bluuebunny/crossref_metadata_2025 huggingface dataset:
Ondansetron and pregnancy: Understanding the data
Authors: Kennedy Debra
Published: December 2015

Nausea and vomiting of pregnancy (NVP) is a common condition affecting 75% of pregnant women. NVP generally commences early in the first trimester, peaking in severity between 7 and 12 weeks and in over 90% symptoms will have abated by week 20. Thus, the time when women are most likely to have NVP and require treatment coincides with the embryonic period when there is maximum susceptibility to any teratogenic risk. Following the thalidomide tragedy of 55 years ago there is a particular awareness and sensitivity about these potential risks, especially in relation to any medication used to treat NVP. Despite several studies showing no clear benefits of ondansetron over other NVP treatments such as doxylamine, and the paucity of safety data, the off-label prescribing and use of ondansetron to treat NVP has increased significantly worldwide. Albeit based on limited human pregnancy data, ondansetron has not been associated with a significantly increased risk of birth defects or other adverse pregnancy outcomes. This review attempts to highlight some of the difficulties in interpreting the available data and the need to follow practical guidelines regarding treatment of NVP.
Echocardiographic assessment of aortic valve annular and left ventricular outflow tract diameter in conscious and anesthetized adult sheep prior to prosthetic aortic valve implantation
Authors: Barka Noah , Bourgoin Jason , Grassl Erin , St. Cyr John A.
Published: December 2015

Objective:

Prosthetic heart valve implantation is commonly performed in patients that have valvular heart disease. Prior to clinical evaluation of newly developed prostheses, preclinical animal studies are performed for the assessment of both acute and chronic valvular function. Commonly, one size of valve is used in these preclinical studies, which can present difficulties with the implantation procedure and assessing valve function. Due to these potential problems, we developed a preoperative screening assessment in potential ovine candidates for prosthetic aortic valve implantation. By determining if there is a correlation between conscious and anesthetized echocardiographic examinations, an improvement in surgical confidence can predict that the animal is deemed a suitable candidate for a particular size of prosthetic valve for implantation prior to subjecting the animal to anesthesia and surgery.

Methods:

A total of 53 crossbred sheep ( Ovis aries), male and female, 10–37 months of age, weighing between 41 and 77 kg, underwent conscious echocardiography and a subset of 29 of these animals underwent echocardiographic assessment under anesthesia for a preoperative valve size comparison in these animals prior to surgical prosthetic aortic valve implantation. Using 2D echocardiographic assessment, left ventricular outflow tract (LVOT) dimensions were assessed.

Results:

The mean paired difference between anesthetized and conscious LVOT diameter measurement was −0.87 mm ( p = 0.0066, standard deviation 1.598, 95% confidence interval, −0.4796, −0.26378, n = 29).

Conclusion:

This pilot study evaluation revealed that conscious echocardiographic assessment can play a role preoperatively in selecting potential candidates for surgical prosthetic aortic valve implantation, thereby minimizing the potential in prosthetic-native annular mismatching, which can contribute to altered LVOT function.
An Actor–Partner Interdependence Model of Attachment and Need Fulfillment in Romantic Dyads
Authors: Hadden Benjamin W. , Rodriguez Lindsey M. , Knee C. Raymond , DiBello Angelo M. , Baker Zachary G.
Published: December 2015

The present research tested the unique associations between attachment and basic psychological need fulfillment in relationships. Past research shows that anxious and avoidant attachment are associated with distinct patterns of relationship behaviors, wherein anxious attachment is related to excessive attention to the relationship and avoidant attachment is related to detachment from the relationship. Specifically, we explored the role of romantic partner’s attachment in predicting each other’s experiences of relatedness, autonomy, and competence. Across two samples of undergraduate romantic couples ( nsample 1 = 156, nsample 2 = 264), one’s own anxious and avoidant attachment predicted generally lower basic psychological need fulfillment. Having a more anxiously attached partner predicted higher relatedness but lower autonomy, whereas having a more avoidantly attached partner predicted lower relatedness but higher autonomy need fulfillment. These results extend prior research, suggesting that one’s partner’s anxious and avoidant attachment has distinct implications for one’s own outcomes.
Effects of relative team size on teams with innovative tasks
Authors: Weiss Matthias , Hoegl Martin
Published: December 2015

