bluuebunny/crossref_metadata_2025 huggingface dataset:
Roundtable Proceedings
Authors: Kleinman Ronald E. , Greer Frank , Cowart Beverly J. , Hetherington Marion M. , Johnson Susan L. , Keller Kathleen L. , Klurfeld David M. , Moshfegh Alanna J. , Murray Robert , Welsh Jean , Coletta Frances A. , Marr Liz
Published: March 2017

The US Agricultural Act of 2014 stipulates that the age range for 2020 Dietary Guidelines for Americans expands to include from birth to 24 months. A group of pediatric nutrition researchers and practitioners met to discuss recent data and research gaps, as well as to generate research and potential public-private partnership ideas for future guidance on the feeding of young children, with a focus on 12 to 24 months old. Specific to this age range, the meeting participants analyzed cross-sectional dietary intake data and reviewed dietary guidance history, developmental feeding, policy considerations, and principles of public-private partnership. The group generated a number of research questions, emphasizing the need to investigate ways to improve acceptance of nutrient-dense foods, including vegetables. Research is needed to understand whether an innate preference for sweetness can be used strategically to help caregivers persevere in feeding less accepted nutrient-dense foods to toddlers.
Developmental Readiness, Caregiver and Child Feeding Behaviors, and Sensory Science as a Framework for Feeding Young Children
Authors: Johnson Susan L. , Hayes John E.
Published: March 2017

Encouraging the development of healthy eating habits early in life is considered to be the best pathway toward the prevention of diet-related chronic diseases. One goal of the 2020–2025 Dietary Guidelines for Americans is to add children from birth to the age of 24 months to those included in the subsequent editions of the guidelines. Although a focus on early childhood is long overdue, the construction of these guidelines will require an integration of evidence from multiple disciplines including nutrition, child development, sensory science, and socioeconomic and environmental factors. This article briefly reviews the rapid trajectory of infant and toddler anatomical and social development as they relate to the acquisition of eating habits, sensory aspects that influence children's food acceptance, and how each of these influences children's food preference development. The effects of caregiver feeding strategies on children's food acceptance patterns, as well as the impact of cultural norms, are also examined. The article closes with identifying opportunities for research that could integrate nutrition and child development principles with individual differences in the sensory perception and could incorporate a focus on interactions within the caregiver-child dyad.
Placental transfer of antibody and its relationship to vaccination in pregnancy
Authors: Calvert Anna , Jones Christine E.
Published: March 2017

Purpose of review

Vaccination in pregnancy boosts maternal vaccine-specific antibody concentration and therefore increases transplacental transfer of antibody to optimize protection of the infant. The purpose of this review is to describe what is known about placental transfer of antibody in the context of vaccination in pregnancy, focussing on the recent literature and areas of debate, particularly about the timing of vaccination.

Recent findings

There is a debate about the timing of pertussis vaccination in pregnancy with some studies reporting that vaccination in the third trimester results in higher pertussis antigen-specific IgG concentrations in cord blood and others finding that the concentration is higher following vaccination in the second trimester. The impact of timing of vaccination on antibody avidity in cord blood has also been investigated and one study suggests that avidity may be increased following vaccination at 27–30+6 gestational weeks compared with later vaccination.

Understanding placental transfer of antibody is vital in informing maternal vaccination strategy. There has been recent research about the timing of pertussis vaccination in pregnancy that has implications for the timing of both current and future vaccines to be used in pregnancy.
EXPLANe: An Extensible Framework for Poster Annotation with Mobile Devices
Authors: Gopal Nikhil , Su Andrew , Wu Chunlei , Mooney Sean D.
Published: March 2017

Scientific posters tend to be brief, unstructured, and generally unsuitable for communication beyond a poster session. This paper describes EXPLANe, a framework for annotating posters using optical text recognition and web services on mobile devices. EXPLANe is demonstrated through an interface to the MyVariant.info variant annotation web services, and provides users a list of biological information linked with genetic variants (as found via extracted RSIDs from annotated posters). This paper delineates the architecture of the application, and includes results of a five-part evaluation we conducted. Researchers and developers can use the existing codebase as a foundation from which to generate their own annotation tabs when analyzing and annotating posters.

Availability

Alpha EXPLANe software is available as an open source application athttps://github.com/ngopal/EXPLANe

Contact

Sean D. Mooney (sdmooney@uw.edu)
Understanding neural circuit development through theory and models
Authors: Richter Leonidas M. A. , Gjorgjieva Julijana
Published: March 2017

How are neural circuits organized and tuned to achieve stable function and produce robust behavior? The organization process begins early in development and involves a diversity of mechanisms unique to this period. We summarize recent progress in theoretical neuroscience that has substantially contributed to our understanding of development at the single neuron, synaptic and network level. We go beyond classical models of topographic map formation, and focus on the generation of complex spatiotemporal activity patterns, their role in refinements of particular circuit features, and the emergence of functional computations. Aided by the development of novel quantitative methods for data analysis, theoretical and computational models have enabled us to test the adequacy of specific assumptions, explain experimental data and propose testable hypotheses. With the accumulation of larger data sets, theory and models will likely play an even more important role in understanding the development of neural circuits.
Modeling the dynamics of progression of chromosomal alterations in cervical cancer: a computational model
Authors: Cabrera-Becerril Augusto , Vargas-De-León Cruz , Hernández Sergio , Miramontes Pedro , Peralta Raúl
Published: March 2017

Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior among non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamic of deleterious and non-deleterious mutations as an outcome of tumor progression. Analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose to cancer progression. The study of somatic alterations by computer simulations during cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Chromosomal alterations non deleterious contributes to this progression.
Iterative model-based density improvement yields better atomic structures from cryo-EM maps
Authors: Jakobi Arjen J. , Wilmanns Matthias , Sachse Carsten
Published: March 2017

Atomic models based on high-resolution density maps are the ultimate result of the cryo-EM structure determination process. Current cryo-EM model refinement procedures work with the experimental density map that remains constant throughout the process. Here, we introduce a general procedure that iteratively improves cryo-EM density maps based on prior knowledge of an atomic reference structure. The procedure optimizes contrast of cryo-EM densities by local amplitude scaling (LocScale) based on an atomic model without introducing model bias. We alternate the procedure with consecutive rounds of model refinement and tested it on four cryo-EM structures of TRPV1, β-galactosidase, γ-secretase and RNA polymerase III. We demonstrate that LocScale density improvement reveals previously undiscovered map features and improves the quality of atomic models. The presented approach enhances the interpretability of cryo-EM density maps and provides an implementation reminiscent of iterative density improvement as it is routinely employed in the refinement of X-ray crystallographic models.
Epithelial-mesenchymal plasticity: How have quantitative mathematical models helped improve our understanding?
Authors: Jolly Mohit Kumar , Tripathi Satyendra C , Somarelli Jason A , Hanash Samir M , Levine Herbert
Published: March 2017

Phenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colonize distant organs. As a result, phenotypic plasticity can accelerate tumor progression. A well-studied example of phenotypic plasticity is the bidirectional conversions among epithelial, mesenchymal, and hybrid epithelial/mesenchymal phenotype(s). These conversions can alter a repertoire of cellular traits associated with multiple hallmarks of cancer, such as metabolism, immune-evasion, and invasion and metastasis. To tackle the complexity and heterogeneity of these transitions, mathematical models have been developed that seek to capture the experimentally-verified molecular mechanisms and act as ‘ hypothesis-generating machines’. Here, we discuss how these quantitative mathematical models have helped us explain existing experimental data, guided further experiments, and provided an improved conceptual framework for understanding how multiple intracellular and extracellular signals can drive epithelial-mesenchymal plasticity at both the single-cell and population levels. We also discuss the implications of this plasticity in driving multiple aggressive facets of tumor progression.
Genetic costs of domestication and improvement
Authors: Moyers Brook T. , Morrell Peter L. , McKay John K.
Published: March 2017

The ‘cost of domestication’ hypothesis posits that the process of domesticating wild species can result in an increase in the number, frequency, and/or proportion of deleterious genetic variants that are fixed or segregating in the genomes of domesticated species. This cost may limit the efficacy of selection and thus reduce genetic gains in breeding programs for these species. Understanding when and how deleterious mutations accumulate can also provide insight into fundamental questions about the interplay of demography and selection. Here we describe the evolutionary processes that may contribute to deleterious variation accrued during domestication and improvement, and review the available evidence for ‘the cost of domestication’ in animal and plant genomes. We identify gaps and explore opportunities in this emerging field, and finally offer suggestions for researchers and breeders interested in understanding or avoiding the consequences of an increased number or frequency of deleterious variants in domesticated species.
Variable-temperature structural studies on valence tautomerism in cobalt bis(dioxolene) molecular complexes
Authors: Hathwar Venkatesha R. , Stingaciu Marian , Richter Bo , Overgaard Jacob , Iversen Bo B.
Published: March 2017

