolution within Diplocynodon. We recover a monophyletic Diplocynodon in three of the four analyses. However, the fourth analysis, with the strongest downweighting of homoplastic characters and missing data (extended implied weighting with k = 4), recovers the Palaeocene Diplocynodon remensis outside Diplocynodon. Our comprehensive revision of one of the most completely known Diplocynodon species facilitates comparisons in the genus, as well as between other basal alligatoroids, and forms the basis for comparing postcranial anatomy in other fossil crocodylians.