A large body of research accumulated on the consequences that absolute team size (i.e., team headcount) entails for the performance of teams working on innovative tasks. However, there is a dearth of research on team size in relation to a team’s assignments and objectives (i.e., relative team size). How this relative team size might influence innovation teams is therefore poorly understood. To stimulate theorizing on relative team size, we derive propositions from understaffing theory on how varying levels of relative team size affect teams with innovative tasks. We provide a more fine-grained analysis by differentiating between different dimensions of these teams’ performance (i.e., team creativity, output quality, and team efficiency) and develop an input-mediator-output model. Implications of our theoretical considerations and avenues for future research are discussed.
Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection
Authors: Spigaglia Patrizia
Published: December 2015

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI.
Isolated Sternal Cleft in a Patient With Coronary Artery Disease
Authors: Ates Mehmet Sanser , Duvan Ibrahim , Onuk Burak Emre , Kurtoglu Murat
Published: December 2015

A cleft sternum is a very rare developmental anomaly. It is caused by failure of fusion of the two lateral mesodermal sternal bars which later form the sternum. Diagnosis of cleft sternum is generally made in the neonatal period, and it is usually associated with other congenital defects. Occasionally, patients with cleft sternum may be reported late in the childhood or even in adulthood. We present the case of an adult patient with sternal cleft diagnosed incidentally in the perioperative period at the time of off-pump coronary artery bypass grafting. No other skeletal or cardiac congenital anomalies had been noted previously in this patient.
Networks in Amino Acids Based on Mutation
Authors: Akhtar Adil , Ali Tazid
Published: December 2015

Network theory has a broad spectrum of application including biological science. In the present study, we have analyzed hydrophobic and hydrophilic amino acids’ network based on mutation. To analyze the relative importance of the amino acids, we have discussed different measures of centrality and investigated the correlation coefficients between these measures. We have also dealt with clustering coefficient. Finally, we have discussed the degree of distribution as well as skewness for the networks.
Collaborative Research and Rate of Interests
Authors: Chatterjee Rittwik , Chattopadhyay Srobonti
Published: December 2015

This article has made an attempt to link collaborative research in industry with government initiative and market rate of interests. Two firms involved in Cournot competition in the market decide whether to conduct research to devise a technique for cost reduction. The amount of cost reduction after the research and the initial amount of capital possessed by each firm are private information to each of the firms. In particular, both of them have capacity constraint. The objective of this article has been to figure out the impacts of the lending and borrowing rates of interest on collaborative research. In the process, we have studied the effectiveness of different policies to encourage collaborative research and development (R&D).
Formation of Stable Strategic Networks with Desired Topologies
Authors: Dhamal Swapnil , Narahari Y.
Published: December 2015

Many real-world networks, such as social networks, consist of strategic agents. The topology of these networks often plays a crucial role in determining the ease and speed with which certain information-driven tasks can be accomplished. Consequently, growing a stable network of a certain desired topology is of interest. Motivated by this, we study the following important problem: Given a certain desired topology, under what conditions would best response link alteration strategies adopted by strategic agents lead to formation of a stable network having the given topology and no other topology. This problem is the inverse of the classical network formation problem where we are concerned with determining stable topologies, given the conditions on the network parameters. We study this interesting inverse problem by proposing (1) a recursive model of network formation and (2) a utility model that captures key determinants of network formation. Building upon these models, we explore relevant topologies such as star graph complete graph, bipartite Turán graph, and multiple stars with interconnected centres. We derive a set of sufficient conditions under which these topologies uniquely emerge, study their social welfare properties and investigate the effects of deviating from the derived conditions.
A New Day: Prime Time to Advance Afghan Clinical Education
Authors: Rosenbaum Stephen A.
Published: December 2015

In a previous issue of the journal, Richard Grimes discussed the role that legal clinics can play in facilitating access to justice in a post-conflict society, such as Afghanistan’s, wracked by decades of civil war, external military intervention and consequential regime changes.3 As foreign military forces withdraw, this Central Asian nation faces renewed security concerns and uncertainty about its politico-economic future. Yet, there is now a critical mass of law and Shari’a professors trained in the principles of experiential education, a few legal clinics are in place and many deans are keen on hosting a clinic, with a vigorous nod of approval from the higher education ministry. Piloting a clinical programme requires a team of faculty members who remain in continuous contact with their peers across the nation and across the globe. This should include a partnership with a reputable law school abroad; support from in-country administrative staff; and periodic visits by consultants.