A variable-temperature single-crystal structural study of five valence tautomeric cobalt molecular complexes, CoII(3,5-DBSQ)2(DBPy)2(1), CoII(3,5-DBSQ)2(DBPy)2·1.33C7H8(1S), CoII(3,5-DBSQ)2(DCPy)2·C7H8(2S), CoII(3,5-DBSQ)2(TBPy)2(3) and CoII(3,5-DBSQ)2(TCPy)2(4) (S = toluene, 3,5-DBSQ = 3,5-di-tert-butylsemiquinonate, DBPy = 3,5-dibromopyridine, DCPy = 3,5-dichloropyridine, TBPy = 3,4,5-tribromopyridine and TCPy = 3,4,5-trichloropyridine) is reported. The re-crystallization of (1S) in toluene at 277 K resulted in a concomitant formation of a solvent-free polymorph, CoII(3,5-DBSQ)2(DBPy)2(1). Thermally induced valence tautomerism (VT) is observed only in (1S), (1) and (2S) [hs-CoII(3,5-DBSQ)2L2↔ ls-CoIII(3,5-DBSQ)(3,5-DBCat)L2(hs = high spin, ls = low spin, 3,5-DBCat = 3,5-di-tert-butylcatecholate)], whereas (3) and (4) remain locked in the hs-CoII(3,5-DBSQ)2state during cooling of the sample. Multi-temperature single-crystal studies demonstrate the change in cobalt coordination environment during the VT conversion. The non-solvated compound (1) shows a sharp VT transition (T1/2∼ 245 K with ΔT∼ 10 K) from hs-CoII(3,5-DBSQ)2(DBPy)2to ls-CoIII(3,5-DBSQ)(3,5-DBCat)(DBPy)2oxidation state, whereas the other polymorph with lattice solvent (1S) results in a broad transition (T1/2∼ 150 K with ΔT∼ 100 K). This increase in the VT transition temperature for (1) relative to (1S) illustrates the effect of lattice solvent on the VT transition mechanism. Additionally, the influence of halogen substitutions on the pyridine ring is discussed with respect to observed VT behaviour in the studied compounds.
Family business internationalisation and networks: emerging pathways
Authors: Kampouri Katerina , Plakoyiannaki Emmanuella , Leppäaho Tanja
Published: March 2017

Purpose

The aim of this study is twofold: to provide a meta-synthesis of the current state of knowledge in family business (FB) internationalisation research, adopting a network perspective, and to highlight emerging themes that may set the stage for future work on FB internationalisation, for the benefit of researchers adopting a network perspective.

Design/methodology/approach

To address the twofold purpose of the study, the current paper provides a state-of-the-art review of 25 peer-reviewed journal articles published from 1993 to 2014. This study also presents a meta-synthesis of the theoretical approaches, key findings and concepts that were pinpointed in the review, and proposes emerging key themes that are likely to set the stage for future work within this specific field.

Findings

The results indicated that since the mid-1990s, research in the field from a network perspective has mainly focused on three aspects, namely, the role of networks and relationships in the internationalisation process, the factors that influence network formation and strategic/managerial issues in the formation and building of network ties. The current paper pinpoints emerging themes within these three aspects and proposes future pathways.

Research limitations/implications

The review and meta-synthesis are restricted to 25 studies identified in this specific field.

Originality/value

This study comprises an initial attempt to encompass the interface of FB internationalisation and networks.
Herbert Simon’s bounded rationality
Authors: Cristofaro Matteo
Published: March 2017

Purpose

The purpose of this paper is to investigate the historical advancements attained on the bounded rationality concept in management research, considering the key influencing discoveries in related fields. Understanding the cross-fertilization that has occurred is the first step to go beyond the current knowledge on bounded rationality and to face its challenges.

Design/methodology/approach

The adopted method is historical. This research approach helps to explain the evolution of a widespread concept in a scientific field and, particularly, to identify the parallel influencing advancements made in related domains.

Findings

Investigation of the irrational forces of human reasoning is at the centre of today’s research agenda on rationality in organizations, claiming to be an extension of the original bounded rationality concept. In this regard, scholars should commit themselves to build a more holistic approach to the investigation of human rationality, conjointly applying socio-biological and behavioural perspectives to explain the real behaviour of people in organizations and society. This reconnection will also help to overcome the inner limits of some “fashion of the month” streams that have yet to demonstrate their contribution.

Originality/value

This is the first study that offers an overall historical evolution of the bounded rationality concept which considers both management research and developments in related fields. The historically educed lessons learned are at the basis of the concluding recommendations for future research.
Analyzing Lean Six Sigma enablers: a hybrid ISM-fuzzy MICMAC approach
Authors: Yadav Gunjan , Desai Tushar N.
Published: March 2017

Purpose

The purpose of this paper is to identify Lean Six Sigma enablers (LSSEs) and analyse the interaction among the enablers via a hierarchical model developed by employing interpretive structural modelling (ISM) and determine the driving and dependence power of enablers through fuzzy MICMAC (Matriced’ Impacts Croise´s Multiplication Applique´ea´un Classement) analysis.

Design/methodology/approach

An expert group of industry professionals and academicians is consulted at the initial stage as an input for ISM methodology to explore the paired relationship among LSSEs for each parameter of Lean Six Sigma (LSS) implementation. The outcome of ISM is further utilized by fuzzy MICMAC analysis to discover the enablers that are strong drivers and highly dependent. Fuzzy set is included in MICMAC analysis in order to obtain more precise output and effective model.

Findings

In total, 20 key enablers are identified through a literature review and expert opinion that emerged as the most significant factors towards LSS implementation. The identified enablers are portrayed into a structural form representing as input and output variables. Later, the driving and the dependence power of each enabler is presented in cluster form.

Research limitations/implications

The paired relationships among LSSEs are obtained through the interpretation made by the experts. The judgments of experts are subjective and may be biased; as difference in expert opinion may influence the final outcome. Conducting a large-scale survey may provide a better catch for interactions of LSSEs.

Practical implications

This study provides strong practical implications for researchers as well as industry practitioners. The industry professionals must deliberately focus on the identified LSSEs more conservatively during LSS implementation and the top management should plan strategically to avoid any implementation failure.