In addition, legal faculties and university administrators need to nurture clinical education by facilitating the development of new curricula, service learning and interdisciplinary and inter-university collaboration and exchange. While they needn’t reinvent policies, protocols or perhaps even priority assessments, they must remain vigilant that clinical legal education not be divorced from the rest of the curriculum. The temptation to purchase durable goods will be great, but the clinic staff should be much more strategic and frugal about ways for students, staff and clients to access information and a space for consultation, training and work. Finally, an essential but elusive goal is to maintain a relationship with donors that is marked by candour and coordination of activities with other funders.
Japanese Law Schools in Crisis: A Study on the Employability of Law School Graduates
Authors: Tanaka Masahiro
Published: December 2015

Fifteen years ago in Japan, the fact that the ratio of legal professionals to the population as a whole was the smallest among G7 countries (for instance, in 1997, the number of legal professionals per 100,000 people was about 345 in the US and 16 in Japan) became a subject of discussion. Moreover, the disproportional distribution of Japanese legal professionals into big cities was also a major challenge. As a policy to increase the number of legal professionals while maintaining their quality, a system of law schools was created in April 2004. However, a decade on, after the creation of this system, these schools are facing an unprecedented crisis, and their existence is extremely precarious. The main purpose of this article is to describe this crisis. The Japanese government has employed a policy to reduce both the number of law schools and the number of slots for enrolled students in the country because many law schools currently operating in Japan fail to attract students, and only 25 per cent of graduates pass the bar examination. As a counterargument against this government policy, this article proposes that Japanese law schools should strengthen their graduates’ employability by improving their career support systems, with a focus on producing and supporting law school graduates who can become not only legal but also non-legal professionals. As support for this position, this article quotes outcomes of previous studies and uses information from questionnaire surveys and field surveys conducted by the author and completed by deans at Japanese law schools.
Exploring Autoethnography as a Method and Methodology in Legal Education Research
Authors: Campbell Elaine
Published: December 2015

Legal education is a new area for autoethnographic research. Indeed, there is a significant lack of autoethnography located in higher education generally. This article explicitly seeks to fill a considerable gap in the literature by fixing the narrative in the law school. Drawing on her own autoethnographic vignettes and reflexive journal entries, the author provides a first-hand account of entering the world of autoethnography. She argues that the hyper-reflexivity at the heart of a narrative approach is valuable and appropriate for legal education research. Yet, she also addresses and explores the challenges of such an approach, including subjectivity, ethics and the politics of discontent.
Resources for Teaching
Authors: Hill Heather C. , Blazar David , Lynch Kathleen
Published: December 2015

Policymakers and researchers have for many years advocated disparate approaches to ensuring teachers deliver high-quality instruction, including requiring that teachers complete specific training requirements, possess a minimum level of content knowledge, and use curriculum materials and professional development resources available from schools and districts. In this paper, we investigate the extent to which these factors, which we conceptualize as resources for teaching, predict instructional quality in upper elementary mathematics classrooms. Results show that teachers’ mathematical knowledge and their district context explained a moderate share of the variation in mathematics-specific teaching dimensions; other factors, such as teacher experience, preparation, non-instructional work hours, and measures of the school environment, explained very little variation in any dimension.
Predictors of Reading Achievement
Authors: Puccioni Jaime
Published: December 2015

Policies increasing the amount of time allocated to reading instruction are popular initiatives to meet the demands of accountability testing. Research suggests that time on instruction and children’s approaches to learning (ATL), which generally includes measures of attention, persistence, motivation, and flexibility, are positively associated with measures of reading achievement. Using data from the Early Childhood Longitudinal Study–Kindergarten cohort, this study simultaneously examines the degree to which time on reading instruction and children’s ATL are related to reading growth during kindergarten and first grade, while also examining whether time on instruction contributes to reading achievement differentially for children with varying ATL. Results indicate that time on reading instruction and children’s ATL were positively associated with children’s reading achievement. Overall, time on instruction was equally beneficial for children regardless of their ATL. Findings highlight the importance of using teaching practices to support children’s ATL.
Moving Beyond Data Transcription
Authors: Hagood Margaret Carmody , Skinner Emily Neil
Published: December 2015

Rigor in qualitative research has been based upon criteria of credibility, dependability, confirmability, and transferability. Drawing upon articles published during our editorship of the Journal of Adolescent & Adult Literacy, we illustrate how the use of digital data in research study reporting may enhance these areas of rigor, and can provide more detailed and nuanced representations that move beyond print-based transcriptions. Data shared demonstrate how including digitally rich artifacts in research articles deepens readers' access to the content, forces authors to show and not just tell of the connections to practice, and ultimately improves the rigor of the study. We also address challenges and solutions to potential problems of using digital data in research reports.
The Quality of Recent Studies in Content-Area Writing in Secondary Classrooms
Authors: Miller Diane M. , McTigue Erin M. , Scott Chyllis E.
Published: December 2015

Situated within the historical and current state of writing and adolescent literacy research, we conducted a systematic literature review in which we screened 2,871 articles to determine the prevalent themes in current research on writing tasks in content-area classrooms. Each of the 37 final studies was evaluated and coded using seven methodological quality indicators. In this article, we further explore the quality analysis step of the review. Specifically, we critique the relative strengths and weaknesses of the current research in the area of content-area writing. Additionally, we identify exemplars for each of our primary recommendations for rigorous literacy research.
The Appropriation of the Coaching With CARE Model With Preservice Teachers
Authors: Maloch Beth , Wetzel Melissa Mosley , Hoffman James V. , A. Taylor Laura , Pruitt Alina , Vlach Saba Khan , Greeter Erin
Published: December 2015

This study is part of a longitudinal, multiphase study on development of literacy mentoring practices particularly with regard to the cooperating teacher. This paper reports on the findings from the first year of the study during which cooperating teachers (CT) participated in a master's program focused on coaching and mentoring while mentoring preservice teachers completing their elementary education degree inside a literacy specialization cohort. Drawing on observational and interview data and employing an activity theory framework, we examine the ways the CTs' involvement in a community of peers and faculty who met regularly in courses was instrumental their appropriation of a model of mentoring known as coaching with CARE. Analysis indicated that coursework, particularly two courses taken during the first year, offered multiple spaces that functioned as ways for participants to work through tensions that arose as the CTs moved across activity systems (from their coaching community at the university to their individual schools situated within area school districts). Specifically, these spaces afforded opportunities to work through understandings of the underlying theories and concepts related to reflective coaching, to share their experiences and beginning enactments of the coaching model, and to coach one another as they interacted around videotaped coaching conferences.
Dialogism
Authors: Kerkhoff Shea N.
Published: December 2015

According to the Common Core State Standards (CCSS), to be college and career ready students must be able to construct logical arguments using facts and reason. A feminist perspective provides an alternative point of view on the value of argumentation. The purpose of this study was to question the theories that frame the current CCSS 9–12 English language arts (ELA) standards and to propose alternative theories to be considered by literacy pedagogues in teaching of the standards. I conducted a thematic content analysis of the 9–12th grade writing standards and related content in the CCSS for ELA. Data revealed two shared areas between feminist pedagogy and ELA CCSS: (a) value of critical thinking; and (b) teachers’ and students’ power to make decisions about class content. However, three points of differences also became clear: (a) view of literacy as classified; (b) lack of women’s voices; and (c) hierarchy of academic writing styles. Implications for practice require teachers to use a dialogic rather than a monologic framework for writing instruction.
Engineering Value into Products and Services
Authors: Sheen Raymond L.
Published: December 2015

A component of increasing value to customers is the interactions that a customer has with the seller both before and after sales transactions. However, many products do not include features within the design of the product that enable a continuing stream of interactions. This is not due to inferior work by design engineers. Rather, most requirements provided to development teams are product-centric and do not address the relationship interactions that occur between the seller and customer. There are no requirements for creating or enabling a steady stream of customer interactions. Development teams create designs based upon the requirements they are given. Product-development methodologies restrict the development teams so that the designs they create do not include features that are not found in the design requirements. Transforming design requirements to include these features will lead to a dimension of customer value creation that can be operationally managed for competitive advantage.
Best Buy and Showrooming: A Critical Thinking Case Exercise Based upon Service Dominant Logic and Value Co-creation
Authors: Taylor Steven A. , Hunter Gary L.
Published: December 2015