Originality/value

The present study identifies 20 crucial enablers of integrated LSS and presents them in a hierarchical form which will be beneficial for researchers and practitioners. The interactions among the enablers shown in cluster form will help in better execution of LSS.
Comparative proteomics reveals signature metabolisms of exponentially growing and stationary phase marine bacteria
Authors: Muthusamy Saraladevi , Lundin Daniel , Mamede Branca Rui Miguel , Baltar Federico , González José M. , Lehtiö Janne , Pinhassi Jarone
Published: March 2017

Much of the phenotype of a microorganism consists of its repertoire of metabolisms and how and when its proteins are deployed under different growth conditions. Hence, analyses of protein expression could provide important understanding of how bacteria adapt to different environmental settings. To characterize the flexibility of proteomes of marine bacteria, we investigated protein profiles of three important marine bacterial lineages – Oceanospirillaceae (Neptuniibacter caesariensis strain MED92), Roseobacter (Phaeobacter sp. MED193) and Flavobacteria (Dokdonia sp. MED134) – during transition from exponential to stationary phase. As much as 59–80% of each species’ total proteome was expressed. Moreover, all three bacteria profoundly altered their expressed proteomes during growth phase transition, from a dominance of proteins involved in translation to more diverse proteomes, with a striking appearance of enzymes involved in different nutrient‐scavenging metabolisms. Whereas the three bacteria shared several overarching metabolic strategies, they differed in important details, including distinct expression patterns of membrane transporters and proteins in carbon and phosphorous metabolism and storage compounds. These differences can be seen as signature metabolisms – metabolisms specific for lineages. These findings suggest that quantitative proteomics can inform about the divergent ecological strategies of marine bacteria in adapting to changes in environmental conditions.
Pseudococcus orchidicola(Hemiptera: Pseudococcidae), a newly found mealybug pest, confused withP. longispinusin Korea
Authors: Koo Hyun‐Na , Kim Seulki , Lee Jae Seon , Kang Won Jin , Cho Woo Seong , Kyung YeJin , Seo Jin‐Won , Kim HyunKyung , Kim Gil‐Hah , Cho Soowon
Published: March 2017

Pseudococcus longispinus, a notorious cosmopolitan pest species of mealybugs, known to be distributed indoors in Korea since 2002, is found to be mixed with another species,Pseudococcus orchidicola. FindingP. orchidicolaas a pest of tropical plants in Korea is rather unexpected because of their main distribution in the Pacific area and South Asia. However, all the available information from morphology, molecule and advice on identification from mealybug specialists indicates this is the best match forP. orchidicola. Morphological, molecular and some biological notes onP. orchidicolaare provided with some adult and nymphal images, and compared withP. longispinus. A full discussion mainly on identity and distribution ofP. orchidicolais given.
Insecticide Susceptibility of Field‐collected Blattella germanica (Blattaria: Blattalidae) in Busan, Republic of Korea during 2014
Authors: Jang Chang‐Won , Ju Young Ran , Chang Kyu‐Sik
Published: March 2017

The susceptibility values for field‐collected (BG‐BG) and laboratory (KS‐BG) strains of German cockroaches (BS‐BG), Blattella germanica (L.) to five synthetic pyrethroid and three organophosphate insecticides were assessed by topical application. Both KS‐BG and BS‐BG strains demonstrated the highest levels of susceptibility to deltamethrin with LD50 values of 0.0035 μg/female and 1.5744 μg/female, respectively. The KS‐BG strain demonstrated the lowest susceptibility level to fenthion with an LD50 value of 0.0698 μg/female, while the BS‐BG field population showed the lowest susceptibility to bifenthrin with 4.6811 μg/female. The BS‐BG field population showed resistance levels of 50 to 640 fold higher against the eight pesticides evaluated compared to the KS‐BG strain. The resistance ratios (RR) of the eight pesticides were compared using populations of B. germanica that were collected from the same locality during 2007 and 2014. The field population of B. germanica collected during 2014 demonstrated significantly high resistance to an organophosphates and all pyrethroids when compared with those collected during 2007, but RR values were <10 except for chlorpyrifos‐methyl and chlorpyrifos with RR values of 74 and 104, respectively.
How well documented is Australia's flora? Understanding spatial bias in vouchered plant specimens
Authors: Haque Md. Mohasinul , Nipperess David A. , Gallagher Rachael V. , Beaumont Linda J.
Published: March 2017