This article shows how a critical thinking perspective in teaching business cases can create value for students and educators. We introduce a free, online case emphasizing value co-creation in a consumer retail setting that was co-developed by marketing faculty at Illinois State University, Best Buy and IBM. The case focuses on the problems of showrooming (i.e., evaluating products in a physical store, but purchasing products via another channel such as online) and webrooming (i.e., researching products online, but purchasing the products in physical stores) that currently challenge many traditional retailers. The extent of the information created through the case videos of involved managers and other means encourage critical thinking which supports the achievement of higher order thinking skills in students’ business decision-making. The case further adds an additional value by (a) providing current summaries of the emerging marketing literature related to service dominant logic, value co-creation and customer engagement, and (b) engendering greater student engagement in learning. The case is freely distributed, and can be found at http://business.illinoisstate.edu/bestbuy/ . Suggestions for extending and/or improving the case are encouraged.
Adding Value to Projects Using Mind Maps
Authors: Dutt Maneesh
Published: December 2015

This article presents the effectiveness of Mind Maps as a thinking tool and explores opportunities for using Mind Mapping to add greater value and effectiveness in managing projects. The article briefly explains what a mind map is and how it positively impacts key skills for managing projects. Four key avenues for creating value in projects are identified: Purpose (or Project Vision), People, Problem solving and Customer. The article puts forward the case for Mind Maps by sharing a real life case study and representative examples on how they can add value in areas mentioned above.
UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma
Authors: Bedekovics Tibor , Hussain Sajjad , Feldman Andrew L. , Galardy Paul J.
Published: December 2015

Key Points

The neuronal marker UCH-L1 is induced in, and specifically augments the oncogene-induced transformation of, GCB cells. High levels of UCHL1 identify patients with GC DLBCL with an increased risk for poor outcomes.
Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII
Authors: Marcos-Contreras Oscar A. , Smith Shannon M. , Bellinger Dwight A. , Raymer Robin A. , Merricks Elizabeth , Faella Armida , Pavani Giulia , Zhou Shangzhen , Nichols Timothy C. , High Katherine A. , Margaritis Paris
Published: December 2015

Key Points

Dogs with an FVII G96E mutation (FVII-G96E) represent the most common human FVII mutation type and are ideal for testing new therapies. cFVII gene delivery in FVII-G96E dogs via AAV at a dose effective in humans showed stable and clinically therapeutic FVII expression.
Diverse roles of cell-specific hypoxia-inducible factor 1 in cancer-associated hypercoagulation
Authors: Evans Colin E. , Bendahl Pär-Ola , Belting Mattias , Branco Cristina , Johnson Randall S.
Published: December 2015

Key Points

Cell-specific hypoxia-inducible factor 1 can regulate cancer-associated hypercoagulation and thrombus formation.
Nestin-expressing vascular wall cells drive development of pulmonary hypertension
Authors: Saboor Farhan , Reckmann Ansgar N. , Tomczyk Claudia U.M. , Peters Dorothea M. , Weissmann Norbert , Kaschtanow Andre , Schermuly Ralph T. , Michurina Tatyana V. , Enikolopov Grigori , Müller Dieter , Mietens Andrea , Middendorff Ralf
Published: December 2015

Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.

The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).

Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor β and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.

Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.
Genetic counselling in a national referral centre for pulmonary hypertension
Authors: Girerd Barbara , Montani David , Jaïs Xavier , Eyries Mélanie , Yaici Azzedine , Sztrymf Benjamin , Savale Laurent , Parent Florence , Coulet Florence , Godinas Laurent , Lau Edmund M. , Tamura Yuichi , Sitbon Olivier , Soubrier Florent , Simonneau Gérald , Humbert Marc
Published: December 2015

Genetic causes of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD) have been identified, leading to a growing need for genetic counselling.

Between 2003 and 2014, genetic counselling was offered to 529 PAH and 100 PVOD patients at the French Referral Centre for Pulmonary Hypertension.