Massive digitization of natural history collections (NHC) has opened the door for researchers to conduct inferential studies on the collection of biological diversity across space and time. The widespread use of NHCs in scientific research makes it essential to characterize potential sources of spatial bias. In this study, we assessed spatial patterns in records from the Australian Virtual Herbarium (AVH), based on >3 000 000 vouchered specimens of around 21 000 native plant species. The AVH is the main database for describing Australia's flora, and identifying its limitations is of paramount interest for the validity of conservation and environmental studies. We characterized how sampling effort is distributed across each Interim Bioregion of Australia (IBRA), then asked: (i) How complete are species inventories for each bioregion? We define completeness (C) as the ratio of observed to estimated species richness, using the Chao 1 estimator, (ii) How is sampling effort related to a commonly used Human Influence Index (HII)? and (iii) What is the probability that additional collections would result in the identification of previously unrecorded species in each bioregion? Sampling effort across bioregions is unequal, which partially reflects the collecting behaviour of naturalists in relation to species richness patterns. The density of records in bioregions ranges from 0.02–8.37 km−2. At the bioregional scale, completeness is generally high with 79% of bioregions estimated to have records for at least 80% of their species. Completeness is partly explained by sampling effort (r = 0.43, p = 0.01), although some bioregions (e.g. Northern Kimberley and Burt Plain) have high completeness yet relatively low sampling effort. The inventory of Hampton, however, is substantially less complete than other bioregions (C = 0.66). Bioregions with high HII consistently have high completeness, while regions with low HII span the full range of completeness values. We calculated that an additional specimen collected from a bioregion has a 0.33% (Wet Tropics) to 11.7% (Arnhem Coast) probability of representing a new species for that region. Our assessment can assist with directing future systematic survey efforts by identifying bioregions where additional surveying may result in the greatest return, in terms of increasing knowledge of species richness and diversity.
Tumor biology remains the main determinant of prognosis in retroperitoneal sarcomas: a 14‐year single‐center experience
Authors: Ng Deanna Wan Jie , Tan Grace Hwei Ching , Chia Claramae Shulyn , Chee Soo Khee , Quek Richard , Farid Mohamad , Teo Melissa Ching Ching
Published: March 2017

Aim

To review our experience in the management of retroperitoneal sarcomas (RPSs) in a single institution, with a predominantly Asian population, and identify associated prognostic factors for overall survival (OS), disease‐free survival (DFS) and local recurrence.

Materials and methods

All RPSs diagnosed and managed at our center between January 2000 and March 2014 were included. Exclusion criteria included patients whose medical records were untraceable and patients who underwent biopsy but did not undergo resection.

The variables studied were age, gender, histological subtype, tumor size, tumor grade, surgical margins, type of presentation of tumor (primary or recurrent) and presence of contiguous organ resection.

The primary outcome measured was OS.

Results

Eighty‐five patients underwent resection of RPS with curative intent. Eight patients underwent adjuvant chemotherapy and 15 patients underwent radiotherapy. The median DFS was 21 months (range: 0–146) and median OS was 45 months (range: 1–233).

On univariate analysis, resection margin (P = 0.04), tumor grade (P = 0.011) and type of presentation of tumor (P = 0.007) were found to significantly affect OS. Patients with tumor adherent to contiguous organs had a greater OS as compared to patients with tumor invasive into the contiguous organs (P = 0.02).

Conclusion

An aggressive surgical approach in primary and recurrent RPS is associated with good OS. Complete resection, with contiguous organ resection if necessary should be performed to achieve microscopically negative surgical margins to allow for long‐term survival. However, tumor biology remains the main determinant for OS.
Maternal rubella immunity status and pre‐eclampsia
Authors: Lao Terence T. , Sahota Daljit S. , Law Lai‐Wa , Leung Tak‐Yeung
Published: March 2017

Problem

To determine if maternal immune maladaptation associated with pre‐eclampsia is reflected in the rubella immunity status.

Method of study

Incidence of pre‐eclampsia was compared between rubella non‐immune and immune gravidae carrying a singleton pregnancy beyond 24 weeks, taking into account maternal characteristics and reported risk factors for pre‐eclampsia.

Results

The 9870 (10.4%) rubella non‐immune gravidae among the 95 024 in the cohort exhibited no difference in incidence of underlying medical disorders, but they were slightly but significantly older, shorter, heavier, and had more pre‐eclampsia (OR1.24, 95%CI1.05‐1.47) despite having fewer nulliparas. Regression analysis confirmed an overall association between rubella non‐immunity with pre‐eclampsia (aOR1.27, 95%CI1.06‐1.54), which was related to multiparas (aOR1.42, 95%CI1.05‐1.91) and carrying a male fetus (aOR1.37, 95%CI1.06‐1.78).

Conclusion

The association between rubella non‐immunity and pre‐eclampsia reflects immune maladaptation in multiparas and toward a male fetus.
Olcegepant blocks neurogenic and non‐neurogenic CGRPergic vasodepressor responses and facilitates noradrenergic vasopressor responses in pithed rats
Authors: Avilés‐Rosas V H , Rivera‐Mancilla E , Marichal‐Cancino B A , Manrique‐Maldonado G , Altamirano‐Espinoza A H , Maassen Van Den Brink A , Villalón C M
Published: March 2017

Background and Purpose

Olcegepant (BIBN4096BS) is a selective non‐peptide CGRP receptor antagonist with acute antimigraine properties. Since systemic vascular tone is modulated by perivascular (primary sensory CGRPergic and sympathetic) nerves, this randomized study investigated in pithed rats the effect of acute i.v. treatment with olcegepant on the neurogenic and non‐neurogenic: (i) CGRPergic vasodepressor responses; and (ii) noradrenergic vasopressor responses. The pithed rat is an experimental model predictive of systemic (cardio) vascular side effects.

Experimental Approach

Seventy‐five male Wistar rats (divided into 15 groups, n = 5 each) were pithed, artificially ventilated and prepared for: (i) spinal stimulation (T9–T12; 0.56–5.6 Hz) of the sensory CGRPergic vasodepressor outflow or i.v. bolus injections (0.1–1 μg·kg−1) of α‐CGRP, substance P or acetylcholine, which induced frequency‐dependent or dose‐dependent vasodepressor responses; or (ii) spinal stimulation (T7–T9; 0.03–3 Hz) of the sympathetic vasopressor outflow or i.v. bolus injections (0.03–3 μg·kg−1) of noradrenaline, which produced frequency‐dependent or dose‐dependent vasopressor responses.

Key Results

Olcegepant (1000 and 3000 μg·kg−1, i.v.) dose‐dependently blocked the vasodepressor responses to sensory nerve stimulation or i.v. α‐CGRP, without affecting those to substance P or acetylcholine. Whereas it potentiated the vasopressor responses to sympathetic nerve stimulation or i.v. noradrenaline.

Conclusions and Implications

Olcegepant (i.v.) selectively blocked the neurogenic and non‐neurogenic CGRPergic vasodepressor responses. This blockade by olcegepant potentiated the neurogenic and non‐neurogenic noradrenergic vasopressor responses in pithed rats, an effect that might result in an increased vascular resistance and, consequently, in a prohypertensive action.
Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy
Authors: Yamashita H. , Matsuhara H. , Miotani S. , Sako Y. , Matsui T. , Tanaka H. , Inagaki N.
Published: March 2017

Background

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur.

Objective

We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives.

Methods

We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea.

Results

Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA‐specific IgE were induced in the murine model of oral tolerance. Analyses of antigen‐presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes.

Conclusions and Clinical Relevance

A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.
Genome‐wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1‐related fundus phenotype
Authors: Khan A.O. , Budde B.S. , Nürnberg P. , Kawalia A. , Lenzner S. , Bolz H.J.
Published: March 2017

To uncover the genotype underlying early‐onset cone‐rod dystrophy and central nummular macular atrophic lesion in 2 siblings from an endogamous Arab family, we performed targeted next‐generation sequencing (NGS) of 44 retinal dystrophy genes, whole‐exome sequencing (WES) and genome‐wide linkage analysis. Targeted NGS and WES in the index patient highlighted 2 homozygous variants, a CCDC66 frameshift deletion and a novel missense NMNAT1 variant, c.500G>A (p.Asn167Ser). Linkage and segregation analysis excluded the CCDC66 variant and confirmed the NMNAT1 mutation. Biallelic NMNAT1 mutations cause Leber congenital amaurosis with a central nummular macular atrophic lesion (LCA9). The NMNAT1 mutation reported here underlied cone‐rod dystrophy rather than LCA but the fundus lesion was compatible with that of LCA9 patients, highlighting that such a fundus appearance should raise suspicion for biallelic mutations in NMNAT1 when in the context of any retinal dystrophy. Although Ccdc66 mutations have been proposed to cause retinal disease in dogs, our results and public databases challenge CCDC66 as a candidate gene for human retinal dystrophy.
Clinical genetic testing in pediatric cardiomyopathy: Is bigger better?
Authors: Ouellette A.C. , Mathew J. , Manickaraj A.K. , Manase G. , Zahavich L. , Wilson J. , George K. , Benson L. , Bowdin S. , Mital S.
Published: March 2017

Background

For clinical genetic testing of cardiomyopathy (CMP), current guidelines do not address which gene panels to use: targeted panels specific to a CMP phenotype or expanded (panCMP) panels that include genes associated with multiple phenotypic subtypes.

Aim

Our objective was to assess the clinical utility of targeted versus panCMP panel testing in pediatric CMPs.

Methods

151 pediatric patients with primary hypertrophic (n = 66), dilated (n = 64), restrictive (n = 8), or left‐ventricular non‐compaction (n = 13) CMP who underwent clinical genetic panel testing at a single centre were included. PanCMP (n = 47) and targeted panel testing (n = 104) were compared for yield of pathogenic variants and variants of unknown significance (VUS).

Results

Pathogenic variants were identified in 26% of patients, 42% had indeterminate results (only VUS detected), and 32% had negative results. Yield was lower (15%) in panCMP vs. targeted panel testing (32%) (P = .03) in all CMP subtypes. VUS detection was higher with panCMP (87%) than targeted panel testing (30%) (P <.0001). PanCMP panel testing only identified pathogenic variants in genes that overlapped targeted panels.