Mutations in PAH-predisposing genes were identified in 72 patients presenting as sporadic PAH (17% of cases; 62 mutations inBMPR2, nine inACVRL1(ALK1) and one inENG) and in 94 patients with a PAH family history (89% of cases; 89 mutations inBMPR2, three inACVRL1(ALK1) and two inKCNK3). Bi-allelic mutations inEIF2AK4were identified in all patients with a family history of PVOD (n=19) and in seven patients (8.6%) presenting as sporadic PVOD. Pre-symptomatic genetic diagnosis was offered to 272 relatives of heritable PAH patients, identifying mutations in 36.4% of them. A screening programme is now offered to asymptomatic mutation carriers to detect PAH in an early phase and to identify predictors of outcomes in asymptomaticBMPR2mutation carriers.BMPR2screening allowed us to offer pre-implantation diagnosis to two couples with aBMPR2mutation.

Genetic counselling can be implemented in pulmonary hypertension centres.
Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma
Authors: Wang Gang , Baines Katherine J. , Fu Juan Juan , Wood Lisa G. , Simpson Jodie L. , McDonald Vanessa M. , Cowan Douglas C. , Taylor D. Robin , Cowan Jan O. , Gibson Peter G.
Published: December 2015

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.

Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).

MCT(n=18) and MCT/CPA3(mRNA expression ofTPSAB1andCPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identifiedCPA3(OR 1.21, p=0.004) rather thanTPSAB1(OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.

Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.
Small cell lung cancer in never-smokers
Authors: Torres-Durán María , Ruano-Ravina Alberto , Kelsey Karl T. , Parente-Lamelas Isaura , Provencio Mariano , Leiro-Fernández Virginia , Abal-Arca José , Montero-Martínez Carmen , Vidal-Garcia Iria , Pena Carolina , Castro-Añón Olalla , Golpe-Gómez Antonio , Martínez Cristina , Guzmán-Taveras Rosirys , Mejuto-Martí María José , Fernández-Villar Alberto , Barros-Dios Juan Miguel
Published: December 2015

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.

Cases of SCLC were selected from a prospective, multicenter, hospital-based case–control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.

We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70–80 years). Median residential radon concentration was 195 Bq·m−3(IQR 130–229 Bq·m−3). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94–496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336versus235 days; 1-year survival 50%versus22.2% and 2-year survival 27%versus0%, respectively). Performance status at diagnosis was closely related to survival.

SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization.
Fischer’s Lexicon of Slavic beliefs and customs: a previously unknown contribution to the ethnobotany of Ukraine and Poland
Authors: Kujawska Monika , Łuczaj Łukasz , Typek Joanna
Published: December 2015

Background

Historical ethnobotanical studies are important, even if they are only descriptive, because they help to throw light on the missing chains needed for diachronic analysis. However, the documentation of traditional uses of plants in some countries, e.g. Ukraine, is still fragmentary. The aim of this contribution is to fill the gap and present a portion of the data set, from western Ukraine, which was collected by Adam Fischer, a Polish ethnographer from Lviv, in the 1930s. These data were originally gathered to be published in the first part of theLexicon of Slavic beliefs and customs,dedicated to plant uses in traditional Slavonic culture. The idea of writing theLexiconarose in 1929 during the I Congress of Slavic Philologists in Prague and was intended to be a joint international enterprise, but has never actually been fulfilled.

Methods

In this article we used information from south-eastern Poland at that time – nowadays western Ukraine, collected in four provinces, 11 counties and 28 localities by Fischer’s collaborators. The majority of the information was accompanied by voucher specimens, which were determined by botanists at the Jan Kazimierz University. These data are still unpublished and stored on filecards in the archives of the Polish Ethnological Society in Wrocław, Poland. In our analysis we applied two indices: one to measure general plant versatility – Use Value, and another regarding medicinal plants – Relative Importance Value.

Results

In total, 179 plant taxa used in peasant culture in the western Ukraine in the 1930s were registered. The species which achieved the highest Use Values were:Achillea millefolium,Allium sativum,Vinca minor,Hypericumsp. andJuniperus communis. Among the collected plant names, Polish names dominate (59 %) over clearly Ukrainian and Ruthenian ones (31 %). The remaining 10 % of names were of unclear origin or could have been used by both groups. The most salient use categories were medicinal, followed by ritual – chiefly plants used in church ceremonies, followed by animal wellbeing (veterinary and fodder). However we learn very little about plant management in the peasant culture from the data set.

Conclusions

Analysis of the archival data threw new light on plant use and management in the Galicja region in the interwar period. It also increased our understanding of the central role of plants in spheres such as folk medicine, church ceremonies and animal wellbeing.
Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale
Authors: Liu Siyang , Huang Shujia , Rao Junhua , Ye Weijian ,   The Genome Denmark Consortium, Krogh Anders , Wang Jun
Published: December 2015

Background

Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism.