Conclusion

PanCMP testing did not increase diagnostic yield compared to targeted panel testing. Until accuracy of variant interpretation with panCMP panels improves, targeted panels may be suitable for clinical testing in pediatric CMP.
MYD88 L265P mutation in cutaneous involvement by Waldenström macroglobulinemia
Authors: Alegría‐Landa Victoria , Prieto‐Torres Lucía , Santonja Carlos , Córdoba Raul , Manso Rebeca , Requena Luis , Rodríguez‐Pinilla Socorro M.
Published: March 2017

Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4‐year history of indolent WM developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations.
Haemophilia patients’ unmet needs and their expectations of the new extended half‐life factor concentrates
Authors: von Mackensen S. , Kalnins W. , Krucker J. , Weiss J. , Miesbach W. , Albisetti M. , Pabinger I. , Oldenburg J.
Published: March 2017

Introduction

National Member Organisations (NMO) of persons with haemophilia (PWH) from the DACH Region (D = Germany, A = Austria, CH = Switzerland) were interested to better understand PWH's expectations and concerns of extended half‐life (EHL) factor concentrates (FC) before availability in these countries.

Methods

Based on an expert meeting and focus groups conducted across Germany a survey for haemophilia patients and their parents was developed and was sent out to 2,644 PWH.

Results

One thousand and seven questionnaires were sent back (38.1%); 743 adults and 262 parents. Most patients had haemophilia A (84.5%), were severely affected (73.7%), received prophylaxis (57%) and used recombinant FC (60.2%). One‐quarter did not know the correct half‐life of their FC [HA/FVIII: 26%, HB/FIX: 31.1%]. Four percent were unsatisfied with their current FC, mainly with short half‐life of FC and difficult manageability. They expected from new EHL products less frequent injections (55.2%), better efficacy (32.1%) and safety/no side effects (15.7%); 59.5% would be willing to switch to new products if they have a prolonged half‐life and the same safety of the current FC. They wish more information about half‐life (84.4%), possible side‐effects (81.3%) and efficacy (77%) and wanted to receive information about new products from their haemophilia treater (76.3%) and the newsletter of their NMO (74.3%). Significant differences across countries were found.

Conclusions

The representative survey could show that although PWH were generally satisfied with their current FC, the majority would be willing to switch to EHL products assuming half‐life is prolonged and has the same safety of the current FC.
The effect of skin moisture,pH, and temperature on the density ofDemodex folliculorumandDemodex brevis(Acari: Demodicidae) in students and staff of the Erzincan University, Turkey
Authors: Zeytun Erhan , Tilki Engin , Doğan Salih , Mumcuoğlu Kosta Yani
Published: March 2017

Background

The aim of this study was to determine the prevalence and density ofDemodex folliculorumandDemodex brevisin students and staff of the Erzincan University, Turkey, and to define the influence of age, gender, educational level, and hygiene as well as skin moisture,pH, and temperature on the presence ofDemodexmites.

Methods

Healthy people without apparent facial dermatoses from nine faculties and five vocational schools of the university were included in the study. The measurements for moisture,pH, and temperature were conducted in the cheek region, while samples for mite presence were taken from the same region using the standard superficial skin biopsy technique.

Results

A total of 538 healthy people, 385 students and 153 university staff, were included in the study.Demodexmites were detected in 50.1% of the students (mean 7.1/cm2) and in 69.3% of the university staff (mean 13.1/cm2). There were statistical differences between the groups of people who were cleaning their face one, two, three, or more times daily and between those who were using and not using personal towels. There was a borderline significant difference between the different age groups and people with different education levels. The density of mites was higher in those with a skin moisture of less than 50%, with apHof 5–6.5 and temperature of 24–28 °C, however the differences between the groups with different skin moisture, skinpH, and skin temperature were not statistically significant.

Conclusion

Demodexmites are very prevalent in healthy individuals of both sexes, and this should be taken into consideration when epidemiological and clinical studies are conducted with patients having different dermatological ailments.
Fabrication of transparent Tb3Al5O12 ceramics by hot isostatic pressing sintering
Authors: Duan Pingping , Liu Peng , Xu Xiaodong , Wang Wei , Wan Zhong , Zhang Shouyi , Wang Yinzhen , Zhang Jian
Published: March 2017

Tb3Al5O12 (TAG) transparent ceramics were prepared by a reactive sintering method using presintering in a muffle furnace combined with hot isostatic pressing (HIP) sintering. The dilatometric, differential scanning calorimetry‐thermogravimetric (DSC‐TG) curves and optical quality were investigated. The microstructure evolution of the TAG ceramic samples was clarified. Two successive transformations were found to generate a TAG phase, as observed in the dilatometric and DSC‐TG curves and XRD patterns of TAG ceramics sintered at different temperature. The changes in average grain size and densification suggest that a 1600°C presintering temperature is suitable for HIP. The optical transmittance of the obtained 0.4 wt% TEOS:TAG transparent ceramics, which were fabricated by a new two‐step sintering of presintering at 1600°C in a muffle furnace followed by HIP at 1650°C, can reach above 80% in the visible (vis) and near‐infrared (NIR) regions. Its transmittance was very close to the theoretical limit. To the best of our knowledge, this is the first time that TAG transparent ceramics with ideal optical quality were obtained without vacuum sintering.
The plantar calcaneal spur: a review of anatomy, histology, etiology and key associations
Authors: Kirkpatrick Joshua , Yassaie Omid , Mirjalili Seyed Ali
Published: March 2017