Findings

We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity.

Conclusions

Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.
Biased agonism at chemokine receptors: obstacles or opportunities for drug discovery?
Authors: Anderson Caroline A , Solari Roberto , Pease James E
Published: December 2015

Chemokine receptors are typically promiscuous, binding more than one ligand, with the ligands themselves often expressed in different spatial localizations by multiple cell types. This is normally a tightly regulated process; however, in a variety of inflammatory disorders, dysregulation results in the excessive or inappropriate expression of chemokines that drives disease progression. Biased agonism, the phenomenon whereby different ligands of the same receptor are able to preferentially activate one signaling pathway over another, adds another level of complexity to an already complex system. In this minireview, we discuss the concept of biased agonism within the chemokine family and report that targeting single signaling axes downstream of chemokine receptors is not only achievable, but may well present novel opportunities to target chemokine receptors, allowing the fine tuning of receptor responses in the context of allergic inflammation and beyond.
New development in studies of formyl-peptide receptors: critical roles in host defense
Authors: Li Liangzhu , Chen Keqiang , Xiang Yi , Yoshimura Teizo , Su Shaobo , Zhu Jianwei , Bian Xiu-wu , Wang Ji Ming
Published: December 2015

Formyl-peptide receptors are a family of 7 transmembrane domain, Gi-protein-coupled receptors that possess multiple functions in many pathophysiologic processes because of their expression in a variety of cell types and their capacity to interact with a variety of structurally diverse, chemotactic ligands. Accumulating evidence demonstrates that formyl-peptide receptors are critical mediators of myeloid cell trafficking in the sequential chemotaxis signal relays in microbial infection, inflammation, and immune responses. Formyl-peptide receptors are also involved in the development and progression of cancer. In addition, one of the formyl-peptide receptor family members, Fpr2, is expressed by normal mouse-colon epithelial cells, mediates cell responses to microbial chemotactic agonists, participates in mucosal development and repair, and protects against inflammation-associated tumorigenesis. These novel discoveries greatly expanded the current understanding of the role of formyl-peptide receptors in host defense and as potential molecular targets for the development of therapeutics.
M-sec regulates polarized secretion of inflammatory endothelial chemokines and facilitates CCL2-mediated lymphocyte transendothelial migration
Authors: Barzilai Sagi , Blecher-Gonen Ronnie , Barnett-Itzhaki Zohar , Zauberman Ayelet , Lebel-Haziv Yaeli , Amit Ido , Alon Ronen
Published: December 2015

Activation of endothelial cells by IL-1β triggers the expression of multiple inflammatory cytokines and leukocyte-attracting chemokines. The machineries involved in the secretion of these inducible proteins are poorly understood. With the use of genome-wide transcriptional analysis of inflamed human dermal microvascular endothelial cells, we identified several IL-1β−induced candidate regulators of these machineries and chose to focus our study on TNF-α-induced protein 2 (myeloid-secretory). The silencing of myeloid-secretory did not affect the ability of inflamed endothelial cells to support the adhesion and crawling of effector T lymphocytes. However, the ability of these lymphocytes to complete transendothelial migration across myeloid-secretory-silenced human dermal microvascular endothelial cells was inhibited significantly. These observed effects on lymphocyte transendothelial migration were recovered completely when exogenous promigratory chemokine CXCL12 was overlaid on the endothelial barrier. A polarized secretion assay suggested that the silencing of endothelial myeloid-secretory impairs T effector transendothelial migration by reducing the preferential secretion of endothelial-produced CCL2, a key transendothelial migration-promoting chemokine for these lymphocytes, into the basolateral endothelial compartment. Myeloid-secretory silencing also impaired the preferential secretion of other endothelial-produced inflammatory chemokines, as well as cytokines, such as IL-6 and GM-CSF, into the basolateral endothelial compartment. This is the first evidence of a novel inflammation-inducible machinery that regulates polarized secretion of endothelial CCL2 and other inflammatory chemokines and cytokines into basolateral endothelial compartments and facilitates the ability of endothelial CCL2 to promote T cell transendothelial migration.
Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404
Authors: Asselin Barbara L. , Devidas Meenakshi , Chen Lu , Franco Vivian I. , Pullen Jeanette , Borowitz Michael J. , Hutchison Robert E. , Ravindranath Yaddanapudi , Armenian Saro H. , Camitta Bruce M. , Lipshultz Steven E.
Published: December 2015

Purpose

To determine the oncologic efficacy, cardioprotective effectiveness, and safety of dexrazoxane added to chemotherapy that included a cumulative doxorubicin dose of 360 mg/m2 to treat children and adolescents with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic non-Hodgkin lymphoma (L-NHL).

Patients and Methods

Patients were treated on Pediatric Oncology Group Protocol POG 9404, which included random assignment to treatment with or without dexrazoxane given as a bolus infusion immediately before every dose of doxorubicin. Cardiac effects were assessed by echocardiographic measurements of left ventricular function and structure.

Results

Of 573 enrolled patients, 537 were eligible, evaluable, and randomly assigned to an arm with or without dexrazoxane. The 5-year event-free survival (with standard error) did not differ between groups: 77.2% (2.7%) for the dexrazoxane group versus 76.0% (2.7%) for the doxorubicin-only group (P = .9). The frequencies of severe grade 3 or 4 hematologic toxicity, infection, CNS events, and toxic deaths were similar in both groups (P ranged from .26 to .64). Of 11 second malignancies, eight occurred in patients who received dexrazoxane (P = .17). The mean left ventricular fractional shortening, wall thickness, and thickness-to-dimension ratio z scores measured 3 years after diagnosis were worse in the doxorubicin-alone group (n = 79-84 per group; P ≤ .01 for all comparisons). Mean fractional shortening z scores measured 3.5 to 6.4 years after diagnosis remained diminished and were lower in the 21 patients who received doxorubicin alone than in the 31 patients who received dexrazoxane (−2.03 v −0.24; P ≤ .001).

Conclusion

Dexrazoxane was cardioprotective and did not compromise antitumor efficacy, did not increase the frequencies of toxicities, and was not associated with a significant increase in second malignancies with this doxorubicin-containing chemotherapy regimen. We recommend dexrazoxane as a cardioprotectant for children and adolescents who have malignancies treated with anthracyclines.
Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers
Authors: van den Broek Alexandra J. , van ’t Veer Laura J. , Hooning Maartje J. , Cornelissen Sten , Broeks Annegien , Rutgers Emiel J. , Smit Vincent T.H.B.M. , Cornelisse Cees J. , van Beek Mike , Janssen-Heijnen Maryska L. , Seynaeve Caroline , Westenend Pieter J. , Jobsen Jan J. , Siesling Sabine , Tollenaar Rob A.E.M. , van Leeuwen Flora E. , Schmidt Marjanka K.
Published: December 2015

Purpose

To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations.

Patients and Methods

A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutations. We report absolute risks and hazard ratios within the cohort from competing risk analyses.

Results

After a median follow-up of 12.5 years, 578 CBCs were observed in our study population. CBC risk for BRCA1 and BRCA2 mutation carriers was two to three times higher than for noncarriers (hazard ratios, 3.31 [95% CI, 2.41 to 4.55; P < .001] and 2.17 [95% CI,1.22 to 3.85; P = .01], respectively). Ten-year cumulative CBC risks were 21.1% (95% CI, 15.4 to 27.4) for BRCA1, 10.8% (95% CI, 4.7 to 19.6) for BRCA2 mutation carriers and 5.1% (95% CI, 4.5 to 5.7) for noncarriers. Age at diagnosis of the first breast cancer was a significant predictor of CBC risk in BRCA1/2 mutation carriers only; those diagnosed before age 41 years had a 10-year cumulative CBC risk of 23.9% (BRCA1: 25.5%; BRCA2: 17.2%) compared with 12.6% (BRCA1: 15.6%; BRCA2: 7.2%) for those 41 to 49 years of age (P = .02); our review of published studies showed ranges of 24% to 31% before age 40 years (BRCA1: 24% to 32%; BRCA2:17% to 29%) and 8% to 21% after 40 years (BRCA1: 11% to 52%; BRCA2: 7% to 18%), respectively.

Conclusion

Age at first breast cancer is a strong risk factor for cumulative CBC risk in BRCA1/2 mutation carriers. Considering the available evidence, age-specific risk estimates should be included in counseling.