The plantar calcaneal spur (PCS) is a bony outgrowth from the calcaneal tuberosity and has been studied using various methods including cadavers, radiography, histology and surgery. However, there are currently a number of discrepancies in the literature regarding the anatomical relations, histological descriptions and clinical associations ofPCS. Historically, authors have described the intrinsic muscles of the foot and/or the plantar fascia as attaching to thePCS. In this article we review the relationship between thePCSand surrounding soft tissues as well as examining the histology of thePCS. We identify a number of key associations withPCS, including age, weight, gender, arthritides, plantar fasciitis and foot position; these factors may function as risk factors inPCSformation. The etiology of these spurs is a contentious issue and it has been explained through a number of theories including the degenerative, inflammatory, traction, repetitive trauma, bone‐formers and vertical compression theories. We review these and finish by looking clinically at the evidence thatPCScauses heel pain.
Efficacy of an emollient containing diethylene glycol/dilinoleic acid copolymer for the treatment of dry skin and pruritus in patients with senile xerosis
Authors: Izumi Runa , Negi Osamu , Suzuki Tamie , Tominaga Mitsutoshi , Kamo Atsuko , Suga Yasushi , Matsukuma Shoko , Takamori Kenji
Published: March 2017

Background and Aims

Pruritus frequently reduces quality of life (QOL) in patients with senile xerosis. This study investigated the moisturizing and antipruritic effects of a topical emollient containing a diethylene glycol/dilinoleic acid copolymer (D/DC) in patients with pruritic senile xerosis.

Methods

This single‐blind study involved 50 subjects, aged 50‐75 years. Patients were randomized to self‐applied treatment of the lower legs with 10% (n = 20) or 20% (n = 20) D/DC‐containing cream, white petrolatum (n = 5), or no treatment (n = 5) thrice daily for four weeks. Clinical scores of skin dryness and scratch marks, skin conductance, and Skindex‐16 were evaluated before and after treatment. The degree of pruritus was evaluated by visual analog scale (VAS) score once a week.

Results

Patients treated with 10% and 20% D/DC showed significant improvements in skin dryness and scratch mark scores, as well as increased skin conductance, compared with the untreated group, whereas white petrolatum treatment improved only skin dryness scores. Moreover, patients treated with 20% D/DC showed significant improvements in skin dryness scores and skin conductance compared with white petrolatum treatment. The VAS scores in the D/DC‐treated and white petrolatum‐treated groups were significantly lower than in the untreated group, being particularly lower after one week of treatment with 20% D/DC.

Conclusion

Topical application of an emollient containing D/DC is effective in improving skin dryness and pruritus in patients with senile xerosis.
Underground life is still safest: comments on ‘Danger underground and in the open – predation on blind mole rats (Rodentia, Spalacinae) revisited’
Authors: Sándor Attila D.
Published: March 2017

Németh et al. (Mammal Review 46, 2016, 204) recently reviewed the relationships between Old World blind mole rats (Spalacidae) and their predators. They concluded that blind mole rats are regularly taken by predators throughout their range, and that predation pressure probably contributed to blind mole rat evolution and underground behaviour. I argue instead that blind mole rats are rare or accidental prey for most predators, and list a number of alternative explanations for cases where a high predation rate was observed. I conclude that no blind mole rat species that has been studied is important prey for any predator species that can encounter it.
The emergence of the hyperinvasive vine, Mikania micrantha (Asteraceae), via admixture and founder events inferred from population transcriptomics
Authors: Yang Ming , He Ziwen , Huang Yelin , Lu Lu , Yan Yubin , Hong Lan , Shen Hao , Liu Ying , Guo Qiang , Jiang Lu , Zhang Yanwu , Greenberg Anthony J. , Zhou Renchao , Ge Xuejun , Wu Chung‐I. , Shi Suhua
Published: March 2017

Biological invasions that involve well‐documented rapid adaptations to new environments provide unequalled opportunities for testing evolutionary hypotheses. Mikania micrantha Kunth (Asteraceae), a perennial herbaceous vine native to tropical Central and South America, successfully invaded tropical Asia in the early 20th century. It is regarded as one of the most aggressive weeds in the world. To elucidate the molecular and evolutionary processes underlying this invasion, we extensively sampled this weed throughout its invaded range in South‐East and South Asia and surveyed its genetic structure using variants detected from population transcriptomics. Clustering results suggest that more than one source population contributed to this invasion. Computer simulations using genomewide genetic variation support a scenario of admixture and founder events during invasion. The genes differentially expressed between native and invasive populations were found to be involved in oxidative and high light intensity stress responses, pointing to a possible ecological mechanism of adaptation. Our results provide a foundation for further detailed mechanistic and population studies of this ecologically and economically important invasion. This line of research promises to provide new mitigation strategies for invasive species as well as insights into mechanisms of adaptation.